bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of insomnia upon inflammatory digestive diseases and biomarkers: a two-sample mendelian randomization research on Europeans
Authors: Dai Lei , Ye Yunyan , Mugaanyi Joseph , Lu Caide , Lu Changjiang
Published: February 2024

Background

A number of observational studies indicate that insomnia is linked to inflammatory digestive diseases (IDDs). However, the definite relationship between insomnia and IDDs remains unclear.

Methods

We obtained the publicly available data from genome-wide association studies (GWAS) to conduct two-sample Mendelian randomization (MR) for association assessment. Five MR analysis methods were used to calculate the odds ratio (OR) and effect estimate, and the heterogeneity and pleiotropy tests were performed to evaluate the robustness of the variable instruments (IVs).

Results

One exposure and twenty outcome datasets based on European populations were included in this study. Using the inverse variance weighted method, we found insomnia was closely correlated with esophageal ulcer (OR = 1.011, 95%CI = 1.004–1.017,p = 0.001) and abdominal pain (effect estimate = 1.016, 95%CI = 1.005–1.026,p = 0.003). Suggestive evidence of a positively association was observed between insomnia and duodenal ulcer (OR = 1.006, 95%CI = 1.002–1.011,p = 0.009), gastric ulcer (OR = 1.008, 95%CI = 1.001–1.014,p = 0.013), rectal polyp (OR = 1.005, 95%CI = 1.000-1.010,p = 0.034), haemorrhoidal disease (OR = 1.242, 95%CI = 1.004–1.535,p = 0.045) and monocyte percentage (effect estimate = 1.151, 95%CI = 1.028–1.288,p = 0.014). No correlations were observed among other IDDs, phenotypes and biomarkers.

Conclusions

Our MR study assessed the relationship between insomnia and IDDs/phenotypes/biomarkers in depth and revealed potential associations between insomnia and ulcers of the esophagus and abdominal pain.
Case report: enzyme replacement therapy for Fabry disease presenting with proteinuria and ventricular septal thickening
Authors: Chen Zewei , Yin Bo , Jiao Juan , Ye Tianyang
Published: February 2024

Fabry disease (FD) is an uncommon, X-linked, lysosomal storage disease that causes defects in the glycosphingolipid metabolic pathway due to deficient or absent lysosomal α-galactosidase (α-Gal A) activity. This leads to the accumulation of globotriaosylceramide (GL-3) within lysosomes in a wide range of cells, including endothelial, cardiac, renal, and corneal cells, and consequently, the progressive appearance of clinical symptoms in target organs. Enzyme replacement therapy (ERT), which involves the exogenous supplementation of α-Gal A enzyme and has been successfully administered for treating FD.

Here, we report a case of a 37-year-old male with complaints of recurrent proteinuria and ventricular septal thickening. A renal biopsy revealed vacuolization and foamy changes in podocytes, and the presence of myelin-like bodies and zebra bodies. The white blood cell α-Gal A activity was very low, while the Lyso-GL-3 level was high. Additionally, genetic analysis revealed a gene variant c.902G > A p. Arg301Gln. The patient was diagnosed with FD, and subsequently received intravenous ERT with a dose of Agalsidase α (0.2 mg/kg, 17.5 mg every 2 weeks). Currently, the values of proteinuria and ventricular septum thickness remain stable during the 6-month follow-up. Initiating ERT at an early age can effectively decrease the deposition of GL-3, attenuate the progressive clinical manifestations of FD, and provide greater long-term benefits.
Single-cell RNA sequencing of anaplastic ependymoma and H3K27M-mutant diffuse midline glioma
Authors: Zang Dongdong , Dong Zilong , Liu Yuecheng , Chen Qian
Published: February 2024

Background

Anaplastic ependymoma and H3K27M-mutant diffuse midline glioma are two common subtypes of brain tumors with poor long-term prognosis. The present study analyzed and compared the differences in cell types between two tumors by single-cell RNA sequencing (scRNA-seq) technology.

Methods

ScRNA-seq was performed to profile cells from cancer tissue from anaplastic ependymoma patient and H3K27M-mutant diffuse midline glioma patient. Cell clustering, marker gene identification, cell type annotation, copy number variation analysis and function analysis of differentially expressed genes were then performed.

Results

A total of 11,219 cells were obtained from anaplastic ependymoma and H3K27M mutant diffuse midline glioma, and these cells categorized into 12 distinct clusters. Each cell cluster could be characterized with specific cell markers to indicate cellular heterogeneity. Five cell types were annotated in each sample, including astrocyte, oligodendrocytes, microglial cell, neural progenitor cell and immune cell. The cluster types and proportion of cell types were not consistent between the two brain tumors. Functional analyses suggest that these cell clusters are involved in tumor-associated pathways, with slight differences in the cells of origin between the two tumors. In addition, cell communication analysis showed that the NRG3-ERBB4 pair is a key Ligand-receptor pair for anaplastic ependymoma, while in H3K27M-mutant diffuse midline glioma it is the PTN-PTPRZ1 pair that establishes contact with other cells.

