bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiovascular risk in children: a burden for future generations
Authors: Candelino Maria , Tagi Veronica Maria , Chiarelli Francesco 
Published: April 2022

AbstractCardiovascular diseases are the main causes of death and health costs in developed countries. Although cardiovascular diseases are thought to affect only adulthood, the underlying process of atherosclerosis begins in the first decade of life. Epidemiological studies show that severity of atherosclerosis depends both on the number and intensity of risk factors. Early detection of cardiovascular risk in childhood is the most powerful tool to prevent cardiovascular accidents in adulthood and possibly reduce its consequent burden for the future.A large amount of cardiovascular risk factors is already detectable in childhood and include non-modifiable elements, among which genetic factors and congenital heart diseases, and modifiable elements, which depend on environmental effects (e.g. lifestyle and nutrition). Regardless of the possibility to intervene on these factors, an early diagnosis is fundamental to ensure an optimal life expectancy in adulthood. The most important cardiovascular risk factors in the paediatric age and adolescence are excess weight, arterial hypertension, glucose metabolism and lipid metabolism alterations.In this review we will discuss the main risk factors strictly correlated with cardiac and vessels diseases, focusing on their pathogenesis, diagnosis, and treatments.
DNA methylation regulates TIGIT expression within the melanoma microenvironment, is prognostic for overall survival, and predicts progression-free survival in patients treated with anti-PD-1 immunotherapy
Authors: Niebel Dennis , Fröhlich Anne , Zarbl Romina , Fietz Simon , de Vos Luka , Vogt Timo J. , Dietrich Jörn , Sirokay Judith , Kuster Pia , Saavedra Gonzalo , Ramírez Valladolid Susana , Hoffmann Friederike , Strieth Sebastian , Landsberg Jennifer , Dietrich Dimo 
Published: April 2022

Abstract
Background
TIGIT is an immune checkpoint under investigation as therapeutic target. Understanding the regulation of TIGIT on an epigenetic level might support the development of companion biomarkers.

Methods
We correlated TIGIT DNA methylation of single CpG sites with gene expression, signatures of immune infiltrates and interferon-γ, and survival in melanoma. We further analyzed methylation levels in immune cell subsets, melanocyte and melanoma cell lines. TIGIT expression patterns within components of the melanoma microenvironment were analyzed by single cell sequencing. We used quantitative methylation-specific PCR, flow cytometry, and immunohistochemistry for correlations between expression and methylation and to assess the effect of pharmacological demethylation of melanoma cells treated with 5‐aza‐2‐deoxycytidine (decitabine). Finally, we investigated the association of patients’ survival with TIGIT mRNA and methylation.

Results
Depending on the sequence context of the analyzed CpG site, we found a cell type-specific TIGIT gene locus methylation pattern and significant correlations of TIGIT methylation with mRNA expression, an interferon γ signature, and distinct immune cell infiltrates, including TIGIT+ lymphocytes. We detected a melanoma cell-intrinsic TIGIT protein expression. Pharmacological demethylation of the A375 melanoma cell line led to a constitutive TIGIT expression. Low promoter flank methylation and high mRNA expression was associated with patients’ prognosis and predicted progression-free survival in patients treated with anti-PD-1 immunotherapy. A high TIGIT+ lymphocyte score was associated with better progression-free survival under anti-PD-1 immunotherapy.

Conclusions
Our data demonstrate an epigenetic regulation of TIGIT expression via DNA methylation within the melanoma microenvironment. TIGIT DNA methylation and expression may serve as predictive biomarkers in the context of immunotherapies in melanoma.
Evaluation of photoreceptor-directed fibroblasts derived from retinitis pigmentosa patients with defects in the EYS gene: a possible cost-effective cellular model for mechanism-oriented drug
Authors: Rai Dilip , Iwanami Masaki , Takahashi Yoriko , Komuta Yukari , Aoi Noriyuki , Umezawa Akihiro , Seko Yuko 
Published: April 2022

