bluuebunny/crossref_metadata_2025 huggingface dataset:
Stroke epidemiology and outcomes of stroke patients in Nepal: a systematic review and meta-analysis
Authors: Paudel Raju , Tunkl Christine , Shrestha Shakti , Subedi Ram Chandra , Adhikari Ayush , Thapa Lekhjung , Gajurel Bikram Prasad , Chandra Avinash , Kharel Ghanashyam , Jalan Pankaj , Phuyal Subash , Pokharel Babu Ram , Acharya Subi , Bogati Kanchan , Jha Pinky , Kharbuja Naresh , Gumbinger Christoph
Published: September 2023

Background

With an increasing burden of stroke, it is essential to minimize the incidence of stroke and improve stroke care by emphasizing areas that bring out the maximum impact. The care situation remains unclear in the absence of a national stroke care registry and a lack of structured hospital-based data monitoring. We conducted this systematic review and meta-analysis to assess the status of stroke care in Nepal and identify areas that need dedicated improvement in stroke care.

Methods

A systematic literature review was conducted to identify all studies on stroke epidemiology or stroke care published between 2000 and 2020 in Nepal. Data analysis was done with Statistical Package for Social Sciences (SPSS) and Comprehensive Meta-analysis (CMA-3).

Results

We identified 2533 studies after database searching, and 55 were included in quantitative and narrative synthesis. All analyses were done in tertiary care settings in densely populated central parts of Nepal. Ischemic stroke was more frequent (70.87%) than hemorrhagic (26.79%), and the mean age of stroke patients was 62,9 years. Mortality occurred in 16.9% (13-21.7%), thrombolysis was performed in 2.39% of patients, and no studies described thrombectomy or stroke unit care.

Conclusion

The provision of stroke care in Nepal needs to catch up to international standards, and our systematic review demonstrated the need to improve access to quality stroke care. Dedicated studies on establishing stroke care units, prevention, rehabilitation, and studies on lower levels of care or remote regions are required.
Neutrophil-to-lymphocyte ratio is an independent predictor for neurological disability in patients with idiopathic transverse myelitis
Authors: Min Je Hong , Sohn Sung-Yeon , Lee Seung Yeon , Seo Sang Hyun , Kim Shin Yeop , Park Bumhee , Kim Seung Il , Joo In Soo
Published: September 2023

Introduction

The neutrophil-to-lymphocyte ratio (NLR) has been found to be useful in the prognostication of immune-mediated neurological disorders because it roughly reflects the systemic innate immune response compared to the adaptive immune response. However, studies on the validity of NLR in demyelinating disorders of the central nervous system have shown conflicting results. Therefore, we aimed to investigate NLR in the idiopathic transverse myelitis (ITM) cohort.

Methods

We retrospectively analyzed the cohort data of patients with ITM between January 2006 and February 2020. The medical data of all patients with myelitis were reviewed to exclude patients with disease-associated myelopathy according to predefined exclusion criteria. The relationship between the natural log-transformed NLR (lnNLR) and the clinical, paraclinical, and imaging data was evaluated. Factors associated with neurological disability were analyzed using a linear mixed-effects model. Predictive factors for moderate-to-severe neurological disability (Expanded Disability Status Scale [EDSS] score ≥ 4) were investigated.

Results

A total of 124 participants were included in the analysis. The lnNLR correlated with EDSS and lesion length. Linear mixed-effects analysis showed that age, lesion length, and lnNLR were independently associated with neurological disabilities. Multivariable logistic regression revealed that lnNLR (odds ratio [OR] = 4.266, 95% confidence interval [CI] = 1.220–14.912, p = 0.023) and lesion length (OR = 1.848, 95% CI = 1.249–2.734, p = 0.002) were independent predictive factors of the worst neurological disability.

Conclusion

NLR may be used as an independent prognostic factor for predicting poor neurological outcomes in patients with ITM.
ICD-11 and mental disorders: important changes, controversies, and future directions
Authors: Seemüller Florian
Published: September 2023

About a year and a half after publishing ICD-11, we aim to gather initial feedback, comments, opinions, and even recent study results from experts in the relevant fields through this collection. We hope to facilitate a preliminary summary of whether the new classification truly represents progress, and how it has changed treatment, and research of mental illnesses.
Blood miRNA levels associated with ADHD traits in children across six European birth cohorts
Authors: Dypås Lene B. , Duale Nur , Olsen Ann-Karin , Bustamante Mariona , Maitre Lea , Escaramis Geòrgia , Julvez Jordi , Aguilar-Lacasaña Sofia , Andrusaityte Sandra , Casas Maribel , Vafeiadi Marina , Grazuleviciene Regina , Heude Barbara , Lepeule Johanna , Urquiza Jose , Wright John , Yang Tiffany C. , Vrijheid Martine , Gützkow Kristine B.
Published: September 2023

Background

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent and highly heritable neurodevelopmental disorder of major societal concern. Diagnosis can be challenging and there are large knowledge gaps regarding its etiology, though studies suggest an interplay of genetic and environmental factors involving epigenetic mechanisms. MicroRNAs (miRNAs) show promise as biomarkers of human pathology and novel therapies, and here we aimed to identify blood miRNAs associated with traits of ADHD as possible biomarker candidates and further explore their biological relevance.

