bluuebunny/crossref_metadata_2025_split huggingface dataset:
Examining the roles of partnerships in enhancing the health systems response to COVID-19 in Nigeria
Authors: Onyedinma Chioma Amarachi , Okeke Chinyere Cecilia , Onwujekwe Obinna 
Published: August 2023

Abstract
Background
The COVID-19 pandemic overwhelmed the health systems and socio-economic foundations of many countries, Nigeria inclusive. The study was carried out to assess, understand, document and report the activities/measures that are considered nationally and sub-nationally significant, both in terms of COVID-19 responses and in terms of strengthening the health system for the future, in response to future threats since this will not be the last pandemic This paper examines how partnerships contributed to the health system and other sectors’ responses to COVID − 19 infection in Nigeria.

Methods
This was a qualitative study. Data was collected using a scoping literature review and key informant interviews with 36 key stakeholders in the COVID-19 response in Nigeria, in Abuja (national level) Lagos and Enugu states (sub-national level). Interviews were recorded and transcribed verbatim. The qualitative data was analysed using thematic analysis.

Results
It was found that many partnerships were formed when responding to the COVID-19 pandemic in Nigeria. The health system leaned towards a horizontal dimension of partnership with non-health governmental sectors, non-governmental sectors, and other countries. All the components of the health system building blocks had a measure of partnership contributing to its accomplishments The partnerships came in varied forms, ranging from advocacy, funding, provision of palliatives to the citizens because of lockdowns, technical assistance, support to research, development of guidelines and health educational materials.

Conclusion
The health sector’s collaboration with other sectors strengthened all the building blocks of the health system and was invaluable in enhancing the response to COVID-19, which needed a whole of government and a multi-sectoral approach. Formal frameworks for quickly initiating whole-of-government and multi-sectoral partnerships should be developed, with clear roles and responsibilities. This should be deployed for health system resilience and for response to shocks such as the COVID-19 pandemic.
Emerging integrated care models for children and youth with mental health difficulties in Norway: a horizon scanning study
Authors: Holmen Ida Charlotte , Waibel Sina , Kaarboe Oddvar 
Published: August 2023

Abstract
Background
The implementation of Integrated Care Models (ICMs) represents a strategy for addressing the increasing issues of system fragmentation and improving service customization according to user needs. Available ICMs have been developed for adult populations, and less is known about ICMs specifically designed for children and youth. The study objective was to summarize and assess emerging ICMs for mental health services targeting children and youth in Norway.

Methods
A horizon scanning study was conducted in the field of child and youth mental health. The study encompassed two key components: (i) the identification of ICMs through a review of both scientific and grey literature, as well as input from key informants, and (ii) the evaluation of selected ICMs using semi-structured interviews with key informants. The aim of the interviews was to identify factors that either promote or hinder the successful implementation or scale up of these ICMs.

Results
Fourteen ICMs were chosen for analysis. These models encompassed a range of treatment philosophies, spanning from self-care and community care to specialized care. Several models placed emphasis on the referral process, prioritizing low-threshold access, and incorporating other sectors such as housing and child welfare. Four of the selected models included family or parents in their target group and five models extended their services to children and youth beyond the legal age of majority. Nine experts in the field willingly participated in the interview phase of the study. Identified challenges and facilitating factors associated with implementation or scale up of ICMs were related to the Norwegian healthcare system, mental health care delivery, as well as child and youth specific factors.

Conclusion
Care delivery targeting children and youth’s mental health requires further adaptation to accommodate the intricate nature of their lives. ICMs have been identified as a means to address this complexity by offering accessible services and adopting a holistic approach. This study highlights a selection of promising ICMs that appear capable of meeting some of the specific needs of children and youth. However, it is recommended to subject these models to further assessment and refinement to ensure their effectiveness and the fulfilment of their intended outcomes.
Fetal alcohol spectrum disorders prevention and clinical guidelines research-workshop report
Authors: Koehlmoos Tracey Pérez , Lee Elizabeth , Wisdahl Jennifer , Donaldson Tom 
Published: August 2023