AbstractBackgroundThe most common gene responsible for autosomal recessive retinitis pigmentosa (RP) isEYS.The manner of decay of genetically defectiveEYSgene transcripts varies depending on the type of mutation using our cellular model, which consists of induced photoreceptor-directed fibroblasts from EYS-RP patients (EYS-RP cells). However, disease-specific profiles have not been clarified in EYS-RP cells. Herein we investigated comprehensive gene expression patterns and restoration of altered expression by low molecular weight molecules in EYS-RP cells.MethodsUsing induced photoreceptor-like cells byCRX,RAX,NeuroD,andOTX2, we employed qRT-PCR and DNA microarray analysis to compare expression levels of disease-related genes in EYS-RP cells. We investigated the effect of antiapoptotic or anti-endoplasmic reticulum (ER) stress/antioxidant reagents on the restoration of altered gene expression.ResultsExpression levels of phototransduction-related genes (blue opsin, rhodopsin, S-antigen, GNAT1, GNAT2) were lower in EYS-RP cells.CRYGDwas extracted by global gene expression analysis, as a downregulated, retina-related and apoptosis-, endoplasmic reticulum (ER) stress- or aging-related gene. Pathway enrichment analysis suggested that “complement and coagulation cascades,” “ECM-receptor interaction” and “PI3K-Akt signaling pathway” could be involved in EYS-RP-associated pathogenesis. Among the matching/overlapping genes involved in those pathways,F2Rwas suggested as an EYS-RP-associated gene. The downregulation ofCRYGDandF2Rwas completely restored by additional 4-PBA, an inhibitor of ER stress, and partially restored by metformin or NAC. In addition, 4-PBA normalized the expression level of cleaved caspase-3.ConclusionsOur cellular model may reflect the ER stress-mediated degenerative retina and serve as a pathogenesis-oriented cost-effective rescue strategy for RP patients.
Reconstructing the pulmonary niche with stem cells: a lung story
Authors: Varghese Barbie , Ling Zihan , Ren Xi 
Published: April 2022

AbstractThe global burden of pulmonary disease highlights an overwhelming need in improving our understanding of lung development, disease, and treatment. It also calls for further advances in our ability to engineer the pulmonary system at cellular and tissue levels. The discovery of human pluripotent stem cells (hPSCs) offsets the relative inaccessibility of human lungs for studying developmental programs and disease mechanisms, all the while offering a potential source of cells and tissue for regenerative interventions. This review offers a perspective on where the lung stem cell field stands in terms of accomplishing these ambitious goals. We will trace the known stages and pathways involved in in vivo lung development and how they inspire the directed differentiation of stem and progenitor cells in vitro.We will also recap the efforts made to date to recapitulate the lung stem cell niche in vitro via engineered cell–cell and cell-extracellular matrix (ECM) interactions.
Adult stem cell sources for skeletal and smooth muscle tissue engineering
Authors: Salemi Souzan , Prange Jenny A. , Baumgartner Valentin , Mohr-Haralampieva Deana , Eberli Daniel 
Published: April 2022

AbstractIntroductionTissue engineering is an innovative field with enormous developments in recent years. These advances are not only in the understanding of how stem cells can be isolated, cultured and manipulated but also in their potential for clinical applications. Thus, tissue engineering when applied to skeletal and smooth muscle cells is an area that bears high benefit for patients with muscular diseases or damage. Most of the recent research has been focused on use of adult stem cells. These cells have the ability to rejuvenate and repair damaged tissues and can be derived from different organs and tissue sources. Recently there are several different types of adult stem cells, which have the potential to function as a cell source for tissue engineering of skeletal and smooth muscles. However, to build neo‐tissues there are several challenges which have to be addressed, such as the selection of the most suitable stem cell type, isolation techniques, gaining control over its differentiation and proliferation process.ConclusionThe usage of adult stem cells for muscle engineering applications is promising. Here, we summarize the status of research on the use of adult stem cells for cell transplantation in experimental animals and humans. In particular, the application of skeletal and smooth muscle engineering in pre-clinical and clinical trials will be discussed.
Trust in COVID-19 policy among public health professionals in Israel during the first wave of the pandemic: a cross-sectional study
Authors: Zohar Tamar , Negev Maya , Sirkin Maia , Levine Hagai 
Published: April 2022

