bluuebunny/crossref_metadata_2025 huggingface dataset:
Unraveling the genetic architecture of blood unfolded p-53 among non-demented elderlies: novel candidate genes for early Alzheimer's disease
Authors: Yaghoobi Arash , Malekpour Seyed Amir
Published: May 2024

Background

Alzheimer's disease (AD) is a heritable neurodegenerative disease whose long asymptomatic phase makes the early diagnosis of it pivotal. Blood U-p53 has recently emerged as a superior predictive biomarker for AD in the early stages. We hypothesized that genetic variants associated with blood U-p53 could reveal novel loci and pathways involved in the early stages of AD.

Results

We performed a blood U-p53 Genome-wide association study (GWAS) on 484 healthy and mild cognitively impaired subjects from the ADNI cohort using 612,843 Single nucleotide polymorphisms (SNPs). We performed a pathway analysis and prioritized candidate genes using an AD single-cell gene program. We fine-mapped the intergenic SNPs by leveraging a cell-type-specific enhancer-to-gene linking strategy using a brain single-cell multimodal dataset. We validated the candidate genes in an independent brain single-cell RNA-seq and the ADNI blood transcriptome datasets. The rs279686 between AASS and FEZF1 genes was the most significant SNP (p-value = 4.82 × 10–7). Suggestive pathways were related to the immune and nervous systems. Twenty-three candidate genes were prioritized at 27 suggestive loci. Fine-mapping of 5 intergenic loci yielded nine cell-specific candidate genes. Finally, 15 genes were validated in the independent single-cell RNA-seq dataset, and five were validated in the ADNI blood transcriptome dataset.

Conclusions

We underlined the importance of performing a GWAS on an early-stage biomarker of AD and leveraging functional omics datasets for pinpointing causal genes in AD. Our study prioritized nine genes (SORCS1, KIF5C, TMEFF2, TMEM63C, HLA-E, ATAT1, TUBB, ARID1B, and RUNX1) strongly implicated in the early stages of AD.
Metabolomics reveals high fructose-1,6-bisphosphate from fluoride-resistant Streptococcus mutans
Authors: Zhu Laikuan , Li Jiehang , Pan Yueping , Huang Jing , Yao Hui
Published: May 2024

Background

Fluoride-resistant Streptococcus mutans (S. mutans) strains have developed due to the wide use of fluoride in dental caries prevention. However, the metabolomics of fluoride-resistant S. mutans remains unclear.

Objective

This study aimed to identify metabolites that discriminate fluoride-resistant from wild-type S. mutans.

Materials and methods

Cell supernatants from fluoride-resistant and wild-type S. mutans were collected and analyzed by liquid chromatography-mass spectrometry. Principal components analysis and partial least-squares discriminant analysis were performed for the statistical analysis by variable influence on projection (VIP > 2.0) and p value (Mann–Whitney test, p < 0.05). Metabolites were assessed qualitatively using the Human Metabolome Database version 2.0 (http://www.hmdb.ca), or Kyoto Encyclopedia of Genes and Genomes (http://www.kegg.jp), and Metaboanalyst 6.0 (https://www.metaboanalyst.ca).

Results

Fourteen metabolites differed significantly between fluoride-resistant and wild-type strains in the early log phase. Among these metabolites, 5 were identified. There were 32 differential metabolites between the two strains in the stationary phase, 13 of which were identified. The pyrimidine metabolism for S. mutans FR was matched with the metabolic pathway.

Conclusions

The fructose-1,6-bisphosphate concentration increased in fluoride-resistant strains under acidic conditions, suggesting enhanced acidogenicity and acid tolerance. This metabolite may be a promising target for elucidating the cariogenic and fluoride resistant mechanisms of S. mutans.
Integrated phenotypic, transcriptomics and metabolomics: growth status and metabolite accumulation pattern of medicinal materials at different harvest periods of Astragalus Membranaceus Mongholicus
Authors: Li Xiaojie , Mu Yingtong , Hua Mei , Wang Junjie , Zhang Xiaoming
Published: May 2024

Background

Astragalus membranaceus var. mongholicus (Astragalus), acknowledged as a pivotal “One Root of Medicine and Food”, boasts dual applications in both culinary and medicinal domains. The growth and metabolite accumulation of medicinal roots during the harvest period is intricately regulated by a transcriptional regulatory network. One key challenge is to accurately pinpoint the harvest date during the transition from conventional yield content of medicinal materials to high and to identify the core regulators governing such a critical transition. To solve this problem, we performed a correlation analysis of phenotypic, transcriptome, and metabolome dynamics during the harvesting of Astragalus roots.

Results

First, our analysis identified stage-specific expression patterns for a significant proportion of the Astragalus root genes and unraveled the chronology of events that happen at the early and later stages of root harvest. Then, the results showed that different root developmental stages can be depicted by co-expressed genes of Astragalus. Moreover, we identified the key components and transcriptional regulation processes that determine root development during harvest. Furthermore, through correlating phenotypes, transcriptomes, and metabolomes at different harvesting periods, period D (Nov.6) was identified as the critical period of yield and flavonoid content increase, which is consistent with morphological and metabolic changes. In particular, we identified a flavonoid biosynthesis metabolite, isoliquiritigenin, as a core regulator of the synthesis of associated secondary metabolites in Astragalus. Further analyses and experiments showed that HMGCR, 4CL, CHS, and SQLE, along with its associated differentially expressed genes, induced conversion of metabolism processes, including the biosynthesis of isoflavones and triterpenoid saponins substances, thus leading to the transition to higher medicinal materials yield and active ingredient content.

