bluuebunny/crossref_metadata_2025 huggingface dataset:
Sputum microbiome α-diversity is a key feature of the COPD frequent exacerbator phenotype
Authors: Pragman Alexa A. , Hodgson Shane W. , Wu Tianhua , Zank Allison , Reilly Cavan S. , Wendt Chris H.
Published: November 2023

Background

The lung microbiome is an inflammatory stimulus whose role in COPD pathogenesis is incompletely understood. We hypothesised that the frequent exacerbator phenotype is associated with decreased α-diversity and increased lung inflammation. Our objective was to assess correlations between the frequent exacerbator phenotype, the microbiome and inflammation longitudinally during exacerbation-free periods.

Methods

We conducted a case–control longitudinal observational study of the frequent exacerbator phenotype and characteristics of the airway microbiome. 81 subjects (41 frequent and 40 infrequent exacerbators) provided nasal, oral and sputum microbiome samples at two visits over 2–4 months. Exacerbation phenotype, relevant clinical factors and sputum cytokine values were associated with microbiome findings.

Results

The frequent exacerbator phenotype was associated with lower sputum microbiome α-diversity (p=0.0031). This decrease in α-diversity among frequent exacerbators was enhanced when the sputum bacterial culture was positive (p<0.001). Older age was associated with decreased sputum microbiome α-diversity (p=0.0030). Between-visit β-diversity was increased among frequent exacerbators and those who experienced a COPD exacerbation between visits (p=0.025 and p=0.014, respectively). Sputum cytokine values did not differ based on exacerbation phenotype or other clinical characteristics. Interleukin (IL)-17A was negatively associated with α-diversity, while IL-6 and IL-8 were positively associated with α-diversity (p=0.012, p=0.012 and p=0.0496, respectively). IL-22, IL-17A and IL-5 levels were positively associated withMoraxellaabundance (p=0.027, p=0.0014 and p=0.0020, respectively).

Conclusions

Even during exacerbation-free intervals, the COPD frequent exacerbator phenotype is associated with decreased sputum microbiome α-diversity and increased β-diversity. Decreased sputum microbiome α-diversity andMoraxellaabundance are associated with lung inflammation.
ERS International Congress 2023: highlights from the Pulmonary Vascular Diseases Assembly
Authors: Cullivan Sarah , Boucly Athénaïs , Jevnikar Mitja , Lechartier Benoit , Ulrich Silvia , Bertoletti Laurent , Sitbon Olivier , Vonk-Noordegraaf Anton , Bokan Aleksandar , Park Da-Hee , Genecand Leon , Guiot Julien , Jutant Etienne-Marie , Piccari Lucilla , Lichtblau Mona
Published: November 2023

Pulmonary vascular diseases such as pulmonary embolism and pulmonary hypertension are important and frequently under-recognised conditions. This article provides an overview of key highlights in pulmonary vascular diseases from the European Respiratory Society International Congress 2023. This includes insights into disease modification in pulmonary arterial hypertension and novel therapies such as sotatercept and seralutinib. Exciting developments in our understanding of the mechanisms underpinning pulmonary hypertension associated with interstitial lung disease are also explored. A comprehensive overview of the complex relationship between acute pulmonary embolism and chronic thromboembolic pulmonary hypertension (CTEPH) is provided along with our current understanding of the molecular determinants of CTEPH. The importance of multidisciplinary and holistic care cannot be understated, and this article also addresses advances beyond medication, with a special focus on exercise training and rehabilitation.
Phytochemical analysis and anti-infective potential of fungal endophytes isolated from Nigella sativa seeds
Authors: Shady Nourhan Hisham , Sobhy Sara Khalid , Mostafa Yaser A. , Yahia Ramadan , Glaeser Stefanie P. , Kämpfer Peter , El-Katatny Mo’men H. , Abdelmohsen Usama Ramadan
Published: November 2023

