bluuebunny/crossref_metadata_2025 huggingface dataset:
Important Contributions to Reducing Nitrogen Oxide Emissions from Internal Combustion Engines
Authors: Buruiana Daniela Laura , Sachelarie Adrian , Butnaru Claudiu , Ghisman Viorica
Published: August 2021

Nitrogen oxides are considered significant pollutants because of their effects on ecosystems and human health. The amount of NOx emitted by internal combustion engines can be reduced, mostly by acting on the conditions in which combustion takes place, respectively by lowering the peak flame temperature, reducing the excess of oxygen, etc. The homogeneous charge compression ignition (HCCI) engine represents a new technology that can simultaneously reduce NOx emissions and fuel consumption. This article presents these benefits of the HCCI engine by comparing the emissions and fuel consumption of a monocylinder engine when it is operated in a conventional way, with spark ignition, with those obtained when the engine is running in the HCCI mode. Moreover, since engine simulation has become an important tool for investigating the HCCI process and for developing new control strategies for it, this was used in this study to determine the effects of the exhaust gas recirculation on the combustion quality, respectively, on emissions.
“We Thought We Were Prepared, but We Were Not”: Experiences from the Management of the Psychosocial Support Response during the COVID-19 Pandemic in Sweden. A Mixed-Methods Study
Authors: Hugelius Karin , Johansson Sara , Sjölin Helena
Published: August 2021

This study aimed to describe experiences of managing mental health and psychosocial activities during the first six months of the COVID-19 pandemic in Sweden. A national survey was answered by a non-probability sample of 340 involved in the psychosocial response. The psychosocial response operations met several challenges, mainly related to the diverse actors involved, lack of competence, and lack of preparations. Less than 20% of the participants had received specific training in the provision of psychosocial support during major incidents. The interventions used varied, and no large-scale interventions were used. The psychosocial response organizations were overwhelmed by the needs of health care staff and failed to meet the needs of patients and family members. An efficient and durable psychosocial response in a long-term crisis requires to be structured, planned and well-integrated into the overall pandemic response. All personnel involved need adequate and specific competence in evidence-based individual and large-scale interventions to provide psychosocial support in significant incidents. By increasing general awareness of mental wellbeing and psychosocial support amongst health professionals and their first-line managers, a more resilient health care system, both in everyday life and during major incidents and disasters, could be facilitated.
Psychometric Properties of the Schizophrenia Oral Health Profile: Preliminary Results
Authors: Denis Frédéric , Rouached Ines , Siu-Paredes Francesca , Delpierre Alexis , Amador Gilles , El-Hage Wissam , Rude Nathalie
Published: August 2021

The Schizophrenia Oral Health Profile questionnaire was developed to assess the oral health-related quality of life among individuals with schizophrenia based on their perceptions rather than from caregivers. A 5-point Likert scale was used to self-report on 42 items. In the present study, different analyses were conducted to determine the dimensional structure of the final scale: (1) inter-item correlation analysis and Cronbach’s α coefficient, (2) Rasch model analysis, (3) exploratory factor analysis and (4) confirmatory factor analysis. The final version of the Schizophrenia Oral Health Profile questionnaire consisted of 20 items and an internal structure composed of three dimensions: (1) emotions related to oral health, (2) oral pain and discomfort and (3) self-image, others’ views and the need for care. We showed that the difficulty and discrimination indices of each of the 20 selected items were acceptable according to the Rasch model, as well as their inter-item and inter-score correlations (α = 0.875). The psychometric study of the Schizophrenia Oral Health Profile questionnaire is still in progress to investigate reproducibility, sensitivity to change and external structure.
Diagnostic Concordance between Optical Coherence Tomography and Histological Investigations for Immune-Mediated Desquamative Gingivitis: Observational Study
Authors: Panzarella Vera , Bartolone Alessia , Coniglio Rita , Rodolico Vito , Maniscalco Laura , Capocasale Giorgia , Iurato Carbone Martina , Campisi Giuseppina
Published: August 2021

Desquamative gingivitis (DG) denotes a heterogeneous immune-mediated disease for which early diagnosis represents a great challenge. The main aim of this study is to validate diagnostic concordance between specific Optical Coherence Tomography (OTC) patterns for DG related to oral Lichen Planus (OLP), Pemphigus Vulgaris (PV), and Mucous Membrane Pemphigoid (MMP) and definitive histological diagnosis. Forty-three patients with suspected immune-mediated DGs, were progressively recruited. Before biopsy, an OCT preliminary evaluation was performed using specific pre-determined OCT diagnostic patterns (i.e., morphology and localization of blisters, status of the basal membrane, epithelial thickness, presence/absence of acantholytic cells into blister and/or inflammatory infiltrate) related to OLP, PV and MMP. After histological confirmation, OCT and histological diagnoses were compared. Using pre-determined patterns, OCT diagnoses of DGs were: 22 (51%) OLP, of which 11 (26%) were with the bullous variant, 4 (9%) PV and 6 (14%) MMP. The same diagnoses were found by histological investigations (with the main OCT discriminatory potential for the bullous variant of OLP). The concordance between the two diagnostic methods was confirmed by the Fisher exact test (p-value < 0.01). These specific OCT patterns show a diagnostic reliability in 100% of the cases investigated, suggesting their accuracy to support the complex diagnosis and management of immune-mediated DGs.
The Critical Role of Coping Strategies in Moderating Loneliness and Quality of Life: Parallel and Unique Processes among Transgender and Heterosexual Cisgender People in Pakistan
Authors: Batool Samiya , Rowland David L.
Published: August 2021

