bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of electronic nursing handover on patient safety in the general (non-COVID-19) and COVID-19 intensive care units: a quasi-experimental study
Authors: Tataei Azadeh , Rahimi Bahlol , Afshar Hadi Lotfnezhad , Alinejad Vahid , Jafarizadeh Hossein , Parizad Naser
Published: May 2023

Background

The unprecedented increase in the nurses’ workload is one of the issues affecting the quality and safety of patient care in the Intensive Care Units (ICUs). The electronic nursing handover can share sufficient, relevant, and necessary data about patients with greater efficiency and accuracy and prevent their information from being deleted. Therefore, this study aimed to determine and compare the effect of the Electronic Nursing Handover System (ENHS) on patient safety in General ICU and COVID-19 ICU.

Method

This is a quasi-experimental study conducted during an 8-month period from 22 to 2021 to 26 June 2022 using a test-retest design. A total of 29 nurses working in the General and COVID-19 ICUs participated in this study. Data were collected using a five-part questionnaire consisting of demographic information, handover quality, handover efficiency, error reduction, and handover time. Data analysis was conducted in IBM SPSS Statistics for Windows, version 26 (IBM Corp., Armonk, N.Y., USA) using the chi-squared test, paired t-test, and Analysis of Covariance (ANCOVA).

Results

The results showed that the mean scores of handover quality and efficiency, reduction of clinical error, and handover time in the electronic handover were significantly higher than those obtained in the paper-based method. The results showed that the mean score of patient safety in the COVID-19 ICU was 177.40 ± 30.416 for the paper-based handover and 251.40 ± 29.049 for the electronic handover (p = .0001). Moreover, the mean score of patient safety in the general ICU was 209.21 ± 23.072 for the paper-based handover and 251.93 ± 23.381 for the electronic one (p = .0001).

Conclusion

The use of ENHS significantly improved the quality and efficiency of shift handover, reduced the possibility of clinical error, saved handover time, and finally increased patient safety compared to the paper-based method. The results also showed the positive perspectives of ICU nurses toward the positive effect of ENHS on the patient safety improvement.
Oral contraceptive pills shortage in Lebanon amidst the economic collapse: a nationwide exploratory study
Authors: Itani Rania , Khojah Hani MJ , Karout Samar , Abu-Farha Rana , Mukattash Tareq L. , Rahme Deema , Housary Khouloud , Achi Hiam El , Safar Ali O. , Al Hajj Ismail Karam , El-Lakany Abdalla
Published: May 2023

Background

The political instability, economic crisis, and devaluation of the national currency left Lebanese females suffering from a scarcity of oral contraceptive pills (OCPs). Therefore, we aimed to identify the incidence of OCPs shortage in Lebanon and its impact on women’s sexual and reproductive health, as well as physical and psychological well-being.

Methods

Community pharmacies were selected randomly across Lebanon, using a stratified sampling approach, where female clients asking for OCPs were interviewed using a standardized data collection form.

Results

A total of 440 females were interviewed. More than three-quarters of the participants (76.4%) reported not finding their preferred OCPs brands, almost 40% were affected by the increased prices, and 28.4% declared stockpiling OCPs. More than half of the participants using OCPs for pregnancy prevention reported adopting alternative traditional contraceptive methods (55.3%). Unplanned pregnancy was reported by 9.5% of participants, where 75% of them disclosed intentional abortion while the remaining (25%) reported experiencing a spontaneous miscarriage. Other consequences of OCPs shortage included mood disturbances (52.3%), dysregulation of menses (49.7%), dysmenorrhea (21.1%), weight gain (19.6%), acne (15.7%), and hirsutism (12.5%). Of the participants taking OCPs for birth control, 48.6% reported a reduced frequency of sexual intercourse, which led to conflicts with their partners (46%) and a decreased libido (26.7%).

Conclusions

OCPs shortage has seriously and negatively exposed women to various undesirable consequences including unplanned pregnancy and dysregulation of menses. Therefore, there is an urgent need to bring the attention of healthcare authorities to support the national pharmaceutical industry in manufacturing affordable OCPs generics to meet women’s reproductive health demands.
Association between circulating fatty acid metabolites and asthma risk: a two-sample bidirectional Mendelian randomization study
Authors: Huang Tingting , Long Yichen , Ou Yang , Li Jia , Huang Yilin , Gao Jinming
Published: May 2023

Background

Fatty acids are involved in a wide range of immunological responses in humans. Supplementation of polyunsaturated fatty acids has been reported to help alleviate symptoms and airway inflammation in asthma patients, whereas the effects of fatty acids on the actual risk of asthma remain controversial. This study comprehensively investigated the causal effects of serum fatty acids on asthma risk using two-sample bidirectional Mendelian Randomization (MR) analysis.

Methods

Genetic variants strongly associated with 123 circulating fatty acid metabolites were extracted as instrumental variables, and a large GWAS data of asthma was used to test effects of the metabolites on this outcome. The inverse-variance weighted method was used for primary MR analysis. The weighted median, MR-Egger regression, MR-PRESSO, and leave-one-out analyses were utilized to evaluate heterogeneity and pleiotropy. Potential confounders were adjusted by performing multivariable MR analyses. Reverse MR analysis was also conducted to estimate the causal effect of asthma on candidate fatty acid metabolites. Further, we performed colocalization analysis to examine the pleiotropy of variants within the fatty acid desaturase 1 (FADS1) locus between the significant metabolite traits and the risk of asthma. Cis-eQTL-MR and colocalization analysis were also performed to determine the association between RNA expression of FADS1 and asthma.

