bluuebunny/crossref_metadata_2025 huggingface dataset:
Perspectives across Canada about implementing a palliative approach in long-term care during COVID-19
Authors: Kruizinga Julia , Lucchese Stephanie , Vellani Shirin , Rivas Vanessa Maradiaga , Shamon Sandy , Diedrich Karine , Gillespie Laurel , Kaasalainen Sharon
Published: March 2023

Background

Long-term care (LTC) homes have been disproportionately impacted during COVID-19.

Purpose

To explore the perspectives of stakeholders across Canada around implementing a palliative approach in LTC home during COVID-19.

Methods

Qualitative, descriptive design using one-to-one or paired semi-structured interviews.

Results

Four themes were identified: (1) the influence of the pandemic on implementing a palliative approach, (2) families are an essential part of implementing a palliative approach, (3) prioritizing advance care planning (ACP) and goals of care (GoC) discussions in anticipation of the overload of deaths and (4) COVID-19 highlighting the need for a palliative approach as well as several subthemes.

Conclusion

The COVID-19 pandemic influenced the implementation of a palliative approach to care, where many LTC homes faced an overwhelming number of deaths and restricted the presence of family members. A more concentrated focus on home-wide ACP and GoC conversations and the need for a palliative approach to care in LTC were identified.
Spiritual well-being correlates with quality of life of both cancer and non-cancer patients in palliative care - further validation of EORTC QLQ-SWB32 in Finnish
Authors: Goyarrola Raimo , Lipsanen Jari , Saarelainen Suvi-Maria , Suviranta Raili , Rahko Eeva , Lamminmäki Annamarja , Klaavuniemi Tuula , Ahtiluoto Satu , Ohvanainen Antti , Metso Pekka , Pöyhiä Reino
Published: March 2023

Background

The European Organisation for Research and Treatment of Cancer (EORTC) has developed the Spiritual Well-being Questionnaire (EORTC QLQ-SWB32), a measure of spiritual well-being validated with people receiving palliative care for cancer, although its usefulness is not restricted to that population. We aimed to translate and validate this tool in Finnish and to study the relationship between spiritual well-being (SWB) and quality of life (QOL).

Methods

A Finnish translation was produced according to the guidelines of EORTC and included forward- and back-translations. Face, content, construct and convergence/divergence validity and reliability were studied in a prospective manner. QOL was assessed with EORTC QLQ-C30 and 15D questionnaires. Sixteen individuals participated in the pilot testing. 101 cancer patients drawn from oncology units, and 89 patients with other chronic diseases drawn from religious communities in different parts of the country participated in the validation stage. Retest was obtained from 16 individuals (8 cancer and 8 non-cancer patients). Inclusion criteria included patients with either a well-defined palliative care plan, or who would benefit from palliative care, as well as the capacity to understand and communicate in Finnish.

Results

The translation appeared understandable and acceptable. Factorial analysis identified four scoring scales with high Cronbach alfa values: Relationship with Self (0.73), Relationship with Others (0.84), Relationship with Something Greater (0.82), Existential (0.81), and, additionally, a scale on Relationship with God (0.85). There was a significant correlation between SWB and QOL in all participants.

Conclusions

The Finnish translation of EORTC QLQ-SWB32 is a valid and reliable measure both for research and clinical practice. SWB is correlated with QOL in cancer and non-cancer patients undergoing palliative care or who are eligible for it.
Prevalence and associated factors of client satisfaction with family planning service among family planning users in Ethiopia: a systematic review and meta-analysis
Authors: Geta Temesgen , Awoke Nefsu , Lankrew Tadele , Elfios Eshetu , Israel Eskinder
Published: March 2023

Background

Considering the importance of client satisfaction in the quality of family planning services, a regular evaluation should be carried out. Several studies have been conducted in Ethiopia, but so far there were no pooled estimates of the prevalence of customer satisfaction with family planning services in the country. Therefore, this systematic review and meta-analysis was intended to estimate the pooled prevalence of client satisfaction with Ethiopian family planning services in Ethiopia. The findings of the review can be used to develop strategies and draft policies in the country.

Methods and materials

This review included articles published only in Ethiopia. The main databases were Medline/PubMed, Web of Science, Google Scholar, Scopus, Ethiopian University Repository Online, and Cochrane Library. Cross-sectional studies conducted in English and meeting the eligibility criteria were included in the review. A random-effects meta-analysis was performed. Data extraction and analysis were performed using Microsoft Excel and STATA version 14 software, respectively.

Result

The pooled prevalence of customer satisfaction with family planning services in Ethiopia was 56.78% [(95% CI (49.99, 63.56); I2 = 96.2%, p < 0.001]. Waiting time > 30 min [OR = 0.2, 95% CI (0.1–0.29), I2 = 75.0%, p < 0.001], privacy maintained [OR = 5.46, 95% CI (1.43–20.9), I2 = 95.8%, p < 0.001], education status [OR = 0.47], 95% CI (0.22–0.98), I2 = 87.4%, p < 0.001] was significant in client satisfaction related to family planning services.