Groups marginalized and/or isolated by minority status—including transgender individuals—are at significant risk for loneliness and diminished quality of life (QoL), effects that can be mitigated to some extent by coping styles. In this study, we examined the relationships among coping styles, loneliness, and QoL outcomes in a marginalized but understudied gender minority group, namely, 200 transgender individuals living in communities in an emerging/developing non-Western geo-cultural region of South-Central Asia (Pakistan), comparing them against a reference group of 100 heterosexual cisgender individuals. Results indicated strong relationships among coping styles, loneliness, and QoL in both transgender and cisgender groups. Moderating variable analysis revealed that coping skills—whether adaptive or maladaptive—help explain differences in loneliness and QoL not only between trans- and cis-gender individuals, but also within just the transgender group. The implications of these findings for intervention strategies to improve QoL among transgender populations are discussed, with reference to both the specific context within Pakistan and the larger context of transgender marginalization within many developing/emerging countries.
Can Exercise Help Regulate Blood Pressure and Improve Functional Capacity of Older Women with Hypertension against the Deleterious Effects of Physical Inactivity?
Authors: Leitão Luis , Marocolo Moacir , Souza Hiago L. R. de , Arriel Rhai André , Vieira João Guilherme , Mazini Mauro , Louro Hugo , Pereira Ana
Published: August 2021

Background: Sedentarism and inactivity are risk factors for the development of hypertension. Thus, the prevention of the natural process of biological and physiological aging of older women through physical exercise results in higher benefits in preventing cardiovascular diseases and can be a key factor for its treatment. Multicomponent exercise (METP) is a training method that may help older women with hypertension by improving their quality of life and their response to treatment. Methods: Twenty-eight older Caucasian women with hypertension (66.7 ± 5.3 years, 1.59 ± 0.11 m) performed a supervised METP program of nine months followed by three months of detraining (DT), and seventeen older women (68.2 ± 4.7 years, 1.57 ± 0.16 cm) with hypertension maintained their daily routine, without exercise. Blood pressure (BP), resting heart rate, and functional capacity (FC) were evaluated at the beginning and at the end of the program, and after three months of DT. Results: The ME program improved (p < 0.05) systolic BP (−5.37%), diastolic BP (−5.67%), resting heart rate (−7.8%), agility (9.8%), lower body strength (27.8%), upper body strength (10.0%), and cardiorespiratory capacity (8.6%). BP and FC deteriorated after the DT period (p < 0.05). Conclusion: Nine months of multicomponent exercise were sufficient to improve functional capacity and promote benefits in blood pressure, although was not sufficient to allow BP to reach the normal values of older women. The three month DT period without exercise caused the reversal of BP improvements but maintained the functional capacity of older women.
Impact of COVID-19 on Czech Dentistry: A Nationwide Cross-Sectional Preliminary Study among Dentists in the Czech Republic
Authors: Schmidt Jan , Waldova Eliska , Balkova Stepanka , Suchanek Jakub , Smucler Roman
Published: August 2021

This work evaluates the impact of the COVID-19 pandemic on Czech dentistry from March 2020 to March 2021. The assessment was based on questionnaires filled out by 3674 Czech dentists representing 42.6% of practicing dentists in the country. During March–May, 2020 (the first COVID-19 wave), 90.7% of dental practices remained open; however, only 22.8% of the practices continued to operate with no changes, 46.5% had fewer patients, 21.4% treated only acute cases, and 3.8% were closed. During September 2020–May 2021 (the second wave of COVID-19), 96.1% of dental practices remained open, 60.8% operated with no changes, 34.5% had fewer patients, 0.8% treated only acute cases, and 0.5% were closed. The reasons leading to the closure of Czech dental practices during the whole pandemic were a shortage of personal protective equipment (50.5%), a COVID-19 outbreak in the workplace (24.5%), fear of a possible self-infection (24.0%), and quarantine (20.5%). The time range of Czech dental practices closure during the whole pandemic was: 1–2 weeks (49.9%), 2–4 weeks (21.2%), and >1 month (0.8%). The greatest professional difficulties of Czech dentists during the pandemic were crisis operating management (55%), health safety and hygiene concerns (21%), shortage of personal protective equipment (21%), and difficulty working with the protective equipment (15%). In addition, 47.3% of dentists also observed a declining interest in preventive dental care, and 16.9% of them observed worse oral care of patients. These results show that despite the lack of protective equipment, dental care was maintained throughout the pandemic. Additionally, the pandemic negatively affected the patients’ approach to dental care, indicating a deterioration in oral health as a possible delayed outcome of the COVID-19 pandemic.
Health Effects Related to Wind Turbine Sound: An Update
Authors: van Kamp Irene , van den Berg Frits
Published: August 2021