AbstractIt is estimated that up to 1 in 20 people in the United States are affected by fetal alcohol spectrum disorders (FASD), an array of cognitive, emotional, physical and social disorders caused by exposure to alcohol during prenatal development. Common diagnoses encompassed within FASD include mood and behavioral disorders, memory and central nervous system deficits, attention-deficit/hyperactivity disorder (ADHD), slow growth and low body weight. While this condition affects a broad range of individuals and families, it is of particular concern in the military community, where cultural factors including an increased prevalence of alcohol misuse pose a unique set of challenges. To shed light on these issues and provide an overview of the existing research, programs, and clinical practice guidelines surrounding FASD, the Uniformed Services University of the Health Sciences (USUHS), in conjunction with FASD United, hosted the Workshop on Fetal Alcohol Spectrum Disorders Prevention and Clinical Guidelines Research on 21 September 2022 in Washington, DC. More than 50 attendees from academia, healthcare, federal agencies, and consumer advocacy organizations gathered to share research findings, lived experiences, and strategies for improving FASD prevention, diagnosis, interventions, and support.The workshop began with a series of presentations on FASD risk factors and causes, strategies for diagnosis and interventions, and impacts and lived experiences. Individuals and families affected by FASD spoke about the ways FASD, its symptoms, and the social stigma associated with it influences their daily lives, experiences at school and work, and access to healthcare. Several speakers highlighted the work of non-profit organizations and advocacy groups in supporting families affected by FASD and other challenges faced by military families more broadly. The workshop closed with a discussion of federal agency perspectives highlighting initiatives aimed at advancing research and access to care for women and families at-risk and those currently affected by FASD.
Fierce poison to others: the phenomenon of bacterial dependence on antibiotics
Authors: Paredes-Amaya Claudia C. , Ulloa María Teresa , García-Angulo Víctor Antonio 
Published: August 2023

AbstractBeyond the development of resistance, the effects of antibiotics on bacteria and microbial communities are complex and far from exhaustively studied. In the context of the current global antimicrobial resistance crisis, understanding the adaptive and physiological responses of bacteria to antimicrobials is of paramount importance along with the development of new therapies. Bacterial dependence on antibiotics is a phenomenon in which antimicrobials instead of eliminating the pathogens actually provide a boost for their growth. This trait comprises an extreme example of the complexities of responses elicited by microorganisms to these drugs. This compelling evolutionary trait was readily described along with the first wave of antibiotics use and dependence to various antimicrobials has been reported. Nevertheless, current molecular characterizations have been focused on dependence on vancomycin, linezolid and colistin, three critically important antibiotics frequently used as last resource therapy for multi resistant pathogens. Outstanding advances have been made in understanding the molecular basis for the dependence to vancomycin, including specific mutations involved. Regarding linezolid and colistin, the general physiological components affected by the dependence, namely ribosomes and membrane function respectively, have been established. Nonetheless the implications of antibiotic dependence in clinically relevant features, such as virulence, epidemics, relationship with development of resistance, diagnostics and therapy effectiveness require clarification. This review presents a brief introduction of the phenomenon of bacterial dependence to antibiotics and a summary on early and current research concerning the basis for this trait. Furthermore, the available information on the effect of dependence in key clinical aspects is discussed. The studies performed so far underline the need to fully disclose the biological and clinical significance of this trait in pathogens to successfully assess its role in resistance and to design adjusted therapies.
Bioinformatic and literature assessment of toxicity and allergenicity of a CRISPR-Cas9 engineered gene drive to control Anopheles gambiae the mosquito vector of human malaria
Authors: Qureshi Alima , Connolly John B. 
Published: August 2023

Abstract
Background
Population suppression gene drive is currently being evaluated, including via environmental risk assessment (ERA), for malaria vector control. One such gene drive involves the dsxFCRISPRh transgene encoding (i) hCas9 endonuclease, (ii) T1 guide RNA (gRNA) targeting the doublesex locus, and (iii) DsRed fluorescent marker protein, in genetically-modified mosquitoes (GMMs). Problem formulation, the first stage of ERA, for environmental releases of dsxFCRISPRh previously identified nine potential harms to the environment or health that could occur, should expressed products of the transgene cause allergenicity or toxicity.