Endophytic fungi, particularly from higher plants have proven to be a rich source of antimicrobial secondary metabolites. The purpose of this study is to examine the antimicrobial potential of three endophytic fungiAspergillussp. SA1,Aspergillussp. SA2, andAspergillussp. SA3, cultivated fromNigella sativaseeds againstStaphylococcus aureus(ATCC 9144),Escherichia coli(ATCC 25922),Pseudomonas aeruginosa(ATCC 27853),Klebsiella pneumoniae(ATCC 13883), MRSA (ATCC 33591), and human pathogenCandida albicans(ATCC 10231). Furthermore, the most active cultivated endophytic fungi were molecularly identified via internal transcribed spacer (ITS) sequencing. HR-ESIMS guided approach has been used successfully in chemical profiling of 26 known bioactive secondary metabolites (1–26), which belongs to different classes of natural compounds such as polyketides, benzenoids, quinones, alcohols, phenols or alkaloids. Finally,in-silicointeractions within active site of fungal Cyp51 and bacterial DNA gyrase revealed possibility of being a hit-target for such metabolites as antimicrobials.
Micro- and macrocirculatory effects of norepinephrine on anaesthesia-induced hypotension: a prospective preliminary study
Authors: Kindermans Manuel , Joachim Jona , Manquat Elsa , Levé Charlotte , Hong Alex , Mateo Joachim , Mebazaa Alexandre , Gayat Etienne , De Backer Daniel , Vallée Fabrice
Published: November 2023

Background

Intraoperative arterial hypotension (IOH) leads to increased postoperative morbidity. Norepinephrine is often use to treat IOH. The question regarding the mode of administration in either a bolus or continuous infusion remains unanswered. The aim of the present study was to describe and compare the effects on macrocirculation and microcirculation of a bolus and a continuous infusion of norepinephrine to treat IOH.

Methods

We conducted a prospective observational study with adult patients who underwent neurosurgery. Patients with invasive arterial blood pressure and cardiac output (CO) monitoring were screened for inclusion. All patients underwent microcirculation monitoring by video-capillaroscopy, laser doppler, near-infrared spectroscopy technology, and tissular CO2. In case of IOH, the patient could receive either a bolus of 10 µg or a continuous infusion of 200 µg/h of norepinephrine. Time analysis for comparison between bolus and continuous infusion were at peak of MAP. The primary outcome was MFI by videocapillaroscopy.

Results

Thirty-five patients were included, with 41 boluses and 33 continuous infusion.

Bolus and continuous infusion induced an maximal increase in mean arterial pressure of +30[20-45] and +23[12-34] %, respectively (P=0,07). For macrocirculatory parameters, continuous infusion was associated with a smaller decrease in CO and stroke volume (p<0.05).

For microcirculatory parameters, microvascular flow index (-0,1 vs. + 0,3, p=0,03), perfusion index (-12 vs. +12%, p=0,008), total vessel density (-0,2 vs. +2,3 mm2/mm2, p=0,002), showed significant opposite variations with bolus and continuous infusion, respectively.

Conclusions

These results on macro and microcirculation enlighten the potential benefits of a continuous infusion of norepinephrine rather than a bolus to treat anaesthesia-induced hypotension.

Trial registration

(NOR-PHARM: 1-17-42 Clinical Trials: NCT03454204), 05/03/2018
Changes of serum TSH, FT3, and FT4 levels in infants received surgical correction of congenital heart disease under cardiopulmonary bypass
Authors: Lin Wen-Hao , Zhou Si-Jia , Chen Xiu-Hua , Cao Hua , Chen Qiang
Published: November 2023

Objective

This study aimed to explore the fluctuations and clinical relevance of serum thyrotropin (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) levels in infants undergoing surgical correction for congenital heart disease (CHD) using cardiopulmonary bypass (CPB).

Methods

In a retrospective design, 58 infants who underwent CHD surgical correction under CPB between January 2021 and January 2022 at our institution were incorporated. These infants were categorized into two groups: simple CHD (n = 34) and complex CHD (n = 24). TSH, FT3, and FT4 serum concentrations were assessed at four intervals: 24 h pre-surgery (T0) and 24 h (T1), 48 h (T2), and 72 h (T3) post-surgery.

Results

The simple CHD group displayed a significantly reduced CPB duration compared to the complex CHD group (P < 0.001). Both groups exhibited a notable decline in serum thyroid hormone concentrations at T1 compared to T0. However, from T1 to T3, an upward trend in hormone levels was observed. By T3, though the levels in both groups had risen notably from T1, they remained significantly diminished from T0 (P < 0.01). In both the simple and complex CHD cohorts, significant fluctuations in thyroid hormone levels (TSH, FT3, FT4) were noted across the different timepoints (T0, T1, T3) (P < 0.01). While no significant disparities were found between the two groups’ hormone concentrations at T0 and T1 (P > 0.05), at T2 and T3, the simple CHD group manifested higher TSH, FT3, and FT4 levels compared to the complex CHD group (P < 0.05).

