bluuebunny/crossref_metadata_2025 huggingface dataset:
Would you like some background? Establishing shared rights and duties in video relay service calls to the police
Authors: Skinner Robert
Published: April 2023

When an interpreter mediates a call from the public to a police force control room (FCR), the partnership established between the interpreter and the call-handler is critical to the caller’s ability to be understood and supported. Using Davies and Harré’s Positioning Theory, this study investigates different approaches to the establishment of relationships and identities during the opening phases of a non-emergency police video relay services (VRS) call. The data consist of four simulated VRS-interpreted calls to a Police Scotland FCR and focus group reflections. This article describes two opening approaches to interpreter-mediated communication, namely the emergent approach, where rights and duties are established and reviewed, and the process-driven approach, which focuses on the completion of tasks. The emergent approach demonstrates the benefits of establishing consent and the multiple roles that are collectively performed, whereas a process-driven approach during the opening phase of a call does not train callers how to participate in a 101VRS call. The findings emphasise the need for trainers and policymakers to support interpreters in handling their auxiliary role as first call receiver.
Classroom Management in K–12 Classroom Music: A Review of the Literature
Authors: Langstaff Jacob
Published: April 2023

Classroom management is reported to be among the greatest difficulties for beginning music educators. The purpose of this literature review was to examine extant research studies on the topic of classroom management in K–12 classroom music. Research topics included the components of classroom management, preservice and inservice teacher beliefs and perceptions regarding classroom management, and approaches to classroom management. Findings indicated no clear agreement on the components of classroom management among researchers. Nevertheless, classroom management is an area of concern for both preservice and inservice teachers, and educators have expressed a desire for more preparation in this area. In addition, results of international studies indicated that preservice teachers from diverse cultures may have had differing expectations for various aspects of classroom management. I found little empirical research on specific strategies for classroom management in the music classroom. Implications for practice and recommendations for further research are included.
Duodenal macrophages control dietary iron absorption via local degradation of transferrin
Authors: Sukhbaatar Nyamdelger , Schöller Maria , Fritsch Stephanie Deborah , Linke Monika , Horer Stefanie , Träger Manuela , Mazic Mario , Forisch Stephan , Gonzales Karine , Kahler Jan Pascal , Binder Carina , Lassnig Caroline , Strobl Birgit , Mueller Mathias , Scheiber-Mojdehkar Barbara , Gundacker Claudia , Dabsch Stefanie , Kain Renate , Hengstschläger Markus , Verhelst Steven , Weiss Günter , Theurl Igor , Weichhart Thomas
Published: April 2023

Iron is an essential cellular metal that is important for many physiological functions including erythropoiesis and host defense. It is absorbed from the diet in the duodenum and loaded onto transferrin, the main iron transport protein. Inefficient dietary iron uptake promotes many diseases, but mechanisms regulating iron absorption remain poorly understood. By assessing mice that harbor a macrophage-specific deletion of the tuberous sclerosis complex 2 (Tsc2), a negative regulator of mTORC1, we found that these mice possessed various defects in iron metabolism including defective steady state erythropoiesis and a reduced saturation of transferrin with iron. This iron-deficiency phenotype was associated with an iron import block from the duodenal epithelial cells into the circulation. Activation of mTORC1 in villous duodenal CD68+ macrophages induced serine protease expression and promoted local degradation of transferrin, whereas depletion of macrophages in mice increased transferrin levels. Inhibition of mTORC1 with everolimus or serine protease activity with nafamostat restored transferrin levels in the Tsc2-deficient mice as well as transferrin saturation. Physiologically, transferrin levels were regulated in the duodenum during the prandial process and Citrobacter rodentium infection. These data suggest that duodenal macrophages determine iron transfer to the circulation by controlling transferrin availability in the lamina propria villi.
Characterization of Bone Marrow Niche in Chronic Myeloid Leukemia Patients Identifies CXCL14 as a New Therapeutic Option
Authors: Dolinska Monika , Cai Huan , Mansson Alma , Shen Jingyi , Xiao Pingnan , Bouderlique Thibault , Li Xidan , Leonard Elory , Chang Marcus , Gao Yuchen , Medina Giménez Juan Pablo , Kondo Makoto , Sandhow Lakshmi , Johansson Anne-Sofie , Deneberg Stefan , Söderlund Stina , Jädersten Martin , Ungerstedt Johanna S , Tobiasson Magnus , Östman Arne , Mustjoki Satu , Stenke Leif , Le Blanc Katarina , Hellstrom-Lindberg Eva S , Lehmann Sören , Ekblom Marja , Olsson-Strömberg Ulla , Sigvardsson Mikael , Qian Hong
Published: April 2023

