bluuebunny/crossref_metadata_2025 huggingface dataset:
Delusion of Pregnancy in Down Syndrome: Two Case Reports
Authors: Ursumando Luciana , Fucà Elisa , Costanzo Floriana , Vicari Stefano
Published: October 2022

Individuals with intellectual disability (ID) are more vulnerable to psychotic disorder and schizophrenia than the general population. However, psychotic symptoms have not been widely described in this population. Here, we deeply investigated the cases of two young women with ID and Down syndrome (DS) who developed a delusion of pregnancy, a rare condition defined as a fixed belief of being pregnant despite factual evidence to the contrary. The assessment included psychopathological and neuropsychological examination, as well as the evaluation of cognitive and adaptive functioning. In these cases, delusion manifested as a psychotic symptom of a cyclothymic disorder (case 1) or as an independent delusional disorder (case 2). However, some similarities emerged: both women exhibited good pre-morbid adaptive functioning and family history of psychiatric disorders; moreover, in both cases delusion emerged in association with an external trigger. Difficulties in verbally expressing one’s thoughts and beliefs were found, as well as poor abstract reasoning skills that may have affected the ability to deeply conceptualize the delusional idea itself. These findings may provide crucial insights into the clinical manifestation of psychosis in individuals with DS and underscore the importance of a routine psychological and neuropsychological follow-up to provide prompt and adequate intervention.
The Age of Mobility: Can Equalization of Public Health Services Alleviate the Poverty of Migrant Workers?
Authors: Zhou Ziming , Jiang Yumeng , Wu Haitao , Jiang Fan , Yu Zhiming
Published: October 2022

Migrants workers are important participants in and contributors to economic and social construction, but they still face the reality of being marginalized. Based on data from the China Migrants Dynamic Survey in 2018, this paper systematically investigated the impact of public health services on the multidimensional poverty of migrant workers. The research found that, first, the current mean of the multidimensional poverty deprivation value of migrant workers is 0.1806, which is one dimension of poverty that exists on average. In addition, migrant workers do not have high access to public health services. The proportions of migrant workers who have not established residents’ health files and who have not received public health education are 74.22% and 29.92%, respectively. Second, public health services can significantly alleviate the multidimensional poverty of migrant workers. After mitigating the potential endogeneity problem by the IV-2SLS method and conducting robustness tests by the PSM method, the conclusion is still robust. Further research found that the impact of public health services on the multidimensional poverty alleviation of migrant workers is heterogeneous. The improvement of public health services has the greatest effect on the multidimensional poverty alleviation of the new generation of migrant female workers in the western region. The research in this paper helps to examine and clarify the policy significance of public health services for the multidimensional poverty alleviation of migrant workers and provides empirical evidence for the use of public health services to tackle the poverty problem.
Original Research: How Will the TNFD Impact the Health Sector’s Nature-Risks Management?
Authors: Deweerdt Tom , Caltabiano Kristin , Dargusch Paul
Published: October 2022

The G20-led TNFD taskforce or TNFD is under development and should be ready in September 2023. With one year to go before its official release, the study of the beta versions of the 0.2 framework is crucial to know the strategy of the taskforce regarding metrics and sectors with high natural risks. Its big sister, the Taskforce on Climate-related Financial Disclosure or TCFD, had defined the health sector as a non-key in terms of climate change and carbon risks, but the TNFD decided that it was a priority in terms of nature-related risks and co-dependencies. This research therefore focuses on the innovations of the TNFD and its impact on future disclosures in the sector. The goal being to predict if the TNFD will lead to more disclosures and therefore better risk management from the health firms. To complete this research, the analysis of the sector’s risks and dependencies on nature-related issues and biodiversity loss was essential. To do so, a policy analysis on the framework of the TNFD was conducted, as well as a literature review on nature related risks and opportunities for the health sector. The Health Sector-Wide Approach (SWAp) was analysed to highlight the Task Force’s focus on the health sector. Finally, a due diligence of the TNFD’s stakeholders and partners was carried out to ascertain the interest and participation of health sector actors in the TNFD. Results have shown that Nature risks were important for the sector and that the TNFD was giving more importance to the sector in terms of priority. On the contrary, the health sector does not show an improved interest in this new taskforce. There is a need for more research in the implementation of Nature-financial metrics for disclosures.
Parenting Styles, Mental Health, and Catastrophizing in Women with Chronic Pelvic Pain: A Case-Control Study
Authors: Siqueira-Campos Vânia Meira , Fernandes Lara Juliana Henrique , de Deus José Miguel , Conde Délio Marques
Published: October 2022