Conclusions

The findings of this work will clarify the differences in the biosynthetic mechanism of astragaloside IV and calycosin 7-O-β-D-glucopyranoside accumulation between the four harvesting periods, which will guide the harvesting and production of Astragalus.
Combined application of arbuscular mycorrhizal fungi and selenium fertilizer increased wheat biomass under cadmium stress and shapes rhizosphere soil microbial communities
Authors: Liu Haiyang , Wang Haoquan , Nie Zhaojun , Tao Zhikang , Peng Hongyu , Shi Huazhong , Zhao Peng , Liu Hongen
Published: May 2024

Background

Selenium (Se) fertilizer and arbuscular mycorrhizal fungi (AMF) are known to modulate cadmium (Cd) toxicity in plants. However, the effects of their co-application on wheat growth and soil microbial communities in Cd-contaminated soil are unclear.

Results

A pot experiment inoculation with two types of AMF and the application of Se fertilizer under Cd stress in wheat showed that inoculation AMF alone or combined with Se fertilizer significantly increased wheat biomass. Se and AMF alone or in combination significantly reduced available Cd concentration in wheat and soil, especially in the Se combined with Ri treatment. High throughput sequencing of soil samples indicated that Se and AMF application had stronger influence on bacterial community compared to fungal community and the bacterial network seemed to have more complex interconnections than the fungal network, and finally shaped the formation of specific microflora to affect Cd availability.

Conclusion

These results indicate that the application of Se and AMF, particularly in combination, could successfully decrease soil Cd availability and relieve the harm of Cd in wheat by modifying rhizosphere soil microbial communities.
Modified diatomite for soil remediation and its implications for heavy metal absorption in Calendula officinalis
Authors: Samani Maryam , Ahlawat Yogesh K. , Golchin Ahmad , Alikhani Hossein Ali , Baybordi Ahmad , Mishra Sadhna
Published: May 2024

Background

Among different adsorbents, natural and inorganic compounds such as diatomite are important and advantageous in terms of high efficiency and cost-effectiveness, and function in stabilizing heavy metals in the environment. Calendula officinalis, a plant known as a high accumulator of heavy metals, was cultivated in soil treated with varying concentrations of modified diatomite to demonstrate the efficiency of modified diatomite in stabilizating of heavy metals in soils,

Results

The modification of diatomite aimed to enhance Calendula officinalis adsorptive properties, particularly towards heavy metals such as lead (Pb), Zinc (Zn), Chromium (Cr), Nickle (Ni), and Copper (Cu), common contaminants in industrial soils. The experimental design included both control and treated soil samples, with assessments at regular intervals. Modified diatomite significantly decreased the bioaccumulation of heavy metals in contaminated soils except Zn, evidenced by decreased DTPA extractable heavy metals in soil and also heavy metal concentrations in plant tissues. Using 10% modified diatomite decreased 91% Pb and Cu, 78% Cr, and 79% Ni concentration of plants compared to the control treatment. The highest concentration of Zn in plant tissue was observed in 2.5% modified diatomite treatment. Remarkably, the application of modified diatomite also appeared to improve the nutrient profile of the soil, leading to enhanced uptake of key nutrients like phosphorus (P) 1.18%, and potassium (K) 79.6% in shoots and 82.3% in roots in Calendula officinalis. Consequently, treated plants exhibited improved growth characteristics, including shoots and roots height of 16.98% and 12.8% respectively, and shoots fresh and dry weight of 48.5% and 50.2% respectively., compared to those in untreated, contaminated soil.

Conclusion

The findings suggest promising implications for using such amendments in ecological restoration and sustainable agriculture, particularly in areas impacted by industrial pollution.
A novel non-negative Bayesian stacking modeling method for Cancer survival prediction using high-dimensional omics data
Authors: Shen Junjie , Wang Shuo , Sun Hao , Huang Jie , Bai Lu , Wang Xichao , Dong Yongfei , Tang Zaixiang
Published: May 2024

Background

Survival prediction using high-dimensional molecular data is a hot topic in the field of genomics and precision medicine, especially for cancer studies. Considering that carcinogenesis has a pathway-based pathogenesis, developing models using such group structures is a closer mimic of disease progression and prognosis. Many approaches can be used to integrate group information; however, most of them are single-model methods, which may account for unstable prediction.

Methods

We introduced a novel survival stacking method that modeled using group structure information to improve the robustness of cancer survival prediction in the context of high-dimensional omics data. With a super learner, survival stacking combines the prediction from multiple sub-models that are independently trained using the features in pre-grouped biological pathways. In addition to a non-negative linear combination of sub-models, we extended the super learner to non-negative Bayesian hierarchical generalized linear model and artificial neural network. We compared the proposed modeling strategy with the widely used survival penalized method Lasso Cox and several group penalized methods, e.g., group Lasso Cox, via simulation study and real-world data application.

Results

The proposed survival stacking method showed superior and robust performance in terms of discrimination compared with single-model methods in case of high-noise simulated data and real-world data. The non-negative Bayesian stacking method can identify important biological signal pathways and genes that are associated with the prognosis of cancer.