Commissioned by the Swiss Federal Office for the Environment, an update of an earlier narrative review was prepared for the literature published between 2017 and mid-2020 about the effects of wind turbine sound on the health of local residents. Specific attention was hereby given to the health effects of low-frequency sound and infrasound. The Netherlands Institute for Public Health and the Environment and Mundonovo sound research collected the scientific literature on the effect of wind turbines on annoyance, sleep disturbance, cardiovascular disease, and metabolic effects, as well as mental and cognitive impacts. It also investigated what is known about annoyance from visual aspects of wind turbines and other non-acoustic factors, such as the local decision-making process. From the literature study, annoyance again came forward as the most important consequence of sound: the louder the sound (in dB) of wind turbines, the stronger the annoyance response was. The literature did not show that “low-frequency sound” (sound with a low pitch) results in extra annoyance on top of normal sound. Results of scientific research for other health effects are either not available or inconsistent, and we can conclude that a clear association with wind turbine related sound levels cannot be confirmed. There is evidence that long-term effects are related to the annoyance people experience. These results confirm earlier conclusions. There is increasing evidence that annoyance is lower when people can participate in the siting process. Worries of residents should be addressed in an early stage, by involving them in the process of planning and decision making.
Effect of Bilateral Quadratus Lumborum Block Type I on Patient Satisfaction and Incidence of Chronic Postsurgical Pain Following Cesarean Section-A Randomized Controlled Trial
Authors: Mieszkowski Marcin , Janiak Marek , Borys Michał , Radkowski Paweł , Mieszkowska Marta , Zhalniarovich Yauheni , Onichimowski Dariusz
Published: August 2021

Background: Quadratus lumborum block (QLB) provides a reduction in pain scores and opioid consumption after cesarean section (CS). Intrathecal morphine (ITM) is still considered as the gold standard of acute postoperative pain therapy, but it does have some significant side effects. The aim of this clinical study was to evaluate whether performing the quadratus lumborum block type I in patients undergoing CS would be associated with an increased satisfaction of pain therapy and a decreased incidence of chronic postsurgical pain (CPSP). Methods: Sixty patients scheduled for elective CS were enrolled. All patients received spinal anesthesia and were randomly allocated to either the QLB group (received bilateral quadratus lumborum block type I with the use of 24 m mL 0.375% ropivacaine) or the control group (received no block). The level of satisfaction was evaluated using a three-step scale and the answers provided in a questionnaire regarding the patients’ satisfaction with the method of postoperative pain treatment in the first 48 h. After a 6-month period, all patients were interviewed to evaluate the incidence and possible severity of CPSP. Results: Satisfaction scores were significantly lower in the QLB group than in the control group (p = 0.0000). There were no significant differences between the QLB and control groups regarding the occurrence of chronic postsurgical pain after 6 months following CS (p = 0.102). No statistical differences between the groups were recorded when we compared the results of the questionnaire after a period of 48 h from CS (the number of participants were limited in number). Conclusions: QLB type I is an analgetic option that increased the satisfaction of parturients with pain therapy after CS compared to patients who did not receive the block, and there is a tendency for a lower incidence of CPSP.
Patients’ Access to Their Psychiatric Notes: Current Policies and Practices in Sweden
Authors: Bärkås Annika , Scandurra Isabella , Rexhepi Hanife , Blease Charlotte , Cajander Åsa , Hägglund Maria
Published: August 2021

Patients’ access to electronic health records (EHRs) is debated worldwide, and access to psychiatry records is even more criticized. There is a nationwide service in Sweden which offers all citizens the opportunity to read their EHR, including clinical notes. This study aims to explore Swedish national and local policy regulations regarding patients’ access to their psychiatric notes and describe to what extent patients currently are offered access to them. The rationale behind the study is that current policies and current practices may differ between the 21 self-governing regions, although there is a national regulation. We gathered web-based information from policy documents and regulations from each region’s website. We also conducted key stakeholder interviews with respondents from the regions and cross-regional private care providers, using a qualitative approach. The results show that 17 of 21 regions share psychiatric notes with patients, where forensic psychiatric care was the most excluded psychiatric care setting. All private care providers reported that they mainly follow the regions’ guidelines. Our findings show that regional differences concerning sharing psychiatric notes persist, despite Swedish regulations and a national policy that stipulates equal care for everyone. The differences, however, appear to have decreased over time, and we report evidence that the regions are moving toward increased transparency for psychiatry patients.
Exploring Weight Stigma in Saudi Arabia: A Nationwide Cross-Sectional Study
Authors: Althumiri Nora A. , Basyouni Mada H. , AlMousa Norah , AlJuwaysim Mohammed F. , Alhamdan Adel A. , Al-Qahtani Faisal Saeed , BinDhim Nasser F. , Alqahtani Saleh A.
Published: August 2021

Background: Weight stigma (WS) in the Middle East, especially in Saudi Arabia, is widely ignored. People with obesity are blamed for their weight, and there is a common perception that weight stigmatization is justifiable and may motivate individuals to adopt healthier behaviors. The authors of this study aimed to explore WS prevalence and factors associated with WS in a large nationwide study of Saudi Arabian adults. Methods: This study was a nationwide cross-sectional survey conducted via phone interviews in June 2020. A proportional quota-sampling technique was adopted to obtain equal distributions of participants by age and sex across the 13 regions of Saudi Arabia. In total, 6239 people were contacted, and 4709 (75.48%) responded and completed the interview. The authors of the study collected data about WS using the Arabic Weight Self-Stigma Questionnaire (WSSQ), BMI, smoking, nutritional knowledge, bariatric surgery, risk of depression, and demographic variables. Results: Participants had a mean age of 36.4 ± 13.5 (18–90), and 50.1% were female. The prevalence of higher WS was 46.4%. Among other risk factors, there was a significant association between WS and obesity (odds ratio (OR): 3.93; 95% CI: 2.83–5.44; p < 0.001), waterpipe smoking (OR: 1.80; 95% CI: 1.20–2.69; p < 0.001), bariatric surgery (OR: 2.07; 95% CI: 1.53–2.81; p < 0.001), and risk of depression (OR: 1.68; 95% CI: 1.36–2.09; p < 0.001). Conclusion: This was the first study to explore WS and its associated factors among adults in a community setting in Saudi Arabia. This study revealed some risk factors associated with WS that may help to identify people at risk of WS and to develop interventions to reduce WS, such as improving nutritional knowledge, correcting the ideas about bariatric surgery and obesity in general, and ceasing waterpipe smoking.
Pre-Hypertension and Its Determinants in Healthy Young Adults: Analysis of Data from the Korean National Health and Nutrition Examination Survey VII
Authors: Jang Insil
Published: August 2021