Conclusions

Infants undergoing CHD surgical correction under CPB experience significant declines in TSH, FT3, and FT4 serum levels. The post-surgery thyroid hormone recovery was more pronounced in infants with simple CHD compared to those with complex CHD. As such, vigilant monitoring of thyroid hormone levels during the perioperative phase is imperative, and timely intervention measures should be employed when necessary.
Integrating scRNA-seq to explore novel macrophage infiltration-associated biomarkers for diagnosis of heart failure
Authors: Li Shengnan , Ge Tiantian , Xu Xuan , Xie Liang , Song Sifan , Li Runqian , Li Hao , Tong Jiayi
Published: November 2023

Objective

Inflammation and immune cells are closely intertwined mechanisms that contribute to the progression of heart failure (HF). Nonetheless, there is a paucity of information regarding the distinct features of dysregulated immune cells and efficient diagnostic biomarkers linked with HF. This study aims to explore diagnostic biomarkers related to immune cells in HF to gain new insights into the underlying molecular mechanisms of HF and to provide novel perspectives for the detection and treatment of HF.

Method

The CIBERSORT method was employed to quantify 22 types of immune cells in HF and normal subjects from publicly available GEO databases (GSE3586, GSE42955, GSE57338, and GSE79962). Machine learning methods were utilized to screen for important cell types. Single-cell RNA sequencing (GSE145154) was further utilized to identify important cell types and hub genes. WGCNA was employed to screen for immune cell-related genes and ultimately diagnostic models were constructed and evaluated. To validate these predictive results, blood samples were collected from 40 normal controls and 40 HF patients for RT-qPCR analysis. Lastly, key cell clusters were divided into high and low biomarker expression groups to identify transcription factors that may affect biomarkers.

Results

The study found a noticeable difference in immune environment between HF and normal subjects. Macrophages were identified as key immune cells by machine learning. Single-cell analysis further showed that macrophages differed dramatically between HF and normal subjects. This study revealed the existence of five subsets of macrophages that have different differentiation states. Based on module genes most relevant to macrophages, macrophage differentiation-related genes (MDRGs), and DEGs in HF and normal subjects from GEO datasets, four genes (CD163, RNASE2, LYVE1, and VSIG4) were identified as valid diagnostic markers for HF. Ultimately, a diagnostic model containing two hub genes was constructed and then validated with a validation dataset and clinical samples. In addition, key transcription factors driving or maintaining the biomarkers expression programs were identified.

Conclusion

The analytical results and diagnostic model of this study can assist clinicians in identifying high-risk individuals, thereby aiding in guiding treatment decisions for patients with HF.
Methods, strategies, and incentives to increase response to mental health surveys among adolescents: a systematic review
Authors: Bidonde Julia , Meneses-Echavez Jose F. , Hafstad Elisabet , Brunborg Geir Scott , Bang Lasse
Published: November 2023

Background

This systematic review aimed to identify effective methods to increase adolescents’ response to surveys about mental health and substance use, to improve the quality of survey information.

Methods

We followed a protocol and searched for studies that compared different survey delivery modes to adolescents. Eligible studies reported response rates, mental health score variation per survey mode and participant variations in mental health scores. We searched CENTRAL, PsycINFO, MEDLINE and Scopus in May 2022, and conducted citation searches in June 2022. Two reviewers independently undertook study selection, data extraction, and risk of bias assessments. Following the assessment of heterogeneity, some studies were pooled using meta-analysis.

Results

Fifteen studies were identified, reporting six comparisons related to survey methods and strategies. Results indicate that response rates do not differ between survey modes (e.g., web versus paper-and-pencil) delivered in classroom settings. However, web surveys may yield higher response rates outside classroom settings. The largest effects on response rates were achieved using unconditional monetary incentives and obtaining passive parental consent. Survey mode influenced mental health scores in certain comparisons.

Conclusions

Despite the mixed quality of the studies, the low volume for some comparisons and the limit to studies in high income countries, several effective methods and strategies to improve adolescents’ response rates to mental health surveys were identified.
Characterization of genomic instability-related genes predicts survival and therapeutic response in lung adenocarcinoma
Authors: Li Shuyang , Wang Wei , Yu Huihan , Zhang Siyu , Bi Wenxu , Sun Suling , Hong Bo , Fang Zhiyou , Chen Xueran
Published: November 2023

Background

Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer (NSCLC) and is the leading cause of cancer death worldwide. Its progression is characterized by genomic instability. In turn, the level of genomic instability affects the prognosis and immune status of patients with LUAD. However, the impact of molecular features associated with genomic instability on the tumor microenvironment (TME) has not been well characterized. In addition, the effect of the genes related to genomic instability in LUAD on individualized treatment of LUAD is unknown.