AbstractBackgroundThe COVID-19 pandemic has highlighted the important role of professionals in designing and communicating effective policies. The purpose of this study was to evaluate the level of trust in the COVID-19 national public health policy among public health professionals in Israel and its correlates during the first wave of the pandemic.MethodsA purposive sampling of public health professionals in Israel, through professional and academic public health networks (N = 112). The survey was distributed online during May 2020. Level of trust was measured by the mean of 18 related statements using a 5-point Likert scale, where 1 means not at all and 5 means to a very high extent, and grouped as low and high trust by median (2.75).ResultsA moderate level of trust in policy was found among professionals (Mean: 2.84, 95% Cl: [2.70, 2.98]). The level of trust among public health physicians was somewhat lower than among researchers and other health professionals (Mean: 2.66 vs. 2.81 and 2.96, respectively,p = 0.286), with a higher proportion expressing low trust (70% vs. 51% and 38%, respectively,p < 0.05). Participants with a low compared to high level of trust in policy were less supportive of the use of Israel Security Agency tools for contact tracing (Mean = 2.21 vs. 3.17,p < 0.01), and reported lower levels of trust in the Ministry of Health (Mean = 2.52 vs. 3.91,p < 0.01). A strong positive correlation was found between the level of trust in policy and the level of trust in the Ministry of Health (rs = 0.782,p < 0.01). Most professionals (77%) rated their involvement in decision making as low or not at all, and they reported a lower level of trust in policy than those with high involvement (Mean = 2.76 vs. 3.12,p < 0.05). Regarding trust in the ability of agencies to deal with the COVID-19 crisis, respondents reported high levels of trust in the Association of Public Health Physicians (80%) and in hospitals (79%), but very low levels of trust in the Minister of Health (5%).ConclusionsThis study shows that Israeli public health professionals exhibited moderate levels of trust in COVID-19 national public health policy and varied levels of trust in government agencies during the first wave of COVID-19. The level of trust in policy was lower among most of the participants who were not involved in decision making. The level of trust found is worrisome and should be monitored, because it may harm cooperation, professional response, and public trust. Professionals’ trust in policy-making during early stages of emergencies is important, and preemptive measures should be considered, such as involving professionals in the decision-making process, maintaining transparency of the process, and basing policy on scientific and epidemiological evidence.
The relationship between rigorous perception of one’s own body and self, unhealthy eating behavior and a high risk of anorexic readiness: a predictor of eating disorders in the group of female ballet dancers and artistic gymnasts at the beginning of their career
Authors: Leonkiewicz Magdalena , Wawrzyniak Agata 
Published: April 2022

Abstract
Background
A group that is particularly exposed to eating disorders are young sportswomen who practice aesthetic disciplines, for whom it is important to keep a slim figure. Hence, the purpose of the study was to present the assessment of perception of one’s own body and self as well as nutritional behavior in the group of ballet dancers and artistic gymnasts (BGA, n = 60) aged 10–12 against the background of the peer group (K, n = 60) and to determine the relationship between the studied elements, as well as anorexic readiness risk assessment to help diagnose premorbid stage of eating disorders with full symptoms.

Methods
Anthropometric measurements (height, body weight) and the assessment of adipose tissue were performed. Using a questionnaire, data on physical activity, perception of one's own body and self, and selected eating behaviors were collected.

Results
Underweight was observed in nearly half of the girls from the BGA group and the content of adipose tissue was significantly lower. Girls from the BGA group were characterized by overestimation of body size (p = 0.032), the need to improve their appearance/body (p = 0.025) and wanting to be the best in many areas of life (p = 0.002) significantly more often than in the K group. Moreover, they significantly more often limited the consumption of fats and carbohydrates (p = 0.044) and felt angry with themselves after too large of a meal (p = 0.050). It was shown that unhealthy eating behavior in the BGA group was significantly associated with rigorous self-perception (r = 0.42; p < 0.001). Students from the BGA group were more often exposed to a higher risk of anorexic readiness (p = 0.001). In a detailed analysis, it was found that eating behaviors, such as fasting, limiting the consumption of fats and carbohydrates, and avoiding eating under stress, were associated with feelings of dissatisfaction with oneself, the belief that appearance is extremely important in achieving life success and the need to improve appearance.