Conclusion

According to this review, client satisfaction with family planning services in Ethiopia was 56.78%. In addition, waiting time, women's educational level, and respect for privacy were identified as factors that both positively and negatively impact women's satisfaction with family planning services. Decisive action, such as educational intervention, continued monitoring and evaluation of family planning services, and arranging training for providers, is required to address identified issues and ensure higher levels of family satisfaction and utilization. This finding is important for shaping strategic policies and improving the quality of family planning services. This finding is important for designing strategic policy and increasing the quality of family planning services.
Acceptance and attitude towards the traditional chinese medicine among asymptomatic COVID-19 patients in Shanghai Fangcang hospital
Authors: Pan Bo , Yin Hong-wei , Yu Yue , Xiang Xing , Yu Cui , Yan Xiao-Jie , Zhai Xiao-feng , Bai Yuan , Hong Jing
Published: March 2023

Objective

The Coronavirus Disease 2019 (COVID-19) has brought severe damage to global health and socioeconomics. In China, traditional Chinese medicine (TCM) is the most important complementary and alternative medicine (CAM) and it has shown a beneficial role in the prevention and treatment of COVID-19. However, it is unknown whether patients are willing to accept TCM treatment. The objective of our study is to investigate the acceptance, attitude, and independent predictors of TCM among asymptomatic COVID-19 patients admitted to Shanghai fangcang hospital during the outbreak of the COVID-19 pandemic in Shanghai in 2022.

Methods

A cross-sectional study was conducted on asymptomatic COVID-19 patients in the largest fangcang hospital in Shanghai, China, from April 22, 2022, to May 25, 2022. Based on the literature review of previous similar studies, a self-report questionnaire was developed to assess the patients’ attitude and acceptance of TCM, and a multivariate logistic regression analysis was conducted to determine the independent predictors of TCM acceptance.

Results

A total of 1,121 patients completed the survey, of whom 91.35% were willing to accept CAM treatment whereas 8.65% of participants showed no willingness. Multivariate logistic regression analysis revealed that the patients who have received two doses of COVID-19 vaccine (OR = 2.069, 95%CI: 1.029–4.162, P = 0.041 vs. not received), understood the culture of TCM (OR = 2.293, 95%CI: 1.029–4.162, P = 0.014 vs. not understood), thought the TCM treatment is safe (OR = 2.856, 95%CI: 1.334–6.112, P = 0.007 vs. not thought), thought the TCM treatment is effective (OR = 2.724, 95%CI: 1.249–5.940, P = 0.012 vs. not thought), and those who informed their attending physician if using TCM for treatment (OR = 3.455, 95%CI:1.867–6.392, P < 0.001 vs. not informed) were more likely to accept TCM treatment. However, patients who thought TCM might delay your treatment (OR = 0.256, 95%CI: 0.142–0.462, P < 0.001 not thought) was an independent predictor for unwillingness to accept TCM treatment.

Conclusion

This study preliminarily investigated the acceptance, attitude, and predictors of intention to receive TCM among asymptomatic COVID-19 patients. It is recommended to increase the publicity of TCM, clarify the impact of TCM and communicate with attending doctors that meet the healthcare needs of asymptomatic COVID-19 patients.
Disseminated Staphylococcus aureus infection after scarification wet cupping therapy: a case report and literature review
Authors: Wang You-yang , Fan Hong-wei , Huang Xiao-ming , Jiao Yang
Published: March 2023

Background

Cupping therapy is a complementary and alternative medical therapy used especially in pain management. It is generally considered a safe procedure, but complications, including life-threatening infection, may still occur. Understanding these complications is essential to safe and evidence-based use of cupping in practice.

Case presentation

Here we report a rare case of disseminatedStaphylococcus aureus infection after cupping therapy. After wet cupping, a 33-year-old immunocompetent woman developed fever, myalgia, and a productive cough accompanied by acute liver and kidney injury, iliopsoas abscess, and gastrointestinal bleeding. The patient was treated successfully with cefmetazole plus levofloxacin after microbiological and antimicrobial sensitivity testing.

Conclusions

Though rarely reported, clinicians, practitioners of cupping therapy, and patients should be aware of the risk of infection after cupping therapy. High hygiene standards are recommended for cupping therapy, even in immunocompetent individuals.
Residential green space improves cognitive performances in primary schoolchildren independent of traffic-related air pollution exposure
Authors: Saenen Nelly D. , Nawrot Tim S. , Hautekiet Pauline , Wang Congrong , Roels Harry A. , Dadvand Payam , Plusquin Michelle , Bijnens Esmée M.
Published: March 2023

Background

Cognitive performances of schoolchildren have been adversely associated with both recent and chronic exposure to ambient air pollution at the residence. In addition, growing evidence indicates that exposure to green space is associated with a wide range of health benefits. Therefore, we aimed to investigate if surrounding green space at the residence improves cognitive performance of primary schoolchildren while taking into account air pollution exposure.

Methods

Cognitive performance tests were administered repeatedly to a total of 307 primary schoolchildren aged 9-12y, living in Flanders, Belgium (2012–2014). These tests covered three cognitive domains: attention (Stroop and Continuous Performance Tests), short-term memory (Digit Span Forward and Backward Tests), and visual information processing speed (Digit-Symbol and Pattern Comparison Tests). Green space exposure was estimated within several radii around their current residence (50 m to 2000 m), using a aerial photo-derived high-resolution (1 m2) land cover map. Furthermore, air pollution exposure to PM2.5 and NO2 during the year before examination was modelled for the child’s residence using a spatial–temporal interpolation method.

Results

An improvement of the children’s attention was found with more residential green space exposure independent of traffic-related air pollution. For an interquartile range increment (21%) of green space within 100 m of the residence, a significantly lower mean reaction time was observed independent of NO2 for both the sustained-selective (-9.74 ms, 95% CI: -16.6 to -2.9 ms, p = 0.006) and the selective attention outcomes (-65.90 ms, 95% CI: -117.0 to -14.8 ms, p = 0.01). Moreover, green space exposure within a large radius (2000 m) around the residence was significantly associated with a better performance in short-term memory (Digit-Span Forward Test) and a higher visual information processing speed (Pattern Comparison Test), taking into account traffic-related exposure. However, all associations were attenuated after taking into account long-term residential PM2.5 exposure.

