bluuebunny/crossref_metadata_2025 huggingface dataset:
IDENTITY OF THE INFORMATION TECHNOLOGY EMPLOYEES AT DIFFERENT STAGES OF PROFESSIONAL DEVELOPMENT
Authors: Abdullaeva Мehirban М. , Titova Мaria А. , Pechkovskaya Еlizaveta М.
Published: March 2023

Background.] e present study of professional identity in the representatives of the information technology sphere is connected to the problem of directing modern specialists in the world of work which is rapidly changing and structuring the system of tasks in a new way. ] is requires the compliance of the psychological characteristics of an employee with computerised forms of job functions. ] e present work aims to research the features of professional identity among representatives of the information technology sector with di^ erent job experience in order to understand identity transformations during the professionalization in a more profound way. Methods. ] e respondents are o^ ered to \ ll in a questionnaire for social status data, the «Trust in technology» questionnaire (Akimova, 2020), semantic di^ erentials for the evaluation of one’s personal qualities (Ginetsinsky, 1994), and the evaluation of oneself as a professional (Serkin, 2016). Sample. It has totaled to 52 respondents studying and working in the \ eld of Network and System Management, Innovation, Information Systems and Technologies related to the IT sphere. Results. ] e data demonstrate two statistically signi\ cant trends in the development of the professional identity in the representatives of the IT sphere: the linear and the structural ones. ] e \ rst trend shows the gradual entry into one’s own specialty which is expressed in a consistent complication of ideas about oneself as a professional, the growth in con\ dence in one’s own quali\ cation, competence, and knowledge. ] e second trend is supported by restructuring the emerging ideas about oneself in the profession with the growth of real practical experience. Unlike students, in working specialists, it is expressed in «ignoring» personal characteristics and emphasizing professionally important qualities against the background of a growing con\ dence in technology and the degree of mastery. Conclusion. ] e common feature of all the participants under the study is a positive attitude towards the introduction of information technologies and experiencing di_ culties in mastering them. Professional identity of the respondents belonging to the same professional \ eld which is characterized by rapid and diverse change has got features that distinguish di^ erent stages of professionalisation. ] e results obtained make it possible to adjust the training programmes of IT specialists, taking into account the required competences as well as personal characteristics in order to approach the model of a specialist in the IT \ eld.
PERCEPTION OF FACE ATTRACTIVENESS IN PEOPLE WITH DIFFERENT LEVELS OF EMOTIONAL INTELLIGENCE
Authors: Menshikova Galina Ya. , Pichugina Anna O.
Published: March 2023

Background. Many studies have been devoted to the relationship between the perception of facial expression and emotional intelligence (EI). As a rule, the study of this issue involved the tasks of expression recognition with stimuli expressing strong basic emotions. However, diX erences in the success of expression recognition in groups with diX erent levels of EI are not always signiY cantly pronounced. Z is may be connected to the fact, that the recognition of basic expressions is too easy for subjects with both high and low EI scores. In order to conduct a more effective study of this issue, it is necessary to complicate the task of facial expressions recognition. To this end, one of the conY gurational eX ects of E. Brunswick stating that neutral faces with diX erent conY gurations of facial features are perceived as emotionally colored, can be used. Under these conditions, a more adequate task is not to assess the success of expression recognition, but to assess the attractiveness of the face, which is closely related to the perceived facial expression. Z us, faces with positive expressions are more o[ en rated as attractive, and vice versa. It is assumed that the study of the perception of neutral faces will reveal the features of the relationship between the perception of facial expression and EI. Objective. Z e study is meant to explore the relationship between the perception of facial attractiveness and EI. It was assumed that subjects with diX erent levels of EI would evaluate the attractiveness of neutral faces diX erently. Sample. Z e experiment involved 49 people (20 men and 29 women, in the age range of 18–35 years). Methods. Images of faces were presented on a monitor screen. Eye movements were recorded during stimuli presentation. Z e level of EI was assessed based on the results of the “Test of emotional intelligence” (TEI) (Sergienko et al., 2019). We calculated indicators of TEI for all branches of EI (the abilities to recognize, understand, manage, and use emotions), as well as the total score of EI. An analysis of face attractiveness scores as well as eye movement parametres (duration and number of Y xations, duration of saccades) was carried out for two groups of subjects with high and low EI scores.
“Strauss-a-Lago”: Branding Trumpism as a Conservative Alternative
Authors: Brühwiler Claudia Franziska
Published: March 2023

When Donald J. Trump announced his presidential candidacy, it seemed as if conservative intellectuals formed a united front against his ideas and persona. Michael Anton challenged this perception in his essay “The Flight 93 Election” (2016) in which he framed Trumpism as the only viable alternative to a sclerotic conservatism. As Anton received support from a prominent West Coast Straussian, Charles Kesler, a debate ensued as to what extent Trumpism reflected Straussian ideas. References to philosopher Leo Strauss and the contextualization of Anton’s quest within a Straussian intellectual space served in part the intellectual branding of a populist strand of conservatism and its differentiation from liberalism. By suggesting a proximity between Straussianism and Trump’s political views, Anton and Kesler tried to provide the Trump candidacy and, eventually, the presidency with a narrative of intellectual legitimacy and continuity, while they could simultaneously build on the Straussian critique of liberalism.
Effects of Autologous Concentrated Growth Factor on Wound Healing in Rats Contaminated with Human Feces by Activating PI3K/AKT and MEK/ERK Pathways
Authors: Shen Zhong , Zhang Xiu-Feng , Wang Hou-Dong , Yu Yan-Yan , Lei Yi-Dian , Qiu Jian-Ming
Published: March 2023