Conclusion

There was intratumor heterogeneity in anaplastic ependymoma and H3K27M mutant diffuse midline glioma, and that the subtype differences may be due to differences in the origin of the cells.
Autophagy Proteins and clinical data reveal the prognosis of polycystic ovary syndrome
Authors: Wu Yuanyuan , Huang Jinge , Liu Cai , Wang Fang
Published: February 2024

Objective

We aimed to investigate the significance of autophagy proteins and their association with clinical data on pregnancy loss in polycystic ovary syndrome (PCOS), while also constructing predictive models.

Methods

This study was a secondary analysis. we collected endometrial samples from 33 patients with polycystic ovary syndrome (PCOS) and 7 patients with successful pregnancy control women at the Reproductive Center of the Second Hospital of Lanzhou University between September 2019 and September 2020. Liquid chromatography tandem mass spectrometry was employed to identify expressed proteins in the endometrium of 40 patients. R was use to identify differential expression proteins(DEPs). Subsequently, Metascape was utilized for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Multivariate Cox analysis was performed to analyze autophagy proteins associated with reproductive outcomes, while logistic regression was used for analyzing clinical data. Linear correlation analysis was conducted to examine the relationship between autophagy proteins and clinical data. We established prognostic models and constructed the nomograms based on proteome data and clinical data respectively. The performance of the prognostic model was evaluated by the receiver operating characteristic curve (ROC) and decision curve analysis (DCA).

Results

A total of 5331 proteins were identified, with 450 proteins exhibiting significant differential expression between the PCOS and control groups. A prognostic model for autophagy protein was developed based on three autophagy proteins (ARSA, ITGB1, and GABARAPL2). Additionally, another prognostic model for clinical data was established using insulin, TSH, TPOAB, and VD3. Our findings revealed a significant positive correlation between insulin and ARSA (R = 0.49), as well as ITGB1 (R = 0.3). Conversely, TSH exhibited a negative correlation with both ARSA (-0.33) and ITGB1 (R = -0.26).

Conclusion

Our research could effectively predict the occurrence of pregnancy loss in PCOS patients and provide a basis for subsequent research.
Fear of depression recurrence among individuals with remitted depression: a qualitative interview study
Authors: Gumuchian Stephanie T. , Boyle Ariel , Hazel Lori H. , Ellenbogen Mark A.
Published: February 2024

Background

Major Depressive Disorder (MDD) is a prevalent psychiatric condition and the largest contributor to disability worldwide. MDD is highly recurrent, yet little is known about the mechanisms that occur following a Major Depressive Episode (MDE) and underlie recurrence. We explored the concept of fear of depression recurrence (FoDR) and its impact on daily functioning among individuals in remission from MDD.

Methods

30 participants (83% female; 37% White; Mage = 27.7, SD = 8.96) underwent semi-structured qualitative interviews. The interviews explored participants’ experiences of FoDR including the frequency, severity, content, triggers, and impact of fears and associated coping strategies. We used content analysis to analyze the transcriptions.

Results

Most participants (73%) reported having FoDR, with varying frequency, severity, and duration of fears. The triggers and content of participants’ fears often mirrored the symptoms (e.g., low mood, anhedonia) and consequences (e.g., job loss, social withdrawal) endured during past MDEs. Some participants reported a minimal impact of FoDR on daily functioning, whereas others reported a positive (e.g., personal growth) or negative (e.g., increased anxiety) influence.

Limitations

Our sample size did not allow for explorations of differences in FoDR across unique MDD subtypes or sociocultural factors.

Conclusions

The concept of FoDR may present a window into understanding the unique cognitive and behavioural changes that occur following MDD remission and underlie depression recurrence. Future research should aim to identify underlying individual differences and characteristics of the disorder that may influence the presence and impact of FoDR. Finally, a FoDR measure should be developed so that associations between FoDR and recurrence risk, depressive symptoms, and other indices of functioning can be determined.
Change in self-reported somatic symptoms among patients in opioid maintenance treatment from baseline to 1-year follow-up
Authors: Bjørnestad Endre Dahlen , Vederhus John-Kåre , Clausen Thomas
Published: February 2024

Background

High somatic comorbidity is common among patients in treatment for opioid use disorder (OUD). The present study aims to investigate changes in self-reported somatic health conditions and somatic symptoms among patients entering opioid maintenance treatment (OMT) programs.

Methods

We used data from the Norwegian Cohort of Patients in OMT and Other Drug Treatment (NorComt) study. Of 283 patients who entered OMT, 176 were included for analysis at a 1-year follow-up. Participants provided self-reported data during structured interviews on somatic conditions, somatic symptoms, substance use severity measures, and mental distress. A multivariable linear regression analysis identified factors associated with changes in the burden of somatic symptoms.

Results

Patients entering OMT reported a high prevalence of somatic conditions at the beginning of treatment, with 3 of 5 patients reporting at least one. The most prevalent condition was hepatitis C, followed by asthma and high blood pressure. Patients reported experiencing a high number of somatic symptoms. The intensity of these symptoms varied across a wide spectrum, with oral health complaints and reduced memory perceived as the most problematic. Overall, for the entire sample, there was no significant change in somatic symptoms from baseline to 1 year. Further analysis indicated that those who reported a higher burden of somatic symptoms at baseline had the greatest improvement at the 1-year follow-up. A higher number of somatic conditions and higher mental distress at baseline was associated with improvements in somatic symptoms burden at follow-up.

