bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating public interest in herpes zoster in Germany by leveraging the internet: a retrospective search data analysis
Authors: Kain Alphina , Tizek Linda , Wecker Hannah , Wallnöfer Fabian , Biedermann Tilo , Zink Alexander
Published: August 2023

Background

Herpes zoster (HZ) and its complication postherpetic neuralgia (PHN), whose incidence are both expected to increase with an ageing population, have demonstrated high costs on healthcare systems and burden on individual quality of life. Previous studies have shown the possibility of assessing public interest in a disease and factors that influence search behaviour using internet search data. The aim of this study was to analyze internet search data for HZ in Germany to evaluate public interest in the disease and relevant influential temporal and geographic factors that modify search behavior.

Methods

Google Ads Keyword Planner was used to generate a list of HZ-related keywords including their search volume for Germany as a whole and its sixteen federal states from October 2016 to September 2020. All keywords were qualitatively categorized, and changes over time and correlations with population density, physician density, and vaccination rates were assessed using Welch’s ANOVA, Bonferroni correction for post-hoc analyses, and Pearson’s correlation.

Results

A total of 1,651 relevant keywords with a search volume of 20,816,210 searches were identified. Overall, national search volume increased each year of the study period with a peak in August 2020. More than half of the total search volume related to general queries (55.1%). The highest average monthly search volumes were observed in the states of Hamburg, Saarland, and Bremen. Average monthly search volume showed strong positive correlations with population density (r = .512, p = .043) and a strong negative correlation with the number of inhabitants per working physician (r = -.689, p = .003).

Conclusions

The study demonstrated that evaluating internet search data is a viable method for assessing public interest in HZ, thereby identifying areas of unmet need to support targeted public health campaigns.
Sexual lives of reproductive-aged people with disabilities in Central Sidama National Regional State, Ethiopia: a mixed-methods study
Authors: Tenaw Zelalem , Gari Taye , Gebretsadik Achamyelesh
Published: August 2023

Background

Sexuality is an important part of human life; people with disabilities have the same sexual desires as people without disabilities. However, the status of the sexual lives of reproductive-aged people with disabilities is unfolded in Ethiopia. Therefore, this study was aimed to assess sexual lives and its associated factors among reproductive-aged people with disabilities in central Sidama National Regional State, Ethiopia.

Methods

A mixed-methods study was conducted among randomly selected 685 reproductive-age people with disabilities and fifteen (15) in-depth interviews among individuals who have sexual practice experience from June 20 to July 15, 2022. The quantitative data were collected through face-to-face interviewing techniques using a structured and semi-structured questionnaire. A multilevel logistic regression analysis model was employed to analyze the data. The adjusted odds ratio (AOR) with a 95% confidence interval (CI) was used to report the measures of associations. The qualitative data were managed and analyzed using the phenomenological research analysis approach.

Results

In this study, 59.9% (95% CI: 56.1, 63.5) of the people with disabilities have practiced sexual intercourse. Of these, 30.8% (95% CI: 27.4, 34.4) were males and 29.1% (95% CI: 25.7, 32.6) were females with disabilities. Being female (AOR = 2.81; 95% CI: 1.70, 4.62), having an occupation (AOR = 7.55; 95% CI: 4.03, 14.1), having a disability and being in a wheelchair (AOR = 0.27; 95% CI: 0.09, 0.82), having a good self-perception (AOR = 0.46; 95% CI: 0.28, 0.77), and having a rich economic status (AOR = 2.05; 95% CI: 1.08, 3.89) were factors associated with the sexual practice. The qualitative findings revealed that having sexuality information (training) is the facilitator, and community discrimination and low economic income are the barriers to sexual practice.

Conclusion

Sexual practice among people with disabilities is low in the Dale and Wonsho districts and Yirgalem city administration. Socio-demographic and economic factors and sexuality training are the associated factors. Therefore, creating job opportunities and economic empowerment, providing sexuality training, and creating community awareness are crucial to improving the sexual practice of reproductive-age people with disabilities.
Anxiety and depression disorders in oncological patients under palliative care at a hospital service: a cross-sectional study
Authors: Gontijo Garcia Gustavo Souza , Meira Karina Cardoso , de Souza Alessandra Hubner , Guimarães Nathalia Sernizon
Published: August 2023

Background

This study aimed to evaluate the risk and protective factors associated with anxiety and depression symptoms in cancer patients at an advanced stage of cancer.

Methods

A cross-sectional study was conducted on patients with advanced cancer who were receiving palliative care. Cancer patients aged 18 years or older, with preserved cognitive function who completed the questionnaires were eligible. The questionnaires of Hospital Anxiety and Depression Scale (HADS) and health related of quality of life questionnaire; the European Organization for Research and Treatment of Cancer (EORTC-C30) were applied. Outcome variables were the depression and anxiety symptoms of cancer patients under palliative care, according to the answers to the 14 items that make up the HADS Scale. The analysis used the R software, version 4.2.0.

Results

Seventy cancer patients with advanced cancer were included. The colon was the most common neoplastic diagnostic (20%), followed by breast (12.9%) and lung (10%). The prevalence of depression was 44.3%, 25.7% anxiety and 52.9% had both symptoms. Patients with a high level of functionality had a lower chance of anxiety (OR = 0.80;p = 0.025), depression (OR = 0.82; p = 0.007), and anxiety and depression (OR = 0.82p = 0.008). We observed a lower chance of depression and depression/anxiety who showed a high level of Overall Performance. Three symptoms increased the chance of depression/anxiety: nausea/vomiting (p = 0.019), fatigue (0.031), loss of appetite (0.048).