Results

Genetically instrumented higher average number of methylene groups was causally associated with a lower risk of asthma in primary MR analysis, while inversely, the higher ratio of bis-allylic groups to double bonds and the higher ratio of bis-allylic groups to total fatty acids, were associated with higher probabilities of asthma. Consistent results were obtained in multivariable MR when adjusted for potential confounders. However, these effects were completely eliminated after SNPs correlated with the FADS1 gene were excluded. The reverse MR also found no causal association. The colocalization analysis suggested that the three candidate metabolite traits and asthma likely share causal variants within the FADS1 locus. In addition, the cis-eQTL-MR and colocalization analyses demonstrated a causal association and shared causal variants between FADS1 expression and asthma.

Conclusions

Our study supports a negative association between several PUFA traits and the risk of asthma. However, this association is largely attributed to the influence of FADS1 polymorphisms. The results of this MR study should be carefully interpreted given the pleiotropy of SNPs associated with FADS1.
Targeting oral tumor microenvironment for effective therapy
Authors: Budi Hendrik Setia , Farhood Bagher
Published: May 2023

Oral cancers are among the common head and neck malignancies. Different anticancer therapy modalities such as chemotherapy, immunotherapy, radiation therapy, and also targeted molecular therapy may be prescribed for targeting oral malignancies. Traditionally, it has been assumed that targeting malignant cells alone by anticancer modalities such as chemotherapy and radiotherapy suppresses tumor growth. In the last decade, a large number of experiments have confirmed the pivotal role of other cells and secreted molecules in the tumor microenvironment (TME) on tumor progression. Extracellular matrix and immunosuppressive cells such as tumor-associated macrophages, myeloid-derived suppressor cells (MDSCs), cancer-associated fibroblasts (CAFs), and regulatory T cells (Tregs) play key roles in the progression of tumors like oral cancers and resistance to therapy. On the other hand, infiltrated CD4 + and CD8 + T lymphocytes, and natural killer (NK) cells are key anti-tumor cells that suppress the proliferation of malignant cells. Modulation of extracellular matrix and immunosuppressive cells, and also stimulation of anticancer immunity have been suggested to treat oral malignancies more effectively. Furthermore, the administration of some adjuvants or combination therapy modalities may suppress oral malignancies more effectively. In this review, we discuss various interactions between oral cancer cells and TME. Furthermore, we also review the basic mechanisms within oral TME that may cause resistance to therapy. Potential targets and approaches for overcoming the resistance of oral cancers to various anticancer modalities will also be reviewed. The findings for targeting cells and potential therapeutic targets in clinical studies will also be reviewed.
Associations between physical and mental health and the utilization of ambulatory and emergency healthcare among asylum-seekers: results from a cross-sectional survey in Berlin, Germany
Authors: Gottlieb Nora , Siegel Martin
Published: May 2023

Background

Despite a high burden of chronic and mental illness, asylum-seekers show low utilization of ambulatory specialist healthcare. Forgoing timely healthcare when facing access barriers may direct them toward emergency care. This paper examines interrelations of physical and mental health and utilization of ambulatory and emergency care, and explicitly addresses associations between the different types of care.

Methods

A structural equation model was applied to a sample of n = 136 asylum-seekers living in accommodation centers in Berlin, Germany. Utilization patterns of emergency care (outcome) and physical and mental ambulatory care (endogenous predictors) were estimated, while controlling for age, gender, chronic conditions, bodily pain, depression, anxiety, length of stay in Germany (exogenous predictors) and self-rated health (endogenous predictor).

Results

Associations were observed between ambulatory care utilization and poor self-rated health (0.207, CI: 0.05; 0.364), chronic illness (0.096, CI: 0.017; 0.175) and bodily pain (0.019, CI: 0.002; 0.036); between mental healthcare utilization and anxiety (0.202, CI: 0.051; 0.352); and between emergency care utilization and poor self-rated health (0.621, CI: 0.059; 1.183), chronic illness (0.287, CI: 0.012; 0.563), mental healthcare utilization (0.842, CI: 0.148; 1.535) and anxiety (0.790, CI: 0.141; 1.438) (values in parentheses show estimated regression coefficients and 95% confidence intervals). We found no associations between the utilization of ambulatory and emergency care.

Conclusions

Our study generates mixed results concerning associations between healthcare needs and ambulatory and emergency care utilization among asylum-seekers. We found no evidence that low utilization of ambulatory care contributes to emergency care utilization; neither did we find evidence that ambulatory treatment obviates the need to seek emergency care. Our results indicate that higher physical healthcare needs and anxiety are associated with more utilization of both ambulatory and emergency care; whereas healthcare needs related to depression tend to remain unmet. Both the undirected and under-utilization of health services may reflect navigation and accessibility issues. To facilitate more needs-based and effective healthcare utilization and thus contribute to health equity, support services such as interpretation and care navigation as well as outreach are warranted.
Fatty acids metabolism affects the therapeutic effect of anti-PD-1/PD-L1 in tumor immune microenvironment in clear cell renal cell carcinoma
Authors: Lin Hansen , Fu Liangmin , Li Pengju , Zhu Jiangquan , Xu Quanhui , Wang Yinghan , Mumin Mukhtar Adan , Zhou Xinwei , Chen Yuhang , Shu Guannan , Yao Gaosheng , Chen Minyu , Lu Jun , Zhang Lizhen , Liu YuJun , Zhao Yiqi , Bao Jiahao , Chen Wei , Luo Junhang , Li Xiaofei , Chen Zhenhua , Cao Jiazheng
Published: May 2023

Background

Clear cell renal cell carcinoma (ccRCC) is a highly invasive and metastatic subtype of kidney malignancy and is correlated with metabolic reprogramming for adaptation to the tumor microenvironment comprising infiltrated immune cells and immunomodulatory molecules. The role of immune cells in the tumor microenvironment (TME) and their association with abnormal fatty acids metabolism in ccRCC remains poorly understood.