Conclusions

Patients in OMT report a range of somatic conditions and somatic symptoms. Given the wide range of symptoms reported by patients in OMT, including some at high intensity levels, healthcare providers should take into consideration the somatic healthcare needs of individuals in OMT populations.

Clinical trial registration

Clinicaltrials.gov no. NCT05182918. Registered 10/01/2022 (the study was retrospectively registered).
The mediating role of coping styles in the relationship between fear of COVID-19 and mental health problems: a cross-sectional study among nurses
Authors: Huda Nurul , Shaw Malissa Kay , Chang Hsiu Ju , Erwin  , Putri Suci Tuty , Pranata Satriya
Published: February 2024

Fear of being infected by coronavirus disease 2019 (COVID-19) could trigger mental health problems among nurses at the frontline. In such a situation, coping strategies are needed to deal with the imminent threat. The purpose of this study was to test the mediating effects of coping on relationships of fear of COVID-19 with anxiety, depression and post-traumatic syndrome among nurses who were in contact with COVID-19 patients. A cross-sectional and correlational research design was used to recruit a sample of 278 nurses who treated COVID-19 patients in four government referral hospitals in Indonesia. A bootstrap resampling procedure was used to test the significance of the total and specific indirect effects of coping on relationships of Fear of COVID-19 with anxiety, depression and post-traumatic syndrome. The nurses reported moderate levels of fear of COVID-19, considerable anxiety and depression, and a moderate level of coping. We found coping to be significantly negatively correlated with the reported levels of anxiety, depression and post-traumatic syndrome (p < 0.001). Coping mediated relationships of fear of COVID-19 on depression, anxiety and post-traumatic syndrome after controlling for relevant confounders for each dependent variable. This shows that enacting coping mechanisms is important to achieve an adaptive effect on nurses' mental health. Proper assessments and interventions should be tailored and implemented for nurses who have contact with COVID-19 patients to facilitate their use of coping strategies when needed in stressful situations.
Unravelling upright events: a descriptive epidemiology of the behavioural composition and temporal distribution of upright events in participants from the 1970 British Cohort Study
Authors: Culverhouse Joshua , Hillsdon Melvyn , Pulsford Richard
Published: February 2024

Background

Continued proliferation of accelerometers in physical activity research has opened new avenues for understanding activity behaviours beyond simple aggregate measures of frequency and duration. This study explores the standing and stepping composition, and the temporal distribution, of upright events, and investigates their associations with sociodemographic and health factors.

Methods

Participants from the 1970 British Cohort Study wore activPAL3 accelerometers for seven days. Event-based analysis was used to extract a time series of upright, standing, and stepping events. Derived metrics included daily number of upright and stepping events, total upright and stepping time, the burstiness of upright events and burstiness of sedentary events (burstiness refers to the pattern of how physical activity and sedentary behaviour are distributed throughout a given time period), within-event stepping proportion, within-event step count, and stepping cadence. Generalized linear regression models, adjusted for total step count, were employed to explore associations between derived metrics and sociodemographic and health-related factors.

Results

A total of 4527 participants, provided 30992 valid days (≥ 10 h of waking wear) and 1.64 million upright events. Upright event composition and temporal distribution varied across a range of sociodemographic and health-related factors. Females had more upright events than males (4.39 [3.41,5.38] n), spent more time upright, and exhibited burstier patterns of upright events (0.05 [0.04,0.05]Bn). Individuals with higher BMI had fewer upright events and a lower daily step count, but their temporal distribution of upright events was less bursty (overweight -0.02 [-0.02,-0.01]Bn; obese -0.03 [-0.04,-0.02]Bn), and upright events had a higher step count. People in active occupations were upright for longer, displayed burstier patterns of upright events (standing 0.04 [0.03,0.05]Bn; physical work 0.05 [0.04,0.05]Bn; heavy manual 0.06 [0.04,0.07]Bn), with more variable durations and shorter, slower paced stepping events compared with sedentary occupations.

Conclusions

This study has revealed novel phenotypes of standing and sitting that go beyond simple aggregate measures of total steps, step event duration or time between events. People with the same volume of stepping and frequency of gaps between upright events can accumulate their steps in very different ways. These differences and associations with population sub-groups, which persisted after adjustment for total stepping volume, may have important relations with functional and health outcomes. The findings lay the groundwork for future studies to investigate how different sitting and standing phenotypes can add to our understanding of the relationship between physical activity and health.
Prevalence of hip femoroacetabular impingement deformities in high-level (La Liga) male professional football players
Authors: Arriaza Rafael , Saavedra-García Miguel , Arriaza Alvaro , Cruz-Cámara Antonio , Leyes Manuel , Cerezal Luis , Maestro Antonio
Published: February 2024

Background

Femoroacetabular impingement (FAI) is considered one of the main causes of hip osteoarthritis in young adults, especially in athletes. In recent years, morphological changes in FAI in the hip have been linked to early and intense sports participation, but studying top-level athlete samples is not easy. This paper presents the prevalence of FAI radiological markers in 120 active white male professional football players in the Spanish First Division League (La Liga) and compares the morphological changes with those of a control group of healthy individuals without significant sport activity.

