bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Textbook Content and Teachers’ Competence in Climate Change Education at the Primary Level
Authors: Batool Aneela , Behlol Malik Ghulam
Published: July 2024

This study aims to examine the climate change education (CCE) provision in grade 5 textbooks (science and social studies) and the competence of teachers in teaching CCE in a primary girls’ schools in Skardu, Baltistan, Pakistan. It employs mixed-method research that uses both qualitative and quantitative approaches to gather data. The first phase of the study involved collecting qualitative data to examine the provision of CCE content in selected textbooks taught in grade 5. The researcher adapted an interview questionnaire to assess the competence of teachers teaching in 38 schools. The provision of themes and topics based on the seven principles of climate literacy given by the U.S. Global Change Research Program was identified by using latent content analysis (LCA). The study concludes that science and social studies textbooks lack the incorporation of CCE content of principles 1, 4, 6, and 7. Furthermore, the majority of teachers have not received training to use digital media and apply activity-based methods to engage campus and community support for CCE. The study also found that the selected schools lack school planting campaigns, CCE committees, and CCE walks. Above all, the respondents possess conflicting views about whether climate change is a natural or human-contributed phenomenon.

Significance Statement

Like other countries around the globe, Pakistan is the victim of climatic disasters which have disastrous effects on the economy, agriculture, healthcare, and weather conditions. These effects are exacerbated by lacking awareness, attitudinal issues, and poor pro-climate-supported practices at the academic and societal levels (Asian Development Bank 2022). Awareness, knowledge, and a supportive environment during childhood form attitudes and promote practices that have lasting impacts throughout the life of the individual (Gulraiz and Ali 2021). Therefore, children need to learn and adopt proclimate lifestyles, such as observing cleanliness, practicing planting, and judicious use of energy resources. With this background, we assessed the textbooks based on seven principles of climate literacy given by the U.S. Global Change Research Program (USGCRP 2009) and observed that principles 1, 4, 6, and 7 are not adequately addressed in science and social studies textbooks taught in public schools. Moreover, teachers have not received training to use digital media and gather campus and community support, and they have a stereotypical understanding of climate change. The study possesses significant implications for curriculum revisions and elementary education management to address the gaps relating to climate change education (CCE).
Metabolomic and transcriptomic analyses of peach leaves and fruits in response to pruning
Authors: Liu Xiao-Fei , An Xiu-Hong , Li Xin-Miao , Zhang He , Cao Hong-Bo , Chen Hai-Jiang , Tian Yi
Published: July 2024

Background

Pruning is an important cultivation management option that has important effects on peach yield and quality. However, the effects of pruning on the overall genetic and metabolic changes in peach leaves and fruits are poorly understood.

Results

The transcriptomic and metabolomic profiles of leaves and fruits from trees subjected to pruning and unpruning treatments were measured. A total of 20,633 genes and 622 metabolites were detected. Compared with those in the control, 1,127 differentially expressed genes (DEGs) and 77 differentially expressed metabolites (DEMs) were identified in leaves from pruned and unpruned trees (pdLvsupdL), whereas 423 DEGs and 29 DEMs were identified in fruits from the pairwise comparison pdFvsupdF. The content of three auxin analogues was upregulated in the leaves of pruned trees, the content of all flavonoids detected in the leaves decreased, and the expression of almost all genes involved in the flavonoid biosynthesis pathway decreased. The phenolic acid and amino acid metabolites detected in fruits from pruned trees were downregulated, and all terpenoids were upregulated. The correlation analysis revealed that DEGs and DEMs in leaves were enriched in tryptophan metabolism, auxin signal transduction, and flavonoid biosynthesis. DEGs and DEMs in fruits were enriched in flavonoid and phenylpropanoid biosynthesis, as well as L-glutamic acid biosynthesis.

Conclusions

Pruning has different effects on the leaves and fruits of peach trees, affecting mainly the secondary metabolism and hormone signalling pathways in leaves and amino acid biosynthesis in fruits.
Tumour-associated and non-tumour-associated bacteria co-abundance groups in colorectal cancer
Authors: Liang Yuxuan , Zhang Qingrong , Yu Jing , Hu Wenyan , Xu Sihua , Xiao Yiyuan , Ding Hui , Zhou Jiaming , Chen Haitao
Published: July 2024

Background & aims

Gut microbiota is closely related to the occurrence and development of colorectal cancer (CRC). However, the differences in bacterial co-abundance groups (CAGs) between tumor tissue (TT) and normal tissue (NT), as well as their associations with clinical features, are needed to be clarified.

Methods

Bacterial 16 S rRNA sequencing was performed by using TT samples and NT samples of 251 patients with colorectal cancer. Microbial diversity, taxonomic characteristics, microbial composition, and functional pathways were compared between TT and NT. Hierarchical clustering was used to construct CAGs.

Results

Four CAGs were grouped in the hierarchical cluster analysis. CAG 2, which was mainly comprised of pathogenic bacteria, was significantly enriched in TT samples (2.27% in TT vs. 0.78% in NT, p < 0.0001). CAG 4, which was mainly comprised of non-pathogenic bacteria, was significantly enriched in NT samples (0.62% in TT vs. 0.79% in NT, p = 0.0004). In addition, CAG 2 was also significantly associated with tumor microsatellite instability (13.2% in unstable vs. 2.0% in stable, p = 0.016), and CAG 4 was positively correlated with the level of CA199 (r = 0.17, p = 0.009).

