bluuebunny/crossref_metadata_2025 huggingface dataset:
Surveillance of the Incidence and Mortality of Oral and Pharyngeal, Esophageal, and Lung Cancer in Nevada: Potential Implications of the Nevada Indoor Clean Air Act
Authors: Foote Kevin , Foote David , Kingsley Karl
Published: July 2021

Reviews of national and state-specific cancer registries have revealed differences in rates of oral, esophageal, and lung cancer incidence and mortality that have implications for public health research and policy. Many significant associations between these types of cancers and major risk factors, such as cigarette usage, may be influenced by public health policy such as smoking restrictions and bans—including the Nevada Clean Indoor Air Act (NCIAA) of 2006 (and subsequent modification in 2011). Although evaluation of general and regional advances in public policy have been previously evaluated, no recent studies have focused specifically on the changes to the epidemiology of oral and pharyngeal, esophageal, and lung cancer incidence and mortality in Nevada. Methods: Cancer incidence and mortality rate data were obtained from the National Cancer Institute (NCI) Division of Cancer Control and Population Sciences (DCCPS) Surveillance, Epidemiology and End Results (SEER) program. Most recently available rate changes in cancer incidence and mortality for Nevada included the years 2012–2016 and are age-adjusted to the year 2000 standard US population. This analysis revealed that the overall rates of incidence and mortality from these types of cancer in Nevada differs from that observed in the overall US population. For example, although the incidence rate of oral cancer is decreasing in the US overall (0.9%), it is stable in Nevada (0.0%). However, the incidence and mortality rates from esophageal cancer are also decreasing in the US (−1.1%, −1.2%, respectively), and are declining more rapidly in Nevada (−1.5%, −1.9%, respectively). Similarly, the incidence and mortality rates from lung are cancer are declining in the US (−2.5%, −2.4%, respectively) and are also declining more rapidly in Nevada (−3.2%, −3.1%, respectively). Analysis of previous epidemiologic data from Nevada (1999–2003) revealed the highest annual percent change (APC) in oral cancer incidence in the US was observed in Nevada (+4.6%), which corresponded with the highest APC in oral cancer mortality (+4.6%). Subsequent studies regarding reduced rates of cigarette use due to smoking restrictions and bans have suggested that follow up studies may reveal changes in the incidence and mortality rates of oral and other related cancers. This study analysis revealed that oral cancer incidence rates are no longer increasing in Nevada and that mortality rates have started to decline, although not as rapidly as the overall national rates. However, rapid decreases in both the incidence and mortality from esophageal and lung cancer were observed in Nevada, which strongly suggest the corresponding changes in oral cancer may be part of a larger epidemiologic shift resulting from improved public health policies that include indoor smoking restrictions and bans.
VCI-Based Analysis on Spatiotemporal Variations of Spring Drought in China
Authors: Liang Liang , Qiu Siyi , Yan Juan , Shi Yanyan , Geng Di
Published: July 2021

The analysis of spatiotemporal variations in drought is important for environmental monitoring and agricultural production. In this study, the spring vegetative drought conditions in China were analyzed by using the vegetation condition index (VCI) as an indicator to reveal the drought characteristics in China from 1981–2015. The results suggest that spring vegetative drought (especially moderate drought) occurs frequently in China, and drought conditions have obvious geographical differences and are highly affected by monsoons. The frequency of spring vegetative drought is relatively high in the southern and northern regions, which are greatly affected by monsoons, and is relatively low in the northwestern and Qinghai-Tibet regions, which are less affected by monsoons. During 1981–2015, the spring VCI in China showed an overall upward trend. In addition, the trend was not a single change but a wave-like increasing trend that can be divided into four stages: (1) a stage of slow growth from 1981–1990, (2) a stage of intense fluctuations from 1991–2000, (3) a stage of steady growth from 2001–2010, and (4) a stage of slow descent after 2010. The Mann–Kendall test confirmed that the spring VCI in China was increasing, and the changes in the southern, northwestern, and Qinghai-Tibet regions reached significant levels. The time point of mutation in the southern region was 2000, and that in the northwestern and Qinghai-Tibet regions was 1992. Wavelet time series analysis showed that spring vegetation drought in China has a short-period oscillation of 5–7 years and a long-period oscillation of approximately 23–28 years. The northwestern and Qinghai-Tibet regions, which are less affected by the monsoons, are dominated by long-period oscillations, while the southern and northern regions, which are more affected by the monsoons, are dominated by short-period oscillations.
Association of Vital Pulp Therapy Outcomes with Tooth Type, Arch Location, Treatment Type, and Number of Surfaces Destroyed in Deciduous Teeth: A Retrospective Study
Authors: Maqbool Manahil , Noorani Tahir Yusuf , Samsudin Norsamsu Arni , Awang Nawi Mohamad Arif , Rossi-Fedele Giampiero , Karobari Mohmed Isaqali , Messina Pietro , Scardina Giuseppe Alessandro
Published: July 2021

