bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of GV1001 in patients with moderate-to-severe Alzheimer’s disease already receiving donepezil: a phase 2 randomized, double-blind, placebo-controlled, multicenter clinical trial
Authors: Koh Seong-Ho , Kwon Hyuk Sung , Choi Seong Hye , Jeong Jee Hyang , Na Hae Ri , Lee Chan Nyoung , Yang YoungSoon , Lee Ae Young , Lee Jae-Hong , Park Kyung Won , Han Hyun Jeong , Kim Byeong C. , Park Jin Se , Lee Jee-Young , Kim Sangjae , Lee Kyu-Yong
Published: March 2021

Background

Our previous studies showed that GV1001 has various protective effects against β-amyloid and other stressors. Based on these findings, we hypothesized that GV1001 might have beneficial effects in patients with Alzheimer’s disease (AD).

Methods

A phase 2, double-blind, parallel-group, placebo-controlled, 6-month randomized clinical trial was performed to evaluate the safety and efficacy of subcutaneously administered GV1001. Between September 2017 and September 2019, 13 centers in South Korea recruited participants. A total of 106 patients were screened, and 96 patients with moderate-to-severe AD were randomized 1:1:1 to the placebo (group 1,n = 31), GV1001 0.56 mg (group 2,n = 33), and 1.12 mg (group 3,n = 32) groups. GV1001 was administered every week for 4 weeks (4 times), followed by every 2 weeks until week 24 (10 times). The primary endpoint was the change in the Severe Impairment Battery (SIB) score from baseline to week 24. The key secondary efficacy endpoints were the change in the Clinical Dementia Rating Sum of Box (CDR-SOB), Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), Neuropsychiatric Inventory (NPI), Mini-Mental State Examination, and Global Deterioration Scale scores. The safety endpoints were also assessed based on adverse events, laboratory test results, vital signs, and other observations related to safety.

Results

Group 3 showed less decrease in the SIB score at 12 and 24 weeks compared with group 1 (P < 0.05). These were not significantly observed in group 2. Among the secondary endpoints, only the NPI score showed significantly better improvement in group 2 than in group 3 at week 12; however, there were no other significant differences between the groups. Although the ADCS-ADL and CDR-SOB scores showed a pattern similar to SIB scores, a statistically significant result was not found. Adverse events were similar across all three groups.

Conclusions

The results indicate that GV1001 1.12 mg met the primary endpoint of a statistically significant difference. GV1001 was well tolerated without safety concerns. This study warrants a larger clinical trial.

Trial registration

ClinicalTrials.govNCT03184467. Registered on June 12, 2017.
Coronavirus disease 2019 and dengue: two case reports
Authors: Hilmy Abdullah Isneen , Dey Rajib Kumar , Imad Hisham Ahmed , Yoosuf Abdul Azeez , Nazeem Ali , Latheef Ali Abdulla
Published: March 2021

Background

The pandemic of this century has overwhelmed the healthcare systems of affected countries, and all resources have been diverted to coronavirus disease 2019. At the onset, coronavirus disease 2019 can present as any other acute febrile undifferentiated illness. In tropical regions, clinicians are increasingly challenged to differentiate these febrile illnesses without the use of diagnostics. With this pandemic, many of these tropical diseases are neglected and go underreported. Dengue is holoendemic in the Maldives, and dengue viruses circulate throughout the year. Reports about coinfections with dengue virus and severe acute respiratory syndrome coronavirus 2 are scarce, and the outcome and the dynamics of the disease may be altered in the presence of coinfection. We have described the clinical manifestation and serial laboratory profile, and highlighted the atypical findings uncommon in dengue infection.

Case presentation

Case 1 was a 39-year old Asian male, presented on day 6 of dengue infection with warning signs. Reverse transcription polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 that was done as per hospital protocol was found to be positive. Case 2 was a 38-year old Asian male, was admitted on day 5 of illness with symptoms of acute respiratory infection with positive reverse transcription polymerase chain reaction for severe acute respiratory syndrome coronavirus 2. Evaluation of progressive leukopenia and thrombocytopenia showed positive dengue serology.

Conclusion

Clinicians must be conscientious when working on the differential diagnosis of possible tropical diseases in cases of coronavirus disease 2019, specifically, when patients develop hemoconcentration, thrombocytopenia, and transaminitis with elevated expression of aspartate higher than alanine transaminase, which is frequently observed in dengue infection. Caution must be taken during the administration of intravenous fluids when treating patients with coronavirus disease 2019 and dengue coinfection, as coronavirus disease 2019 patients are more prone to develop pulmonary edema. Timely diagnosis and appropriate management are essential to avoid the devastating complications of severe forms of dengue infection. It is important to repeat and reconfirm the dengue serology in coronavirus disease 2019 patients to avoid false positivity. Diligence and care must be taken not to neglect other endemic tropical diseases in the region during the present pandemic.
Aldose reductase deficiency inhibits LPS-induced M1 response in macrophages by activating autophagy
Authors: Cheng Peng , Xie Jianwei , Liu Zhiyong , Wang Jian
Published: March 2021