Methods

The RNA-Sequencing, somatic mutation, and clinical data of LUAD patients were downloaded from publicly available databases. A genetic signature associated with genomic instability (GSAGI) was constructed by univariate Cox regression, Lasso regression, and multivariate Cox regression analysis. Bioinformatics analysis investigated the differences in prognosis, immune characteristics, and the most appropriate treatment strategy among different subtypes of LUAD patients. CCK-8 and colony formation verified the various effects of Etoposide on different subtypes of LUAD cell lines. Cell-to-cell communication analysis was performed using the “CellChat” R package. The expression of the risk factors in the GSAGI was verified using real-time quantitative PCR (qRT-PCR) and Immunohistochemistry (IHC).

Results

We constructed and validated the GSAGI, consisting of five genes: ANLN, RHOV, KRT6A, SIGLEC6, and KLRG2. The GSAGI was an independent prognostic factor for LUAD patients. Patients in the high-risk group distinguished by the GSAGI are more suitable for chemotherapy. More immune cells are infiltrating the tumor microenvironment of patients in the low-risk group, especially B cells. Low-risk group patients are more suitable for receiving immunotherapy. The single-cell level analysis confirmed the influence of the GSAGI on TME and revealed the Mode of action between tumor cells and other types of cells. qRT-PCR and IHC showed increased ANLN, RHOV, and KRT6A expression in the LUAD cells and tumor tissues.

Conclusion

This study confirms that genes related to genomic instability can affect the prognosis and immune status of LUAD patients. The GSAGI we identified has the potential to guide clinicians in predicting clinical outcomes, assessing immunological status, and even developing personalized treatment plans for LUAD patients.
Altered fractional amplitude of low-frequency fluctuations in the superior temporal gyrus: a resting-state fMRI study in anxious depression
Authors: Zhao Peng , Wang Xinyi , Wang Qiang , Yan Rui , Chattun Mohammad Ridwan , Yao Zhijian , Lu Qing
Published: November 2023

Background

Anxious depression, which is a common subtype of major depressive disorder, has distinct clinical features from nonanxious depression. However, little is known about the neurobiological characteristics of anxious depression. In this study, we explored resting-state regional brain activity changes between anxious depression and nonanxious depression.

Method

Resting-state functional magnetic resonance (rs-fMRI) imaging data were collected from 60 patients with anxious depression, 38 patients with nonanxious depression, and 60 matched healthy controls (HCs). One-way analysis of variance was performed to compare the whole-brain fractional amplitude of low-frequency fluctuation (fALFF) in the three groups. The correlation between the fALFF values and the clinical measures was examined.

Results

Compared with those of HCs, the fALFF values in the left superior temporal gyrus (STG) in patients with anxious depression were significantly increased, while the fALFF values in the left middle temporal gyrus (MTG), left STG, and right STG in patients with nonanxious depression were significantly increased. Patients with anxious depression showed reduced fALFF values in the right STG compared with patients with nonanxious depression (p < 0.001, corrected). Within the anxious depression group, fALFF value in the right STG was positively correlated with the cognitive disturbance score (r = 0.36, p = 0.005 corrected).

Conclusion

The bilateral STG and left MTG, which are related to the default mode network, appear to be key brain regions in nonanxious depression, while the right STG plays an essential role in the neuropathological mechanism of anxious depression.
Interrater agreement of multi-professional case review as reference standard for specialist palliative care need: a mixed-methods study
Authors: Müller Evelyn , Müller Michael Josef , Seibel Katharina , Boehlke Christopher , Schäfer Henning , Klein Carsten , Heckel Maria , Simon Steffen T. , Becker Gerhild
Published: November 2023

Background

A wide variety of screening tools for the need for specialist palliative care (SPC) have been proposed for the use in oncology. However, as there is no established reference standard for SPC need to compare their results with, their sensitivity and specificity have not yet been determined. The aim of the study was to explore whether SPC need assessment by means of multi-professional case review has sufficient interrater agreement to be employed as a reference standard.