Methods

Our study population consisted of 1126 children (aged 5–12 years, 46% female) from the Human Early Life Exposome study, a study spanning six ongoing population-based European birth cohorts. Expression profiles of miRNAs in whole blood samples were quantified by microarray and tested for association with ADHD-related measures of behavior and neuropsychological functions from questionnaires (Conner’s Rating Scale and Child Behavior Checklist) and computer-based tests (the N-back task and Attention Network Test).

Results

We identified 29 miRNAs significantly associated (false discovery rate < .05) with the Conner’s questionnaire-rated trait hyperactivity, 15 of which have been linked to ADHD in previous studies. Investigation into their biological relevance revealed involvement in several pathways related to neurodevelopment and function, as well as being linked with other neurodevelopmental or psychiatric disorders known to overlap with ADHD both in symptomology, genetic risk, and co-occurrence, such as autism spectrum disorder or schizophrenia. An additional three miRNAs were significantly associated with Conner’s-rated inattention. No associations were found with questionnaire-rated total ADHD index or with computer-based tests.

Conclusions

The large overlap of our hyperactivity-associated miRNAs with previous studies on ADHD is intriguing and warrant further investigation. Though this study should be considered explorative and preliminary, these findings contribute towards identifying a set of miRNAs for use as blood-based biomarkers to aid in earlier and easier ADHD diagnosis.
Microvesicle-associated and circulating microRNAs in diabetic dyslipidemia: miR-218, miR-132, miR-143, and miR-21, miR-122, miR-155 have biomarker potential
Authors: Nemecz Miruna , Stefan Diana Simona , Comarița Ioana Karla , Constantin Alina , Tanko Gabriela , Guja Cristian , Georgescu Adriana
Published: September 2023

Background

Circulating MicroRNAs (miRNAs) carried by microvesicles (MVs) have various physiological and pathological functions by post-transcriptional regulation of gene expression being considered markers for many diseases including diabetes and dyslipidemia. We aimed to identify new common miRNAs both in MVs and plasma that could be predictive biomarkers for diabetic dyslipidemia evolution.

Methods

For this purpose, plasma from 63 participants in the study (17 type 2 diabetic patients, 17 patients with type 2 diabetes and dyslipidemia, 14 patients with dyslipidemia alone and 15 clinically healthy persons without diabetes or dyslipidemia) was used for the analysis of circulating cytokines, MVs, miRNAs and MV-associated miRNAs.

Results

The results uncovered three miRNAs, miR-218, miR-132 and miR-143, whose expression was found to be significantly up-regulated in both circulating MVs and plasma from diabetic patients with dyslipidemia. These miRNAs showed significant correlations with important plasma markers, representative of this pathology. Thus, MV/plasma miR-218 was negatively correlated with the levels of erythrocyte MVs, plasma miR-132 was positively connected with MV miR-132 and negatively with uric acid and erythrocyte plasma levels, and plasma miR-143 was negatively related with creatinine levels and diastolic blood pressure. Also, three miRNAs common to MV and plasma, namely miR-21, miR-122, and miR-155, were identified to be down-regulated and up-regulated, respectively, in diabetic dyslipidemia. In addition, MV miR-21 was positively linked with cholesterol plasma levels and plasma miR-21 with TNFα plasma levels, MV miR-122 was negatively correlated with LDL-c levels and plasma miR-122 with creatinine and diastolic blood pressure and positively with MV miR-126 levels, MV miR-155 was positively associated with cholesterol and total MV levels and negatively with HDL-c levels, whereas plasma miR-155 was positively correlated with Il-1β plasma levels and total MV levels and negatively with MV miR-223 levels.

Conclusions

In conclusion, miR-218, miR-132, miR-143, and miR-21, miR-122, miR-155 show potential as biomarkers for diabetic dyslipidemia, but there is a need for more in-depth studies. These findings bring new information regarding the molecular biomarkers specific to diabetic dyslipidemia and could have important implications for the treatment of patients affected by this pathology.
A fine-tuned yeast surface-display/secretion platform enables the rapid discovery of neutralizing antibodies against Clostridioides difficile toxins
Authors: Sun Ying , Zhang Yongrong , Yu Hua , Saint Fleur Ashley , Yu Di , Yang Zhiyong , Feng Hanping
Published: September 2023

Background

Neutralizing antibody plays a key role in protecting hosts from invasive pathogens and their virulent components. Current high-throughput assays for antibody screening are based on binding activities. However, those antibodies with high affinity may not have neutralizing activities. Subsequent functionality assays are necessary to identify neutralizing antibodies from binders with high affinity to their target antigens, which is laborious and time-consuming. Therefore, a versatile platform that can rapidly identify antibodies with both high binding affinity and neutralizing activity is desired to curb future pandemics like COVID-19.

Results

In this proof-of-concept study, we adapted Saccharomyces cerevisiae to either display human antibodies on the yeast surface or secrete soluble antibodies into the cultivation supernatant under a controllable ‘switch’ through different carbon source induced promoters. Initially, an engineered chimeric-bispecific Fab antibody, derived from humanized nanobodies against both Clostridioides difficile toxin A and B (TcdA and TcdB), was successfully expressed either on the yeast cell surface or in the culture medium with intact bioactivity, suggesting the applicability of our system in antibody display and secretion. Next, a combinatorial Fab library was constructed from B cells isolated from a convalescent patient with a high serological neutralizing titer against TcdB. Following three rounds of magnetic bead enrichment and one round of flow cytometry sorting, antibodies against TcdB were enriched efficiently. We then sorted out single binders with high binding affinity and induced them to express soluble antibodies in culture medium. The neutralizing activity of culture supernatant was analyzed using cell-based assay immediately. This way, we rapidly identified two unique neutralizers (out of seven binders) that can neutralize the cytotoxicity of TcdB.