Conclusion
The obtained research results can be used as a source of information for specialists (including dietitians and psychologists), for the preparation of educational and repair programs in the group of ballet dancers or artistic gymnasts aged 10–12, including nutritional education and psychological care.
Clinical features and outcomes of four atypical hemolytic uremic syndrome cases at a single institution in Miyazaki Prefecture from 2015 to 2019
Authors: Kawano Noriaki , Abe Tomohiro , Ikeda Naoko , Nagahiro Yuri , Kawano Sayaka , Tochigi Taro , Nakaike Takashi , Yamashita Kiyoshi , Kubo Keisuke , Yamanaka Atsushi , Terasaka Sohshi , Marutsuka Kousuke , Mashiba Koichi , Kikuchi Ikuo , Shimoda Kazuya , Matsumoto Masanori , Ochiai Hidenobu 
Published: April 2022

Abstract
Background
Although atypical hemolytic uremic syndrome (aHUS) is a life-threatening clinical entity that was characterized by thrombotic microangiopathy (TMA) with the activation of the complement system and the efficient treatment of eculizumab, the clinical features of aHUS have been unclear because of the rare incidence.

Case presentation
We retrospectively analyzed 4 aHUS cases at a single institution during 2015–2019. Here, we presented 4 aHUS cases with renal transplantation (one case), influenza/acute interstitial pneumonia/disseminated intravascular coagulation (two cases), and severe fever with thrombocytopenia syndrome (one case), respectively. Initial clinical symptoms were microangiopathic hemolytic anemia (four cases), renal dysfunction (four cases), thrombocytopenia (four cases), and pulmonary hemorrhage (three cases) consisted with TMA features. Subsequent further examinations ruled out thrombotic thrombocytopenic purpura, Shiga toxin-producing E.coli-induced hemolytic uremic syndrome, and secondary TMA. Taken these findings together, we made the clinical diagnosis of aHUS. Furthermore, all cases also presented the high levels of plasma soluble C5b-9 (871.1 ng/ml, 1144.3 ng/ml, 929.2 ng/ml, and 337.5 ng/ml), suggesting persistent activation of complementary system. Regarding the treatment, plasma exchange (PE) (four cases) and eculizumab (two cases) therapy were administered for aHUS cases. Consequently, case 2 and case 4 were still alive with 768 days and 235 days, respectively. The other two cases were dead at 34 days and 13 days, respectively. Finally, although the previous reported genetic pathogenetic mutations were not detected in our cases, multiple genetic variants of complement factors were detected as CFH (H402Y, E936D), and THBD (A473V) in case 1, CFH (V62I, H402Y, V837I) in case 2, and CFH (H402Y, E 936D) and THBD (A473V) in case 3, CFH (V62I, H402Y, E936D) and THBD (473V) in case 4, respectively.

Conclusions
Because of still high mortality in our study, an urgent diagnosis of aHUS and subsequent immediate treatment including PE and eculizumab should be essential in clinical practice. Furthermore, the multiple genetic variants and the triggers may be related to one of the pathogenesis of aHUS. Thus, we assume that such a case-oriented study would be highly useful to the physicians who directly care for aHUS cases in clinical practice.
Remdesivir administration for Japanese COVID-19 patients undergoing maintenance hemodialysis: a retrospective observation with six case reports
Authors: Ito Jun , Kimura Moritsugu , Toya Tomoyuki , Isozumi Konomi , Kawaji Atsuro , Isozaki Yudai , Fukagawa Masafumi 
Published: April 2022

Abstract
Background
The mortality rate of novel coronaviral disease (COVID-19) patients undergoing dialysis is considerably higher than that of patients with normal kidney function. As of August 2021, only remdesivir has been approved in Japan as an antiviral drug for the treatment of COVID-19. However, in cases of kidney failure, remdesivir administration should be considered only if the therapeutic benefits outweigh the risks because of concern about the accumulation of its solubilizing excipient sulfobutylether-beta-cyclodextrin and subsequent renal tubular injury or liver injury. Recently, reports from overseas indicating the safety of the use of remdesivir for COVID-19 patients on dialysis have been gathered.

Case presentation
From June 2021, in our hospital, we started the administration of remdesivir to patients with moderate cases of COVID-19 undergoing hemodialysis, with careful consideration of the dosage and timing. Since then, six out of seven COVID-19 patients on hemodialysis who had received remdesivir have completely recovered. In a patient who died, the initial dose of remdesivir was administered after the case developed into severe COVID-19. All six patients who were able to start receiving remdesivir immediately at the stage of moderate COVID-19 recovered and were discharged without the need for mechanical ventilation. While, two out of four patients before May 2021 who had not been administered remdesivir at admission became severe, transferred to another tertiary hospital, and died. During and after remdesivir administration, no increase in serum transaminase to five times or more of the normal upper limit was observed in any of the cases. There were no other adverse drug reactions, such as infusion reaction, gastrointestinal symptoms, or anemia.

