bluuebunny/crossref_metadata_2025 huggingface dataset:
Cystic fibrosis macrophage function and clinical outcomes after elexacaftor/tezacaftor/ivacaftor
Authors: Zhang Shuzhong , Shrestha Chandra L. , Robledo-Avila Frank , Jaganathan Devi , Wisniewski Benjamin L. , Brown Nevian , Pham Hanh , Carey Katherine , Amer Amal O. , Hall-Stoodley Luanne , McCoy Karen S. , Bai Shasha , Partida-Sanchez Santiago , Kopp Benjamin T.
Published: October 2022

Background

Abnormal macrophage function caused by dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) is a critical contributor to chronic airway infections and inflammation in people with cystic fibrosis (PWCF). Elexacaftor/tezacaftor/ivacaftor (ETI) is a new CFTR modulator therapy for PWCF. Host–pathogen and clinical responses to CFTR modulators are poorly described. We sought to determine how ETI impacts macrophage CFTR function, resulting effector functions and relationships to clinical outcome changes.

Methods

Clinical information and/or biospecimens were obtained at ETI initiation and 3, 6, 9 and 12 months post-ETI in 56 PWCF and compared with non-CF controls. Peripheral blood monocyte-derived macrophages (MDMs) were isolated and functional assays performed.

Results

ETI treatment was associated with increased CF MDM CFTR expression, function and localisation to the plasma membrane. CF MDM phagocytosis, intracellular killing of CF pathogens and efferocytosis of apoptotic neutrophils were partially restored by ETI, but inflammatory cytokine production remained unchanged. Clinical outcomes including increased forced expiratory volume in 1 s (+10%) and body mass index (+1.0 kg·m−2) showed fluctuations over time and were highly individualised. Significant correlations between post-ETI MDM CFTR function and sweat chloride levels were observed. However, MDM CFTR function correlated with clinical outcomes better than sweat chloride.

Conclusion

ETI is associated with unique changes in innate immune function and clinical outcomes.
Multi-objective data enhancement for deep learning-based ultrasound analysis
Authors: Piao Chengkai , Lv Mengyue , Wang Shujie , Zhou Rongyan , Wang Yuchen , Wei Jinmao , Liu Jian
Published: October 2022

Recently, Deep Learning based automatic generation of treatment recommendation has been attracting much attention. However, medical datasets are usually small, which may lead to over-fitting and inferior performances of deep learning models. In this paper, we propose multi-objective data enhancement method to indirectly scale up the medical data to avoid over-fitting and generate high quantity treatment recommendations. Specifically, we define a main and several auxiliary tasks on the same dataset and train a specific model for each of these tasks to learn different aspects of knowledge in limited data scale. Meanwhile, a Soft Parameter Sharing method is exploited to share learned knowledge among models. By sharing the knowledge learned by auxiliary tasks to the main task, the proposed method can take different semantic distributions into account during the training process of the main task. We collected an ultrasound dataset of thyroid nodules that contains Findings, Impressions and Treatment Recommendations labeled by professional doctors. We conducted various experiments on the dataset to validate the proposed method and justified its better performance than existing methods.
The health equity characteristics of research exploring the unmet community mobility needs of older adults: a scoping review
Authors: van Biljon Hester , van Niekerk Lana , Margot-Cattin Isabel , Adams Fasloen , Plastow Nicola , Bellagamba David , Kottorp Anders , Patomella Ann-Helen
Published: October 2022

Background

Unmet community mobility needs of older adults, published since the announcement of the UN sustainable development goals was synthesised to describe the health equity characteristics of research identifying unmet community mobility needs of older adults.

Methods

Searches were conducted in March and April 2020, 2275 articles were screened and 100 identified for data extraction.

Results

Findings showed underrepresentation of articles considering rural settings [9%] and originating in the global South [14%]. Gender, disability, education, and transport / driving were identified as key health equity characteristics and only 10 articles provided detail on all four of these. External factors inhibiting community mobility included built environments, service availability, and societal attitudes. Internal factors included finances, fear and apprehension, and functional limitations.

Conclusions

The need for standardised reporting of participant characteristics in the community mobility of older adults was highlighted. These characteristics are required by research consumers to judge equity dimensions, and the extent to which findings represent minority or marginalised groups. Fifteen years after the UN pledge to reduce inequalities, peer reviewed primary research does not reflect a global drive to end discrimination, exclusion and reduce the inequalities and vulnerabilities that leave people behind.
Quantitative DCE-MRI prediction of breast cancer recurrence following neoadjuvant chemotherapy: a preliminary study
Authors: Thawani Rajat , Gao Lina , Mohinani Ajay , Tudorica Alina , Li Xin , Mitri Zahi , Huang Wei
Published: October 2022

Introduction

Breast cancer patients treated with neoadjuvant chemotherapy (NACT) are at risk of recurrence depending on clinicopathological characteristics. This preliminary study aimed to investigate the predictive performances of quantitative dynamic contrast-enhanced (DCE) MRI parameters, alone and in combination with clinicopathological variables, for prediction of recurrence in patients treated with NACT.