Conclusion

The antibody screening platform described here simplifies the neutralizing antibody discovery procedure and will be an attractive alternative for screening functional antibodies against infectious diseases.
A survey of Transformer applications for histopathological image analysis: New developments and future directions
Authors: Atabansi Chukwuemeka Clinton , Nie Jing , Liu Haijun , Song Qianqian , Yan Lingfeng , Zhou Xichuan
Published: September 2023

Transformers have been widely used in many computer vision challenges and have shown the capability of producing better results than convolutional neural networks (CNNs). Taking advantage of capturing long-range contextual information and learning more complex relations in the image data, Transformers have been used and applied to histopathological image processing tasks. In this survey, we make an effort to present a thorough analysis of the uses of Transformers in histopathological image analysis, covering several topics, from the newly built Transformer models to unresolved challenges. To be more precise, we first begin by outlining the fundamental principles of the attention mechanism included in Transformer models and other key frameworks. Second, we analyze Transformer-based applications in the histopathological imaging domain and provide a thorough evaluation of more than 100 research publications across different downstream tasks to cover the most recent innovations, including survival analysis and prediction, segmentation, classification, detection, and representation. Within this survey work, we also compare the performance of CNN-based techniques to Transformers based on recently published papers, highlight major challenges, and provide interesting future research directions. Despite the outstanding performance of the Transformer-based architectures in a number of papers reviewed in this survey, we anticipate that further improvements and exploration of Transformers in the histopathological imaging domain are still required in the future. We hope that this survey paper will give readers in this field of study a thorough understanding of Transformer-based techniques in histopathological image analysis, and an up-to-date paper list summary will be provided athttps://github.com/S-domain/Survey-Paper.
Factors that influence evidence-informed meso-level regional primary health care planning: a qualitative examination and conceptual framework
Authors: Windle Alice , Javanparast Sara , Freeman Toby , Baum Fran
Published: September 2023

Background

Evidence-informed primary health care (PHC) planning in decentralised, meso-level regional organisations has received little research attention. In this paper we examine the factors that influence planning within this environment, and present a conceptual framework.

Methods

We employed mixed methods: case studies of five Australian Primary Health Networks (PHNs), involving 29 primary interviews and secondary analysis of 38 prior interviews; and analysis of planning documents from all 31 PHNs. The analysis was informed by a WHO framework of evidence-informed policy-making, and institutional theory.

Results

Influential actors included federal and state/territory governments, Local Health Networks, Aboriginal Community Controlled Health Organisations, local councils, public hospitals, community health services, and providers of allied health, mental health and aged care services. The federal government was most influential, constraining PHNs’ planning scope, time and funding. Other external factors included: the health service landscape; local socio-demographic and geographic characteristics; (neoliberal) ideology; interests and politics; national policy settings and reforms; and system reorganisation. Internal factors included: organisational structure; culture, values and ideology; various capacity factors; planning processes; transition history; and experience. The additional regional layer of context adds to the complexity of planning.

Conclusions

Like national health policy-making, meso-level PHC planning occurs in a complex environment, but with additional regional factors and influences. We have developed a conceptual framework of the meso-level PHC planning environment, which can be employed by similar regional organisations to elucidate influential factors, and develop strategies and tools to promote transparent, evidence-informed PHC planning for better health outcomes.
“It’s important to foster open discussion about the topic”: development, implementation, and evaluation of an ethics of abortion independent learning module for second year medical students
Authors: McCarty Catherine A. , Hutto Sarah L. , Shaw Aubie K.
Published: September 2023

Purpose

Despite the frequency of abortions, one-third of medical schools in the US and Canada did not include coverage of that topic, according to a survey conducted in 2002–2005. The purpose of this project was to develop, implement, and evaluate a module for second year medical students related to the ethics of abortion.

Methods

The module was designed as Independent Learning Time (ILT). The stated purpose was for students to consider some of the recent debate in the ethics literature related to conscientious objection and abortion and how personal views may influence future practice. The ILT included readings and Power Points to view. Students were asked to write a one-page reflection on one of three writing prompts.

Results

The most commonly selected writing prompt in three classes was on personal values in relation to abortion (56.5%), followed by information about nearest provider of reproductive services to rural preceptor site (34.7%), followed by conscientious objection (23.3%). We received many positive comments about the ILT, including: “First, I would like to acknowledge my gratitude for this assignment and its subject. I believe it is very important that future physicians learn the entirety of women’s reproductive health care, including abortion and contraception, but unfortunately this is not always the case in medical training”.