There is a paucity of information concerning vital pulp treatment outcomes in the undergraduate teaching setting. This study aimed to determine which type of deciduous molar, arch location, type of vital pulp therapy, and the number of carious surfaces involved had a better prognosis when carried out by undergraduate dental students. The method used was the review of clinical records of 590 patients with 600 deciduous molars, that visited the outpatient undergraduate dental clinics for vital pulp therapy. Statistical analysis used to determine the associations of tooth type, arch location, treatment type, and the number of carious surfaces involved in successful outcomes was logistic regression analysis with significance set at p < 0.05. According to the regression analysis model results, there was a significant association based on tooth type (p < 0.05) and arch location (p = 0.003). In addition, there was a significant association based on the type of treatment performed (p = 0.036). However, there was no significant association in success rates based on the number of carious surfaces involved (p = 0.873). In conclusion, second deciduous molars and maxillary deciduous molars had a better overall prognosis, and indirect pulp therapy was revealed to be more highly associated with successful treatment outcomes in comparison to ferric sulfate pulpotomy in our setting.
Introducing Copula as a Novel Statistical Method in Psychological Analysis
Authors: Dehghani Elham , Ranjbar Somayeh Hadad , Atashafrooz Moharram , Negarestani Hossein , Mosavi Amir , Kovacs Levente
Published: July 2021

During the past decades, the relationship between various psychological parameters had been studied in detail. However, the dependency structure of correlated parameters was rarely investigated. Knowing the dependence structure helps in finding the probability matrix of the interaction between the parameters. In this research, a novel approach was introduced in psychological analysis using copula functions. For this purpose, the self-esteem and anxiety of 141 university students in Iran were extracted using the Coopersmith Self-esteem Inventory and the Zang Anxiety Scale. Then the dependence structure of self-esteem and anxiety were established using copula functions. The Frank copula achieved the best fit for the joint variables of self-esteem and anxiety. Finally, the probability matrix of different classes of anxiety, taking into account self-esteem classes, was extracted. The results indicated that poor self-esteem leads to severe or very severe anxiety, with more than 98% probability, while strong self-esteem may lead to normal and mild anxiety, with about 80% probability. It can be concluded that the method was promising, and that copula functions can open a window to the dependence structure analysis of psychological parameters.
“Better If They Laugh with Me than at Me”: The Role of Humor in Coping with Obesity-Related Stigma in Women
Authors: Mazurkiewicz Natalia , Lipowski Mariusz , Krefta Jarosław , Lipowska Małgorzata
Published: July 2021

This study investigated the role of perceived stigmatization in the relationship between humor styles and coping with stress among young women suffering from stigma due to obesity. In the 21st century, obesity is an increasing global health issue with many physical and mental consequences for obese women. As a chronic stigmatizing disease, it requires that the affected individuals cope with social consequences; women with obesity are more prone to such consequences than men. Humor fosters the breaking of stereotypes and alleviating the consequences of stigmatization. A total of 127 young adult women (age M = 25.74, SD = 2.73) participated in the study (n = 54 with overfat and n = 73 with healthy fat). Participants filled out the Humor Styles Questionnaire, Perceived Stigmatization Questionnaire, and the Brief COPE Scale. Anthropometric data were gathered using a body composition analyzer. Results indicate that, when perceiving hostile behaviors toward themselves and using humor as a coping strategy, women with overfat select maladaptive styles of humor (i.e., self-defeating and aggressive styles). Women with overfat were also more likely to use humor as a coping strategy in difficult situations. Furthermore, none of the participants were satisfied with their body mass. At the same time, among women without obesity, a lack of compliments was not treated as a problem, even if they had high body fat.
Exploring Social Media Recruitment Strategies and Preliminary Acceptability of an mHealth Tool for Teens with Eating Disorders
Authors: Kasson Erin , Vázquez Melissa M. , Doroshenko Christine , Fitzsimmons-Craft Ellen E. , Wilfley Denise E. , Taylor C. Barr , Cavazos-Rehg Patricia A.
Published: July 2021

(1) Background: The current study leveraged social media to connect with teens with EDs to identify population specific characteristics and to gather feedback on an mHealth intervention. (2) Methods: We recruited teens with EDs from social media in two phases: (1) Discovery Group, (2) Testing Group. The Discovery Group (n = 14) participants were recruited from Facebook/Instagram and were asked to review the app for up to one week and provide qualitative feedback. After incorporating feedback from the Discovery Group, we refined our social media outreach methods to connect with 30 teens with EDs to pilot this mobile app. Recruitment from a variety of platforms on social media was successful, with the majority of enrolled participants in the Testing Group coming from Snapchat (60%) and a large percentage of participants belonging to gender and sexual minority groups (63%). (3) Results: Participants from both groups experienced extremely high rates of depression (100% Discovery, 90% Testing) and/or anxiety symptoms (100% Discovery, 93% Testing) in addition to ED symptoms, and noted this as a possible barrier to app engagement. (4) Conclusion: Use of social media for recruitment of teens with EDs is feasible and may connect with groups who may be more difficult to reach using traditional recruitment methods. Among the Discovery Group there was high acceptability of and interest in an app to support ED recovery, and characteristics of both groups demonstrated need for support in other mental health domains. Future studies should evaluate the preliminary efficacy of such tools among teens to determine the effects of such interventions on ED symptoms and other mental health outcomes.
COVID-19 Preparedness and Perceived Safety in Nursing Homes in Southern Portugal: A Cross-Sectional Survey-Based Study in the Initial Phases of the Pandemic
Authors: Brito Fernandes Óscar , Lobo Julião Pedro , Klazinga Niek , Kringos Dionne , Marques Nuno
Published: July 2021