Methods

Forty-seven patients underwent pre- and post-NACT MRI exams including high spatiotemporal resolution DCE-MRI. The Shutter-Speed model was employed to perform pharmacokinetic analysis of the DCE-MRI data and estimate the Ktrans, ve, kep, and τi parameters. Univariable logistic regression was used to assess predictive accuracy for recurrence for each MRI metric, while Firth logistic regression was used to evaluate predictive performances for models with multi-clinicopathological variables and in combination with a single MRI metric or the first principal components of all MRI metrics.

Results

Pre- and post-NACT DCE-MRI parameters performed better than tumor size measurement in prediction of recurrence, whether alone or in combination with clinicopathological variables. Combining post-NACT Ktrans with residual cancer burden and age showed the best improvement in predictive performance with ROC AUC = 0.965.

Conclusion

Accurate prediction of recurrence pre- and/or post-NACT through integration of imaging markers and clinicopathological variables may help improve clinical decision making in adjusting NACT and/or adjuvant treatment regimens to reduce the risk of recurrence and improve survival outcome.
Efficacy of diet on fatigue, quality of life and disability status in multiple sclerosis patients: rapid review and meta-analysis of randomized controlled trials
Authors: Guerrero Aznar María Dolores , Villanueva Guerrero María Dolores , Cordero Ramos Jaime , Eichau Madueño Sara , Morales Bravo María , López Ruiz Rocío , Beltrán García Margarita
Published: October 2022

Background

Multiple sclerosis is an inflammatory and neurodegenerative disease. People with multiple sclerosis (pwMS) experience chronic fatigue which is difficult to deal with therapeutically and greatly affects health-related quality of life (QOL).

PwMS are aware of the lack of generalized dietary advice related to their disease, leading to self-experimentation with diet.

It is necessary to provide objective information about dietary interventions for pwMS. We aim to provide an objective synthesis of the evidence for efficacy and safety of specific diets in pwMS through a rapid review and meta-analyses of randomized controlled trials (RCTs), examining symptomatic fatigue (MFIS), QOL, Expanded-Disability-Status-Scale (EDSS), and severe adverse events.

Methods

We have carried out a rapid review (MEDLINE and EMBASE) up to December 2021, with PRISMA methodology, and meta-analyses, of (RCTs). All statistical analyses were performed using the comprehensive meta-analysis (CMA) -RStudio 4.1.3. The analysis used weighted mean differences (WMD) and a 95% confidence interval (CI) using a random-effects model to compare the effects of the dietary intervention with the control.

Results

Eight studies met the inclusion criteria. Of these eight studies, five analyzed EDSS, three MFIS, and three QOL. A total of 515 patients were analyzed. These meta-analyses cumulative evidence support that dietary intervention is associated with a trend of reduction in fatigue (308 patients studied) -the difference between means (SMD) of the control group and intervention group was -2,033, 95%-IC (-3,195, -0,152), a p-value of 0.0341)-, an increase in QOL (77 patients studied), no significant effect on EDSS (337 patients studied), and no severe adverse events.

Conclusions

It is difficult to reach a high level of evidence in dietary studies. Our findings show that dietary intervention is associated with a trend of reduction in fatigue in MS. Taking into account the potential of dietary interventions and the benefit/risk ratio in their favor, neurologists must be aware of the great importance of making interventions on diet in MS if necessary. There are dietary interventions with some evidence of benefit for patients with MS, which could be chosen based on adherence, patient preferences, and individual outcomes. Large prospective clinical trials are needed to shed further light on this topic.
Determinants affecting utilisation of health services and treatment for children under-5 in rural Nepali health centres: a cross-sectional study
Authors: Shrestha Binod , Green Dan J. , Baidya Manish , Chater Tim , Karki Jiban , Lee Andrew CK , Khadka Seema , Pohl Gerda , Neupane Rudra , Rushton Simon
Published: October 2022

Background

Large inequalities in child health remain in Nepal, with caste, ethnicity and sex being major determinants of deprivation and negative outcomes. The purpose of this study was to explore whether key demographics of under 5s were associated with health seeking behaviours, utilisation of health care, and treatment received.

Methods

Data came from Integrated Management of Neonatal & Childhood Illness (IMNCI) records of 23 health centres across five districts. After digitising the paper records, the data was analysed by district, caste/ethnicity, sex, and age to investigate differences in the time taken to present at a health facility after the onset of symptoms of ARI, diarrhoea and fever; accuracy of diagnosis for pneumonia; and whether the correct treatment was prescribed for pneumonia as per IMNCI guidelines.

Results

From 116 register books spanning 23 health centres, 30,730 child patient records were considered for analysis. The median age of attendance was 18 months (Inter-Quartile Range = 10, 32), while were more male children that attended (55.7% vs. 44.3% for females). There were statistically significant differences for the time taken to attend a health centre between different districts for ARI, diarrhoea and fever, with children in the remote Humla and Mugu districts taking significantly longer to present at a health facility after the onset of symptoms (all p < 0.001, except Mugu for ARI days). Children from underprivileged ethnic groups, Madhesi and Dalit, were less likely to be given a correct diagnosis of pneumonia (p = 0.014), while males were more likely to receive a correct diagnosis than females (73% vs. 67%, p = 0.001). This sex difference remained in the adjusted regression models for diagnosis of pneumonia (p < 0.001) but not for treatment of pneumonia (p = 0.628). All districts, in comparison to Gorkha, had increased odds of correct diagnosis and treatment of pneumonia, but only significant in children from Mugu after adjustment (p ≤ 0.001).