The purpose of this cross-sectional study was to identify risk factors in the normotensive and pre-hypertensive group based on the blood pressure results of healthy young adults from the Korean National Health and Nutrition Examination Survey 2018. The participants were 2225 healthy young adults between the ages of 19 and under 45, excluding those with a diagnosis of hypertension or taking antihypertensive medications. Of the 2225 participants, the normotensive group was 1498 (67.3%) and the pre-hypertensive group 727 (32.7%). Determinants of pre-hypertension were analyzed using multiple logistic regression based on a complex sample design. Factors related to pre-hypertension in young adults were age, smoking, waist circumference, diabetes, anemia, cholesterol levels including HDL cholesterol, and uric acid levels. Pre-hypertension is a pre-stage that can prevent the morbidity of hypertension through lifestyle control, so its management is very important. Furthermore, a young adult is a stage in the growth and development of human beings, in which lifestyles such as healthy behaviors, eating habits, and exercise are fixed. Therefore, it is very important to improve lifestyles such as diet, exercise, and smoking cessation and to control risk factors in young adults who are at the pre-hypertension stage for health promotion. Continuous health examinations should be conducted for young adults, and education that can be practiced based on clinical data through this should be implemented for community health.
An Overview of Neonatal Lupus with Anti-Ro Characteristics
Authors: Gryka-Marton Malgorzata , Szukiewicz Dariusz , Teliga-Czajkowska Justyna , Olesinska Marzena
Published: August 2021

Neonatal lupus erythematosus (NLE) is a syndrome of clinical symptoms observed in neonates born to mothers with antibodies to soluble antigens of the cell nucleus. The main factors contributing to the pathogenesis of this disease are anti-Sjögren Syndrome A (anti-SS-A) antibodies, known as anti-Ro, and anti-Sjögren Syndrome B (anti-SS-B) antibodies, known as anti-La. Recent publications have also shown the significant role of anti-ribonucleoprotein antibodies (anti-RNP). Seropositive mothers may have a diagnosed rheumatic disease or they can be asymptomatic without diagnosis at the time of childbirth. These antibodies, after crossing the placenta, may trigger a cascade of inflammatory reactions. The symptoms of NLE can be divided into reversible symptoms, which concern skin, hematological, and hepatological changes, but 2% of children develop irreversible symptoms, which include disturbances of the cardiac stimulatory and conduction system. Preconceptive care and pharmacological prophylaxis of NLE in the case of mothers from the risk group are important, as well as the monitoring of the clinical condition of the mother and fetus throughout pregnancy and the neonatal period. The aim of this manuscript is to summarize the previous literature and current state of knowledge about neonatal lupus and to discuss the role of anti-Ro in the inflammatory process.
Muscimol Directly Activates the TREK-2 Channel Expressed in GABAergic Neurons through Its N-Terminus
Authors: Kim Eun-Jin , Kwon Oh-Sang , Hur Chang-Gi , Nyiramana Marie Merci , Lee Dong-Kun , Hong Seong-Geun , Han Jaehee , Kang Dawon
Published: August 2021

The two-pore domain K+ (K2P) channel, which is involved in setting the resting membrane potential in neurons, is an essential target for receptor agonists. Activation of the γ-aminobutyric acid (GABA) receptors (GABAAR and GABABR) reduces cellular excitability through Cl- influx and K+ efflux in neurons. Relatively little is known about the link between GABAAR and the K+ channel. The present study was performed to identify the effect of GABAR agonists on K2P channel expression and activity in the neuroblastic B35 cells that maintain glutamic acid decarboxylase (GAD) activity and express GABA. TASK and TREK/TRAAK mRNA were expressed in B35 cells with a high level of TREK-2 and TRAAK. In addition, TREK/TRAAK proteins were detected in the GABAergic neurons obtained from GABA transgenic mice. Furthermore, TREK-2 mRNA and protein expression levels were markedly upregulated in B35 cells by GABAAR and GABABR agonists. In particular, muscimol, a GABAAR agonist, significantly increased TREK-2 expression and activity, but the effect was reduced in the presence of the GABAAR antagonist bicuculine or TREK-2 inhibitor norfluoxetine. In the whole-cell and single-channel patch configurations, muscimol increased TREK-2 activity, but the muscimol effect disappeared in the N-terminal deletion mutant. These results indicate that muscimol directly induces TREK-2 activation through the N-terminus and suggest that muscimol can reduce cellular excitability by activating the TREK-2 channel and by inducing Cl- influx in GABAergic neurons.
Ptk7 Is Dynamically Localized at Neural Crest Cell–Cell Contact Sites and Functions in Contact Inhibition of Locomotion
Authors: Grund Anita , Till Katharina , Giehl Klaudia , Borchers Annette
Published: August 2021