(1) Background: Nursing homes’ preparedness in managing a public health emergency has been poor, with effects on safety culture. The objective of this study was to assess nursing homes’ COVID-19 preparedness in southern Portugal, including staff’s work experiences during the pandemic. (2) Methods: We used a COVID-19 preparedness checklist to be completed by management teams, followed by follow-up calls to nursing homes. Thereafter, a survey of staff was applied. Data analysis included descriptive statistics, exploratory factor analysis, and thematic analysis of open-end questions. (3) Results: In total, 71% (138/195) of eligible nursing homes returned the preparedness checklist. We conducted 83 follow-up calls and received 720 replies to the staff survey. On average, 25% of nursing homes did not have an adequate decision-making structure to respond to the pandemic. Outbreak capacity and training were areas for improvement among nursing homes’ contingency plans. We identified teamwork as an area of strength for safety culture, whereas compliance with procedures and nonpunitive response to mistakes need improvement. (4) Conclusions: To strengthen how nursing homes cope with upcoming phases of the COVID-19 pandemic or future public health emergencies, nursing homes’ preparedness and safety culture should be fostered and closely monitored.
Parental Attitudes toward Consent for Music Intervention Studies in Preterm Infants: A Cross-Sectional Study
Authors: Bauer Sofia , Epstein Shulamit , Bieleninik Łucja , Yakobson Dana , Elefant Cochavit , Arnon Shmuel
Published: July 2021

(1) Background: This study investigated parents’ motives for enrolling preterm infants into music therapy intervention studies during Neonatal Intensive Care hospitalization. (2) Methods: We surveyed Israeli parents of preterm infants after they consented or refused to participate in such studies. The pre-piloted questionnaires evaluated attitudes toward research and music therapy intervention studies. The study included 116 (57%) parents who agreed to participate in music therapy studies and 87 (43%) who declined. (3) Results: Infants of those who agreed to participate were younger (17 ± 2.3 vs. 28 ± 4.7 days old, p = 0.03) and sicker (Clinical Risk Index for Babies score 6.1 ± 2.7 vs. 3.68 ± 4.1, p = 0.04). More single-parent families declined to participate (p = 0.05). Parents agreed to participate because they thought the study might help their child, would improve future care of preterm infants and increase medical knowledge (all p < 0.05). In addition, they perceived music as beneficial for brain development, thought it might improve bonding, and routinely listened to music daily. (4) Conclusions: When recruiting parents and preterm infants for music therapy intervention studies, one should highlight potential contributions to the child’s health, future children’s health and medical knowledge. Stressing music as a potential tool for brain development and augmenting bonding is important. The best time to recruit is when improvements are still anticipated.
Do Current Measures of Social Exclusion Depict the Multidimensional Challenges of Marginalized Urban Areas? Insights, Gaps and Future Research
Authors: Vela-Jiménez Rocío , Sianes Antonio
Published: July 2021

According to the United Nations, 70% of the world’s population will live in cities by 2050, increasing the proliferation of areas of social exclusion and thus polarization and segregation. The establishment of multidimensional measures seeks to identify such situations of social exclusion to inform social policies and interventions. However, some concerns emerge: Are these measures catching the needs of people living in particularly disadvantages areas? Do they offer a human-centred approach or a territorial focus? Is the multidimensionality of such measures reflecting nonmaterial aspects such as health, access to liveable environments or political participation? To analyse how the scientific literature is addressing the measurement of social exclusion to tackle such urban challenges, a systematic review following the PRISMA guidelines was performed in the Web of Science database. After screening following the inclusion criteria, 28 studies were identified that analysed systems of indicators that multidimensionally examined social exclusion at the individual and/or family level in urban contexts. Despite studies being eminently limited to some Western countries, the results revealed a broad diversity. However, very few of them fully focused on the specific characteristics of marginalized urban areas, and most found serious difficulties in overcoming a material approach.
Analysis of Sexual Inhibition and Satisfaction from a Gender Perspective among University Students
Authors: León Samuel P. , Abengózar Sánchez Cristina Abengózar , Augusto-Landa José María , García-Martínez Inmaculada
Published: July 2021

University is characterized by a critical stage where students experience their sexuality, across a range of relationships. From these experiences, university students consolidate their personality and their sexual role. Factors such as age, sex, or traumatic experiences of violence or sexual abuse can affect their sexual role. The present study aims to analyze how the variables age, sex and having suffered abuse or violence may predict sexual satisfaction and inhibition. In addition, we analyze the mediating effect that sexual role plays on these relationships. For this purpose, Bem Sex Role Inventory (BSRI-12), Sociosexual Orientation Inventory (SOI-R), Inhibited Sexual Desire Test (ISD) and New Sexual Satisfaction Scale (NESS) were administered to 403 university students. The findings report that sex (β = −0.313), age (β = −0.116) and being a survivor of sexual assault (β = 0.413) are predictive of male role, but not from the female role. Also, people with more male features tend to have lower levels of commitment and inhibition than those who have more female ones.
Association of Short-Term Particulate Matter Exposure among 5-Year Cancer Survivors with Incident Cardiovascular Disease: A Time-Stratified Case-Crossover Study
Authors: Choi Seulggie , Kim Kyae Hyung , Choi Daein , Jeong Seogsong , Kim Kyuwoong , Chang Jooyoung , Kim Sung Min , Kim Seong Rae , Cho Yoosun , Lee Gyeongsil , Son Joung Sik , Park Sang Min
Published: July 2021