Although tyrosine kinase inhibitors are effective for treating chronic myeloid leukemia (CML), they often fail to eradicate the leukemia-initiating stem cells (LSCs), causing disease persistence and relapse. Evidence indicates that LSC persistence may be due to bone marrow (BM) niche protection. However, little is known about the underlying mechanisms. We here molecularly and functionally characterized BM niches in CML patients at diagnosis and revealed the altered niche composition and function in the CML patients. Long-term culture initiating cell (LTC-IC) assay showed that the mesenchymal stem cells from CML patients displayed an enhanced supporting capacity for normal and CML BM CD34+CD38- cells. Molecularly, RNA sequencing detected dysregulated cytokine and growth factor expression in CML patient BM cellular niches. Among them, CXCL14 was lost in the BM cellular niches in contrast to its expression in healthy BM. Restoring CXCL14 significantly inhibited CML LSC maintenance and enhanced their response to imatinib in vitro, and CML engraftment in vivo in NSG-SGM3 mice. Importantly, CXCL14 treatment dramatically inhibited CML engraftment in xenografted NSG-SGM3 mice, even to a greater degree than imatinib, and this inhibition persisted in patients with suboptimal TKI response. Mechanistically, CXCL14 upregulated inflammatory cytokine signaling but downregulated mTOR signaling and oxidative phosphorylation in CML LSCs. Together, we have discovered a suppressive role of CXCL14 in CML LSC growth. CXCL14 might offer a treatment option targeting CML LSCs.
Microstructure, Properties and Crack Suppression Mechanism of High-speed Steel Fabricated by Selective Laser Melting at Different Process Parameters
Authors: Ji Wenbin , Liu Chuncheng , Dai Shijie , Deng Riqing
Published: April 2023

To enrich material types applied to additive manufacturing and enlarge application scope of additive manufacturing in conformal cooling tools, M2 high-speed steel specimens were fabricated by selective laser melting (SLM). Effects of SLM parameters on the microstructure and mechanical properties of M2 high-speed steel were investigated. The results showed that substrate temperature and energy density had significant influence on the densification process of materials and defects control. Models to evaluate the effect of substrate temperature and energy density on hardness were studied. The optimized process parameters, laser power, scan speed, scan distance, and substrate temperature, for fabricated M2 are 220 W, 960 mm/s, 0.06 mm, and 200 ℃, respectively. Based on this, the hardness and tensile strength reached 60 HRC and 1000 MPa, respectively. Interlaminar crack formation and suppression mechanism and the relationship between temperature gradient and thermal stress were illustrated. The inhibition effect of substrate temperature on the cracks generated by residual stresses was also explained. AM showed great application potential in the field of special conformal cooling cutting tool preparation.
Assessment of acute and chronic ecotoxicological effects of aqueous eluates of stone wool insulation materials
Authors: Smollich Esther , Döbbeler Eberhard , Müller-Geipel Tina , Stratmann Lars , Koch Christoph , Merkus Valentina I. , Kostka Kathrin , Okhrimenko Denis V. , Solvang Mette , Nachev Milen , Zimmermann Sonja , Schmidt Torsten C. , Sures Bernd
Published: April 2023

Background

Stone wool is an inorganic mineral insulation material increasingly used to reduce the climate impact of buildings. The acute and chronic ecotoxicological potential of stone wool eluates have been studied in a battery of standardized laboratory ecotoxicological tests. The experiments were conducted with stone wool test materials in fibrous and milled form, with and without the presence of organic binder. For the preparation of eluates, the OECD protocol on the transformation/dissolution of metals and metal compounds was applied. The resulting eluates were used in acute tests, i.e., bioluminescence test with Aliivibrio fischeri (DIN EN ISO 11348-1:2009), algae growth test with Desmodesmus subspicatus (OECD No. 201) and immobilization test with Daphnia magna (OECD No. 202), as well as chronic tests, i.e., the Daphnia magna reproduction test (OECD No. 211) and the nematode growth and reproduction test with Caenorhabditis elegans (ISO 10872:2010).

Results

While no acute or chronic ecotoxicological effects of the eluates were observed for fibrous stone wool material, the milled test materials showed some chronic effects on aquatic invertebrates. Depending on the test materials and concentrations of milled stone wool used in the eluate preparation, these chronic effects included significant stimulation or inhibition of daphnid reproduction and nematode growth. The chemical analysis conducted in parallel to the ecotoxicological assessment indicated no leaching of organic substances from the applied binder or mineral oils and no formation of nanoparticles by the milling of stone wool. Furthermore, ICP-MS and ICP-OES analysis of eighteen elements revealed that only aluminum and nickel could be quantified in the eluates, at concentrations of approximately 750 µg/L and 7 µg/L, respectively.

Conclusions

Based on the present ecotoxicological assessment, eluates from stone wool fibers cannot be considered as chemically hazardous to the aquatic environment. However, additional investigations of the ecotoxicological potential of the milled material and the environmental exposure of stone wool products are necessary for a complete evaluation of potentially negative effects of stone wool insulation materials.
Whole genome sequencing of simmental cattle for SNP and CNV discovery
Authors: Sun Ting , Pei Shengwei , Liu Yangkai , Hanif Quratulain , Xu Haiyue , Chen Ningbo , Lei Chuzhao , Yue Xiangpeng
Published: April 2023

Backgroud

The single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) are two major genomic variants, which play crucial roles in evolutionary and phenotypic diversity.

Results

In this study, we performed a comprehensive analysis to explore the genetic variations (SNPs and CNVs) of high sperm motility (HSM) and poor sperm motility (PSM) Simmental bulls using the high-coverage (25×) short-read next generation sequencing and single-molecule long reads sequencing data. A total of ~ 15 million SNPs and 2,944 CNV regions (CNVRs) were detected in Simmental bulls, and a set of positive selected genes (PSGs) and CNVRs were found to be overlapped with quantitative trait loci (QTLs) involving immunity, muscle development, reproduction, etc. In addition, we detected two new variants in LEPR, which may be related to the artificial breeding to improve important economic traits. Moreover, a set of genes and pathways functionally related to male fertility were identified. Remarkably, a CNV on SPAG16 (chr2:101,427,468 − 101,429,883) was completely deleted in all poor sperm motility (PSM) bulls and half of the bulls in high sperm motility (HSM), which may play a crucial role in the bull-fertility.