Neural crest (NC) cells are highly migratory cells that contribute to various vertebrate tissues, and whose migratory behaviors resemble cancer cell migration and invasion. Information exchange via dynamic NC cell–cell contact is one mechanism by which the directionality of migrating NC cells is controlled. One transmembrane protein that is most likely involved in this process is protein tyrosine kinase 7 (PTK7), an evolutionary conserved Wnt co-receptor that is expressed in cranial NC cells and several tumor cells. In Xenopus, Ptk7 is required for NC migration. In this study, we show that the Ptk7 protein is dynamically localized at cell–cell contact zones of migrating Xenopus NC cells and required for contact inhibition of locomotion (CIL). Using deletion constructs of Ptk7, we determined that the extracellular immunoglobulin domains of Ptk7 are important for its transient accumulation and that they mediate homophilic binding. Conversely, we found that ectopic expression of Ptk7 in non-NC cells was able to prevent NC cell invasion. However, deletion of the extracellular domains of Ptk7 abolished this effect. Thus, Ptk7 is sufficient at protecting non-NC tissue from NC cell invasion, suggesting a common role of PTK7 in contact inhibition, cell invasion, and tissue integrity.
In Situ Hydroxyapatite Synthesis Enhances Biocompatibility of PVA/HA Hydrogels
Authors: Chocholata Petra , Kulda Vlastimil , Dvorakova Jana , Supova Monika , Zaloudkova Margit , Babuska Vaclav
Published: August 2021

Bone tissue engineering tries to simulate natural behavior of hard tissues. This study aimed to produce scaffolds based on polyvinyl alcohol (PVA) and hyaluronic acid (HA) with hydroxyapatite (HAp) incorporated in two different ways, by in situ synthesis and physical mixing of pre-prepared HAp. In situ synthesis resulted in calcium deficient form of HAp with lower crystallinity. The proliferation of human osteoblast-like cells MG-63 proved to be better in the scaffolds with in situ synthesized HAp compared to those with physically mixed pre-prepared HAp. For scaffolds with PVA/HA/HAp ratio 3:1:2, there was significantly higher initial adhesion (p = 0.0440), as well as the proliferation in the following days (p < 0.001). It seemed to be advantageous improve the properties of the scaffold by in situ synthesizing of HAp directly in the organic matrix.
The Role of Noncoding RNA in the Pathophysiology and Treatment of Premature Ovarian Insufficiency
Authors: Pankiewicz Katarzyna , Laudański Piotr , Issat Tadeusz
Published: August 2021

Premature ovarian insufficiency (POI) is defined as a loss of ovarian function before the age of 40 years, with a prevalence rate estimated at approximately 1%. It causes infertility and is related to serious long-term health consequences, including reduced life expectancy, increased cardiovascular risk, decreased bone mineral density and neurological disorders. There is currently no effective therapy for POI that is widely available in clinical practice; therefore, the treatment of patients with POI is based on hormone replacement therapy. One of the recent advances in the understanding of the pathophysiology of POI has been the role of microRNAs (miRNAs) and other noncoding RNAs (ncRNAs) in the disease. Moreover, intensive research on human folliculogenesis and reproductive biology has led to the development of novel promising therapeutic strategies with the use of exosomal miRNAs derived from mesenchymal stem cells to restore ovarian function in POI patients. This narrative review focuses on the new studies concerning the role of ncRNAs in the pathogenesis of POI, together with their potential as biomarkers of the disease and targets for therapy.
Altered DNA Methylation Profiles in SF3B1 Mutated CLL Patients
Authors: Pacholewska Alicja , Grimm Christina , Herling Carmen D. , Lienhard Matthias , Königs Anja , Timmermann Bernd , Altmüller Janine , Mücke Oliver , Reinhardt Hans Christian , Plass Christoph , Herwig Ralf , Hallek Michael , Schweiger Michal R.
Published: August 2021

Mutations in splicing factor genes have a severe impact on the survival of cancer patients. Splicing factor 3b subunit 1 (SF3B1) is one of the most frequently mutated genes in chronic lymphocytic leukemia (CLL); patients carrying these mutations have a poor prognosis. Since the splicing machinery and the epigenome are closely interconnected, we investigated whether these alterations may affect the epigenomes of CLL patients. While an overall hypomethylation during CLL carcinogenesis has been observed, the interplay between the epigenetic stage of the originating B cells and SF3B1 mutations, and the subsequent effect of the mutations on methylation alterations in CLL, have not been investigated. We profiled the genome-wide DNA methylation patterns of 27 CLL patients with and without SF3B1 mutations and identified local decreases in methylation levels in SF3B1mut CLL patients at 67 genomic regions, mostly in proximity to telomeric regions. These differentially methylated regions (DMRs) were enriched in gene bodies of cancer-related signaling genes, e.g., NOTCH1, HTRA3, and BCL9L. In our study, SF3B1 mutations exclusively emerged in two out of three epigenetic stages of the originating B cells. However, not all the DMRs could be associated with the methylation programming of B cells during development, suggesting that mutations in SF3B1 cause additional epigenetic aberrations during carcinogenesis.
The Impact of Probiotics on Intestinal Mucositis during Chemotherapy for Colorectal Cancer: A Comprehensive Review of Animal Studies
Authors: Miknevicius Povilas , Zulpaite Ruta , Leber Bettina , Strupas Kestutis , Stiegler Philipp , Schemmer Peter
Published: August 2021