Conclusions

There has been an extremely positive response to the ILT. With the exception of the prompt specific to our regional campus mission that includes rural preceptorships during the preclinical years, this module could be implementable at other medical schools.
Well-being is associated with cortical thickness network topology of human brain
Authors: Li Yubin , Li Chunlin , Jiang Lili
Published: September 2023

Background

Living a happy and meaningful life is an eternal topic in positive psychology, which is crucial for individuals’ physical and mental health as well as social functioning. Well-being can be subdivided into pleasure attainment related hedonic well-being or emotional well-being, and self-actualization related eudaimonic well-being or psychological well-being plus social well-being. Previous studies have mostly focused on human brain morphological and functional mechanisms underlying different dimensions of well-being, but no study explored brain network mechanisms of well-being, especially in terms of topological properties of human brain morphological similarity network.

Methods

Therefore, in the study, we collected 65 datasets including magnetic resonance imaging (MRI) and well-being data, and constructed human brain morphological network based on morphological distribution similarity of cortical thickness to explore the correlations between topological properties including network efficiency and centrality and different dimensions of well-being.

Results

We found emotional well-being was negatively correlated with betweenness centrality in the visual network but positively correlated with eigenvector centrality in the precentral sulcus, while the total score of well-being was positively correlated with local efficiency in the posterior cingulate cortex of cortical thickness network.

Conclusions

Our findings demonstrated that different dimensions of well-being corresponded to different cortical hierarchies: hedonic well-being was involved in more preliminary cognitive processing stages including perceptual and attentional information processing, while hedonic and eudaimonic well-being might share common morphological similarity network mechanisms in the subsequent advanced cognitive processing stages.
Characteristics of hindfoot morphology and ankle range of motion in young women with hallux valgus
Authors: Yokozuka Mieko , Okazaki Kanako
Published: September 2023

Background

Hallux valgus occurs more frequently in women as they age; therefore, it is beneficial to prevent hallux valgus in younger women. The purpose of this study was to clarify the characteristics of hindfoot morphology and the range of motion of the ankle joint with hallux valgus in young women.

Methods

The participants were 140 young women (mean age 18.8 ± 0.6 years). A three‐dimensional footprint automatic measurement apparatus was used to measure the hallux valgus angle in the standing position and the arch‐height ratio and heel‐floor angle (HFA) in the standing and chair‐sitting positions. The amount of change in foot morphology owing to differences in posture was calculated. The range of motion of the ankle joint dorsiflexion, plantarflexion, inversion, and eversion was measured. Participants were classified into two groups according to the presence of hallux valgus. Statistical analysis was used to compare hindfoot morphology and range of motion between the two groups, and the correlation between foot morphology and range of motion was investigated depending on the presence of hallux valgus.

Results

With hallux valgus, the HFA tilted inwards (p = 0.010), and the change in the arch‐height ratio due to the difference in posture was large (p = 0.021). There was no difference in the range of motion of the ankle joints with or without hallux valgus. In women with hallux valgus, the amount of change in arch height and HFA was correlated with the range of motion of eversion (r = 0.391, p = 0.027; r = ‐0.362, p = 0.042).

Conclusions

With hallux valgus, the hindfoot pronated, and the arch height decreased from sitting to standing. Furthermore, the amount of change in the hindfoot and midfoot due to posture was related to the range of motion of eversion.
Pretreatment with a long-acting GnRH agonist for frozen-thawed embryo transfer cycles: how to improve live birth?
Authors: Xu Bin , Hou Zhaojuan , Liu Nenghui , Zhao Jing , Li Yanping
Published: September 2023

Background

Whether pretreatment with gonadotropin-releasing hormone agonist (GnRHa) can improve the pregnancy outcomes in frozen-thawed embryo transfer (FET) cycles is controversial. The inconsistencies in the results of different studies would be related to the characteristics of the included patients and the protocol of GnRHa use. In this study, we investigated the efficacy of pretreatment with a long-acting GnRH agonist in the early follicular phase of FET cycles and determined which population was suitable for the protocol.

Results

We retrospectively included 630 and 1141 patients in the GnRHa FET and hormone replacement treatment (HRT) FET without GnRHa groups respectively, between October 2017 and March 2019 at a university-affiliated in vitro fertilization center. On the second or third day of menstruation, 3.75 mg of leuprorelin was administered. After 14 days, HRT was initiated for endometrial preparation. No significant differences were observed between the two groups in terms of patient characteristics. However, the GnRHa FET group showed a higher percentage of endometrium with a triple line pattern (94.8% vs 89.6%, p < 0.001) on the day of progesterone administration, with increased implantation (35.6% vs 29.8%, p = 0.005), clinical pregnancy (49.8% vs 43.3%, p = 0.008), and live birth rate (39.4% vs 33.7%, p = 0.016), than the HRT FET cycles with similar endometrial thickness, ectopic pregnancy and early miscarriage rates. Binary logistic regression analysis showed the GnRHa FET group to be associated with an increased chance of clinical pregnancy (P=0.028, odds ratio [OR] 1.32, 95% confidence interval [CI] 1.03–1.70) and live birth (P=0.013, odds ratio [OR] 1.34, 95% confidence interval [CI] 1.06–1.70) compared to the HRT FET without GnRHa group. After subgroup analysis, we found that the GnRHa FET group showed a significantly higher live birth rate in the subgroups of age < 40 years, primary infertility, with polycystic ovary syndrome (PCOS), and irregular menstruation.