Conclusion

Significant demographic differences were found based on ethnicity, sex, and district when examining health seeking behaviours for ARI, diarrhoea, and fever. Significant associations were seen for these same factors when exploring accuracy of diagnoses of pneumonia, but not for treatment. This study has emphasised the importance of a digitalised healthcare system, where inequalities can be identified without the reliance on anecdotal evidence.
Knowledge of Silesia adult inhabitants regarding preventive vaccinations effect on cardiovascular diseases
Authors: Dąbek Józefa , Sierka Oskar
Published: October 2022

Objectives

Protective vaccinations are important in maintaining health and reducing suffering from infectious diseases. Also, vaccine-preventable infectious diseases are associated with the development and progression of cardiovascular diseases.

Aim

The study aimed to test adults' knowledge of the role of protective vaccinations in the prevention of cardiovascular diseases, and their opinions on the quantity of the information provided by doctors in this regard.

Methods

A total of 700 adults participated in the study, most of whom were women (500; 71.43%). The study used an original questionnaire containing questions covering vaccinations and cardiovascular diseases, and the general characteristics of the participants. The inclusion criteria for the study were 18 years of age and written informed consent to participate in the study.

Results

Over 60% of the participants did not know of, or denied the possibility of, developing cardiovascular diseases as a result of avoiding required preventive vaccinations. More than half of the participants stated that there is no need to recommend influenza vaccination to patients with cardiovascular diseases. Over 70% of participants stated that family doctors did not provide sufficient information about protective vaccinations.

Conclusion

In these adults, knowledge of the role of preventive vaccinations in the prevention of cardiovascular diseases was low, and the quantity of the information provided by doctors about preventive vaccinations were considered to be insufficient. Public awareness of the effects of avoiding preventive vaccinations should be raised especially among people with CVD.
Influence of hyaluronic acid on intra-articular friction – a biomechanical study in whole animal joints
Authors: Mederake Moritz , Trappe Dominik , Jacob Christopher , Hofmann Ulf Krister , Schüll Daniel , Dalheimer Philipp , Exner Lisanne , Walter Christian
Published: October 2022

Background

Cartilage is a mechanically highly stressed tissue in the human body and an important part of synovial joints. The joint cartilage is lubricated by synovial fluid with hyaluronic acid (HA) as main component. However, in joints with osteoarthritis HA has a lower concentration and molecular weight compared to healthy joints. In recent years, the intra-articular injection of therapeutic HA lubricant, has become a popular therapy. The effect of HA application on the friction of a complete joint with physiological movement needs to be further determined.

Methods

The aim of the present study was to evaluate the lubrication effect of the joint by three lubricants (NaCl, fetal calf serum (FCS) and HA) and their effect on the friction in nine complete ovine carpo-metacarpal joints. The joints were mounted on a material testing machine and a physiological movement with 10° rotation was simulated with ascending axial load (100 – 400 N). Specimens were tested native, with cartilage damage caused by drying out and relubricated. Dissipated energy (DE) as a measure of friction was recorded and compared.

Results

Investigating the effect of axial load, we found significant differences in DE between all axial load steps (p < .001), however, only for the defect cartilage. Furthermore, we could document an increase in DE from native (Mean: 15.0 mJ/cycle, SD: 8.98) to cartilage damage (M: 74.4 mJ/cycle, SD: 79.02) and a decrease after relubrication to 23.6 mJ/cycle (SD: 18.47). Finally, we compared the DE values for NaCl, FCS and HA. The highest values were detected for NaCl (MNorm = 16.4 mJ/cycle, SD: 19.14). HA achieved the lowest value (MNorm = 4.3 mJ/cycle, SD: 4.31), although the gap to FCS (MNorm = 5.1 mJ/cycle, SD: 7.07) was small.

Conclusions

We were able to elucidate three effects in joints with cartilage damage. First, the friction in damaged joints increases significantly compared to native joints. Second, especially in damaged joints, the friction increases significantly more with increased axial load compared to native or relubricated joints. Third, lubricants can achieve an enormous decrease in friction. Comparing different lubricants, our results indicate the highest decrease in friction for HA.
Effects of vitamin D on insulin resistance and fasting blood glucose in pregnant women with insufficient or deficient vitamin D: a randomized, placebo-controlled trial
Authors: Mirzaei-Azandaryani Zahra , Mohammad-Alizadeh-Charandabi Sakineh , Shaseb Elnaz , Abbasalizadeh Shamsi , Mirghafourvand Mojgan
Published: October 2022

Background

Gestational diabetes is one of the most common metabolic disorders during pregnancy. Some studies have reported the effect of vitamin D deficiency on the incidence of this disorder. Therefore, the purpose of the present study was to determine the effect of vitamin D supplementation on fasting blood glucose (FBG) levels, fasting blood insulin (FBI) levels and insulin resistance index (HOMA-IR) (primary outcomes) and symptoms of depression, musculoskeletal pain, frequency of gestational diabetes and the frequency of abortion (secondary outcomes).