Macrophage M1 polarization mediates inflammatory responses and tissue damage. Recently, aldose reductase (AR) has been shown to play a critical role in M1 polarization in macrophages. However, the underlying mechanisms are unknown. Here, we demonstrated, for the first time, that AR deficiency repressed the induction of inducible nitric oxide synthase in lipopolysaccharide (LPS)-stimulated macrophages via activation of autophagy. This suppression was related to a defect in the inhibitor of nuclear factor κB (NF-κB) kinase (IKK) complex in the classical NF-κB pathway. However, the mRNA levels of IKKβ and IKKγ were not reduced in LPS-treated AR knockout (KO) macrophages, indicating that their proteins were downregulated at the post-transcriptional level. We discovered that LPS stimuli induced the recruitment of more beclin1 and increased autophagosome formation in AR-deficient macrophages. Blocking autophagy through 3-methyladenine and ammonium chloride treatment restored IKKβ and IKKγ protein levels and increased nitric oxide synthase production in LPS-stimulated AR-deficient macrophages. More assembled IKKβ and IKKγ underwent ubiquitination and recruited the autophagic adaptor p62 in LPS-induced AR KO macrophages, promoting their delivery to autophagosomes and lysosomes. Collectively, these findings suggest that AR deficiency is involved in the regulation of NF-κB signaling, and extends the role of selective autophagy in fine-tuned M1 macrophage polarization.
Sero-epidemiological survey of bluetongue disease in one-humped camel (Camelus dromedarius) in Kassala State, Eastern Sudan
Authors: Elmahi Molhima M. , Hussien Mohammed O. , Karrar Abdel Rahim E. , Elhassan Amira M. , El Hussein Abdel Rahim M.
Published: March 2021

Background

Bluetongue (BT) is a vector-borne viral disease of ruminant and camelid species which is transmitted by Culicoides spp. The causative agent of BT is bluetongue virus (BTV) that belongs to genus Orbivirus of the family Reoviridae. The clinical disease is seen mainly in sheep but mostly sub-clinical infections of BT are seen in cattle, goats and camelids. The clinical reaction of camels to infection is usually not apparent. The disease is notifiable to the World Organization for Animal Health (OIE), causing great economic losses due to decreased trade and high mortality and morbidity rates associated with bluetongue outbreaks. The objective of this study was to investigate the seroprevalence of BTV in camels in Kassala State, Eastern Sudan and to identify the potential risk factors associated with the infection. A cross sectional study using a structured questionnaire survey was conducted during 2015–2016. A total of 210 serum samples were collected randomly from camels from 8 localities of Kassala State. The serum samples were screened for the presence of BTV specific immunoglobulin (IgG) antibodies using a competitive enzyme-linked immunosorbent assay (cELISA).

Results

Seropositivity to BTV IgG was detected in 165 of 210 camels’ sera accounting for a prevalence of 78.6%. Potential risk factors to BTV infection were associated with sex (OR = 0.061, p-value = 0.001) and seasonal river as water source for drinking (OR = 32.257, p-value = 0.0108).

Conclusions

Sex and seasonal river as water source for drinking were considered as potential risk factors for seropositivity to BTV in camels. The high prevalence of BTV in camels in Kassala State, Eastern Sudan, necessitates further epidemiological studies of BTV infection in camels and other ruminant species to better be able to control BT disease in this region.
Representations of degenerate poly-Bernoulli polynomials
Authors: Kim Taekyun , Kim Dae San , Kwon Jongkyum , Lee Hyunseok
Published: March 2021

As is well known, poly-Bernoulli polynomials are defined in terms of polylogarithm functions. Recently, as degenerate versions of such functions and polynomials, degenerate polylogarithm functions were introduced and degenerate poly-Bernoulli polynomials were defined by means of the degenerate polylogarithm functions, and some of their properties were investigated. The aim of this paper is to further study some properties of the degenerate poly-Bernoulli polynomials by using three formulas coming from the recently developed ‘λ-umbral calculus’. In more detail, among other things, we represent the degenerate poly-Bernoulli polynomials by higher-order degenerate Bernoulli polynomials and by higher-order degenerate derangement polynomials.
Gut microbiota signatures in Schistosoma japonicum infection-induced liver cirrhosis patients: a case–control study
Authors: Gui Qi-Feng , Jin Hui-Lin , Zhu Feng , Lu Hai-Feng , Zhang Qin , Xu Jia , Yang Yun-Mei , Xiao Chi
Published: March 2021

Background

Several studies have assessed the role of gut microbiota in various cirrhosis etiologies, however, none has done so in the context of Schistosoma japonicum infection in humans. We, therefore, sought to determine whether gut microbiota is associated with S. japonicum infection-induced liver cirrhosis.

Methods

From December 2017 to November 2019, 24 patients with S. japonicum infection-induced liver cirrhosis, as well as 25 age- and sex-matched controls from the Zhejiang Province, China, were enrolled. Fecal samples were collected and used for 16S rRNA gene sequencing (particularly, the hypervariable V4 region) using the Illumina MiSeq system. Wilcoxon Rank-Sum and PERMANOVA tests were used for analysis.

Results

Eight hundred and seven operational taxonomic units (OTUs) were detected, of which, 491 were common between the two groups, whereas 123 and 193 were unique to the control and cirrhosis groups, respectively. Observed species, Chao, ACE, Shannon, Simpson, and Good’s coverage indexes, used for alpha diversity analysis, showed values of 173.4 ± 63.8, 197.7 ± 73.0, 196.3 ± 68.9, 2.96 ± 0.57, 0.13 ± 0.09, and 1.00 ± 0.00, respectively, in the control group and 154.0 ± 68.1, 178.6 ± 75.1, 179.9 ± 72.4, 2.68 ± 0.76, 0.19 ± 0.18, and 1.00 ± 0.00, respectively, in the cirrhosis group, with no significant differences observed between the groups. Beta diversity was evaluated by weighted UniFrac distances, with values of 0.40 ± 0.13 and 0.40 ± 0.11 in the control and cirrhosis groups, respectively (P > 0.05). PCA data also confirmed this similarity (P > 0.05). Meanwhile, the relative abundance of species belonging to the Bacilli class was higher in cirrhosis patients [median: 2.74%, interquartile range (IQR): 0.18–7.81%] than healthy individuals (median: 0.15%, IQR: 0.47–0.73%; P < 0.01), and that of Lactobacillales order was also higher in cirrhosis patients (median: 2.73%, IQR: 0.16–7.80%) than in healthy individuals (median: 0.12%, IQR: 0.03–0.70%; P < 0.05).