The most recent generation of bioactive substances, autologous concentrated growth factor, is rich in numerous endogenous growth factors, platelets, fibrin, and leukocytes, but its function in fistula repair is unclear. A wound model operation with human feces-contaminated wounds was prepared and ACGF from rats was collected to treat wounds. Besides, rat skin fibroblasts (RSF) were intervened with ACGF, PI3K inhibitor (LY294002), and MEK1/2 inhibitor (PD98059) alone or together. Cell viability, proliferation, cell cycle, migration, and collagen of RSF were estimated via cell counting kit-8, cell cycle assay, EdU staining, scratch assay, and ELISA assay. Extracellular matrix, MEK/ERK, and PI3K/AKT pathway-related markers in RSF were assessed with Western blot assay. ACGF augmented wound healing ability and ameliorated pathological changes but lessened the contents of inflammatory mediators of wound granulation tissue. Also, ACGF advanced proliferation-, vascular growth-related factors, collagen synthesis, and ECM function of granulation tissue and RSF. Furthermore, ACGF advanced the proliferation and migration of RSF through activating MEK/ERK and PI3K/AKT pathways, which was reversed by LY294002 and PD98059, respectively. In summary, ACGF advanced the healing of wounds in rats, and its mechanism might be associated with the aggrandizement of MEK/ERK and PI3K/AKT pathways.
Protective Effects of Maprotiline in 6-Hydroxydopamine (6-OHDA)-Induced Ferroptosis in Neuronal Cells
Authors: Cheng Hong , Chen Ying , Yang Haifan , Tang Xin , Zhu Weiyi
Published: March 2023

Neurotoxin 6-Hydroxydopamine (6-OHDA) has been associated with pathological progress of Parkinson’s disease (PD). Maprotiline is a licensed drug widely used in clinics as an antidepressant. However, maprotiline’s effect on PD is unclear. We constructed an in vitro
model in SH-SY5Y neuronal cells using 6-OHDA, followed by introduction of 2.5 and 5 μM maprotiline for 24 h. Increased intracellular reactive oxygen species (ROS) and markedly enhanced Malondialdehyde (MDA) levels were found in SH-SY5Y cells challenged by 6-OHDA, which were signally
alleviated by maprotiline.Moreover, the increased Fe2+ level, upregulated ferroportin (FPN), prostaglandin-endoperoxide synthase 2 (PTGS2), and anti-acyl-CoA synthetase long-chain family member 4 (ACSL4), downregulated Ferritin and enhanced Lactate dehydrogenase (LDH) release were
observed in 6-OHDA-challenged SH-SY5Y cells, which were observably rescued by maprotiline. Furthermore, Nrf2 was found to be extremely downregulated in SH-SY5Y neuronal challenged with 6-OHDA, the level of which was increased by maprotiline. The regulatory function of maprotiline on ferroptosis-associated
biomarkers was markedly abrogated by ML385, which is an antagonist of Nrf2. Collectively, maprotiline ameliorated ferroptosis in 6-OHDA-challenged SH-SY5Y cells by activating Nrf2.
The Impact of religiosity/spirituality on slowing the progression of substance use: Based on the National Epidemiological Survey of Alcohol and Related Conditions (NESARC-III)
Authors: Hassan Ahmed N. , Agabani Zena , Ahmed Fardowsa , Shapiro Benjamin , Le Foll Bernard
Published: March 2023

Background:

Religiosity has been suggested to be protective against substance use disorder (SUD) initiation but its impact of the progression of development is not known.

Aims:

This study investigated the impact of religiosity/spirituality on the development of heavy use and SUD following substance use initiation (alcohol, cannabis, and tobacco) utilizing data from the 2012 to 2013 National Epidemiologic Survey on Alcohol and Related Conditions-III.

Method:

Individuals with a known age at onset of substance initiation were included ( n = 30,590, n = 11,126, and n = 14,083; for alcohol, cannabis, or tobacco users, respectively). Religiosity was measured by importance of religious/spiritual beliefs and frequency of religious service attendance. The percentage of individuals who progressed to an SUD after substance initiation in each substance was estimated. Discrete-time analysis and survival analysis were used to measure the impact of religiosity on the progression from substance initiation to heavy use and from heavy use to SUD.

Results:

After controlling for various variables, religious services attendance frequency was statistically associated with a slower progression from substance initiation to heavy use for all three substances: tobacco by 8% to 15%, cannabis by 5% to 26%, and alcohol 9% ( p ⩽ .01). Religious importance was associated with slower progression to heavy use in cannabis users by 16% to 21% ( p ⩽ .02). Religiosity (believes and attendance) was associated with slowed progression from heavy use to SUD development in alcohol users only.