Methods
Amino acid sequences of hCas9 and DsRed were interrogated against those of toxins or allergens from NCBI, UniProt, COMPARE and AllergenOnline bioinformatic databases and the gRNA was compared with microRNAs from the miRBase database for potential impacts on gene expression associated with toxicity or allergenicity. PubMed was also searched for any evidence of toxicity or allergenicity of Cas9 or DsRed, or of the donor organisms from which these products were originally derived.

Results
While Cas9 nuclease activity can be toxic to some cell types in vitro and hCas9 was found to share homology with the prokaryotic toxin VapC, there was no evidence from previous studies of a risk of toxicity to humans and other animals from hCas9. Although hCas9 did contain an 8-mer epitope found in the latex allergen Hev b 9, the full amino acid sequence of hCas9 was not homologous to any known allergens. Combined with a lack of evidence in the literature of Cas9 allergenicity, this indicated negligible risk to humans of allergenicity from hCas9. No matches were found between the gRNA and microRNAs from either Anopheles or humans. Moreover, potential exposure to dsxFCRISPRh transgenic proteins from environmental releases was assessed as negligible.

Conclusions
Bioinformatic and literature assessments found no convincing evidence to suggest that transgenic products expressed from dsxFCRISPRh were allergens or toxins, indicating that environmental releases of this population suppression gene drive for malaria vector control should not result in any increased allergenicity or toxicity in humans or animals. These results should also inform evaluations of other GMMs being developed for vector control and in vivo clinical applications of CRISPR-Cas9.
Prenatal and childhood exposure to per-/polyfluoroalkyl substances (PFASs) and its associations with childhood overweight and/or obesity: a systematic review with meta-analyses
Authors: Frigerio Gianfranco , Ferrari Chiara Matilde , Fustinoni Silvia 
Published: August 2023

Abstract
Background
Per-/polyfluoroalkyl substances (PFASs) are persistent organic pollutants and suspected endocrine disruptors.

Objective
The aim of this work was to conduct a systematic review with meta-analysis to summarise the associations between prenatal or childhood exposure to PFASs and childhood overweight/obesity.

Methods
The search was performed on the bibliographic databases PubMed and Embase with text strings containing terms related to prenatal, breastfeeding, childhood, overweight, obesity, and PFASs. Only papers describing a biomonitoring study in pregnant women or in children up to 18 years that assessed body mass index (BMI), waist circumference (WC), or fat mass in children were included. When the estimates of the association between a PFAS and an outcome were reported from at least 3 studies, a meta-analysis was conducted; moreover, to correctly compare the studies, we developed a method to convert the different effect estimates and made them comparable each other. Meta-analyses were performed also stratifying by sex and age, and sensitivity analyses were also performed.

Results
In total, 484 and 779 articles were retrieved from PubMed and Embase, respectively, resulting in a total of 826 articles after merging duplicates. The papers included in this systematic review were 49: 26 evaluating prenatal exposure to PFASs, 17 childhood exposure, and 6 both. Considering a qualitative evaluation, results were conflicting, with positive, negative, and null associations. 30 papers were included in meta-analyses (19 prenatal, 7 children, and 4 both). Positive associations were evidenced between prenatal PFNA and BMI, between PFOA and BMI in children who were more than 3 years, and between prenatal PFNA and WC. Negative associations were found between prenatal PFOS and BMI in children who were 3 or less years, and between PFHxS and risk of overweight. Relatively more consistent negative associations were evidenced between childhood exposure to three PFASs (PFOA, PFOS, and PFNA) and BMI, in particular PFOS in boys. However, heterogeneity among studies was high.

Conclusion
Even though heterogeneous across studies, the pooled evidence suggests possible associations, mostly positive, between prenatal exposure to some PFASs and childhood BMI/WC; and relatively stronger evidence for negative associations between childhood exposure to PFASs and childhood BMI.
Predictors of functional and morphological arterial wall properties in coronary artery disease patients with increased lipoprotein (a) levels before and after treatment with proprotein convertase subtilisin-kexin type 9 inhibitors
Authors: Likozar Andreja Rehberger , Šebeštjen Miran 
Published: August 2023

Abstract
Background
In addition to proatherogenic properties, lipoprotein (a) (Lp(a)) has also pro-inflammatory, antifibrinolytic and prothrombogenic features. The aim of the current study was to identify the predictors of functional and morphological properties of the arterial wall in patients after myocardial infarction and increased Lp(a) levels at the beginning and after treatment with proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors.