The association of short-term particulate matter concentration with cardiovascular disease (CVD) among cancer survivors is yet unclear. Using the National Health Insurance Service database from South Korea, the study population consisted of 22,864 5-year cancer survivors with CVD events during the period 2015–2018. Using a time-stratified case-crossover design, each case date (date of incident CVD) was matched with three or four referent dates, resulting in a total of 101,576 case and referent dates. The daily average particulate matter 10 (PM10), 2.5 (PM2.5), and 2.5–10 (PM2.5–10) on the day of case or referent date (lag0), 1–3 days before the case or referent date (lag1, lag2, and lag3), and the mean value 0–3 days before the case or referent date (lag0–3) were determined. Conditional logistic regression was conducted to calculate the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for CVD according to quartiles of PM10, PM2.5, and PM2.5–10. Compared to the 1st (lowest) quartile of lag0–3 PM10, the 4th (highest) quartile of lag0–3 PM10 was associated with higher odds for CVD (aOR 1.13, 95% CI 1.06–1.21). The 4th quartiles of lag1 (aOR 1.12, 95% CI 1.06–1.19), lag2 (aOR 1.09, 95% CI 1.03–1.16), lag3 (aOR 1.06, 95% CI 1.00–1.12), and lag0–3 (aOR 1.11, 95% CI 1.05–1.18) PM2.5 were associated with higher odds for CVD compared to the respective 1st quartiles. Similarly, the 4th quartile of lag0–3 PM2.5–10 was associated with higher CVD events (aOR 1.11, 95% CI 1.03–1.19) compared to the 1st quartile. Short-term exposure to high levels of PM may be associated with increased CVD risk among cancer survivors.
Full Zirconia Implant-Born Prosthetic Rehabilitation with CAD/CAM Technology after Accurate Digital Planning. A Case Report
Authors: Scaringi Riccardo , Nannelli Michele , Franchina Alessio , Lizio Giuseppe , Stefanelli Luigi V. , Pagliarulo Michele , De Angelis Francesca , Pellegrino Gerardo
Published: July 2021

CAD/CAM technology can enhance the dentistry application of ceramic materials that meet the more relevant biocompatibility and aesthetics demands. In implant-borne prosthesis rehabilitation, yttria-stabilized zirconia appeared to be a valid alternative to metal-alloys and titanium, with comparable mechanical properties and even better interaction with bone and soft tissues. The improvement of monolithic CAD/CAM manufacturing allows for a reliable, predictable, and rapid workflow that can correspond to a holistic treatment philosophy associated with zirconia fixtures. This reported clinical case highlights the advantages of this approach in resolving particularly functionally and aesthetically complex situations. A 40-year-old patient with permanent canine impaction and the persistence of a deciduous tooth compromised by caries was successfully rehabilitated with the surgical removal of the enclosed tooth, the seating of a mono-phase zirconia implant after the deciduous extraction and its loading with a zirconia single crown, without any clinical or radiographical alteration up to seven years follow-up.
Are We Ready to Build Back “Healthier?” An Exploratory Analysis of U.S. State-Level Disaster Recovery Plans
Authors: Kennedy Mallory , Gonick Shannon A. , Errett Nicole A.
Published: July 2021

As communities recover from disasters, it is crucial to understand the extent to which states are prepared to support the recovery of health systems and services. This need has been emphasized by the United States’ experience with COVID-19. This study sought to assess public health activities in state disaster recovery implementation plans. In this exploratory, descriptive study, state-wide disaster recovery implementation plans were collected from emergency management agency websites and verified (n = 33). We reviewed and coded the recovery plans to identify health-related activities. While 70% and 64% of reviewed plans included activities to address short-term healthcare and behavioral health needs, respectively, one-third or less of the plans included activities to address long-term healthcare and behavioral health needs. Further, plans have limited descriptions of health-related data collection, analysis, or data-driven processes. Additional evidence-informed public health requirements and activities are needed in disaster recovery implementation plans. State disaster recovery plans would benefit from additional description of public health roles, responsibilities, and activities, as well as additional plans for collecting and analyzing public health data to drive recovery decision making and activities. Plans should include approaches for ongoing evaluation of recovery activities.
Unsupervised Exercise Training Was Not Found to Improve the Metabolic Health or Phenotype over a 6-Month Dietary Intervention: A Randomised Controlled Trial with an Embedded Economic Analysis
Authors: Hens Wendy , Vissers Dirk , Verhaeghe Nick , Gielen Jan , Van Gaal Luc , Taeymans Jan
Published: July 2021

Ectopic fat leads to metabolic health problems. This research aimed to assess the effectiveness of a hypocaloric diet intervention together with an unsupervised exercise training program in comparison with a hypocaloric diet alone to reduce ectopic fat deposition. Sixty-one premenopausal women with overweight or obesity participated in this controlled trial and were each randomised into either a usual care group (hypocaloric diet) or intervention group (hypocaloric diet + unsupervised exercise training). Ectopic fat deposition, metabolic parameters, incremental costs from a societal perspective and incremental quality-adjusted life years (QALYs) were assessed before, during and after the six-month intervention period. In the total sample, there was a significant decrease in visceral adipose tissue (VAT: −18.88 cm2, 95% CI −11.82 to −25.95), subcutaneous abdominal adipose tissue (SAT: −46.74 cm2, 95% CI −29.76 to −63.18), epicardial fat (ECF: −14.50 cm3, 95% CI −10.9 to −18.98) and intrahepatic lipid content (IHL: −3.53%, 95% CI −1.72 to −5.32). Consequently, an “adapted” economic analysis revealed a non-significant decrease in costs and an increase in QALYs after the intervention. No significant differences were found between groups. A multidisciplinary lifestyle approach seems successful in reducing ectopic fat deposition and improving the metabolic risk profile in women with overweight and obesity. The addition of unsupervised exercise training did not further improve the metabolic health or phenotype over the six months.
3D Agent-Based Model of Pedestrian Movements for Simulating COVID-19 Transmission in University Students
Authors: Alvarez Castro David , Ford Alistair
Published: July 2021