Conclusions

Cumulatively, our results suggest that the gut microbiota of S. japonicum infection-induced liver cirrhosis patients is similar to that of healthy individuals, indicating that bacterial taxa cannot be used as non-invasive biomarkers for S. japonicum infection-induced liver cirrhosis.
The impact of lockdown policy on depressive symptoms among pregnant women in China: mediating effects of internet use and family support
Authors: Zhou Yongjie , Wang Ruoxi , Liu Lei , Ding Ting , Huo Lijuan , Qi Ling , Xiong Jie , Yan Jie , Zeng Lingyun , Yang Jiezhi , Song Suyi , Dai Gaolanxin
Published: March 2021

Background

Although more and more attention has been paid to the psychological consequences of the lockdown policy amongst pregnant women, the underlying mechanism linking the lockdown policy to maternal depression has not been studied in the context of China. This study aimed to explore the association between the lockdown policy and maternal depressive symptoms, and whether such association was mediated by internet use and/or family support.

Methods

This cross-sectional study used multi-stage sampling techniques in central and western China. Data were collected from 1266 pregnant women using a structtured questionnaire that measured internet use, family support, and depressive symptoms. The Patient Health Questionnaire-9 (PHQ-9) was used to measure depressive symptoms. Internet use was measured by length of usage and varierity of purpose for internet use. Family support was measureed by spousal support and parental support. The structural equation modelling was employed to conduct mediation analysis to test the specificity of the hypothetical paths.

Results

Overall, 527 respondents (41.63%) presented depressive symptoms. The lockdown policy was negatively associated with depressive symptoms in pregnant women (β = − 0.925, 95% CI = −1.510, − 0.360). The impact of the lockdown policy on depressive symptoms was partially mediated by internet use (β = 1.589, 95% CI = 0.730, 2.807) and family support (β = − 0.162, 95% CI = − 0.341, − 0.017), accounting for 42.67% of the total effect.

Conclusions

The lockdown policy was generally associated with fewer depressive symptoms in pregnant women. The lockdown policy increased maternal depressive symptoms through increased internet use, but decreased maternal depressive symptoms through enhanced family support. The findings suggest that the psychological consequence of the lockdown policy may vary across different populations, and warrant the need to take into consideration the features of subgroups.
Effects of whole-body vibration on quadriceps and hamstring muscle strength, endurance, and power in children with hemiparetic cerebral palsy: a randomized controlled study
Authors: Hegazy Rania G. , Abdel-aziem Amr Almaz , El Hadidy Eman I. , Ali Yosra M.
Published: March 2021

Background

Hemiplegic cerebral palsy (CP) enormously affects the quadriceps and hamstring muscles. It causes weakness in the affected lower-extremity muscles in addition to muscle imbalance and inadequate power production, especially in the ankle plantar-flexor and knee extensor muscles. It also causes anomalous delayed myoelectrical action of the medial hamstring. A whole-body vibration (WBV) exercise can diminish muscle spasticity and improve walking speed, muscle strength, and gross motor function without causing unfavorable impacts in adults suffering from CP. Thus, the aim of this study is to investigate the impacts of WBV training associated with conventional physical therapy on the quadriceps and hamstring muscle strength, endurance, and power in children with hemiparetic CP.

Results

The post-intervention values of the quadriceps and hamstring muscle force, endurance, and power were significantly higher than the pre-intervention values for both groups (p = 0.001). The post-intervention values of the study group were significantly higher than the control group (quadriceps force, p = 0.015; hamstring force, p = 0.030; endurance, p = 0.025; power, p = 0.014).

Conclusion

The 8 weeks of WBV training that was added to traditional physical therapy was more successful in improving the quadriceps and hamstring muscle strength, endurance, and power in children with hemiparetic CP when compared to traditional physical therapy alone.
Correlative Biomarker Analysis of Intrinsic Subtypes and Efficacy Across the MONALEESA Phase III Studies
Authors: Prat Aleix , Chaudhury Anwesha , Solovieff Nadia , Paré Laia , Martinez Débora , Chic Nuria , Martínez-Sáez Olga , Brasó-Maristany Fara , Lteif Agnes , Taran Tetiana , Babbar Naveen , Su Fei
Published: March 2021

PURPOSE

The prognostic and predictive value of intrinsic subtypes in hormone receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer treated with endocrine therapy and ribociclib (RIB) is currently unknown. We evaluated the association of intrinsic subtypes with progression-free survival (PFS) in the MONALEESA trials.

METHODS

A retrospective and exploratory PAM50-based analysis of tumor samples from the phase III MONALEESA-2, MONALEESA-3, and MONALEESA-7 trials was undertaken. The prognostic relationship of PAM50-based subtypes with PFS and risk of disease progression by subtype and treatment were evaluated using a multivariable Cox proportional hazards model, adjusting for age, prior chemotherapy, performance status, visceral disease, bone-only metastases, histological grade, number of metastatic sites, prior endocrine therapy, and de novo metastatic disease.

RESULTS

Overall, 1,153 tumors from the RIB (n = 667) and placebo (n = 486) cohorts were robustly profiled. Subtype distribution was luminal A (LumA), 46.8%; luminal B (LumB), 24.0%; normal-like, 14.1%; HER2-enriched (HER2E), 12.6%; and basal-like, 2.4% and was generally consistent across treatment arms and trials. The associations between subtypes and PFS were statistically significant in both arms ( P < .001). The risks of disease progression for LumB, HER2E, and basal-like subtypes were 1.44, 2.32, and 3.87 times higher compared with those for LumA, respectively. All subtypes except basal-like demonstrated significant PFS benefit with RIB. HER2E (hazard ratio [HR], 0.40; P < .0001), LumB (HR, 0.52; P < .0001), LumA (HR, 0.63; P = .0007), and normal-like (HR, 0.47; P = .0005) subtypes derived benefit from RIB. Patients with basal-like subtype (n = 28) did not derive benefit from RIB (HR, 1.14; P = .78).