Conclusion

This study found high prevalence of anxiety and depression.Better quality of life and functionality were negatively associated with these outcomes. Examining the patient’s functions will assist the clinician in alleviating symptoms of anxiety and depression, giving cancer patients in palliative care more dignity.

Trial registration

Not applicable.
Roles of increased NUCKS1 expression in endometriosis
Authors: Li Bo , Chen Bocen , Wang Xiaoli , Xiao Man , Zhang Kan , Ye Wenjiao , Zhao Da , Wang Xiaohua , Yu Yan , Li Jun , Xu Xun , Zhang Wenhui , Zhang Yanhua
Published: August 2023

Background

Endometriosis is still a difficult problem for women. The Nuclear Ubiquitous Casein and cyclin-dependent Kinase Substrate 1 (NUCKS1) gene is located on human chromosome 1q32.1. It encodes the NUCKS1 protein, a 27 kDa nuclear DNA binding protein that plays an important role in cell growth and proliferation. NUCKS1 plays an important role in the development of many diseases. However, its role in endometriosis is unclear.

Methods

Ectopic endometrial tissues and normal tissue specimens were collected, and the expression of NUCKS1, NF-κB and PI3K was detected by RT-qPCR and immunohistochemistry. Inhibition of NUCKS1 in hEM15A cells, study the changes in cell viability, apoptosis, migration and protein expression by CCK8 assay, flow cytometry, wound-healing assay, western blot and ELISA techniques. The comparison of differences between the two groups was implemented using unpaired sample t test or Mann-whitney U test. One-way analysis of variance or Kruskal-wallis test was used for comparisons among the three groups.

Results

(1) NUCKS1 is highly expressed in endometriosis tissues. (2) Inhibition of NUCKS1 decreases cell viability and capability of migration, and increases apoptosis in endometriosis cells. (3) Expressions of NF-κB and PI3K are increased in endometriosis tissues, and inhibition of NUCKS1 decreases the expression levels of PI3K and NF-κB in endometriosis cells. (4) Inhibition of NUCKS1 decreases the expression of VEGF.

Conclusion

(1) NUCKS1 is overexpressed in endometriosis, and inhibition of NUCKS1 inhibits cell viability and capability of migration, and increases apoptosis. (2) NUCKS1 promotes the progress of endometriosis through activating PI3K and NF-κB pathways, and VEFG is also involved in this process.
Validation of the Polish version of the DREEM questionnaire – a confirmatory factor analysis
Authors: Wójcik Dorota , Szalewski Leszek , Bęben Adam , Ordyniec-Kwaśnica Iwona , Roff Sue
Published: August 2023

Aim

The aim of our study was to translate and adapt the Dundee Ready Education Environment Measure (DREEM) questionnaire developed by Roff et al. to the cultural conditions in Poland and also to validate it. Studying the learning environment is beneficial because it can identify students’ perceptions of their environment and support the staff in reflecting on, planning for and combining proper teaching approaches to improve it.

Methods

The DREEM questionnaire was completed by students of all years (first–fifth) in the faculties of dental medicine at the Medical University of Lublin and the Medical University of Gdańsk. The total surveyed population consisted of 650 students. Validity was separated into four phases: (1) translation validity, (2) confirmatory factor analysis, (3) concurrent validity and (4) criterion-related validity.

Results

Our study confirmed the original structure of the DREEM tool (GFI = 0.955, AGFI = 0.951, NFI = 0.931, TLI = 0.962, CFI = 0.964, RNI = 0.964, IFI = 0.964, RFI = 0.928, PNFI = 0.885, SRMR = 0.062, RMSEA = 0.043, 90% CI = 0.041–0.046) and obtained very good reliability rates, with Cronbach’s alpha > 0.7 for all scales. Only Subscale V achieved a lower Cronbach’s alpha of > 0.5. The study was conducted using the test–retest method, which is why the intraclass correlation coefficients for reliability were also calculated; individual items showed both medium and good correspondence.

Conclusions

Our study provided good evidence for the reliability and validity of the Polish version of the DREEM. In conclusion, the Polish-language version of the DREEM questionnaire is a reliable and valid instrument for analysing the learning environment for dental students and its factor structure is supported by the data.
FAAP100 is required for the resolution of transcription-replication conflicts in primordial germ cells
Authors: Xu Weiwei , Yang Yajuan , Yu Yongze , Wen Canxin , Zhao Simin , Cao Lili , Zhao Shidou , Qin Yingying , Chen Zi-Jiang
Published: August 2023

Background

The maintenance of genome stability in primordial germ cells (PGCs) is crucial for the faithful transmission of genetic information and the establishment of reproductive reserve. Numerous studies in recent decades have linked the Fanconi anemia (FA) pathway with fertility, particularly PGC development. However, the role of FAAP100, an essential component of the FA core complex, in germ cell development is unexplored.

Results

We find that FAAP100 plays an essential role in R-loop resolution and replication fork protection to counteract transcription-replication conflicts (TRCs) during mouse PGC proliferation. FAAP100 deletion leads to FA pathway inactivation, increases TRCs as well as cotranscriptional R-loops, and contributes to the collapse of replication forks and the generation of DNA damage. Then, the activated p53 signaling pathway triggers PGC proliferation defects, ultimately resulting in insufficient establishment of reproductive reserve in both sexes of mice.