Conclusions

This study proposed a novel survival stacking strategy incorporating biological group information into the cancer prognosis models. Additionally, this study extended the super learner to non-negative Bayesian model and ANN, enriching the combination of sub-models. The proposed Bayesian stacking strategy exhibited favorable properties in the prediction and interpretation of complex survival data, which may aid in discovering cancer targets.
The association of depressive symptoms with handgrip strength and gait speed in community-dwelling older adults: data from the baseline phase of Birjand Longitudinal Aging Study
Authors: Nazari Tina , Moodi Mitra , Fakhrzadeh Hossein , Khodabakhshi Huriye , Khorashadizadeh Masoumeh , Arzaghi Seyed Masoud , Shoaee Shervan , Varmaghani Mehdi , Ejtahed Hanieh-Sadat , Sharifi Farshad
Published: May 2024

Background

Depression is a multifaceted condition with a high prevalence and burden to society. Handgrip strength (HGS) and gait speed (GS) are indices of physical health, which is linked to mental health. Previous studies have shown heterogeneity among countries in the association of physical parameters and depression. In this study, we aimed to investigate the association of HGS and GS with depressive symptoms in older adults.

Methods

This is a cross-sectional study analyzing data from the Birjand Longitudinal Aging Study, a cohort of community-dwelling older adults (≥ 60 years old). Depressive symptoms were assessed by the nine-item Patient Health Questionnaire. HGS was measured with a hand dynamometer in a sitting position, and GS was estimated by a 15-foot walk test at usual pace.

Results

Compared to participants in the first quartile, those in the second quartile of HGS had significantly lower odds of suffering from depressive symptoms, while GS was not significantly associated with depressive symptoms. A higher HGS was associated with a lower risk of moderate depressive symptoms, while a higher GS was related to a lower risk of moderately severe and severe symptoms.

Conclusions

Our findings suggest that older people residing in Birjand, Iran with a moderate HGS are less likely to suffer from depressive symptoms than those with lower HGS.
New framework to assess tracing and testing based on South Korea’s response to COVID-19
Authors: Kim Junhyoung , Jo Suyoung , Cho Sung-il
Published: May 2024

South Korea’s remarkable success in controlling the spread of COVID-19 during the pre-Omicron period was based on extensive contact tracing and large-scale testing. Here we suggest a general criterion for tracing and testing based on South Korea’s experience, and propose a new framework to assess tracing and testing. We reviewed papers on South Korea’s response to COVID-19 to capture its concept of tracing and testing. South Korea expanded its testing capabilities to enable group tracing combined with preemptive testing, and to conduct open testing. According to our proposed model, COVID-19 cases are classified into 4 types: confirmed in quarantine, source known, source unknown, and unidentified. The proportion of the first two case types among confirmed cases is defined as “traced proportion”, and used as the indicator of tracing and testing effectiveness. In conclusion, South Korea successfully suppressed COVID-19 transmission by maintaining a high traced proportion (> 60%) using group tracing in conjunction with preemptive testing as a complementary strategy to traditional contact tracing.
Medullary sponge kidney with IgA nephropathy: a case report and literature review
Authors: Zeng Chuchu , Jin Yunjie , Wang Yanzhe , Zhu Dingyu , Zhang Zhigang , Wang Xiaoxia
Published: May 2024

Background

Medullary sponge kidney (MSK)is rare in association with glomerulonephritis. We report a patient with medullary sponge kidney, and the kidney biopsy revealed a diagnosis of IgA nephropathy.

Case presentation

A 27-year-old female presented with hematuria and proteinuria, and imaging studies indicated the presence of medullary spongy kidney. With appropriate preparation, a kidney biopsy was performed. Considering the patient’s clinical and pathological characteristics, the final diagnosis was determined to be medullary sponge kidney associated by IgA nephropathy. The combination of corticosteroids and angiotensin receptor blockers (ARBs) proved to be significantly effective in reducing proteinuria in the current case. To the best of our knowledge, this is the first reported case that demonstrates the coexistence of MSK and IgA nephropathy.

Conclusions

Administering precise therapy based on renal pathology can potentially enhance outcomes for patients with renal conditions, necessitating the need for clinicians to be vigilant about differential diagnosis in order to reduce the rates of missed diagnoses and misdiagnosis.
Radiation-induced upregulation of FGL1 promotes esophageal squamous cell carcinoma metastasis via IMPDH1
Authors: Huang Shan , Zhang Jiayi , He Pu , Cui Xinyue , Hou Yuzhu , Su Wanghui , Li Fang
Published: May 2024

Background

While radiation therapy remains pivotal in esophageal squamous cell carcinoma (ESCC) treatment, the perplexing phenomenon of post-radiation metastasis presents a formidable clinical challenge. This study investigates the role of fibrinogen-like protein 1 (FGL1) in driving ESCC metastasis following radiation exposure.

Methods

FGL1 expression in post-radiation ESCC cells was meticulously examined using qRT-PCR, western blotting, and immunofluorescence. The impact of FGL1 on ESCC cell invasion and migration was assessed through Transwell and wound healing assays. In vivo, the metastatic potential of ESCC in response to FGL1 was scrutinized using nude mice models. Comprehensive RNA sequencing and functional experiments elucidated the intricate mechanism associated with FGL1.

Results

Radiation induced upregulation of FGL1 in ESCC cells through FOXO4, intensifying ESCC cell invasion and migration. Targeted knockdown of FGL1 effectively alleviated these characteristics both in vitro and in vivo. FGL1 depletion concurrently suppressed IMPDH1 expression. Rescue experiments underscored that IMPDH1 knockdown robustly reversed the pro-invasive effects induced by FGL1 in ESCC cells. ESCC tissues exhibited heightened IMPDH1 mRNA levels, demonstrating a correlation with patient survival.