Colorectal cancer (CRC) is the second most commonly diagnosed cancer in females (incidence 16.4/10,000) and the third in males (incidence 23.4/10,000) worldwide. Surgery, chemotherapy (CTx), radiation therapy (RTx), or a combined treatment of those are the current treatment modalities for primary CRC. Chemotherapeutic drug-induced gastrointestinal (GIT) toxicity mainly presents as mucositis and diarrhea. Preclinical studies revealed that probiotic supplementation helps prevent CTx-induced side effects by reducing oxidative stress and proinflammatory cytokine production and promoting crypt cell proliferation. Moreover, probiotics showed significant results in preventing the loss of body weight (BW) and reducing diarrhea. However, further clinical studies are needed to elucidate the exact doses and most promising combination of strains to reduce or prevent chemotherapy-induced side effects. The aim of this review is to overview currently available literature on the impact of probiotics on CTx-induced side effects in animal studies concerning CRC treatment and discuss the potential mechanisms based on experimental studies’ outcomes.
PRC2 Regulated Atoh8 Is a Regulator of Intestinal Microfold Cell (M Cell) Differentiation
Authors: George Joel Johnson , Martin-Diaz Laura , Ojanen Markus J. T. , Gasa Rosa , Pesu Marko , Viiri Keijo
Published: August 2021

Intestinal microfold cells (M cells) are a dynamic lineage of epithelial cells that initiate mucosal immunity in the intestine. They are responsible for the uptake and transcytosis of microorganisms, pathogens, and other antigens in the gastrointestinal tract. A mature M cell expresses a receptor Gp2 which binds to pathogens and aids in the uptake. Due to the rarity of these cells in the intestine, their development and differentiation remain yet to be fully understood. We recently demonstrated that polycomb repressive complex 2 (PRC2) is an epigenetic regulator of M cell development, and 12 novel transcription factors including Atoh8 were revealed to be regulated by the PRC2. Here, we show that Atoh8 acts as a regulator of M cell differentiation; the absence of Atoh8 led to a significant increase in the number of Gp2+ mature M cells and other M cell-associated markers such as Spi-B and Sox8. In vitro organoid analysis of RankL treated organoid showed an increase of mature marker GP2 expression and other M cell-associated markers. Atoh8 null mice showed an increase in transcytosis capacity of luminal antigens. An increase in M cell population has been previously reported to be detrimental to mucosal immunity because some pathogens like orally acquired prions have been able to exploit the transcytosis capacity of M cells to infect the host; mice with an increased population of M cells are also susceptible to Salmonella infections. Our study here demonstrates that PRC2 regulated Atoh8 is one of the factors that regulate the population density of intestinal M cell in the Peyer’s patch.
Brain Plasticity in Humans and Model Systems: Advances, Challenges, and Future Directions
Authors: Bonfanti Luca , Charvet Christine J.
Published: August 2021

Plasticity, and in particular, neurogenesis, is a promising target to treat and prevent a wide variety of diseases (e.g., epilepsy, stroke, dementia). There are different types of plasticity, which vary with age, brain region, and species. These observations stress the importance of defining plasticity along temporal and spatial dimensions. We review recent studies focused on brain plasticity across the lifespan and in different species. One main theme to emerge from this work is that plasticity declines with age but that we have yet to map these different forms of plasticity across species. As part of this effort, we discuss our recent progress aimed to identify corresponding ages across species, and how this information can be used to map temporal variation in plasticity from model systems to humans.
Network Pharmacology Study on Morus alba L. Leaves: Pivotal Functions of Bioactives on RAS Signaling Pathway and Its Associated Target Proteins against Gout
Authors: Oh Ki Kwang , Adnan Md. , Cho Dong Ha
Published: August 2021

M. alba L. is a valuable nutraceutical plant rich in potential bioactive compounds with promising anti-gouty arthritis. Here, we have explored bioactives, signaling pathways, and key proteins underlying the anti-gout activity of M. alba L. leaves for the first-time utilizing network pharmacology. Bioactives in M. alba L. leaves were detected through GC-MS (Gas Chromatography-Mass Spectrum) analysis and filtered by Lipinski’s rule. Target proteins connected to the filtered compounds and gout were selected from public databases. The overlapping target proteins between bioactives-interacted target proteins and gout-targeted proteins were identified using a Venn diagram. Bioactives-Proteins interactive networking for gout was analyzed to identify potential ligand-target and visualized the rich factor on the R package via the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway on STRING. Finally, a molecular docking test (MDT) between bioactives and target proteins was analyzed via AutoDock Vina. Gene Set Enrichment Analysis (GSEA) demonstrated that mechanisms of M. alba L. leaves against gout were connected to 17 signaling pathways on 26 compounds. AKT1 (AKT Serine/Threonine Kinase 1), γ-Tocopherol, and RAS signaling pathway were selected as a hub target, a key bioactive, and a hub signaling pathway, respectively. Furthermore, three main compounds (γ-Tocopherol, 4-Dehydroxy-N-(4,5-methylenedioxy-2-nitrobenzylidene) tyramine, and Lanosterol acetate) and three key target proteins—AKT1, PRKCA, and PLA2G2A associated with the RAS signaling pathway were noted for their highest affinity on MDT. The identified three key bioactives in M. alba L. leaves might contribute to recovering gouty condition by inactivating the RAS signaling pathway.
Reconnoitering the Role of Long-Noncoding RNAs in Hypertrophic Cardiomyopathy: A Descriptive Review
Authors: Shahzadi Syeda K. , Naidoo Nerissa , Alsheikh-Ali Alawi , Rizzo Manfredi , Rizvi Ali A. , Santos Raul D. , Banerjee Yajnavalka
Published: August 2021

