bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and genotype diversity of Campylobacter jejuni in hunted reared pheasants (Phasianus colchicus) in Finland
Authors: Kivistö Rauni , Sauvala Mikaela , Fredriksson-Ahomaa Maria , Björkroth Johanna
Published: August 2023

Campylobacter spp., especially C. jejuni, is the most common zoonotic pathogen in humans worldwide. In Nordic countries, the prevalence of C. jejuni in broilers, which is an important reservoir of human infections, is generally low. Thus, other sources of domestically acquired infections besides chicken meat need to be considered. Game birds are known to carry a variety of zoonotic agents, including Campylobacter. The aim of this study was to investigate Campylobacter spp. carriage in a flock of reared pheasants at hunting in two successive samplings to better understand the dynamics of Campylobacter infections in pheasants. Overall, 72% of the intestinal samples were positive for Campylobacter spp. by direct culture on mCCDA. C. jejuni was the only species identified. The isolates were genotyped using whole genome sequencing (WGS), multilocus sequence typing (MLST), and ad hoc whole genome MLST (wgMLST). Two distinct C. jejuni clones were identified among the 18 isolates studied, representing MLST sequence types (STs) ST-45 and ST-699. The ST-45 isolates were closely related to previous human clinical isolates using core genome MLST (cgMLST). In contrast, the ST-699 isolates forming the dominant clone in the latter sampling were quite distinct from previously described cgMLST profiles from different hosts and sources worldwide. In conclusion, the intestine of reared pheasants is commonly colonized by C. jejuni and may carry genotypes relevant to infections in livestock and humans. Hygienic measures are needed to limit the spread of infection in reared flocks. Especially farmers and hunters having direct contact with pheasant offal need to be aware of the associated zoonosis risk to protect themselves and their working dogs alike. Biosecurity measures to improve the safety and reduce the zoonosis risk associated with pheasant farming should be further investigated.
Novel covalent CDK7 inhibitor potently induces apoptosis in acute myeloid leukemia and synergizes with Venetoclax
Authors: Gaur Tarang , Poddutoori Ramulu , Khare Leena , Bagal Bhausaheb , Rashmi Sonal , Patkar Nikhil , Tembhare Prashant , PG Subramanian , Shetty Dhanlaxmi , Dutt Amit , Zhang Qi , Konopleva Marina , Platzbeckar Uwe , Gupta Sudeep , Samajdar Susanta , Ramchandra Murali , Khattry Navin , Hasan Syed K.
Published: July 2023

Introduction

The emergence of resistance to the highly successful BCL2-directed therapy is a major unmet need in acute myeloid leukemia (AML), an aggressive malignancy with poor survival rates. Towards identifying therapeutic options for AML patients who progress on BCL2-directed therapy, we studied a clinical-stage CDK7 inhibitor XL102, which is being evaluated in solid tumors (NCT04726332).

Materials and methods

To determine the anti-proliferative effects of XL102, we performed experiments including time-resolved fluorescence resonance energy transfer, target occupancy, cell cycle and apoptosis-based assays. We also included genetically characterized primary myeloid blasts from de novo and relapsed/refractory AML patients. For mechanistic studies, CRISPR/Cas9 mediated knockout of CDK7 and c-Myc and immunoblotting were performed. NOD/SCID orthotropic and subcutaneous AML xenografts were used to determine anti-leukemic effects. To assess the synergistic effects of XL102 with Venetoclax, we performed RNA sequencing and gene set enrichment analysis using Venetoclax sensitive and resistant model systems.

Results

XL102, a highly specific, orally bioavailable covalent inhibitor of CDK7. Inhibitory effect on CDK7 by XL102 in primary myeloid blasts (n = 54) was in nanomolar range (mean = 300 nM; range = 4.0-952 nM). XL102 treated AML cells showed a reduction in phosphorylation levels of Serine 2/5/7 at carboxy-terminal domain of RNA polymerase II. T-loop phosphorylation of CDK1(Thr161) and CDK2(Thr160) was inhibited by XL102 in dose-dependent manner leading to cell-cycle arrest. c-Myc downregulation and enhanced levels of p53 and p21 in XL102 treated cells were observed. Increased levels of p21 and activation of p53 by XL102 were mimicked by genetic ablation of CDK7, which supports that the observed effects of XL102 are due to CDK7 inhibition. XL102 treated AML xenografts showed remarkable reduction in hCD45 + marrow cells (mean = 0.60%; range = 0.04%-3.53%) compared to vehicle control (mean = 38.2%; range = 10.1%-78%), with corresponding increase in p53, p21 and decrease in c-Myc levels. The data suggests XL102 induces apoptosis in AML cells via CDK7/c-Myc/p53 axis. RNA-sequencing from paired Venetoclax-sensitive and Venetoclax-resistant cells treated with XL102 showed downregulation of genes involved in proliferation and apoptosis.