Conclusions
We were able to administer remdesivir to six Japanese patients with moderate COVID-19 on hemodialysis safely. It is expected that the safe use of remdesivir will bring an increase in treatment options for moderate cases of COVID-19 in dialysis patients as well as subsequent improvement in treatment outcomes. However, to confirm the efficacy and safety of such use, further careful observation in more cases is required.
Carrier RNA is a key factor affecting fully integrated short tandem repeats profiling in challenging forensic samples models
Authors: El-Shorbagy Haidan M. , El-Liethy Shereen S. , Moussa Mona K. , Elghor Akmal A. 
Published: April 2022

Abstract
Background
Short tandem repeats (STRs) are used today to provide discriminatory power for DNA fingerprinting. The present results showed that different factors may affect STR profiles in challenging samples including DNA quantity, DNA quality, PCR inhibitors and storage time. In the present study, blood stain samples were applied on two types of fabrics (black cotton and denim) to compare the efficiency of two different DNA-extraction methods (automated magnetic based beads method (EZ1), and manual organic method), with and without adding carrier RNA molecules, and to assess the quality and quantity of the extracted DNA and their capabilities for producing reportable STR-profiles in the presence of PCR inhibitors at two different storage times.

Results
Carrier RNA caused a dramatic increase in DNA recovery from black cotton or denim using EZ1 in contrast to organic method. EZ1 was found to be preferred than organic, especially when a time passed over, while organic method was preferred when samples are available in small quantities. In addition, using carrier RNA within the organic method steps showed no improvement in STR profiling. EZ1 with carrier RNA was preferred for bloodstained samples on fabrics with textile dyes (black dye or denim indigo), especially when stored for a long time.

Conclusions
Denim was found to be more problematic than black cotton due to presence of challenging inhibitors (indigo dye). DNA concentration, storage time and types of fabrics are key factors for choosing the appropriate extraction method for reportable STR profile. Using EZ1 with carrier RNA gives less dropout profile than not using it, or when using organic method even in presence or absence of carrier RNA. Anyway, innovation of more sensitive, more robust analytical protocols could result in a better understanding of these inhibitory samples.
Hyperbaric oxygen therapy as a conservative approach for osteoradionecrosis of the jaw in an osteoporotic patient receiving oral bisphosphonate therapy: a case report
Authors: Shudo Atsushi 
Published: April 2022

Abstract
Background
Osteoradionecrosis of the jaw (ORNJ) is a well-known chronic side effect of radiotherapy (RT) for head and neck malignancies. Osteonecrosis of the jaw (ONJ), similar pathology to ORNJ, may be induced by bisphosphonate (BP) therapy and is known as BP-related ONJ (BRONJ). Although differences exist between ORNJ and BRONJ in terms of clinical features and management methods, ONJ in a patient with history of both RT and BP therapy is categorized as ORNJ in the diagnostic criteria, despite the possibility that the ONJ may be affected by BP considering the pharmacology and mechanism of action. To date, management of ORNJ with a history of BP therapy has been scarcely discussed.

Case presentation
We report here our experience of serious ORNJ in an 82-year-old osteoporotic woman receiving oral BP therapy. She had undergone partial maxillectomy to treat left maxillary gingival cancer and had received RT of 60 Gy as postoperative treatment. She had a history of osteoporosis, for which she had been administered BP for 8 years and 5 months. A bony sequestrum 45 × 25 mm in size was found at the site of the mandibular ramus, and the clinical diagnosis was ORNJ. We administered hyperbaric oxygen therapy (HBOT), scheduled for 3–5 days per week in 2 courses, 35 times. After HBOT, we performed sequestrectomy avoiding invasive surgery such as mandibulectomy. After the surgical procedure the wound healed completely. Bone regeneration was confirmed by computed tomography postoperatively. There have been no signs of recurrence as of 4 years after the operation.

Conclusions
We undertook a multimodality approach with HBOT and conservative surgery and achieved a satisfactory outcome. HBOT may be worthy of consideration as a conservative approach for ORNJ in patients receiving BP therapy, leading to the possibility of avoiding invasive surgery such as mandibulectomy.