Conclusions

Pretreatment with a long-acting GnRHa during the early follicular phase improved the live birth rate in FET cycles. Age < 40 years, primary infertility, PCOS, and irregular menstruation are effective indications for endometrial preparation with GnRHa pretreatment in FET cycles. However, further randomized controlled trials are required to verify these results.
Sonometric assessment of cough predicts extubation failure: SonoWean—a proof-of-concept study
Authors: Bonny Vincent , Joffre Jeremie , Gabarre Paul , Urbina Tomas , Missri Louai , Ladoire Mathilde , Gasperment Maxime , Baudel Jean-Luc , Guidet Bertrand , Dumas Guillaume , Maury Eric , Brochard Laurent , Ait-Oufella Hafid
Published: September 2023

Background

Extubation failure is associated with increased mortality. Cough ineffectiveness may be associated with extubation failure, but its quantification for patients undergoing weaning from invasive mechanical ventilation (IMV) remains challenging.

Methods

Patients under IMV for more than 24 h completing a successful spontaneous T-tube breathing trial (SBT) were included. At the end of the SBT, we performed quantitative sonometric assessment of three successive coughing efforts using a sonometer. The mean of the 3-cough volume in decibels was named Sonoscore.

Results

During a 1-year period, 106 patients were included. Median age was 65 [51–75] years, mainly men (60%). Main reasons for IMV were acute respiratory failure (43%), coma (25%) and shock (17%). Median duration of IMV at enrollment was 4 [3–7] days. Extubation failure occurred in 15 (14%) patients. Baseline characteristics were similar between success and failure extubation groups, except percentage of simple weaning which was lower and MV duration which was longer in extubation failure patients. Sonoscore was significantly lower in patients who failed extubation (58 [52–64] vs. 75 [70–78] dB, P < 0.001). After adjustment on MV duration and comorbidities, Sonoscore remained associated with extubation failure. Sonoscore was predictive of extubation failure with an area under the ROC curve of 0.91 (IC95% [0.83–0.99], P < 0.001). A threshold of Sonoscore < 67.1 dB predicted extubation failure with a sensitivity of 0.93 IC95% [0.70–0.99] and a specificity of 0.82 IC95% [0.73–0.90].

Conclusion

Sonometric assessment of cough strength might be helpful to identify patients at risk of extubation failure in patients undergoing IMV.
Factors influencing the outcome of volumetry tools for pulmonary nodule analysis: a systematic review and attempted meta-analysis
Authors: Guedes Pinto Erique , Penha Diana , Ravara Sofia , Monaghan Colin , Hochhegger Bruno , Marchiori Edson , Taborda-Barata Luís , Irion Klaus
Published: September 2023

Health systems worldwide are implementing lung cancer screening programmes to identify early-stage lung cancer and maximise patient survival. Volumetry is recommended for follow-up of pulmonary nodules and outperforms other measurement methods. However, volumetry is known to be influenced by multiple factors. The objectives of this systematic review (PROSPERO CRD42022370233) are to summarise the current knowledge regarding factors that influence volumetry tools used in the analysis of pulmonary nodules, assess for significant clinical impact, identify gaps in current knowledge and suggest future research. Five databases (Medline, Scopus, Journals@Ovid, Embase and Emcare) were searched on the 21st of September, 2022, and 137 original research studies were included, explicitly testing the potential impact of influencing factors on the outcome of volumetry tools. The summary of these studies is tabulated, and a narrative review is provided. A subset of studies (n = 16) reporting clinical significance were selected, and their results were combined, if appropriate, using meta-analysis. Factors with clinical significance include the segmentation algorithm, quality of the segmentation, slice thickness, the level of inspiration for solid nodules, and the reconstruction algorithm and kernel in subsolid nodules. Although there is a large body of evidence in this field, it is unclear how to apply the results from these studies in clinical practice as most studies do not test for clinical relevance. The meta-analysis did not improve our understanding due to the small number and heterogeneity of studies testing for clinical significance.

Critical relevance statement

Many studies have investigated the influencing factors of pulmonary nodule volumetry, but only 11% of these questioned their clinical relevance in their management. The heterogeneity among these studies presents a challenge in consolidating results and clinical application of the evidence.

Key points

• Factors influencing the volumetry of pulmonary nodules have been extensively investigated.

• Just 11% of studies test clinical significance (wrongly diagnosing growth).

• Nodule size interacts with most other influencing factors (especially for smaller nodules).

• Heterogeneity among studies makes comparison and consolidation of results challenging.

• Future research should focus on clinical applicability, screening, and updated technology.

Graphical abstract
Value of placental virtual magnetic resonance elastography and intravoxel incoherent motion-based diffusion and perfusion in predicting adverse outcomes of small-for-gestational-age infants
Authors: Deng Jing , Cao Yuwei , Lu Yao , Song Jiacheng , Zhang Aining , Zhao Meng , Zhou Xin , Mu Xihu , Qu Feifei , Wu Feiyun , Chen Ting
Published: September 2023

Objective

It is critical to early monitor and manage small-for-gestational age (SGA) infants with truly adverse outcomes not detected by conventional methods. We aimed to explore the value of diffusion-weighted imaging (DWI)-based virtual magnetic resonance elastography (vMRE) and intravoxel incoherent motion (IVIM)-based biexponential and stretched exponential parameters in predicting adverse outcomes of SGA infants.