Chronic pelvic pain (CPP) in women is a highly prevalent condition worldwide and requires multimodal treatment. Adverse childhood experiences have been associated with CPP in women, while allodynia and poor outcomes have been linked to pain catastrophizing in these patients. Pain perception has been associated with parenting style during childhood. The objective of this study was to investigate the association between parenting style, pain catastrophizing, anxiety, depression and CPP in women. A case–control study was conducted between May 2018 and August 2021 with 123 women with CPP and 123 pain-free controls. Questionnaires were used to collect participants’ data. The association between parenting style and CPP was assessed using multiple logistic regression, with odds ratios (OR) and 95% confidence intervals (CI) being calculated. The correlation between catastrophizing, pain intensity, pain duration, anxiety, depression, and parenting style in women with CPP was assessed using Spearman’s rank correlation coefficient (r). A higher frequency of low maternal care (60.7% versus 45.2%; p = 0.026), anxiety (79.7% versus 56.9%; p < 0.001), depression (73.2% versus 56.1%; p = 0.008) and physical violence (31.7% versus 14.6%; p = 0.003) was found in the CPP group compared to the controls. There was no association between parenting style and CPP in the adjusted analysis. A positive correlation was found between catastrophizing and pain intensity (r = 0.342; p < 0.001), anxiety (r = 0.271; p = 0.002), depression (r = 0.272; p = 0.002), and maternal overprotection (r = 0.185; p = 0.046). A negative correlation was found between anxiety and maternal (r = −0.184; p = 0.047) and paternal (r = −0.286; p = 0.006) care and between depression and maternal (r = −0.219; p = 0.018) and paternal (r = −0.234; p = 0.026) care. The present results suggest a significant but weak association of parenting style with pain catastrophizing, the mental health of women with CPP, and the way in which they experience pain.
The Impact on the Stress-Associated Autonomic Response of Physiotherapy Students Receiving Interferential Current in an Electrotherapy Training Session
Authors: Espejo-Antúnez Luis , Fernández-Morales Carlos , Hernández-Sánchez Sergio , Cardero-Durán María de los Ángeles , Toledo-Marhuenda José Vicente , Albornoz-Cabello Manuel
Published: October 2022

Electrical currents are didactic contents widely applied in the training of physiotherapy students, but the treatment is considered a stressful situation for both the patient who receives it and the student who applies it. The aim of this study was to evaluate the stress-associated autonomic response of physiotherapy students receiving interferential current by measuring and analysing heart rate variability. An observational case–control study was conducted. Ninety healthy male volunteers, all physiotherapy degree students, were enrolled while attending laboratory practice during the 2020–2021 academic year. Participants were randomly allocated to a sham electrotherapy group (44 subjects), in which heart rate variability was recorded for 10 min, both at rest and during the application of sham technique on the lower back (10 min), and an electrotherapy group (46 subjects), applying the same procedure with the electrical current flowing. Outcome measures included baseline (seated position) and postintervention (prone position) time domain parameter, diameters of the Poincaré plot 1 and 2, stress score, and sympathetic/parasympathetic ratio. The sham electrotherapy group exhibited significant increases in time domain parameter (p = 0.027) and diameters of the Poincaré plot 1 (p = 0.032), with a small effect size (d ≤ 0.5). The electrotherapy group exhibited significant increases in time domain parameter and diameters of the Poincaré plot 1 and 2 (p < 0.001) and decreases in the stress score and sympathetic/parasympathetic ratio (p < 0.001), with a large effect size (d > 0.8) other than for the time domain parameter (d = 0.42), indicating increased parasympathetic and decreased sympathetic activity. After interventions, there were significant differences between groups in diameters of the Poincaré plot 2 (p < 0.001), stress score (p = 0.01) and sympathetic/parasympathetic ratio (p = 0.003), with moderate effect size (d > 0.5). The application of the interferential current technique produces stress-associated autonomic response characterized by greater parasympathetic activity and decreased sympathetic activity. Further studies are needed to determine possible adverse effects.
Analysis of Acoustic Emission Characteristics and Failure Mode of Deep Surrounding Rock of Sanshandao Gold Mine
Authors: Li Guang , Lu Rong , Ma Fengshan , Guo Jie
Published: October 2022

In mining engineering, crack distribution has a considerable influence on the mechanical behavior and stability of the surrounding rock mass. Using the granite of the Sanshandao gold mine as experimental samples, the deformation and failure of fractured rock were analyzed based on a rock uniaxial compression test with acoustic emission monitoring. We analyzed the characteristics of different stages of rock sample deformation, and evaluated the failure mode of seven types of rock samples. The results show that the cracks had a considerable impact on rock sample strength and mechanical behavior, and the strength of intact rock was the highest, while that of the sample with parallel double cracks was the lowest. The acoustic emission parameters, AF, RA, and lg(AF/RA), have different change trends in different stages of rock deformation and failure. Based on these change trends, the failure modes of rock samples with different crack distributions were identified. Additionally, for the rock samples with seven types of crack distribution, a sudden or progressive failure caused by the b-value curves was observed. The research findings provide a database for deep surrounding rock stability in the study area and provide suggestions for failure prediction.
A Practical Framework for Academics to Implement Public Engagement Interventions and Measure Their Impact
Authors: Busch Isolde Martina , Savazzi Silvia , Bertini Giuseppe , Cesari Paola , Guaraldo Olivia , Nosè Michela , Barbui Corrado , Rimondini Michela
Published: October 2022