Conclusions

Our research will deepen our understanding of the interactions among multiple bacteria and offer insights into the potential mechanism of NT to TT transition.
Genome-wide identification and expression analysis of calmodulin and calmodulin-like genes in passion fruit (Passiflora edulis) and their involvement in flower and fruit development
Authors: Zhang Dan , Du Lumiao , Lin Jinting , Wang Lulu , Zheng Ping , Deng Biao , Zhang Wenbin , Su Weiqiang , Liu Yanhui , Lu Yuming , Qin Yuan , Wang Xiaomei
Published: July 2024

Background

The calmodulin (CaM) and calmodulin-like (CML) proteins play regulatory roles in plant growth and development, responses to biotic and abiotic stresses, and other biological processes. As a popular fruit and ornamental crop, it is important to explore the regulatory mechanism of flower and fruit development of passion fruit.

Results

In this study, 32 PeCaM/PeCML genes were identified from passion fruit genome and were divided into 9 groups based on phylogenetic analysis. The structural analysis, including conserved motifs, gene structure and homologous modeling, illustrates that the PeCaM/PeCML in the same subgroup have relative conserved structural features. Collinearity analysis suggested that the expansion of the CaM/CML gene family likely took place mainly by segmental duplication, and the whole genome replication events were closely related with the rapid expansion of the gene group. PeCaM/PeCMLs were potentially required for different floral tissues development. Significantly, PeCML26 had extremely high expression levels during ovule and fruit development compared with other PeCML genes, suggesting that PeCML26 had potential functions involved in the development of passion fruit flowers and fruits. The co-presence of various cis-elements associated with growth and development, hormone responsiveness, and stress responsiveness in the promoter regions of these PeCaM/PeCMLs might contribute to their diverse regulatory roles. Furthermore, PeCaM/PeCMLs were also induced by various abiotic stresses. This work provides a comprehensive understanding of the CaM/CML gene family and valuable clues for future studies on the function and evolution of CaM/CML genes in passion fruit.

Conclusion

A total of 32 PeCaM/PeCML genes were divided into 9 groups. The PeCaM/PeCML genes showed differential expression patterns in floral tissues at different development stages. It is worth noting that PeCML26, which is highly homologous to AtCaM2, not only interacts with multiple BBR-BPC TFs, but also has high expression levels during ovule and fruit development, suggesting that PeCML26 had potential functions involved in the development of passion fruit flowers and fruits. This research lays the foundation for future investigations and validation of the potential function of PeCaM/PeCML genes in the growth and development of passion fruit.
Ginsenoside Rb1 reduces oxidative/carbonyl stress damage and dysfunction of RyR2 in the heart of streptozotocin-induced diabetic rats
Authors: feng Chunpeng , Song Jianping , Deng Lan , Zhang Jinfeng , Lian Xinyi , Zhen Zhong , Liu Jinfeng
Published: July 2024

Background

Oxidative stress may contribute to cardiac ryanodine receptor (RyR2) dysfunction in diabetic cardiomyopathy. Ginsenoside Rb1 (Rb1) is a major pharmacologically active component of ginseng to treat cardiovascular diseases. Whether Rb1 treat diabetes injured heart remains unknown. This study was to investigate the effect of Rb1 on diabetes injured cardiac muscle tissue and to further investigate its possible molecular pharmacology mechanisms.

Methods

Male Sprague-Dawley rats were injected streptozotocin solution for 2 weeks, followed 6 weeks Rb1 or insulin treatment. The activity of SOD, CAT, Gpx, and the levels of MDA was measured; histological and ultrastructure analyses, RyR2 activity and phosphorylated RyR2(Ser2808) protein expression analyses; and Tunel assay were performed.

Results

There was decreased activity of SOD, CAT, Gpx and increased levels of MDA in the diabetic group from control. Rb1 treatment increased activity of SOD, CAT, Gpx and decreased the levels of MDA as compared with diabetic rats. Neutralizing the RyR2 activity significantly decreased in diabetes from control, and increased in Rb1 treatment group from diabetic group. The expression of phosphorylation of RyR2 Ser2808 was increased in diabetic rats from control, and were attenuated with insulin and Rb1 treatment. Diabetes increased the apoptosis rate, and Rb1 treatment decreased the apoptosis rate. Rb1 and insulin ameliorated myocardial injury in diabetic rats.

Conclusions

These data indicate that Rb1 could be useful for mitigating oxidative damage, reduced phosphorylation of RyR2 Ser2808 and decreased the apoptosis rate of cardiomyocytes in diabetic cardiomyopathy.
Reduction in ACE2 expression in peripheral blood mononuclear cells during COVID-19 – implications for post COVID-19 conditions
Authors: Ahmed Gulrayz , Abdelgadir Yasir , Abdelghani Amro , Simpson Pippa , Barbeau Jody , Basel Donald , Barrios Christy S. , Smith Brandon A , Schilter Kala F , Udani Rupa , Reddi Honey V. , Willoughby Rodney E.
Published: July 2024

Background

Severe COVID-19 is uncommon, restricted to 19% of the total population. In response to the first virus wave (alpha variant of SARS-CoV-2), we investigated whether a biomarker indicated severity of disease and, in particular, if variable expression of angiotensin converting enzyme 2 (ACE2) in blood might clarify this difference in risk and of post COVID -19 conditions (PCC).