Conclusions

In conclusion, this study provides a valuable genetic variation resource for the cattle breeding and selection programs.
Genome-wide identification of the geranylgeranyl pyrophosphate synthase (GGPS) gene family involved in chlorophyll synthesis in cotton
Authors: Feng Wenxiang , Mehari Teame Gereziher , Fang Hui , Ji Meijun , Qu Zijian , Jia Mengxue , Wang Dongmei , Ditta Allah , Khan Muhammad K. R. , Cao Yunying , Wu Jianyong , Wang Baohua
Published: April 2023

Background

Geranylgeranyl pyrophosphate synthase (GGPS) is a structural enzyme of the terpene biosynthesis pathway that is involved in regulating plant photosynthesis, growth and development, but this gene family has not been systematically studied in cotton.

Results

In the current research, genome-wide identification was performed, and a total of 75 GGPS family members were found in four cotton species,Gossypium hirsutum,Gossypium barbadense,Gossypium arboreumandGossypium raimondii. The GGPS genes were divided into three subgroups by evolutionary analysis. Subcellular localization prediction showed that they were mainly located in chloroplasts and plastids. The closely related GGPS contains a similar gene structure and conserved motif, but some genes are quite different, resulting in functional differentiation. Chromosome location analysis, collinearity and selection pressure analysis showed that many fragment duplication events occurred in GGPS genes. Three-dimensional structure analysis and conservative sequence analysis showed that the members of the GGPS family contained a large number of α-helices and random crimps, and all contained two aspartic acid-rich domains, DDxxxxD and DDxxD (x is an arbitrary amino acid), suggesting its key role in function. Cis-regulatory element analysis showed that cotton GGPS may be involved in light response, abiotic stress and other processes. A GGPS gene was silenced successfully by virus-induced gene silencing (VIGS), and it was found that the chlorophyll content in cotton leaves decreased significantly, suggesting that the gene plays an important role in plant photosynthesis.

Conclusions

In total, 75 genes were identified in fourGossypiumspecies by a series of bioinformatics analysis. Gene silencing from GGPS members ofG. hirsutumrevealed that GGPS plays an important regulatory role in photosynthesis. This study provides a theoretical basis for the biological function of GGPS in cotton growth and development.
GelFAP v2.0: an improved platform for Gene functional analysis in Gastrodia elata
Authors: Yang Jiaotong , Li Pengfei , Li Yuping , Xiao Qiaoqiao
Published: April 2023

Background

Gastrodia elata(tianma), a well-known medicinal orchid, is widely used to treat various kinds of diseases with its dried tuber. In recent years, new chromosome-level genomes ofG.elatahave been released in succession, which offer an enormous resource pool for understanding gene function. Previously we have constructed GelFAP for gene functional analysis ofG.elata. As genomes are updated and transcriptome data is accumulated, collection data in GelFAP cannot meet the need of researchers.

Results

Based on new chromosome-level genome and transcriptome data, we constructed co-expression network ofG. elata, and then we annotated genes by aligning with sequences from NR, TAIR, Uniprot and Swissprot database. GO (Gene Ontology) and KEGG (Kyoto Encylopaedia of Genes and Genomes) annotations were predicted by InterProScan and GhostKOALA software. Gene families were further predicted by iTAK (Plant Transcription factor and Protein kinase Identifier and Classifier), HMMER (hidden Markov models), InParanoid. Finally, we developed an improved platform for gene functional analysis inG. elata(GelFAP v2.0) by integrating new genome, transcriptome data and processed functional annotation. Several tools were also introduced to platform including BLAST (Basic Local Alignment Search Tool), GSEA (Gene Set Enrichment Analysis), Heatmap, JBrowse, Motif analysis and Sequence extraction. Based on this platform, we found that the flavonoid biosynthesis might be regulated by transcription factors (TFs) such as MYB, HB and NAC. We also tookC4HandGAFP4as examples to show the usage of our platform.

Conclusion

An improved platform for gene functional analysis inG. elata(GelFAP v2.0,www.gzybioinformatics.cn/Gelv2) was constructed, which provides better genome data, more transcriptome resources and more analysis tools. The updated platform might be preferably benefit researchers to carry out gene functional research for their project.
Comparative genomics analyses reveal sequence determinants underlying interspecies variations in injury-responsive enhancers
Authors: Ji Luzhang , Shi Yuanyuan , Bian Qian
Published: April 2023

Background

Injury induces profound transcriptional remodeling events, which could lead to only wound healing, partial tissue repair, or perfect regeneration in different species. Injury-responsive enhancers (IREs) are cis-regulatory elements activated in response to injury signals, and have been demonstrated to promote tissue regeneration in some organisms such as zebrafish and flies. However, the functional significances of IREs in mammals remain elusive. Moreover, whether the transcriptional responses elicited by IREs upon injury are conserved or specialized in different species, and what sequence features may underlie the functional variations of IREs have not been elucidated.

Results

We identified a set of IREs that are activated in both regenerative and non-regenerative neonatal mouse hearts upon myocardial ischemia-induced damage by integrative epigenomic and transcriptomic analyses. Motif enrichment analysis showed that AP-1 and ETS transcription factor binding motifs are significantly enriched in both zebrafish and mouse IREs. However, the IRE-associated genes vary considerably between the two species. We further found that the IRE-related sequences in zebrafish and mice diverge greatly, with the loss of IRE inducibility accompanied by a reduction in AP-1 and ETS motif frequencies. The functional turnover of IREs between zebrafish and mice is correlated with changes in transcriptional responses of the IRE-associated genes upon injury. Using mouse cardiomyocytes as a model, we demonstrated that the reduction in AP-1 or ETS motif frequency attenuates the activation of IREs in response to hypoxia-induced damage.