Academic institutions have shown an increased interest in the so-called third mission to offer an impactful contribution to society. Indeed, public engagement programs ensure knowledge transfer and help to inspire positive public discourse. We aimed to propose a comprehensive framework for academic institutions planning to implement a public engagement intervention and to suggest potential indicators to measure its impact. To inform the framework development, we searched the literature on public engagement, the third mission, and design theory in electronic databases and additional sources (e.g., academic recommendations) and partnered with a communication agency offering non-academic advice. In line with this framework, we designed a public engagement intervention to foster scientific literacy in Italian youth, actively involving them in the development of the intervention. Our framework is composed of four phases (planning/design, implementation, immediate impact assessment, and medium- and long-term assessment). Impact indicators were subdivided into outcome variables that were immediately describable (e.g., changed understanding and awareness of the target population) and measurable only in the medium or long run (e.g., adoption of the intervention by other institutions). The framework is expected to maximize the impact of public engagement interventions and ultimately lead to better reciprocal listening and mutual understanding between academia and the public.
Efficacy and Safety of Cytisine in Combination with a Community Pharmacists’ Counselling for Smoking Cessation in Thailand: A Randomized Double-Blinded Placebo-Controlled Trial
Authors: Phusahat Pum , Dilokthornsakul Piyameth , Boonsawat Watchara , Zaeoue Uraiwan , Hansuri Nadthatida , Tawinkan Nirachara , Theeranut Ampornpan , Lertsinudom Sunee
Published: October 2022

Background: Cytisine is a prospective pharmacological alternative for community pharmacy smoking cessation services. However, it has not yet been licensed because of a lack of efficacy and safety information in Thailand. Objective: The aim of this study was to evaluate the efficacy of cytisine in combination with community pharmacists’ counselling on smoking cessation in a community pharmacy in ThailandDesign. Setting, participants, and interventions: A double-blinded randomized placebo-controlled trials was carried out. Participants aged >18 years old who smoked >10 tobaccos/day were randomly assigned to receive cytisine or placebo and five sessions of counselling by a community pharmacist. The primary outcome was a continuous abstinence rate (CAR) at week 48. The CAR was also measured at weeks 2, 4, 12, and 24. Adverse events were monitored. Results: A total of 132 participants were included, with 67 receiving cytisine and 65 receiving a placebo. Approximately 95% of participants were male. The CARs were determined to be 14.93% and 6.15% for cytisine and placebo, respectively, at week 48. The relative risk (RR) was 2.41 (95% confidence interval (CI); 0.80–7.35, p = 0.102). The RRs for CAR at weeks 2, 4, 12, and 24 were 2.43, 2.91, 2.50, and 1.78, respectively. Only the RRs for weeks 2, 4, and 12 were statistically significant. Common and non-serious gastrointestinal and neurological adverse events were observed. Conclusion: Cytisine, when combined with community pharmacists’ counselling, did not statistically improve the CAR at week 48, although it did improve the CAR at weeks 2, 4, and 12. Adverse events of cytisine were common and non-serious (registration number: TCTR20180312001).
The Opinions of Poles about the Need to Provide Humanitarian Aid to Refugees from the Area Covered by the Russian–Ukrainian War
Authors: Karakiewicz-Krawczyk Katarzyna , Zdziarski Krzysztof , Landowski Marek , Nieradko-Heluszko Agnieszka , Kotwas Artur , Szumilas Paweł , Knyszyńska Anna , Karakiewicz Beata
Published: October 2022

The armed conflict in Ukraine has caused a lot of emotions around the world. Many countries have been involved in helping brutally attacked people, especially mothers and children. The versatile involvement of large powers is monitored and noticeable by the media. Active help from Poland is a very visible sign of human solidarity with the suffering Ukrainian nation. Open hearts, houses and institutions and humanitarian and medical aid are elements of Polish kindness and empathy. The aim of the research was to collect Poles’ opinions about the need to provide humanitarian aid to Ukrainians from the territories of the Russian–Ukrainian war. Capturing feelings of Poles towards Ukrainians during the war is an interesting issue that shows subjective opinions about the existential situation perceived in the space of mutual personal interactions. The results showing opinions on help were collected from a group of 1012 people throughout Poland with the help of an authorial questionnaire. The obtained data shows a positive attitude of Poles to Ukrainians. The most willing to help are people over 49 years old, more often with a good and very good financial situation. Respondents believe that general assistance from other countries and the European Parliament is not sufficient. Military support is accepted the most by the oldest participants of research, and less by the age group up to 30 years who support medical help more. More concerned about the ongoing conflict are respondents under the age of 30 and the least wealthy, including, more often, women. The richest respondents are least afraid of the effects of the ongoing Russian–Ukrainian conflict. The conducted research confirms the openness of Polish society to refugees and brings opinions about existential solidarity with the suffering Ukrainian nation.
Age Estimation Using Maxillary Central Incisor Analysis on Cone Beam Computed Tomography Human Images
Authors: Santos María Arminda , Muinelo-Lorenzo Juan , Fernández-Alonso Ana , Cruz-Landeira Angelines , Aroso Carlos , Suárez-Cunqueiro María Mercedes
Published: October 2022