Method

RNA-seq and clinical data of KIRC from The Cancer Genome Atlas (TCGA) and E-MTAB-1980 from the ArrayExpress dataset. The Nivolumab group and Everolimus group of the CheckMate 025 study, the Atezolizumab arm of IMmotion150 and the Atezolizumab plus Bevacizumab group of IMmotion151 cohort were obtained for subsequent analysis. After differential expression genes identification, the signature was constructed through univariate Cox proportional hazard regression and simultaneously the least absolute shrinkage and selection operator (Lasso) analysis and the predictive performance of our signature was assessed by using receiver operating characteristic (ROC), Kaplan–Meier (KM) survival analysis, nomogram, drug sensitivity analysis, immunotherapeutic effect analysis and enrichment analysis. Immunohistochemistry (IHC), qPCR and western blot were performed to measure related mRNA or protein expression. Biological features were evaluated by wound healing, cell migration and invasion assays and colony formation test and analyzed using coculture assay and flow cytometry.

Results

Twenty fatty acids metabolism-related mRNA signatures were constructed in TCGA and possessed a strong predictive performance demonstrated through time-dependent ROC and KM survival analysis. Notably, the high-risk group exhibited an impaired response to anti-PD-1/PD-L1 (Programmed death-1 receptor/Programmed death-1 receptor-ligand) therapy compared to the low-risk group. The overall levels of the immune score were higher in the high-risk group. Additionally, drug sensitivity analysis observed that the model could effectively predict efficacy and sensitivity to chemotherapy. Enrichment analysis revealed that the IL6-JAK-STAT3 signaling pathway was a major pathway. IL4I1 could promote ccRCC cells’ malignant features through JAK1/STAT3 signaling pathway and M2-like macrophage polarization.

Conclusion

The study elucidates that targeting fatty acids metabolism can affect the therapeutic effect of PD-1/PD-L1 in TME and related signal pathways. The model can effectively predict the response to several treatment options, underscoring its potential clinical utility.
The role of mitochondria in the resistance of melanoma to PD-1 inhibitors
Authors: Du Fei , Yang Lu-han , Liu Jiao , Wang Jian , Fan Lianpeng , Duangmano Suwit , Liu Hao , Liu Minghua , Wang Jun , Zhong Xiaolin , Zhang Zhuo , Wang Fang
Published: May 2023

Malignant melanoma is one of the most common tumours and has the highest mortality rate of all types of skin cancers worldwide. Traditional and novel therapeutic approaches, including surgery, targeted therapy and immunotherapy, have shown good efficacy in the treatment of melanoma. At present, the mainstay of treatment for melanoma is immunotherapy combined with other treatment strategies. However, immune checkpoint inhibitors, such as PD-1 inhibitors, are not particularly effective in the clinical treatment of patients with melanoma. Changes in mitochondrial function may affect the development of melanoma and the efficacy of PD-1 inhibitors. To elucidate the role of mitochondria in the resistance of melanoma to PD-1 inhibitors, this review comprehensively summarises the role of mitochondria in the occurrence and development of melanoma, targets related to the function of mitochondria in melanoma cells and changes in mitochondrial function in different cells in melanoma resistant to PD-1 inhibitors. This review may help to develop therapeutic strategies for improving the clinical response rate of PD-1 inhibitors and prolonging the survival of patients by activating mitochondrial function in tumour and T cells.
High levels of endothelial ICAM-1 prohibit natalizumab mediated abrogation of CD4+ T cell arrest on the inflamed BBB under flow in vitro
Authors: Soldati Sasha , Bär Alexander , Vladymyrov Mykhailo , Glavin Dale , McGrath James L. , Gosselet Fabien , Nishihara Hideaki , Goelz Susan , Engelhardt Britta
Published: May 2023

Introduction

The humanized anti-α4 integrin blocking antibody natalizumab (NTZ) is an effective treatment for relapsing–remitting multiple sclerosis (RRMS) that is associated with the risk of progressive multifocal leukoencephalopathy (PML). While extended interval dosing (EID) of NTZ reduces the risk for PML, the minimal dose of NTZ required to maintain its therapeutic efficacy remains unknown.

Objective

Here we aimed to identify the minimal NTZ concentration required to inhibit the arrest of human effector/memory CD4+ T cell subsets or of PBMCs to the blood–brain barrier (BBB) under physiological flow in vitro.