Conclusions

By performing comparative genomics analyses on IREs, we demonstrated that inter-species variations in AP-1 and ETS motifs may play an important role in defining the functions of enhancers during injury response. Our findings provide important insights for understanding the molecular mechanisms of transcriptional remodeling in response to injury across species.
Comparative protein analysis of two maize genotypes with contrasting tolerance to low temperature
Authors: Ramazan Salika , Jan Nelofer , John Riffat
Published: April 2023

Background

Low temperature (LT) stress is one of the major environmental stress factors affecting the growth and yield of maize (Zea mays L.). Hence, it is important to unravel the molecular mechanisms behind LT stress tolerance to improve molecular breeding in LT tolerant genotypes. In the present study, two maize genotypes viz. Gurez local from Kashmir Himalaya and tropical grown GM6, were dissected for their LT stress response in terms of accumulation of differentially regulated proteins (DRPs). Leaf proteome analysis at three-leaf stage of maize seedlings subjected to LT stress of 6 °C for a total of 12 h duration was performed using two dimensional gel electrophoresis (2D-PAGE) followed by subsequent identification of the proteins involved.

Results

After MALDI-TOF (Matrix-assisted laser desorption/ionization-time of flight) and bioinformatics analysis, 19 proteins were successfully identified in Gurez local, while as 10 proteins were found to get successful identification in GM6. The interesting observations from the present investigation is the identification of three novel proteins viz. threonine dehydratase biosynthetic chloroplastic, thylakoidal processing peptidase 1 chloroplastic, and nodulin-like protein, whose role in abiotic stress tolerance, in general, and LT stress, in particular, has not been reported so far. It is important to highlight here that most of LT responsive proteins including the three novel proteins were identified from Gurez local only, owing to its exceptional LT tolerance. From the protein profiles, obtained in both genotypes immediately after LT stress perception, it was inferred that stress responsive protein accumulation and their expression fashion help the Gurez local in seedling establishment and withstand unfavorable conditions as compared to GM6. This was inferred from the findings of pathway enrichment analysis like regulation of seed growth, timing of floral transition, lipid glycosylation, and aspartate family amino acid catabolic processes, besides other key stress defense mechanisms. However, in GM6, metabolic pathways enriched were found to be involved in more general processes including cell cycle DNA replication and regulation of phenylpropanoid metabolism. Furthermore, majority of the qRT-PCR results of the selected proteins demonstrated positive correlation between protein levels and transcript abundance, thereby strengthening our findings.

Conclusions

In conclusion, our findings reported majority of the identified proteins in Gurez local exhibiting up-regulated pattern under LT stress as compared to GM6. Furthermore, three novel proteins induced by LT stress were found in Gurez local, requiring further functional validation. Therefore, our results offer more insights for elucidating the molecular networks mediating LT stress tolerance in maize.
Longitudinal association between N-terminal B-type natriuretic peptide, anxiety and social support in patients with HFpEF: results from the multicentre randomized controlled Aldo-DHF trial
Authors: Wilke Marieke R. , Broschmann Daniel , Sandek Anja , Wachter Rolf , Edelmann Frank , Herrmann-Lingen Christoph
Published: April 2023

Background

Higher plasma levels of natriuretic peptides (NPs) have been associated with reduced anxiety in experimental research and a number of patient samples. As NP levels are elevated in heart failure patients, we investigate whether this elevation is related to anxiety in patients with heart failure with preserved ejection fraction (HFpEF).

Methods

Post-hoc regression and mediation analyses were conducted, using data of 422 patients with HFpEF from the randomized, placebo-controlled, double-blinded, two-armed, multicentre aldosterone in diastolic heart failure trial, testing associations and their mediators between the N-terminal B-type natriuretic peptide (NT-proBNP) and anxiety at baseline and over 12-month follow-up. Anxiety was measured by the Hospital Anxiety and Depression Scale (HADS), social support by the ENRICHD Social Support Inventory and physical functioning by the Short Form 36 Health Survey.

Results

The mean age of the study population was 66.8 ± 7.6 years, 47.6% were male and 86.0% had NYHA class II. NT-proBNP showed a weak negative correlation with HADS anxiety scores at baseline (r = − 0.087; p = 0.092), which was significant (r = − 0.165; p = 0.028) in men but not in women. NT-proBNP also tended to predict lower anxiety at 12-months in men. On the other hand, higher anxiety at baseline was associated with lower NT-proBNP scores 12 months later (r = − 0.116; p = 0.026). All associations lost significance in multivariate regression for age, perceived social support (ESSI), physical function (SF-36) and study arm. Mediation analyses revealed that social support acts as a full mediator for the link between NT-proBNP levels and anxiety.

Conclusion

The mechanisms linking NT-proBNP to anxiety may be more complex than originally assumed. While effects of NT-proBNP on anxiety may be mediated by perceived social support, there may be an additional negative effect of anxiety on NT-proBNP. Future research should consider this possible bi-directionality of the association and assess the potential influence of gender, social support, oxytocin and vagal tone on the interaction of anxiety and natriuretic peptide levels.