Methods

The precontract medical evaluation hip X-rays of 120 white male professional football players from four different First Division Spanish football teams were prospectively filed and retrospectively reviewed by a dedicated skeletal radiologist. The footballers’ hip X-rays were compared with those of a control group of 80 healthy individuals (age-sex matched) without significant sport activity (obtained from routine work medical checks).

Results

The femoral head-neck deformity associated with the Cam type of femoroacetabular impingement was observed in 61.6% of professional football players and only in 11.6% of the control group (p <0.01). The presence of “herniation pit” (11.6%) and os acetabuli (13.3%) also reached statistical significance in the professional football players group. In the other analyzed parameters, no statistically significant differences between the groups were observed.

Conclusions

White professional top-level football players have an increased incidence of abnormal lateral epiphyseal extension ("pistol grip deformity"), os acetabuli and herniation pits.
Distribution and antimicrobial resistance patterns of urinary pathogens in preoperative midstream urine cultures from Chinese patients with urinary calculi: a meta-analysis
Authors: Mei Xin , Zhang Shike , Xu Peng , He Zhican , Tang Ruizheng , Yang Baotong , Sarfaraz Iqbal Muhammad , Wu Wenqi
Published: February 2024

Background and objective

This study comprehensively evaluates the distribution patterns and antimicrobial resistance profiles of urinary pathogens in Preoperative midstream urine cultures collected from patients with urinary calculi in China over the last two decades.

Methods

A cross-sectional analysis of 41 studies was conducted. A systematic search across various databases, including Wanfang Data, CNKI, SinoMed, Embase, PubMed, and Web of Science, was carried out, covering the time period from 2002 to 2022. Using R 4.2.1 software, a meta-analysis was performed to assess heterogeneity using Cochran’s Q test and the I2 statistic.

Results

In the analysis of preoperative midstream urine cultures from Chinese patients with urinary calculi, gram-negative bacteria dominated at 69%, with Escherichia coli (43%), Klebsiella pneumoniae (8%), Proteus mirabilis (6%), Pseudomonas aeruginosa (5%), Acinetobacter baumannii (3%), and Enterobacter cloacae (4%) being prominent. Gram-positive organisms included Enterococcus faecalis (9%), Enterococcus faecium (5%), and Staphylococcus aureus (4%). Over time, proportions of Proteus mirabilis, Enterococcus faecalis, and Staphylococcus aureus decreased, while Klebsiella pneumoniae and Pseudomonas aeruginosa increased. Notably, Escherichia coli proportion reduced from 37 to 33% within the last two decades. Antimicrobial resistance analysis indicated declining resistance in E. coli (e.g., co-trimoxazole from 73 to 55%, gentamicin from 64 to 40%), but rising resistance in piperacillin and cefotaxime (34–60%). Enterococcus faecalis exhibited increasing resistance to ampicillin (5–69%), gentamicin (59–94%), and tetracycline (77–89%) over time, while resistance to levofloxacin and ciprofloxacin notably decreased (72–16% and 49–8%, respectively).

Conclusion

Over the past two decades, the proportion of gram-negative bacteria was declined, while the proportion of gram-positive bacteria increased. Escherichia coli remained the most common pathogen in the urine culture of patients with urinary calculi in China and the resistance of Escherichia coli to commonly used antibiotics increased. Clinicians should select appropriate antibiotics according to the results of urine culture and drug sensitivity test to reduce the occurrence of antibiotic resistance.
School-based comprehensive sexuality education for prevention of adolescent pregnancy: a scoping review
Authors: Myat Su Mon , Pattanittum Porjai , Sothornwit Jen , Ngamjarus Chetta , Rattanakanokchai Siwanon , Show Kyaw Lwin , Jampathong Nampet , Lumbiganon Pisake
Published: February 2024

Background

Adolescent pregnancy is a global public health problem. Numerous approaches for Comprehensive Sexuality Education (CSE) delivery in schools have been implemented around the world. Previous reviews on CSE did not follow the International Technical Guidance on Sexuality Education (ITGSE) because CSE is very diverse in terms of population, interventions, settings and outcomes. We conducted this scoping review to identify and map the evidence of school-based CSE for prevention of adolescent pregnancy with emphasis on adolescents’ contraceptive use, unintended pregnancy and abortion.

Methods

We searched PubMed, CENTRAL, Scopus, ISI Web of Science, CINAHL, and WHO ICTRP to identify potential eligible studies from their inception to 4th Nov 2023.We included randomized controlled trials (RCTs) and non-RCTs of CSE implemented in public or private schools for adolescents. CSE was defined as a multi-session intervention in school that covered topics including contraception, pregnancy, abortion, and HIV/STI. School-based interventions were the main intervention that may be either stand-alone or multicomponent. There was no limitation on study’s geographical area, but only English-language studies were considered. Two reviewers selected and extracted data independently, discussed for consensus or consulted the third reviewer if there were discrepancies for final conclusion. Data were presented using figures, map and table.

Results

Out of 5897 records, 79 studies (101 reports) were included in this review. Most studies were conducted in the United States and other high-income countries in secondary or high schools with cluster RCTs. All studies included participatory methods. Almost all studies included Sexual and Reproductive Health which is the eighth concept of CSE. Very few studies reported the prespecified primary outcomes of contraceptive use during last sex, unintended pregnancy and abortion and hence this highlighted the gaps of available evidence for these outcomes. The number of concepts, components, duration and providers of CSE varied across the included studies. However, none of the interventions identified in this scoping review adhered to the ITGSE recommended approach.