Results

Making use of three different human in vitro BBB models and in vitro live-cell imaging we observed that NTZ mediated inhibition of α4-integrins failed to abrogate T cell arrest to the inflamed BBB under physiological flow. Complete inhibition of shear resistant T cell arrest required additional inhibition of β2-integrins, which correlated with a strong upregulation of endothelial intercellular adhesion molecule (ICAM)-1 on the respective BBB models investigated. Indeed, NTZ mediated inhibition of shear resistant T cell arrest to combinations of immobilized recombinant vascular cell adhesion molecule (VCAM)-1 and ICAM-1 was abrogated in the presence of tenfold higher molar concentrations of ICAM-1 over VCAM-1. Also, monovalent NTZ was less potent than bivalent NTZ in inhibiting T cell arrest to VCAM-1 under physiological flow. In accordance with our previous observations ICAM-1 but not VCAM-1 mediated T cell crawling against the direction of flow.

Conclusion

Taken together, our in vitro observations show that high levels of endothelial ICAM-1 abrogate NTZ mediated inhibition of T cell interaction with the BBB. EID of NTZ in MS patients may thus require consideration of the inflammatory status of the BBB as high levels of ICAM-1 may provide an alternative molecular cue allowing for pathogenic T cell entry into the CNS in the presence of NTZ.
Functional and evolutionary study of MLO gene family in the regulation of Sclerotinia stem rot resistance in Brassica napus L.
Authors: Liu Jie , Wu Yupo , Zhang Xiong , Gill Rafaqat Ali , Hu Ming , Bai Zetao , Zhao Chuanji , Zhang Yi , Liu Yueying , Hu Qiong , Cheng Xiaohui , Huang Junyan , Liu Lijiang , Yan Shunping , Liu Shengyi
Published: May 2023

Background

Oilseed rape (Brassica napus L.) is known as one of the most important oilseed crops cultivated around the world. However, its production continuously faces a huge challenge of Sclerotinia stem rot (SSR), a destructive disease caused by the fungus Sclerotinia sclerotiorum, resulting in huge yield loss annually. The SSR resistance in B. napus is quantitative and controlled by a set of minor genes. Identification of these genes and pyramiding them into a variety are a major strategy for SSR resistance breeding in B. napus.

Results

Here, we performed a genome-wide association study (GWAS) using a natural population of B. napus consisting of 222 accessions to identify BnaA08g25340D (BnMLO2_2) as a candidate gene that regulates the SSR resistance. BnMLO2_2 was a member of seven homolog genes of Arabidopsis Mildew Locus O 2 (MLO2) and the significantly SNPs were mainly distributed in the promoter of BnMLO2_2, suggesting a role of BnMLO2_2 expression level in the regulation of SSR resistance. We expressed BnMLO2_2 in Arabidopsis and the transgenic plants displayed an enhanced SSR resistance. Transcriptome profiling of different tissues of B. napus revealed that BnMLO2_2 had the most expression level in leaf and silique tissues among all the 7 BnMLO2 members and also expressed higher in the SSR resistant accession than in the susceptible accession. In Arabidopsis, mlo2 plants displayed reduced resistance to SSR, whereas overexpression of MLO2 conferred plants an enhanced SSR resistance. Moreover, a higher expression level of MLO2 showed a stronger SSR resistance in the transgenic plants. The regulation of MLO2 in SSR resistance may be associated with the cell death. Collinearity and phylogenetic analysis revealed a large expansion of MLO family in Brassica crops.

Conclusion

Our study revealed an important role of BnMLO2 in the regulation of SSR resistance and provided a new gene candidate for future improvement of SSR resistance in B. napus and also new insights into understanding of MLO family evolution in Brassica crops.
An association of CSF apolipoprotein E glycosylation and amyloid-beta 42 in individuals who carry the APOE4 allele
Authors: Meuret Cristiana J. , Hu Yueming , Smadi Sabrina , Bantugan Mikaila Ann , Xian Haotian , Martinez Ashley E. , Krauss Ronald M. , Ma Qiu-Lan , Nedelkov Dobrin , Yassine Hussein N.
Published: May 2023

Carrying the apolipoprotein E (ApoE) Ɛ4 allele is associated with an increased risk of cerebral amyloidosis and late-onset Alzheimer’s disease, but the degree to which apoE glycosylation affects its development is not clear. In a previous pilot study, we identified distinct total and secondary isoform-specific cerebral spinal fluid (CSF) apoE glycosylation profiles, with the E4 isoform having the lowest glycosylation percentage (E2 > E3 > E4). In this work, we extend the analysis to a larger cohort of individuals (n = 106), utilizing matched plasma and CSF samples with clinical measures of AD biomarkers. The results confirm the isoform-specific glycosylation of apoE in CSF, resulting from secondary CSF apoE glycosylation patterns. CSF apoE glycosylation percentages positively correlated with CSF Aβ42 levels (r = 0.53, p < 0.0001). These correlations were not observed for plasma apoE glycosylation. CSF total and secondary apoE glycosylation percentages also correlated with the concentration of CSF small high-density lipoprotein particles (s-HDL-P), which we have previously shown to be correlated with CSF Aβ42 levels and measures of cognitive function. Desialylation of apoE purified from CSF showed reduced Aβ42 degradation in microglia with E4 > E3 and increased binding affinity to heparin. These results indicate that apoE glycosylation has a new and important role in influencing brain Aβ metabolism and can be a potential target of treatment.
Identifying the neurodevelopmental and psychiatric signatures of genomic disorders associated with intellectual disability: a machine learning approach
Authors: Donnelly Nicholas , Cunningham Adam , Salas Sergio Marco , Bracher-Smith Matthew , Chawner Samuel , Stochl Jan , Ford Tamsin , Raymond F. Lucy , Escott-Price Valentina , van den Bree Marianne B. M.
Published: May 2023

Background

Genomic conditions can be associated with developmental delay, intellectual disability, autism spectrum disorder, and physical and mental health symptoms. They are individually rare and highly variable in presentation, which limits the use of standard clinical guidelines for diagnosis and treatment. A simple screening tool to identify young people with genomic conditions associated with neurodevelopmental disorders (ND-GCs) who could benefit from further support would be of considerable value. We used machine learning approaches to address this question.