Trial Registrationhttp://www.controlled-trials.com (ISRCTN94726526) on 07/11/2006.

Eudra-CT-number: 2006–002,605-31.
Trends in predicted 10-year risk for cardiovascular diseases among patients with type 2 diabetes in Thailand, from 2014 to 2018
Authors: Lertsakulbunlue Sethapong , Mungthin Mathirut , Rangsin Ram , Kantiwong Anupong , Sakboonyarat Boonsub
Published: April 2023

Background

Cardiovascular diseases (CVD) are the leading causes of death globally, including Thailand. Approximately one-tenth of Thai adults have type 2 diabetes (T2D), a significantly increasing CVD. Our study aimed to determine the trends of predicted 10-year CVD risk among patients with T2D.

Methods

A series of hospital-based cross-sectional studies were conducted in 2014, 2015 and 2018. We included Thai patients with T2D aged 30–74-year-old without a history of CVD. The predicted 10-year risk for CVD was calculated based on Framingham Heart Study equations both with simple office-based nonlaboratory and laboratory-based. Age- and sex-adjusted means and proportions of predicted 10-year risk for CVD were calculated.

Results

A total of 84,602 patients with T2D were included in the present study. The average SBP among study participants was 129.3 ± 15.7 mmHg in 2014 and rose to 132.6 ± 14.9 mmHg in 2018. Likewise, the average body mass index was 25.7 ± 4.5 kg/m2 in 2014 and elevated to 26.0 ± 4.8 kg/m2 in 2018. The age- and sex-adjusted mean of the predicted 10-year CVD risk (simple office-based) was 26.2% (95% CI: 26.1–26.3%) in 2014 and rose to 27.3% (95% CI: 27.2–27.4%) in 2018 (p-for trend < 0.001). While the age- and sex-adjusted mean of the predicted 10-year CVD risk (laboratory-based) ranged from 22.4–22.9% from 2014 to 2018 (p-for trend < 0.001). The age- and sex-adjusted prevalence of the high predicted 10-year CVD risk (simple office-based) was 67.2% (95% CI: 66.5–68.0%) in 2014 and significantly rose to 73.1% (95% CI: 72.4–73.7%) in 2018 (p-for trend < 0.001). Nevertheless, the age- and sex-adjusted prevalence of the high predicted 10-year CVD risk (laboratory-based) ranged from 46.0–47.4% from 2014 to 2018 (p-for trend = 0.405). However, among patients with available laboratory results, a significantly positive correlation was noted between predicted 10-year CVD risk, simple office-based and laboratory-based (r = 0.8765, p-value < 0.001).

Conclusion

Our study demonstrated significant rising trends in the predicated 10-year CVD risk among Thai patients with T2D. In addition, the results empowered further improved modifiable CVD risks, especially regarding high BMI and high blood pressure.
A new data driven method for summarising multiple cause of death data
Authors: Dobson Annette , McElwee Paul , Baneshi Mohammad Reza , Eynstone-Hinkins James , Moran Lauren , Waller Michael
Published: April 2023

Background

National mortality statistics are based on a single underlying cause of death. This practice does not adequately represent the impact of the range of conditions experienced in an ageing population in which multimorbidity is common.

Methods

We propose a new method for weighting the percentages of deaths attributed to different causes that takes account of the patterns of associations among underlying and contributing causes of death. It is driven by the data and unlike previously proposed methods does not rely on arbitrary choices of weights which can over-emphasise the contribution of some causes of death. The method is illustrated using Australian mortality data for people aged 60 years or more.

Results

Compared to the usual method based only on the underlying cause of death the new method attributes higher percentages of deaths to conditions like diabetes and dementia that are frequently mentioned as contributing causes of death, rather than underlying causes, and lower percentages to conditions to which they are closely related such as ischaemic heart disease and cerebrovascular disease. For some causes, notably cancers, which are usually recorded as underlying causes with few if any contributing causes the new method produces similar percentages to the usual method. These different patterns among groups of related conditions are not apparent if arbitrary weights are used.

Conclusion

The new method could be used by national statistical agencies to produce additional mortality tables to complement the current tables based only on underlying causes of death.
Associations between diabetes status and grip strength trajectory sub-groups in adulthood: findings from over 16 years of follow-up in the MRC National Survey of Health and Development
Authors: Norris T. , Johnson W. , Cooper R. , Pereira S. M. Pinto
Published: April 2023

Background

Cross-sectional studies suggest a relationship between diabetes status and weaker grip strength (GS) in adulthood and limited evidence from longitudinal studies has focussed on the association with average change in GS. We aimed to investigate whether diabetes status was related to membership of distinct GS trajectories in mid-to-late adulthood in 2,263 participants in the Medical Research Council National Survey of Health and Development.

Methods

Grip strength (kg) was measured at 53, 60–64 and 69 years. Pre-/diabetes was defined at 53 years based on HbA1c > 5.6% and/or doctor-diagnosis of diabetes. Sex-specific latent class trajectory models were developed and multinomial logistic regression was used to investigate the association between pre-/diabetes status and membership into GS trajectory classes.

Results

For both males and females, a 3-class solution (‘High’, ‘Intermediate’, ‘Low’) provided the best representation of the GS data and the most plausible solution. There was no evidence that pre-/diabetes status was associated with class membership in either sex: e.g., adjusted odds ratios of being in the ‘Low’ class (vs. ‘High’) for males with pre-/diabetes (vs. no-diabetes) was 1.07 (95% CI:0.45,2.55).