Methods

In this triple-blind randomized controlled trial, 88 pregnant women at 8–10 weeks of pregnancy who had the vitamin D of less than 30 ng/ml were randomly assigned to the vitamin D group (n = 44) and control group (n = 44) using block randomization. The vitamin D group received 4,000 units of vitamin D tablets daily and the control group received placebo tablets for 18 weeks. Independent t-test, Mann-Whitney U and ANCOVA tests were used to analyze the data.

Results

After the intervention, there was no statistically significant difference between the two groups in terms of FBG (P = 0.850), FBI (P = 0.353), HOMA-IR (P = 0.632), mean score of depressive symptoms (P = 0.505), frequency of gestational diabetes (P = 0.187) and frequency of abortion (P = 1.000) and there was only a difference in terms of serum vitamin D level (P = 0.016) and musculoskeletal pain including knee pain (P = 0.025), ankle pain (P < 0.001) and leg pain (P < 0.001).

Conclusion

Vitamin D could improve the musculoskeletal pain in pregnant women but couldn’t decrease FBG, FBI, HOMA-IR, depression symptoms score, incidence of GDM and abortion.

Trial registration:

Iranian Registry of Clinical Trials (IRCT): IRCT20120718010324N59. Date of registration: 4/11/2020. URL:https://en.irct.ir/user/trial/50973/view; Date of first registration: 21/11/2020.
The prevalence of thyroid dysfunction in Jordan: a national population-based survey
Authors: Ajlouni Kamel M. , Khawaja Nahla , EL-Khateeb Mohammed , Batieha Anwar , Farahid Oraib
Published: October 2022

Background

The objectives of this study are to assess the prevalence of clinical and subclinical hypo- and hyperthyroidism and their associated factors among Jordanian adults.

Methods

In a cross-sectional population-based survey, a representative sample that included 3753 Jordanian adults was selected from the 12 governorates that represent the three regions of the country, in the year 2017. Sociodemographic and clinical data were obtained and blood samples were collected from all participants. Thyroid stimulating hormone (TSH), free tri-iodothyronine (FT3), free thyroxine (FT4), thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) were measured to evaluate the thyroid function.

Results

The overall prevalence of thyroid dysfunction was 11.9%. Around 76% of patients with thyroid dysfunction were previously undiagnosed. The prevalence of hypothyroidism and subclinical hypothyroidism was 3.1 and 5.3%, respectively. The prevalence of hyperthyroidism and subclinical hyperthyroidism was 1.0 and 2.5%, respectively. Female preponderance which was mainly related to hypothyroid disorders was evident. The prevalence of positive TPOAb and TgAb in the study population was 14.9 and 15.3%, respectively. The prevalence of detectable TPOAb and TgAb in the euthyroid participants was10.3 and 11.9%, respectively. Logistic regression analysis revealed that female sex, age ≥ 50 years and the presence of TgAb and TPOAb were strongly associated with hypothyroidism. Hyperthyroidism was significantly associated with the presence of TPOAb and age ≥ 50 years.

Conclusion

The prevalence of unrecognized thyroid dysfunction is high among Jordanians. A public health policy of screening high risk groups particularly those ≥50 years of age is recommended.
Knowledge, attitude and perceptions of medical students towards mental health in a university in Uganda
Authors: Kihumuro Raymond Bernard , Kaggwa Mark Mohan , Kintu Timothy Mwanje , Nakandi Rachael Mukisa , Muwanga David Richard , Muganzi David Jolly , Atwau Pius , Ayesiga Innocent , Najjuma Josephine Nambi , Ashaba Scholastic
Published: October 2022

Background

The prevalence of mental illness among medical students is high. A gap remains on what knowledge should be given to improve the attitudes and perceptions towards mental health. Despite the vast body of literature globally, no study has been conducted in Uganda to assess the levels of knowledge, attitude, and perception among medical students in Uganda.

Objective

To determine the level of knowledge, attitude, and perception and their associated factors among medical students in Uganda.

Methods

A cross-sectional study was done among 259 undergraduate medical students in a public university capturing information on knowledge, attitude, and perception towards mental health. Linear regression analysis was used to determine the factors associated with knowledge, attitude, and perception.

Results

About 77.72% had high knowledge, 49.29% had positive attitudes, and 46.92% had good perceptions of mental health. There was a significant positive relationship between attitude and perceptions towards mental illness. At multilevel analysis, being in year 4 increased the level of knowledge (β = 1.50 [95% confidence interval (CI) = 0.46–2.54], p = 0.005) while a positive history of mental illness worsened perceptions towards mental illness (β = -4.23 [95% CI = −7.44–1.03], p = 0.010).