Methods

Comprehensive case descriptions were prepared for 20 inpatients with advanced oncologic disease at the University Hospital Freiburg (Germany). All cases were presented to the palliative care teams of three different hospitals in independent, multi-professional case review sessions. The teams assessed whether patients had support needs in nine categories and subsequently concluded SPC need (yes / no). Interrater agreement regarding SPC need was determined by calculating Fleiss’ Kappa.

Results

In 17 out of 20 cases the three teams agreed regarding their appraisal of SPC need (substantial interrater agreement: Fleiss’ Kappa κ = 0.80 (95% CI: 0.55–1.0; p < 0.001)). The number of support needs was significantly lower for patients who all teams agreed had no SPC need than for those with agreed SPC need.

Conclusions

The proposed expert case review process shows sufficient reliability to be used as a reference standard. Key elements of the case review process (e.g. clear definition of SPC need, standardized review of the patients’ support needs) and possible modifications to simplify the process are discussed.

Trial registration

German Clinical Trials Register, DRKS00021686, registered 17.12.2020.
The impact of SARS-COV-2 infection on menstruation
Authors: Zhong Xiaozhu , Lu Keji , Liang Weiying , Jihu Luozi , Zeng Anqi , Ding Miao , Chen Dongmei , Xie Meiqing
Published: November 2023

Background

Recent study has demonstrated that the GnRH system in patients with post-COVID syndrome may be influenced by SARS-CoV-2. However, the impact of COVID-19 infection on women’s menstruation is still unknown.

Objective

We aimed to investigate the the relationship between coronavirus disease 2019 (COVID-19) and menstruation in premenopausal women.

Methods

This was a retrospective cohort study. Pre-menopausal women were invited to participate in the online questionnaire on wechat. Participants were divided into four groups according to whether they were infected with severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) and whether they had menstrual changes during the pandemic. Sociodemographic characteristics, history of COVID-19, menstruation and menstrual changes of the participants were collected. Statistical analyses were performed using SPSS, version 25.0 (SPSS Inc., Chicago, IL, USA).

Results

A total of 1946 women were included in the study. 1800 participants had been or were currently infected with SARS-COV-2, and 146 people had not been infected. Among 1800 patients with COVID-19, 666 (37.0%) had changes in menstruation, and 1134 (63.0%) did not, which was significantly higher than the uninfected participants (c2 = 12.161, P = 0.000). The proportion of participants with menstrual cycle changes (450/67.6%) is larger than that of uninfected participants (c2 = 6.904, P = 0.009). COVID-19 vaccination was associated with lower odds of menstrual cycle change (OR, 0.855; 95% CI, 0.750–0.976). Participants who reported chest pain (OR, 1.750, 95% CI, 1.209–2.533) and dyspnea (OR, 1.446; 95% CI, 1.052–1.988) during infection had greater odds of changes to their menstrual cycle compared with the participants who did not.

Conclusions

The association between the COVID-19 and increased prevalence of menstrual cycle irregularity. COVID-19 vaccination is a protective factor in the long term, and participants with chest pain and dyspnea are more likely to develop AUB.
Female infertility and dietary antioxidant index (DAI); a case-control study
Authors: Kabodmehri Roya , Javaheri Fatemeh Sadat Hashemi , Alami Farkhondeh , Mahmoudi Zahra , Amjadi Arezoo , Saeedirad Zahra , Omidi Saeed , Sadeghi Shiva , Hoseini Mohadeseh Sadat Mousavi , Mohamadiyan Zahra , Salimi Zahra , Shafaei Hanieh , Rasekhmagham Reyhaneh , Sharami Seyedeh Hajar , Karimian Maryam , Karimi Hoora , Doaei Saeid
Published: November 2023

Background

Adequate intake of natural antioxidants may improve female fertility. The aim of this study was to examine the link between female infertility and dietary antioxidant index (DAI).

Methods

This case-control study was conducted on 125 women with recently diagnosis of reduced ovarian reserves (AMH < 1.1) as the case group and 125 women with normal ovarian reserve as the control group in Rasht, Iran. The amount of food intake was assessed using the food frequency questionnaire (FFQ) and the DAI was calculated to estimate the antioxidant capacity of the diet.