Methods

The IRB-approved study compared patients hospitalized with severe COVID-19 to healthy controls. Severe infection was defined requiring oxygen or increased oxygen need from baseline at admission with positive COVID-19 PCR. A single blood sample was obtained from patients within a day of admission. ACE2 RNA expression in blood cells was measured by an RT-PCR assay. Plasma ACE1 and ACE2 enzyme activities were quantified by fluorescent peptides. Plasma TIMP-1, PIIINP and MMP-9 antigens were quantified by ELISA. Data were entered into REDCap and analyzed using STATA v 14 and GraphPad Prism v 10.

Results

Forty-eight patients and 72 healthy controls were recruited during the pandemic. ACE2 RNA expression in peripheral blood mononuclear cells (PBMC) was rarely detected acutely during severe COVID-19 but common in controls (OR for undetected ACE2: 12.4 [95% CI: 2.62-76.1]). ACE2 RNA expression in PBMC did not determine plasma ACE1 and ACE2 activity, suggesting alternative cell-signaling pathways. Markers of fibrosis (TIMP-1 and PIIINP) and vasculopathy (MMP-9) were additionally elevated. ACE2 RNA expression during severe COVID-19 often responded within hours to convalescent plasma. Analogous to oncogenesis, we speculate that potent, persistent, cryptic processes following COVID-19 (the renin-angiotensin system (RAS), fibrosis and vasculopathy) initiate or promote post-COVID-19 conditions (PCC) in susceptible individuals.

Conclusions

This work elucidates biological and temporal plausibility for ACE2, TIMP1, PIIINP and MMP-9 in the pathogenesis of PCC. Intersection of these independent systems is uncommon and may in part explain the rarity of PCC.
Timely initiation of complementary feeding and associated factors among mothers having children aged 6 to 24 months in North-West Ethiopia: a comparative cross-sectional study
Authors: Kegne Tilahun , Alemu Yihun Mulugeta , Wassie Gizachew Tadesse
Published: July 2024

Background

The timely introduction of complementary foods during infancy is necessary for nutritional reasons, and to enable the transition from milk feeding to family foods. In the past years, despite efforts that have been put to increase the utilization of timely initiation of complementary feeding practice in Ethiopia, improvements are not satisfactory.

Objective

To compare the prevalence of timely initiation of complementary feeding and its associated factors among mothers who have Children 6–24 months in Debre Tabor town and rural Farta district, North-west Ethiopia, 2021.

Methods

A community-based comparative cross-sectional study was employed from December 1/2020 to 30/ 2020 among 1100 mothers. Data were collected using a structured questioner and analyzed using Statistical Product and Service Solutions. Logistic regression analysis with a 95% confidence interval carried out to determine the association between explanatory and the outcome variables. A P-value of < 0.05 was considered statistically significant.

Results

The prevalence of timely initiation of complementary feeding among urban and rural mothers was 69.8% with (95% CI: 66%, 74%) and 51.9% with (95% CI: 48- 56%) respectively. Urban residence [AOR = 1.39, 95% CI: (1.02–1.94)], had antenatal care visits [AOR = 0.24 (95%CI: (0.13, 0.44)], had post natal care checkups [AOR = 0.44, 95%CI: (0. 27- 0.72)] and being a governmental employee [AOR = 2.82; 95% CI: (1.91–6.1)] were factors associated with timely initiation of complementary feeding among urban mothers. Whereas in rural settings: institutional delivery [(AOR = 2.21, CI: 1.35–3.65)], post natal care checkups [(AOR = 0.53, CI: (0.36–0.77)] being daily laborer [AOR = 3.47; 95% CI: (1.78–6.75)] were associated with timely initiation of complementary feeding.

Conclusion

The prevalence of timely introduction of complementary feeding in children aged 6–24 months is still low in the study areas. There was also disparity between urban and rural mothers in which urban mothers practiced better.
Association between childhood family structure and longitudinal health behaviour changes in adulthood –Northern Finland birth cohort 1966 study
Authors: Varis Heidi , Hagnäs Maria , Mikkola Ilona , Nordström Tanja , Taanila Anja , Keinänen-Kiukaanniemi Sirkka , Heikkala Eveliina
Published: July 2024

Background

Childhood family structure is considered to play a role in person’s health and welfare. This study investigated the relationships between the longitudinal changes of adult health behaviours and childhood family structure.

Methods

From Northern Finland Birth Cohort 1966 questionnaires, we collected data on childhood family structure at the age of 14 (‘two-parent family’, ‘one parent not living at home/no information on father’, and ‘father or mother deceased’), and on health behaviours (smoking, alcohol consumption and physical activity status) at the ages of 31 and 46. We used the multinomial logistic regression model to estimate the unadjusted and adjusted associations between childhood family structures and the longitudinal changes between 31 and 46 years of health behaviours (four-category variables).

Results

Of the study sample (n = 5431; 55.5% females), 7.1% of the offspring were represented in the ‘One parent not living at home/no information on father’ subgroup, 6.3% in the ‘Father or mother deceased’ subgroup and 86.6% in the ‘Two-parent family’. ‘One parent not living at home/no information on father’ offspring were approximately twice as likely to smoke (adjusted OR 2.19, 95% CI 1.70–2.81) and heavily consume alcohol (adjusted OR 1.99, 95% CI 1.25–3.16) at both times in adulthood, relative to not smoking or not heavily consume alcohol, and compared with ‘two-parent family’ offspring. We found no statistically significant associations between childhood family structure and physical activity status changes in adulthood.