Conclusions

Radiation-induced upregulation of FGL1 propels ESCC metastasis through IMPDH1, proposing a potential therapeutic target to mitigate post-radiotherapy metastasis in ESCC patients.
Perceptions on support, challenges and needs among parents and caregivers of children with developmental disabilities in Croatia, North Macedonia and Serbia: a cross-sectional study
Authors: Međaković Jelena , Čivljak Antonia , Zorčec Tatjana , Vučić Vesna , Ristić-Medić Danijela , Veselinović Aleksandra , Čivljak Marta , Puljak Livia
Published: May 2024

Background

Parents/caregivers of children with developmental disabilities (CDD) have a wide range of support needs and there are various interventions available. Support, challenges, and needs among parents/caregivers of CDD likely vary in different geographical settings. This study aimed to analyze the perceptions of support, challenges, and needs among parents/caregivers of CDD in Croatia, North Macedonia, and Serbia.

Methods

We conducted a cross-sectional study in March-April 2023 within the Erasmus + SynergyEd project. The eligible participants were parents and caregivers of CDD in Croatia, North Macedonia, and Serbia, who filled out a modified Caregiver Needs Survey online.

Results

Among 953 participants, 542 (57%) were from Croatia, 205 (21%) were from North Macedonia and 206 (22%) were from Serbia. The most common diagnosis of participants’ children was autism spectrum disorder (26%). The child most often received the first diagnosis at the median of 2 years, diagnosed by a team of professionals. More than half (58%) of children attended preschool and public school, while 22% did not attend any schooling. Additional support from the state/city/county was received by 66% of CDD. Most participants declared not participating in association/organization for family support. Participants mostly (68%) used experts who work with the child as a source of information about their child’s condition, followed by the Internet (53%). In the last 12 months, 60% of participants had difficulties with the availability of services in their area or problems getting appointments. The biggest problem in getting support was ensuring the child’s basic rights were protected. Participants stated that ensuring greater rights for CDD was the greatest need for their families.

Conclusion

Parents/caregivers of CDD in Croatia, North Macedonia, and Serbia faced multiple challenges, but most of them were satisfied with the services provided to their children. Future efforts to develop policies and services related to CDD should consider the opinions of their parents/caregivers and disparities in access to services.
Self-reported sexual coercion among in-school young people with disabilities in Ghana
Authors: Seidu Abdul-Aziz , Kumi-Kyereme Akwasi , Darteh Eugene K. M.
Published: May 2024

Background

Sexual coercion is one of the major public health concerns globally. This is even more worrying among young people with disabilities (YPWDs). This study assessed the prevalence and factors associated with sexual coercion among in-school young people with disabilities in Ghana.

Methods

Using a cross-sectional study design, pre-tested questionnaires were used to collect data from 979 YPWDs in 15 special schools for the visually and hearing impaired in Ghana. Sexual coercion was the outcome variable. Both descriptive (frequencies and percentages) and inferential analysis (binary logistic regression) were conducted.

Results

About 68% reported that they had been sexually coerced at some point in their lifetime. This was higher among males (69.9%) compared to females (66.8%). Those aged 15–19 (72.19%) had the highest prevalence compared to those aged 20–24 (61.74%). YPWDs in Junior High School [JHS] [aOR = 1.722; CI = 1.227,2.417], and those in the coastal zone [aOR = 1.616; CI = 1.068,2.443] had higher odds of being coerced. However, those belonging to the Islamic religion [aOR = 0.266; CI = 0.0764,0.928] and the visually impaired [aOR = 0.477; CI = 0.318,0.716] had lower odds of being coerced compared to those with no religion, and the hearing impaired, respectively.

Conclusion

There is a relatively high prevalence of sexual coercion among in- school YPWDs in Ghana. This is significantly associated with level of education, ecological zone, religion, and the type of disability. This calls for a concerted effort by policy makers such as the Ghana Education Service, Ghana Federation of the Disabled, Ministry of Education, Ministry of Gender, Children and Social Protection to intensify sex education and put in pragmatic steps to halt this serious public health issue.
Food security status and cardiometabolic health by sex/gender and race/ethnicity among adults in the United States
Authors: Murkey Jamie A. , Gaston Symielle A. , Alhasan Dana M. , Payne Christopher W. , Jackson W. Braxton , Jackson Chandra L.
Published: May 2024

Background

Minoritized racial/ethnic groups and women in the United States (US) are disproportionately burdened by food insecurity, which likely contributes to disparities in cardiovascular health (CVH). Disparities are projected to widen due to the worsening climate crisis that is straining the agricultural system including food supplies. Nonetheless, studies have not investigated the relationship between food security status and ‘ideal’ CVH in a large, nationally-representative and racially/ethnically diverse US sample.