Conclusion

Medical students have a high level of knowledge about mental illness but the majority had poor attitudes and perceptions of mental illness. Exposure to psychiatry knowledge about mental illness in year four increased students’ knowledge while prior experience with mental illness conditions was associated with poorer perceptions. The information present in this study can be used by policymakers and future researchers to design future studies and interventions to improve knowledge, perceptions, and attitudes especially among students who have a history of mental illness. Improvements in knowledge, attitude, and perception may improve the mental health services for the future patients of these medical students.
Identifying stroke diagnosis-related features from medical imaging reports to improve clinical decision-making support
Authors: Xu Xiaowei , Qin Lu , Ding Lingling , Wang Chunjuan , Wang Meng , Li Zixiao , Li Jiao
Published: October 2022

Background

Medical imaging reports play an important role in communication of diagnostic information between radiologists and clinicians. Head magnetic resonance imaging (MRI) reports can provide evidence that is widely used in the diagnosis and treatment of ischaemic stroke. The high-signal regions of diffusion-weighted imaging (DWI) images in MRI reports are key evidence. Correctly identifying high-signal regions of DWI images is helpful for the treatment of ischaemic stroke patients. Since most of the multiple signals recorded in head MRI reports appear in the same part, it is challenging to identify high-signal regions of DWI images from MRI reports.

Methods

We developed a deep learning model to automatically identify high-signal regions of DWI images from head MRI reports. We proposed a fine-grained entity typing model based on machine reading comprehension that transformed the traditional two-step fine-grained entity typing task into a question-answering task.

Results

To prove the validity of the model proposed, we compared it with the fine-grained entity typing model, of which the F1 measure was 5.9% and 3.2% higher than the F1 measures of the models based on LSTM and BERT, respectively.

Conclusion

In this study, we explore the automatic identification of high-signal regions of DWI images from the description part of a head MRI report. We transformed the identification of high-signal regions of DWI images to an FET task and proposed an MRC-FET model. Compared with the traditional two-step FET method, the model we proposed not only simplifies the task but also has better performance. The comparable result shows that the work in this study can contribute to improving the clinical decision support system.
Five years’ experience with value-based quality improvement teams: the key factors to a successful implementation in hospital care
Authors: Daniels Kirsten , Rouppe van der Voort Marc B. V. , Biesma Douwe H. , van der Nat Paul B.
Published: October 2022

Background

In recent years, value-based healthcare (VBHC) has become one of the most accepted concepts for fixing the ‘broken’ healthcare systems. Numerous hospitals have embraced VBHC and are trying to implement value-based quality improvement (VBQI) into their practice. However, there is a lack of knowledge on how to practically implement VBHC and organizations differ in their approach. The aim of this study was to explore the main factors that were experienced as hindering and/or supporting in the implementation of VBQI teams in hospital care.

Methods

A qualitative study was performed with semi-structured interviews with 43 members of eight VBQI teams in a large Dutch top-clinical teaching hospital. Participants included physicians, physician assistants, nurses, VBHC project leaders, managers, social workers, researchers and paramedics. Interview grids were structured according to the RE-AIM model (reach, effectiveness, adoption, implementation and maintenance). A thematic content analysis with open coding was used to identify emerging (sub)themes.

Results

We identified nine main factors divided over three domains (organization, culture and practice) that determined whether the implementation of VBQI teams was successful or not: 1). Practical organization of value-based quality improvement teams, 2). Organizational structure 3). Integration of VBHC with existing quality improvement approaches and research 4). Adoption and knowledge of the VBHC concept in the hospital 5). Multidisciplinary engagement 6). Medical leadership 7). Goal setting and selecting quality improvement initiatives 8). Long-cycle benchmarking and short-cycle feedback 9). Availability of outcome data.

Conclusions

Overall, this study goes beyond the general VBHC theory and provides healthcare providers with more detailed knowledge on how to practically implement value-based quality improvement in a hospital care setting. Factors in the ‘organization’ and ‘practice’ domain were mentioned in the strategic value agenda of Porter and Lee. Though, this study provides more practical insight in these two domains. Factors in the ‘culture’ domain were not mentioned in the strategic value agenda and have not yet been thoroughly researched before.
Circadian rhythms in the plant host influence rhythmicity of rhizosphere microbiota
Authors: Newman Amy , Picot Emma , Davies Sian , Hilton Sally , Carré Isabelle A. , Bending Gary D.
Published: October 2022

Background

Recent studies demonstrated that microbiota inhabiting the plant rhizosphere exhibit diel changes in abundance. To investigate the impact of plant circadian rhythms on bacterial and fungal rhythms in the rhizosphere, we analysed temporal changes in fungal and bacterial communities in the rhizosphere ofArabidopsisplants overexpressing or lacking function of the circadian clock geneLATE ELONGATED HYPOCOTYL(LHY).

Results

Under diel light–dark cycles, the knock-out mutantlhy-11and the gain-of-function mutantlhy-oxboth exhibited gene expression rhythms with altered timing and amplitude compared to wild-type plants. Distinct sets of bacteria and fungi were found to display rhythmic changes in abundance in the rhizosphere of both of these mutants, suggesting that abnormal patterns of rhythmicity in the plant host caused temporal reprogramming of the rhizosphere microbiome. This was associated with changes in microbial community structure, including changes in the abundance of fungal guilds known to impact on plant health. Under constant environmental conditions, microbial rhythmicity persisted in the rhizosphere of wild-type plants, indicating control by a circadian oscillator. In contrast, loss of rhythmicity inlhy-oxplants was associated with disrupted rhythms for the majority of rhizosphere microbiota.