Conclusion

Taken together, XL102 with Venetoclax led to synergistic effects in overcoming resistance and provided a strong rationale for clinical evaluation of XL102 as a single agent and in combination with Venetoclax.
A GATA2-CDC6 axis modulates androgen receptor blockade-induced senescence in prostate cancer
Authors: Mourkioti Ioanna , Polyzou Aikaterini , Veroutis Dimitris , Theocharous George , Lagopati Nefeli , Gentile Emanuela , Stravokefalou Vasiliki , Thanos Dimitris-Foivos , Havaki Sophia , Kletsas Dimitris , Panaretakis Theocharis , Logothetis Christopher J. , Stellas Dimitris , Petty Russell , Blandino Giovanni , Papaspyropoulos Angelos , Gorgoulis Vassilis G.
Published: July 2023

Background

Prostate cancer is a major cause of cancer morbidity and mortality in men worldwide. Androgen deprivation therapy (ADT) has proven effective in early-stage androgen-sensitive disease, but prostate cancer gradually develops into an androgen-resistant metastatic state in the vast majority of patients. According to our oncogene-induced model for cancer development, senescence is a major tumor progression barrier. However, whether senescence is implicated in the progression of early-stage androgen-sensitive to highly aggressive castration-resistant prostate cancer (CRPC) remains poorly addressed.

Methods

Androgen-dependent (LNCaP) and –independent (C4-2B and PC-3) cells were treated or not with enzalutamide, an Androgen Receptor (AR) inhibitor. RNA sequencing and pathway analyses were carried out in LNCaP cells to identify potential senescence regulators upon treatment. Assessment of the invasive potential of cells and senescence status following enzalutamide treatment and/or RNAi-mediated silencing of selected targets was performed in all cell lines, complemented by bioinformatics analyses on a wide range of in vitro and in vivo datasets. Key observations were validated in LNCaP and C4-2B mouse xenografts. Senescence induction was assessed by state-of-the-art GL13 staining by immunocytochemistry and confocal microscopy.

Results

We demonstrate that enzalutamide treatment induces senescence in androgen-sensitive cells via reduction of the replication licensing factor CDC6. Mechanistically, we show that CDC6 downregulation is mediated through endogenous activation of the GATA2 transcription factor functioning as a CDC6 repressor. Intriguingly, GATA2 levels decrease in enzalutamide-resistant cells, leading to CDC6 stabilization accompanied by activation of Epithelial-To-Mesenchymal Transition (EMT) markers and absence of senescence. We show that CDC6 loss is sufficient to reverse oncogenic features and induce senescence regardless of treatment responsiveness, thereby identifying CDC6 as a critical determinant of prostate cancer progression.

Conclusions

We identify a key GATA2-CDC6 signaling axis which is reciprocally regulated in enzalutamide-sensitive and -resistant prostate cancer environments. Upon acquired resistance, GATA2 repression leads to CDC6 stabilization, with detrimental effects in disease progression through exacerbation of EMT and abrogation of senescence. However, bypassing the GATA2-CDC6 axis by direct inhibition of CDC6 reverses oncogenic features and establishes senescence, thereby offering a therapeutic window even after acquiring resistance to therapy.
Alzheimer’s polygenic risk scores, APOE, Alzheimer’s disease risk, and dementia-related blood biomarker levels in a population-based cohort study followed over 17 years
Authors: Stocker Hannah , Trares Kira , Beyer Léon , Perna Laura , Rujescu Dan , Holleczek Bernd , Beyreuther Konrad , Gerwert Klaus , Schöttker Ben , Brenner Hermann
Published: July 2023

Background

In order to utilize polygenic risk scores (PRSs) for Alzheimer’s disease (AD) in a meaningful way, influential factors (i.e. training set) and prediction across groups such asAPOE e4 (APOE4)genotype as well as associations to dementia-related biomarkers should be explored. Therefore, we examined the association ofAPOE4and various PRSs, based on training sets that utilized differing AD definitions, with incident AD and all-cause dementia (ACD) within 17 years, and with levels of phosphorylated tau181 (P-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) in blood. Secondarily, effect modification byAPOE4status and sex was examined.

Methods

In this prospective, population-based cohort study and nested case–control study, 9,940 participants in Germany were enrolled between 2000 and 2002 by their general practitioners and followed for up to 17 years. Participants were included in this study if dementia status and genetic data were available. A subsample of participants additionally had measurements of P-tau181, NfL, and GFAP obtained from blood samples. Cox and logistic regression analyses were used to assess the association of genetic risk (APOEgenotype and PRSnoAPOE) with incident ACD/AD and log-transformed blood levels of P-tau181, NfL, and GFAP.

Results

Five thousand seven hundred sixty-five participants (54% female, aged 50-75years at baseline) were included in this study, of whom 464 received an all-cause dementia diagnosis within 17 years. The PRSs were not more predictive of dementia thanAPOE4. AnAPOE4specific relationship was apparent with PRSs only exhibiting associations to dementia amongAPOE4carriers. In the nested case–control study including biomarkers (n = 712),APOE4status and polygenic risk were significantly associated to levels of GFAP in blood.