Hypertrophic cardiomyopathy (HCM) is the most common form of hereditary cardiomyopathy. It is characterized by an unexplained non-dilated hypertrophy of the left ventricle with a conserved or elevated ejection fraction. It is a genetically heterogeneous disease largely caused by variants of genes encoding for cardiac sarcomere proteins, including MYH7, MYBPC3, ACTC1, TPM1, MYL2, MYL3, TNNI3, and TNNT23. Preclinical evidence indicates that the enhanced calcium sensitivity of the myofilaments plays a key role in the pathophysiology of HCM. Notably, this is not always a direct consequence of sarcomeric variations but may also result from secondary mutation-driven alterations. Long non-coding RNAs (lncRNAs) are a large class of transcripts ≥200 nucleotides in length that do not encode proteins. Compared to coding mRNAs, most lncRNAs are not as well-annotated and their functions are greatly unexplored. Nevertheless, increasing evidence shows that lncRNAs are involved in a variety of biological processes and diseases including HCM. Accumulating evidence has indicated that lncRNAs are dysregulated in HCM, and closely related to sarcomere construction, calcium channeling and homeostasis of mitochondria. In this review, we have summarized the known regulatory and functional roles of lncRNAs in HCM.
ZFP36L2 Role in Thyroid Functionality
Authors: Albano Francesco , Tucci Valeria , Blackshear Perry J. , Reale Carla , Roberto Luca , Russo Filomena , Marotta Pina , Porreca Immacolata , Colella Marco , Mallardo Massimo , de Felice Mario , Ambrosino Concetta
Published: August 2021

Thyroid hormone levels are usually genetically determined. Thyrocytes produce a unique set of enzymes that are dedicated to thyroid hormone synthesis. While thyroid transcriptional regulation is well-characterized, post-transcriptional mechanisms have been less investigated. Here, we describe the involvement of ZFP36L2, a protein that stimulates degradation of target mRNAs, in thyroid development and function, by in vivo and in vitro gene targeting in thyrocytes. Thyroid-specific Zfp36l2-/- females were hypothyroid, with reduced levels of circulating free Thyroxine (cfT4) and Triiodothyronine (cfT3). Their hypothyroidism was due to dyshormonogenesis, already evident one week after weaning, while thyroid development appeared normal. We observed decreases in several thyroid-specific transcripts and proteins, such as Nis and its transcriptional regulators (Pax8 and Nkx2.1), and increased apoptosis in Zfp36l2-/- thyroids. Nis, Pax8, and Nkx2.1 mRNAs were also reduced in Zfp36l2 knock-out thyrocytes in vitro (L2KO), in which we confirmed the increased apoptosis. Finally, in L2KO cells, we showed an altered response to TSH stimulation regarding both thyroid-specific gene expression and cell proliferation and survival. This result was supported by increases in P21/WAF1 and p-P38MAPK levels. Mechanistically, we confirmed Notch1 as a target of ZFP36L2 in the thyroid since its levels were increased in both in vitro and in vivo models. In both models, the levels of Id4 mRNA, a potential inhibitor of Pax8 activity, were increased. Overall, the data indicate that the regulation of mRNA stability by ZFP36L2 is a mechanism that controls the function and survival of thyrocytes.
circBTBD7 Promotes Immature Porcine Sertoli Cell Growth through Modulating miR-24-3p/MAPK7 Axis to Inactivate p38 MAPK Signaling Pathway
Authors: Bian Qiao , Chen Bin , Weng Bo , Chu Dan , Tang Xiangwei , Yan Saina , Yin Yanfei , Ran Maoliang
Published: August 2021

Sertoli cells are the crucial coordinators to guarantee normal spermatogenesis and male fertility. Although circular RNAs (circRNAs) exhibit developmental-stage-specific expression in porcine testicular tissues and have been thought of as potential regulatory molecules in spermatogenesis, their functions and mechanisms of action remain largely unknown, especially in domestic animals. A novel circBTBD7 was identified from immature porcine Sertoli cells using reverse transcription PCR, Sanger sequencing, and fluorescence in situ hybridization assays. Functional assays illustrated that circBTBD7 overexpression promoted cell cycle progression and cell proliferation, as well as inhibited cell apoptosis in immature porcine Sertoli cells. Mechanistically, circBTBD7 acted as a sponge for the miR-24-3p and further facilitated its target mitogen-activated protein kinase 7 (MAPK7) gene. Overexpression of miR-24-3p impeded cell proliferation and induced cell apoptosis, which further attenuated the effects of circBTBD7 overexpression. siRNA-induced MAPK7 deficiency resulted in a similar effect to miR-24-3p overexpression, and further offset the effects of miR-24-3p inhibition. Both miR-24-3p overexpression and MAPK7 knockdown upregulated the p38 phosphorylation activity. The SB202190 induced the inhibition of p38 MAPK pathway and caused an opposite effect to that of miR-24-3p overexpression and MAPK7 knockdown. Collectively, circBTBD7 promotes immature porcine Sertoli cell growth through modulating the miR-24-3p/MAPK7 axis to inactivate the p38 MAPK signaling pathway. This study expanded our knowledge of noncoding RNAs in porcine normal spermatogenesis through deciding the fate of Sertoli cells.
Genome-Wide Identification of ARF Transcription Factor Gene Family and Their Expression Analysis in Sweet Potato
Authors: Pratt Isaac Seth , Zhang Baohong
Published: August 2021