Conclusions

Our panel study showed that exposure to residential surrounding green space was associated with better cognitive performances at 9–12 years of age, taking into account traffic-related air pollution exposure. These findings support the necessity to build attractive green spaces in the residential environment to promote healthy cognitive development in children.
PROTAC’ing oncoproteins: targeted protein degradation for cancer therapy
Authors: Kelm Jeremy M. , Pandey Deepti S. , Malin Evan , Kansou Hussein , Arora Sahil , Kumar Raj , Gavande Navnath S.
Published: March 2023

Molecularly targeted cancer therapies substantially improve patient outcomes, although the durability of their effectiveness can be limited. Resistance to these therapies is often related to adaptive changes in the target oncoprotein which reduce binding affinity. The arsenal of targeted cancer therapies, moreover, lacks coverage of several notorious oncoproteins with challenging features for inhibitor development. Degraders are a relatively new therapeutic modality which deplete the target protein by hijacking the cellular protein destruction machinery. Degraders offer several advantages for cancer therapy including resiliency to acquired mutations in the target protein, enhanced selectivity, lower dosing requirements, and the potential to abrogate oncogenic transcription factors and scaffolding proteins. Herein, we review the development of proteolysis targeting chimeras (PROTACs) for selected cancer therapy targets and their reported biological activities. The medicinal chemistry of PROTAC design has been a challenging area of active research, but the recent advances in the field will usher in an era of rational degrader design.
Reprogramming anchorage dependency by adherent-to-suspension transition promotes metastatic dissemination
Authors: Huh Hyunbin D. , Sub Yujin , Oh Jongwook , Kim Ye Eun , Lee Ju Young , Kim Hwa-Ryeon , Lee Soyeon , Lee Hannah , Pak Sehyung , Amos Sebastian E. , Vahala Danielle , Park Jae Hyung , Shin Ji Eun , Park So Yeon , Kim Han Sang , Roh Young Hoon , Lee Han-Woong , Guan Kun-Liang , Choi Yu Suk , Jeong Joon , Choi Junjeong , Roe Jae-Seok , Gee Heon Yung , Park Hyun Woo
Published: March 2023

Background

Although metastasis is the foremost cause of cancer-related death, a specialized mechanism that reprograms anchorage dependency of solid tumor cells into circulating tumor cells (CTCs) during metastatic dissemination remains a critical area of challenge.

Methods

We analyzed blood cell-specific transcripts and selected key Adherent-to-Suspension Transition (AST) factors that are competent to reprogram anchorage dependency of adherent cells into suspension cells in an inducible and reversible manner. The mechanisms of AST were evaluated by a series of in vitro and in vivo assays. Paired samples of primary tumors, CTCs, and metastatic tumors were collected from breast cancer and melanoma mouse xenograft models and patients with de novo metastasis. Analyses of single-cell RNA sequencing (scRNA-seq) and tissue staining were performed to validate the role of AST factors in CTCs. Loss-of-function experiments were performed by shRNA knockdown, gene editing, and pharmacological inhibition to block metastasis and prolong survival.

Results

We discovered a biological phenomenon referred to as AST that reprograms adherent cells into suspension cells via defined hematopoietic transcriptional regulators, which are hijacked by solid tumor cells to disseminate into CTCs. Induction of AST in adherent cells 1) suppress global integrin/ECM gene expression via Hippo-YAP/TEAD inhibition to evoke spontaneous cell–matrix dissociation and 2) upregulate globin genes that prevent oxidative stress to acquire anoikis resistance, in the absence of lineage differentiation. During dissemination, we uncover the critical roles of AST factors in CTCs derived from patients with de novo metastasis and mouse models. Pharmacological blockade of AST factors via thalidomide derivatives in breast cancer and melanoma cells abrogated CTC formation and suppressed lung metastases without affecting the primary tumor growth.

Conclusion

We demonstrate that suspension cells can directly arise from adherent cells by the addition of defined hematopoietic factors that confer metastatic traits. Furthermore, our findings expand the prevailing cancer treatment paradigm toward direct intervention within the metastatic spread of cancer.
Seminoma arising in splenogonadal fusion: a case report and literature review
Authors: Shen Donglai , Li Yuzhu , Zhang Yu , Chang Xiao , Zhao Xupeng , Li Jiabin , Zhang Xu , Guo Gang
Published: March 2023

Background

Splenogonadal fusion (SGF) is a rare congenital malformation in which the spleen is abnormally connected to the gonads or to the mesonephric derivatives. There is no obvious causality between SGF and testicular neoplasm. However, cryptorchidism, which is a well-known risk factor of testicular germ cell tumors, are the most frequent malformations associated with SGF. To our knowledge, there are only four reported cases of SGF associated with testicular neoplasm so far. Herein, we reported a patient of this condition, and briefly reviewed the related literature.