Conclusions

The use of PRSs may be beneficial for increased precision in risk estimates amongAPOE4carriers. WhileAPOE4may play a crucial etiological role in initial disease processes such as Aβ deposition, the PRS may be an indicator of further disease drivers as well as astrocyte activation. Further research is necessary to confirm these findings, especially the association to GFAP.
Secure massive MIMO system with two-way relay cooperative transmission in 6G networks
Authors: Su Yumeng , Gao Hongyuan , Zhang Shibo
Published: July 2023

With the advent of Internet of Everything and the era of big data, massive multiple-input multiple-output (MIMO) is considered as an essential technology to meet the growing communication requirements for beyond 5G and the forthcoming 6G networks. This paper considers a secure massive MIMO system, where the legitimate user and the base station exchange messages via two-way relays with the presence of passive eavesdroppers. To achieve the trade-off between the physical-layer security and communication reliability, we design a cooperative transmission mode based on multiple-relay collaboration, where some relays broadcast the received signals and other relays act as friendly jammers to prevent the interception by eavesdroppers. A quantum chemical reaction optimization (QCRO) algorithm is proposed to find the most suitable scheme for multiple-relay collaboration. Simulation results highlight excellent performance of the proposed transmission mode under QCRO in different communication scenarios, which can be considered as a potential solution for the security issue in future wireless networks.
Best practice guidance for antibiotic audit and feedback interventions in primary care: a modified Delphi study from the Joint Programming Initiative on Antimicrobial resistance: Primary Care Antibiotic Audit and Feedback Network (JPIAMR-PAAN)
Authors: Schwartz Kevin L. , Xu Alice X. T. , Alderson Sarah , Bjerrum Lars , Brehaut Jamie , Brown Benjamin C. , Bucher Heiner C. , De Sutter An , Francis Nick , Grimshaw Jeremy , Gunnarsson Ronny , Hoye Sigurd , Ivers Noah , Lecky Donna M. , Lindbæk Morten , Linder Jeffrey A. , Little Paul , Michalsen Benedikte Olsen , O’Connor Denise , Pulcini Celine , Sundvall Pär-Daniel , Lundgren Pia Touboul , Verbakel Jan Y. , Verheij Theo J.
Published: July 2023

Background

Primary care is a critical partner for antimicrobial stewardship efforts given its high human antibiotic usage. Peer comparison audit and feedback (A&F) is often used to reduce inappropriate antibiotic prescribing. The design and implementation of A&F may impact its effectiveness. There are no best practice guidelines for peer comparison A&F in antibiotic prescribing in primary care.

Objective

To develop best practice guidelines for peer comparison A&F for antibiotic prescribing in primary care in high income countries by leveraging international expertise via the Joint Programming Initiative on Antimicrobial Resistance—Primary Care Antibiotic Audit and Feedback Network.

Methods

We used a modified Delphi process to achieve convergence of expert opinions on best practice statements for peer comparison A&F based on existing evidence and theory. Three rounds were performed, each with online surveys and virtual meetings to enable discussion and rating of each best practice statement. A five-point Likert scale was used to rate consensus with a median threshold score of 4 to indicate a consensus statement.

Results

The final set of guidelines include 13 best practice statements in four categories: general considerations (n = 3), selecting feedback recipients (n = 1), data and indicator selection (n = 4), and feedback delivery (n = 5).

Conclusion

We report an expert-derived best practice recommendations for designing and evaluating peer comparison A&F for antibiotic prescribing in primary care. These 13 statements can be used by A&F designers to optimize the impact of their quality improvement interventions, and improve antibiotic prescribing in primary care.
A prediction model for permanent pacemaker implantation after transcatheter aortic valve replacement
Authors: Qi Yiming , Lin Xiaolei , Pan Wenzhi , Zhang Xiaochun , Ding Yuefan , Chen Shasha , Zhang Lei , Zhou Daxin , Ge Junbo
Published: July 2023

Background

This study aims to develop a post-procedural risk prediction model for permanent pacemaker implantation (PPMI) in patients treated with transcatheter aortic valve replacement (TAVR).

Methods

336 patients undergoing TAVR at a single institution were included for model derivation. For primary analysis, multivariate logistic regression model was used to evaluate predictors and a risk score system was devised based on the prediction model. For secondary analysis, a Cox proportion hazard model was performed to assess characteristics associated with the time from TAVR to PPMI. The model was validated internally via bootstrap and externally using an independent cohort.

Results

48 (14.3%) patients in the derivation set had PPMI after TAVR. Prior right bundle branch block (RBBB, OR: 10.46; p < 0.001), pre-procedural aortic valve area (AVA, OR: 1.41; p = 0.004) and post- to pre-procedural AVA ratio (OR: 1.72; p = 0.043) were identified as independent predictors for PPMI. AUC was 0.7 and 0.71 in the derivation and external validation set. Prior RBBB (HR: 5.07; p < 0.001), pre-procedural AVA (HR: 1.33; p = 0.001), post-procedural AVA to prosthetic nominal area ratio (HR: 0.02; p = 0.039) and post- to pre-procedural troponin-T difference (HR: 1.72; p = 0.017) are independently associated with time to PPMI.

Conclusions

The post-procedural prediction model achieved high discriminative power and accuracy for PPMI. The risk score system was constructed and validated, providing an accessible tool in clinical setting regarding the Chinese population.
Novel agents and clinical trials in castration-resistant prostate cancer: latest updates from 2023 ASCO-GU Cancers Symposium
Authors: Jiang Yuanhong , Wu Siyu , Li Rong , Yu Jiazheng , Zheng Jianyi , Li Zeyu , Li Mingyang , Xin Kerong , Xu Zhenqun , Li Shijie , Chen Xiaonan
Published: August 2023