Method

A total of 493 individuals were included: 389 with a ND-GC, mean age = 9.01, 66% male) and 104 siblings without known genomic conditions (controls, mean age = 10.23, 53% male). Primary carers completed assessments of behavioural, neurodevelopmental and psychiatric symptoms and physical health and development. Machine learning techniques (penalised logistic regression, random forests, support vector machines and artificial neural networks) were used to develop classifiers of ND-GC status and identified limited sets of variables that gave the best classification performance. Exploratory graph analysis was used to understand associations within the final variable set.

Results

All machine learning methods identified variable sets giving high classification accuracy (AUROC between 0.883 and 0.915). We identified a subset of 30 variables best discriminating between individuals with ND-GCs and controls which formed 5 dimensions: conduct, separation anxiety, situational anxiety, communication and motor development.

Limitations

This study used cross-sectional data from a cohort study which was imbalanced with respect to ND-GC status. Our model requires validation in independent datasets and with longitudinal follow-up data for validation before clinical application.

Conclusions

In this study, we developed models that identified a compact set of psychiatric and physical health measures that differentiate individuals with a ND-GC from controls and highlight higher-order structure within these measures. This work is a step towards developing a screening instrument to identify young people with ND-GCs who might benefit from further specialist assessment.
Caroli syndrome associated with atrial septal defect and polydactyly: a case report
Authors: Ghassa Ali , Khouri Lina
Published: May 2023

Introduction

Caroli disease is multifocal segmental dilatation of the large intrahepatic bile ducts that connect to the main duct. It is considered a rare disease with an incidence rate of 1 in 1,000,000 births. There are two types of Caroli: the first type is the simple type, Caroli disease, which includes only cystic dilatation of the intrahepatic bile ducts. The second is called Caroli syndrome, which consists of Caroli disease and congenital hepatic fibrosis and might lead to portal hypertension leading to esophageal varices and splenomegaly. Atrial septal defect is one of the most common congenital heart diseases, occurring when the connection between the left and the right atriums fails to close. Polydactyly is one of the most common congenital malformations of the hands and feet. It manifests in excess fingers on the hands or toes.

Case presentation

A 6-year-old Arab girl presented to the hospital with abdominal pain for the last month with abdominal enlargement. The patient was already diagnosed with Caroli disease and polydactyly (six fingers on each limb) when she was born. Investigations including complete blood count, blood smear, bone marrow biopsy, esophagoscopy, abdominal ultrasound, and computed tomography scan showed splenomegaly associated with hypersplenism, fourth-grade non-bleeding varices, intrahepatic cystic formations in the left and right lobes, and an atrial septal defect with a left-to-right shunt. The patient was scheduled for a splenectomy after she was vaccinated with the appropriate vaccines. After follow-up for a week in the hospital, complete blood count showed an improvement. A month after that, the patient had liver abscesses and biliary fistula that were treated appropriately and her symptoms resolved.

Conclusion

The association of liver diseases, polydactyly, and congenital heart diseases is extremely rare and was only documented few times in the literature. However, to our knowledge, atrial septal defect has never been part of this combination before. The family history also makes this case unique and strongly suggests genetic etiology.
Menopause causes metabolic and cognitive impairments in a chronic cerebral hypoperfusion model of vascular contributions to cognitive impairment and dementia
Authors: Gannon Olivia J. , Naik Janvie S. , Riccio David , Mansour Febronia M. , Abi-Ghanem Charly , Salinero Abigail E. , Kelly Richard D. , Brooks Heddwen L. , Zuloaga Kristen L.
Published: May 2023

Background

The vast majority of women with dementia are post-menopausal. Despite clinical relevance, menopause is underrepresented in rodent models of dementia. Before menopause, women are less likely than men to experience strokes, obesity, and diabetes—known risk factors for vascular contributions to cognitive impairment and dementia (VCID). During menopause, ovarian estrogen production stops and the risk of developing these dementia risk factors spikes. Here, we aimed to determine if menopause worsens cognitive impairment in VCID. We hypothesized that menopause would cause metabolic dysfunction and increase cognitive impairment in a mouse model of VCID.

Methods

We performed a unilateral common carotid artery occlusion surgery to produce chronic cerebral hypoperfusion and model VCID in mice. We used 4-vinylcyclohexene diepoxide to induce accelerated ovarian failure and model menopause. We evaluated cognitive impairment using behavioral tests including novel object recognition, Barnes maze, and nest building. To assess metabolic changes, we measured weight, adiposity, and glucose tolerance. We explored multiple aspects of brain pathology including cerebral hypoperfusion and white matter changes (commonly observed in VCID) as well as changes to estrogen receptor expression (which may mediate altered sensitivity to VCID pathology post-menopause).