Methods and results

We investigated household food security status in relation to ‘ideal’ CVH among US adults (N = 157,001) using 2014–2018/2020 National Health Interview Survey data. Food security status was defined as very low, low, marginal, or high. A summed score of 4 health behaviors and 3 clinical factors totaling 7 different measures was dichotomized (yes/no) to assess modified ‘ideal’ CVH (mICVH). Using Poisson regression with robust variance, we estimated prevalence ratios (PRs) and 95% CIs of mICVH by household food security status. We stratified models by sex/gender and race/ethnicity. Very low food security prevalence was higher among non-Hispanic (NH)-Black (8.0%) compared to Hispanic/Latinx (5.1%), NH-White (3.1%) and NH-Asian (1.7%) adults. The association between very low versus high food security and mICVH was stronger among women (PR = 0.23 [95% CI: 0.17–0.31]) than men (PR = 0.48 [95% CI: 0.35–0.66]). Compared to NH-White adults with high food security, racially/ethnically minoritized groups with very low to high food security were generally less likely (range: [PRvery low = 0.25[95% CI: 0.14–0.44] – [PRhigh = 0.88 [95% CI: 0.79–0.97]) to meet mICVH criteria.

Conclusions

Food insecurity was associated with lower mICVH prevalence and racially/ethnically minoritized groups were disproportionately burdened.
Long-term survival after hepatic resection for colorectal liver metastases: a single-center study in Iran
Authors: Pourfaraji Seyed Morteza , Moghadam Mehdi Nazari , Moradi Ali Mohammad , Shirmard Fatemeh Ojaghi , Mohammadzadeh Narjes , Jafarian Ali
Published: May 2024

Background

Surgical resection of colorectal cancer liver metastasis (CRLM) has been associated with improved survival in these patients. The purpose of this study was to investigate the usefulness of liver metastasectomy, also finding independent factors related to survival after liver metastasectomy.

Methods

In a retrospective study, all patients with CRLM who underwent resection of liver metastases between 2012 and 2022 at Imam Khomeini Hospital Complex in Tehran, Iran, were enrolled. All patients were actively followed based on clinicopathologic and operative data.

Results

A total of 248 patients with a median follow-up time of 46 months (Range, 12 to 122) were studied. Eighty-six patients (35.0%) underwent major hepatectomy, whereas 160 (65.0%) underwent minor hepatectomy. The median overall survival was 43 months (Range, 0 to 122 months), with estimated 1-, 3- and 5-year overall survival rates of 91%, 56%, and 42%, respectively. Multivariate analysis demonstrated that a metastasis size > 6 cm, major hepatectomy, rectum as the primary tumor site, and involved margin (< 1 mm) were independent factors associated with decreased overall survival (OS).

Conclusion

Surgical resection is an effective treatment for patients with CRLM that is associated with relatively favorable survival. A negative margin of 1 mm seems to be sufficient for oncological resection.
Survival benefit of radical prostatectomy in patients with advanced TURP-diagnosed prostate cancer: a population-based real-world study
Authors: Lin Deng , Lin Le , Ye Liefu , Li Tao , Wei Yongbao , Li Lizhi
Published: May 2024

Objectives

A considerable number of patients are diagnosed with prostate cancer (PCa) by transurethral resection of the prostate (TURP). We aimed to evaluate whether radical prostatectomy (RP) brings survival benefits for these patients, especially in the elderly with advanced PCa.

Patients and methods

We used the Surveillance, Epidemiology, and End Results (SEER) database to obtain PCa cases diagnosed with TURP. After the propensity matching score (PSM) for case matching, univariate, multivariate, and subgroup analyses were performed to investigate whether RP impacts the survival benefit.

Results

4,677 cases diagnosed with PCa by TURP from 2010 to 2019 were obtained, including 1,313 RP patients and 3,364 patients with no RP (nRP). 9.6% of RP patients had advanced PCa. With or without PSM, cancer-specific mortality (CSM) and overall mortality (OM) were significantly reduced in the RP patients compared to the nRP patients, even for older (> 75 ys.) patients with advanced stages (all p < 0.05). Except for RP, younger age (≤ 75 ys.), being married, and earlier stage (localized) contributed to a significant reduction of CSM risk (all p < 0.05). These survival benefits had no significant differences among patients of different ages, married or single, and at different stages (all p for interaction > 0.05).

Conclusions

Based on this retrospective population-matched study, we first found that in patients diagnosed with PCa by TURP, RP treatment may lead to a survival benefit, especially a reduction in CSM, even in old aged patients (> 75 ys.) with advanced PCa.
Consensus-based recommendations for the development and expansion of palliative day care clinics in Germany: results of a Delphi study
Authors: Stiel Stephanie , Ernst Alexandra , Apolinarski Beate , Röwer Hanna A. A. , de Jong Lea , Burger Birte , Schütte Sabrina , Schneider Nils , Damm Kathrin , Stahmeyer Jona T. , Herbst Franziska A.
Published: May 2024

Background

Needs-based, patient-oriented palliative care includes palliative day care clinics as a specialized semi-inpatient care offer. However, the establishment and development of these facilities has been unsystematic. Research is needed to strengthen their transparency and ensure their accessibility, quality, and structural adequacy. A national Delphi study was conducted to generate appropriate recommendations for the establishment and development of palliative day care clinics in Germany.

Methods

Recommendations were formulated from focus group data on the development and expansion of palliative day care clinics in Germany. Experts on in- and outpatient palliative care rated 28 recommendations for relevance and feasibility, respectively, using a 4-point Likert-type scale. Suggestions for improvement were captured via free text comments. Items were considered consented when more than 80% of the experts scored them 4 (strongly agree) or 3 (somewhat agree), regarding both relevance and feasibility.

Results

A total of 23 experts (32% response rate) completed three Delphi rounds. Following the first round, 10 of 28 recommendations were revised according to participants’ comments; 1 recommendation was rejected. After the second round, 3 of these 10 recommendations were revised, while 3 were rejected. Consensus was achieved after the third round for 22 of the initial recommendations.