Case presentation

A 48-year-old man was diagnosed with bilateral cryptorchidism 30 years prior, and only underwent a right orchiopexy for the left testicle could not be explored during the operation. At that time, doctors failed to realize the possibility of SGF due to the lack of sufficient knowledge of this condition. This time, the patient was treated for a left abdomen mass that was diagnosed as stage III metastatic seminoma. Then, a right orchiectomy, robot-assisted laparoscopic left retroperitoneal tumor resection, and left retroperitoneal lymph node dissection was performed after four cycles of BEP (bleomycin + etoposide + cisplatin) systemic chemotherapy in our center. The final diagnosis of SGF was made by postoperative pathology. The patient was re-examined in our center at 3 months and 6 months after the operation, and no obvious abnormalities were found.

Conclusions

Surgeons should always bear in mind the possibility of association between bilateral cryptorchidism and splenogonadal fusion to avoid malignant transformation caused by delayed treatment.
Protective effects of Qing-Re-Huo-Xue formula on bleomycin-induced pulmonary fibrosis through the p53/IGFBP3 pathway
Authors: Yang Fangyong , Du Wenjing , Tang Zhao , Wei Ying , Dong Jingcheng
Published: March 2023

Background

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing lung disease with high mortality. Inflammation and epithelial mesenchymal transformation (EMT) may play an important role in the occurrence and development of IPF. Qing-Re-Huo-Xue formula (QRHXF) has been used clinically by our team for half a century and has obvious therapeutic effects on lung disease. Nevertheless, the role and mechanism of QRHXF in the treatment of IPF have never been studied.

Methods

A mouse pulmonary fibrosis model was established by intratracheal injection of BLM. The effects of QRHXF on the treatment of pulmonary fibrosis were studied by pulmonary function testing, imaging examination, pathological staining, transmission electron microscopy (TEM) observation and mRNA expression. Tandem mass tag (TMT)-based quantitative proteomics was carried out to analyse the lung protein expression profiles between the control (CTL), bleomycin (BLM) and QRHXF (BLM + QRHXF) groups. Immunohistochemistry and qRT-PCR were used to verify the possible existence of drug target proteins and signalling pathways.

Results

The results of pulmonary function, lung pathology and imaging examinations showed that QRHXF could significantly alleviate BLM-induced pulmonary fibrosis in vivo. Additionally, inflammatory cell infiltration and EMT were markedly reduced in BLM-induced PF mice administered QRHXF. Proteomics detected a total of 35 proteins, of which 17 were upregulated and 18 were downregulated. A total of 19 differentially expressed proteins (DEPs) overlapped between the BLM versus CTL groups and the BLM + QRHXF versus BLM groups. The expression of p53 and IGFBP3 was reversed in the QRHXF intervention group, which was verified by immunohistochemistry and qRT-PCR.

Conclusions

QRHXF attenuated BLM-induced pulmonary fibrosis, and regulation of the p53/IGFBP3 pathway might be associated with its efficacy, which holds promise as a novel treatment strategy for pulmonary fibrosis patients.

Graphical Abstract
Thinning effects on stand growth, carbon stocks, and soil properties in Brutia pine plantations
Authors: Erkan Neşat , Güner Şükrü Teoman , Aydın Ali Cem
Published: March 2023

Background

The purpose of this study was to investigate the effects of thinning on stand growth, carbon (C) sequestration, and soil properties in Brutia pine (Pinus brutiaTen.) plantations. The study was conducted at two experimental sites -the Antalya-Kaş and Isparta-Eğirdir plantation areas- in Turkey between 1985 and 2015. Different thinning intensities -unthinned (control), moderate, and heavy- were replicated in four blocks. We determined the C in the living biomass, litter, soil, and some soil features for each experimental parcel.

Results

We found no statistically significant difference in total stand volume between thinning-intensity treatments 30 years after thinning. This may be due to more light availability and less competition between trees and faster tree-diameter growth rate after thinning, thus explaining the volume in the treated parcels compared to the control over time. The C stocks in the biomass, litter, and soil were not significantly influenced by the thinning intensity. The nutrients in the litter and soil, and other soil properties, were not significantly different among thinning parcels. This implies that the C and other nutrients in the litter and soil are related to the stand volume and biomass, which were not changed by thinning in time.

Conclusion

This finding is important in terms of showing that there was no change in total stand volume by thinning, which has been debated in the literature. This information is useful for forest managers when determining thinning strategy.
circACTR2 attenuates gemcitabine chemoresiatance in pancreatic cancer through PTEN mediated PI3K/AKT signaling pathway
Authors: Xu Chao , Ye Qinwen , Ye Chao , Liu Shaojun
Published: March 2023

Background

Recently, accumulating studies have unveiled that circRNAs exert critical function in a variety of tumor biological processes including chemoresistance. Our previous study has found circACTR2 is significantly down-regulated in acquired gemcitabine (GEM)- resistant pancreatic cancer (PC) cells, which has not been well-explored. Our study aimed to research the function and molecular mechanism of circACTR2 in PC chemoresistance.

Methods

qRT-PCR and western blot analysis was performed to detect gene expression. The effect of circACTR2 on PC GEM resistance were examined by CCK-8 and flow cytometry assays. Whether circACTR2 could sponge miR-221-3p and regulate PTEN expression were determined by bioinformatics analysis, RNA pull-down, and Dual-luciferase reporter assay.

Results

circACTR2 was notably down-regulated in a panel of GEM-resistant PC cells lines, and negatively associated with aggressive phenotype and poor prognosis of PC. circACTR2 downregulation contributed to GEM chemoresistance of PC cells with decreased S phase ratio of cell cycle and cell apoptosis, as confirmed by gain- and loss-of-function assays in vitro. In addition, circACTR2 overexpression retarded GEM resistance in vivo. Further, circACTR2 acted as a ceRNA against miR-221-3p, which directly targeted PTEN. The mechanistic studies revealed that loss of circACTR2 promoted GEM resistance in PC through activating the PI3K/AKT signaling pathway by downregulating PTEN expression in a miR-221-3p dependent manner.