Results

Menopause increased weight gain, glucose intolerance, and visceral adiposity. VCID caused deficits in spatial memory regardless of menopausal status. Post-menopausal VCID specifically led to additional deficits in episodic-like memory and activities of daily living. Menopause did not alter resting cerebral blood flow on the cortical surface (assessed by laser speckle contrast imaging). In the white matter, menopause decreased myelin basic protein gene expression in the corpus callosum but did not lead to overt white matter damage (assessed by Luxol fast blue). Menopause did not significantly alter estrogen receptor expression (ERα, ERβ, or GPER1) in the cortex or hippocampus.

Conclusions

Overall, we have found that the accelerated ovarian failure model of menopause caused metabolic impairment and cognitive deficits in a mouse model of VCID. Further studies are needed to identify the underlying mechanism. Importantly, the post-menopausal brain still expressed estrogen receptors at normal (pre-menopausal) levels. This is encouraging for any future studies attempting to reverse the effects of estrogen loss by activating brain estrogen receptors.
Sertraline treatment influences [18F]FE-PE2I PET imaging for Parkinsonism
Authors: Justesen Thomas E. H. , Borghammer Per , Aanerud Joel , Hovind Peter , Marner Lisbeth
Published: May 2023

Background

The dopamine transporter (DaT) PET ligand [18F]FE-PE2I is used to aid the diagnosis of Parkinson’s disease. After encountering four patients with a history of daily sertraline use, who all showed atypical findings on [18F]FE-PE2I PET, we suspected that the selective serotonin reuptake inhibitor (SSRI), sertraline, might interfere with the results and lead to globally reduced striatal [18F]FE-PE2I binding due to sertraline’s high affinity for DaT.

Methods

We rescanned the four patients with [18F]FE-PE2I PET after a 5-day sertraline pause. Sertraline plasma concentration was estimated based on body weight and dose, and specific binding ratios (SBR) in caudate nucleus, known to be more preserved in Parkinson’s, were used to estimate the effect on tracer binding. Comparison was made to a patient with [18F]FE-PE2I PET before and after a 7-day Modafinil pause.

Results

We found a significant effect of sertraline on caudate nucleus SBR (p = 0.029). The effect showed a linear dose-dependent relationship that corresponds to a reduction in SBR by 0.32 or 0.44 for a 75 kg male or a 65 kg female, respectively, taking a daily dose of 50 mg sertraline.

Conclusion

Sertraline is one of the most commonly used antidepressants and in contrast to other SSRI’s, sertraline show high affinity for DaT. We recommend that sertraline treatment is taken into account when patients are undergoing [18F]FE-PE2I PET especially in patients showing apparent globally reduced PE2I binding. If tolerable, pausing of the sertraline treatment should be considered, especially for doses above 50 mg/day.
Macroeconomic impacts of energy communities and individual prosumers: an assessment of transformation pathways
Authors: Vögele Stefan , Broska Lisa Hanna , Ross Andrew , Rübbelke Dirk
Published: May 2023

Background

Active citizen participation, especially as collective prosumers in energy communities or as individual prosumers, is vital for a sustainable energy transition. As such, it is explicitly supported by European Union policy. It is the aim of policy-makers that a large proportion of the residential energy demand will be met in this way. At present, there is limited analysis on the macroeconomic impacts of such an increase in prosumers. In this study, we develop and apply an approach for assessing the macroeconomic impacts of transformation pathways, which depict potential developments of individual and collective prosumers.

Results

The paper methodologically demonstrates how to macroeconomically assess scenarios and transformation pathways originating from cross-impact balance analyses by means of an input–output analysis. In particular, it is shown how qualitative data on future developments can be transformed into financial flows so as to enable an input–output analysis. Based on the assessment of two transformation pathways, our main findings suggest that there might be positive regional and national effects on net value added and employment as well as reductions in CO2 emissions. We find that the scale of the effects strongly depends on the spatial distribution of heterogeneous households and the underlying economic structure.

Conclusions

Our study represents a methodological advancement by showing how scenarios and transformation pathways can be assessed in terms of their macroeconomic consequences. This study shows that energy communities and individual prosumers might generate positive effects on value added and on employment. Given that households fix their energy supply options for decades, political decisions to support the energy transition in the residential sector should be taken as soon as possible.
Bibliometric analysis and visualisation of heritage buildings preservation
Authors: Mohamed Basma , Marzouk Mohamed
Published: May 2023

Heritage buildings are considered a source of pride for countries, and their preservation is an important pursuit. Different techniques have been adopted in this regard, and many review papers have addressed them either qualitatively or quantitatively through bibliometric analysis. Nevertheless, none of these review studies conducted a general dynamic quantitative analysis of the vast amount of scientific literature about heritage buildings preservation (HBP) research domain over time. Therefore, the current study performs a bibliometric analysis of the relevant literature considering a time of two decades (2002–2022). A total of 863 peer-reviewed journal articles were extracted from the Web of Science Core Collection database. A five-step methodology was followed employing VOSviewer, CiteSpace, and Biblioshiny as the bibliometric software tools. The main findings revealed the annual publication trends and the most prominent articles. It was also found that 60% of the literature publications were published in journals, and only 2.4% corresponded to review studies. The scientific collaboration networks showed the most prolific researchers and countries. Further, the citation analysis of journals identified the most reliable information sources for academic researchers. Finally, the conceptual and intellectual knowledge structures were visualised and studied via science mapping analysis to map the research domain evolution and determine its trending patterns and promising areas for future exploration. The conducted review provides fellow researchers with a systematic summarised database to be familiarized with the HBP literature and identify potential research opportunities to conduct state-of-the-art research with the top contributors in the field (researchers, journals, and countries). In addition, policymakers can utilize the results from this research to find expert authors and academic support to facilitate forming partnerships to plan and fund relevant research and address the practical implications of preserving valuable heritage buildings.
Effects of dietary supplementation with a carvacrol–cinnamaldehyde–thymol blend on growth performance and intestinal health of nursery pigs
Authors: Zhao Bi-Chen , Wang Tian-Hao , Chen Jian , Qiu Bai-Hao , Xu Ya-Ru , Zhang Qing , Li Jian-Jie , Wang Chun-Jiang , Nie Qiu-Feng , Li Jin-Long
Published: May 2023