Methods

Twenty SGA infants with adverse outcomes and forty without adverse outcomes were included in this prospective study. One DWI-based vMRE parameter [the stiffness value (μdiff)], five IVIM–based parameters [true diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), diffusion distribution coefficient (DDC), and diffusion heterogeneity index (Alpha)] and apparent diffusion coefficient (ADC) were calculated and compared between groups. The predictive efficiency was compared by the logistic regression analysis and receiver operating characteristic curve analysis. The relationship between the μdiff value with gestational age was also evaluated.

Results

The placental μdiff value was remarkably higher, and the f, DDC, and ADC values were considerably lower in the SGA infants with adverse outcomes compared with those without adverse outcomes. The μdiff and f value were predictive risk factors for SGA infants with adverse outcomes. A combined predictive model (μdiff and f) improved the predictive efficacy. Moreover, there was no statistically significant correlation between the placental stiffness value and gestational age.

Conclusions

Functional MRI parameters to quantify placenta elastography and microcirculation in SGA patients. This might be a useful tool to assess placental function and a vital non-invasive supplement for predicting adverse outcomes of SGA infants.

Critical relevance statement

This prospective study shows DWI-based virtual magnetic resonance elastography and intravoxel incoherent motion-based functional parameters to quantify placenta elastography and microcirculation in small-for-gestational-age patients, which could complement existing non-invasive methods for monitoring and predicting neonatal perinatal adverse outcome.

Key points

• vMRE is an emerging non-invasive imaging technique for evaluating placenta stiffness.

• SGA infants with adverse outcome have stiffer placental elasticity and lower microcirculation.

• Risk factors combination displayed better efficacy in predicting adverse outcomes of SGA.

Graphical Abstract
Myocardial extracellular volume quantification with computed tomography—current status and future outlook
Authors: Cundari Giulia , Galea Nicola , Mergen Victor , Alkadhi Hatem , Eberhard Matthias
Published: September 2023

Non-invasive quantification of the extracellular volume (ECV) is a method for the evaluation of focal and diffuse myocardial fibrosis, potentially obviating the need for invasive endomyocardial biopsy. While ECV quantification with cardiac magnetic resonance imaging (ECVMRI) is already an established method, ECV quantification with CT (ECVCT) is an attractive alternative to ECVMRI, similarly using the properties of extracellular contrast media for ECV calculation. In contrast to ECVMRI, ECVCT provides a more widely available, cheaper and faster tool for ECV quantification and allows for ECV calculation also in patients with contraindications for MRI. Many studies have already shown a high correlation between ECVCT and ECVMRI and accumulating evidence suggests a prognostic value of ECVCT quantification in various cardiovascular diseases. Adding a late enhancement scan (for dual energy acquisitions) or a non-enhanced and late enhancement scan (for single-energy acquisitions) to a conventional coronary CT angiography scan improves risk stratification, requiring only minor adaptations of the contrast media and data acquisition protocols and adding only little radiation dose to the entire scan.

Critical relevance statement

This article summarizes the technical principles of myocardial extracellular volume (ECV) quantification with CT, reviews the literature comparing ECVCT with ECVMRI and histopathology, and reviews the prognostic value of myocardial ECV quantification for various cardiovascular disease.

Key points

• Non-invasive quantification of myocardial fibrosis can be performed with CT.

• Myocardial ECV quantification with CT is an alternative in patients non-eligible for MRI.

• Myocardial ECV quantification with CT strongly correlates with ECV quantification using MRI.

• Myocardial ECV quantification provides incremental prognostic information for various pathologies affecting the heart (e.g., cardiac amyloidosis).

Graphical Abstract
Carbapenem is not always the best choice in the treatment of septic shock
Authors: Wang Lu , Ma Xudong , Chen Yujie , Gao Sifa , He Huaiwu , Su Longxiang , Guo Yanhong , Shan Guangliang , Hu Yaoda , Zhou Xiang , Liu Dawei ,   China National Critical Care Quality Control Centre Group (China-NCCQC), Wang Xue , Guan Xiangdong , Kang Yan , Xiong Bin , Qin Bingyu , Qian Kejian , Wang Chunting , Zhao Mingyan , Ma Xiaochun , Yu Xiangyou , Lin Jiandong , Pan Aijun , Qiu Haibo , Shen Feng , Li Shusheng , Ai Yuhang , Xie Xiaohong , Yan Jing , Wu Weidong , Duan Meili , Wan Linjun , Yang Xiaojun , Liu Jian , Xu Hang , Jiang Dongpo , Xu Lei , Chen Zhuang , Lin Guoying , Yang Zhengping , Hu Zhenjie
Published: September 2023

Background

Septic shock is a global public health burden. In addition to the improvement of the level of individual care, the improvement of the overall hospital quality control management is also an essential key aspect of the Surviving Sepsis Campaign (SSC). Using of antibiotics is a cornerstone in the treatment of septic shock, so we conducted this study to investigate the influence of antibiotics and pathogenic bacteria on the mortality of septic shock at the level of overall hospital in China.

Methods

This was an observational database study in 2021 enrolled the data of 787 hospitals from 31 provinces/municipalities/autonomous regions of Mainland China collected in a survey from January 1, 2021 to December 31, 2021.