Conclusions

Our findings suggest that FAAP100 is required for the resolution of TRCs in PGCs to safeguard their genome stability.
Impact of data source choice on multimorbidity measurement: a comparison study of 2.3 million individuals in the Welsh National Health Service
Authors: MacRae Clare , Morales Daniel , Mercer Stewart W. , Lone Nazir , Lawson Andrew , Jefferson Emily , McAllister David , van den Akker Marjan , Marshall Alan , Seth Sohan , Rawlings Anna , Lyons Jane , Lyons Ronan A. , Mizen Amy , Abubakar Eleojo , Dibben Chris , Guthrie Bruce
Published: August 2023

Background

Measurement of multimorbidity in research is variable, including the choice of the data source used to ascertain conditions. We compared the estimated prevalence of multimorbidity and associations with mortality using different data sources.

Methods

A cross-sectional study of SAIL Databank data including 2,340,027 individuals of all ages living in Wales on 01 January 2019. Comparison of prevalence of multimorbidity and constituent 47 conditions using data from primary care (PC), hospital inpatient (HI), and linked PC-HI data sources and examination of associations between condition count and 12-month mortality.

Results

Using linked PC-HI compared with only HI data, multimorbidity was more prevalent (32.2% versus 16.5%), and the population of people identified as having multimorbidity was younger (mean age 62.5 versus 66.8 years) and included more women (54.2% versus 52.6%). Individuals with multimorbidity in both PC and HI data had stronger associations with mortality than those with multimorbidity only in HI data (adjusted odds ratio 8.34 [95% CI 8.02-8.68] versus 6.95 (95%CI 6.79-7.12] in people with ≥ 4 conditions). The prevalence of conditions identified using only PC versus only HI data was significantly higher for 37/47 and significantly lower for 10/47: the highest PC/HI ratio was for depression (14.2 [95% CI 14.1–14.4]) and the lowest for aneurysm (0.51 [95% CI 0.5–0.5]). Agreement in ascertainment of conditions between the two data sources varied considerably, being slight for five (kappa < 0.20), fair for 12 (kappa 0.21–0.40), moderate for 16 (kappa 0.41–0.60), and substantial for 12 (kappa 0.61–0.80) conditions, and by body system was lowest for mental and behavioural disorders. The percentage agreement, individuals with a condition identified in both PC and HI data, was lowest in anxiety (4.6%) and highest in coronary artery disease (62.9%).

Conclusions

The use of single data sources may underestimate prevalence when measuring multimorbidity and many important conditions (especially mental and behavioural disorders). Caution should be used when interpreting findings of research examining individual and multiple long-term conditions using single data sources. Where available, researchers using electronic health data should link primary care and hospital inpatient data to generate more robust evidence to support evidence-based healthcare planning decisions for people with multimorbidity.
Nationwide spatiotemporal drug resistance genetic profiling from over three decades in Indian Plasmodium falciparum and Plasmodium vivax isolates
Authors: Kojom Foko Loick P. , Narang Geetika , Jakhan Jahnvi , Tamang Suman , Moun Amit , Singh Vineeta
Published: August 2023

Background

Drug resistance is a serious impediment to efficient control and elimination of malaria in endemic areas.

Methods

This study aimed at analysing the genetic profile of molecular drug resistance in Plasmodium falciparum and Plasmodium vivax parasites from India over a ~ 30-year period (1993–2019). Blood samples of P. falciparum and/or P. vivax-infected patients were collected from 14 regions across India. Plasmodial genome was extracted and used for PCR amplification and sequencing of drug resistance genes in P. falciparum (crt, dhps, dhfr, mdr1, k13) and P. vivax (crt-o, dhps, dhfr, mdr1, k12) field isolates.

Results

The double mutant pfcrtSVMNT was highly predominant across the country over three decades, with restricted presence of triple mutant CVIET from Maharashtra in 2012. High rates of pfdhfr-pfdhps quadruple mutants were observed with marginal presence of “fully resistant” quintuple mutant ACIRNI-ISGEAA. Also, resistant pfdhfr and pfdhps haplotype has significantly increased in Delhi between 1994 and 2010. For pfmdr1, only 86Y and 184F mutations were present while no pfk13 mutations associated with artemisinin resistance were observed. Regarding P. vivax isolates, the pvcrt-o K10 “AAG” insertion was absent in all samples collected from Delhi in 2017. Pvdhps double mutant SGNAV was found only in Goa samples of year 2008 for the first time. The pvmdr1 908L, 958M and 1076L mutations were highly prevalent in Delhi and Haryana between 2015 and 2019 at complete fixation. One nonsynonymous novel pvk12 polymorphism was identified (K264R) in Goa.

Conclusions

These findings support continuous surveillance and characterization of P. falciparum and P. vivax populations as proxy for effectiveness of anti-malarial drugs in India, especially for independent emergence of artemisinin drug resistance as recently seen in Africa.
The mediating role of job satisfaction and presenteeism on the relationship between job stress and turnover intention among primary health care workers
Authors: Ning Liangwen , Jia Huanhuan , Gao Shang , Liu Minghui , Xu Jiaying , Ge Sangyangji , Li Ming , Yu Xihe
Published: August 2023

Background

Turnover problems among primary health care workers are a significant contributor to the shortage of health human resources. This study aims to determine the relationship between job stress and turnover intention among primary health care workers, as well as to examine the mediating effects of job satisfaction and presenteeism on this relationship.

Methods

Stratified random sampling and quota sampling were used to select 703 primary health care workers in Jilin Province, China in January 2020. Validated scales were used to measure turnover intention, job stress, job satisfaction, and presenteeism among primary health care workers. The study utilized a partial least squares structural equation modeling (PLS-SEM) approach to test the research hypotheses.