Conclusions

circACTR2 reversed the chemoresistance of PC cells to GEM through inhibiting PI3K/AKT signaling pathway by sponging miR-221-3p and upregulating PTEN expression.
Development of models to predict 10-30-year cardiovascular disease risk using the Da Qing IGT and diabetes study
Authors: Chen Fei , Wang Jinping , Chen Xiaoping , Yu Liping , An Yali , Gong Qiuhong , Chen Bo , Xie Shuo , Zhang Lihong , Shuai Ying , Zhao Fang , Chen Yanyan , Li Guangwei , Zhang Bo
Published: March 2023

Background

This study aimed to develop cardiovascular disease (CVD) risk equations for Chinese patients with newly diagnosed type 2 diabetes (T2D) to predict 10-, 20-, and 30-year of risk.

Methods

Risk equations for forecasting the occurrence of CVD were developed using data from 601 patients with newly diagnosed T2D from the Da Qing IGT and Diabetes Study with a 30-year follow-up. The data were randomly assigned to a training and test data set. In the training data set, Cox proportional hazard regression was used to develop risk equations to predict CVD. Calibration was assessed by the slope and intercept of the line between predicted and observed probabilities of outcomes by quintile of risk, and discrimination was examined using Harrell’s C statistic in the test data set. Using the Sankey flow diagram to describe the change of CVD risk over time.

Results

Over the 30-year follow-up, corresponding to a 10,395 person-year follow-up time, 355 of 601 (59%) patients developed incident CVD; the incidence of CVD in the participants was 34.2 per 1,000 person-years. Age, sex, smoking status, 2-h plasma glucose level of oral glucose tolerance test, and systolic blood pressure were independent predictors. The C statistics of discrimination for the risk equations were 0.748 (95%CI, 0.710–0.782), 0.696 (95%CI, 0.655–0.704), and 0.687 (95%CI, 0.651–0.694) for 10-, 20-, and 30- year CVDs, respectively. The calibration statistics for the CVD risk equations of slope were 0.88 (P = 0.002), 0.89 (P = 0.027), and 0.94 (P = 0.039) for 10-, 20-, and 30-year CVDs, respectively.

Conclusions

The risk equations forecast the long-term risk of CVD in patients with newly diagnosed T2D using variables readily available in routine clinical practice. By identifying patients at high risk for long-term CVD, clinicians were able to take the required primary prevention measures.
Ethnicity and survival after a dementia diagnosis: a retrospective cohort study using electronic health record data
Authors: Co Melissa , Mueller Christoph , Mayston Rosie , Das-Munshi Jayati , Prina Matthew
Published: March 2023

Background

Individuals from minority ethnic groups in the UK are thought to be at higher risk of developing dementia while facing additional barriers to receiving timely care. However, few studies in the UK have examined if there are ethnic disparities in survival once individuals receive a dementia diagnosis.

Methods

We conducted a retrospective cohort study using electronic health record data of individuals diagnosed with dementia from a large secondary mental healthcare provider in London. Patients from Black African, Black Caribbean, South Asian, White British, and White Irish ethnic backgrounds were followed up for a 10-year period between 01 January 2008 and 31 December 2017. Data were linked to death certificate data from the Office of National Statistics to determine survival from dementia diagnosis. Standardised mortality ratios were calculated to estimate excess deaths in each ethnicity group as compared to the gender- and age-standardised population of England and Wales. We used Cox regression models to compare survival after dementia diagnosis across each ethnicity group.

Results

Mortality was elevated at least twofold across all ethnicity groups with dementia compared to the general population in England and Wales. Risk of death was lower in Black Caribbean, Black African, White Irish, and South Asian groups as compared to the White British population, even after adjusting for age, gender, neighbourhood-level deprivation, indicators of mental and physical comorbidities. Risk of death remained lower after additionally accounting for those who emigrated out of the cohort.

Conclusions

While mortality in dementia is elevated across all ethnic groups as compared to the general population, reasons for longer survival in minority ethnic groups in the UK as compared to the White British group are unclear and merit further exploration. Implications of longer survival, including carer burden and costs, should be considered in policy and planning to ensure adequate support for families and carers of individuals with dementia.
Asymptomatic surveillance testing for COVID-19 in health care professional students: lessons learned from a low prevalence setting
Authors: Burrows Alyssa G. , Linton Sophia , Thiele Jenny , Sheth Prameet M. , Evans Gerald A. , Archer Stephen , Doliszny Katharine M. , Finlayson Marcia , Flynn Leslie , Huang Yun , Kasmani Azim , Hugh Guan T. , Maier Allison , Hansen-Taugher Adrienne , Moore Kieran , Sanfilippo Anthony , Snelgrove-Clarke Erna , Tripp Dean A. , Walker David M. C. , Vanner Stephen , Ellis Anne K.
Published: March 2023