Results

Regarding dietary intake, the infertile women had a lower intake of potassium (2789.25 ± 777 vs. 2593.68 ± 443 mg/d, P = 0.02), magnesium (204.12 ± 66 vs. 189.73 ± 34 mg/d, P = 0.03), copper (0.93 ± 0.40 vs. 0.82 ± 0.20 mg/d, P < 0.01), vitamin C (133.99 ± 46 vs. 122.62 ± 24 mg/d, P = 0.02), and fiber (14.53 ± 3 vs. 13.44 ± 2 g/d, P < 0.05), and a higher intake of cholesterol (205.61 ± 58 vs. 227.02 ± 46 mg/d, P < 0.01) than the control group (All P < 0.05). The DAI was negatively associated with infertility (OR: 0.94, CI 95%: 0.88–0.97, P = 0.03). The association remained significant after adjustments for age, BMI, the underlying diseases, fertility frequency, IVF failure, and calorie intake.

Conclusion

Following an antioxidant-rich diet may reduce the risk of infertility. More longitudinal studies are warranted to confirm these results and discover the underlying mechanisms.
Ethics education among obstetrics and gynecologists in Saudi Arabia: a cross-sectional study
Authors: Althagafi Noha Abed , Alahmad Ghiath
Published: November 2023

There are a lot of efforts to promote ethics education and training at an undergraduate and postgraduate level around the world, including in Saudi Arabia. However, there is still a lack of structured ethics education curricula in obstetrics and gynecology residency programs in Saudi Arabia. In the current scenario, where new ethical dilemmas are emerging, an ethics education that only focuses on teaching the ethical principles does not enhance the competence to deal with the ethical challenges in daily practice. This study evaluates the lack of ethics education and training in obstetrics and gynecology residency programs in Saudi Arabia. A cross-sectional survey of working obstetricians and gynecologists in Saudi Arabia was conducted among all working levels of doctors (the residents, registrars, consultants, and program directors) from various hospitals of Saudi Arabia. 391 practitioners responded to the survey, representing a response rate of 39.1%, including 257 (66.4%) females and 130 (33.6%) males. 74 (23.0%) received formal education (medical school = 35%; residency programs = 11.8%; sub-specialty programs = 4.3%; postgraduate programs = 7.4%), 85 (26.4%) received informal education (online training = 12.8%; conferences = 18.9%; courses and workshops = 13.3%; self-learning = 31.7% and daily practices = 20.7%), and 78 (19.95%) received no ethics education. Almost all the respondents had a positive attitude towards ethical principles, but a least percent were competent to deal with the ethical challenges. The bottom line of this survey is the imperativeness of reinforcement of formal ethics education in obstetrics and gynecology postgraduate programs in Saudi Arabia.
Grading reflective essays: the construct validity and reliability of a newly developed Tool- GRE-9
Authors: Makarem Nisrine N. , Rahme Diana V. , Brome Dayana , Saab Bassem R
Published: November 2023

Background

The main objective of this study is to assess the construct validity and reliability of the Grading Reflective Essays-9 (GRE-9).

Methods

This study took place in a major tertiary academic medical center in Beirut, Lebanon. 104 reflective essays written by years 1–3 residents in the department of Family Medicine at the American University of Beirut Medical Center (AUBMC) were graded by 2 trained raters who independently scored the essays using GRE-9. GRE-9 scores were then correlated with scores on communication skills OSCE stations and in-training examinations to investigate, respectively, convergent and divergent validity. One of the 2 raters scored the essays twice one month apart to assess the reliability of the GRE-9 using intra rater reliability and internal consistency.

Results

There was a weak, non-significant correlation between GRE-9 score and In training examination (ITE) score (r = − .213, p = .395). There was a moderate, non-significant correlation between GRE-9 scores and the Objective structured clinical examination (OSCE) communication station scores (r = − .412 p = .162). The correlation coefficient between trails 1 and 2 was significant (r = .832, p = .000). Intra class correlation coefficient (ICC) analysis demonstrated almost perfect intra-rater agreement (0.819; 95% CI: 0.741–0.875) of the test ratings over time.

Conclusions

GRE-9, is a short, concise, easy-to-use reliable grading tool for reflective essays that has demonstrated moderate to substantial intra-rater reliability and evidence of divergent validity. The study found non-significant correlations between reflective writing scores OSCE communication scores demonstrating a lack of relationship between reflective writing and this measure of performance.
ClotCatcher: a novel natural language model to accurately adjudicate venous thromboembolism from radiology reports
Authors: Wang Jeffrey , de Vale Joao Souza , Gupta Saransh , Upadhyaya Pulakesh , Lisboa Felipe A. , Schobel Seth A. , Elster Eric A. , Dente Christopher J. , Buchman Timothy G. , Kamaleswaran Rishikesan
Published: November 2023

Introduction

Accurate identification of venous thromboembolism (VTE) is critical to develop replicable epidemiological studies and rigorous predictions models. Traditionally, VTE studies have relied on international classification of diseases (ICD) codes which are inaccurate – leading to misclassification bias. Here, we developed ClotCatcher, a novel deep learning model that uses natural language processing to detect VTE from radiology reports.