Results

The turnover intention score of primary health care workers in Jilin Province was 2.15 ± 1.03, and 19.5% of respondents reported a higher turnover intention. Significant sex and occupation differences were found, with a higher rate of turnover intention for male and doctor groups among primary health care workers. This study also revealed a positive correlation between job stress and turnover intention (β = 0.235, P < 0.001), a significant negative correlation between job satisfaction and turnover intention (β= -0.347, P < 0.001), and a significant positive correlation between presenteeism and turnover intention (β = 0.153, P < 0.001). Moreover, the study revealed a significant indirect effect of job stress on turnover intention which was mediated by job satisfaction (β = 0.183, P < 0.001) and presenteeism (β = 0.078, P < 0.001).

Conclusion

We confirmed the positive association between job stress and presenteeism with turnover intention, as well as the negative association between job satisfaction and turnover intention. Moreover, our study confirmed the mediating role of job satisfaction and presenteeism in the relationship between job stress and turnover intention. This study provides scientific evidence to address the turnover problem among primary health care workers.
Psychometric properties of EQ-5D-5L for use in patients with Graves’ disease
Authors: Liu Xiaodong , Chan Wendy WL , Tang Eric HM , Suen Alex HY , Fung Matrix MH , Woo Yu Cho , Liu Shirley YW , Lam Cindy LK , Luo Nan , Wong Carlos KH , Lang Brian HH
Published: August 2023

Background

The EQ-5D-5 L is a commonly used generic measure of health. This study aimed to evaluate the psychometric properties of the EQ-5D-5 L in patients with Graves’ disease (GD).

Methods

A prospective cohort of patients with GD recruited at three public hospitals in Hong Kong completed the EQ-5D-5 L and ThyPRO-39 questionnaires at baseline, 1-month, and 6-month follow-ups. Convergent validity was tested by examining the Spearman correlation between EQ-5D-5 L and ThyPRO-39 scores at baseline. 1-month test-retest reliability was assessed by Intraclass Correlation Coefficient (ICC), Gwet’s Agreement Coefficient 2 (AC2), and percentage agreement. Responsiveness of EQ-5D-5 L index and EQ-VAS scores was assessed using effect size statistics (standardized effect size [SES] and standardized response mean [SRM]).

Results

Of 125 recruited patients, 101 (80.8%) and 100 (80.0%) patients were followed up at 1- and 6-month, respectively. For convergent validity, there was a moderate negative correlation between EQ-5D-5 L index or EQ-VAS score and ThyPRO-39 overall QoL-impact score (-0.350, -0.451), between EQ-VAS score and composite score (-0.483), and strong negative correlation between EQ-5D-5 L index score and composite score (-0.567). The Gwet’s AC2 and percentage agreement were the highest in self-care (0.964 and 0.967), followed by mobility (0.952 and 0.962), usual activities (0.934 and 0.948), pain/discomfort (0.801 and 0.887), and anxiety/depression (0.788 and 0.882). The ICC for the EQ-5D-5 L index and the EQ-VAS was 0.707 and 0.700. For patients who reported having ‘worsened’ health at 6-month follow-up, the SES and SRM were − 0.66 and − 0.42 for EQ-5D-5 L index and − 1.15 and − 1.00 for EQ-VAS, respectively.

Conclusions

The EQ-5D-5 L demonstrated convergent validity, test-retest reliability, and responsiveness to worsened health status among patients with GD.
Towards PPG-based anger detection for emotion regulation
Authors: How Tuck-Voon , Green Robin E. A. , Mihailidis Alex
Published: August 2023

Background

Anger dyscontrol is a common issue after traumatic brain injury (TBI). With the growth of wearable physiological sensors, there is new potential to facilitate the rehabilitation of such anger in the context of daily life. This potential, however, depends on how well physiological markers can distinguish changing emotional states and for such markers to generalize to real-world settings. Our study explores how wearable photoplethysmography (PPG), one of the most widely available physiological sensors, could be used detect anger within a heterogeneous population.

Methods

This study collected the TRIEP (Toronto Rehabilitation Institute Emotion-Physiology) dataset, which comprised of 32 individuals (10 TBI), exposed to a variety of elicitation material (film, pictures, self-statements, personal recall), over two day sessions. This complex dataset allowed for exploration into how the emotion-PPG relationship varied over changes in individuals, endogenous/exogenous drivers of emotion, and day-to-day differences. A multi-stage analysis was conducted looking at: (1) times-series visual clustering, (2) discriminative time-interval features of anger, and (3) out-of-sample anger classification.

Results

Characteristics of PPG are largely dominated by inter-subject (between individuals) differences first, then intra-subject (day-to-day) changes, before differentiation into emotion. Both TBI and non-TBI individuals showed evidence of linear separable features that could differentiate anger from non-anger classes within time-interval analysis. However, what is more challenging is that these separable features for anger have various degrees of stability across individuals and days.

Conclusion

This work highlights how there are contextual, non-stationary challenges to the emotion-physiology relationship that must be accounted for before emotion regulation technology can perform in real-world scenarios. It also affirms the need for a larger breadth of emotional sampling when building classification models.
Promoting employee wellbeing and preventing non-clinical mental health problems in the workplace: a preparatory consultation survey
Authors: Coppens Evelien , Hogg Bridget , Greiner Birgit A. , Paterson Charlotte , de Winter Lars , Mathieu Sharna , Cresswell-Smith Johanna , Aust Birgit , Leduc Caleb , Van Audenhove Chantal , Pashoja Arlinda C. , Kim Dooyoung , Reich Hanna , Fanaj Naim , Dushaj Arilda , Thomson Katherine , O’Connor Cliodhna , Moreno-Alcázar Ana , Amann Benedikt L. , Arensman Ella
Published: August 2023

Background

Small and medium-sized enterprises (SMEs) face major financial losses due to mental health issues affecting employees at all levels but seldom apply programs to promote wellbeing and prevent mental health issues among employees. To support the development of a multi-country workplace-based mental health intervention for SMEs (MENTUPP), a multinational consultation study was conducted. The study aimed to examine the experiences and needs of SMEs concerning the promotion of employee wellbeing, and the prevention and management of non-clinical mental health problems in workplaces.