CONCLUSION

In this retrospective exploratory analysis of hormone receptor–positive and human epidermal growth factor receptor 2–negative advanced breast cancer, each intrinsic subtype exhibited a consistent PFS benefit with RIB, except for basal-like.
Cranial MRI Abnormalities and Long-term Follow-up of the Lesions in 770 Girls With Central Precocious Puberty
Authors: Helvacıoğlu Didem , Demircioğlu Turan Serap , Güran Tülay , Atay Zeynep , Dağçınar Adnan , Bezen Diğdem , Özturan Esin Karakılıç , Darendeliler Feyza , Yüksel Ayşegül , Dursun Fatma , Kılınç Suna , Semiz Serap , Abalı Saygın , Yıldız Metin , Önder Aşan , Bereket Abdullah
Published: March 2021

Context

Central precocious puberty (CPP) may arise from central nervous system (CNS) lesions in a few affected girls. Recently, the incidence of girls with CPP has increased mostly in 6-8 year olds, in whom the necessity of magnetic resonance imaging (MRI) is debated.

Objective

To investigate the frequency, long-term outcome and potential predictors of CNS lesions in a large cohort of girls with CPP.

Methods

A multicenter cohort of 770 Turkish girls with CPP who had systematic cranial MRI between 2005 and 2017. Age at puberty onset was <6 years in 116 and 6-8 years in 654. CNS lesions were followed until final decision(6.2 ± 3.1 years). Potential predictors of CNS lesions were evaluated by univariate analyses.

Results

A total of 104/770 (13.5%) girls had abnormal brain MRI. Of these, 2.8% were previously known CNS lesions, 3.8% had newly detected and causally related CNS lesions, 3.1 % were possibly, related and 3.8% were incidental. Only 2 (0.25%) neoplastic lesions (1 low grade glioma and 1 meningioma) were identified; neither required intervention over follow-up of 6 and 3.5 years respectively. Age at breast development <6 years (odds ratio [OR] 2.38; 95% CI 1.08-5.21) and the peak luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio >0.6 (OR 3.13; 95% CI 1.02-9.68) were significantly associated with CNS lesions. However, both patients with neoplastic lesions were >6 years old.

Conclusion

Although age and LH/FSH ratio are significant predictors of CNS lesions, their predictive power is weak. Thus, systematic MRI seems to be the most efficient current approach to avoid missing an occult CNS lesion in girls with CPP, despite the low likelihood of finding a lesion requiring intervention.
Deletion of Intestinal SHP Impairs Short-term Response to Cholic Acid Challenge in Male Mice
Authors: Nguyen James T , Riessen Ryan , Zhang Tongyu , Kieffer Collin , Anakk Sayeepriyadarshini
Published: March 2021

Small heterodimer partner (SHP) is a crucial regulator of bile acid (BA) transport and synthesis; however, its intestine-specific role is not fully understood. Here, we report that male intestine-specific Shp knockout (IShpKO) mice exhibit higher intestinal BA but not hepatic or serum BA levels compared with the f/f Shp animals when challenged with an acute (5-day) 1% cholic acid (CA) diet. We also found that BA synthetic genes Cyp7a1 and Cyp8b1 are not repressed to the same extent in IShpKO compared with control mice post-CA challenge. Loss of intestinal SHP did not alter Fxrα messenger RNA (mRNA) but increased Asbt (BA ileal uptake transporter) and Ostα (BA ileal efflux transporter) expression even under chow-fed conditions. Surprisingly, the acute CA diet in IShpKO did not elicit the expected induction of Fgf15 but was able to maintain the suppression of Asbt, and Ostα/β mRNA levels. At the protein level, apical sodium-dependent bile acid transporter (ASBT) was downregulated, while organic solute transporter-α/β (OSTα/β) expression was induced and maintained regardless of diet. Examination of ileal histology in IShpKO mice challenged with acute CA diet revealed reduced villi length and goblet cell numbers. However, no difference in villi length, and the expression of BA regulator and transporter genes, was seen between f/f Shp and IShpKO animals after a chronic (14-day) CA diet, suggesting a potential adaptive response. We found the upregulation of the Pparα-Ugt axis after 14 days of CA diet may reduce the BA burden and compensate for the ileal SHP function. Thus, our study reveals that ileal SHP expression contributes to both overall intestinal structure and BA homeostasis.
State Policy and Mental Health Outcomes under COVID-19
Authors: Sances Michael W. , Campbell Andrea Louise
Published: March 2021

Context: The COVID-19 pandemic has caused enormous damage to physiological health and economic security, especially among racial and ethnic minorities. We examined downstream effects on mental health, how effects vary by race and ethnicity, and the role of existing state-level social policies in softening the pandemic's impact.

Methods: We analyze an online, multi-wave Census Bureau survey fielded to nearly a million respondents between late April and July 2020. The survey includes questions measuring psychological distress as well as indirect measures of experience with the pandemic. We combined these data with state-level measures of COVID-19 cases, lockdown orders, unemployment filings, and safety net policy.

Findings: We find significant mental stress among all respondents and a sizeable gap between nonwhite and white respondents. Adjusting for pandemic experiences eliminates this gap. The effect of losing work as a result of the pandemic is slightly offset by state policies such as unemployment benefit size and Medicaid expansion. The magnitude of these offsetting effects is similar across racial/ethnic groups.