Forensic dentistry plays an important role in human identification, and dental age estimation is an important part of the process. Secondary dentin deposition throughout an individual’s lifetime and consequent modification in teeth anatomy is an important parameter for age estimation procedures. The aim of the present study was to develop regression equations to determine age in adults by means of linear measurements and ratios on sagittal, coronal and axial slices of maxillary central incisors using cone bean computed tomography (CBCT). Multiplanar measurements of upper central incisors were taken for a sample of 373 CBCTs. Subsequently, one-way analysis of variance (ANOVA) and multivariate linear regressions were performed for age estimation. The equations obtained from axial linear measurements and ratios presented a standard error of the estimate (SEE) of ±10.9 years (R2 = 0.49), and a SEE of ±10.8 years (R2 = 0.50), respectively. The equation obtained for multiplanar linear measurements presented a SEE of ±10.9 years (R2 = 0.52), while the equation for multiplanar ratios presented a SEE of ±10.7 years (R2 = 0.51). Thus, CBCT measurements on upper central incisors were found to be an acceptable method for age estimation. Horizontal measurements, especially pulp measurements, improve the accuracy of age estimate equations.
The Effect of COVID-19 Perceived Risk on Internet Addiction among College Students in China: An Empirical Study Based on the Structural Equation Model
Authors: Pan Ling , Li Jun , Hu Ziao , Wu Henan
Published: October 2022

This study focused on COVID-19 perceived risk and Internet addiction among Chinese college students during the lockdown. On the basis of the Social Cognitive Theory, this study proposed a mediating model to evaluate the mediating role of difficulties in regulating emotion between the COVID-19 perceived risk and Internet addiction. A questionnaire survey was conducted among 690 college students during the COVID-19 lockdown in China. The results showed that the COVID-19 perceived risk was significantly positively associated with Internet addiction (r = 0.236, p < 0.001) and difficulties in emotion regulation (r = 0.220, p < 0.001), difficulties in emotion regulation was significantly positively associated with Internet addiction (r = 0.368, p < 0.001). The COVID-19 perceived risk had a significant and positive predictive effect on Internet addiction (β = 0.233, p < 0.001) among Chinese college students. The analysis of the mediation model showed that difficulties in emotion regulation partially mediated the relationship between COVID-19 perceived risk and Internet addiction (indirect effect value was 0.051 with 95% Confidence Interval ranging from 0.027 to 0.085). The findings not only enhanced our understanding of the internal influence mechanism of COVID-19 perceived risk on Internet addiction but also provided a practical basis for college education works. Finally, discussions and suggestions were provided on the basis of the results.
Spatiotemporal Change in Livestock Population and Its Correlation with Meteorological Disasters during 2000–2020 across Inner Mongolia
Authors: Bai Hui , Wang Baizhu , Zhu Yuanjun , Kwon Semyung , Yang Xiaohui , Zhang Kebin
Published: October 2022

Inner Mongolia (IM) is one of the five major pastoral areas in China, and animal husbandry is its traditional industry. The population of livestock is an important factor affecting the sustainable development of livestock and grassland. Due to the special geographical location of IM, various meteorological disasters occur frequently, which have a significant impact on the local livestock population. In this study, principal component analysis (PCA) and geographically weighted principal component analysis (GWPCA) were used to explore the spatial and temporal patterns of small livestock and large livestock populations in county-level administrative units from 2000 to 2020, and the effects of meteorological disasters on livestock populations were also considered. We found that the cumulative proportion of total variance (CPTV) of the first two principal components of global PCA for small livestock and the first principal component for large livestock reached 94.54% and 91.98%, respectively, while the CPTV of GWPCA was in the range of 93.23–96.45% and 88.47–92.49%, respectively, which showed stronger spatial explanation; the small livestock population was significantly correlated with spring drought, summer drought, spring–summer drought and snow disaster. However, the correlation between large livestock and summer drought and spring–summer drought is greater. We conclude that GWPCA can better explain the spatial change of livestock populations; meteorological disasters have both advantages and disadvantages on the livestock population, and the drought types that have a greater impact on livestock are summer drought and spring–summer drought. There are geographical differences in the impact of meteorological disasters, with drought affecting most of IM and snow disaster mainly affecting the eastern region; large livestock were mainly affected by drought, while small livestock were affected by both drought and snow disaster.
miRNA Expression May Have Implications for Immunotherapy in PDGFRA Mutant GISTs
Authors: Ravegnini Gloria , Nannini Margherita , Indio Valentina , Serrano Cesar , Gorini Francesca , Astolfi Annalisa , Di Vito Aldo , Morroni Fabiana , Pantaleo Maria Abbondanza , Hrelia Patrizia , Angelini Sabrina
Published: October 2022

Gastrointestinal stromal tumors (GISTs) harboring mutations in the PDGFRA gene occur in only about 5–7% of patients. The most common PDGFRA mutation is exon 18 D842V, which is correlated with specific clinico-pathological features compared to the other PDGFRA mutated GISTs. Herein, we present a miRNA expression profile comparison of PDGFRA D842V mutant GISTs and PDGFRA with mutations other than D842V (non-D842V). miRNA expression profiling was carried out on 10 patients using a TLDA miRNA array. Then, miRNA expression was followed by bioinformatic analysis aimed at evaluating differential expression, pathway enrichment, and miRNA-mRNA networks. We highlighted 24 differentially expressed miRNAs between D842V and non-D842V GIST patients. Pathway enrichment analysis showed that deregulated miRNAs targeted genes that are mainly involved in the immune response pathways. The miRNA-mRNA networks highlighted a signature of miRNAs/mRNA that could explain the indolent behavior of the D842V mutated GIST. The results highlighted a different miRNA fingerprint in PDGFRA D842V GISTs compared to non-D842Vmutated patients, which could explain the different biological behavior of this GIST subset.
KLK12 Regulates MMP-1 and MMP-9 via Bradykinin Receptors: Biomarkers for Differentiating Latent and Active Bovine Tuberculosis
Authors: Wang Yuanzhi , Qu Mengjin , Liu Yiduo , Wang Haoran , Dong Yuhui , Zhou Xiangmei
Published: October 2022