Conclusions

The Delphi-consented recommendations provide a basis for the targeted evidence- and needs-based development of palliative day care clinics. The findings show a need for standards setting and the meaningful integration of these clinics into existing structures.

Trial registration

The present study was prospectively registered on April 20, 2020, with the German Clinical Trials Register (DRKS00021446).
Factors of pre-war educational migration: an investigation of polish medical and dental students in Ukraine
Authors: Rokita-Poskart Diana , Koziarska Anna , Ostrowska Aleksandra , Kucińska-Landwójtowicz Aneta , Tataruch Magdalena
Published: May 2024

Background

Low admission rates at Polish medical universities led many students to study abroad. Ukraine provided an appealing option for years. The purpose of the study is to investigate the most important factors that motived Polish students enrolled at I. Horbachevsky Ternopil National Medical University in Ukraine to pursue medical and dentistry studies in lower middle-income countries, just before the outbreak of the war. It has become incredibly important to determine crucial economic and non-economic factors.

Methods

The paper draws on a quantitative survey (N = 94) conducted among medical and dental students from Poland who had studied at I. Horbachevsky Ternopil National Medical University in Ukraine using a semi-structured questionnaire. To test whether there was a relationship between the importance of the motives, Pearson’s chi-square independence test was employed.

Results

The study found the key economic and non-economic factors for pursuing Ukrainian studies were rejection from Polish tuition-free programs, lower Ukrainian tuition and living costs compared to Poland and to other European Union countries. Determining reasons for choosing Ternopil University were recruiter and friend recommendations and its prestige among Ukrainian medical schools. Gender influenced the ranking of motives.

Conclusion

The article examines the unique pre-war educational migration from Poland to Ukraine – occurring counter to typical flows from lower to higher a lower income country. The study showed that universities should strengthen recruiting efforts and highlight competitive tuition and living costs to attract international students, especially from relatively more developed nations.
The role of governance in shaping health system reform: a case study of the design and implementation of new health regions in Ireland, 2018–2023
Authors: Schulmann Katharine , Bruen Carlos , Parker Sarah , Siersbaek Rikke , Conghail Luisne Mac , Burke Sara
Published: May 2024

Background

Effective governance arrangements are central to the successful functioning of health systems. While the significance of governance as a concept is acknowledged within health systems research, its interplay with health system reform initiatives remains underexplored in the literature. This study focuses on the development of new regional health structures in Ireland in the period 2018–2023, one part of a broader health system reform programme aimed at greater universalism, in order to scrutinise how aspects of governance impact on the reform process, from policy design through to implementation.

Methods

This qualitative, multi-method study draws on document analysis of official documents relevant to the reform process, as well as twelve semi-structured interviews with key informants from across the health sector. Interviews were analysed according to thematic analysis methodology. Conceiving governance as comprising five domains (Transparency, Accountability, Participation, Integrity, Capacity) the research uses the TAPIC framework for health governance as a conceptual starting point and as initial, deductive analytic categories for data analysis.

Results

The analysis reveals important lessons for policymakers across the five TAPIC domains of governance. These include deficiencies in accountability arrangements, poor transparency within the system and vis-à-vis external stakeholders and the public, and periods during which a lack of clarity in terms of roles and responsibilities for various process and key decisions related to the reform were identified. Inadequate resourcing of implementation capacity, competing policy visions and changing decision-making arrangements, among others, were found to have originated in and continuously reproduced a lack of trust between key institutional actors. The findings highlight how these challenges can be addressed through strengthening governance arrangements and processes. Importantly, the research reveals the interwoven nature of the five TAPIC dimensions of governance and the need to engage with the complexity and relationality of health system reform processes.

Conclusions

Large scale health system reform is a complex process and its governance presents distinct challenges and opportunities for stakeholders. To understand and be able to address these, and to move beyond formulaic prescriptions, critical analysis of the historical context surrounding the policy reform and the institutional relationships at its core are needed.
Effect of video angle on detection of induced front limb lameness in horses
Authors: Valle Alessandro P. , Brown Kara A. , Reilly Patrick , Ciamillo Sarah A. , Davidson Elizabeth J. , Stefanovski Darko , Stewart Holly L. , Ortved Kyla F.
Published: May 2024

Background

Lameness examinations are commonly performed in equine medicine. Advancements in digital technology have increased the use of video recordings for lameness assessment, however, standardization of ideal video angle is not available yielding videos of poor diagnostic quality. The objective of this study was to evaluate the effect of video angle on the subjective assessment of front limb lameness. A randomized, blinded, crossover study was performed. Six horses with and without mechanically induced forelimb solar pain were recorded using 9 video angles including horses trotting directly away and towards the video camera, horses trotting away and towards a video camera placed to the left and right side of midline, and horses trotting in a circle with the video camera placed on the inside and outside of the circle. Videos were randomized and assessed by three expert equine veterinarians using a 0–5 point scoring system. Objective lameness parameters were collected using a body-mounted inertial sensor system (Lameness Locator®, Equinosis LLC). Interobserver agreement for subjective lameness scores and ease of grading scores were determined.

Results

Induction of lameness was successful in all horses. There was excellent agreement between objective lameness parameters and subjective lameness scores (AUC of the ROC = 0.87). For horses in the “lame” trials, interobserver agreement was moderate for video angle 2 when degree of lameness was considered and perfect for video angle 2 and 9 when lameness was considered as a binary outcome. All other angles had no to fair agreement. For horses in the “sound” trials, interobserver agreement was perfect for video angle 5. All other video angles had slight to moderate agreement.