Numerous novel and effective therapeutic agents and clinical trials addressing castration-resistant prostate cancer (CRPC) were reported during the 2023 American Society of Clinical Oncology-Genitourinary (ASCO-GU) Cancers Symposium. Notably, radionuclide drug conjugates (RDC), specifically 177Lu/111In-J591 and 225Ac-J591, exhibited enhanced therapeutic efficacy in treating patients with CRPC. Furthermore, promising treatment approaches for CRPC included dual anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death-1 (PD-1) blockade in rare tumors (DART)-Lorigerlimab, prostate stem cell antigen (PSCA)-directed chimeric antigen receptor (CAR)-T cell immunotherapy-BPX-601, and protein kinase inhibitor (AKTi)-CAPltello-280. We have summarized the latest CRPC treatment strategies presented at the 2023 ASCO-GU Cancers Symposium, along with recent advances in CRPC clinical trials.
Results of a national survey of substance use treatment services for youth under community supervision
Authors: Knight Danica K. , Funk Rod R. , Belenko Steven , Dennis Michael , Wiese Amanda L. , Bartkowski John P. , Dembo Richard , Elkington Katherine S. , Flynn Patrick M. , Harris Philip W. , Hogue Aaron , Palinkas Lawrence A. , Robertson Angela A. , Scott Christy K.
Published: July 2023

Background

Despite the heightened risk for substance use (SU) among youth in the juvenile justice system, many do not receive the treatment that they need.

Objectives

The purpose of this study is to examine the extent to which youth under community supervision by juvenile justice agencies receive community-based SU services and the factors associated with access to such services.

Methods

Data are from a nationally representative sample of Community Supervision (CS) agencies and their primary behavioral health (BH) partners. Surveys were completed by 192 CS and 271 BH agencies.

Results

SU services are more often available through BH than CS for all treatment modalities. EBPs are more likely to be used by BH than by CS. Co-location of services occurs most often in communities with fewer treatment options and is associated with higher interagency collaboration. Youth are more likely to receive services in communities with higher EBP use, which mediates the relationship between the availability of SU treatment modalities and the proportion of youth served.

Conclusion

Findings identify opportunities to strengthen community systems and improve linkage to care.
Single nucleotide polymorphisms associated with wine fermentation and adaptation to nitrogen limitation in wild and domesticated yeast strains
Authors: Kessi-Pérez Eduardo I. , Acuña Eric , Bastías Camila , Fundora Leyanis , Villalobos-Cid Manuel , Romero Andrés , Khaiwal Sakshi , De Chiara Matteo , Liti Gianni , Salinas Francisco , Martínez Claudio
Published: July 2023

For more than 20 years, Saccharomyces cerevisiae has served as a model organism for genetic studies and molecular biology, as well as a platform for biotechnology (e.g., wine production). One of the important ecological niches of this yeast that has been extensively studied is wine fermentation, a complex microbiological process in which S. cerevisiae faces various stresses such as limited availability of nitrogen. Nitrogen deficiencies in grape juice impair fermentation rate and yeast biomass production, leading to sluggish or stuck fermentations, resulting in considerable economic losses for the wine industry. In the present work, we took advantage of the “1002 Yeast Genomes Project” population, the most complete catalogue of the genetic variation in the species and a powerful resource for genotype-phenotype correlations, to study the adaptation to nitrogen limitation in wild and domesticated yeast strains in the context of wine fermentation. We found that wild and domesticated yeast strains have different adaptations to nitrogen limitation, corroborating their different evolutionary trajectories. Using a combination of state-of-the-art bioinformatic (GWAS) and molecular biology (CRISPR-Cas9) methodologies, we validated that PNP1, RRT5 and PDR12 are implicated in wine fermentation, where RRT5 and PDR12 are also involved in yeast adaptation to nitrogen limitation. In addition, we validated SNPs in these genes leading to differences in fermentative capacities and adaptation to nitrogen limitation. Altogether, the mapped genetic variants have potential applications for the genetic improvement of industrial yeast strains.
Effects of the level of household access to water, sanitation and hygiene on the nutritional status of children under five, Benin
Authors: Gaffan Nicolas , Kpozehouen Alphonse , Degbey Cyriaque , Ahanhanzo Yolaine Glele , Paraïso Moussiliou Noël
Published: August 2023

Background

Whether or not the Water, Sanitation and Hygiene (WASH) conditions in which children under five live determine their nutritional status is still under discussion. The work aimed to study the effects of household WASH conditions to which children under five are exposed on their nutritional status in Benin.

Methods

The study utilized a cross-sectional design and consisted of secondary analyses using datasets from the fifth Demographic and Health Survey (DHS-V) conducted in Benin. Stunting, wasting and underweight were the dependent variables. The WASH conditions in which children live were evaluated in the immediate environment, i.e., at the level of their households. After describing the study variables, the relationships between the dependent variables and the exposures were checked using multivariate logistic regression. Data analysis was performed with Stata 15 and took into account the survey’s sampling design.

Results

The prevalence of stunting, wasting and underweight was 31.15% (95% CI = 29.90-32.42), 4.79% (95% CI = 4.33–5.31) and 15.82% (95% CI = 14.92–16.76), respectively. The stunting odds were 1.35 (95% CI = 1.15–1.59) and 1.27 (95% CI = 1.01–1.59) times higher for children from households with no water and sanitation services, respectively, compared to children living in households with basic water and sanitation services. Children under five from households with no hygiene facilities and using limited hygiene services had 1.31 (95% CI = 1.05–1.63) and 1.35 (95% CI = 1.10–1.67) times the odds of being stunted, respectively, compared to children covered by basic hygiene facilities. There is no evidence of a significant relationship between household access to WASH and wasting in children under five. The odds of being underweight were 1.33 (95% CI = 1.02–1.72) times higher among children under five from households with limited hygiene facilities than among children from households with basic hygiene facilities.