On the 30 January 2020, the WHO declared a public health emergency of international concern due to the coronavirus disease 2019 (COVID-19). Social restrictions with different efficiencies were put in place to avoid transmission. Students living in student accommodation constitute an interesting group to test restrictions because they share living places, workplaces and daily routines, which are key factors in the transmission. In this paper, we present a new geospatial agent-based simulation model to explore the transmission of COVID-19 between students living in Newcastle University accommodation and the efficiency of simulated restrictions (e.g., facemask, lockdown, self-isolation). Results showed that facemasks could reduce infection peak by 30% if worn by all students; an early lockdown could keep 65% of the students safe in the best case; self-isolation could keep 86% of the students safe; while the combination of these measures could prevent disease in 95% of students in the best case-scenario. Spatial analyses showed that the most dangerous places were those where many students interact for a long time, such as faculties and accommodation. The developed ABM could help university managers to respond to current and future epidemics and plan effective responses to keep safe as many students as possible.
Burned Area Mapping over the Southern Cape Forestry Region, South Africa Using Sentinel Data within GEE Cloud Platform
Authors: Xulu Sifiso , Mbatha Nkanyiso , Peerbhay Kabir
Published: July 2021

Planted forests in South Africa have been affected by an increasing number of economically damaging fires over the past four decades. They constitute a major threat to the forestry industry and account for over 80% of the country’s commercial timber losses. Forest fires are more frequent and severe during the drier drought conditions that are typical in South Africa. For proper forest management, accurate detection and mapping of burned areas are required, yet the exercise is difficult to perform in the field because of time and expense. Now that ready-to-use satellite data are freely accessible in the cloud-based Google Earth Engine (GEE), in this study, we exploit the Sentinel-2-derived differenced normalized burned ratio (dNBR) to characterize burn severity areas, and also track carbon monoxide (CO) plumes using Sentinel-5 following a wildfire that broke over the southeastern coast of the Western Cape province in late October 2018. The results showed that 37.4% of the area was severely burned, and much of it occurred in forested land in the studied area. This was followed by 24.7% of the area that was burned at a moderate-high level. About 15.9% had moderate-low burned severity, whereas 21.9% was slightly burned. Random forests classifier was adopted to separate burned class from unburned and achieved an overall accuracy of over 97%. The most important variables in the classification included texture, NBR, and the NIR bands. The CO signal sharply increased during fire outbreaks and marked the intensity of black carbon over the affected area. Our study contributes to the understanding of forest fire in the dynamics over the Southern Cape forestry landscape. Furthermore, it also demonstrates the usefulness of Sentinel-5 for monitoring CO. Taken together, the Sentinel satellites and GEE offer an effective tool for mapping fires, even in data-poor countries.
FAM20C Overview: Classic and Novel Targets, Pathogenic Variants and Raine Syndrome Phenotypes
Authors: Palma-Lara Icela , Pérez-Ramírez Monserrat , García Alonso-Themann Patricia , Espinosa-García Ana María , Godinez-Aguilar Ricardo , Bonilla-Delgado José , López-Ornelas Adolfo , Victoria-Acosta Georgina , Olguín-García María Guadalupe , Moreno José , Palacios-Reyes Carmen
Published: July 2021

FAM20C is a gene coding for a protein kinase that targets S-X-E/pS motifs on different phosphoproteins belonging to diverse tissues. Pathogenic variants of FAM20C are responsible for Raine syndrome (RS), initially described as a lethal and congenital osteosclerotic dysplasia characterized by generalized atherosclerosis with periosteal bone formation, characteristic facial dysmorphisms and intracerebral calcifications. The aim of this review is to give an overview of targets and variants of FAM20C as well as RS aspects. We performed a wide phenotypic review focusing on clinical aspects and differences between all lethal (LRS) and non-lethal (NLRS) reported cases, besides the FAM20C pathogenic variant description for each. As new targets of FAM20C kinase have been identified, we reviewed FAM20C targets and their functions in bone and other tissues, with emphasis on novel targets not previously considered. We found the classic lethal and milder non-lethal phenotypes. The milder phenotype is defined by a large spectrum ranging from osteonecrosis to osteosclerosis with additional congenital defects or intellectual disability in some cases. We discuss our current understanding of FAM20C deficiency, its mechanism in RS through classic FAM20C targets in bone tissue and its potential biological relevance through novel targets in non-bone tissues.
Interleukin-17 and Th17 Lymphocytes Directly Impair Motoneuron Survival of Wildtype and FUS-ALS Mutant Human iPSCs
Authors: Jin Mengmeng , Akgün Katja , Ziemssen Tjalf , Kipp Markus , Günther Rene , Hermann Andreas
Published: July 2021