Background

Stress, herd transfer, and food changes experienced by nursery and fattening pigs can lead to reduced performance, reduced digestion and absorption, and impaired intestinal health. Given the role of essential oils in relieving stress and improving animal welfare, we hypothesized that essential oils may improve pig performance via promoting gut health and gut homeostasis laid by EOs supplementation during nursery continuously impacts performance in fattening pigs.

Results

A total of 100 piglets (Landrace × Large White; weighted 8.08 ± 0.34 kg, weaned at d 28) were randomly selected and divided into 2 treatments: (1) basal diet (Con); (2) basal diet supplement with 0.1% complex essential oils (CEO). The experiment period was 42 days. Then weaned piglets’ growth performance and indications of intestinal health were assessed. Compared to the Con group, dietary supplemented CEO enhanced BW at 14 d (P < 0.05), and increased ADG during 1 ~ 14 d and 1 ~ 42 d (P < 0.05). Furthermore, CEO group had lower FCR during 1 ~ 42 d (P < 0.05). The CEO group also showed higher VH and VH:CD in duodenum and ileum (P < 0.05). Additionally, dietary CEO supplementation improved gut barrier function, as manifested by increased the mRNA expression of tight-junction protein and decreased serum DAO, ET and D-LA levels (P < 0.05). Finally, CEO supplementation alleviated gut inflammation, increased the activity of digestive enzymes. Importantly, piglets supplemented with CEOs during nursery also had better performance during fattening, suggesting that the establishment of intestinal health will also continuously affect subsequent digestion and absorption capacity. In short, dietary supplemented CEO improved performance and gut health via modulating increased intestine absorptive area, barrier integrity, digestive enzyme activity, and attenuating intestine inflammation. Meanwhile, essential oil supplementation during the nursery period also had a favorable effect on the performance of growing pigs.

Conclusions

Therefore, the strategy of adding CEO to pig diets as a growth promoter and enhancing intestinal health is feasible.
Quality of family planning services and associated factors among reproductive age women attending family planning unit at public health facilities in Dire Dawa, Eastern Ethiopia, 2021
Authors: Abera Legesse , Ejigu Ezira , Hailu Mickiale , Tadesse Daniel , Omer Abdu
Published: May 2023

Introduction

Improving the quality of care has been a necessary goal for family planning programs worldwide. Even though extensive work has been done, the contraceptive prevalence rate is still low (41% in Ethiopia, 30.5% in Dire Dawa) and the unmet need for contraception is high (26%) in Ethiopia. Moreover, quality of care in family planning services has an important role in increasing coverage of services and program sustainability. Therefore, the objective of this study was to assess quality of family planning services and associated factors among reproductive age women attending family planning unit in public health facilities in Dire Dawa, Eastern Ethiopia.

Methods

A facility-based cross-sectional study was conducted among reproductive-age women attending a family planning unit in Dire Dawa, Eastern Ethiopia, from September 1–30/2021. A total of 576 clients were selected by systematic random sampling and interviewed using a pre-tested structured questionnaire. SPSS version 24 was used to analyze the data, which included descriptive statistics, bi-variable and multivariable logistic regression analyses. To determine the presence of an association between dependent and independent variables, AOR, P-value 0.05, and 95% CI were used.

Results

A total of 576 clients participated in the study and provided a response rate of 99%. The overall satisfaction of clients with FP services was 79%[95% CI:75.2%, 82.9%]. Having primary education (AOR = 2.11, 95% CI(1.11–4.24), convenient facility opening hours (AOR = 3.13, 95% CI (2.12–5.75), maintaining privacy (AOR = 4.1, 95% CI(2.50–8.12), demonstrating how to use F/P method (AOR = 1.98, 95% CI (1.01–5.20), and discussing F/P issues with husbands (AOR = 5.05, 95% CI: 3.33–7.64) were positively significantly associated with client satisfaction.