It has been established that kallikrein12 (KLK12) expression is closely related to bovine tuberculosis (bTB) development. Herein, we sought to clarify the regulatory mechanism of KLK12 and its application in tuberculosis diagnosis. KLK12 knockdown macrophages were produced by siRNA transfection. Bradykinin receptors (BR, including B1R and B2R) were blocked with specific inhibitors. Mannose-capped lipoarabinomannan (ManLAM) was extracted from Mycobacterium bovis (M. bovis) and used to study the mechanism of KLK12 activation. In addition, we constructed different mouse models representing the latent and active stages of M. bovis infection. Mouse models and clinical serum samples were used to assess the diagnostic value of biomarkers. Through the above methods, we confirmed that KLK12 regulates MMP-1 and MMP-9 via BR. KLK12 upregulation is mediated by the M. bovis-specific antigen ManLAM. KLK12, MMP-1, and MMP-9 harbor significant value as serological markers for differentiating between latent and active bTB, especially KLK12. In conclusion, we identified a novel signaling pathway, KLK12/BR/ERK/MMPs, in M. bovis-infected macrophages, which is activated by ManLAM. From this signaling pathway, KLK12 can be used as a serological marker to differentiate between latent and active bTB. Importantly, KLK12 also has enormous potential for the clinical diagnosis of human tuberculosis (TB).
Molecular Mechanisms of Takotsubo Syndrome
Authors: Couch Liam S. , Channon Keith , Thum Thomas
Published: October 2022

Takotsubo syndrome (TTS) is a severe but reversible acute heart failure syndrome that occurs following high catecholaminergic stress. TTS patients are similar to those with acute coronary syndrome, with chest pain, dyspnoea and ST segment changes on electrocardiogram, but are characterised by apical akinesia of the left ventricle, with basal hyperkinesia in the absence of culprit coronary artery stenosis. The pathophysiology of TTS is not completely understood and there is a paucity of evidence to guide treatment. The mechanisms of TTS are thought to involve catecholaminergic myocardial stunning, microvascular dysfunction, increased inflammation and changes in cardiomyocyte metabolism. Here, we summarise the available literature to focus on the molecular basis for the pathophysiology of TTS to advance the understanding of the condition.
Understanding Ocular Findings and Manifestations of Systemic Lupus Erythematosus: Update Review of the Literature
Authors: Luboń Wojciech , Luboń Małgorzata , Kotyla Przemysław , Mrukwa-Kominek Ewa
Published: October 2022

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease. Up to one-third of patients suffering from SLE have various ocular manifestations. The ocular findings may represent the initial manifestation of the systemic disease and may lead to severe ocular complications, and even loss of vision. Ocular manifestations are often associated with degree of systemic inflammation, but also can precede the occurrence of systemic symptoms. Early diagnosis and adequate management of patients with SLE are crucial and require cooperation between various specialists. Proper preparation of ophthalmologists can help to differentiate between complication of SLE and other ocular disorders. New therapies for SLE are promising for potential benefits, however, ocular side effects are still unknown.
Radiation as a Tool against Neurodegeneration—A Potential Treatment for Amyloidosis in the Central Nervous System
Authors: Coelho Carina Marques , Pereira Lia , Teubig Pamela , Santos Pedro , Mendes Filipa , Viñals Sílvia , Galaviz Daniel , Herrera Federico
Published: October 2022

Radiotherapy (RT) is a relatively safe and established treatment for cancer, where the goal is to kill tumoral cells with the lowest toxicity to healthy tissues. Using it for disorders involving cell loss is counterintuitive. However, ionizing radiation has a hormetic nature: it can have deleterious or beneficial effects depending on how it is applied. Current evidence indicates that radiation could be a promising treatment for neurodegenerative disorders involving protein misfolding and amyloidogenesis, such as Alzheimer’s or Parkinson’s diseases. Low-dose RT can trigger antioxidant, anti-inflammatory and tissue regeneration responses. RT has been used to treat peripheral amyloidosis, which is very similar to other neurodegenerative disorders from a molecular perspective. Ionizing radiation prevents amyloid formation and other hallmarks in cell cultures, animal models and pilot clinical trials. Although some hypotheses have been formulated, the mechanism of action of RT on systemic amyloid deposits is still unclear, and uncertainty remains regarding its impact in the central nervous system. However, new RT modalities such as low-dose RT, FLASH, proton therapy or nanoparticle-enhanced RT could increase biological effects while reducing toxicity. Current evidence indicates that the potential of RT to treat neurodegeneration should be further explored.
Transcription Factors as Important Regulators of Changes in Behavior through Domestication of Gray Rats: Quantitative Data from RNA Sequencing
Authors: Oshchepkov Dmitry , Chadaeva Irina , Kozhemyakina Rimma , Shikhevich Svetlana , Sharypova Ekaterina , Savinkova Ludmila , Klimova Natalya V. , Tsukanov Anton , Levitsky Victor G. , Markel Arcady L.
Published: October 2022