Conclusions

Our scoping review shows gaps in school-based CSE implementation in terms of completeness of concepts, components, providers, duration and outcomes recommended by ITGSE.
Value-based healthcare implementation in the Netherlands: a quantitative analysis of multidisciplinary team performance
Authors: Westerink Henrike J. , Steinmann Gijs , Koomans Maarten , van der Kemp Michèle H. , van der Nat Paul B.
Published: February 2024

Background

Many hospitals worldwide have set up multidisciplinary Value Improvement (VI) teams that use the Value-Based Health Care (VBHC) theory to improve patient value. However, it remains unclear what the level of VBHC implementation is within these teams. We therefore studied the current level of VBHC implementation in VI teams.

Methods

A questionnaire was developed based on the strategic agenda for value transformation and real-world experiences with VBHC implementation. The questionnaire consisted of 21 questions, mapped to seven domains, and was sent out to 25 multidisciplinary VI teams. Median scores for individual questions (scale = 1–5) and average scores per domain were calculated.

Results

One hundred forty VI team members completed the questionnaire. The overall average score is 3.49. The ‘culture and responsibility’ domain obtained the highest average score (µ = 4.11). The domain ‘measure and improve outcomes’ and the domain ‘multidisciplinary team’ obtained average scores that are slightly higher than the overall average (µ = 3.78 and µ = 3.76 respectively), and the domains ‘strategy and organizational policy,’ ‘collaboration and sharing,’ and ‘IT and data’ scored a little below the overall average (µ = 3.41, µ = 3.32, and µ = 3.29 respectively). The domain ‘costs and reimbursement’ obtained the lowest average score (µ = 2.42) of all domains, indicating that the implementation of this particular aspect of VBHC remains lagging behind.

Conclusions

Our results indicate activity in each of the questionnaire domains. To bring VBHC implementation to the next level, more attention should be given to the financial aspects. Our questionnaire can be used in future studies to identify improvements or differences within VI teams.
Growth performance, nutrient digestibility, fecal microbial diversity and volatile fatty acid, and blood biochemical indices of suckling donkeys fed diets supplemented with multienzymes
Authors: Li Chao , Li Xuan Yue , Li Xiao Bin , Ma Chen , Chen Hui , Yang Fan
Published: February 2024

Background

As the foal grows, the amount of breast milk produced by the donkey decreases. In such cases, early supplemental feeding is particularly important to meet the growth needs of the foal. Foals have an incompletely developed gastrointestinal tract with a homogenous microbiota and produce insufficient amounts of digestive enzymes, which limit their ability to digest and utilize forage. Improving the utilization of early supplemental feeds, promoting gastrointestinal tract development, and enriching microbial diversity are the hotspots of rapid growth research in dairy foals. Plant-based feeds usually contain non-starch polysaccharides (NSPs), including cellulose, xylan, mannan, and glucan, which hinder nutrient digestion and absorption. In addition, proteins and starch (both biomolecules) form a composite system mainly through non-covalent interactions. The proteins wrap around the surface of starch granules and act as a physical obstacle, thereby inhibiting water absorption and expansion of starch and decreasing the enzyme's catalytic effect on starch. Glyanase, β-mannanase, β-glucanase, cellulase, protease, and amylase added to cereal diets can alleviate the adverse effects of NSPs. The current study determined the effects of adding multienzymes (glyanase, β-mannanase, β-glucanase, cellulase, protease, and amylase) to the diet of 2-month-old suckling donkeys on their growth performance, apparent nutrient digestibility, fecal volatile fatty acid (VFA) and pH, fecal bacterial composition, and blood biochemical indices.

Results

On day 120 of the trial, fecal samples were collected from the rectum of donkeys for determining bacterial diversity, VFA content, and pH. Moreover, fresh fecal samples were collected from each donkey on days 110 and 115 to determine apparent digestibility. The multienzymes supplementations did not affect growth performance and apparent nutrient digestibility in the donkeys; however, they tended to increase total height gain (P = 0.0544). At the end of the study, the multienzymes supplementations increased (P < 0.05) the Observed species, ACE, Chao1, and Shannon indices by 10.56%, 10.47%, 10.49%, and 5.01%, respectively. The multienzymes supplementations also increased (P < 0.05) the abundance of Firmicutes, Oscillospiraceae, Lachnospiraceae, Christensenellaceae, Christensenellaceae_R-7_group, and Streptococcus in feces, whereas decreased (P = 0.0086) the abundance of Proteobacteria.