Conclusions: The racialized impacts of the pandemic are exacerbated by inequalities in state policy exemplifying structural racism. If the least generous states matched the policies of the most generous, inequalities caused by the pandemic would be diminished.
Joint development recovery on resumption of embryonic movement following paralysis
Authors: Rolfe Rebecca A. , Scanlon O'Callaghan David , Murphy Paula
Published: March 2021

Fetal activity in utero is a normal part of pregnancy and reduced or absent movement can lead to long-term skeletal defects, such as Fetal Akinesia Deformation Sequence, joint dysplasia and arthrogryposis. A variety of animal models with decreased or absent embryonic movements show a consistent set of developmental defects, providing insight into the aetiology of congenital skeletal abnormalities. At developing joints, defects include reduced joint interzones with frequent fusion of cartilaginous skeletal rudiments across the joint. At the spine, defects include shortening and a spectrum of curvature deformations. An important question, with relevance to possible therapeutic interventions for human conditions, is the capacity for recovery with resumption of movement following short-term immobilisation. Here, we use the well-established chick model to compare the effects of sustained immobilisation from embryonic day (E)4-10 to two different recovery scenarios: (1) natural recovery from E6 until E10 and (2) the addition of hyperactive movement stimulation during the recovery period. We demonstrate partial recovery of movement and partial recovery of joint development under both recovery conditions, but no improvement in spine defects. The joints examined (elbow, hip and knee) showed better recovery in hindlimb than forelimb, with hyperactive mobility leading to greater recovery in the knee and hip. The hip joint showed the best recovery with improved rudiment separation, tissue organisation and commencement of cavitation. This work demonstrates that movement post paralysis can partially recover specific aspects of joint development, which could inform therapeutic approaches to ameliorate the effects of human fetal immobility.

This article has an associated First Person interview with the first author of the paper.
WNT-responsive SUMOylation of ZIC5 promotes murine neural crest cell development, having multiple effects on transcription
Authors: Ali Radiya G. , Bellchambers Helen M. , Warr Nicholas , Ahmed Jehangir N. , Barratt Kristen S. , Neill Kieran , Diamand Koula E. M. , Arkell Ruth M.
Published: March 2021

Zinc finger of the cerebellum (Zic) proteins act as classic transcription factors to promote transcription of the Foxd3 gene during neural crest cell specification. Additionally, they can act as co-factors that bind proteins from the T-cell factor/lymphoid enhancing factor (TCF/LEF) family (TCFs) to repress WNT–β-catenin-dependent transcription without contacting DNA. Here, we show that ZIC activity at the neural plate border is influenced by WNT-dependent SUMOylation. In the presence of high canonical WNT activity, a lysine residue within the highly conserved zinc finger N-terminally conserved (ZF-NC) domain of ZIC5 is SUMOylated, which reduces formation of the ZIC–TCF co-repressor complex and shifts the balance towards transcription factor function. The modification is crucial in vivo, as a ZIC5 SUMO-incompetent mouse strain exhibits neural crest specification defects. This work reveals the function of the ZF-NC domain within ZIC, provides in vivo validation of target protein SUMOylation and demonstrates that WNT–β-catenin signalling directs transcription at non-TCF DNA-binding sites. Furthermore, it can explain how WNT signals convert a broad region of Zic ectodermal expression into a restricted region of neural crest cell specification.
Exposure to artificial light at night alters innate immune response in wild great tit nestlings
Authors: Ziegler Ann-Kathrin , Watson Hannah , Hegemann Arne , Meitern Richard , Canoine Virginie , Nilsson Jan-Åke , Isaksson Caroline
Published: March 2021

The large-scale impact of urbanization on wildlife is rather well documented; however, the mechanisms underlying the effects of urban environments on animal physiology and behaviour are still poorly understood. Here, we focused on one major urban pollutant – artificial light at night (ALAN) – and its effects on the capacity to mount an innate immune response in wild great tit (Parus major) nestlings. Exposure to ALAN alters circadian rhythms of physiological processes, by disrupting the nocturnal production of the hormone melatonin. Nestlings were exposed to a light source emitting 3 lx for seven consecutive nights. Subsequently, nestlings were immune challenged with a lipopolysaccharide injection, and we measured haptoglobin and nitric oxide levels pre- and post-injection. Both haptoglobin and nitric oxide are important markers for innate immune function. We found that ALAN exposure altered the innate immune response, with nestlings exposed to ALAN having lower haptoglobin and higher nitric oxide levels after the immune challenge compared with dark-night nestlings. Unexpectedly, nitric oxide levels were overall lower after the immune challenge than before. These effects were probably mediated by melatonin, as ALAN-treated birds had on average 49% lower melatonin levels than the dark-night birds. ALAN exposure did not have any clear effects on nestling growth. This study provides a potential physiological mechanism underlying the documented differences in immune function between urban and rural birds observed in other studies. Moreover, it gives evidence that ALAN exposure affects nestling physiology, potentially causing long-term effects on physiology and behaviour, which ultimately can affect their fitness.
The Dawn of Sumanene Chemistry: My Personal History with π-Figuration
Authors: Sakurai Hidehiro
Published: March 2021

A personal history of sumanene chemistry: from the encounter with Prof. Mehta’s first report to the synthesis of pristine triazasumanene is described.
Methodological Criticism of Nationalism
Authors: Akyiğit Handan
Published: March 2021

Theories of nationalism have become questionable in their own contexts with increasing interest in critical theory in sociology. Particulalry, the methods and principles of the methodological nationalism approach called as fundamentalist are questioned. The reason for the questioning of methodological nationalism is mainly attributed to its positivist understanding, universalist view of the nation and history and Eurocentric expansionist understanding. A common problem at this point of criticism is connected to the disregard of human action and social culture. The main theme of this study is the issues that methodological nationalism is in a dilemma due to its epistemological and ontological assumptions. By doing this, particular concepts of two areas will be used: constructivist theory and dialectical integrity. In this context, the principles of a new method will be discussed in order to overcome the shortcomings of methodological nationalism. The principles of the proposed method will be exemplified in the context of multiculturalism which is the subject of debate in Turkey and imagination of culture and society presented by identity politics. Therefore, the aim of this study is to show how a reading of nationalism based on historical sociology and constructivist sensibility can pave the way for new perspectives rather than a deconstruction of theories of nationalism.
Urban Life Experiences of Syrians in Turkey: The Cases of Gaziantep and Izmir
Authors: Vesek Sait , Suğur Nadir
Published: March 2021