Methods

Radiology reports to detect VTE were obtained from patients admitted to Emory University Hospital (EUH) and Grady Memorial Hospital (GMH). Data augmentation was performed using the Google PEGASUS paraphraser. This data was then used to fine-tune ClotCatcher, a novel deep learning model. ClotCatcher was validated on both the EUH dataset alone and GMH dataset alone.

Results

The dataset contained 1358 studies from EUH and 915 studies from GMH (n = 2273). The dataset contained 1506 ultrasound studies with 528 (35.1%) studies positive for VTE, and 767 CT studies with 91 (11.9%) positive for VTE. When validated on the EUH dataset, ClotCatcher performed best (AUC = 0.980) when trained on both EUH and GMH dataset without paraphrasing. When validated on the GMH dataset, ClotCatcher performed best (AUC = 0.995) when trained on both EUH and GMH dataset with paraphrasing.

Conclusion

ClotCatcher, a novel deep learning model with data augmentation rapidly and accurately adjudicated the presence of VTE from radiology reports. Applying ClotCatcher to large databases would allow for rapid and accurate adjudication of incident VTE. This would reduce misclassification bias and form the foundation for future studies to estimate individual risk for patient to develop incident VTE.
Identification of compound heterozygous deletion of the WWOX gene in WOREE syndrome
Authors: Dong Xing-sheng , Wen Xiao-jun , Zhang Sheng , Wang De-gang , Xiong Yi , Li Zhi-ming
Published: November 2023

Background

Biallelic loss-of-function variants in WWOX cause WWOX-related epileptic encephalopathy (WOREE syndrome), which has been reported in 60 affected individuals to date. In this study, we report on an affected individual with WOREE syndrome who presented with early-onset refractory seizures and global neurodevelopmental delay and died at the age of two and a half years.

Methods

We present clinical and molecular findings in the affected individual, including biallelic pathogenic variants in the WWOX gene. We employed different molecular approaches, such as whole exome sequencing, quantitative real-time polymerase chain reaction (qPCR), and whole-genome sequencing, to identify the genetic variants. The breakpoints were determined through gap PCR and Sanger sequencing.

Result

Whole exome sequencing revealed homozygous exon 6 deletion in the WWOX gene in the proband. Quantitative real-time PCR confirmed that the parents were heterozygous carriers of exon 6 deletion. However, using whole-genome sequencing, we identified three larger deletions (maternal allele with exon 6–8 deletion and paternal allele with two deletions in proximity one in intron 5 and the other in exon 6) involving the WWOX gene in the proband, with deletion sizes of 13,261 bp, 53,904 bp, and 177,200 bp. The exact breakpoints were confirmed through gap PCR and Sanger sequencing. We found that the proband inherited the discontinuous deletion of intron 5 and exon 6 from the father, and the exons 6–8 deletion from the mother using gap PCR.

Conclusion

Our findings extend the variant spectrum of WOREE syndrome and support the critical role of the WWOX gene in neural development.
Clinical nomogram assisting in discrimination of juvenile dermatomyositis-associated interstitial lung disease
Authors: Hu Minfei , Shen Chencong , Zheng Fei , Zhou Yun , Teng Liping , Zheng Rongjun , Hu Bin , Wang Chaoying , Lu Meiping , Xu Xuefeng
Published: November 2023

Objective

To establish a prediction model using non-invasive clinical features for early discrimination of DM-ILD in clinical practice.

Method

Clinical data of pediatric patients with JDM were retrospectively analyzed using machine learning techniques. The early discrimination model for JDM-ILD was established within a patient cohort diagnosed with JDM at a children’s hospital between June 2015 and October 2022.