Results

The proportion of ICU patients with septic shock was 3.55%, while the patient mortality of septic shock was 23.08%. While carbapenem was the most preferred antibiotic medication used in 459 of the 782 hospitals, the preference for carbapenem did not show significant effect on the patient mortality in the treatment of septic shock (p-value 0.59). Compared with patients with fermenting bacteria as the most common pathogenic bacteria causing septic shock, patients with non-fermenting bacteria had a higher mortality (p-value 0.01).

Conclusions

Whether using carbapenem as the preferred antibiotic or not, did not show effect on the patient mortality of septic shock. Compared with patients with fermenting bacteria as the most common pathogenic bacteria, patients of septic shock with non-fermenting bacteria had a higher mortality.
Understanding the “individual drug reaction” from the perspective of the interaction between probiotics and lovastatin in vitro and in vivo
Authors: Shen Siyuan , Wang Jun , Ma Chenchen , Chen Yanni , Ding Hao , Zhang Jiachao
Published: September 2023

Background

The existence of the gut microbiota produces an “individual drug reaction.” As members of the intestinal microbiota, probiotics, although they have prebiotic functions, may accelerate the degradation of drugs, thereby affecting drug efficacy. Lovastatin is one of the well-recognized lipid-lowering drugs. Its main action site is the liver. Therefore, if it is degraded in advance by gastrointestinal probiotics, its efficacy may be reduced.

Results

Here, we designed a two-stage experiment in vitro and in vivo to explore the degradation of lovastatin by probiotics. In vitro, the degradation of lovastatin by 83 strains of Lactiplantibacillus plantarum and the “star strain” Lacticaseibacillus paracasei strain Shirota was investigated by high-performance liquid chromatography (HPLC). The results showed that probiotics could degrade lovastatin to varying degrees. Subsequently, we selected Lactiplantibacillus plantarum A5 (16.87%) with the strongest ability to degrade lovastatin, Lactiplantibacillus plantarum C3 (4.61%) with the weakest ability to degrade lovastatin and Lacticaseibacillus paracasei strain Shirota (17.6%) as representative probiotics for in vivo experiments. In vivo, the therapeutic effect of lovastatin combined with probiotics on golden hamsters with mixed hyperlipidemia was evaluated by measuring blood indicators, intestinal microbiota metagenomic sequencing, and the liver transcriptome. The results showed that the intake of probiotics did not affect the efficacy of lovastatin and could slow the inflammatory reaction of the liver.

Conclusions

The supplementation of probiotics produced beneficial metabolites in the intestine by promoting beneficial microbes. Intestinal metabolites affected the expression of the liver genes through the gut-liver axis, increased the relative content of the essential amino acids, and finally improved the liver inflammatory response of the host. This study aims to reveal the impact of probiotics on the human body from a unique perspective, suggesting the impact of taking probiotics while taking drugs.
Female genital schistosomiasis, human papilloma virus infection, and cervical cancer in rural Madagascar: a cross sectional study
Authors: Kutz Jean-Marc , Rausche Pia , Rasamoelina Tahinamandranto , Ratefiarisoa Sonya , Razafindrakoto Ravo , Klein Philipp , Jaeger Anna , Rakotomalala Rivo Solotiana , Rakotomalala Zoly , Randrianasolo Bodo Sahondra , McKay-Chopin Sandrine , May Jürgen , Rakotozandrindrainy Rapahel , Puradiredja Dewi Ismajani , Sicuri Elisa , Hampl Monika , Lorenz Eva , Gheit Tarik , Rakotoarivelo Rivo Andry , Fusco Daniela
Published: September 2023

Background

Women’s health in resource-limited settings can benefit from the integrated management of high-burden diseases, such as female genital schistosomiasis (FGS) and human papilloma virus (HPV)-related cervical cancer. In schistosomiasis-endemic countries such as Madagascar, data on FGS and HPV prevalence are lacking as well as preventive measures for both conditions. This study aims to estimate the prevalence of FGS and HPV in rural Madagascar, and to examine associated risk factors to identify opportunities for improving women’s health.

Methods

After initial community outreach activities, interested women aged 18–49 years were recruited consecutively in 2021 at three primary health care centers in the district of Marovoay. FGS was detected by colposcopy. Colposcopy images were double-blind reviewed by two independent specialists. A Luminex bead-based assay was performed on cervical vaginal lavage specimens for HPV typing. Crude (CPR) and adjusted prevalence ratios (APR) of associations between selected factors and FGS and HPV positivity were estimated using univariable and multivariable binary Poisson regression with 95% confidence intervals (CIs).

Results

Among 500 women enrolled, 302 had complete information on FGS and HPV diagnosis, and were thus eligible for analysis. Within the sample, 189 (62.6%, 95% CI: 56.9–68.1) cases of FGS were detected. A total of 129 women (42.7%, 95% CI: 37.1–48.5) tested positive for HPV. In total, 80 women (26.5%, 95% CI: 21.6–31.8]) tested positive for both conditions. No association was observed between FGS and HPV positivity, while previous pregnancy (APR = 0.65, 95% CI: 0.43–0.78) and older age (APR = 0.59, 95% CI: 0.42–0.81) are showing a negative association with HPV infection compared to no previous pregnancy and younger age groups.

Conclusions

The results of the study show that FGS and HPV are highly prevalent in rural Madagascar. The concurrent prevalence of these two conditions requires urgent adaptations of public health strategies to improve women’s health, such as integrated services at primary level of care.