Conclusions:

The findings illustrate strongest association between attending religious services and lower probabilities of progressing to heavy/daily use after substance use initiation for alcohol, tobacco, and cannabis users. This indicates the potential use of religious services as social support for individuals with risky substance use.
Backfilling cohorts in phase I dose-escalation studies
Authors: Barnett Helen , Boix Oliver , Kontos Dimitris , Jaki Thomas
Published: March 2023

Background:

The use of ‘backfilling’, assigning additional patients to doses deemed safe, in phase I dose-escalation studies has been used in practice to collect additional information on the safety profile, pharmacokinetics and activity of a drug. These additional patients help ensure that the maximum tolerated dose is reliably estimated and give additional information to determine the recommended phase II dose.

Methods:

In this article, we study the effect of employing backfilling in a phase I trial on the estimation of the maximum tolerated dose and the duration of the study. We consider the situation where only one cycle of follow-up is used for escalation as well as the case where there may be delayed onset toxicities.

Results:

We find that, over a range of scenarios, the use of backfilling gives an increase in the percentage of correct selections by up to 9%. On average, for a treatment with a cycle length of 6 weeks, each additional backfilling patient reduces the trial duration by half a week.

Conclusions:

Backfilling in phase I dose-escalation studies can substantially increase the accuracy of estimation of the maximum tolerated dose, with a larger impact in the setting with a dose-limiting toxicity event assessment period of only one cycle. This increased accuracy and reduction in the trial duration are at the cost of increased sample size.
Evolution hesitancy: challenges and a way forward for teachers and teacher educators
Authors: Newall Emma , Reiss Michael J.
Published: March 2023

Background

It has long been acknowledged that evolution is a difficult topic for many students, partly because of the conceptual demands it makes, and partly because for some students an acceptance of evolution conflicts with their religious beliefs. The study we report on here was designed to see if there were additional reasons why evolution might be a difficult topic for certain students.

Results

Using in-depth, semi-structured interviews with seventeen adults studying for education qualifications, we show that evolution is a difficult topic for certain people because it can give rise to existential concerns. Thematic content analysis of interview transcripts revealed six themes associated with existential concerns: time, identity, death, responsibility/freedom, meaninglessness, and isolation. Analysis revealed that the topic of evolution frequently gave rise to feelings of disquiet.

Conclusions

Because it concerns issues to do with death, extinction and change, evolution can be deeply unsettling for many people, even if they may have difficulty articulating why this is so. Teachers when they teach evolution therefore need to consider at least three overlapping constituencies who may find evolution difficult: those for whom it is cognitively challenging; those who reject aspects of evolution on religious grounds; and those who are uncomfortable with evolution for existential reasons. Teacher educators need to decide how best to prepare new teachers for these challenges. We argue that a pedagogy based on two approaches—treating evolution as a conceptually demanding topic and treating it as a sensitive issue—may provide a way forward.
Detection of anomalies in cycling behavior with convolutional neural network and deep learning
Authors: Yaqoob Shumayla , Cafiso Salvatore , Morabito Giacomo , Pappalardo Giuseppina
Published: March 2023

Background

Cycling has always been considered a sustainable and healthy mode of transport. With the increasing concerns of greenhouse gases and pollution, policy makers are intended to support cycling as commuter mode of transport. Moreover, during Covid-19 period, cycling was further appreciated by citizens as an individual opportunity of mobility. Unfortunately, bicyclist safety has become a challenge with growing number of bicyclists in the 21st century. When compared to the traditional road safety network screening, availability of suitable data for bicycle based crashes is more difficult. In such framework, new technologies based smart cities may require new opportunities of data collection and analysis.

Methods

This research presents bicycle data requirements and treatment to get suitable information by using GPS device. Mainly, this paper proposed a deep learning-based approach “BeST-DAD” to detect anomalies and spot dangerous points on map for bicyclist to avoid a critical safety event (CSE). BeST-DAD follows Convolutional Neural Network and Autoencoder (AE) for anomaly detection. Proposed model optimization is carried out by testing different data features and BeST-DAD parameter settings, while another comparison performance is carried out between BeST-DAD and Principal Component Analysis (PCA).

Result

BeST-DAD over perform than traditional PCA statistical approaches for anomaly detection by achieving 77% of the F-score. When the trained model is tested with data from different users, 100% recall is recorded for individual user’s trained models.

Conclusion

The research results support the notion that proper GPS trajectory data and deep learning classification can be applied to identify anomalies in cycling behavior.
Genome-wide mapping of signatures of selection using a high-density array identified candidate genes for growth traits and local adaptation in chickens
Authors: Mastrangelo Salvatore , Ben-Jemaa Slim , Perini Francesco , Cendron Filippo , Biscarini Filippo , Lasagna Emiliano , Penasa Mauro , Cassandro Martino
Published: March 2023

Background

Availability of single nucleotide polymorphism (SNP) genotyping arrays and progress in statistical analyses have allowed the identification of genomic regions and genes under selection in chicken. In this study, SNP data from the 600 K Affymetrix chicken array were used to detect signatures of selection in 23 local Italian chicken populations. The populations were categorized into four groups for comparative analysis based on live weight (heavy vs light) and geographical area (Northern vs Southern Italy). Putative signatures of selection were investigated by combining three extended haplotype homozygosity (EHH) statistical approaches to quantify excess of haplotype homozygosity within (iHS) and between (RsbandXP-EHH) groups. Presence of runs of homozygosity (ROH) islands was also analysed for each group.