Methods
Seventy-six post-myocardial infarction patients with high Lp(a) levels were included in the study. Ultrasound measurements of flow-mediated dilation of brachial artery (FMD), carotid intima-media thickness (c-IMT) and pulse wave velocity (PWV) were performed initially and after 6 months of treatment. At the same time points lipids, Lp(a), inflammatory and hemostasis markers were measured in blood samples.

Results
In linear regression model FMD significantly correlated with age at first myocardial infarction (β = 0.689; p = 0.022), high-sensitivity C-reactive protein (β = -1.200; p = 0.009), vascular cell adhesion protein 1 (VCAM-1) (β = -0.992; p = 0.006), overall coagulation potential (β = 1.428; p = 0.014) and overall hemostasis potential (β = -1.473; p = 0.008). c-IMT significantly correlated with age at first myocardial infarction (β = 0.574; p = 0.033) and Lp(a) (β = 0.524; p = 0.040). PWV significantly correlated with systolic blood pressure (β = 0.332; p = 0.002), tumor necrosis factor alpha (β = 0.406; p = 0.002), interleukin-8 (β = -0.315; p = 0.015) and plasminogen activator inhibitor 1 (β = 0.229; p = 0.031). After treatment FMD reached statistical significance only in univariant analysis with systolic blood pressure (r = -0.286; p = 0.004) and VCAM-1 (r = -0.229; p = 0.024). PWV and c-IMT correlated with age (r = 0.334; p = 0.001 and r = 0.486; p < 0.0001, respectively) and systolic blood pressure (r = 0.556; p < 0.0001 and r = 0.233; p = 0.021, respectively).

Conclusions
Our results suggest that age, systolic blood pressure, Lp(a) levels and other biochemical markers associated with Lp(a) are predictors of functional and morphological properties of the arterial vessel wall in post-myocardial patients with high Lp(a) levels initially. However, after 6 months of treatment with PCSK9 inhibitors only age and systolic blood pressure seem to be predictors of these properties.

Trial registration
The protocol for this study was registered with clinicaltrials.gov on November, 3 2020 under registration number NCT04613167.

Graphical Abstract
The impact of non-caloric artificial sweetener aspartame on female reproductive system in mice model
Authors: Naik Ab Qayoom , Zafar Tabassum , Shrivastava Vinoy K 
Published: August 2023

Abstract
Background
Artificial sweeteners, used as sugar substitutes have found their ways into almost all the food items due to the notion that they are non-caloric. Aspartame is used in numerous food products throughout the world. The primary users of aspartame include diabetics and calorie conscious people who intend to limit their calorie intake.

Methods
Female Swiss albino mice were divided into three groups (12 mice each) for the duration of 30 and 60 days consecutively. The treatment groups received 40 mg/kg b. w. aspartame orally. Hormone assays using ELISA and tissue histopathology have been performed along with the fertility assay to access the treatment outcomeon the fertility of treated mice in comparison to controls.

Results
Present study reports that female mice treated with aspartame for 30 and 60 days showed significant reduction in body weight, relative organ weight of (liver and kidney) and gonadosomatic index. These changes were more significantly recorded in 60 days treatment group. Aspartame treated animals for 30 and 60 days showed duration-dependent decrease gonandotropins (follicle stimulating hormone and luteinizing hormone), and steroids (estradiol and progesterone). Moreover, severe histopathological changes, reduction in number of growing follicles, degenerative changes in follicular structure, corona radiata and zonagranulosa were also observed. Besides, histomorphological changes were also observed in the uterine structure including atrophic uterine endometrial glands, contracted endometrial lining, disruption of the endometrial structure and the shapes of blood vessels were also altered.