Graphical Abstract
Rapid isolation of intact retinal astrocytes: a novel approach
Authors: Cullen Paul F. , Mazumder Arpan G. , Sun Daniel , Flanagan John G.
Published: September 2023

Astrocytes are a major category of glial support cell in the central nervous system and play a variety of essential roles in both health and disease. As our understanding of the diverse functions of these cells improves, the extent of heterogeneity between astrocyte populations has emerged as a key area of research. Retinal astrocytes, which form the direct cellular environment of retinal ganglion cells somas and axons, undergo a reactive response in both human glaucoma and animal models of the disease, yet their contributions to its pathology and progression remain relatively unknown. This gap in knowledge is largely a function of inadequate isolation techniques, driven in part by the sparseness of these cells and their similarities with the more abundant retinal Müller cells. Here, we present a novel method of isolating retinal astrocytes and enriching their RNA, tested in both normal and ocular hypertensive mice, a common model of experimental glaucoma. Our approach combines a novel enzyme assisted microdissection of retinal astrocytes with selective ribosome immunoprecipitation using the Ribotag method. Our microdissection method is rapid and preserves astrocyte morphology, resulting in a brief post-mortem interval and minimizing loss of RNA from distal regions of these cells. Both microdissection and Ribotag immunoprecipitation require a minimum of specialized equipment or reagents, and by using them in conjunction we are able to achieve > 100-fold enrichment of astrocyte RNA.
The effect of space arrangement between anterior teeth on their retraction with clear aligners in first premolar extraction treatment: a finite element study
Authors: Cao Yuan , Wang Zhi-Wei , Chen Da , Liu Lu , Li Deng-Xin , Li Ni , Ying Si-Qi , Liu Xin , Jin Fang
Published: September 2023

Introduction

Clear aligner therapy has become increasingly popular in recent years, although it has encountered several difficulties in premolar extraction treatment. These difficulties include anterior dentition, lingual tipping and extrusion. The design of the present clinical scheme usually set a tiny space between the anterior teeth before retraction in order to obtain an ideal outcome. The objective of our research was to analyze the effect of the existing spaces during retraction.

Methods

Models including maxillary dentition without first premolars, maxilla, periodontal ligaments, gingiva, or aligners were constructed and imported to an ANSYS workbench. Five groups of models were created: without spaces and with 0.25, 0.50, 0.75 and 1.00 mm spaces between the anterior dentition. A 0.20 mm retraction step was applied to all the groups.

Results

As the spaces between the anterior dentition increased, the bowing effect of the aligner caused by the passive forces decreased gradually. Accordingly, the degree of extrusion of the anterior dentition was alleviated significantly, while sagittal movement was reduced. However, the overall movement tended to be a bodily displacement rather than tipping. Meanwhile, maximum Von Mises stress of the periodontal ligaments (PDLs) was markedly decreased.

Conclusion

These analyses indicate that spaces between the anterior dentition during anterior retraction are beneficial for decreasing the tendency for extrusion of the anterior dentition and require provision of anchorage. Appropriate spaces can be designed to lest the lingual tipping and extrusion effect of the anterior teeth while simultaneously reducing the maximum stresses on PDLs.
Calcium dynamics during the growth of Agaricus bisporus: implications for mushroom development and nutrition
Authors: Wu Juan , Wang Rui , Liu Xue , Ni Ying , Sun Hui , Deng Xiaonan , Wan Lingzhong , Liu Fangzhi , Tang Jun , Yu Junjie , Yan Xiaoming
Published: September 2023

Background

Agaricus bisporus (A. bisporus) is highly valued for its nutritional benefits and delicious taste, making it one of the most widely cultivated, highest yielding, and most consumed edible mushrooms worldwide. The yield and quality of A. bisporus were affected by its culture medium and environment. Among the culture base, the precise impact of calcium on A. bisporus cultivation and the dynamic changes in calcium concentration and chemical environment during the cultivation process remain unclear. This study aims to investigate the changes in calcium content and forms during the growth of A. bisporus and their implications for mushroom growth and nutrition.

Results

Through the analysis of samples collected during the composting phase, mycelial development phase, and A. bisporus harvesting phase, the role of calcium in the growth process of button mushrooms is revealed. During the composting phase, the calcium content remains relatively stable, suggesting a consistent calcium source in the compost. The fermentation process shows a significant decrease in carbon content and an increase in oxygen content, indicating the degradation and oxidation of organic matter. In the mycelial development phase, both the cover soil and compost experience a decrease in calcium content, with a more pronounced reduction observed in the covering soil, indicating its primary role as an energy source for enzymatic activity and metabolic processes of the mycelium. During the A. bisporus harvesting phase, the changes in calcium, carbon, and oxygen content become less prominent, indicating a stable state of fruiting bodies growth that no longer requires a significant supply of organic matter.

Conclusions

Analysis of calcium forms reveals the presence of different calcium compounds, likely influenced by soil calcium sources, microbial activities, and mushroom metabolic byproducts. Calcium plays a crucial regulatory role in the growth and quality of A. bisporus. This study provides valuable insights into the significance of calcium in A. bisporus growth and offers theoretical guidance for optimizing mushroom production and quality improvement.

Graphical Abstract