Amyotrophic lateral sclerosis (ALS) is a progressive disease leading to the degeneration of motor neurons (MNs). Neuroinflammation is involved in the pathogenesis of ALS; however, interactions of specific immune cell types and MNs are not well studied. We recently found a shift toward T helper (Th)1/Th17 cell-mediated, pro-inflammatory immune responses in the peripheral immune system of ALS patients, which positively correlated with disease severity and progression. Whether Th17 cells or their central mediator, Interleukin-17 (IL-17), directly affects human motor neuron survival is currently unknown. Here, we evaluated the contribution of Th17 cells and IL-17 on MN degeneration using the co-culture of iPSC-derived MNs of fused in sarcoma (FUS)-ALS patients and isogenic controls with Th17 lymphocytes derived from ALS patients, healthy controls, and multiple sclerosis (MS) patients (positive control). Only Th17 cells from MS patients induced severe MN degeneration in FUS-ALS as well as in wildtype MNs. Their main effector, IL-17A, yielded in a dose-dependent decline of the viability and neurite length of MNs. Surprisingly, IL-17F did not influence MNs. Importantly, neutralizing IL-17A and anti-IL-17 receptor A treatment reverted all effects of IL-17A. Our results offer compelling evidence that Th17 cells and IL-17A do directly contribute to MN degeneration.
Review of Dendritic Cells, Their Role in Clinical Immunology, and Distribution in Various Animal Species
Authors: Zanna Mohammed Yusuf , Yasmin Abd Rahaman , Omar Abdul Rahman , Arshad Siti Suri , Mariatulqabtiah Abdul Razak , Nur-Fazila Saulol Hamid , Mahiza Md Isa Nur
Published: July 2021

Dendritic cells (DCs) are cells derived from the hematopoietic stem cells (HSCs) of the bone marrow and form a widely distributed cellular system throughout the body. They are the most efficient, potent, and professional antigen-presenting cells (APCs) of the immune system, inducing and dispersing a primary immune response by the activation of naïve T-cells, and playing an important role in the induction and maintenance of immune tolerance under homeostatic conditions. Thus, this review has elucidated the general aspects of DCs as well as the current dynamic perspectives and distribution of DCs in humans and in various species of animals that includes mouse, rat, birds, dog, cat, horse, cattle, sheep, pig, and non-human primates. Besides the role that DCs play in immune response, they also play a pathogenic role in many diseases, thus becoming a target in disease prevention and treatment. In addition, its roles in clinical immunology have also been addressed, which include its involvement in transplantation, autoimmune disease, viral infections, cancer, and as a vaccine target. Therefore, based on the current knowledge and understanding of the important roles they play, DCs can be used in the future as a powerful tool for manipulating the immune system.
Computational Insights into the Deleterious Impacts of Missense Variants on N-Acetyl-d-glucosamine Kinase Structure and Function
Authors: Dash Raju , Mitra Sarmistha , Munni Yeasmin Akter , Choi Ho Jin , Ali Md. Chayan , Barua Largess , Jang Tae Jung , Moon Il Soo
Published: July 2021

An enzyme of the mammalian amino-sugar metabolism pathway, N-acetylglucosamine kinase (NAGK), that synthesizes N-acetylglucosamine (GlcNAc)-6-phosphate, is reported to promote dynein functions during mitosis, axonal and dendritic growth, cell migration, and selective autophagy, which all are unrelated to its enzyme activity. As non-enzymatic structural functions can be altered by genetic variation, we made an effort in this study aimed at deciphering the pathological effect of nonsynonymous single-nucleotide polymorphisms (nsSNPs) in NAGK gene. An integrated computational approach, including molecular dynamics (MD) simulation and protein–protein docking simulation, was used to identify the damaging nsSNPs and their detailed structural and functional consequences. The analysis revealed the four most damaging variants (G11R, G32R, G120E, and A156D), which are highly conserved and functional, positioned in both small (G11R and G32R) and large (G120E and A156D) domains of NAGK. G11R is located in the ATP binding region, while variants present in the large domain (G120E and A156D) were found to induce substantial alterations in the structural organizations of both domains, including the ATP and substrate binding sites. Furthermore, all variants were found to reduce binding energy between NAGK and dynein subunit DYNLRB1, as revealed by protein–protein docking and MM-GBSA binding energy calculation supporting their deleteriousness on non-canonical function. We hope these findings will direct future studies to gain more insight into the role of these variants in the loss of NAGK function and their role in neurodevelopmental disorders.
Development of [18F]LU14 for PET Imaging of Cannabinoid Receptor Type 2 in the Brain
Authors: Teodoro Rodrigo , Gündel Daniel , Deuther-Conrad Winnie , Ueberham Lea , Toussaint Magali , Bormans Guy , Brust Peter , Moldovan Rareş-Petru
Published: July 2021

Cannabinoid receptors type 2 (CB2R) represent an attractive therapeutic target for neurodegenerative diseases and cancer. Aiming at the development of a positron emission tomography (PET) radiotracer to monitor receptor density and/or occupancy during a CB2R-tailored therapy, we herein describe the radiosynthesis of cis-[18F]1-(4-fluorobutyl-N-((1s,4s)-4-methylcyclohexyl)-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxamide ([18F]LU14) starting from the corresponding mesylate precursor. The first biological evaluation revealed that [18F]LU14 is a highly affine CB2R radioligand with >80% intact tracer in the brain at 30 min p.i. Its further evaluation by PET in a well-established rat model of CB2R overexpression demonstrated its ability to selectively image the CB2R in the brain and its potential as a tracer to further investigate disease-related changes in CB2R expression.
Critical Role of LSEC in Post-Hepatectomy Liver Regeneration and Failure
Authors: De Rudder Maxime , Dili Alexandra , Stärkel Peter , Leclercq Isabelle A.
Published: July 2021