Conclusion

Interventions to fight malnutrition in children under five should include a WASH dimension.
Players’, Head Coaches', And Medical Personnels' Knowledge, Understandings and Perceptions of Injuries and Injury Prevention in Elite-Level Women’s Football in Ireland
Authors: Horan Dan , Kelly Seamus , Hägglund Martin , Blake Catherine , Roe Mark , Delahunt Eamonn
Published: July 2023

Background

To manage injuries effectively, players, head coaches, and medical personnel need to have excellent knowledge, attitudes, and behaviours in relation to the identification of risk factors for injuries, the implementation of injury prevention initiatives, as well as the implementation of effective injury management strategies. Understanding the injury context, whereby specific personal, environmental, and societal factors can influence the implementation of injury prevention initiatives and injury management strategies is critical to player welfare. To date, no qualitative research investigating the context of injuries, has been undertaken in elite-level women’s football. The aim of our study was to explore the knowledge, attitudes, and behaviours of players, head coaches, and medical personnel in the Irish Women’s National League (WNL) to injury prevention and injury management.

Methods

We used qualitative research methods to explore the knowledge, attitudes, and behaviours of players, head coaches, and medical personnel in the Irish WNL to injury prevention and injury management. Semi-structured interviews were undertaken with 17 players, 8 medical personnel, and 7 head coaches in the Irish WNL. The data were analysed using thematic analysis. Our study is located within an interpretivist, constructivist research paradigm.

Results

The participants had incomplete knowledge of common injuries in elite-level football, and many held beliefs about risk factors for injuries, such as menstrual cycle stage, which lacked evidence to support them. Jumping and landing exercises were commonly used to reduce the risk of injuries but evidence-based injury prevention exercises and programmes such as the Nordic hamstring curl, Copenhagen adduction exercise, and the FIFA 11+ were rarely mentioned. Overall, there was dissatisfaction amongst players with their medical care and strength and conditioning (S & C) support, with resultant inadequate communication between players, head coaches, and medical personnel.

Conclusion

Poor quality and availability of medical care and S & C support were considered to be a major obstacle in the effective implementation of injury risk reduction strategies and successful return-to-sport practices. More original research is required in elite-level women’s football to explore injury risk factors, injury prevention initiatives, and contextual return-to-sport strategies, so that players, head coaches, and medical personnel can use evidence that is both up-to-date and specific to their environment.
How should multiple myeloma research change in a patient-oriented world? Findings and lessons from the pan-Canadian myeloma priority setting partnership
Authors: Bridges Sarah , Fowler Samantha , McLaughlin Lauren , Robichaud Marc , Ridgway Barbara , Reece Donna , Song Kevin , Dalrymple Lorelei , Sully Robin , Nason Sharon , Rowland Suzanne , MacDonald Trish , Paine William , Gulliver Adrienne , Reiman Anthony
Published: July 2023

Background

Over the last decade there has been considerable research into the treatment, management, and quality of life of people living with multiple myeloma. However, there has been limited investigation into topics deemed important to patients and caregivers within this community. We conducted a James Lind Alliance Priority Setting Partnership to establish the ‘Top 10 Priorities for Myeloma Research’, informed by patient and public partners.

Methods

A research team and steering group were established in 2019 to conduct the myeloma priority setting partnership. Steering group members included patients, caregivers, and healthcare providers who advised the research team and oversaw the scope of the project, grounded on their lived experience. Following the James Lind Alliance guidelines for identification and ranking of research questions, we used surveys and a virtual workshop to collect and prioritize questions posed by myeloma patients, caregivers, and healthcare providers across Canada.

Results

The Top 10 list of priorities for myeloma research was finalized at the consensus-building workshop and encompassed questions related to diagnosis, treatment, management, and living well with myeloma. A final participant evaluation survey elicited a positive response.

Interpretation

The myeloma priority setting partnership identified the research priorities of people living with myeloma, caregivers, and healthcare providers to inform clinical research on this disease going forward. This project underscores the importance of patient and public engagement in the identification of research questions, highlighting the concerns of people affected by myeloma to ultimately improve the lives of people living with this disease.
The association between 24-hour activity, sedentary and sleep compositions and mental health in Australian adults: a cross-sectional study
Authors: Curtis Rachel G , Dumuid Dot , McCabe Hamish , Singh Ben , Ferguson Ty , Maher Carol
Published: August 2023

Background

Physical activity, sedentary behaviour, and sleep are key components to health and well-being. Compositional data analysis of activity data overcomes the limitations of traditional statistical approaches and comprehensively assesses the association of all activities throughout a 24-hour day. Few studies have used compositional analysis to explore associations between movement behaviours and mental health. This study examined the association between 24-hour activity compositions and mental health in middle-aged Australian adults.

Methods

This study used cross-sectional data from participants (n = 322; mean age 40.4 years; 58.1% female; 47.8% university degree; 84.8% partnered) in the longitudinal Annual Rhythms in Adults’ lifestyle and health study (Adelaide, Australia). Activity composition (sleep, sedentary behaviour, light physical activity, and moderate-to-vigorous physical activity) was derived using 24-hour Fitbit accelerometry from the first month of participation (December). Mental health outcomes (depression, anxiety, and stress) were obtained from the Depression Anxiety Stress Scale 21-item short-form (DASS-21). The associations between activity composition (conveyed as isometric log ratios) and DASS-21 scores were examined using compositional multi-level linear regression models with a random intercept for clustering of individuals within families. Using the compositional time reallocation model, expected differences in mental health were examined for hypothetical time reallocations between individual activities.