Conclusion

Using a flexible data-driven approach to identify GS trajectories between 53 and 69 years, we observed three distinct GS trajectories, all declining, in both sexes. There was no association between pre-/diabetes status at 53 years and membership into these GS trajectories. Understanding the diabetes status―GS trajectories association is vital to ascertain the consequences that projected increases in pre-/diabetes prevalence’s are likely to have.
Prevalence of early postpartum depression and associated risk factors among selected women in southern Malawi: a nested observational study
Authors: Moya E , Mzembe G , Mwambinga M , Truwah Z , Harding R , Ataide R , Larson Leila M , Fisher J , Braat S , Pasricha SR , Mwangi MN , Phiri KS
Published: April 2023

Background

The birth of a child should be a time of celebration. However, for many women, childbirth represents a time of great vulnerability to becoming mentally unwell, a neglected maternal morbidity. This study aimed to determine the prevalence of early postpartum depression (PPD) and its associated risk factors among women giving birth at health facilities in southern Malawi. Identifying women vulnerable to PPD will help clinicians provide appropriately targeted interventions before discharge from the maternity ward.

Method

We conducted a nested cross-sectional study. Women were screened for early PPD using a locally validated Edinburgh Postpartum Depression Scale (EPDS) as they were discharged from the maternity ward. The prevalence of moderate or severe (EPDS ≥ 6) and severe (EPDS ≥ 9) PPD was determined, including 95% confidence intervals (CI). Data on maternal age, education and marital status, income source, religion, gravidity, and HIV status, among others, were collected during the second trimester of pregnancy, and obstetric and infant characteristics during childbirth were examined as potential risk factors for early PPD using univariable and multivariable logistic regression analyses.

Results

Data contributed by 636 women were analysed. Of these women, 9.6% (95% CI; 7.4–12.1%) had moderate to severe early PPD using an EPDS cut-off of ≥ 6, and 3.3% (95% CI; 2.1–5.0%) had severe early PPD using an EPDS cut-off of ≥ 9. Multivariable analyses indicated that maternal anaemia at birth (aOR; 2.65, CI; 1.49–4.71, p-value; 0.001) was associated with increased risk for moderate and/or severe early PPD, while live birth outcome (aOR; 0.15, 95% CI; 0.04–0.54, p-value; 0.004), being single compared to divorced/widowed (aOR; 0.09, 95% CI; 0.02–0.55, p-value; 0.009), and lower education level (aOR; 0.36, 95% CI; 0.20–0.65, p-value; 0.001) were associated with decreased risk. Being HIV positive (aOR; 2.88, 95% CI; 1.08–7.67, p-value; 0.035) was associated with severe PPD only.

Conclusion

The prevalence of early PPD was slightly lower in our selected sample compared to previous reports in Malawi and was associated with maternal anaemia at birth, non-live birth, being divorced/widowed and HIV-positive status. Therefore, health workers should screen for depressive symptoms in women who are at increased risk as they are discharged from the maternity ward for early identification and treatment.
Co-occurrence of depression, anxiety, and perinatal posttraumatic stress in postpartum persons
Authors: Howard Shelby , Witt Caitlin , Martin Karla , Bhatt Ateshi , Venable Emily , Buzhardt Sarah , Chapple Andrew G. , Sutton Elizabeth F.
Published: April 2023

Background

The study aim was to describe the incidence of depression, anxiety, perinatal-post-traumatic stress disorder (PTSD), and their co-occurrences in the early postpartum period in a low-resource OB/GYN clinic serving majority Medicaid-eligible persons. We hypothesized that postpartum persons screening positive for depression will have an increased risk of a positive screen for anxiety and perinatal PTSD.

Methods

A retrospective study of postpartum persons receiving care in Baton Rouge, Louisiana was conducted using responses abstracted from the electronic medical record (EMR) of the Patient Health Questionnaire-9 (PHQ9), Generalized Anxiety Disorder-7 (GAD7), and Perinatal Post Traumatic Stress Disorder Questionnaire-II (PPQII). Categorical distributions were compared using Fisher exact tests, while t-tests were used to compare continuous covariates. Multivariable logistic regression was used to predict anxiety (GAD7) and perinatal PTSD (PPQII) scores while adjusting for potential confounders, as well as to predict continuous PPQII and GAD7 based on continuous PHQ9 scores.

Results

There were 613 birthing persons 4–12 weeks postpartum that completed mental health screening (PHQ9, GAD7, and PPQII) between November 2020 and June 2022 as part of routine postpartum care in the clinic. The incidence of screening positive for symptoms of depression (PHQ9 > 4) was 25.4% (n = 156), while the incidence of positive screening for symptoms of anxiety (GAD7 > 4) and perinatal PTSD (PPQII $$\ge$$
≥
19) were 23.0% (n = 141) and 5.1% (n = 31) respectively. Postpartum patients with mild anxiety or more (i.e. GAD7 > 4) had 26 times higher odds of screening positive for symptoms of depression (PHQ9 > 4) (adjusted odds ratio [aOR] 26.3; 95% confidence interval [CI] 15.29–46.92; p < 0.001). Postpartum persons with a PPQII score indicating symptoms of perinatal PTSD (PPQII $$\ge$$
≥
19) had 44 times higher odds of screening positive for symptoms of depression (PHQ > 4) (aOR 44.14; 95%CI 5.07–5856.17; p < 0.001).