Conclusions

When video assessment of forelimb lameness is required, a video of the horse trotting directly towards the video camera at a minimum is recommended. Other video angles may provide supportive information regarding lameness characteristics.
Identification of sepsis-associated mitochondrial genes through RNA and single-cell sequencing approaches
Authors: Li Shilin , Li Xiang , Jiang Sishi , Wang Chenglin , Hu Yingchun
Published: May 2024

Background

Sepsis ranks among the most formidable clinical challenges, characterized by exorbitant treatment costs and substantial demands on healthcare resources. Mitochondrial dysfunction emerges as a pivotal risk factor in the pathogenesis of sepsis, underscoring the imperative to identify mitochondrial-related biomarkers. Such biomarkers are crucial for enhancing the accuracy of sepsis diagnostics and prognostication.

Methods

In this study, adhering to the SEPSIS 3.0 criteria, we collected peripheral blood within 24 h of admission from 20 sepsis patients at the ICU of the Southwest Medical University Affiliated Hospital and 10 healthy volunteers as a control group for RNA-seq. The RNA-seq data were utilized to identify differentially expressed RNAs. Concurrently, mitochondrial-associated genes (MiAGs) were retrieved from the MitoCarta3.0 database. The differentially expressed genes were intersected with MiAGs. The intersected genes were then subjected to GO (Gene Ontology), and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses and core genes were filtered using the PPI (Protein-Protein Interaction) network. Subsequently, relevant sepsis datasets (GSE65682, GSE28750, GSE54514, GSE67652, GSE69528, GSE95233) were downloaded from the GEO (Gene Expression Omnibus) database to perform bioinformatic validation of these core genes. Survival analysis was conducted to assess the prognostic value of the core genes, while ROC (Receiver Operating Characteristic) curves determined their diagnostic value, and a meta-analysis confirmed the accuracy of the RNA-seq data. Finally, we collected 5 blood samples (2 normal controls (NC); 2 sepsis; 1 SIRS (Systemic Inflammatory Response Syndrome), and used single-cell sequencing to assess the expression levels of the core genes in the different blood cell types.

Results

Integrating high-throughput sequencing with bioinformatics, this study identified two mitochondrial genes (COX7B, NDUFA4) closely linked with sepsis prognosis. Survival analysis demonstrated that patients with lower expression levels of COX7B and NDUFA4 exhibited a higher day survival rate over 28 days, inversely correlating with sepsis mortality. ROC curves highlighted the significant sensitivity and specificity of both genes, with AUC values of 0.985 for COX7B and 0.988 for NDUFA4, respectively. Meta-analysis indicated significant overexpression of COX7B and NDUFA4 in the sepsis group in contrast to the normal group (P < 0.01). Additionally, single-cell RNA sequencing revealed predominant expression of these core genes in monocytes-macrophages, T cells, and B cells.

Conclusion

The mitochondrial-associated genes (MiAGs) COX7B and NDUFA4 are intimately linked with the prognosis of sepsis, offering potential guidance for research into the mechanisms underlying sepsis.
Prevalence and genetic basis of Mycobacterium tuberculosis resistance to pretomanid in China
Authors: Zhao Bing , Zheng Huiwen , Timm Juliano , Song Zexuan , Pei Shaojun , Xing Ruida , Guo Yajie , Ma Ling , Li Feina , Li Qing , Li Yan , Huang Lin , Teng Chong , Wang Ni , Gupta Aastha , Juneja Sandeep , Huang Fei , Zhao Yanlin , Ou Xichao
Published: May 2024

Background

Pretomanid is a key component of new regimens for the treatment of drug-resistant tuberculosis (TB) which are being rolled out globally. However, there is limited information on the prevalence of pre-existing resistance to the drug.

Methods

To investigate pretomanid resistance rates in China and its underlying genetic basis, as well as to generate additional minimum inhibitory concentration (MIC) data for epidemiological cutoff (ECOFF)/breakpoint setting, we performed MIC determinations in the Mycobacterial Growth Indicator Tube™ (MGIT) system, followed by WGS analysis, on 475 Mycobacterium tuberculosis (MTB) isolated from Chinese TB patients between 2013 and 2020.

Results

We observed a pretomanid MIC distribution with a 99% ECOFF equal to 0.5 mg/L. Of the 15 isolates with MIC values > 0.5 mg/L, one (MIC = 1 mg/L) was identified as MTB lineage 1 (L1), a genotype previously reported to be intrinsically less susceptible to pretomanid, two were borderline resistant (MIC = 2–4 mg/L) and the remaining 12 isolates were highly resistant (MIC ≥ 16 mg/L) to the drug. Five resistant isolates did not harbor mutations in the known pretomanid resistant genes.

Conclusions

Our results further support a breakpoint of 0.5 mg/L for a non-L1 MTB population, which is characteristic of China. Further, our data point to an unexpected high (14/475, 3%) pre-existing pretomanid resistance rate in the country, as well as to the existence of yet-to-be-discovered pretomanid resistance genes.
Single-cell transcriptome analysis reveals subtype-specific clonal evolution and microenvironmental changes in liver metastasis of pancreatic adenocarcinoma and their clinical implications
Authors: Park Joo Kyung , Jeong Hyoung-oh , Kim Hyemin , Choi Jin Ho , Lee Eun Mi , Kim Seunghoon , Jang Jinho , Choi David Whee-Young , Lee Se-Hoon , Kim Kyoung Mee , Jang Kee-Taek , Lee Kwang Hyuck , Lee Kyu Taek , Lee Min Woo , Lee Jong Kyun , Lee Semin
Published: May 2024

Background

Intratumoral heterogeneity (ITH) and tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) play important roles in tumor evolution and patient outcomes. However, the precise characterization of diverse cell populations and their crosstalk associated with PDAC progression and metastasis is still challenging.