Results

After editing, 541 animals and 313,508 SNPs were available for statistical analyses. In total, 15 candidate genomic regions that are potentially under selection were detected among the four groups: eight within a group byiHSand seven by combining the results ofRsbandXP-EHH, which revealed divergent selection between the groups. The largest overlap between genomic regions identified to be under selection by the three approaches was on chicken chromosome 8. Twenty-one genomic regions were identified with the ROH approach but none of these overlapped with regions identified with the three EHH-derived statistics. Some of the identified regions under selection contained candidate genes with biological functions related to environmental stress, immune responses, and disease resistance, which indicate local adaptation of these chicken populations.

Conclusions

Compared to commercial lines, local populations are predominantly reared as backyard chickens, and thus, may have developed stronger resistance to environmental challenges. Our results indicate that selection can play an important role in shaping signatures of selection in local chicken populations and can be a starting point to identify gene mutations that could have a useful role with respect to climate change.
Determining the survival benefit of postoperative radiotherapy in patients with pT1-3N1M0 rectal cancer undergoing total mesorectal excision: a retrospective analysis
Authors: Chen Jin-hu , Ye Qing , Huang Feng
Published: March 2023

Background

The National Comprehensive Cancer Network guidelines recommend routine postoperative adjuvant radiotherapy and chemotherapy for patients with stage III rectal cancer who do not receive neoadjuvant therapy before surgery. The present study aimed to evaluate the value of postoperative radiotherapy in patients with low-risk disease (pT1-3N1M0) who did not receive neoadjuvant therapy prior to total mesorectal excision.

Methods

We used the Surveillance, Epidemiology, and End Results database (2004–2016) to retrospectively recruit patients with pT1-3N1M0 rectal cancer whose initial treatment was radical surgery with postoperative adjuvant chemotherapy. A propensity score model was used to balance the baseline covariates.

Results

Of the 2012 patients included in the present study, 1384 received adjuvant chemoradiotherapy (radio group), whereas the remaining 718 received chemotherapy alone (no-radio group). There was no significant difference in cancer-specific survival rate between the two groups (log-rank test χ2 = 2.372, P = 0.124) in the overall sample. Additionally, in the propensity score−matched cohort, adjuvant radiotherapy did not improve cancer-specific survival. Subgroup analysis showed that having three positive lymph nodes and a tumor > 50 mm, combined with postoperative adjuvant chemotherapy, could lead to an improved tumor-specific survival rate, while other cases did not benefit from postoperative radiotherapy.

Conclusions

For patients with pT1-3N1M0 rectal cancer who did not receive neoadjuvant therapy before surgery, postoperative radiotherapy in addition to adjuvant chemotherapy did not significantly improve survival rates. The number of positive nodes (n = 3) and tumor size (> 50 mm) were found to be potential screening indicators for postoperative adjuvant radiotherapy.
The RESISTANT study (Respiratory Muscle Training in Patients with Spinal Muscular Atrophy): study protocol for a randomized controlled trial
Authors: Kant-Smits Kim , Bartels Bart , Asselman Fay-Lynn , Veldhoen Esther S. , van Eijk Ruben P. A. , van der Pol W. Ludo , Hulzebos Erik H. J.
Published: March 2023

Background

Spinal Muscular Atrophy (SMA) is characterized by progressive and predominantly proximal and axial muscle atrophy and weakness. Respiratory muscle weakness results in impaired cough with recurrent respiratory tract infections, nocturnal hypoventilation, and may ultimately lead to fatal respiratory failure in the most severely affected patients. Treatment strategies to either slow down the decline or improve respiratory muscle function are wanting.

Objective

The aim of this study is to assess the feasibility and efficacy of respiratory muscle training (RMT) in patients with SMA and respiratory muscle weakness.

Methods

The effect of RMT in patients with SMA, aged ≥ 8 years with respiratory muscle weakness (maximum inspiratory mouth pressure [PImax] ≤ 80 Centimeters of Water Column [cmH2O]), will be investigated with a single blinded randomized sham-controlled trial consisting of a 4-month training period followed by an 8-month open label extension phase.

Intervention

The RMT program will consist of a home-based, individualized training program involving 30-breathing cycles through an inspiratory and expiratory muscle training device. Patients will be instructed to perform 10 training sessions over 5–7 days per week. In the active training group, the inspiratory and expiratory threshold will be adjusted to perceived exertion (measured on a Borg scale). The sham-control group will initially receive RMT at the same frequency but against a constant, non-therapeutic resistance. After four months the sham-control group will undergo the same intervention as the active training group (i.e., delayed intervention). Individual adherence to the RMT protocol will be reviewed every two weeks by telephone/video call with a physiotherapist.

Main study parameters/endpoints

We hypothesize that the RMT program will be feasible (good adherence and good acceptability) and improve inspiratory muscle strength (primary outcome measure) and expiratory muscle strength (key secondary outcome measure) as well as lung function, patient reported breathing difficulties, respiratory infections, and health related quality of life (additional secondary outcome measures, respectively) in patients with SMA.

Discussion

RMT is expected to have positive effects on respiratory muscle strength in patients with SMA. Integrating RMT with recently introduced genetic therapies for SMA may improve respiratory muscle strength in this patient population.