Liver sinusoids are lined by liver sinusoidal endothelial cells (LSEC), which represent approximately 15 to 20% of the liver cells, but only 3% of the total liver volume. LSEC have unique functions, such as fluid filtration, blood vessel tone modulation, blood clotting, inflammatory cell recruitment, and metabolite and hormone trafficking. Different subtypes of liver endothelial cells are also known to control liver zonation and hepatocyte function. Here, we have reviewed the origin of LSEC, the different subtypes identified in the liver, as well as their renewal during homeostasis. The liver has the exceptional ability to regenerate from small remnants. The past decades have seen increasing awareness in the role of non-parenchymal cells in liver regeneration despite not being the most represented population. While a lot of knowledge has emerged, clarification is needed regarding the role of LSEC in sensing shear stress and on their participation in the inductive phase of regeneration by priming the hepatocytes and delivering mitogenic factors. It is also unclear if bone marrow-derived LSEC participate in the proliferative phase of liver regeneration. Similarly, data are scarce as to LSEC having a role in the termination phase of the regeneration process. Here, we review what is known about the interaction between LSEC and other liver cells during the different phases of liver regeneration. We next explain extended hepatectomy and small liver transplantation, which lead to “small for size syndrome” (SFSS), a lethal liver failure. SFSS is linked to endothelial denudation, necrosis, and lobular disturbance. Using the knowledge learned from partial hepatectomy studies on LSEC, we expose several techniques that are, or could be, used to avoid the “small for size syndrome” after extended hepatectomy or small liver transplantation.
Matrix Metalloproteinases (MMPs) and Inhibitors of MMPs in the Avian Reproductive System: An Overview
Authors: Hrabia Anna
Published: July 2021

Many matrix metalloproteinases (MMPs) are produced in the mammalian reproductive system and participate in the regulation of its functions. In birds, the limited information available thus far indicates that MMPs are significant regulators of avian ovarian and oviductal functions, too. Some MMPs and inhibitors of MMPs are present in the hen reproductive tissues and their abundances and/or activities change according to the physiological state. The intraovarian role of MMPs likely includes the remodeling of the extracellular matrix (ECM) during folliculogenesis, follicle atresia, and postovulatory regression. In the oviduct, MMPs are also involved in ECM turnover during oviduct development and regression. This study provides a review of the current knowledge on the presence, activity, and regulation of MMPs in the female reproductive system of birds.
SARS-CoV-2 Infected Pediatric Cerebral Cortical Neurons: Transcriptomic Analysis and Potential Role of Toll-like Receptors in Pathogenesis
Authors: Gugliandolo Agnese , Chiricosta Luigi , Calcaterra Valeria , Biasin Mara , Cappelletti Gioia , Carelli Stephana , Zuccotti Gianvincenzo , Avanzini Maria Antonietta , Bramanti Placido , Pelizzo Gloria , Mazzon Emanuela
Published: July 2021

Different mechanisms were proposed as responsible for COVID-19 neurological symptoms but a clear one has not been established yet. In this work we aimed to study SARS-CoV-2 capacity to infect pediatric human cortical neuronal HCN-2 cells, studying the changes in the transcriptomic profile by next generation sequencing. SARS-CoV-2 was able to replicate in HCN-2 cells, that did not express ACE2, confirmed also with Western blot, and TMPRSS2. Looking for pattern recognition receptor expression, we found the deregulation of scavenger receptors, such as SR-B1, and the downregulation of genes encoding for Nod-like receptors. On the other hand, TLR1, TLR4 and TLR6 encoding for Toll-like receptors (TLRs) were upregulated. We also found the upregulation of genes encoding for ERK, JNK, NF-κB and Caspase 8 in our transcriptomic analysis. Regarding the expression of known receptors for viral RNA, only RIG-1 showed an increased expression; downstream RIG-1, the genes encoding for TRAF3, IKKε and IRF3 were downregulated. We also found the upregulation of genes encoding for chemokines and accordingly we found an increase in cytokine/chemokine levels in the medium. According to our results, it is possible to speculate that additionally to ACE2 and TMPRSS2, also other receptors may interact with SARS-CoV-2 proteins and mediate its entry or pathogenesis in pediatric cortical neurons infected with SARS-CoV-2. In particular, TLRs signaling could be crucial for the neurological involvement related to SARS-CoV-2 infection.
Metal Oxide Nanoparticles: Evidence of Adverse Effects on the Male Reproductive System
Authors: Vassal Mariana , Rebelo Sandra , Pereira Maria de Lourdes
Published: July 2021