Results

Favourable associations were observed when time (15 min) was reallocated to light physical activity from sleep (depression: -0.31 [95% CI=-0.57: -0.06]; anxiety: -0.20 [95% CI=-0.37: -0.03] and from sedentary behaviour (depression: -0.29 [95% CI=-0.46: -0.13]; anxiety: -0.14 [95% CI=-0.25: -0.03]; stress: -0.16 [95% CI=-0.31: -0.01]). Detrimental associations were observed when time was reallocated away from light physical activity to sleep (depression: 0.32 [95% CI = 0.07: 0.58]; anxiety: 0.20 [95% CI = 0.03: 0.37]) and to sedentary behaviour (depression: 0.30 [95% CI = 0.13: 0.48); anxiety: 0.15 [95% CI = 0.03: 0.26]; stress: 0.17 [95% CI = 0.01: 0.32]). There were no associations when time was allocated to or from moderate-to-vigorous physical activity.

Conclusion

The way adults spend their time across a 24-hour day is associated with their mental health. Spending more time in light physical activity appears favourable if this time is taken from sleep and sedentary behaviour. These findings provide support for “move more, sit less” public health messages.

Trial registration

This study was prospectively registered on the Australian New Zealand Clinical Trial Registry (Trial ID: ACTRN12619001430123) on the 16/10/2019.
Improving the vibrator ground force on unconsolidated ground surfaces in Middle East desert environments
Authors: Qi Yongfei , Wei Zhouhong , Liang Fuhe , Zhao Lizhong , Criss Jason , Li Guofa
Published: August 2023

Seismic vibrators have become the preferred sources for land seismic exploration. The objective of the vibrator is to transmit a known and spatially stable source wavelet so that any variations in seismic reflection data can be used to estimate the rock properties and geometries of subsurface geology. Unfortunately, the spatial variation of the ground surface can impact the vibrator performance. Field tests have revealed that the vibrator ground force decreases dramatically on unconsolidated sandy surface conditions, and the effect increases as the vibrator shakes toward high frequencies. A theoretical study is provided to explain this repeatable phenomenon that is independent of vibrator source control systems. Moreover, a practical solution, “BP control,” remedies this reduction in ground force over unconsolidated surfaces, especially sand, by introducing a new effective baseplate weight factor into the vibrator source controller. Field test results illustrate an increase in vibrator ground force at higher-frequency conditions over unconsolidated sand when implementing this new effective baseplate into the vibrator source controller. This increase in ground force may improve the recoverable bandwidth and lead to higher-resolution seismic images when encountering these surface conditions.
The Meter Reader: Early magnetic studies in the Lake Superior region
Authors: Hinze William J.
Published: August 2023

In the mid-19th century, the quality of life in the United States was improving rapidly with widespread electrification of the nation and growth in the industrial revolution. These advances were dependent on the increasing availability of copper for instruments and electric wires and iron ore for the production of iron and steel. Accordingly, reconnaissance geologic investigations in the Lake Superior region of North America that discovered copper and iron-rich rocks in the 1840s rapidly attracted the attention of prospectors and mining companies. However, ore deposits were a challenge to find in this region because of superimposed geologic events and limited rock exposures due to the widespread cover of unconsolidated sediment deposited from Pleistocene glaciation, the abundant lakes, and, locally, the cover of Phanerozoic sedimentary rocks. Limitations to surface geologic mapping were evidenced by the few outcrops of iron formation in the iron ranges and the even fewer ore exposures. As a result, geologic mapping was restricted to locating regions for constructing test shafts and pits and drilling that would lead to identifying favorable mining sites.
Association of Gestational Diabetes Mellitus Complicated With Short Sleep Duration and Child Neurodevelopmental Delay
Authors: Zhu Yuanyuan , Wang Haixia , Ma Ruirui , Zhang Lei , Wang Yuhong , Zhang Yu , Shao Ziyu , Zhu Daomin , Zhu Peng
Published: July 2023

Context

Gestational diabetes mellitus (GDM) is a risk factor for child neurodevelopmental delay. Maternal short sleep duration (SSD) may aggravate glucose metabolism disorder in women with GDM. However, it is unclear whether maternal SSD will further affect the neurodevelopmental outcomes of children.

Objective

To identify the association of GDM complicated with SSD and child neurodevelopmental delay.

Methods

This prospective study included 7069 mother-child pairs. Between 24 and 28 weeks of gestation, GDM was based on the 75-g oral-glucose-tolerance test. Self-reported sleep duration was collected via the Pittsburgh Sleep Quality Index questionnaire in the second (24-28 weeks) and third (32-36 weeks) trimesters. Outcomes of neurodevelopmental delay in 6 to 36 months postpartum were evaluated using Denver Developmental Screening Test-II and Gesell Development Diagnosis Scale.

Results

Compared with the unexposed group, women with “GDM + SSD” have the greatest risks of child neurodevelopmental delay (hazard ratio with 95% CI: 1.58 [1.03-2.44]). “GDM + SSD” was associated with the greatest risks of maternal-fetal glucose metabolic disorder. An interquartile ratio (0.58 mmol/L) increase in cord blood C-peptide was associated with the risk of child neurodevelopmental delay (hazard ratio with 95% CI: 1.28 [1.12-1.48]). The stronger linear association of maternal glucose metabolism profiles and C-peptide in women with “GDM + SSD” was also demonstrated. The proportion of association between “GDM + SSD” and child neurodevelopmental delay mediated by C-peptide was 14.4%.