Trial registration

Retrospectively registered at clinicaltrial.gov: NCT05632666.
Exposure to nonanoic acid alters small intestinal neuroendocrine tumor phenotype
Authors: Almobarak Bilal , Amlani Vishal , Inge Linda , Hofving Tobias , Muth Andreas , Nilsson Ola , Johansson Martin , Arvidsson Yvonne , Elias Erik
Published: March 2023

Background

Small intestinal neuroendocrine tumors (SI-NET) are highly differentiated and genetically stable malignant tumors, yet they often present with advanced metastatic spread at the time of diagnosis. In contrast to many other types of malignant tumors, primary SI-NET are often asymptomatic and typically smaller in size compared to adjacent lymph node metastases. This study explores the hypothesis that stimulating the chemosensing olfactory receptor 51E1 (OR51E1) decreases SI-NET proliferation suggesting a mechanism that explains a difference in proliferative rate based on tumor location.

Methods

Clinical data was used to address difference in tumor size depending on location. A SI-NET tissue microarray was used to evaluate expression of OR51E1 and olfactory marker protein (OMP). Primary cultured tumor cells from 5 patients were utilized to determine the effect of OR51E1 agonist nonanoic acid on metabolic activity. The SI-NET cell line GOT1 was used to determine effects of nonanoic acid on the transcriptome as well as long-term effects of nonanoic acid exposure with regards to cell proliferation, serotonin secretion, alterations of the cell-cycle and morphology.

Results

Tumor size differed significantly based on location. OR51E1 and OMP were generally expressed in SI-NET. Primary SI-NET cells responded to nonanoic acid with a dose dependent altered metabolic activity and this was replicated in the GOT1 cell line but not in the MCF10A control cell line. Nonanoic acid treatment in GOT1 cells upregulated transcripts related to neuroendocrine differentiation and hormone secretion. Long-term nonanoic acid treatment of GOT1 cells decreased proliferation, induced senescence, and altered cell morphology.

Conclusion

Our results raise the possibility that exposure of intraluminal metabolites could represent a mechanism determining aspects of the SI-NET tumor phenotype. However, we could not causally link the observed effects of nonanoic acid exposure to the OR51E1 receptor.
Exposure to interparental violence and justification of intimate partner violence among women in Papua New Guinea
Authors: Aboagye Richard Gyan , Asare Bernard Yeboah-Asiamah , Adu Collins , Cadri Abdul , Seidu Abdul-Aziz , Ahinkorah Bright Opoku , Yaya Sanni
Published: March 2023

Background

Previous studies have demonstrated that exposure to interparental violence is associated with intimate partner violence justification in a variety of contexts. In this study, we examined the association between exposure to interparental violence and justification of intimate partner violence among women in Papua New Guinea.

Methods

We used data from the 2016–18 Papua New Guinea Demographic and Health Survey. We included 2839 women of reproductive age (15–49 years) in a sexual union (married and cohabiting) in the study. We used a multivariable binary multilevel regression analysis to examine the association between interparental violence and justification of intimate partner violence. We presented the results of the regression analysis using crude odds ratio (cOR) and adjusted odds ratios (aORs), with their 95% confidence intervals (CIs).

Results

Women exposed to interparental violence were 1.26 (95%CI = 1.05, 1.53) times more likely to justify intimate partner violence than those who were not exposed. Women who resided in the Highlands (aOR = 2.50, 95%CI = 1.78, 3.51), Momase (aOR = 1.96, 95%CI = 1.40, 2.75), and Islands (aOR = 1.42, 95%CI = 1.01, 1.99) were more likely to justify intimate partner violence compared to those in the Southern region. Women who were exposed to one (aOR = 1.38, 95%CI = 1.06, 1.82) mass media were more likely to justify intimate partner violence compared to those who had no exposure to mass media. On the other hand, women aged 25–34 years (aOR = 0.66, 95%CI = 0.48, 0.91) and 35–49 years (aOR = 0.66, 95%CI = 0.44, 0.97) were less likely to justify intimate partner violence compared to those aged 15–24 years.

Conclusions

Our study has shown that exposure to interparental violence is a predictor of intimate partner violence justification. This study suggests the need for conscious and continuous efforts to identify and assist women who have been exposed to interparental violence to help prevent its transition to later life. Policies and interventions should be developed and implemented to curtail children’s exposure to domestic violence in their households. Also, laws and policies need to condemn any violence and demystify community justification and acceptance of intimate partner violence, taking into consideration the significant sociodemographic characteristics of the women highlighted in the study.
Metabolically healthy obesity is associated with higher risk of both hyperfiltration and mildly reduced estimated glomerular filtration rate: the role of serum uric acid in a cross-sectional study
Authors: Zhang Hong , Chen Rui , Xu Xiaohong , Yang Minxing , Xu Wenrong , Xiang Shoukui , Wang Long , Jiang Xiaohong , Hua Fei , Huang Xiaolin
Published: March 2023

Background

The impact of metabolically healthy obesity (MHO) on kidney dysfunction remains debatable. Moreover, few studies have focused on the early stages of kidney dysfunction indicated by hyperfiltration and mildly reduced eGFR. Thus, we aimed to investigate the association between the MHO and early kidney dysfunction, which is represented by hyperfiltration and mildly reduced estimated glomerular filtration rate (eGFR), and to further explore whether serum uric acid affects this association.