Conclusions

Depression, anxiety, and perinatal PTSD are each independent risk factors for each other. To comply with the American College of Obstetricians and Gynecologists (ACOG) recommendations, providers should universally screen postpartum persons with validated screening tools for mood disturbances. However, if a complete full mood assessment is not feasible, this study provides evidence to support screening patients for depression, and if the patient screens positive, prompt additional screening for anxiety and perinatal PTSD.
The potential of PARP as a therapeutic target across pediatric solid malignancies
Authors: Keller Kaylee M. , Koetsier Joost , Schild Linda , Amo-Addae Vicky , Eising Selma , van den Handel Kim , Ober Kimberley , Koopmans Bianca , Essing Anke , van den Boogaard Marlinde L. , Langenberg Karin P. S. , Jäger Natalie , Kool Marcel , Pfister Stefan , Dolman M. Emmy M. , Molenaar Jan J. , van Hooff Sander R.
Published: April 2023

Background

Pediatric cancer is the leading cause of disease-related death in children and the need for better therapeutic options remains urgent. Due to the limited number of patients, target and drug development for pediatrics is often supplemented by data from studies focused on adult cancers. Recent evidence shows that pediatric cancers possess different vulnerabilities that should be explored independently from adult cancers.

Methods

Using the publicly available Genomics of Drug Sensitivity in Cancer database, we explore therapeutic targets and biomarkers specific to the pediatric solid malignancies Ewing sarcoma, medulloblastoma, neuroblastoma, osteosarcoma, and rhabdomyosarcoma. Results are validated using cell viability assays and high-throughput drug screens are used to identify synergistic combinations.

Results

Using published drug screening data, PARP is identified as a drug target of interest across multiple different pediatric malignancies. We validate these findings, and we show that efficacy can be improved when combined with conventional chemotherapeutics, namely topoisomerase inhibitors. Additionally, using gene set enrichment analysis, we identify ribosome biogenesis as a potential biomarker for PARP inhibition in pediatric cancer cell lines.

Conclusion

Collectively, our results provide evidence to support the further development of PARP inhibition and the combination with TOP1 inhibition as a therapeutic approach in solid pediatric malignancies. Additionally, we propose ribosome biogenesis as a component to PARP inhibitor sensitivity that should be further investigated to help maximize the potential utility of PARP inhibition and combinations across pediatric solid malignancies.
Aberrant methylation in neurofunctional gene serves as a hallmark of tumorigenesis and progression in colorectal cancer
Authors: Li Xuan , Cai Du , Huang Yaoyi , Xie Yumo , Shen Dingcheng , Yuan Ze , Liu Xiaoxia , Huang Meijin , Luo Yanxin , Yu Huichuan , Wang Xiaolin
Published: April 2023

Background

DNA methylation is one of the most promising biomarkers in predicting the prognosis of colorectal cancer (CRC). We aimed to develop a DNA methylation biomarker that could evaluate the prognosis of CRC.

Methods

A promising DNA methylation biomarker was developed by hypermethylated genes in cancer tissue that were identified from Illumina EPIC methylation arrays. A cohort comprising 30 pairs of snap-frozen tumor tissue and adjacent normal tissue was used for correlation analysis between the methylation and expression status of the marker. The other cohort comprising 254 formalin-fixed paraffin-embedded (FFPE) tumor tissue from 254 CRC patients was used for prognosis analysis.

Results

Regulating synaptic membrane exocytosis 2 (RIMS2) was hypermethylated and lowly expressed in CRC comparing to adjacent normal tissue. Hypermethylation of RIMS2 in CRC was correlated with less frequent KRAS mutant and high differentiation. RIMS2 promoter methylation showed independent predictive value for survival outcome (P = 0.015, HR 1.992, 95% CI [(1.140–3.48)]), and a combination of RIMS2 methylation with KRAS status could predict prognosis better.

Conclusions

RIMS2 is frequently hypermethylated in CRC, which can silence the expression of RIMS2. RIMS2 methylation is a novel biomarker for predicting the prognosis of CRC.
Incidence, survival comparison, and novel prognostic evaluation approaches for stage iii-iv pulmonary large cell neuroendocrine carcinoma and small cell lung cancer
Authors: Huang Liling , Feng Yu , Xie Tongji , Zhu Haohua , Tang Le , Shi Yuankai
Published: April 2023

Background

Pulmonary large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC) are two types of high-grade neuroendocrine carcinomas of the lung with poor prognosis. LCNEC has not been thoroughly studied due to its rarity, data are also lacking regarding the survival comparison and prognosis analysis of patients with locally advanced or metastatic LCNEC and SCLC.

Methods

Data of patients with LCNEC, SCLC, and other NSCLC who were diagnosed from 1975 to 2019 were extracted from the Surveillance, Epidemiology and End Results (SEER) database to estimate incidence. Those in stage III-IV and being diagnosed from 2010 to 2015 were utilized further to investigate their clinical characteristics and prognosis. Propensity score matching (PSM) analyses at a ratio of 1:2 was used to compare their survival outcomes. Nomograms of LCNEC and SCLC were established with internal validation, and the nomogram of SCLC was externally validated by 349 patients diagnosed in Cancer hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from January 1, 2012 to December 31, 2018.