Conclusions

Our findings suggest that the offspring of single-parent families in particular should be supported in early life to diminish their risk of unhealthy behaviours in adulthood.
Psychometric properties of the modified Drug Abuse Screening Test Sinhala version (DAST-SL): evaluation of reliability and validity in Sri Lanka
Authors: Nawaratne Sashiprabha Dulanjalee , Vidanapathirana Janaki
Published: July 2024

Background

Psychoactive drug use is an important public health issue in Sri Lanka as it causes substantial health, social and economic burden to the country. Screening for substance use disorders in people who use drugs is vital in preventive health care, as it can help to identify problematic use early. Screening can aid in referring those in need, for the most appropriate treatment and care. Thus, preventing them from developing severe substance use disorders with complications. The Drug Abuse Screening Test (DAST-10) is an evidence-based tool widely used to assess the severity of psychoactive drug use. This study aimed to culturally adapt and evaluate the validity and reliability of the Drug Abuse Screening Test (DAST-10) in Sri Lanka.

Methods

The DAST-10 was culturally adapted, and the nine-item Sinhala version (DAST-SL) was validated using exploratory and confirmatory factor analysis. The validation study was conducted in the Kandy district among people who use drugs, recruited using respondent-driven sampling. Criterion validity of the questionnaire was assessed by taking the diagnosis by a psychiatrist as the gold standard. Cut-off values for the modified questionnaire were developed by constructing Receiver Operating Characteristic (ROC) curves. The reliability of the DAST-SL was assessed by measuring its internal consistency and test re-test reliability.

Results

The validated DAST-SL demonstrated a one-factor model. A cut-off value of ≥ 2 demonstrated the presence of substance use disorder and had a sensitivity of 98.7%, specificity of 91.7%, a positive predictive value of 98.8% and a negative predictive value of 91.3%. The area under the curve of the ROC curve was 0.98. A cut-off score of ≤ 1 was considered a low level of problems associated with drug use. The DAST-SL score of 2–3 demonstrated a moderate level of problem severity, a score of 4–6 demonstrated a substantial level of problems, and a score of ≥ 7 demonstrated a severe level of drug-related problems. The questionnaire demonstrated high reliability with an internal consistency of 0.80 determined by Kuder–Richardson Formula-20 and an inter-class correlation coefficient of 0.97 for test re-test reliability.

Conclusion

The DAST-SL questionnaire is a valid and reliable tool to screen for drug use problem severity in people who use drugs in Sri Lanka.
A qualitative study of maternal and paternal parenting knowledge and practices in rural Mozambique
Authors: Ahun Marilyn N. , Bliznashka Lilia , Karuskina-Drivdale Svetlana , Regina Gino , Yousafzai Aisha K. , Jeong Joshua
Published: July 2024

Background

Providing nurturing care for young children is essential for promoting early child development (ECD). However, there is limited knowledge about how mothers and fathers across diverse contexts in sub-Saharan Africa care for their children and from whom they receive guidance and support in their caregiving roles. We aimed to examine caregivers’ nurturing care practices and sources of parenting knowledge in rural Mozambique.

Methods

This is a secondary analysis using data from a qualitative evaluation of a pilot intervention to improve nurturing care for early child health and development within existing health systems. The evaluation was conducted across three primary care health facilities and their catchment areas in Nampula province, Mozambique. For this study, we analyzed data from in-depth interviews conducted with 36 caregivers (32 mothers and 4 fathers) to investigate mothers’ and fathers’ daily caregiving experiences. Data were analyzed using thematic content analysis.

Results

Caregivers described various caregiving roles relating to general caregiving of young children (e.g., feeding, bathing, caring for child’s health) and stimulation (e.g., play and communication) activities. Mothers more commonly engaged in general caregiving activities than fathers, whereas both mothers and fathers engaged in stimulation activities. Other family members, including siblings, grandparents, and aunts/uncles, were also actively engaged in general caregiving activities. With respect to sources of parenting knowledge, caregivers received parenting guidance and support primarily from their own mothers/parents and facility-based health providers.

Conclusions

These findings highlight the importance of adopting a holistic approach involving caregivers and their context and reveal potential strategies to promote caregiving and ECD in rural Mozambique and similar contexts.
Vertebral bone quality score was associated with paraspinal muscles fat infiltration, but not modic classification in patients with chronic low back pain: a prospective cross-sectional study
Authors: Chen Jiaxin , Huang Yilong , Yang Yingjuan , Wang Zhongwei , Zhao Derong , Luo Mingbin , Pu Fushun , Yang Juntao , Zhang Zhenguang , He Bo
Published: July 2024

Background

The lumbar vertebra and paraspinal muscles play an important role in maintaining the stability of the lumbar spine. Therefore, the aim of this study was to investigate the relationship between paraspinal muscles fat infiltration and vertebral body related changes [vertebral bone quality (VBQ) score and Modic changes (MCs)] in patients with chronic low back pain (CLBP).

Methods

Patients with CLBP were prospectively collected in four hospitals and all patients underwent 3.0T magnetic resonance scanning. Basic clinical information was collected, including age, sex, course of disease (COD), and body mass index (BMI). MCs were divided into 3 types based on their signal intensity on T1 and T2-weighted imaging. VBQ was obtained by midsagittal T1-weighted imaging (T1WI) and calculated using the formula: SIL1−4/SICSF. The Proton density fat fraction (PDFF) values and cross-sectional area (CSA) of paraspinal muscles were measured on the fat fraction map from the iterative decomposition of water and fat with the echo asymmetry and least-squares estimation quantitation (IDEAL-IQ) sequences and in/out phase images at the central level of the L4/5 and L5/S1 discs.