Methods

We performed single-cell RNA sequencing (scRNA-seq) of treatment-naïve primary PDAC samples with and without paired liver metastasis samples to understand the interplay between ITH and TME in the PDAC evolution and its clinical associations.

Results

scRNA-seq analysis revealed that even a small proportion (22%) of basal-like malignant ductal cells could lead to poor chemotherapy response and patient survival and that epithelial-mesenchymal transition programs were largely subtype-specific. The clonal homogeneity significantly increased with more prevalent and pronounced copy number gains of oncogenes, such as KRAS and ETV1, and losses of tumor suppressor genes, such as SMAD2 and MAP2K4, along PDAC progression and metastasis. Moreover, diverse immune cell populations, including naï﻿ve SELLhi regulatory T cells (Tregs) and activated TIGIThi Tregs, contributed to shaping immunosuppressive TMEs of PDAC through cellular interactions with malignant ductal cells in PDAC evolution. Importantly, the proportion of basal-like ductal cells negatively correlated with that of immunoreactive cell populations, such as cytotoxic T cells, but positively correlated with that of immunosuppressive cell populations, such as Tregs.

Conclusion

We uncover that the proportion of basal-like subtype is a key determinant for chemotherapy response and patient outcome, and that PDAC clonally evolves with subtype-specific dosage changes of cancer-associated genes by forming immunosuppressive microenvironments in its progression and metastasis.
The chain-mediating effect of Crp, BMI on the relationship between dietary intake of live microbes and hyperlipidaemia
Authors: Chen Jingyi , Fang Shuhua , Huo Jinlin , Yang Nian
Published: May 2024

Background

Inflammation and obesity are the risk factors for hyperlipidaemia. Nonetheless, research regarding the association between dietary live microbes intake and hyperlipidaemia is lacking. Therefore, this study focused on revealing the relationship between them and mediating roles of inflammation and obesity.

Methods

Totally 16,677 subjects were enrolled from the National Health and Nutrition Examination Survey (NHANES) (1999–2010 and 2015–2020). To explore the correlation between live microbes and hyperlipidaemia as well as blood lipid levels, respectively, multiple logistic regression and linear regression were employed. Furthermore, the mediating roles of body mass index (BMI), C-reactive protein (Crp) and their chain effect were explored through mediating analysis.

Results

High dietary live microbes intake was the protective factor for hyperlipidaemia. In addition, high dietary live microbes intake exhibited a positive relationship to the high-density lipoprotein cholesterol (HDL-C) among males (β = 2.52, 95% CI: 1.29, 3.76, P < 0.0001) and females (β = 2.22, 95% CI: 1.05, 3.38, P < 0.001), but exhibited a negative correlation with triglyceride (TG) levels in males (β = -7.37, 95% CI: -13.16, -1.59, P = 0.02) and low-density lipoprotein cholesterol (LDL-C) levels in females (β = -2.75, 95% CI: -5.28, -0.21, P = 0.02). Crp, BMI and their chain effect mediated the relationship between live microbes with HDL-C levels. Moreover, BMI and the chain effect mediated the relationship between live microbes with LDL-C levels.

Conclusion

Dietary live microbes intake is related to a lower hyperlipidaemia risk. Crp, BMI and their chain effect make a mediating impact on the relationship.
A mitochondrion-targeted cyanine agent for NIR-II fluorescence-guided surgery combined with intraoperative photothermal therapy to reduce prostate cancer recurrence
Authors: Liu Chenchen , Chang Zong , Chen Kailei , Xue Qiang , Shu Bingxin , Wei Zhihao , Zhou Xuan , Guo Like , Zhang Yuling , Pan Yingying , Cao Qi , Liang Huageng , Sun Qinchao , Zhang Xiaoping
Published: May 2024

Poorly identified tumor boundaries and nontargeted therapies lead to the high recurrence rates and poor quality of life of prostate cancer patients. Near-infrared-II (NIR-II) fluorescence imaging provides certain advantages, including high resolution and the sensitive detection of tumor boundaries. Herein, a cyanine agent (CY7-4) with significantly greater tumor affinity and blood circulation time than indocyanine green was screened. By binding albumin, the absorbance of CY7-4 in an aqueous solution showed no effects from aggregation, with a peak absorbance at 830 nm and a strong fluorescence emission tail beyond 1000 nm. Due to its extended circulation time (half-life of 2.5 h) and high affinity for tumor cells, this fluorophore was used for primary and metastatic tumor diagnosis and continuous monitoring. Moreover, a high tumor signal-to-noise ratio (up to ~ 10) and excellent preferential mitochondrial accumulation ensured the efficacy of this molecule for photothermal therapy. Therefore, we integrated NIR-II fluorescence-guided surgery and intraoperative photothermal therapy to overcome the shortcomings of a single treatment modality. A significant reduction in recurrence and an improved survival rate were observed, indicating that the concept of intraoperative combination therapy has potential for the precise clinical treatment of prostate cancer.

Graphical Abstract