Auxin response factors (ARFs) are a family of transcription factors that play an important role of auxin regulation through their binding with auxin response elements. ARF genes are represented by a large multigene family in plants; however, to our knowledge, the ARF gene family has not been well studied and characterized in sweet potatoes. In this study, a total of 25 ARF genes were identified in Ipomea trifida. The identified ItrARF genes’ conserved motifs, chromosomal locations, phylogenetic relationships, and their protein characteristics were systemically investigated using different bioinformatics tools. The expression patterns of ItfARF genes were analyzed within the storage roots and normal roots at an early stage of development. ItfARF16b and ItfARF16c were both highly expressed in the storage root, with minimal to no expression in the normal root. ItfARF6a and ItfARF10a exhibited higher expression in the normal root but not in the storage root. Subsequently, ItfARF1a, ItfARF2b, ItfARF3a, ItfARF6b, ItfARF8a, ItfARF8b, and ItfARF10b were expressed in both root types with moderate to high expression for each. All ten of these ARF genes and their prominent expression signify their importance within the development of each respective root type. This study provides comprehensive information regarding the ARF family in sweet potatoes, which will be useful for future research to discover further functional verification of these ItfARF genes.
Comparative Proteomic Analysis of Tolerant and Sensitive Varieties Reveals That Phenylpropanoid Biosynthesis Contributes to Salt Tolerance in Mulberry
Authors: Gan Tiantian , Lin Ziwei , Bao Lijun , Hui Tian , Cui Xiaopeng , Huang Yanzhen , Wang Hexin , Su Chao , Jiao Feng , Zhang Minjuan , Qian Yonghua
Published: August 2021

Mulberry, an important woody tree, has strong tolerance to environmental stresses, including salinity, drought, and heavy metal stress. However, the current research on mulberry resistance focuses mainly on the selection of resistant resources and the determination of physiological indicators. In order to clarify the molecular mechanism of salt tolerance in mulberry, the physiological changes and proteomic profiles were comprehensively analyzed in salt-tolerant (Jisang3) and salt-sensitive (Guisangyou12) mulberry varieties. After salt treatment, the malondialdehyde (MDA) content and proline content were significantly increased compared to control, and the MDA and proline content in G12 was significantly lower than in Jisang3 under salt stress. The calcium content was significantly reduced in the salt-sensitive mulberry varieties Guisangyou12 (G12), while sodium content was significantly increased in both mulberry varieties. Although the Jisang3 is salt-tolerant, salt stress caused more reductions of photosynthetic rate in Jisang3 than Guisangyou12. Using tandem mass tags (TMT)-based proteomics, the changes of mulberry proteome levels were analyzed in salt-tolerant and salt-sensitive mulberry varieties under salt stress. Combined with GO and KEGG databases, the differentially expressed proteins were significantly enriched in the GO terms of amino acid transport and metabolism and posttranslational modification, protein turnover up-classified in Guisangyou12 while down-classified in Jisang3. Through the comparison of proteomic level, we identified the phenylpropanoid biosynthesis may play an important role in salt tolerance of mulberry. We clarified the molecular mechanism of mulberry salt tolerance, which is of great significance for the selection of excellent candidate genes for saline-alkali soil management and mulberry stress resistance genetic engineering.
Pemafibrate Prevents Retinal Dysfunction in a Mouse Model of Unilateral Common Carotid Artery Occlusion
Authors: Lee Deokho , Tomita Yohei , Jeong Heonuk , Miwa Yukihiro , Tsubota Kazuo , Negishi Kazuno , Kurihara Toshihide
Published: August 2021

Cardiovascular diseases lead to retinal ischemia, one of the leading causes of blindness. Retinal ischemia triggers pathological retinal glial responses and functional deficits. Therefore, maintaining retinal neuronal activities and modulating pathological gliosis may prevent loss of vision. Previously, pemafibrate, a selective peroxisome proliferator-activated receptor alpha modulator, was nominated as a promising drug in retinal ischemia. However, a protective role of pemafibrate remains untouched in cardiovascular diseases-mediated retinal ischemia. Therefore, we aimed to unravel systemic and retinal alterations by treating pemafibrate in a new murine model of retinal ischemia caused by cardiovascular diseases. Adult C57BL/6 mice were orally administered pemafibrate (0.5 mg/kg) for 4 days, followed by unilateral common carotid artery occlusion (UCCAO). After UCCAO, pemafibrate was continuously supplied to mice until the end of experiments. Retinal function (a-and b-waves and the oscillatory potentials) was measured using electroretinography on day 5 and 12 after UCCAO. Moreover, the retina, liver, and serum were subjected to qPCR, immunohistochemistry, or ELISA analysis. We found that pemafibrate enhanced liver function, elevated serum levels of fibroblast growth factor 21 (FGF21), one of the neuroprotective molecules in the eye, and protected against UCCAO-induced retinal dysfunction, observed with modulation of retinal gliosis and preservation of oscillatory potentials. Our current data suggest a promising pemafibrate therapy for the suppression of retinal dysfunction in cardiovascular diseases.
A Mutation in DNA Polymerase α Rescues WEE1KO Sensitivity to HU
Authors: Eekhout Thomas , Pedroza-Garcia José Antonio , Kalhorzadeh Pooneh , De Jaeger Geert , De Veylder Lieven
Published: August 2021

During DNA replication, the WEE1 kinase is responsible for safeguarding genomic integrity by phosphorylating and thus inhibiting cyclin-dependent kinases (CDKs), which are the driving force of the cell cycle. Consequentially, wee1 mutant plants fail to respond properly to problems arising during DNA replication and are hypersensitive to replication stress. Here, we report the identification of the polα-2 mutant, mutated in the catalytic subunit of DNA polymerase α, as a suppressor mutant of wee1. The mutated protein appears to be less stable, causing a loss of interaction with its subunits and resulting in a prolonged S-phase.