Conclusions

Multienzymes supplementations added to a basal diet for suckling donkeys can increase fecal microbial diversity and abundance.
Correlative light-electron microscopy methods to characterize the ultrastructural features of the replicative and dormant liver stages of Plasmodium parasites
Authors: Mitchell Gabriel , Torres Laura , Fishbaugher Matthew E. , Lam Melanie , Chuenchob Vorada , Zalpuri Reena , Ramasubban Shreya , Baxter Caitlin N. , Flannery Erika L. , Harupa Anke , Mikolajczak Sebastian A. , Jorgens Danielle M.
Published: February 2024

Background

The infection of the liver by Plasmodium parasites is an obligatory step leading to malaria disease. Following hepatocyte invasion, parasites differentiate into replicative liver stage schizonts and, in the case of Plasmodium species causing relapsing malaria, into hypnozoites that can lie dormant for extended periods of time before activating. The liver stages of Plasmodium remain elusive because of technical challenges, including low infection rate. This has been hindering experimentations with well-established technologies, such as electron microscopy. A deeper understanding of hypnozoite biology could prove essential in the development of radical cure therapeutics against malaria.

Results

The liver stages of the rodent parasite Plasmodium berghei, causing non-relapsing malaria, and the simian parasite Plasmodium cynomolgi, causing relapsing malaria, were characterized in human Huh7 cells or primary non-human primate hepatocytes using Correlative Light-Electron Microscopy (CLEM). Specifically, CLEM approaches that rely on GFP-expressing parasites (GFP-CLEM) or on an immunofluorescence assay (IFA-CLEM) were used for imaging liver stages. The results from P. berghei showed that host and parasite organelles can be identified and imaged at high resolution using both CLEM approaches. While IFA-CLEM was associated with more pronounced extraction of cellular content, samples’ features were generally well preserved. Using IFA-CLEM, a collection of micrographs was acquired for P. cynomolgi liver stage schizonts and hypnozoites, demonstrating the potential of this approach for characterizing the liver stages of Plasmodium species causing relapsing malaria.

Conclusions

A CLEM approach that does not rely on parasites expressing genetically encoded tags was developed, therefore suitable for imaging the liver stages of Plasmodium species that lack established protocols to perform genetic engineering. This study also provides a dataset that characterizes the ultrastructural features of liver stage schizonts and hypnozoites from the simian parasite species P. cynomolgi.

Graphical Abstract
Resistance of HNSCC cell models to pan-FGFR inhibition depends on the EMT phenotype associating with clinical outcome
Authors: Broghammer Felix , Korovina Irina , Gouda Mahesh , Celotti Martina , van Es Johan , Lange Inga , Brunner Cornelia , Mircetic Jovan , Coppes Robert P. , Gires Olivier , Dahl Andreas , Seifert Michael , Cordes Nils
Published: February 2024

Background

Focal adhesion signaling involving receptor tyrosine kinases (RTK) and integrins co-controls cancer cell survival and therapy resistance. However, co-dependencies between these receptors and therapeutically exploitable vulnerabilities remain largely elusive in HPV-negative head and neck squamous cell carcinoma (HNSCC).

Methods

The cytotoxic and radiochemosensitizing potential of targeting 10 RTK and β1 integrin was determined in up to 20 3D matrix-grown HNSCC cell models followed by drug screening and patient-derived organoid validation. RNA sequencing and protein-based biochemical assays were performed for molecular characterization. Bioinformatically identified transcriptomic signatures were applied to patient cohorts.

Results

Fibroblast growth factor receptor (FGFR 1–4) targeting exhibited the strongest cytotoxic and radiosensitizing effects as monotherapy and combined with β1 integrin inhibition, exceeding the efficacy of the other RTK studied. Pharmacological pan-FGFR inhibition elicited responses ranging from cytotoxicity/radiochemosensitization to resistance/radiation protection. RNA sequence analysis revealed a mesenchymal-to-epithelial transition (MET) in sensitive cell models, whereas resistant cell models exhibited a partial epithelial-to-mesenchymal transition (EMT). Accordingly, inhibition of EMT-associated kinases such as EGFR caused reduced adaptive resistance and enhanced (radio)sensitization to FGFR inhibition cell model- and organoid-dependently. Transferring the EMT-associated transcriptomic profiles to HNSCC patient cohorts not only demonstrated their prognostic value but also provided a conclusive validation of the presence of EGFR-related vulnerabilities that can be strategically exploited for therapeutic interventions.

Conclusions

This study demonstrates that pan-FGFR inhibition elicits a beneficial radiochemosensitizing and a detrimental radioprotective potential in HNSCC cell models. Adaptive EMT-associated resistance appears to be of clinical importance, and we provide effective molecular approaches to exploit this therapeutically.
Younger patients with colorectal cancer may have better long-term survival after surgery: a retrospective study based on propensity score matching analysis
Authors: Liao Weihao , Li Yuanxi , Zou Yuheng , Xu Qinchen , Wang Xiaodong , Li Li
Published: February 2024

Background

The relationship between postoperative long-term prognosis and age in colorectal cancer patients remains controversial. The purpose of this study based on a Chinese CRC cohort is to determine the disparity in long-term survival outcomes between younger and older colorectal cancer (CRC) patients after surgery using a propensity score matching (PSM).

Methods

Data for this study was derived from the CRC cohort of the Database from Colorectal Cancer (DACCA) at West China Hospital of Sichuan University from January 2007 to September 2022. The long‑term prognoses were compared between younger and older groups.