Results

This study included 476 patients with CLBP, including 189 males and 287 females. 69% had no Modic changes and 31% had Modic changes. There was no difference in CSA and PDFF for multifidus(MF) and erector spinae (ES) at both levels between Modic type I and type II, all P values>0.05. Spearman correlation analysis showed that VBQ was weakly negatively correlated with paraspinal muscles CSA (all r values < 0.3 and all p values < 0.05), moderately positive correlation with PDFF of MF at L4/5 level (r values = 0.304, p values<0.001) and weakly positively correlated with PDFF of other muscles (all r values<0.3 and all p values<0.001). Multivariate linear regression analysis showed that age (β = 0.141, p < 0.001), gender (β = 4.285, p < 0.001) and VBQ (β = 1.310, p = 0.001) were related to the total PDFF of muscles. For MCs, binary logistic regression showed that the odds ratio values of age, BMI and COD were 1.092, 1.082 and 1.004, respectively (all p values ＜  0.05).

Conclusions

PDFF of paraspinal muscles was not associated with Modic classification. In addition to age and gender, PDFF of paraspinal muscles is also affected by VBQ. Age and BMI are considered risk factors for the MCs in CLBP patients.
In silico exploration of anti-prostate cancer compounds from differential expressed genes
Authors: Ajiboye Basiru Olaitan , Fatoki Toluwase Hezekiah , Akinola Olamilekan Ganiu , Ajeigbe Kazeem Olasunkanmi , Bamisaye Abraham Fisayo , Domínguez-Martín Eva-María , Rijo Patricia , Oyinloye Babatunji Emmanuel
Published: July 2024

Prostate cancer (PCa) is a complex and biologically diverse disease with no curative treatment options at present. This study aims to utilize computational methods to explore potential anti-PCa compounds based on differentially expressed genes (DEGs), with the goal of identifying novel therapeutic indications or repurposing existing drugs. The methods employed in this study include DEGs-to-drug prediction, pharmacokinetics prediction, target prediction, network analysis, and molecular docking. The findings revealed a total of 79 upregulated DEGs and 110 downregulated DEGs in PCa, which were used to identify drug compounds capable of reversing the dysregulated conditions (dexverapamil, emetine, parthenolide, dobutamine, terfenadine, pimozide, mefloquine, ellipticine, and trifluoperazine) at a threshold probability of 20% on several molecular targets, such as serotonin receptors 2a/2b/2c, HERG protein, adrenergic receptors alpha-1a/2a, dopamine D3 receptor, inducible nitric oxide synthase (iNOS), epidermal growth factor receptor erbB1 (EGFR), tyrosine-protein kinases, and C-C chemokine receptor type 5 (CCR5). Molecular docking analysis revealed that terfenadine binding to inducible nitric oxide synthase (-7.833 kcal.mol−1) and pimozide binding to HERG (-7.636 kcal.mol−1). Overall, binding energy ΔGbind (Total) at 0 ns was lower than that of 100 ns for both the Terfenadine-iNOS complex (-101.707 to -103.302 kcal.mol−1) and Ellipticine-TOPIIα complex (-42.229 to -58.780 kcal.mol−1). In conclusion, this study provides insight on molecular targets that could possibly contribute to the molecular mechanisms underlying PCa. Further preclinical and clinical studies are required to validate the therapeutic effectiveness of these identified drugs in PCa disease.
Primary care and abortion provider perspectives on mail-order medication abortion: a qualitative study
Authors: Raifman Sarah , Gurazada Tanvi , Beaman Jessica , Biggs M. Antonia , Schwarz Eleanor Bimla , Gold Marji , Grossman Daniel
Published: July 2024

Background

This qualitative study aims to assess perspectives of clinicians and clinic staff on mail-order pharmacy dispensing for medication abortion.

Methods

Participants included clinicians and staff involved in implementing a mail-order dispensing model for medication abortion at eleven clinics in seven states as part of a prospective cohort study, which began in January 2020 (before the FDA removed the in-person dispensing requirement for mifepristone). From June 2021 to July 2022, we invited participants at the participating clinics, including six primary care and five abortion clinics, to complete a semi-structured video interview about their experiences. We then conducted qualitative thematic analysis of interview data, summarizing themes related to perceived benefits and concerns about the mail-order model, perceived patient interest, and potential barriers to larger-scale implementation.

Results

We conducted 24 interviews in total with clinicians (13 physicians and one nurse practitioner) and clinic staff (n = 10). Participants highlighted perceived benefits of the mail-order model, including its potential to expand abortion services into primary care, increase patient autonomy and privacy, and to normalize abortion services. They also highlighted key logistical, clinical, and feasibility concerns about the mail-order model, and specific challenges related to integrating abortion into primary care.

Conclusion

Clinicians and clinic staff working in primary care and abortion clinics were optimistic that mail-order dispensing of medication abortion can improve the ability of some providers to provide abortion and enable more patients to access services. The feasibility of mail-order pharmacy dispensing of medication abortion following the Supreme Court Dobbs decision is to be determined.