Conclusions

These results show that aberrant function of the plant circadian clock is associated with altered rhythmicity of rhizosphere bacteria and fungi. In the long term, this leads to changes in composition of the rhizosphere microbiome, with potential consequences for plant health. Further research will be required to understand the functional implications of these changes and how they impact on plant health and productivity.
HP1a-mediated heterochromatin formation promotes antimicrobial responses against Pseudomonas aeruginosa infection
Authors: Wu Po-Jen , Yan Shian-Jang
Published: October 2022

Background

Pseudomonas aeruginosa is a Gram-negative bacterium that causes severe infectious disease in diverse host organisms, including humans. Effective therapeutic options for P. aeruginosa infection are limited due to increasing multidrug resistance and it is therefore critical to understand the regulation of host innate immune responses to guide development of effective therapeutic options. The epigenetic mechanisms by which hosts regulate their antimicrobial responses against P. aeruginosa infection remain unclear. Here, we used Drosophila melanogaster to investigate the role of heterochromatin protein 1a (HP1a), a key epigenetic regulator, and its mediation of heterochromatin formation in antimicrobial responses against PA14, a highly virulent P. aeruginosa strain.

Results

Animals with decreased heterochromatin levels showed less resistance to P. aeruginosa infection. In contrast, flies with increased heterochromatin formation, either in the whole organism or specifically in the fat body—an organ important in humoral immune response—showed greater resistance to P. aeruginosa infection, as demonstrated by increased host survival and reduced bacterial load. Increased heterochromatin formation in the fat body promoted the antimicrobial responses via upregulation of fat body immune deficiency (imd) pathway-mediated antimicrobial peptides (AMPs) before and in the middle stage of P. aeruginosa infection. The fat body AMPs were required to elicit HP1a-mediated antimicrobial responses against P. aeruginosa infection. Moreover, the levels of heterochromatin in the fat body were downregulated in the early stage, but upregulated in the middle stage, of P. aeruginosa infection.

Conclusions

These data indicate that HP1a-mediated heterochromatin formation in the fat body promotes antimicrobial responses by epigenetically upregulating AMPs of the imd pathway. Our study provides novel molecular, cellular, and organismal insights into new epigenetic strategies targeting heterochromatin that have the potential to combat P. aeruginosa infection.
Endoplasmic reticulum-quality control pathway and endoplasmic reticulum-associated degradation mechanism regulate the N-glycoproteins and N-glycan structures in the diatom Phaeodactylum tricornutum
Authors: Chen Jichen , Du Hong , Liu Zidong , Li Tangcheng , Du Hua , Wang Wanna , Aslam Muhammad , Chen Weizhou , Li Ping , Luo Haodong , Fang Hao , Liu Xiaojuan
Published: October 2022

Tunicamycin inhibits the first step of protein N-glycosylation modification. However, the physiological, transcriptomic, and N-glycomic effects of tunicamycin on important marine diatom Phaeodactylum tricornutum are still unknown. In this study, comprehensive approaches were used to study the effects of tunicamycin stress. The results showed that cell growth and photosynthesis were significantly inhibited in P. tricornutum under the tunicamycin stress. The soluble protein content was significantly decreased, while the soluble sugar and neutral lipid were dramatically increased to orchestrate the balance of carbon and nitrogen metabolisms. The stress of 0.3 μg ml−1 tunicamycin resulted in the differential expression of ERQC and ERAD related genes. The upregulation of genes involved in ERQC pathway, the activation of anti-oxidases and the differential expression of genes related with ERAD mechanism might be important for maintaining homeostasis in cell. The identification of N-glycans, especially complex-type N-glycan structures enriched the N-glycan database of diatom P. tricornutum and provided important information for studying the function of N-glycosylation modification on proteins. As a whole, our study proposed working models of ERQC and ERAD will provide a solid foundation for further in-depth study of the related mechanism and the diatom expression system.
A review on the role of cyclin dependent kinases in cancers
Authors: Ghafouri-Fard Soudeh , Khoshbakht Tayyebeh , Hussen Bashdar Mahmud , Dong Peixin , Gassler Nikolaus , Taheri Mohammad , Baniahmad Aria , Dilmaghani Nader Akbari
Published: October 2022

The Cyclin-dependent kinase (CDK) class of serine/threonine kinases has crucial roles in the regulation of cell cycle transition and is mainly involved in the pathogenesis of cancers. The expression of CDKs is controlled by a complex regulatory network comprised of genetic and epigenetic mechanisms, which are dysregulated during the progression of cancer. The abnormal activation of CDKs results in uncontrolled cancer cell proliferation and the induction of cancer stem cell characteristics. The levels of CDKs can be utilized to predict the prognosis and treatment response of cancer patients, and further understanding of the function and underlying mechanisms of CDKs in human tumors would pave the way for future cancer therapies that effectively target CDKs. Defects in the regulation of cell cycle and mutations in the genes coding cell-cycle regulatory proteins lead to unrestrained proliferation of cells leading to formation of tumors. A number of treatment modalities have been designed to combat dysregulation of cell cycle through affecting expression or activity of CDKs. However, effective application of these methods in the clinical settings requires recognition of the role of CDKs in the progression of each type of cancer, their partners, their interactions with signaling pathways and the effects of suppression of these kinases on malignant features. Thus, we designed this literature search to summarize these findings at cellular level, as well as in vivo and clinical levels.
Combined association of triglyceride-glucose index and systolic blood pressure with all-cause and cardiovascular mortality among the general population
Authors: Yu Yu , Gu Min , Huang Hao , Cheng Sijing , Deng Yu , Cai Chi , Chen Xuhua , Niu Hongxia , Ning Xiaohui , Hua Wei
Published: October 2022

Background

The combined association of triglyceride-glucose (TyG) index and different systolic blood pressure (SBP) levels with all-cause and cardiovascular mortality among the general population remains unclear.