Conclusion
Non-nutritive artificial sweeteners including aspartame negatively impact the function of ovaries and feedback mechanism of reproductive hormones by affecting the hypothalamic–pituitary–gonadal axis. In light of present findings the aspartame negatively impacted the reproductive system of female mice. More studies are required to identify the molecular mechanism and the pathways involved.
Inhibition of ERK downregulates autophagy via mitigating mitochondrial fragmentation to protect SH-SY5Y cells from OGD/R injury
Authors: Yuan Zhang-Li , Mo Yan-Zi , Li De-Li , Xie Lu , Chen Meng-Hua 
Published: August 2023

Abstract
Background
Cerebral ischemia-reperfusion injury (CIRI) is the main cause leading to high mortality and neurological disability in patients with cardiac arrest/cardiopulmonary resuscitation (CA/CPR). Our previous study found that extracellular signal-regulated kinase (ERK) activation, dynamin-related protein1 (Drp1)/Mitofusin2 (Mfn2)-dependent mitochondrial dynamics imbalance, and excessive autophagy were involved in the mechanism of nerve injury after CA/CPR. However, the specific pathological signaling pathway is still unknown. This study aimed to explore the molecular function changes of ERK-Drp1/Mfn2-autophagy signaling pathway in SH-SY5Y cell oxygen-glucose deprivation/reoxygenation (OGD/R) model, to further clarify the pathophysiological mechanism of CIRI, and to provide a new strategy for cerebral protection after CIRI.

Methods
SH-SY5Y cells were pretreated with drugs 24 h before OGD/R. The Drp1 and Mfn2 knockdown were adopted small interfering RNAs. The overexpression of p-Drp1S616 and Mfn2 were used recombinant plasmids. The expression levels of mitochondrial dynamics proteins (p-Drp1, Drp1, Mfn2, Mfn1 and Opa1) and autophagy markers (LC3, Beclin1 and p62) were measured with the Western blotting. The mRNA levels after transfection were determined by PCR. Cell injury and viability were evaluated with released LDH activity and CCK8 assay kits. Mitochondria morphology and autophagosome were observed under transmission electron microscopy. Mitochondrial function was detected by the mitochondrial permeability transition pore assay kit. The co-expression of p-ERK, p-Drp1 and LC3 was assessed with multiple immunofluorescences. One-way analysis of variance followed by least significance difference post hoc analysis (for equal homogeneity) or Dunnett’s T3 test (for unequal homogeneity) were used for statistical tests.

Results
ERK inhibitor-PD98059 (PD) protects SH-SY5Y cells from OGD/R-induced injury; while ERK activator-TPA had the opposite effect. Similar to autophagy inhibitor 3-MA, PD downregulated autophagy to improve cell viability; while autophagy activator-rapamycin further aggravated cell death. PD and Drp1-knockdown synergistically attenuated OGD/R-induced Drp1 activation, mPTP opening and cell injury; overexpression of Drp1S616E or ablating Mfn2 partly abolished the protective effects of PD. Multiple immunofluorescences showed that p-ERK, p-Drp1 and LC3 were co-expressed.

Conclusion
Inhibition of ERK downregulates autophagy via reducing Drp1/Mfn2-dependent mitochondrial fragmentation to antagonize mitochondrial dysfunction and promotes cell survival in the SH-SY5Y cells OGD/R model.
PI3K/AKT signaling pathway as a critical regulator of epithelial-mesenchymal transition in colorectal tumor cells
Authors: Maharati Amirhosein , Moghbeli Meysam 
Published: August 2023

AbstractColorectal cancer (CRC) is one of the most frequent gastrointestinal malignancies that are considered as a global health challenge. Despite many progresses in therapeutic methods, there is still a high rate of mortality rate among CRC patients that is associated with poor prognosis and distant metastasis. Therefore, investigating the molecular mechanisms involved in CRC metastasis can improve the prognosis. Epithelial-mesenchymal transition (EMT) process is considered as one of the main molecular mechanisms involved in CRC metastasis, which can be regulated by various signaling pathways. PI3K/AKT signaling pathway has a key role in CRC cell proliferation and migration. In the present review, we discussed the role of PI3K/AKT pathway CRC metastasis through the regulation of the EMT process. It has been shown that PI3K/AKT pathway can induce the EMT process by down regulation of epithelial markers, while up regulation of mesenchymal markers and EMT-specific transcription factors that promote CRC metastasis. This review can be an effective step toward introducing the PI3K/AKT/EMT axis to predict prognosis as well as a therapeutic target among CRC patients.