Methods

A survey consisting of open and closed questions was designed to assess key informants’ opinion about the acceptability, the use, and the implementation of interventions to promote wellbeing and prevent mental health issues in the workplace. Academic experts and representatives of SME organisations, specific sector organisations, labour or advocacy groups, and occupational health organisations across the nine MENTUPP intervention countries (eight European countries and Australia) were invited to complete the survey. Data were collected via the online platform Qualtrics. Sixty-five of 146 informants responded, representing a 44.5% response rate. Descriptive statistics were used to analyse the quantitative data and qualitative data were analysed through thematic analysis.

Results

Measures to create mentally healthy workplaces were most used in SMEs, while more specific mental health interventions, such as training staff on how to promote wellbeing, were hardly used. Managers lack resources to implement mental health interventions and are concerned about employees spending too much time on these interventions during working hours. Receiving information about the economic benefits of mental health interventions and hearing successful testimonials from other SMEs can persuade managers otherwise. Employees have concerns about confidentiality, discrimination and stigma, and career opportunities when using such interventions.

Conclusions

The study identifies a variety of challenges, needs and possibilities related to implementing mental health interventions in SMEs. Employers need to be convinced that investing in mental health in the workplace is worth their time and money. This requires more studies on the (cost-)effectiveness of mental health interventions. Once employers are engaged, their knowledge and competencies about how to implement such interventions should be increased and privacy concerns of employees to participate in them should be addressed.
Oleoylethanolamide facilitates PPARα and TFEB signaling and attenuates Aβ pathology in a mouse model of Alzheimer’s disease
Authors: Comerota Michele M. , Gedam Manasee , Xiong Wen , Jin Feng , Deng Lisheng , Wang Meng C. , Wang Jin , Zheng Hui
Published: August 2023

Background

Age is the strongest risk factor for the development of Alzheimer’s disease (AD). Besides the pathological hallmarks of β-amyloid (Aβ) plaques and neurofibrillary tangles, emerging evidence demonstrates a critical role of microglia and neuroinflammation in AD pathogenesis. Oleoylethanolamide (OEA) is an endogenous lipid amide that has been shown to promote lifespan and healthspan in C. elegans through regulation of lysosome-to-nucleus signaling and cellular metabolism. The goal of our study was to determine the role of OEA in the mediation of microglial activity and AD pathology using its stable analog, KDS-5104.

Methods

We used primary microglial cultures and genetic and pharmacological approaches to examine the signaling mechanisms and functional roles of OEA in mediating Aβ phagocytosis and clearance, lipid metabolism and inflammasome formation. Further, we tested the effect of OEA in vivo in acute LPS-induced neuroinflammation and by chronic treatment of 5xFAD mice.

Results

We found that OEA activates PPARα signaling and its downstream cell-surface receptor CD36 activity. In addition, OEA promotes TFEB lysosomal function in a PPARα-dependent but mTORC1-independent manner, the combination of which leads to enhanced microglial Aβ uptake and clearance. These are associated with the suppression of LPS-induced lipid droplet accumulation and inflammasome activation. Chronic treatment of 5xFAD mice with KDS-5104 restored dysregulated lipid profiles, reduced reactive gliosis and Aβ pathology and rescued cognitive impairments.

Conclusion

Together, our study provides support that augmenting OEA-mediated lipid signaling may offer therapeutic benefit against aging and AD through modulating lipid metabolism and microglia phagocytosis and clearance.
Host, reproductive, and lifestyle factors in relation to quantitative histologic metrics of the normal breast
Authors: Abubakar Mustapha , Klein Alyssa , Fan Shaoqi , Lawrence Scott , Mutreja Karun , Henry Jill E. , Pfeiffer Ruth M. , Duggan Maire A. , Gierach Gretchen L.
Published: August 2023

Background

Emerging data indicate that variations in quantitative epithelial and stromal tissue composition and their relative abundance in benign breast biopsies independently impact risk of future invasive breast cancer. To gain further insights into breast cancer etiopathogenesis, we investigated associations between epidemiological factors and quantitative tissue composition metrics of the normal breast.

Methods

The study participants were 4108 healthy women ages 18–75 years who voluntarily donated breast tissue to the US-based Susan G. Komen Tissue Bank (KTB; 2008–2019). Using high-accuracy machine learning algorithms, we quantified the percentage of epithelial, stromal, adipose, and fibroglandular tissue, as well as the proportion of fibroglandular tissue that is epithelium relative to stroma (i.e., epithelium-to-stroma proportion, ESP) on digitized hematoxylin and eosin (H&E)-stained normal breast biopsy specimens. Data on epidemiological factors were obtained from participants using a detailed questionnaire administered at the time of tissue donation. Associations between epidemiological factors and square root transformed tissue metrics were investigated using multivariable linear regression models.