Studies on hereditary fixation of the tame-behavior phenotype during animal domestication remain relevant and important because they are of both basic research and applied significance. In model animals, gray rats Rattus norvegicus bred for either an enhancement or reduction in defensive response to humans, for the first time, we used high-throughput RNA sequencing to investigate differential expression of genes in tissue samples from the tegmental region of the midbrain in 2-month-old rats showing either tame or aggressive behavior. A total of 42 differentially expressed genes (DEGs; adjusted p-value  <  0.01 and fold-change  >  2) were identified, with 20 upregulated and 22 downregulated genes in the tissue samples from tame rats compared with aggressive rats. Among them, three genes encoding transcription factors (TFs) were detected: Ascl3 was upregulated, whereas Fos and Fosb were downregulated in tissue samples from the brains of tame rats brain. Other DEGs were annotated as associated with extracellular matrix components, transporter proteins, the neurotransmitter system, signaling molecules, and immune system proteins. We believe that these DEGs encode proteins that constitute a multifactorial system determining the behavior for which the rats have been artificially selected. We demonstrated that several structural subtypes of E-box motifs—known as binding sites for many developmental TFs of the bHLH class, including the ASCL subfamily of TFs—are enriched in the set of promoters of the DEGs downregulated in the tissue samples of tame rats’. Because ASCL3 may act as a repressor on target genes of other developmental TFs of the bHLH class, we hypothesize that the expression of TF gene Ascl3 in tame rats indicates longer neurogenesis (as compared to aggressive rats), which is a sign of neoteny and domestication. Thus, our domestication model shows a new function of TF ASCL3: it may play the most important role in behavioral changes in animals.
Protective Effect of D-Panthenol in Rhabdomyolysis-Induced Acute Kidney Injury
Authors: Semenovich Dmitry S. , Plotnikov Egor Y. , Lukiyenko Elena P. , Astrowski Alexander A. , Kanunnikova Nina P.
Published: October 2022

We investigated the nephroprotective effect of D-panthenol in rhabdomyolysis-induced acute kidney injury (AKI). Adult male Wistar rats were injected with 50% glycerol solution to induce rhabdomyolysis. Animals with rhabdomyolysis were injected with D-panthenol (200 mg/kg) for 7 days. On day 8, we examined AKI markers, renal histology, antioxidant capacity, and protein glutathionylation in kidneys to uncover mechanisms of D-panthenol effects. Rhabdomyolysis kidneys were shown to have pathomorphological alterations (mononuclear infiltration, dilatation of tubules, and hyaline casts in Henle’s loops and collecting ducts). Activities of skeletal muscle damage markers (creatine kinase and lactate dehydrogenase) increased, myoglobinuria was observed, and creatinine, BUN, and pantetheinase activity in serum and urine rose. Signs of oxidative stress in the kidney tissue of rhabdomyolysis rats, increased levels of lipid peroxidation products, and activities of antioxidant enzymes (SOD, catalase, and glutathione peroxidase) were all alleviated by administration of D-panthenol. Its application improved kidney morphology and decreased AKI markers. Mechanisms of D-panthenol’s beneficial effects were associated with an increase in total coenzyme A levels, activity of Krebs cycle enzymes, and attenuation of protein glutathionylation. D-Panthenol protects kidneys from rhabdomyolysis-induced AKI through antioxidant effects, normalization of mitochondrial metabolism, and modulation of glutathione-dependent signaling.
Checkpoint Kinase 2 Inhibition Can Reverse Tamoxifen Resistance in ER-Positive Breast Cancer
Authors: Tsoi Ho , Tsang Wai-Chung , Man Ellen P. S. , Leung Man-Hong , You Chan-Ping , Chan Sum-Yin , Chan Wing-Lok , Khoo Ui-Soon
Published: October 2022

Breast cancer is a heterogeneous disease. Tamoxifen is frequently used to treat ER-positive breast cancer. Our team has identified a novel splice variant of NCOR2, BQ323636.1 (BQ), that mediates tamoxifen resistance. However, the upstream factors that modulate BQ expression are not apparent. This study reveals that tamoxifen treatment causes induction of DNA damage which can enhance BQ expression. We show that DNA damage can activate the ATM/CHK2 and ATR/CHK1 signalling cascades and confirm that ATM/CHK2 signalling is responsible for enhancing the protein stability of BQ. siRNA or a small inhibitor targeting CHK2 resulted in the reduction in BQ expression through reduced phosphorylation and enhanced poly-ubiquitination of BQ. Inhibition of CHK2 by CCT241533 could reverse tamoxifen resistance in vitro and in vivo. Using clinical samples in the tissue microarray, we confirmed that high p-CHK2 expression was significantly associated with high nuclear BQ expression, tamoxifen resistance and poorer overall and disease-specific survival. In conclusion, tamoxifen treatment can enhance BQ expression in ER-positive breast cancer by activating the ATM/CHK2 axis. Targeting CHK2 is a promising approach to overcoming tamoxifen resistance in ER-positive breast cancer.
Chi-Circ_0006511 Positively Regulates the Differentiation of Goat Intramuscular Adipocytes via Novel-miR-87/CD36 Axis
Authors: Li Xin , Zhang Hao , Wang Yong , Li Yanyan , Wang Youli , Zhu Jiangjiang , Lin Yaqiu
Published: October 2022