Conclusion and recommendation

This study revealed that about four-fifth of the clients was satisfied with the service they received. Clients’ education, facility opening hour, maintained privacy, discussion with husband, and demonstration of how to use the methods were associated with client satisfaction. Therefore, health facility heads should improve facility opening hour. Health care providers should maintain client privacy every time, and should consistently utilize information, education, and communication materials during consultation sessions by giving more attention to client who has no education. Partner’s discussion on family planning issues should also be encouraged.
Metastatic Hormone-Sensitive Prostate Cancer: Toward an Era of Adaptive and Personalized Treatment
Authors: Hamid Anis A. , Sayegh Nicolas , Tombal Bertrand , Hussain Maha , Sweeney Christopher J. , Graff Julie N. , Agarwal Neeraj
Published: May 2023

The advent of more effective treatment combinations for metastatic hormone-sensitive prostate cancer (mHSPC) has been built on successes in therapy development for metastatic, castration-resistant prostate cancer (mCRPC). Both disease phases hold similar challenges and questions. Is there an optimal therapy sequence to maximize disease control and balance treatment burden? Are there clinical and biologically based subgroups that inform personalized and/or adaptive strategies? How can clinicians interpret data from clinical trials in the context of rapidly evolving technologies? Herein, we review the contemporary landscape of treatment for mHSPC, including disease subgroups informing both intensification and potential deintensification strategies. Furthermore, we provide current insights into the complex biology of mHSPC and discuss the potential clinical application of biomarkers to guide therapy selection and the development of novel personalized approaches.
Cemetery Rounds
Authors: Steensma David
Published: May 2023

@DavidSteensma The author describes the complex emotions that result from encountering graves of former patients on walks through a cemetery in his New England hometown. He reflects the joy that memories of these patients bring and the sadness that medicine ultimately failed them.
On-Site Nurse-Led Cancer Genetics Program Increases Cancer Genetic Testing Completion in Black Veterans
Authors: Shevach Jeffrey W. , Aiello Lisa B. , Lynch Julie A. , Petersen Jeffrey , Hoffman-Hogg Lori , Hartzfeld Deborah , Lundquist Margaret , Kelley Michael J. , Scheuner Maren T. , Montgomery Robert , Damjanov Nevena , Robinson Kyle , Wong Yu-Ning , Jhala Darshana , Parikh Ravi B. , Maxwell Kara N.
Published: May 2023

PURPOSE

Telegenetics services can expand access to guideline-recommended cancer genetic testing. However, access is often not distributed equitably to all races and ethnicities. We evaluated the impact of an on-site nurse-led cancer genetics service in a diverse Veterans Affairs Medical Center (VAMC) oncology clinic on likelihood of germline testing (GT) completion.

METHODS

We conducted an observational retrospective cohort study of patients who were referred for cancer genetics services at the Philadelphia VAMC between October 1, 2020, and February 28, 2022. We evaluated the association between genetics service (on-site v telegenetics) and likelihood of GT completion in a subcohort of new consults, excluding patients with prior consults and those referred for known history of germline mutations.

RESULTS

A total of 238 Veterans, including 108 (45%) seen on site, were identified for cancer genetics services during the study period, with the majority referred for a personal (65%) or family (26%) history of cancer. In the subcohort of new consults, 121 Veterans (54% self-identified race/ethnicity [SIRE]-Black), including 60 (50%) seen on site, were included in the analysis of germline genetic testing completion. In a univariate analysis, patients who were seen by the on-site genetics service had 3.2-fold higher likelihood of completing GT (relative risk, 3.22; 95% CI, 1.89 to 5.48) compared with the telegenetics service. In multivariable regression analysis, the on-site genetics service was associated with higher likelihood of GT completion, but this association was only statistically significant in SIRE-Black compared with SIRE-White Veterans (adjusted RR, 4.78; 95% CI, 1.53 to 14.96; P < .001; P-interaction of race × genetics service = .016).

CONCLUSION

An on-site nurse-led cancer genetics service embedded in a VAMC Oncology practice was associated with higher likelihood of germline genetic testing completion than a telegenetics service among self-identified Black Veterans.
Metabolomic Profiles of Nonobese and Obese Women With Gestational Diabetes
Authors: Sormunen-Harju Heidi , Huvinen Emilia , Girchenko Polina V , Kajantie Eero , Villa Pia M , Hämäläinen Esa K , Lahti-Pulkkinen Marius , Laivuori Hannele , Räikkönen Katri , Koivusalo Saila B
Published: May 2023

Context

In non-pregnant population, nonobese individuals with obesity-related metabolome have increased risk for type 2 diabetes and cardiovascular diseases. The risk of these diseases is also increased after gestational diabetes.

Objective

This work aimed to examine whether nonobese (body mass index [BMI] < 30) and obese (BMI ≥ 30) women with gestational diabetes mellitus (GDM) and obese non-GDM women differ in metabolomic profiles from nonobese non-GDM controls.

Methods

Levels of 66 metabolic measures were assessed in early (median 13, IQR 12.4-13.7 gestation weeks), and across early, mid (20, 19.3-23.0), and late (28, 27.0-35.0) pregnancy blood samples in 755 pregnant women from the PREDO and RADIEL studies. The independent replication cohort comprised 490 pregnant women.

Results

Nonobese and obese GDM, and obese non-GDM women differed similarly from the controls across early, mid, and late pregnancy in 13 measures, including very low-density lipoprotein-related measures, and fatty acids. In 6 measures, including fatty acid (FA) ratios, glycolysis-related measures, valine, and 3-hydroxybutyrate, the differences between obese GDM women and controls were more pronounced than the differences between nonobese GDM or obese non-GDM women and controls. In 16 measures, including HDL-related measures, FA ratios, amino acids, and inflammation, differences between obese GDM or obese non-GDM women and controls were more pronounced than the differences between nonobese GDM women and controls. Most differences were evident in early pregnancy, and in the replication cohort were more often in the same direction than would be expected by chance alone.

Conclusion

Differences between nonobese and obese GDM, or obese non-GDM women and controls in metabolomic profiles may allow detection of high-risk women for timely targeted preventive interventions.