Results

With increasing age, the amount of stromal, epithelial, and fibroglandular tissue declined and adipose tissue increased, while that of ESP demonstrated a bimodal pattern. Several epidemiological factors were associated with individual tissue composition metrics, impacting ESP as a result. Compared with premenopausal women, postmenopausal women had lower ESP [β (95% Confidence Interval (CI)) = −0.28 (− 0.43, − 0.13); P < 0.001] with ESP peaks at 30–40 years and 60–70 years among pre- and postmenopausal women, respectively. Pregnancy [β (95%CI) vs nulligravid = 0.19 (0.08, 0.30); P < 0.001] and increasing number of live births (P-trend < 0.001) were positively associated with ESP, while breastfeeding was inversely associated with ESP [β (95%CI) vs no breastfeeding = −0.15 (− 0.29, − 0.01); P = 0.036]. A positive family history of breast cancer (FHBC) [β (95%CI) vs no FHBC = 0.14 (0.02–0.26); P = 0.02], being overweight or obese [β (95%CI) vs normal weight = 0.18 (0.06–0.30); P = 0.004 and 0.32 (0.21–0.44); P < 0.001, respectively], and Black race [β (95%CI) vs White = 0.12 (− 0.005, 0.25); P = 0.06] were positively associated with ESP.

Conclusion

Our findings revealed that cumulative exposure to etiological factors over the lifespan impacts normal breast tissue composition metrics, individually or jointly, to alter their dynamic equilibrium, with potential implications for breast cancer susceptibility and tumor etiologic heterogeneity.
Genome sequencing of 2000 canids by the Dog10K consortium advances the understanding of demography, genome function and architecture
Authors: Meadows Jennifer R. S. , Kidd Jeffrey M. , Wang Guo-Dong , Parker Heidi G. , Schall Peter Z. , Bianchi Matteo , Christmas Matthew J. , Bougiouri Katia , Buckley Reuben M. , Hitte Christophe , Nguyen Anthony K. , Wang Chao , Jagannathan Vidhya , Niskanen Julia E. , Frantz Laurent A. F. , Arumilli Meharji , Hundi Sruthi , Lindblad-Toh Kerstin , Ginja Catarina , Agustina Kadek Karang , André Catherine , Boyko Adam R. , Davis Brian W. , Drögemüller Michaela , Feng Xin-Yao , Gkagkavouzis Konstantinos , Iliopoulos Giorgos , Harris Alexander C. , Hytönen Marjo K. , Kalthoff Daniela C. , Liu Yan-Hu , Lymberakis Petros , Poulakakis Nikolaos , Pires Ana Elisabete , Racimo Fernando , Ramos-Almodovar Fabian , Savolainen Peter , Venetsani Semina , Tammen Imke , Triantafyllidis Alexandros , vonHoldt Bridgett , Wayne Robert K. , Larson Greger , Nicholas Frank W. , Lohi Hannes , Leeb Tosso , Zhang Ya-Ping , Ostrander Elaine A.
Published: August 2023

Background

The international Dog10K project aims to sequence and analyze several thousand canine genomes. Incorporating 20 × data from 1987 individuals, including 1611 dogs (321 breeds), 309 village dogs, 63 wolves, and four coyotes, we identify genomic variation across the canid family, setting the stage for detailed studies of domestication, behavior, morphology, disease susceptibility, and genome architecture and function.

Results

We report the analysis of > 48 M single-nucleotide, indel, and structural variants spanning the autosomes, X chromosome, and mitochondria. We discover more than 75% of variation for 239 sampled breeds. Allele sharing analysis indicates that 94.9% of breeds form monophyletic clusters and 25 major clades. German Shepherd Dogs and related breeds show the highest allele sharing with independent breeds from multiple clades. On average, each breed dog differs from the UU_Cfam_GSD_1.0 reference at 26,960 deletions and 14,034 insertions greater than 50 bp, with wolves having 14% more variants. Discovered variants include retrogene insertions from 926 parent genes. To aid functional prioritization, single-nucleotide variants were annotated with SnpEff and Zoonomia phyloP constraint scores. Constrained positions were negatively correlated with allele frequency. Finally, the utility of the Dog10K data as an imputation reference panel is assessed, generating high-confidence calls across varied genotyping platform densities including for breeds not included in the Dog10K collection.

Conclusions

We have developed a dense dataset of 1987 sequenced canids that reveals patterns of allele sharing, identifies likely functional variants, informs breed structure, and enables accurate imputation. Dog10K data are publicly available.
Continuous passive paracentesis versus large-volume paracentesis in the prevention and treatment of intra-abdominal hypertension in the critically ill cirrhotic patient with ascites (COPPTRIAHL): study protocol for a randomized controlled trial
Authors: Pereira Rui Antunes , Virella Daniel , Perdigoto Rui , Marcelino Paulo , Saliba Faouzi , Germano Nuno
Published: August 2023

Background

Critically ill patients with cirrhosis and ascites are at high risk for intra-abdominal hypertension (IAH) which increases mortality. Clinical guidelines recommend maintaining intra-abdominal pressure (IAP) below 16 mmHg; nonetheless, more than three quarters of critically ill patients with cirrhosis develop IAH during their first week of ICU stay. Standard-of-care intermittent large-volume paracentesis (LVP) relieves abdominal wall tension, reduces IAP, optimizes abdominal perfusion pressure, and is associated with short-term improvement in renal and pulmonary dysfunction. However, there is no evidence of the superiority of different paracentesis strategies in the prevention and treatment of IAH in critically ill patients with cirrhosis.

This trial aims to compare the outcomes of continuous passive paracentesis versus LVP in the prevention and treatment of IAH in patients with cirrhosis and ascites.