Results

The incidence of LCNEC has been increasing in recent decades, meanwhile that of SCLC and other types of NSCLC were decreasing. A total of 91,635 lung cancer patients, including 785 with LCNEC, 15,776 with SCLC, and 75,074 with other NSCLC were enrolled for further analysis. The survival of stage III-IV LCNEC resembles that of SCLC, and significantly worse than other types of NSCLC before and after PSM analysis. In pretreatment prognostic analysis, age, T stage, N stage, M stage, bone metastasis, liver metastasis, and brain metastasis were found to be associated with the survival of both LCNEC and SCLC, besides sex, bilaterality, and lung metastasis were additional prognostic factors for SCLC. Two nomograms and convenient online tools respectively for LCNEC and SCLC were established accordingly with favorable predicting accuracy of < 1-year, < 2-year, < 3-year survival probabilities. In external validation of the SCLC nomogram with a Chinese cohort, the AUCs of 1-year, 2-year and 3-year ROC were 0.652, 0.669, and 0.750, respectively. All the results of 1-, 2-, 3- year variable-dependent ROC curves verified the superior prognostic value of our nomograms for LCNEC and SCLC over the traditional T/N/M staging system.

Conclusions

Based on large sample-based cohort, we compared the epidemiological trends and survival outcomes between locally advanced or metastatic LCNEC, SCLC, and other NSCLC. Furthermore, two prognostic evaluation approaches respectively for LCNEC and SCLC might present as practical tools for clinicians to predict the survival outcome of these patients and facilitate risk stratification.
Perceived parenting styles and incidence of major depressive disorder: results from a 6985 freshmen cohort study
Authors: Cheng Jing , Liu Debiao , Zheng Huancheng , Jin Zhou , Wang Deborah Baofeng , Liu Yan , Wu Yili
Published: April 2023

Background

Even though a fair amount of studies focus on depression among college students, the effect of perceived parenting styles on the incidence of major depressive disorder (MDD) among representative freshmen in Chinese context is scarcely studied. The aim of this study is to investigate the effect of parenting styles on MDD in Chinese freshmen.

Methods

A total of 9,928 Chinese freshmen were recruited in 2018. 6985 valid questionnaires were collected at one-year follow-up. Composite International Diagnostic Interview 3.0 (CIDI-3.0) was used for the diagnosis of MDD. Egna Minnen Beträffande Uppfostran (EMBU) questionnaire and Beck Depression Inventory-II (BDI-II) were used to assess parenting styles and baseline depressive symptoms, respectively. The associations between parenting styles and MDD incidence was analyzed with logistic regression.

Results

The incidence of MDD in freshmen was 2.23% (95%CI: 1.91-2.60%). Maternal overprotection (OR = 1.03, 95%CI: 1.01–1.05) and disharmony relationship between parents (OR = 2.35, 95% CI: 1.42–3.89) increased the risk of new-onset MDD in freshmen, respectively. Mild depressive symptoms (OR = 2.06, 95%CI: 1.06–4.02), moderate (OR = 4.64, 95%CI: 2.55–8.44) and severe depressive symptoms (OR = 7.46, 95%CI: 2.71–20.52) at baseline increased the risk of new-onset MDD.

Conclusions

Maternal overprotection, disharmony relationship between parents and baseline depressive symptoms are risk factors for new-onset MDD in Chinese freshmen.
Mental health challenges, treatment experiences, and care needs of post-secondary students: a cross-sectional mixed-methods study
Authors: Moghimi Elnaz , Stephenson Callum , Gutierrez Gilmar , Jagayat Jasleen , Layzell Gina , Patel Charmy , McCart Amber , Gibney Cynthia , Langstaff Caryn , Ayonrinde Oyedeji , Khalid-Khan Sarosh , Milev Roumen , Snelgrove-Clarke Erna , Soares Claudio , Omrani Mohsen , Alavi Nazanin
Published: April 2023

Background

Post-secondary students frequently experience high rates of mental health challenges. However, they present meagre rates of treatment-seeking behaviours. This elevated prevalence of mental health problems, particularly after the COVID-19 pandemic, can lead to distress, poor academic performance, and lower job prospects following the completion of education. To address the needs of this population, it is important to understand students' perceptions of mental health and the barriers preventing or limiting their access to care.

Methods

A broad-scoping online survey was publicly distributed to post-secondary students, collecting demographic, sociocultural, economic, and educational information while assessing various components of mental health.

Results

In total, 448 students across post-secondary institutions in Ontario, Canada, responded to the survey. Over a third (n = 170; 38.6%) of respondents reported a formal mental health diagnosis. Depression and generalized anxiety disorder were the most commonly reported diagnoses. Most respondents felt that post-secondary students did not have good mental health (n = 253; 60.5%) and had inadequate coping strategies (n = 261; 62.4%). The most frequently reported barriers to care were financial (n = 214; 50.5%), long wait times (n = 202; 47.6%), insufficient resources (n = 165; 38.9%), time constraints (n = 148; 34.9%), stigma (n = 133; 31.4%), cultural barriers (n = 108; 25.5%), and past negative experiences with mental health care (n = 86; 20.3%). The majority of students felt their post-secondary institution needed to increase awareness (n = 231; 56.5%) and mental health resources (n = 306; 73.2%). Most viewed in-person therapy and online care with a therapist as more helpful than self-guided online care. However, there was uncertainty about the helpfulness and accessibility of different forms of treatment, including online interventions. The qualitative findings highlighted the need for personal strategies, mental health education and awareness, and institutional support and services.

Conclusions

Various barriers to care, perceived lack of resources, and low knowledge of available interventions may contribute to compromised mental health in post-secondary students. The survey findings indicate that upstream approaches such as integrating mental health education for students may address the varying needs of this critical population. Therapist-involved online mental health interventions may be a promising solution to address accessibility issues.