Methods

This cross-sectional study enrolled 1188 residents aged ≥ 40 years old from Yonghong Communities. Metabolically healthy phenotypes were categorized based on Adult Treatment Panel III criteria. Obesity was defined as body mass index (BMI) ≥ 25 kg/m2. Mildly reduced eGFR was defined as being in the range 60 < eGFR ≤ 90 ml/min/1.73m2. Hyperfiltration was defined as eGFR > 95th percentile after adjusting for sex, age, weight, and height.

Results

Overall, MHO accounted for 12.8% of total participants and 24.6% of obese participants. Compared to metabolically healthy non-obesity (MHNO), MHO was significantly associated with an increased risk of mildly reduced eGFR (odds ratio [OR] = 1.85, 95% confidence interval [CI]  1.13–3.01) and hyperfiltration (OR = 2.28, 95% CI 1.03–5.09). However, upon further adjusting for uric acid, the association between the MHO phenotype and mildly reduced eGFR was reduced to null. Compared with MHNO/non-hyperuricemia, MHO/non-hyperuricemia was associated with an increased risk of mildly reduced eGFR (OR = 2.04, 95% CI  1.17–3.58), whereas MHO/hyperuricemia was associated with an observably increased risk (OR = 3.07, 95% CI  1.34–7.01).

Conclusions

MHO was associated with an increased risk of early kidney dysfunction, and the serum uric acid partially mediated this association. Further prospective studies are warranted to clarify the causality.
DNA methylation patterns at birth predict health outcomes in young adults born very low birthweight
Authors: Cameron Vicky A. , Jones Gregory T. , Horwood L. John , Pilbrow Anna P. , Martin Julia , Frampton Chris , Ip Wendy T. , Troughton Richard W. , Greer Charlotte , Yang Jun , Epton Michael J. , Harris Sarah L. , Darlow Brian A.
Published: March 2023

Background

Individuals born very low birthweight (VLBW) are at increased risk of impaired cardiovascular and respiratory function in adulthood. To identify markers to predict future risk for VLBW individuals, we analyzed DNA methylation at birth and at 28 years in the New Zealand (NZ) VLBW cohort (all infants born < 1500 g in NZ in 1986) compared with age-matched, normal birthweight controls. Associations between neonatal methylation and cardiac structure and function (echocardiography), vascular function and respiratory outcomes at age 28 years were documented.

Results

Genomic DNA from archived newborn heel-prick blood (n = 109 VLBW, 51 controls) and from peripheral blood at ~ 28 years (n = 215 VLBW, 96 controls) was analyzed on Illumina Infinium MethylationEPIC 850 K arrays. Following quality assurance and normalization, methylation levels were compared between VLBW cases and controls at both ages by linear regression, with genome-wide significance set to p < 0.05 adjusted for false discovery rate (FDR, Benjamini-Hochberg). In neonates, methylation at over 16,400 CpG methylation sites differed between VLBW cases and controls and the canonical pathway most enriched for these CpGs was Cardiac Hypertrophy Signaling (p = 3.44E−11). The top 20 CpGs that differed most between VLBW cases and controls featured clusters in ARID3A, SPATA33, and PLCH1 and these 3 genes, along with MCF2L, TRBJ2-1 and SRC, led the list of 15,000 differentially methylated regions (DMRs) reaching FDR-adj significance. Fifteen of the 20 top CpGs in the neonate EWAS showed associations between methylation at birth and adult cardiovascular traits (particularly LnRHI). In 28-year-old adults, twelve CpGs differed between VLBW cases and controls at FDR-adjusted significance, including hypermethylation in EBF4 (four CpGs), CFI and UNC119B and hypomethylation at three CpGs in HIF3A and one in KCNQ1. DNA methylation GrimAge scores at 28 years were significantly greater in VLBW cases versus controls and weakly associated with cardiovascular traits. Four CpGs were identified where methylation differed between VLBW cases and controls in both neonates and adults, three reversing directions with age (two CpGs in EBF4, one in SNAI1 were hypomethylated in neonates, hypermethylated in adults). Of these, cg16426670 in EBF4 at birth showed associations with several cardiovascular traits in adults.

Conclusions

These findings suggest that methylation patterns in VLBW neonates may be informative about future adult cardiovascular and respiratory outcomes and have value in guiding early preventative care to improve adult health.
Metformin regulates expression of DNA methyltransferases through the miR-148/-152 family in non-small lung cancer cells
Authors: Lee Bo Bin , Kim Dongho , Kim Yujin , Han Joungho , Shim Young Mog , Kim Duk-Hwan
Published: March 2023

Background

To understand the molecular mechanisms involved in regulation of DNA methyltransferases (DNMTs) by metformin in non-small cell lung cancer (NSCLC) cells.

Methods

Expression levels of DNMTs in response to metformin were analyzed in NSCLC cells. MicroRNAs regulating expression of DNMTs at the post-transcriptional level were searched using miRNA-target databases (miRDB and miRTarBase), TCGA RNASeqV2 lung cancer data, and miRNA-seq.