The civil war in Syria resulted in a massive population influx into the neighboring countries since 2011. Geographical proximity of Turkey and its position as a gateway to Europe have made Turkey a host country for most Syrians refugees. Prolonging civil war in Syria and difficulties to get access to Europe compelled them to stay in Turkey. The reason why they have settled down in certain cities and difficulties that they have encountered in their everyday life merit attention to understand the very issue of refugee problems in Turkey. On that purpose, we conducted a sociological research on Syrians who settled in Gaziantep and İzmir. This paper tries to examine the degree to which Syrians are integrated into the local labour market and problems that Syrians endure in everyday life activities. The research is drawn from a fieldwork conducted on 30 semi-depth interviews in Gaziantep and 27 in İzmir. The results show that the reasons for Syrian to make a living in Gaziantep are its proximity to Syria, cultural familiarity and opportunities for Syrians entrepreneurs to do business. As for İzmir, Syrians stated its closeness to Europe, availability of jobs and better life prospect.
Ανίχνευση μεταλλικών ιόντων στο εγκεφαλονωτιαίο υγρό ασθενών μετά από ολική αρθροπλαστική γόνατος ή ισχίου
Authors: Παπαδόπουλος Παύλος
Published: March 2021

Αυτή η έρευνα αξιολόγησε τη συγκέντρωση μεταλλικών ιόντων που απελευθερώνονται στο εγκεφαλονωτιαίο υγρό σε ασθενείς που είχαν υποβληθεί σε αρθροπλαστική, αλλά και σε υγιή άτομα. Το βασικό ερώτημα που εξετάστηκε ήταν, αν η διάρκεια των προθέσεων μπορεί να επηρεάσει την συγκέντρωση των στοιχείων και συγκεκριμένα να αυξήσει την παρατηρούμενη συγκέντρωση. Μια πρώτη προσπάθεια ανίχνευσης και προσδιορισμού ιόντων μετάλλων και ιχνοστοιχείων στο αίμα ,τα ούρα και το ΕΝΥ ασθενών με ολική αρθροπλαστική γόνατος ή ισχίου πραγματοποιήθηκε στο εργαστήριο Χημείας του Α.Π.Θ. .Δέκα ασθενείς συμμετείχαν στην μελέτη αυτή, οκτώ εκ των οποίων είχαν υποβληθεί σε ολική αρθροπλαστική γόνατος ή ισχίου. Οι υπόλοιποι δύο ασθενείς δεν έφεραν εμφύτευμα και αποτέλεσαν την ομάδα ελέγχου. Οι χειρουργημένοι ασθενείς ταξινομή-θηκαν σε δύο κατηγορίες:Σε αυτούς που έφεραν αρθροπλαστκή μέχρι 5 έτη και σε αυτούς που έφεραν αρθροπλαστική από 5 εως 10 έτη. Οι ασθενείς αυτοί νοσηλεύτηκαν όλοι στην Γ΄ Πανεπιστημιακή Κλινική του Γ.Ν.΄΄Παπαγεωργίου΄΄κατά την περίοδο του Φεβρουαρίου του 2001 έως τον Απρίλιο του 2013.Τα δείγματα αίματος, ούρων και εγκεφαλονωτιίου υγρού (ΕΝΥ) των ασθενών επεξεργάστηκαν στο εργαστήριο Χημείας του Α.Π.Θ. και εστάλησαν προς ανάλυση στην Ολλανδία με την μέθοδο της νετρονικής ενεργοποίησης. Η συγκέντρωση του Co και του Cr, αυξήθηκε μόνο κατά την πρώτη περίοδο μετά την αρθροπλαστική, όπως προέκυψε από τις μετρήσεις μας στο αίμα και τα ούρα . Στην περίπτωση δειγμάτων ΕΝΥ παρατηρήθηκε μια "ανισορροπία" μεταξύ της ομάδας ελέγχου και των χειρουργημένων ασθενών με σημαντικά αυξημένες συγκεντρώσεις βρωμίου στην ομάδες που έφεραν εμφυτεύμα για 5 και 10 έτη, αλλά και του ψευδαργύρου στην ομάδα ελέγχου. Ωστόσο, δεν είναι δυνατή η εξαγωγή συμπερασμάτων, όσον αφορά την πιθανή απελευθέρωση των ιόντων Cr και Mo από προσθέσεις κράματος CrCoMo στο ΕΝΥ, λόγω της ανεπαρκούς ευαισθησίας της μεθόδου της νετρονικής ενεργοποίησης ,γεγονός που αποτελεί και την αιτία αδυναμίας λήψης αποτελεσμάτων για τα στοιχεία Ti,AL,V. Λάμβάνοντας υπόψη όλα τα παραπάνω,στην επόμενη μελέτη συμπεριελήφθησαν ασθενείς οι οποίοι κατηγο-ριοποιήθηκαν σε 5 ομάδες ανάλογα με τη διάρκεια των προθέσεων. Τα στοιχεία που μετρήθηκαν ήταν 6: Αλουμίνιο, Χρώμιο, Κοβάλτιο, Τιτάνιο, Βανάδιο και Μολυβδαίνιο και υπολογίστηκαν με τη μέθοδο ICP-MS. Όσον αφορά την συγκέντρωση αλουμινίου και χρωμίου, παρατηρήθηκε μια στατιστικά σημαντική αυξανόμενη τάση, με τους ασθενείς με τη μεγαλύτερη διάρκεια της πρόθεσης να παρουσιάζουν και υψηλότερες συγκε-ντρώσεις. Το βανάδιο παρουσίασε παρόμοια κατανομή σε όλες τις ομάδες, εκτός από την ομάδα "1" όπου οι παρατηρούμενες τιμές ήταν μικρότερες. Οι διαφορές συγκεντρώσεων τιτανίου, κοβαλτίου και μολυβδαινίου μεταξύ των ομάδων διάρκειας της πρόθεσης ήταν στατιστικά μη σημαντικές. Η αυξημένη συγκέντρωση αλουμινίου σε ασθενείς με αρθροπλαστική επιβε-βαιώνεται, επίσης, και από τον έλεγχο δειγμάτων αίματος, όπου η μέση συγκέντρωση για την ομάδα των χειρουργημένων AOP ήταν σημαντικά μεγαλύτερη από αυτή των υγιών ατόμων.
Μελέτη πολυηλεκτρολυτικών βουρτσών και μικκυλίων
Authors: Μήλιου Καλλιόπη
Published: March 2021