Methods

An investigator-initiated, open label, randomized controlled trial, set in a general ICU specialized in liver disease, was initiated in August 2022, with an expected duration of 36 months. Seventy patients with cirrhosis and ascites will be randomly assigned, in a 1:1 ratio, to receive one of two methods of therapeutic paracentesis. A stratified randomization method, with maximum creatinine and IAP values as strata, will homogenize patient baseline characteristics before trial group allocation, within 24 h of admission.

In the control group, LVP will be performed intermittently according to clinical practice, with a maximum duration of 8 h, while, in the intervention group, continuous passive paracentesis will drain ascitic fluid for up to 7 days.

The primary endpoint is serum creatinine concentration, and secondary endpoints include IAP, measured creatinine clearance, daily urine output, stage 3 acute kidney injury and multiorgan dysfunction assessed at day 7 after enrollment, as well as 28-day mortality rate and renal replacement therapy-free days, and length-of-stay. Prespecified values will be used in case of renal replacement therapy or, beforehand ICU discharge, liver transplant and death. Safety analysis will include paracentesis-related complication rate and harm. Data will be analyzed with an intention-to-treat approach.

Discussion

This is the first trial to compare the impact of different therapeutic paracentesis strategies on organ dysfunction and outcomes in the prevention and treatment of IAH in critically ill patients with cirrhosis and ascites.

Trial registration

ClinicalTrials.gov NCT04322201. Registered on 20 December 2019
Effect of free-weight vs. machine-based strength training on maximal strength, hypertrophy and jump performance – a systematic review and meta-analysis
Authors: Haugen Markus E. , Vårvik Fredrik T. , Larsen Stian , Haugen Arvid S. , van den Tillaar Roland , Bjørnsen Thomas
Published: August 2023

Background

The effectiveness of strength training with free-weight vs. machine equipment is heavily debated. Thus, the purpose of this meta-analysis was to summarize the data on the effect of free-weight versus machine-based strength training on maximal strength, jump height and hypertrophy.

Methods

The review was conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, and the systematic search of literature was conducted up to January 1st, 2023. Studies that directly compared free-weight vs. machine-based strength training for a minimum of 6 weeks in adults (18–60 yrs.) were included.

Results

Thirteen studies (outcomes: maximal strength [n = 12], jump performance [n = 5], muscle hypertrophy [n = 5]) with a total sample of 1016 participants (789 men, 219 women) were included. Strength in free-weight tests increased significantly more with free-weight training than with machines (SMD: -0.210, CI: -0.391, -0.029,p = 0.023), while strength in machine-based tests tended to increase more with machine training than with free-weights (SMD: 0.291, CI: -0.017, 0.600,p = 0.064). However, no differences were found between modalities in direct comparison (free-weight strength vs. machine strength) for dynamic strength (SMD: 0.084, CI: -0.106, 0.273,p = 0.387), isometric strength (SMD: -0.079, CI: -0.432, 0.273,p = 0.660), countermovement jump (SMD: -0.209, CI: -0.597, 0.179,p = 0.290) and hypertrophy (SMD: -0.055, CI: -0.397, 0.287,p = 0.751).

Conclusion

No differences were detected in the direct comparison of strength, jump performance and muscle hypertrophy. Current body of evidence indicates that strength changes are specific to the training modality, and the choice between free-weights and machines are down to individual preferences and goals.
Exploring the antibiogram of soil isolates from an indian hospital precinct: link to antibiotic usage
Authors: Kunhikannan Shalini , Thomas Colleen J. , Sumana M. N. , Franks Ashley E. , Kumar Sumana , Nagarathna S. , Petrovski Steve , Shindler Anya E.
Published: August 2023

Objective

Hospitals serve as hotspots of antibiotic resistance. Despite several studies exploring antibiotic resistance in hospitals, none have explored the resistance profile of soil bacteria from a hospital precinct. This study examined and compared the antibiogram of the soil isolates from a hospital and its affiliated university precinct, to determine if antibiotic resistant bacteria were present closer to the hospital.

Results

120 soil samples were collected from JSS Hospital and JSS University in Mysore, India across three consecutive seasons (monsoon, winter and summer). 366 isolates were randomly selected from culture. Antibiotic susceptibility testing was performed on 128 isolates of Pseudomonas (n = 73), Acinetobacter (n = 30), Klebsiella species (n = 15) and Escherichia coli (n = 10). Pseudomonas species exhibited the highest antibiotic resistance. Ticarcillin-clavulanic acid, an extended-spectrum carboxypenicillin antibiotic used to treat moderate-to-severe infections, ranked highest amongst the antibiotics to whom these isolates were resistant (n = 51 out of 73, 69.9%). Moreover, 56.8% (n = 29) were from the hospital and 43.1% (n = 22) were from the university precinct, indicating antibiotic resistant bacteria were closer to the hospital setting. This study highlights the effect of antibiotic usage in hospitals and the influence of anthropogenic activities in the hospital on the dissemination of antibiotic resistance into hospital precinct soil.
Cross-platform comparisons for targeted bisulfite sequencing of MGISEQ-2000 and NovaSeq6000
Authors: Sun Jin , Su Mingyang , Ma Jianhua , Xu Minjie , Ma Chengcheng , Li Wei , Liu Rui , He Qiye , Su Zhixi
Published: August 2023

Background

An accurate and reproducible next-generation sequencing platform is essential to identify malignancy-related abnormal DNA methylation changes and translate them into clinical applications including cancer detection, prognosis, and surveillance. However, high-quality DNA methylation sequencing has been challenging because poor sequence diversity of the bisulfite-converted libraries severely impairs sequencing quality and yield. In this study, we tested MGISEQ-2000 Sequencer’s capability of DNA methylation sequencing with a published non-invasive pancreatic cancer detection assay, using NovaSeq6000 as the benchmark.