The novel coronavirus disease of 2019 (COVID-19) pandemic has severely impacted the training of health care professional students because of concerns of potential asymptomatic transmission to colleagues and vulnerable patients. From May 27th, 2020, to June 23rd 2021; at a time when B.1.1.7 (alpha) and B.1.617.2 (delta) were the dominant circulating variants, PCR testing was conducted on 1,237 nasopharyngeal swabs collected from 454 asymptomatic health care professional students as they returned to their studies from across Canada to Kingston, ON, a low prevalence area during that period for COVID-19. Despite 46.7% of COVID-19 infections occurring in the 18–29 age group in Kingston, severe-acute-respiratory coronavirus-2 was not detected in any of the samples suggesting that negligible asymptomatic infection occurred in this group and that PCR testing in this setting may not be warranted as a screening tool.
Integrative diagnostics: the time is now—a report from the International Society for Strategic Studies in Radiology
Authors: Beauchamp Norman J. , Bryan R. Nick , Bui Marilyn M. , Krestin Gabriel P. , McGinty Geraldine B. , Meltzer Carolyn C. , Neumaier Michael
Published: March 2023

Enormous recent progress in diagnostic testing can enable more accurate diagnosis and improved clinical outcomes. Yet these tests are increasingly challenging and frustrating; the volume and diversity of results may overwhelm the diagnostic acumen of even the most dedicated and experienced clinician. Because they are gathered and processed within the “silo” of each diagnostic discipline, diagnostic data are fragmented, and the electronic health record does little to synthesize new and existing data into usable information. Therefore, despite great promise, diagnoses may still be incorrect, delayed, or never made. Integrative diagnostics represents a vision for the future, wherein diagnostic data, together with clinical data from the electronic health record, are aggregated and contextualized by informatics tools to direct clinical action. Integrative diagnostics has the potential to identify correct therapies more quickly, modify treatment when appropriate, and terminate treatment when not effective, ultimately decreasing morbidity, improving outcomes, and avoiding unnecessary costs. Radiology, laboratory medicine, and pathology already play major roles in medical diagnostics. Our specialties can increase the value of our examinations by taking a holistic approach to their selection, interpretation, and application to the patient’s care pathway. We have the means and rationale to incorporate integrative diagnostics into our specialties and guide its implementation in clinical practice.

Graphic abstract
Dual-energy CT quantification of extracellular liver volume predicts short-term disease progression in patients with hepatitis B liver cirrhosis-acute decompensation
Authors: Xu Yuan , Li Yufeng , Li Shenglin , Xue Shouxiao , Liu Jianli
Published: March 2023

Background

Liver cirrhosis-acute decompensation (LC-AD) has rapid short-term disease progression and difficult early risk stratification. The purpose is to develop and validate a model based on dual-energy CT quantification of extracellular liver volume (ECVIC-liver) for predicting the occurrence of acute-on-chronic liver failure (ACLF) within 90 days in patients with hepatitis B (HBV) LC-AD.

Methods

The retrospective study included patients with HBV LC-AD who underwent dual-energy CT scans of the liver from January 2018 to March 2022 and were randomized to training group (215 patients) and validation group (92 patients). The primary outcome was the need for readmission within 90 days due to ACLF. Based on the training group data, independent risk factors for disease progression in clinical and dual-energy CT parameters were identified and modeled by logistic regression analysis. Based on the training and validation groups data, receiver operating characteristic (ROC) curves, calibration curves, and decision analysis curves (DCA) were used to verify the discrimination, calibration, and clinical validity of the nomogram.

Results

Chronic liver failure consortium-acute decompensation score (CLIF-C ADs) (p = 0.008) and ECVIC-liver (p < 0.001) were independent risk factors for ACLF within 90 days. The AUC of the model combined ECVIC-liver and CLIF-C ADs were 0.893 and 0.838 in the training and validation groups, respectively. The calibration curves show good agreement between predicted and actual risks. The DCA indicates that the model has good clinical application.

Conclusion

The model combined ECVIC-liver and CLIF-C ADs can early predict the occurrence of ACLF within 90 days in HBV LC-AD patients.
Stem cell sources and characterization in the development of cell-based products for treating retinal disease: An NEI Town Hall report
Authors: Fortress Ashley M. , Miyagishima Kiyoharu J. , Reed Amberlynn A. , Temple Sally , Clegg Dennis O. , Tucker Budd A. , Blenkinsop Timothy A. , Harb George , Greenwell Thomas N. , Ludwig Tenneille E. , Bharti Kapil
Published: March 2023

National Eye Institute recently issued a new Strategic Plan outlining priority research areas for the next 5 years. Starting cell source for deriving stem cell lines is as an area with gaps and opportunities for making progress in regenerative medicine, a key area of emphasis within the NEI Strategic Plan. There is a critical need to understand how starting cell source affects the cell therapy product and what specific manufacturing capabilities and quality control standards are required for autologous vs allogeneic stem cell sources. With the goal of addressing some of these questions, in discussion with the community-at-large, NEI hosted a Town Hall at the Association for Research in Vision and Ophthalmology annual meeting in May 2022. This session leveraged recent clinical advances in autologous and allogeneic RPE replacement strategies to develop guidance for upcoming cell therapies for photoreceptors, retinal ganglion cells, and other ocular cell types. Our focus on stem cell-based therapies for RPE underscores the relatively advanced stage of RPE cell therapies to patients with several ongoing clinical trials. Thus, this workshop encouraged lessons learned from the RPE field to help accelerate progress in developing stem cell-based therapies in other ocular tissues. This report provides a synthesis of the key points discussed at the Town Hall and highlights needs and opportunities in ocular regenerative medicine.
H3K27me3-H3K4me1 transition at bivalent promoters instructs lineage specification in development
Authors: Yu Yue , Li Xinjie , Jiao Rui , Lu Yang , Jiang Xuan , Li Xin
Published: March 2023

Background

Bivalent genes, of which promoters are marked by both H3K4me3 (trimethylation of histone H3 on lysine 4) and H3K27me3 (trimethylation of histone H3 on lysine 27), play critical roles in development and tumorigenesis. Monomethylation on lysine 4 of histone H3 (H3K4me1) is commonly associated with enhancers, but H3K4me1 is also present at promoter regions as an active bimodal or a repressed unimodal pattern. Whether the co-occurrence of H3K4me1 and bivalent marks at promoters plays regulatory role in development is largely unknown.