Goats are an important livestock and goat meat is essential to local people. The intramuscular fat (IMF) content has a great influence on the quality of goat meat. The intramuscular preadipocytes differentiation is closely related to the IMF deposition; however, its potential regulatory mechanisms remain unclear. CircRNAs were revealed to be involved in multiple biological progressions. In this study, we took primary goat intramuscular preadipocyte (GIMPA) as the study model to verify the function and mechanism of chi-circ_0006511, which was abundant and up-regulated in mature adipocytes (GIMA). The results showed that the expression level of chi-circ_0006511 gradually increased in the early stage of GIMPA differentiation, and chi-circ_0006511 was confirmed to promote GIMPA lipid droplets aggregation and up-regulate the adipogenic differentiation determinants, further promoting GIMPA differentiation. Mechanistically, chi-circ_0006511 exerts its function by sponging novel-miR-87, thereby regulating the expression of CD36. The results from this study provided novel significant information to better understand the molecular regulatory mechanism of intramuscular preadipocytes differentiation, thereby providing a new reference for the intramuscular fat adipogenesis in goats.
Effect of Obesity and High-Density Lipoprotein Concentration on the Pathological Characteristics of Alzheimer’s Disease in High-Fat Diet-Fed Mice
Authors: Choi Moonseok , Kim Dongsoo , Youn Young-Jin , Ryu Junghwa , Jeong Yun Ha
Published: October 2022

The typical pathological features of Alzheimer’s disease (AD) are the accumulation of amyloid plaques in the brain and reactivity of glial cells such as astrocytes and microglia. Clinically, the development of AD and obesity are known to be correlated. In this study, we analyzed the changes in AD pathological characteristics in 5XFAD mice after obesity induction through a high-fat diet (HFD). Surprisingly, high-density lipoprotein and apolipoprotein AI (APOA-I) serum levels were increased without low-density lipoprotein alteration in both HFD groups. The reactivity of astrocytes and microglia in the dentate gyrus of the hippocampus and fornix of the hypothalamus in 5XFAD mice was decreased in the transgenic (TG)-HFD high group. Finally, the accumulation of amyloid plaques in the dentate gyrus region of the hippocampus was also significantly decreased in the TG-HFD high group. These results suggest that increased high-density lipoprotein level, especially with increased APOA-I serum level, alleviates the pathological features of AD and could be a new potential therapeutic strategy for AD treatment.
Meta-Analysis Reveals Challenges and Gaps for Genome-to-Phenome Research Underpinning Plant Drought Response
Authors: Melton Anthony E. , Galla Stephanie J. , Dumaguit Carlos Dave C. , Wojahn John M. A. , Novak Stephen , Serpe Marcelo , Martinez Peggy , Buerki Sven
Published: October 2022

Severe drought conditions and extreme weather events are increasing worldwide with climate change, threatening the persistence of native plant communities and ecosystems. Many studies have investigated the genomic basis of plant responses to drought. However, the extent of this research throughout the plant kingdom is unclear, particularly among species critical for the sustainability of natural ecosystems. This study aimed to broaden our understanding of genome-to-phenome (G2P) connections in drought-stressed plants and identify focal taxa for future research. Bioinformatics pipelines were developed to mine and link information from databases and abstracts from 7730 publications. This approach identified 1634 genes involved in drought responses among 497 plant taxa. Most (83.30%) of these species have been classified for human use, and most G2P interactions have been described within model organisms or crop species. Our analysis identifies several gaps in G2P research literature and database connectivity, with 21% of abstracts being linked to gene and taxonomy data in NCBI. Abstract text mining was more successful at identifying potential G2P pathways, with 34% of abstracts containing gene, taxa, and phenotype information. Expanding G2P studies to include non-model plants, especially those that are adapted to drought stress, will help advance our understanding of drought responsive G2P pathways.
Genome-Wide SNP Markers Accelerate Perennial Forest Tree Breeding Rate for Disease Resistance through Marker-Assisted and Genome-Wide Selection
Authors: Younessi-Hamzekhanlu Mehdi , Gailing Oliver
Published: October 2022

The ecological and economic importance of forest trees is evident and their survival is necessary to provide the raw materials needed for wood and paper industries, to preserve the diversity of associated animal and plant species, to protect water and soil, and to regulate climate. Forest trees are threatened by anthropogenic factors and biotic and abiotic stresses. Various diseases, including those caused by fungal pathogens, are one of the main threats to forest trees that lead to their dieback. Genomics and transcriptomics studies using next-generation sequencing (NGS) methods can help reveal the architecture of resistance to various diseases and exploit natural genetic diversity to select elite genotypes with high resistance to diseases. In the last two decades, QTL mapping studies led to the identification of QTLs related to disease resistance traits and gene families and transcription factors involved in them, including NB-LRR, WRKY, bZIP and MYB. On the other hand, due to the limitation of recombination events in traditional QTL mapping in families derived from bi-parental crosses, genome-wide association studies (GWAS) that are based on linkage disequilibrium (LD) in unstructured populations overcame these limitations and were able to narrow down QTLs to single genes through genotyping of many individuals using high-throughput markers. Association and QTL mapping studies, by identifying markers closely linked to the target trait, are the prerequisite for marker-assisted selection (MAS) and reduce the breeding period in perennial forest trees. The genomic selection (GS) method uses the information on all markers across the whole genome, regardless of their significance for development of a predictive model for the performance of individuals in relation to a specific trait. GS studies also increase gain per unit of time and dramatically increase the speed of breeding programs. This review article is focused on the progress achieved in the field of dissecting forest tree disease resistance architecture through GWAS and QTL mapping studies. Finally, the merit of methods such as GS in accelerating forest tree breeding programs is also discussed.
Fine-Tuned Reactivity of N-Containing Naphthol Analogues
Authors: Csuvik Oszkár , Barta Petra , Csámpai Antal , Szatmári István
Published: October 2022