Στην παρούσα εργασία έγινε προσομοίωση Μοριακής Δυναμικής με σκοπό την μελέτη πολυ- ηλεκτρολυτικών μικκυλίων και πολυηλεκτρολυτικών βουρτσών. Αυτές οι δομές αποτελούν αντικείμενο έρευνας για αρκετά χρόνια λόγω της σπουδαιότητάς τους. Αρχικά μελετήθηκαν πολυηλεκτρολυτικά μικκύλια, σε διαλύματα χωρίς άλας, τα οποία σχηματίζονται από δισυσταδικά συμπολυμερή με μία υδρόφιλη και μια υδρόφοβη συστάδα. Η έρευνα εστιάζει στην επίδραση του μήκους Bjerrun, του μοριακού βάρους και του βαθμού φόρτισης της υδρόφιλης συστάδας σε διάφορα μεγέθη. Αυτά είναι ο αριθμός συσσωμάτωσης και το μέγεθος των σχηματιζόμενων μικκυλίων, το ποσοστό των αντισταθμιστικών ιόντων που περιέχονται στην κορώνα τους και το δυναμικό ζήτα. Στη συνέχεια μελετήσαμε την κίνηση των μικκυλίων που προαναφέρθηκαν μέσα σε πολυηλεκτρολυτικές βούρτσες. Οι βούρτσες σχηματίζονται από γραμμικές αλυσίδες με αντίθετη φόρτιση από τα μικκύλια, με μεταβαλλόμενη πυκνότητα εμβολιασμού και μεταβαλλόμενο ποσοστό φόρτισης. Τα μικκύλια εκτελούν μια κατευθυνόμενη κίνηση κατακόρυφα στην επιφάνεια εμβολιασμού των αλυσίδων. Από τον υπολογισμό της μέσης τετραγωνικής μετατόπισης έγινε ο χαρακτηρισμός της κίνησης ως Fickian, υπερδιάχυση ή υποδιάχυση. Τέλος μελετήσαμε μικτές βούρτσες που σχηματίζονται από αντίθετα φορτισμένα πολυμερή σχήματος Y σε διαλύματα χωρίς άλας και σε διαλύματα με μονοσθενή και δισθενή άλατα. Μελετήθηκαν διαφορετικές περιπτώσεις όσον αφορά τον σχηματισμό των βουρτσών. Αυτές αναφέρονται σε μεταβολές α) στη πυκνότητα εμβολιασμού, β) στη συγκέντρωση άλατος, γ) στο ποσοστό φόρτισης των θετικά φορτισμένων αλυσίδων, δ) στο μήκος του κλάδου των θετικά φορτισμένων αλυσίδων, ε) στον αριθμό των αλυσίδων. Βρέθηκαν οι σχέσεις κλιμάκωσης του ύψους της βούρτσας σε σχέση με την επιφάνεια εμβολιασμού ανά αλυσίδα, με το λόγο του συνολικού θετικού προς το συνολικό αρνητικό φορτίο των αλυσίδων και με τις συγκεντρώσεις του άλατος. Παρατηρήσαμε ότι η μείωση της πυκνότητας εμβολιασμού οδηγεί στο σχηματισμό μικροφάσεων. Επίσης η προσθήκη δισθενούς άλατος οδηγεί στο διαχωρισμό φυλλοειδών μικροφάσεων και στο σχηματισμό κυλινδρικών περιοχών.
M.M. Speransky: at the origins of the Political system of the RF
Authors: Matyuhin A. , Sinchuk Yu. , Panin E.
Published: March 2021

The purpose of this work is to identify the role and significance of M.M. Speransky as the founder of a theoretically sound, holistic and systemic liberal doctrine in Russia. The article uses such methods of scientific research as the historical method, the retrospective method, and the hermeneutical method. The question of the founding fathers of Russian liberalism, which ideologically has a serious impact on all spheres of modern public life, continues to be quite controversial in the historical and political science literature. From the research position of the author of the article, it is M.M. Speransky stands at the origins of Russian liberalism. During the were identified the most important theoretical parameters of the richest philosophical, political, legal heritage of Speransky, on which were based all the ideologues of Russian liberalism, till our days: the adoption of Western political experience, a focus on the formation of civil society in Russia, the need for government guarantees the rights and freedoms of the individual, etc. these parameters are presented as individual subsections, at the end conclusions and generalizations. The article also provides information about the personality of M.M. Speransky, the most important stages of his biography and political and legal activities. According to Speransky, the effectiveness of ways, methods and forms of Russian transformations increases with the skillful borrowing of Western experience, gradual "grafting" of useful elements of the legal system and political culture of the advanced countries of Western Europe. He saw his political mission as the reorganization of Russian absolutism and potential despotism into a form of constitutional monarchy based on the separation of powers and subordination to a single ("root") law. The "root law" should provide for the interests and aspirations of all the main elements of society, and the rights and freedoms of all Russian citizens will be firmly respected. This will also ensure a response from the bottom up, an increase in social activity of the population, the development of social and individual self-activity, and the emancipation of entrepreneurial talents. M.M. Speransky justified the relationship between the development of liberal trends and the need to form a full-fledged civil society in Russia. The importance of M.M. Speransky gave social mobility for the successful development of society, defended the facilitated opportunities for intersectional movements of Russian subjects.
Necessary knowledge for students about countering extremism (textbook «The Policy of countering extremism» edited by A. P. Koshkin
Authors: Matyuhin A.
Published: March 2021