Results

We report that in the process of lineage differentiation, bivalent promoters undergo H3K27me3-H3K4me1 transition, the loss of H3K27me3 accompanies by bimodal pattern loss or unimodal pattern enrichment of H3K4me1. More importantly, this transition regulates tissue-specific gene expression to orchestrate the development. Furthermore, knockout of Eed (Embryonic Ectoderm Development) or Suz12 (Suppressor of Zeste 12) in mESCs (mouse embryonic stem cells), the core components of Polycomb repressive complex 2 (PRC2) which catalyzes H3K27 trimethylation, generates an artificial H3K27me3-H3K4me1 transition at partial bivalent promoters, which leads to up-regulation of meso-endoderm related genes and down-regulation of ectoderm related genes, thus could explain the observed neural ectoderm differentiation failure upon retinoic acid (RA) induction. Finally, we find that lysine-specific demethylase 1 (LSD1) interacts with PRC2 and contributes to the H3K27me3-H3K4me1 transition in mESCs.

Conclusions

These findings suggest that H3K27me3-H3K4me1 transition plays a key role in lineage differentiation by regulating the expression of tissue specific genes, and H3K4me1 pattern in bivalent promoters could be modulated by LSD1 via interacting with PRC2.
A note on inhomogeneous fractional Schrödinger equations
Authors: Saanouni Tarek , Boulaaras Salah , Peng Congming
Published: March 2023

We study some energy well-posedness issues of the Schrödinger equation with an inhomogeneous mixed nonlinearity and radial data$$ i\dot{u}-(-\Delta )^{s} u \pm \vert x \vert ^{\rho} \vert u \vert ^{p-1}u\pm \vert u \vert ^{q-1}u=0, \quad 0< s< 1, \rho \neq 0, p,q>1. $$iu˙−(−Δ)su±|x|ρ|u|p−1u±|u|q−1u=0,0<s<1,ρ≠0,p,q>1.Our aim is to treat the competition between the homogeneous term$|u|^{q-1}u$|u|q−1uand the inhomogeneous one$|x|^{\rho}|u|^{p-1}u$|x|ρ|u|p−1u. We simultaneously treat two different regimes,$\rho >0$ρ>0and$\rho <-2s$ρ<−2s. We deal with three technical challenges at the same time: the absence of a scaling invariance, the presence of the singular decaying term$|\cdot |^{\rho}$|⋅|ρ, and the nonlocality of the fractional differential operator$(-\Delta )^{s}$(−Δ)s. We give some sufficient conditions on the datum and the parametersN,s,ρ,p,qto have the global versus nonglobal existence of energy solutions. We use the associated ground states and some sharp Gagliardo–Nirenberg inequalities. Moreover, we investigate the$L^{2}$L2concentration of the mass-critical blowing-up solutions. Finally, in the attractive regime, we prove the scattering of energy global solutions. Since there is a loss of regularity in Strichartz estimates for the fractional Schrödinger problem with nonradial data, in this work, we assume that$u_{|t=0}$u|t=0is spherically symmetric. The blowup results use ideas of the pioneering work by Boulenger el al. (J. Funct. Anal. 271:2569–2603, 2016).
Exploiting E3 ubiquitin ligases to reeducate the tumor microenvironment for cancer therapy
Authors: Li Xian-Miao , Zhao Zhen-Yu , Yu Xiao , Xia Qi-Dong , Zhou Peng , Wang Shao-Gang , Wu Huan-Lei , Hu Jia
Published: March 2023

Tumor development relies on a complex and aberrant tissue environment in which cancer cells receive the necessary nutrients for growth, survive through immune escape, and acquire mesenchymal properties that mediate invasion and metastasis. Stromal cells and soluble mediators in the tumor microenvironment (TME) exhibit characteristic anti-inflammatory and protumorigenic activities. Ubiquitination, which is an essential and reversible posttranscriptional modification, plays a vital role in modulating the stability, activity and localization of modified proteins through an enzymatic cascade. This review was motivated by accumulating evidence that a series of E3 ligases and deubiquitinases (DUBs) finely target multiple signaling pathways, transcription factors and key enzymes to govern the functions of almost all components of the TME. In this review, we systematically summarize the key substrate proteins involved in the formation of the TME and the E3 ligases and DUBs that recognize these proteins. In addition, several promising techniques for targeted protein degradation by hijacking the intracellular E3 ubiquitin-ligase machinery are introduced.
Shaping the subway microbiome through probiotic-based sanitation during the COVID-19 emergency: a pre–post case–control study
Authors: D’Accolti Maria , Soffritti Irene , Bini Francesca , Mazziga Eleonora , Cason Carolina , Comar Manola , Volta Antonella , Bisi Matteo , Fumagalli Daniele , Mazzacane Sante , Caselli Elisabetta
Published: March 2023

Background

The COVID-19 pandemic has highlighted the extent to which the public transportation environment, such as in subways, may be important for the transmission of potential pathogenic microbes among humans, with the possibility of rapidly impacting large numbers of people. For these reasons, sanitation procedures, including massive use of chemical disinfection, were mandatorily introduced during the emergency and remain in place. However, most chemical disinfectants have temporary action and a high environmental impact, potentially enhancing antimicrobial resistance (AMR) of the treated microbes. By contrast, a biological and eco-sustainable probiotic-based sanitation (PBS) procedure was recently shown to stably shape the microbiome of treated environments, providing effective and long-term control of pathogens and AMR spread in addition to activity against SARS-CoV-2, the causative agent of COVID-19. Our study aims to assess the applicability and impact of PBS compared with chemical disinfectants based on their effects on the surface microbiome of a subway environment.