Metal oxide nanoparticles (MONPs) are inorganic materials that have become a valuable tool for many industrial sectors, especially in healthcare, due to their versatility, unique intrinsic properties, and relatively inexpensive production cost. As a consequence of their wide applications, human exposure to MONPs has increased dramatically. More recently, their use has become somehow controversial. On one hand, MONPs can interact with cellular macromolecules, which makes them useful platforms for diagnostic and therapeutic interventions. On the other hand, research suggests that these MONPs can cross the blood–testis barrier and accumulate in the testis. Although it has been demonstrated that some MONPs have protective effects on male germ cells, contradictory reports suggest that these nanoparticles compromise male fertility by interfering with spermatogenesis. In fact, in vitro and in vivo studies indicate that exposure to MONPs could induce the overproduction of reactive oxygen species, resulting in oxidative stress, which is the main suggested molecular mechanism that leads to germ cells’ toxicity. The latter results in subsequent damage to proteins, cell membranes, and DNA, which ultimately may lead to the impairment of the male reproductive system. The present manuscript overviews the therapeutic potential of MONPs and their biomedical applications, followed by a critical view of their potential risks in mammalian male fertility, as suggested by recent scientific literature.
Benzo[a]pyrene-Induced Genotoxicity in Rats Is Affected by Co-Exposure to Sudan I by Altering the Expression of Biotransformation Enzymes
Authors: Dračínská Helena , Indra Radek , Jelínková Sandra , Černá Věra , Arlt Volker , Stiborová Marie
Published: July 2021

The environmental pollutant benzo[a]pyrene (BaP) is a human carcinogen that reacts with DNA after metabolic activation catalysed by cytochromes P450 (CYP) 1A1 and 1B1 together with microsomal epoxide hydrolase. The azo dye Sudan I is a potent inducer of CYP1A1/2. Here, Wistar rats were either treated with single doses of BaP (150 mg/kg bw) or Sudan I (50 mg/kg bw) alone or with both compounds in combination to explore BaP-derived DNA adduct formation in vivo. Using 32P-postlabelling, DNA adducts generated by BaP-7,8-dihydrodiol-9,10-epoxide were found in livers of rats treated with BaP alone or co-exposed to Sudan I. During co-exposure to Sudan I prior to BaP treatment, BaP-DNA adduct levels increased 2.1-fold in comparison to BaP treatment alone. Similarly, hepatic microsomes isolated from rats exposed to Sudan I prior to BaP treatment were also the most effective in generating DNA adducts in vitro with the activated metabolites BaP-7,8-dihydrodiol or BaP-9-ol as intermediates. DNA adduct formation correlated with changes in the expression and/or enzyme activities of CYP1A1, 1A2 and 1B1 in hepatic microsomes. Thus, BaP genotoxicity in rats in vivo appears to be related to the enhanced expression and/or activity of hepatic CYP1A1/2 and 1B1 caused by exposure of rats to the studied compounds. Our results indicate that the industrially employed azo dye Sudan I potentiates the genotoxicity of the human carcinogen BaP, and exposure to both substances at the same time seems to be hazardous to humans.
Mouse Models of Achromatopsia in Addressing Temporal “Point of No Return” in Gene-Therapy
Authors: Wang Nan-Kai , Liu Pei-Kang , Kong Yang , Levi Sarah R. , Huang Wan-Chun , Hsu Chun-Wei , Wang Hung-Hsi , Chen Nelson , Tseng Yun-Ju , Quinn Peter M. J. , Tai Ming-Hong , Lin Chyuan-Sheng , Tsang Stephen H.
Published: July 2021

Achromatopsia is characterized by amblyopia, photophobia, nystagmus, and color blindness. Previous animal models of achromatopsia have shown promising results using gene augmentation to restore cone function. However, the optimal therapeutic window to elicit recovery remains unknown. Here, we attempted two rounds of gene augmentation to generate recoverable mouse models of achromatopsia including a Cnga3 model with a knock-in stop cassette in intron 5 using Easi-CRISPR (Efficient additions with ssDNA inserts-CRISPR) and targeted embryonic stem (ES) cells. This model demonstrated that only 20% of CNGA3 levels in homozygotes derived from target ES cells remained, as compared to normal CNGA3 levels. Despite the low percentage of remaining protein, the knock-in mouse model continued to generate normal cone phototransduction. Our results showed that a small amount of normal CNGA3 protein is sufficient to form “functional” CNG channels and achieve physiological demand for proper cone phototransduction. Thus, it can be concluded that mutating the Cnga3 locus to disrupt the functional tetrameric CNG channels may ultimately require more potent STOP cassettes to generate a reversible achromatopsia mouse model. Our data also possess implications for future CNGA3-associated achromatopsia clinical trials, whereby restoration of only 20% functional CNGA3 protein may be sufficient to form functional CNG channels and thus rescue cone response.
Role of Amine Neurotransmitters and Their Receptors in Skin Pigmentation: Therapeutic Implication
Authors: Enkhtaivan Enkhmend , Lee Chang Hoon
Published: July 2021

Skin pigmentation can occur due to increased melanin, including melanocyte proliferation, melanin biosynthesis, or melanocyte migration. There are many factors that influence the melanin production process, but the role of neurotransmitters in this process is still unclear. We found that histamine and serotonin influence the different stages of melanogenesis and melanogenesis, which increase melanogenesis. Since then, several related papers have been published, and from these papers, it has been recognised that the role of neurotransmitters in skin-pigment-related diseases needs to be summarised. By introducing the role of neurotransmitters in the regulation of various pigment disorders, including vitiligo and melasma, through this review, many researchers can be expected to try to apply neurotransmitter-related agonists and antagonists as treatments for skin pigment disorders.