Results

A total of 2374 CRC patients were evaluated in this study, including 1039 older patients and 1335 younger ones. After 1:1 ratio PSM, each group contained 784 CRC patients. There was no significant difference in baseline information after PSM (p < 0.05). Multivariate analysis showed that younger age was an independent predictor of better overall survival (OS) (p < 0.001, HR = 1.750, 95% CI = 1.407–2.177) and disease-specific survival (DSS) (p < 0.001, HR = 1.718, 95% CI = 1.369–2.157). In terms of different tumor pathological stages after PSM, in comparison to older group, younger group had better OS in stage II (p < 0.001), stage III (p = 0.0085), and stage IV (p = 0.0014) and better DSS in stage II (p = 0.0035), stage III (p = 0.0081), and stage IV (p < 0.001).

Conclusion

Younger CRC patients have better prognosis than older CRC patients after surgery, especially, and have better OS and DSS in stages II, III, and IV CRC. Younger CRC patient may gain greater benefit from CRC resection and combined therapy. As for the cut-off age, it may be determined by a specific model suitable for local patients.
Radiation-induced cutaneous vasculopathy of the breast: a rare case report
Authors: Van Parijs Hilde , Sinove Yves , Carprieaux Marilyn , De Ridder Mark
Published: February 2024

Background

Radiation therapy is often indicated as part of the treatment for breast cancer and is therefore used frequently worldwide. Vasculopathy is a general term used to describe any condition that affects blood vessels. We present a case report of a patient who presented with vasculopathy as a rare late side effect of radiation therapy to the breast.

Case presentation

This 66-year-old woman was initially treated with breast-conserving surgery for early-stage receptor-positive left breast carcinoma. She received postoperative radiation therapy and hormonal treatment with tamoxifen. She developed sudden spontaneous painless ecchymosis spread over the whole irradiated area 1.5 years after finishing her radiation therapy. Tumor relapse was excluded. There was no associated vasculitis. The cause was presumed to be multifactorial. She had a history of smoking and was known to have hyperlipidemia. She had undergone several surgical treatments at the left breast one year after her initial breast-conserving treatment and was taking tamoxifen. Anti-inflammatory medicine and treatments increasing local blood flow were prescribed. The ecchymosis resolved completely within one month.

Conclusions

Vasculopathy can occur as a rare late side effect of radiation therapy. It can be reversible. Prevention begins with carefully treating precipitating factors.
Multi-modal assessment of a cardiac stem cell therapy reveals distinct modulation of regional scar properties
Authors: Schweins Moritz , Gäbel Ralf , Raitza Matti , Vasudevan Praveen , Lemcke Heiko , Joksch Markus , Schildt Anna , Kurth Jens , Lindner Tobias , Meinel Felix G. , Öner Alper , Ince Hüseyin , Vollmar Brigitte , Krause Bernd Joachim , David Robert , Lang Cajetan Immanuel
Published: February 2024

Background

The initial idea of functional tissue replacement has shifted to the concept that injected cells positively modulate myocardial healing by a non-specific immune response of the transplanted cells within the target tissue. This alleged local modification of the scar requires assessment of regional properties of the left ventricular wall in addition to commonly applied measures of global morphological and functional parameters. Hence, we aimed at investigating the effect of cardiac cell therapy with cardiovascular progenitor cells, so-called cardiac induced cells, on both global and regional properties of the left ventricle by a multimodal imaging approach in a mouse model.

Methods

Myocardial infarction was induced in mice by ligation of the left anterior descending artery, the therapy group received an intramyocardial injection of 1 × 106 cardiac induced cells suspended in matrigel, the control group received matrigel only. [18F]FDG positron emission tomography imaging was performed after 17 days, to assess regional glucose metabolism. Three weeks after myocardial infarction, cardiac magnetic resonance imaging was performed for morphological and functional assessment of the left ventricle. Following these measurements, hearts were excised for histological examinations.

Results

Cell therapy had no significant effect on global morphological parameters. Similarly, there was no difference in scar size and capillary density between therapy and control group. However, there was a significant improvement in contractile function of the left ventricle – left ventricular ejection fraction, stroke volume and cardiac output. Regional analysis of the left ventricle identified changes of wall properties in the scar area as the putative mechanism. Cell therapy reduced the thinning of the scar and significantly improved its radial contractility. Furthermore, the metabolic defect, assessed by [18F]FDG, was significantly reduced by the cell therapy.

Conclusion

Our data support the relevance of extending the assessment of global left ventricular parameters by a structured regional wall analysis for the evaluation of therapies targeting at modulation of healing myocardium. This approach will enable a deeper understanding of mechanisms underlying the effect of experimental regenerative therapies, thus paving the way for a successful translation into clinical application.
Parkinson’s disease-derived α-synuclein assemblies combined with chronic-type inflammatory cues promote a neurotoxic microglial phenotype
Authors: Yildirim-Balatan Cansu , Fenyi Alexis , Besnault Pierre , Gomez Lina , Sepulveda-Diaz Julia E. , Michel Patrick P. , Melki Ronald , Hunot Stéphane
Published: February 2024