Results

Metformin dose-dependently downregulated expression of DNMT1 and DNMT3a at the post-transcriptional level and expression of DNMT3b at the transcriptional level in A549 lung cancer cells. Activity of DNMTs was reduced by about 2.6-fold in A549 cells treated with 10 mM metformin for 72 h. miR-148/-152 family members (miR-148a, miR-148b, and miR-152) targeting the 3′UTR of DNMTs were associated with post-transcriptional regulation of DNMTs by metformin. Metformin upregulated expression of miR-148a, miR-148b, and miR-152 in A549 and H1650 cells. Transfection with an miR-148b plasmid or a mimic suppressed expression of DNMT1 and DNMT3b in A549 cells. Transfection with the miR-148a mimic in A549 and H1650 cells decreased the luciferase activity of DNMT1 3′UTR. A combination of metformin and cisplatin synergistically increased expression levels of miR-148/-152 family members but decreased expression of DNMTs in A549 cells. Low expression of miR-148b was associated with poor overall survival (HR = 2.56, 95% CI 1.09—6.47; P = 0.04) but not with recurrence-free survival.

Conclusions

The present study suggests that metformin inhibits expression of DNMTs by upregulating miR-148/-152 family members in NSCLC cells.
Clusters of co-abundant proteins in the brain cortex associated with fronto-temporal lobar degeneration
Authors: Bridel Claire , van Gils Juami H. M. , Miedema Suzanne S. M. , Hoozemans Jeroen J. M. , Pijnenburg Yolande A. L. , Smit August B. , Rozemuller Annemieke J. M. , Abeln Sanne , Teunissen Charlotte E.
Published: March 2023

Background

Frontotemporal lobar degeneration (FTLD) is characterized pathologically by neuronal and glial inclusions of hyperphosphorylated tau or by neuronal cytoplasmic inclusions of TDP43. This study aimed at deciphering the molecular mechanisms leading to these distinct pathological subtypes.

Methods

To this end, we performed an unbiased mass spectrometry-based proteomic and systems-level analysis of the middle frontal gyrus cortices of FTLD-tau (n = 6), FTLD-TDP (n = 15), and control patients (n = 5). We validated these results in an independent patient cohort (total n = 24).

Results

The middle frontal gyrus cortex proteome was most significantly altered in FTLD-tau compared to controls (294 differentially expressed proteins at FDR = 0.05). The proteomic modifications in FTLD-TDP were more heterogeneous (49 differentially expressed proteins at FDR = 0.1). Weighted co-expression network analysis revealed 17 modules of co-regulated proteins, 13 of which were dysregulated in FTLD-tau. These modules included proteins associated with oxidative phosphorylation, scavenger mechanisms, chromatin regulation, and clathrin-mediated transport in both the frontal and temporal cortex of FTLD-tau. The most strongly dysregulated subnetworks identified cyclin-dependent kinase 5 (CDK5) and polypyrimidine tract-binding protein 1 (PTBP1) as key players in the disease process. Dysregulation of 9 of these modules was confirmed in independent validation data sets of FLTD-tau and control temporal and frontal cortex (total n = 24). Dysregulated modules were primarily associated with changes in astrocyte and endothelial cell protein abundance levels, indicating pathological changes in FTD are not limited to neurons.

Conclusions

Using this innovative workflow and zooming in on the most strongly dysregulated proteins of the identified modules, we were able to identify disease-associated mechanisms in FTLD-tau with high potential as biomarkers and/or therapeutic targets.
GlyLES: Grammar-based Parsing of Glycans from IUPAC-condensed to SMILES
Authors: Joeres Roman , Bojar Daniel , Kalinina Olga V.
Published: March 2023

Glycans are important polysaccharides on cellular surfaces that are bound to glycoproteins and glycolipids. These are one of the most common post-translational modifications of proteins in eukaryotic cells. They play important roles in protein folding, cell-cell interactions, and other extracellular processes. Changes in glycan structures may influence the course of different diseases, such as infections or cancer. Glycans are commonly represented using the IUPAC-condensed notation. IUPAC-condensed is a textual representation of glycans operating on the same topological level as the Symbol Nomenclature for Glycans (SNFG) that assigns colored, geometrical shapes to the main monomers. These symbols are then connected in tree-like structures, visualizing the glycan structure on a topological level. Yet for a representation on the atomic level, notations such as SMILES should be used. To our knowledge, there is no easy-to-use, general, open-source, and offline tool to convert the IUPAC-condensed notation to SMILES. Here, we present the open-access Python package GlyLES for the generalizable generation of SMILES representations out of IUPAC-condensed representations. GlyLES uses a grammar to read in the monomer tree from the IUPAC-condensed notation. From this tree, the tool can compute the atomic structures of each monomer based on their IUPAC-condensed descriptions. In the last step, it merges all monomers into the atomic structure of a glycan in the SMILES notation. GlyLES is the first package that allows conversion from the IUPAC-condensed notation of glycans to SMILES strings. This may have multiple applications, including straightforward visualization, substructure search, molecular modeling and docking, and a new featurization strategy for machine-learning algorithms. GlyLES is available at https://github.com/kalininalab/GlyLES.
Production of gathering spaces in post-disaster recovery scenarios: case studies from the Great East Japan Earthquake and Tsunami-2011
Authors: Ghezelloo Yegane , Hokugo Akihiko , Tsukihashi Osamu
Published: March 2023