Trial registration

Registry: Clinicaltrials.gov. Trial registration number: NCT03913104. Date of registration: first submitted on April 3, 2019 and first posted on April 12, 2019.
Development and validation of a nomogram model of depression and sleep disorders and the risk of disease progression in patients with breast cancer
Authors: Shen Jun , Zhou Dan , Wang Meng , Li Fan , Yan Huan-Huan , Zhou Jun , Sun Wen-Wen
Published: July 2024

Background

In this study, we investigated the relationship between the risk of postoperative progressive disease (PD) in breast cancer and depression and sleep disorders in order to develop and validate a suitable risk prevention model.

Methods

A total of 750 postoperative patients with breast cancer were selected from the First People’s Hospital of LianYunGang, and the indices of two groups (an event group and a non-event group) were compared to develop and validate a risk prediction model. The relationship between depression, sleep disorders, and PD events was investigated using the follow-up data of the 750 patients.

Results

SAS, SDS, and AIS scores differed in the group of patients who experienced postoperative disease progression versus those who did not; the differences were statistically significant and the ability to differentiate prognosis was high. The area under the receiver operating characteristic (ROC) curves (AUC) were: 0.8049 (0.7685–0.8613), 0.768 (0.727–0.809), and 0.7661 (0.724-–0.808), with cut-off values of 43.5, 48.5, and 4.5, respectively. Significant variables were screened by single-factor analysis and multi-factor analysis to create model 1, by lasso regression and cross-lasso regression analysis to create model 2, by random forest calculation method to create model 3, by stepwise regression method (backward method) to create model 4, and by including all variables for Cox regression to include significant variables to create model 5. The AUC of model 2 was 0.883 (0.848–0.918) and 0.937 (0.893–0.981) in the training set and validation set, respectively. The clinical efficacy of the model was evaluated using decision curve analysis and clinical impact curve, and then the model 2 variables were transformed into scores, which were validated in two datasets, the training and validation sets, with AUCs of 0.884 (0.848–0.919) and 0.885 (0.818–0.951), respectively.

Conclusion

We established and verified a model including SAS, SDS and AIS to predict the prognosis of breast cancer patients, and simplified it by scoring, making it convenient for clinical use, providing a theoretical basis for precise intervention in these patients. However, further research is needed to verify the generalization ability of our model.
Healthcare leaders navigating complexity: a scoping review of key trends in future roles and competencies
Authors: Spanos Samantha , Leask Elle , Patel Romika , Datyner Michael , Loh Erwin , Braithwaite Jeffrey
Published: July 2024

Background

As healthcare systems rapidly become more complex, healthcare leaders are navigating expanding role scopes and increasingly varied tasks to ensure the provision of high-quality patient care. Despite a range of leadership theories, models, and training curricula to guide leadership development, the roles and competencies required by leaders in the context of emerging healthcare challenges (e.g., disruptive technologies, ageing populations, and burnt-out workforces) have not been sufficiently well conceptualized. This scoping review aimed to examine these roles and competencies through a deep dive into the contemporary academic and targeted gray literature on future trends in healthcare leadership roles and competencies.

Methods

Three electronic databases (Business Source Premier, Medline, and Embase) were searched from January 2018 to February 2023 for peer-reviewed literature on key future trends in leadership roles and competencies. Websites of reputable healthcare- and leadership-focused organizations were also searched. Data were analyzed using descriptive statistics and thematic analysis to explore both the range and depth of literature and the key concepts underlying leadership roles and competencies.

Results

From an initial 348 articles identified in the literature and screened for relevance, 39 articles were included in data synthesis. Future leadership roles and competencies were related to four key themes: innovation and adaptation (e.g., flexibility and vision setting), collaboration and communication (e.g., relationship and trust building), self-development and self-awareness (e.g., experiential learning and self-examination), and consumer and community focus (e.g., public health messaging). In each of these areas, a broad range of strategies and approaches contributed to effective leadership under conditions of growing complexity, and a diverse array of contexts and situations for which these roles and competencies are applicable.

Conclusions

This research highlights the inherent interdependence of leadership requirements and health system complexity. Rather than as sets of roles and competencies, effective healthcare leadership might be better conceptualized as a set of broad goals to pursue that include fostering collaboration amongst stakeholders, building cultures of capacity, and continuously innovating for improved quality of care.
Efficacy of MAGE-A4 long peptide as a universal immunoprevention cancer vaccine
Authors: Cen Lanqi , Zhang Zhe , Sun Yi , Wu Nandie , Shao Jie , Qian Zhaoye , Tian Manman , Ke Yaohua , Liu Baorui
Published: July 2024

Background

The clinical application of peptide vaccines in tumor immunotherapy holds significant promise. Peptide-based tumor vaccines are currently subject to certain limitations in clinical trials, including the challenge of inducing a sustained response from CD4+ T helper cells and cytotoxic T lymphocytes (CTL), as well as human leukocyte antigen (HLA) restrictions.

Methods

Through the utilization of biological information methodology, a screening process was conducted to identify three potential long peptides that are specifically targeted by the MAGE-A4 antigen. The candidate long peptides were subjected to in vitro testing using human peripheral blood lymphocytes as samples to evaluate their immunogenicity and immune function. The antitumor properties and preliminary mechanism of the long peptide vaccine were investigated through the use of a mouse model designed for the prevention of triple negative breast cancer (TNBC).