Conclusion

GDM complicated with SSD was associated with increased risk for child neurodevelopmental delay by enhancing the intergenerational association of maternal-fetal glucose metabolism disorder.
Systematic analysis of the Frazzled receptor interactome establishes previously unreported regulators of axon guidance
Authors: Zang Yixin , Bashaw Greg J.
Published: August 2023

The Netrin receptor Dcc and its Drosophila homolog Frazzled play crucial roles in diverse developmental process, including axon guidance. In Drosophila, Fra regulates midline axon guidance through a Netrin-dependent and a Netrin-independent pathway. However, what molecules regulate these distinct signaling pathways remain unclear. To identify Fra-interacting proteins, we performed affinity purification mass spectrometry to establish a neuronal-specific Fra interactome. In addition to known interactors of Fra and Dcc, including Netrin and Robo1, our screen identified 85 candidate proteins, the majority of which are conserved in humans. Many of these proteins are expressed in the ventral nerve cord, and gene ontology, pathway analysis and biochemical validation identified several previously unreported pathways, including the receptor tyrosine phosphatase Lar, subunits of the COP9 signalosome and Rho-5, a regulator of the metalloprotease Tace. Finally, genetic analysis demonstrates that these genes regulate axon guidance and may define as yet unknown signaling mechanisms for Fra and its vertebrate homolog Dcc. Thus, the Fra interactome represents a resource to guide future functional studies.
Gastruloid-derived primordial germ cell-like cells develop dynamically within integrated tissues
Authors: Cooke Christopher B. , Barrington Christopher , Baillie-Benson Peter , Nichols Jennifer , Moris Naomi
Published: August 2023

Primordial germ cells (PGCs) are the early embryonic precursors of gametes – sperm and egg cells. PGC-like cells (PGCLCs) can currently be derived in vitro from pluripotent cells exposed to signalling cocktails and aggregated into large embryonic bodies, but these do not recapitulate the native embryonic environment during PGC formation. Here, we show that mouse gastruloids, a three-dimensional in vitro model of gastrulation, contain a population of gastruloid-derived PGCLCs (Gld-PGCLCs) that resemble early PGCs in vivo. Importantly, the conserved organisation of mouse gastruloids leads to coordinated spatial and temporal localisation of Gld-PGCLCs relative to surrounding somatic cells, even in the absence of specific exogenous PGC-specific signalling or extra-embryonic tissues. In gastruloids, self-organised interactions between cells and tissues, including the endodermal epithelium, enables the specification and subsequent maturation of a pool of Gld-PGCLCs. As such, mouse gastruloids represent a new source of PGCLCs in vitro and, owing to their inherent co-development, serve as a novel model to study the dynamics of PGC development within integrated tissue environments.
Conserved chamber-specific polyploidy maintains heart function in Drosophila
Authors: Chakraborty Archan , Peterson Nora G. , King Juliet S. , Gross Ryan T. , Pla Michelle Mendiola , Thennavan Aatish , Zhou Kevin C. , DeLuca Sophia , Bursac Nenad , Bowles Dawn E. , Wolf Matthew J. , Fox Donald T.
Published: August 2023

Developmentally programmed polyploidy (whole-genome duplication) of cardiomyocytes is common across evolution. Functions of such polyploidy are essentially unknown. Here, in both Drosophila larvae and human organ donors, we reveal distinct polyploidy levels in cardiac organ chambers. In Drosophila, differential growth and cell cycle signal sensitivity leads the heart chamber to reach a higher ploidy/cell size relative to the aorta chamber. Cardiac ploidy-reduced animals exhibit reduced heart chamber size, stroke volume and cardiac output, and acceleration of circulating hemocytes. These Drosophila phenotypes mimic human cardiomyopathies. Our results identify productive and likely conserved roles for polyploidy in cardiac chambers and suggest that precise ploidy levels sculpt many developing tissues. These findings of productive cardiomyocyte polyploidy impact efforts to block developmental polyploidy to improve heart injury recovery.
Development of Photoremovable Protecting Groups Responsive to Near-Infrared Two-Photon Excitation and Their Application to Drug Delivery Research
Authors: Nguyen Linh Tran Bao , Abe Manabu
Published: August 2023

Researchers have been actively pursuing the development of photoremovable protecting groups (PPGs) that respond to near-infrared (NIR) two-photon (2P) excitation and the use of their caged compounds in cellular experiments. Our recent developments are summarized in this Account. This research on 2P excitation reactions will considerably contribute to the elucidation of the mechanism of functional expression of biologically active substances in biological samples and will lead to the development of novel drugs and new disease treatment methods. Other active research areas include imaging of materials that are responsive to 2P excitation and nanomaterial synthesis. We hope that these research fields will be useful for designing molecules sensitive to 2P excitation in the NIR region.
SOWN AREAS AS A FACTOR IN THE FORMATION OF FOOD INDEPENDENCE OF THE JEWISH AUTONOMOUS REGION
Authors: Stelmakh Elena V. , Komarova Tatiana M. , Solovchenkov Sergey A.
Published: July 2023

The aim of this study is to determine the impact of the ratio of sown areas and own production of agricultural products on the food independence of the Jewish Autonomous Region in 2005-2020.