Parkinson’s disease (PD) is a common age-related neurodegenerative disorder characterized by the aggregation of α-Synuclein (αSYN) building up intraneuronal inclusions termed Lewy pathology. Mounting evidence suggests that neuron-released αSYN aggregates could be central to microglial activation, which in turn mounts and orchestrates neuroinflammatory processes potentially harmful to neurons. Therefore, understanding the mechanisms that drive microglial cell activation, polarization and function in PD might have important therapeutic implications. Here, using primary microglia, we investigated the inflammatory potential of pure αSYN fibrils derived from PD patients. We further explored and characterized microglial cell responses to a chronic-type inflammatory stimulation combining PD patient-derived αSYN fibrils (FPD), Tumor necrosis factor-α (TNFα) and prostaglandin E2(PGE2) (TPFPD). We showed that FPDhold stronger inflammatory potency than pure αSYN fibrils generated de novo. When combined with TNFα and PGE2, FPDpolarizes microglia toward a particular functional phenotype departing from FPD-treated cells and featuring lower inflammatory cytokine and higher glutamate release. Whereas metabolomic studies showed that TPFPD-exposed microglia were closely related to classically activated M1 proinflammatory cells, notably with similar tricarboxylic acid cycle disruption, transcriptomic analysis revealed that TPFPD-activated microglia assume a unique molecular signature highlighting upregulation of genes involved in glutathione and iron metabolisms. In particular, TPFPD-specific upregulation ofSlc7a11(which encodes the cystine-glutamate antiporter xCT) was consistent with the increased glutamate response and cytotoxic activity of these cells toward midbrain dopaminergic neurons in vitro. Together, these data further extend the structure–pathological relationship of αSYN fibrillar polymorphs to their innate immune properties and demonstrate that PD-derived αSYN fibrils, TNFα and PGE2act in concert to drive microglial cell activation toward a specific and highly neurotoxic chronic-type inflammatory phenotype characterized by robust glutamate release and iron retention.
Pro-inflammatory cerebrospinal fluid profile of neonates with intraventricular hemorrhage: clinical relevance and contrast with CNS infection
Authors: Garcia-Bonilla Maria , Yahanda Alexander T. , Isaacs Albert M. , Baksh Brandon , Akbari S. Hassan A. , Botteron Haley , Morales Diego M. , Han Rowland H. , McAllister II James P. , Mathur Amit M. , Strahle Jennifer M. , Smyser Christopher D. , Limbrick David D.
Published: February 2024

Background

Interpretation of cerebrospinal fluid (CSF) studies can be challenging in preterm infants. We hypothesized that intraventricular hemorrhage (IVH), post-hemorrhagic hydrocephalus (PHH), and infection (meningitis) promote pro-inflammatory CSF conditions reflected in CSF parameters.

Methods

Biochemical and cytological profiles of lumbar CSF and peripheral blood samples were analyzed for 81 control, 29 IVH grade 1/2 (IVH1/2), 13 IVH grade 3/4 (IVH3/4), 15 PHH, 20 culture-confirmed bacterial meningitis (BM), and 27 viral meningitis (VM) infants at 36.5 ± 4 weeks estimated gestational age.

Results

PHH infants had higher (p < 0.02) CSF total cell and red blood cell (RBC) counts compared to control, IVH1/2, BM, and VM infants. No differences in white blood cell (WBC) count were found between IVH3/4, PHH, BM, and VM infants. CSF neutrophil counts increased (p ≤ 0.03) for all groups compared to controls except IVH1/2. CSF protein levels were higher (p ≤ 0.02) and CSF glucose levels were lower (p ≤ 0.003) for PHH infants compared to all other groups. In peripheral blood, PHH infants had higher (p ≤ 0.001) WBC counts and lower (p ≤ 0.03) hemoglobin and hematocrit than all groups except for IVH3/4.

Conclusions

Similarities in CSF parameters may reflect common pathological processes in the inflammatory response and show the complexity associated with interpreting CSF profiles, especially in PHH and meningitis/ventriculitis.
Adaptive strategies used by surgical teams under pressure: an interview study among senior healthcare professionals in four major hospitals in the United Kingdom
Authors: Irving Dulcie , Page Bethan , Carthey Jane , Higham Helen , Undre Shabnam , Vincent Charles
Published: February 2024

Background

Healthcare systems are operating under substantial pressures, and often simply cannot provide the standard of care they aspire to within the available resources. Organisations, managers, and individual clinicians make constant adaptations in response to these pressures, which are typically improvised, highly variable and not coordinated across clinical teams. The purpose of this study was to identify and describe the types of everyday pressures experienced by surgical teams and the adaptive strategies they use to respond to these pressures.

Methods

We conducted interviews with 20 senior multidisciplinary healthcare professionals from surgical teams in four major hospitals in the United Kingdom. The interviews explored the types of everyday pressures staff were experiencing, the strategies they use to adapt, and how these strategies might be taught to others.

Results

The primary pressures described by senior clinicians in surgery were increased numbers and complexity of patients alongside shortages in staff, theatre space and post-surgical beds. These pressures led to more difficult working conditions (e.g. high workloads) and problems with system functioning such as patient flow and cancellation of lists. Strategies for responding to these pressures were categorised into increasing or flexing resources, controlling and prioritising patient demand and strategies for managing the workload (scheduling for efficiency, communication and coordination, leadership, and teamwork strategies).

Conclusions

Teams are deploying a range of strategies and making adaptations to the way care is delivered. These findings could be used as the basis for training programmes for surgical teams to develop coordinated strategies for adapting under pressure and to assess the impact of different combinations of strategies on patient safety and surgical outcomes.