6-Hydroxyquinoline and 3-hydroxyisoquinoline as N-containing naphthol analogues were tested in modified Mannich reactions (mMr’s). In the case of 6-hydroxyquinoline, the outcomes of the attempted Mannich reactions were strongly influenced by the amine components. Aminoalkylation of this substrate with reagents 1-naphthaldehyde and N-benzylmethylamine led to the isolation of a diol regarded as a stabilised water adduct of an ortho-quinone methide (o-QM), of which formation can be ascribed to the presence of a hydroxide ion in a relatively higher concentration generated by the bulky and basic amine component with decreased nucleophilicity. The classical Mannich base was isolated as a single product when the amine component was replaced for morpholine, featuring nucleophilicity rather than basic character under the applied reaction conditions. Starting from the isomer substrate 3-hydroxyisoquinoline, independently on the nucleophile (methanol or morpholine) besides the formation of the classical Mannich base, the nucleophilic attack at position one of the heterocyclic substrate was also observed. The DFT analysis of the acceptor molecular orbitals of the potential electrophilic components and the thermodynamics of the assumed-possible transformations demonstrated that this regioselective addition is a feasible process on the investigated heterocyclic skeleton. DFT modelling studies also suggest that besides the steric bulk, the orbital-controlled electronic properties of the aryl group, originating from the aldehyde components, have a strong influence on the ratios and the NMR-monitored interconversions of the C-1-substituted 3-hydroxyisoquinolines and the classical Mannich bases formed in multistep reaction sequences. On the basis of the DFT analysis of the thermodynamics of alternative pathways, a reaction mechanism was proposed for the rationalization of these characteristic substrate-controlled interconversions.
In Vitro Anti-Proliferative and Apoptotic Effects of Hydroxytyrosyl Oleate on SH-SY5Y Human Neuroblastoma Cells
Authors: Laghezza Masci Valentina , Bernini Roberta , Villanova Noemi , Clemente Mariangela , Cicaloni Vittoria , Tinti Laura , Salvini Laura , Taddei Anna Rita , Tiezzi Antonio , Ovidi Elisa
Published: October 2022

The antitumor activity of polyphenols derived from extra virgin olive oil and, in particular the biological activity of HTyr, has been studied extensively. However, the use of HTyr as a therapeutic agent for clinical applications is limited by its low bioavailability and rapid excretion in humans. To overcome these limitations, several synthetic strategies have been optimized to prepare lipophenols and new compounds derived from HTyr to increase lipophilicity and bioavailability. One very promising ester is hydroxytyrosyl oleate (HTyr-OL) because the chemical structure of HTyr, which is responsible for several biological activities, is linked to the monounsaturated chain of oleic acid (OA), giving the compound high lipophilicity and thus bioavailability in the cellular environment. In this study, the in vitro cytotoxic, anti-proliferative, and apoptotic induction activities of HTyr-OL were evaluated against SH-SY5Y human neuroblastoma cells, and the effects were compared with those of HTyr and OA. The results showed that the biological activity of HTyr was maintained in HTyr-OL treatments at lower dosages. In addition, the shotgun proteomic approach was used to study HTyr-OL-treated and untreated neuroblastoma cells, revealing that the antioxidant, anti-proliferative and anti-inflammatory activities of HTyr-OL were observed in the unique proteins of the two groups of samples.
Novel Class of Proteasome Inhibitors: In Silico and In Vitro Evaluation of Diverse Chloro(trifluoromethyl)aziridines
Authors: Ielo Laura , Patamia Vincenzo , Citarella Andrea , Efferth Thomas , Shahhamzehei Nasim , Schirmeister Tanja , Stagno Claudio , Langer Thierry , Rescifina Antonio , Micale Nicola , Pace Vittorio
Published: October 2022

The ubiquitin-proteasome pathway (UPP) is the major proteolytic system in the cytosol and nucleus of all eukaryotic cells. The role of proteasome inhibitors (PIs) as critical agents for regulating cancer cell death has been established. Aziridine derivatives are well-known alkylating agents employed against cancer. However, to the best of our knowledge, aziridine derivatives showing inhibitory activity towards proteasome have never been described before. Herein we report a new class of selective and nonPIs bearing an aziridine ring as a core structure. In vitro cell-based assays (two leukemia cell lines) also displayed anti-proliferative activity for some compounds. In silico studies indicated non-covalent binding mode and drug-likeness for these derivatives. Taken together, these results are promising for developing more potent PIs.