Material and methods. The authors, in carrying out a comparative analysis of the dynamic series on the indicators of the land area by type of land and indicators of agricultural production, used the economic-statistical method, the method of analysis and synthesis, as well as methods of vertical and horizontal analysis.

Results. The data obtained indicate a decrease in the indicators of agricultural production on the territory of the subject. It is determined that the indicators of agricultural areas remain unchanged. At the same time, in 2020 there is a significant increase in the sown areas from 87.2 thousand hectares to 136.1 thousand hectares. However, when considering the indicators of own production of agricultural products, there is clearly a steady trend, with a general decline in indicators in 2020 compared with 2005, which forms a low level of food independence
BIOCOMPATIBLE BIOMIMETIC POLYMER STRUCTURES WITH AN ACTIVE RESPONSE FOR IMPLANTOLOGY AND REGENERATIVE MEDICINE PART I: BASIC PRINCIPLES OF THE ACTIVE IMPLANT’S BIOCOMPATIBILITY
Authors: Gradov Oleg V. , Gradova Margarita A. , Kochervinskii Valentin V.
Published: July 2023

Physical and chemical criteria of biocompatibility of the active polymer implants and stimuli-responsive scaffolds are considered. From the standpoint of the surface physics and controlled wetting, the possibilities of dynamic control of biocompatibility and adaptive changes in the implant properties in response to the signal from the surrounding tissues are considered. The basic properties of the active biocompatible and biomimetic implantable materials, which distinguish them from the passive implants, are summarized. The latter include: electrophysical and electrophysiological membrane biocompatibility (up to the analogy with biomembranes – the so-called Fendler’s “membrane mimetics”); excitability, that is, the ability to qualitatively change their state in response to the external stimulus; compatibility of the matching parameters and impedances of biomembranes and active implantable materials; the presence of the main types of the energy conversion characteristic of biomembranes (chemiosmotic, electrochemical, electromechanical, etc.); the ability to transport and release pharmaceuticals consistent with the parameters of the cellular microenvironment and regulated by its state. Due to the qualitative change in the biomedical aim of such implants (from replacing the natural function to its regeneration and maintenance), there is a possibility of implementing various new biologically relevant functions using these materials, such as the ability to sensing and actuation, based on their reactivity and signal / energy conversion capacity. Of particular interest is the adaptive realization of the above functions in a growing and developing organism during its ontogenesis.
ASSESSMENT OF THE CURRENT STATE OF THE AGRICULTURAL STRUCTURE OF ARGENTINA
Authors: Aksenov Ilia A. , Afonin Petr N. , Grekov Ivan V. , Abramov Aleksandr S.
Published: July 2023

Background. Argentina is one of the largest and most developed socio-economic countries in Latin America. The use of modern agricultural technologies in the Argentine plains and new methods of shipping allowed Argentina to start exporting agricultural products to Europe. A series of commodity booms enriched Argentina and made it one of the largest economies in the world at the beginning of the 20th century.

Purpose is to analyze and identify problems and prospects for the development of the agricultural structure in Argentina.

Materials and methods. In the study, the authors used analytical materials of the UN Economic Commission and other international organizations on the countries of Latin America, reviews and reports of the Central Bank, the Institute of Statistics, the Ministry of Economy and Public Finance, the Ministry of Foreign Affairs. In this work, dialectical, systemic, historical, logical, formal-legal, comparative research methods were used.

Results. Due to the abundance of appropriate land and natural resources, the favorable climate in most of the country and the generally low activity of pests, agricultural in Argentina is not particularly limited by natural conditions. However, there are a number of other factors that prevent Argentine farmers from fully operating as efficiently as possible.

Conclusion. Argentina’s agro-industrial policy is quite contradictory. Despite the development of digital services and modern information technologies to support agricultural producers, the introduction of progressive export support programs, a fairly powerful infrastructure throughout the entire production cycle of agricultural products, the Argentine government from time to time resorts to using serious export barriers to maintaining the domestic market, which in general affects the Agar sector is not always positive.
CLUSTER AS THE BASIS FOR THE SUSTAINABLE FUNCTIONING OF ENTERPRISES IN THE AGRO-INDUSTRIAL COMPLEX
Authors: Tsuglenok Olga M. , Abushenkova Marina V. , Akhmadeev Ravil G. , Tyupakov Konstantin E.
Published: July 2023

Objective. This article is devoted to the analysis of the concept of an agro-industrial cluster and the development of recommendations for improving competitiveness in the agro-industrial complex.

Materials and methods. The research methodology is based on the collection and analysis of initial data and information. The article uses a systematic approach to the study of socio-economic processes and phenomena. The study is based on modern theories of competition, innovation, as well as the modern paradigm of the cluster development of the economy.

Results. The conducted research makes a certain contribution to the development of theoretical science. A model of the structure of a regional industrial agricultural cluster is proposed. Practical recommendations can be used by economic and state authorities, heads of agricultural organizations, peasant (farm) enterprises, LPH.

Conclusion. It is concluded that the characteristic features of the cluster and the effects arising in it increase the competitiveness of both individual members of the cluster and the cluster as a whole, and the competitiveness of the region in which the cluster is located, which, in turn, leads to an increase in the competitiveness of the national economy.