Results

Three predicted multi-epitope long peptides targeting MAGE-A4 have shown to have a strong immunogenicity, with a total positive rate of 72% across different HLA subtypes in Chinese populations. they can also increase the levels of the costimulatory factor CD137 and tumor necrosis factor-alpha (TNF-α), activate T cells, and boost the cytotoxic activity. Results from an animal study have revealed that the long-peptide vaccine, both on its own and in combination with R848, has displayed impressive anti-tumor and target-specific capabilities. Moreover, it has the ability to increase the expression of effector memory T cells and central memory T cells.

Conclusions

This study was the first to screen three multi-epitope long peptides targeting MAGE-A4 and assess their immunogenicity, immune function, and potential as adjuvant peptides. The results showed that the MAGE-A4 long peptide vaccine can be used as a novel immunoprophylaxis method to prevent TNBC. Moreover, the proposed development model is capable of screening multiple target antigens, which lead to its clinical application.
Recruiting refugees to reduce labour shortages in health care professions: experimental evidence on the potential of foreign-language outreach on social media
Authors: Tjaden Jasper , Seuthe Miriam , Weinert Sebastian
Published: July 2024

Background

Many high-income countries are grappling with severe labour shortages in the healthcare sector. Refugees and recent migrants present a potential pool for staff recruitment due to their higher unemployment rates, younger age, and lower average educational attainment compared to the host society's labour force. Despite this, refugees and recent migrants, often possessing limited language skills in the destination country, are frequently excluded from traditional recruitment campaigns conducted solely in the host country’s language. Even those with intermediate language skills may feel excluded, as destination-country language advertisements are perceived as targeting only native speakers. This study experimentally assesses the effectiveness of a recruitment campaign for nursing positions in a German care facility, specifically targeting Arabic and Ukrainian speakers through Facebook advertisements.

Methods

We employ an experimental design (AB test) approximating a randomized controlled trial, utilizing Facebook as the delivery platform. We compare job advertisements for nursing positions in the native languages of Arabic and Ukrainian speakers (treatment) with the same advertisements displayed in German (control) for the same target group in the context of a real recruitment campaign for nursing jobs in Berlin, Germany. Our evaluation includes comparing link click rates, visits to the recruitment website, initiated applications, and completed applications, along with the unit cost of these indicators. We assess statistical significance in group differences using the Chi-squared test.

Results

We find that recruitment efforts in the origin language were 5.6 times (Arabic speakers) and 1.9 times (Ukrainian speakers) more effective in initiating nursing job applications compared to the standard model of German-only advertisements among recent migrants and refugees. Overall, targeting refugees and recent migrants was 2.4 (Ukrainians) and 10.8 (Arabic) times cheaper than targeting the reference group of German speakers indicating higher interest among these groups.

Conclusions

The results underscore the substantial benefits for employers in utilizing targeted recruitment via social media aimed at foreign-language communities within the country. This strategy, which is low-cost and low effort compared to recruiting abroad or investing in digitalization, has the potential for broad applicability in numerous high-income countries with sizable migrant communities. Increased employment rates among underemployed refugee and migrant communities, in turn, contribute to reducing poverty, social exclusion, public expenditure, and foster greater acceptance of newcomers within the receiving society.
SETDB1 regulates short interspersed nuclear elements and chromatin loop organization in mouse neural precursor cells
Authors: Sun Daijing , Zhu Yueyan , Peng Wenzhu , Zheng Shenghui , Weng Jie , Dong Shulong , Li Jiaqi , Chen Qi , Ge Chuanhui , Liao Liyong , Dong Yuhao , Liu Yun , Meng Weida , Jiang Yan
Published: July 2024

Background

Transposable elements play a critical role in maintaining genome architecture during neurodevelopment. Short Interspersed Nuclear Elements (SINEs), a major subtype of transposable elements, are known to harbor binding sites for the CCCTC-binding factor (CTCF) and pivotal in orchestrating chromatin organization. However, the regulatory mechanisms controlling the activity of SINEs in the developing brain remains elusive.

Results

In our study, we conduct a comprehensive genome-wide epigenetic analysis in mouse neural precursor cells using ATAC-seq, ChIP-seq, whole genome bisulfite sequencing, in situ Hi-C, and RNA-seq. Our findings reveal that the SET domain bifurcated histone lysine methyltransferase 1 (SETDB1)-mediated H3K9me3, in conjunction with DNA methylation, restricts chromatin accessibility on a selective subset of SINEs in neural precursor cells. Mechanistically, loss of Setdb1 increases CTCF access to these SINE elements and contributes to chromatin loop reorganization. Moreover, de novo loop formation contributes to differential gene expression, including the dysregulation of genes enriched in mitotic pathways. This leads to the disruptions of cell proliferation in the embryonic brain after genetic ablation of Setdb1 both in vitro and in vivo.

Conclusions

In summary, our study sheds light on the epigenetic regulation of SINEs in mouse neural precursor cells, suggesting their role in maintaining chromatin organization and cell proliferation during neurodevelopment.
Efficient synthesis of limonene production in Yarrowia lipolytica by combinatorial engineering strategies
Authors: Park Young-Kyoung , Sellés Vidal Lara , Bell David , Zabret Jure , Soldat Mladen , Kavšček Martin , Ledesma-Amaro Rodrigo
Published: July 2024

Background

Limonene has a variety of applications in the foods, cosmetics, pharmaceuticals, biomaterials, and biofuels industries. In order to meet the growing demand for sustainable production of limonene at industry scale, it is essential to find an alternative production system to traditional plant extraction. A promising and eco-friendly alternative is the use of microbes as cell factories for the synthesis of limonene.