Gathering and public spaces, along with infrastructure and houses, are demolished because of disasters, which weakens the community ties. Different approaches, such as government-led and community-driven, to recovery initiate the recovery of gatherings and public spaces, and the long-term impact of each recovery approach on community recovery may not be overseen. This study attempts to determine incorporation of community participation in different recovery approaches and its corresponding result in the production of gathering spaces, based on two main background theories: Arnstein’s ladder of citizen participation and Henri Lefebvre’s production of space triad. We attempted to determine the results by reviewing case studies with different recovery processes after the Great East Japan Earthquake and Tsunami-2011 and through interviews and questionnaire surveys. The results showed that the production of gathering spaces may be associated with the recovery scenario in each case study. In community-driven cases, the main gathering spaces are small open spaces, evenly superimposed and accessible, and diverse in spatial configuration, provide services for the users at a good level, and are in a sync with other gathering spaces. By contrast, in government-led cases, gathering spaces contain primary and secondary spaces that lack connections with each other. These main gathering spaces are centralized near disaster public housing sites, are highly accessible to disaster public housing residents, provide a high range of leisure-based activities, and provide services to users from inside and outside of the communities. These main gathering spaces are extended by inclusive open space (Hiroba) and this spatial planning is closer to the concept of public spaces compared to others.
Acute myocarditis during adjuvant therapies for breast cancer: a case report
Authors: Ushiyama Yumiko , Horimoto Yoshiya , Uomori Toshitaka , Ishizuka Yumiko , Okazaki Misato , Onagi Hiroko , Hayashi Takuo , Watanabe Junichiro , Saito Mitsue
Published: March 2023

Background

With the improvement of optimal perioperative drug therapy for breast cancer patients, physicians now have to treat the adverse effects and comorbidities associated with long-term treatments. We report a case who suffered cardiac arrest due to acute myocarditis developed after initiation of adjuvant treatment.

Case presentation

After completing preoperative chemotherapy and undergoing curative surgery for right breast cancer, a 46-year-old female patient started adjuvant tamoxifen and resumed trastuzumab. Two months later, she complained fever and dyspnea. Blood tests showed a marked increase in hepatic enzymes, and the patient was rushed to our emergency room on suspicion of drug-induced liver injury. In the emergency room, the patient went into cardiac arrest shortly after tachycardia with ST-segment elevation appeared on the monitored electrocardiogram. Resuscitation was started immediately and tracheal intubation, intra-aortic balloon pumping, and extracorporeal membrane oxygenation were started. Coronary angiography results were negative for ischemic heart disease. A diagnosis of fulminant myocarditis was made and steroid pulse therapy and immunoglobulin therapy were started. After the start of treatment, the symptoms of heart failure improved steadily and the patient was discharged on the 28th day. Histological findings of the myocardial biopsy revealed degeneration and necrosis of myocardial cells with marked lymphocytic infiltration, consistent with the histology of lymphocytic myocarditis. Serum cytomegalovirus, coxsackie B virus and adenovirus antibodies were all elevated and these findings were consistent with acute viral myocarditis.

Conclusions

We report a case with strong indications for therapy-induced liver damage, who was ultimately diagnosed with acute viral myocarditis and successfully treated with multidisciplinary therapy. We believe that our findings would be useful for other clinicians in managing similar patients.
Designing a generic, adaptive protocol resource for the measurement of health impact in cash transfer pilot and feasibility studies and trials in high-income countries
Authors: Johnson Elliott Aidan , Johnson Matthew Thomas , Kypridemos Christodoulos , Villadsen Aase , Pickett Kate E.
Published: March 2023

Introduction

In the context of the COVID-19 pandemic, upstream interventions that tackle social determinants of health inequalities have never been more important. Evaluations of upstream cash transfer trials have failed to capture comprehensively the impacts that such systems might have on population health through inadequate design of the interventions themselves and failure to implement consistent, thorough research measures that can be used in microsimulations to model long-term impact. In this article, we describe the process of developing a generic, adaptive protocol resource to address this issue and the challenges involved in that process. The resource is designed for use in high-income countries (HIC) but draws on examples from a UK context to illustrate means of development and deployment. The resource is capable of further adaptation for use in low- and middle-income countries (LMIC). It has particular application for trials of Universal Basic Income but can be adapted to those covering other kinds of cash transfer and welfare system changes.

Methods

We outline two types of prospective intervention based on pilots and trials currently under discussion. In developing the remainder of the resource, we establish six key principles, implement a modular approach based on types of measure and their prospective resource intensity, and source (validated where possible) measures and baseline data primarily from routine collection and large, longitudinal cohort studies. Through these measures, we seek to cover all areas of health impact identified in our theoretical model for use in pilot and feasibility studies.

Results

We find that, in general, self-reported measures alongside routinely collected linked respondent data may provide a feasible means of producing data capable of demonstrating comprehensive health impact. However, we also suggest that, where possible, physiological measures should be included to elucidate underlying biological effects that may not be accurately captured through self-reporting alone and can enable modelling of long-term health outcomes. In addition, accurate self-reported objective income data remains a challenge and requires further development and testing. A process of development and implementation of the resource in pilot and feasibility studies will support assessment of whether or not our proposed health outcome measures are acceptable, feasible and can be used with validity and reliability in the target population.

Discussion

We suggest that while Open Access evaluation instruments are available and usable to measure most constructs of interest, there remain some areas for which further development is necessary. This includes self-reported wellbeing measures that require paid licences but are used in a range of nationally important longitudinal studies instead of Open Access alternatives.