The purpose of this review is to analyze and identify the socio-political, scientific and methodological significance of the textbook "The Policy of Countering Extremism". This original and extremely important textbook for Russian students, under the general editorship of Doctor of Political Sciences, Professor A. P. Koshkin, was prepared by the author's team of the Department of Political Science and Sociology of the Plekhanov Russian University of Economics and published in 2021. The textbook has a clear structure, justification of the social significance of teaching such a course in Russian universities, and the necessary methodological set for studying and consolidating the material. The concept of "countering extremism" is defined here as an activity aimed at protecting the state, society and the individual from manifestations that are actually or potentially destructive and violent. The authors of the textbook highlight the basic blocks of studying this issue, reflected in the main sections of the material, devoted to the legal aspects of countering extremism in modern Russia, as well as targeted countering extremism in the space of information culture. The author's team of the textbook gives not only scientific ideas about the realities of the policy of countering extremism in the Russian Federation, but also allocates the necessary reserves to improve the effectiveness of this policy in the regulatory and information areas of public life. The purpose of the textbook is seen as an important material that contributes to the rationalization of the consciousness of Russian students, the formation of a full-fledged picture of the world, the education of citizenship and patriotism.
Saudi Arabia migration policy in the light of the «Vision 2030»
Authors: Arshin Konstantin
Published: March 2021

The migration system of Saudi Arabia is considered as one of the most rigid in the world. Nevertheless, this state remains attractive to migrants due to due to earning opportunities. The purpose of this work is to study the key aspects of the migration policy of Saudi Arabia (ideological, social and political) that determine its state at the present stage. Within the framework of this research, the methods of systemic and logical analysis, as well as the historical method were used. These methods made it possible, on the one hand, to generalize, logically structure and interpret the collected data, on the other hand, to highlight the factors that have a significant impact on migration processes in Saudi Arabia and to present their development in historical dynamics. The study found that the migration policy of Saudi Arabia is largely based on the historical context in which the formation of the state took place, and on those ideological postulates (Wahhabism) that were used to ensure the social unity of the kingdom. The experience of Saudi Arabia in the formation and implementation of migration policy is quite specific and cannot serve as a universal model for states with different ideological values and norms. Moreover, the Kingdom itself, in order to modernize the state's economy, is ready to revise the foundations on which the country's migration system is based.
PHILOSOPHISING TOWARDS WISDOM ENTENDIDO COMO ALIMENTACIÓN DEL ÁRBOL DE LA VIDA QUE RESIDE EN NOSOTROS.
Authors: Hansen Helskog Guro
Published: March 2021

In this essay the author poses the hypothesis that the metaphor “to philosophise is to nurture the Tree of life in us” is a better metaphor than “to philosophise is to cease living” when it comes to conceptualizing what people might experience when philosophising the so called “Dialogos Way”. First, the author outlines different usages of the Tree of life metaphor. In line with reflective practice research methodology, she then explores how the metaphor corresponds to the Dialogos approach as a process- and wisdom oriented form of philosophical practice. Further, through original reflection, she narrates six examples from her experience as a philosophical practitioner. From this, six themes are extracted through critical reflection: aha-experience, peak-experience, heart-to-heart synchronization, life-guiding concepts, plateau experience and pluralism. The themes are then reflected upon theoretically and generally. Summing up, the participants seemed to have experienced forms of psychological growth rather than psychological suffering and “death” through participation in Dialogos dialogue series or workshops. The author concludes that even though the long term aim of philosophy might well be to cope with death, and even though philosophising might imply practicing “dying” through letting go of one`s more or less well founded opinions and stances, this might lead to a new “birth” and thus to psychological growth rather than psychological suffering and death, supporting the initial hypothesis.
Burundi: Państwo i społeczeństwo (od kolonializmu do współczesności)
Authors: Bar Joanna
Published: March 2021

BURUNDI: THE STATE AND SOCIETY (FROM THE COLONIAL PERIOD UNTIL THE PRESENT DAY) Burundi, a small country located in east-central Africa, is one of the most unstable countries on the continent. Similarly to the neighbouring Rwanda, over the last 50 years, the country has suffered tragic consequences of a civil war resulting from the conflict between politicians from the Tutsi and Hutu ethnic groups. The presented monograph covers a period of 130 years in a chronological manner, starting from the establishment of the foundations of the European colonial administration in the 1890s; however, the main emphasis is placed on the problems connected with the development of an independent country and strengthening (or even establishing) the national identity of its citizens. Burundi gained independence in 1962; the existing time gap allows for drawing certain conclusions and conducting an evaluation of the first 50 years of the independent existence of the country, which has little prospect of really changing the unfavorable development trends of, at least, the last three decades. At the moment, there are still no positive indications of a possible stable development of the country in the future, and the relatively stable years of the first half of the 20th century have been overshadowed by the subsequent decades of coups, genocides, and the governments’ lack of will to effectively establish peace and the rule of law.