Methods

In this study, 6245 individuals were from the National Health and Nutrition Examination Survey (1999–2002). The study endpoints were all-cause and cardiovascular mortality. Multivariate Cox proportional hazards regression models were used to explore the combined association of TyG index and different SBP levels with all-cause and cardiovascular mortality.

Results

During a mean follow-up period of 66.8 months, a total of 284 all-cause deaths (331/100000 person-years) and 61 cardiovascular deaths (66/100000 person-years) were recorded. Multivariate Cox regression analysis revealed that the combination of low TyG index and low SBP (< 120 mmHg and < 130 mmHg) was associated with a reduced risk of all-cause and cardiovascular mortality than others. However, survival benefit was not observed in the combined group with the low TyG index and SBP < 140 mmHg. Furthermore, the mortality rate in the combined group of low TyG index and low SBP gradually increased with the elevation of SBP level.

Conclusion

The combination of low TyG index and low SBP (< 120 mmHg and < 130 mmHg) was associated with a lower risk of all-cause and cardiovascular mortality. However, no survival benefit was observed in the combined group of low TyG index and SBP < 140 mmHg.
Integrative analysis of m3C associated genes reveals METTL2A as a potential oncogene in breast Cancer
Authors: Wang Shuai , Li Huiting , Liu Jiheng , Zhang Qianqian , Xu Wei , Xiang Juanjuan , Fang Li , Xu Ping , Li Zheng
Published: October 2022

RNA methylation modifications, especially m6A mRNA modification, are known to be extensively involved in tumor development. However, the relationship between N3-methylcytidine (m3C) related genes and tumorigenesis has rarely been studied. In this research, we found that m3C-related genes were expressed at different levels and affected patients’ prognosis across multiple cancer types from The Cancer Genome Atlas and multi-omics levels. Importantly, methyltransferase-like proteins 2A (METTL2A) had a high amplification frequency (~ 7%) in patients with breast invasive carcinoma (BRCA), and its overexpression was an independent predictor of poor overall survival. Enrichment analysis of associated genes revealed that METTL2A may activate DNA synthesis and cell proliferation pathways in BRCA cells. Through drug sensitivity analysis, Trifluridine, PD407824, and Taselisib were shown to be effective drugs for METTL2A-positive BRCA patients. Overall, our research conducts a holistic view of the expression level and prognostic signature of m3C-related genes with multiple malignancies. Importantly, METTL2A has been intensely explored as a potential oncogene in BRCA, to aid the development of potential drug agents for precision therapy in breast cancer patients.
HPV 16 E7 alters translesion synthesis signaling
Authors: Wendel Sebastian O. , Stoltz Avanelle , Xu Xuan , Snow Jazmine A. , Wallace Nicholas
Published: October 2022

A subset of human papillomaviruses (HPVs) are the cause of virtually every cervical cancer. These so-called “high-risk” HPVs encode two major oncogenes (HPV E6 and E7) that are necessary for transformation. Among "high-risk” HPVs, HPV16 causes most cervical cancers and is often used as a representative model for oncogenic HPVs. The HPV16 E7 oncogene facilitates the HPV16 lifecycle by binding and destabilizing RB, which ensures the virus has access to cellular replication machinery. RB destabilization increases E2F1-responsive gene expression and causes replication stress. While HPV16 E6 mitigates some of the deleterious effects associated with this replication stress by degrading p53, cells undergo separate adaptations to tolerate the stress. Here, we demonstrate that this includes the activation of the translesion synthesis (TLS) pathway, which prevents replication stress from causing replication fork collapse. We show that significantly elevated TLS gene expression is more common in cervical cancers than 15 out of the 16 the other cancer types that we analyzed. In addition to increased TLS protein abundance, HPV16 E7 expressing cells have a reduced ability to induct a critical TLS factor (POLη) in response to replication stress-inducing agents. Finally, we show that increased expression of at least one TLS gene is associated with improved survival for women with cervical cancer.
Whether individualized dose escalation should be recommended for lymph nodes with different sizes in the definitive radiotherapy of cervical cancer?
Authors: Lv Xiaojuan , Rao Huiting , Feng Tao , Wu Chufan , Lou Hanmei
Published: October 2022

Background and purpose

Dose escalation for positive node maybe improve the regional control of patients with node-positive cervical cancer, but the optimal dose for nodes of different sizes remains controversial. The purpose of this study was to explore the individualized dose escalation for lymph nodes (LNs) with different sizes in the definitive radiotherapy of cervical cancer.