Results

We sequenced a series of synthetic cell-free DNA (cfDNA) samples with different tumor fractions and found MGISEQ-2000 yielded data with similar quality as NovaSeq6000. The methylation levels measured by MGISEQ-2000 demonstrated high consistency with NovaSeq6000. Moreover, MGISEQ-2000 showed a comparable analytic sensitivity with NovaSeq6000, suggesting its potential for clinical detection. As to evaluate the clinical performance of MGISEQ-2000, we sequenced 24 clinical samples and predicted the pathology of the samples with a clinical diagnosis model, PDACatch classifier. The clinical model performance of MGISEQ-2000’s data was highly consistent with that of NovaSeq6000’s data, with the area under the curve of 1. We also tested the model’s robustness with MGISEQ-2000’s data when reducing the sequencing depth. The results showed that MGISEQ-2000’s data showed matching robustness of the PDACatch classifier with NovaSeq6000’s data.

Conclusions

Taken together, MGISEQ-2000 demonstrated similar data quality, consistency of the methylation levels, comparable analytic sensitivity, and matching clinical performance, supporting its application in future non-invasive early cancer detection investigations by detecting distinct methylation patterns of cfDNAs.
Stem cells and extracellular vesicles to improve preclinical orofacial soft tissue healing
Authors: Wang Zhihao , Knight Rob , Stephens Phil , Ongkosuwito E. M. , Wagener Frank A. D. T. G. , Von den Hoff Johannes W.
Published: August 2023

Orofacial soft tissue wounds caused by surgery for congenital defects, trauma, or disease frequently occur leading to complications affecting patients' quality of life. Scarring and fibrosis prevent proper skin, mucosa and muscle regeneration during wound repair. This may hamper maxillofacial growth and speech development. To promote the regeneration of injured orofacial soft tissue and attenuate scarring and fibrosis, intraoral and extraoral stem cells have been studied for their properties of facilitating maintenance and repair processes. In addition, the administration of stem cell-derived extracellular vesicles (EVs) may prevent fibrosis and promote the regeneration of orofacial soft tissues. Applying stem cells and EVs to treat orofacial defects forms a challenging but promising strategy to optimize treatment. This review provides an overview of the putative pitfalls, promises and the future of stem cells and EV therapy, focused on orofacial soft tissue regeneration.
Optimization of differential filtration-based mitochondrial isolation for mitochondrial transplant to cerebral organoids
Authors: Bodenstein David F. , Powlowski Pavel , Zachos Kassandra A. , El Soufi El Sabbagh Dana , Jeong Hyunjin , Attisano Liliana , Edgar Landon , Wallace Douglas C. , Andreazza Ana Cristina
Published: August 2023

Background

Mitochondrial dysfunction is involved in several diseases ranging from genetic mitochondrial disorders to chronic metabolic diseases. An emerging approach to potentially treat mitochondrial dysfunction is the transplantation of autologous live mitochondria to promote cell regeneration. We tested the differential filtration-based mitochondrial isolation protocol established by the McCully laboratory for use in cellular models but found whole cell contaminants in the mitochondrial isolate.

Methods

Therefore, we explored alternative types of 5-μm filters (filters A and B) for isolation of mitochondria from multiple cell lines including HEK293 cells and induced pluripotent stem cells (iPSCs). MitoTracker™ staining combined with flow cytometry was used to quantify the concentration of viable mitochondria. A proof-of-principle mitochondrial transplant was performed using mitoDsRed2-tagged mitochondria into a H9-derived cerebral organoid.

Results

We found that filter B provided the highest quality mitochondria as compared to the 5-μm filter used in the original protocol. Using this method, mitochondria were also successfully isolated from induced pluripotent stem cells. To test for viability, mitoDsRed2-tagged mitochondria were isolated and transplanted into H9-derived cerebral organoids and observed that mitochondria were engulfed as indicated by immunofluorescent co-localization of TOMM20 and MAP2.

Conclusions

Thus, use of filter B in a differential filtration approach is ideal for isolating pure and viable mitochondria from cells, allowing us to begin evaluating long-term integration and safety of mitochondrial transplant using cellular sources.
RETRACTED ARTICLE: Intelligent monitoring methodology for large-scale logistics transport vehicles based on parallel Internet of Vehicles
Authors: Liang Chengzhang
Published: August 2023

The essence of the Internet of Vehicles is a social and physical information system, including the psychological and organizational factors of human beings. The complexity of the Internet will lead to certain deviations when monitoring vehicles. Therefore, the Parallel Internet of Vehicles is employed to monitor the information on large-scale logistics transport vehicles. This platform is built based on the ACP intelligent approach, which consists of three parts: An artificial system (A), a computational experiment (C), and parallel execution (P). The Adaboost algorithm is used to extract information on large-scale logistics transport vehicles from the ACP parallel Internet of Vehicles, and the Tabu search strategy is applied to optimize the Monte Carlo positioning algorithm. The approximate optimal estimation is obtained by optimizing the filtering to eliminate vehicle positions with fewer possibilities. The weight of important sampling values of the independent vehicle node positions is integrated to complete the posterior probability distribution estimation of the possible positions of vehicles, in order to realize vehicle position monitoring. It is verified that the root-mean square error of the algorithm when positioning a vehicle is less than 0.18, and the monitoring deviation is quite small.