Results

In this study, the oleaginous yeast Yarrowia lipolytica has been engineered to produce d- and l-limonene. Four target genes, l- or d-LS (limonene synthase), HMG (HMG-CoA reductase), ERG20 (geranyl diphosphate synthase), and NDPS1 (neryl diphosphate) were expressed individually or fused together to find the optimal combination for higher limonene production. The strain expressing HMGR and the fusion protein ERG20-LS was the best limonene producer and, therefore, selected for further improvement. By increasing the expression of target genes and optimizing initial OD, 29.4 mg/L of l-limonene and 24.8 mg/L of d-limonene were obtained. We also studied whether peroxisomal compartmentalization of the synthesis pathway was beneficial for limonene production. The introduction of d-LS and ERG20 within the peroxisome improved limonene titers over cytosolic expression. Then, the entire MVA pathway was targeted to the peroxisome to improve precursor supply, which increased d-limonene production to 47.8 mg/L. Finally, through the optimization of fermentation conditions, d-limonene production titer reached 69.3 mg/L.

Conclusions

In this work, Y. lipolytica was successfully engineered to produce limonene. Our results showed that higher production of limonene was achieved when the synthesis pathway was targeted to the peroxisome, which indicates that this organelle can favor the bioproduction of terpenes in yeasts. This study opens new avenues for the efficient synthesis of valuable monoterpenes in Y. lipolytica.
Phosphate limitation enhances malic acid production on nitrogen-rich molasses with Ustilago trichophora
Authors: Grebe Luca Antonia , Lichtenberg Philipp Georg , Hürter Katharina , Forsten Eva , Miebach Katharina , Büchs Jochen , Magnus Jørgen Barsett
Published: July 2024

Background

An important step in replacing petrochemical products with sustainable, cost-effective alternatives is the use of feedstocks other than, e.g., pure glucose in the fermentative production of platform chemicals. Ustilaginaceae offer the advantages of a wide substrate spectrum and naturally produce a versatile range of value-added compounds under nitrogen limitation. A promising candidate is the dicarboxylic acid malic acid, which may be applied as an acidulant in the food industry, a chelating agent in pharmaceuticals, or in biobased polymer production. However, fermentable residue streams from the food and agricultural industry with high nitrogen content, e.g., sugar beet molasses, are unsuited for processes with Ustilaginaceae, as they result in low product yields due to high biomass and low product formation.

Results

This study uncovers challenges in evaluating complex feedstock applicability for microbial production processes, highlighting the role of secondary substrate limitations, internal storage molecules, and incomplete assimilation of these substrates. A microliter-scale screening method with online monitoring of microbial respiration was developed using malic acid production with Ustilago trichophora on molasses as an application example. Investigation into nitrogen, phosphate, sulphate, and magnesium limitations on a defined minimal medium demonstrated successful malic acid production under nitrogen and phosphate limitation. Furthermore, a reduction of nitrogen and phosphate in the elemental composition of U. trichophora was revealed under the respective secondary substrate limitation. These adaptive changes in combination with the intricate metabolic response hinder mathematical prediction of product formation and make the presented screening methodology for complex feedstocks imperative. In the next step, the screening was transferred to a molasses-based complex medium. It was determined that the organism assimilated only 25% and 50% of the elemental nitrogen and phosphorus present in molasses, respectively. Due to the overall low content of bioavailable phosphorus in molasses, the replacement of the state-of-the-art nitrogen limitation was shown to increase malic acid production by 65%.

Conclusion

The identification of phosphate as a superior secondary substrate limitation for enhanced malic acid production opens up new opportunities for the effective utilization of molasses as a more sustainable and cost-effective substrate than, e.g., pure glucose for biobased platform chemical production.
Amphiphilic block and random copolymers: aggregation and hydrophobic modification on metal-free tanned collagen fibers
Authors: Yi Yudan , Fan Xinxin , Li Qijun , Wang Ya-nan
Published: July 2024

Hydrophobicity enhancement of metal-free leather, which is crucial for improving its comprehensive performance, can be achieved by using amphiphilic copolymer retanning agents. However, the relationship between the sequential structure and the hydrophobic modification effect of amphiphilic copolymers remains unclear. Herein, an amphiphilic block copolymer was synthesized using stearyl methacrylate and 2-(dimethylamino)ethyl methacrylate via atom transfer radical polymerization, and the corresponding random copolymer with similar monomer compositions and molecular weights was prepared for comparison. The aggregation behavior of block and random copolymers was investigated. DLS and TEM results indicate that the block copolymer exhibits a larger aggregate size than the corresponding random copolymer. Molecular dynamics simulations suggest that the block copolymer aggregate exhibit a thicker hydrophilic shell and more concentrated distribution of cationic DMA block than the random copolymer aggregate. Subsequently, the block and random copolymers were used for the hydrophobic modification of metal-free tanned collagen fibers (CFs). The block copolymer shows superior binding capacity to CFs than the random one because of its larger size and more concentrated charge distribution. Hence, the block copolymer can form a dense and uniform hydrophobic film on the surface of collagen fibrils and endow CFs with higher hydrophobicity than the random one. This work provides theoretical guidance for modulating the hydrophobicity of CFs by tailoring the sequential structure of amphiphilic copolymers, which is expected to inspire the manufacturing of high-performance metal-free leather.

Graphical Abstract