Results

The train microbiome was characterized by both culture-based and culture-independent molecular methods, including 16S rRNA NGS and real-time qPCR microarray, for profiling the train bacteriome and its resistome and to identify and quantify specific human pathogens. SARS-CoV-2 presence was also assessed in parallel using digital droplet PCR. The results showed a clear and significant decrease in bacterial and fungal pathogens (p < 0.001) as well as of SARS-CoV-2 presence (p < 0.01), in the PBS-treated train compared with the chemically disinfected control train. In addition, NGS profiling evidenced diverse clusters in the population of air vs. surface while demonstrating the specific action of PBS against pathogens rather than the entire train bacteriome.

Conclusions

The data presented here provide the first direct assessment of the impact of different sanitation procedures on the subway microbiome, allowing a better understanding of its composition and dynamics and showing that a biological sanitation approach may be highly effective in counteracting pathogens and AMR spread in our increasingly urbanized and interconnected environment.
Qualitative evaluation of the implementation of “Tuning in to Kids” in Norwegian Kindergartens
Authors: Skåland Vilde Randen , Havighurst Sophie Seychelle , Nygaard Egil , Teig Inger Lise
Published: March 2023

Background

From January to June 2020, 22 FUS kindergartens across Norway implemented Tuning in to Kids for Kindergarten Teachers (TIK-KT) as part of a randomized control trial (RCT). Between the evaluation of an intervention and use of it in daily practice, a research-to-practice gap can often occur. The theory of planned behavior constituted the theoretical basis for the qualitative interviews that were administered to explore these gaps. This study aimed to explore motivation among kindergarten staff regarding the implementation of TIK-KT.

Methods

Participants from the FUS kindergartens RCT were part of the current study. A stepwise deductive inductive strategy was used in the thematic content analysis. The data were from eleven semi-structured telephone interviews with kindergarten leaders and teachers. Codes from interviews before and after implementation were grouped based on thematic connections, and code groups were further combined into themes. The Consolidated criteria for reporting qualitative research were used as a reporting standard.

Results

The interviews resulted in four main themes: (1) understanding the rationale of implementation, (2) "aha"-experiences, (3) the research-to-practice gap and (4) the main motivation. Kindergarten leaders and teachers expressed positive attitudes toward the intervention ideas and motivation to practice emotion coaching skills and toward implementing TIK-KT both before and after implementation.

Conclusion

Kindergarten leaders’ and teachers’ motivation for implementation came from having a good understanding of the ideas of Tuning in to Kids for Kindergarten Teachers (TIK-KT), experiencing moments of “aha” regarding the intervention, not being held back by practical issues, and working toward their ultimate goal, the wellbeing of the children. These findings have implications for future implementation of TIK-KT and other mental health-promoting interventions and guide further areas of research to examine implementation mechanisms.

Trial registration: The study was registered with the Clinical Trials Registry (NCT03985124), June 13th, 2019.
Boosting neuregulin 1 type-III expression hastens SMA motor axon maturation
Authors: Kong Lingling , Hassinan Cera W. , Gerstner Florian , Buettner Jannik M. , Petigrow Jeffrey B. , Valdivia David O. , Chan-Cortés Michelle H. , Mistri Amy , Cao Annie , McGaugh Scott Alan , Denton Madeline , Brown Stephen , Ross Joshua , Schwab Markus H. , Simon Christian M. , Sumner Charlotte J.
Published: March 2023

Intercellular communication between axons and Schwann cells is critical for attaining the complex morphological steps necessary for axon maturation. In the early onset motor neuron disease spinal muscular atrophy (SMA), many motor axons are not ensheathed by Schwann cells nor grow sufficiently in radial diameter to become myelinated. These developmentally arrested motor axons are dysfunctional and vulnerable to rapid degeneration, limiting efficacy of current SMA therapeutics. We hypothesized that accelerating SMA motor axon maturation would improve their function and reduce disease features. A principle regulator of peripheral axon development is neuregulin 1 type III (NRG1-III). Expressed on axon surfaces, it interacts with Schwann cell receptors to mediate axon ensheathment and myelination. We examined NRG1 mRNA and protein expression levels in human and mouse SMA tissues and observed reduced expression in SMA spinal cord and in ventral, but not dorsal root axons. To determine the impact of neuronal NRG1-III overexpression on SMA motor axon development, we bred NRG1-III overexpressing mice to SMA∆7 mice. Neonatally, elevated NRG1-III expression increased SMA ventral root size as well as axon segregation, diameter, and myelination resulting in improved motor axon conduction velocities. NRG1-III was not able to prevent distal axonal degeneration nor improve axon electrophysiology, motor behavior, or survival of older mice. Together these findings demonstrate that early SMA motor axon developmental impairments can be ameliorated by a molecular strategy independent of SMN replacement providing hope for future SMA combinatorial therapeutic approaches.