Methods

A total of 1002 cervical cancer patients with the International Federation of Gynecology and Obstetrics (FIGO 2009) stage IB1–IVA, who were treated by definitively radiotherapy between September 2013 and December 2016 were enrolled. All LNs identified by computed tomography/magnetic resonance imaging (CT/MRI) were assigned into three groups according to the short diameters of < 1 cm, 1–2 cm or ≥ 2 cm at pretreatment.

Results

In total, 580 patients with 1310 LNs were detected. The nodal control rate in groups of LNs < 1 cm, 1–2 cm and ≥ 2 cm was 99.4%, 96%, and 75.9%, respectively (P = 0.000). Among LNs < 1 cm, the control, overall survival (OS) and progression-free survival (PFS) rates did not significantly differ among three dose-based groups (≤ 50.4 Gy, 50.4–60 Gy, > 60 Gy) (control rate, 99.4% vs. 99.3% vs. 100%, P = 0.647) (5-year OS, 76.2% vs. 79% vs. 81.6%, P = 0.682) (5-year PFS, 74.1% vs. 73.9% vs. 78.9% P = 0.713). Among LNs of 1–2 cm, the control and PFS rates were significantly higher in the group of dose ≥ 55 Gy than the group of dose < 55 Gy (control rate, 98% vs. 93.6%, P = 0.028) (5-year PFS, 69.6% vs. 56.7%, P = 0.025). However, this did not cause a significant difference for 5-year OS rate (72.6% vs. 68.3%, P = 0.5). Among LNs ≥ 2 cm, the control, OS, and PFS rates were higher in the group of dose ≥ 55 Gy than the group of dose < 55 Gy, while no significant difference was found (control rate, 82.1% vs. 63.2%, P = 0.107) (5-year OS, 60.6% vs. 37.5%, P = 0.141) (5-year PFS, 51.5% vs.37.5%, P = 0.232).

Conclusions

Radiation dose escalation is not necessary for LNs < 1 cm, and dose escalation of 55 Gy is enough for LNs of 1–2 cm.
LncRNA CASC9 promotes cell proliferation and invasion in osteosarcoma through targeting miR-874-3p/SOX12 axis
Authors: Qiu Haiyan , Yang Di , Li Xiaolin , Feng Fabo
Published: October 2022

Background

Osteosarcoma (OS) is a common primary malignant bone tumor. This study aimed to explore the biological role of long on-coding RNA (lncRNA) CASC9 and its regulatory mechanism in OC.

Methods

The CASC9 expressions in OS cells and tissues were measured using qRT-PCR. The functional role of CASC9 in OC was studied using MTT assay, colony formation assay, transwell invasion assay, and xenograft tumor assay. In addition, the mechanism of CASC9 function was determined using luciferase reporter assay. Western blot was used to analyze protein expressions in our paper.

Results

LncRNA CASC9 was found to be up-regulated in OS. Knockdown of CASC9 inhibited the proliferation and invasion of OS cells. Besides, miR-874-3p was identified as the target of CASC9, and SOX12 acted as a potential target of miR-874-3p. The down-regulation of miR-874-3p recovered the reduction in cell invasion and proliferation in vitro which were induced by CASC9 knockdown and delayed the tumor progression in vivo.

Conclusion

LncRNA CASC9 promotes cell proliferation and invasion in OS via miR-874-3p/SOX12 axis. Our study might provide novel biomarkers and potential therapeutic targets for OS treatment.
Effect of different feeding methods on gastrointestinal function in critical patients (DFM-GFC): study protocol for a randomized controlled trial
Authors: Yang Guang , Deng Aijing , Zheng Bojun , Li Jian , Yu Yi , Ouyang Honglian , Huang Xin , Chen Hong
Published: October 2022

Background

Enteral nutrition is a major pathway of nutrition for patients requiring critical care. However, it remains unclear whether intermittent or continuous feeding is the better approach, especially after nasogastric enteral nutrition via a gastric tube. Therefore, this randomized controlled clinical study was designed to observe the effects of different methods on critically ill patients.

Methods

Different Feeding Methods on Gastrointestinal Function of Critical patients (DFM-GFC) is a randomized clinical study that will be performed to assess the effects of three feeding methods on critically ill patients. A total of 90 critically ill patients will be equally randomized into three groups: continuous feeding, cyclic feeding, and intermittent feeding. The patients will be administered a gastrointestinal nutrition preparation over 24 h via a gastric tube or over 16 h via an intermittent pump. The primary outcome is the mean duration (days) to reach the caloric goal in each group. Secondary outcomes include the rate of onset of gastric residual, abdominal pressure, the rate of onset pneumonia, and the proportion of individuals achieving the caloric goal. Additionally, the length of intensive care unit (ICU) stay and mortality rate at 28 days post-enrolment will be evaluated.

Discussion

This study will observe the effects of different feeding methods on various parameters, such as the energy target and gastrointestinal motility, in critically ill patients to improve quality of life and reduce the case fatality rate. The purpose of this study is to explore whether there is a more effective, safer and cost-efficient feeding method for the clinical treatment of critically ill patients.

Trial registration

ID: NCT04224883, ClinicalTrials.gov, registered January 9, 2020