Results

A total of 93 children were included in the study, with the cohort divided into a discovery cohort (n = 58) and a validation cohort (n = 35). Univariate and multivariate analyses identified factors associated with JDM-ILD, including higher ESR (OR, 3.58; 95% CI 1.21–11.19, P = 0.023), higher IL-10 levels (OR, 1.19; 95% CI, 1.02–1.41, P = 0.038), positivity for MDA-5 antibodies (OR, 5.47; 95% CI, 1.11–33.43, P = 0.045). A nomogram was developed for risk prediction, demonstrating favorable discrimination in both the discovery cohort (AUC, 0.736; 95% CI, 0.582–0.868) and the validation cohort (AUC, 0.792; 95% CI, 0.585–0.930). Higher nomogram scores were significantly associated with an elevated risk of disease progression in both the discovery cohort (P = 0.045) and the validation cohort (P = 0.017).

Conclusion

The nomogram based on the ESIM predictive model provides valuable guidance for the clinical evaluation and long-term prognosis prediction of JDM-ILD.
Primary cardiac myxofibrosarcoma of the left atrium and pericardium: a case report
Authors: Azuma Ryota , Sato Kazuyoshi , Sunadoi Hiroki , Ishii Yasushi , Tomaru Utano , Motohashi Masatoshi
Published: November 2023

Background

Primary cardiac myxofibrosarcoma is rare and commonly occurs in the left atrium. Myxofibrosarcoma is aggressive and has a high mortality rate due to its high rate of recurrence. Complete surgical resection is considered important; however, effective treatment options have not been established.

Case presentation

We report the case of a 75-year-old woman who developed a myxofibrosarcoma spreading to the left atrium and pericardium. We performed surgical resection of the tumor to prevent sudden death due to mitral valve obstruction or cerebral infarction due to embolism of the scattered mass. However, we were unable to complete the resection of the tumors. The patient developed brain metastasis 2 months after surgery and eventually died due to brain hemorrhage 3 months after surgery.

Conclusions

In this report, we described a rare case of primary cardiac myxofibrosarcoma located not only in the left atrium but also in the pericardium. Considering preoperative laboratory findings, surgical and adjuvant therapy, and the patient’s wishes are important for the best therapeutic course for an individual.
Biochemical and molecular characterization of a novel glycerol dehydratase from Klebsiella pneumoniae 2e with high tolerance against crude glycerol impurities
Authors: Lin Zifeng , Xiao Yuting , Zhang Lu , Li Le , Dong Congying , Ma Jiangshan , Liu Gao-Qiang
Published: November 2023

Background

The direct bioconversion of crude glycerol, a byproduct of biodiesel production, into 1,3-propanediol by microbial fermentation constitutes a remarkably promising value-added applications. However, the low activity of glycerol dehydratase, which is the key and rate-limiting enzyme in the 1,3-propanediol synthetic pathway, caused by crude glycerol impurities is one of the main factors affecting the 1,3-propanediol yield. Hence, the exploration of glycerol dehydratase resources suitable for crude glycerol bioconversion is required for the development of 1,3-propanediol-producing engineered strains.

Results

In this study, the novel glycerol dehydratase 2eGDHt, which has a tolerance against crude glycerol impurities from Klebsiella pneumoniae 2e, was characterized. The 2eGDHt exhibited the highest activity toward glycerol, with Km and Vm values of 3.42 mM and 58.15 nkat mg−1, respectively. The optimum pH and temperature for 2eGDHt were 7.0 and 37 °C, respectively. 2eGDHt displayed broader pH stability than other reported glycerol dehydratases. Its enzymatic activity was increased by Fe2+ and Tween-20, with 294% and 290% relative activities, respectively. The presence of various concentrations of the crude glycerol impurities, including NaCl, methanol, oleic acid, and linoleic acid, showed limited impact on the 2eGDHt activity. In addition, the enzyme activity was almost unaffected by the presence of an impurity mixture that mimicked the crude glycerol environment. Structural analyses revealed that 2eGDHt possesses more coil structures than reported glycerol dehydratases. Moreover, molecular dynamics simulations and site-directed mutagenesis analyses implied that the existence of unique Val744 from one of the increased coil regions played a key role in the tolerance characteristic by increasing the protein flexibility.

Conclusions

This study provides insight into the mechanism for enzymatic action and the tolerance against crude glycerol impurities, of a novel glycerol dehydratase 2eGDHt, which is a promising glycerol dehydratase candidate for biotechnological conversion of crude glycerol into 1,3-PDO.
Key genes of electron transfer, the nitrogen cycle and tetracycline removal in bioelectrochemical systems
Authors: Zhao Xiaodong , Qin Xiaorui , Jing Xiuqing , Wang Teng , Qiao Qingqing , Li Xiaojing , Yan Pingmei , Li Yongtao
Published: November 2023

Background

Soil microbial fuel cells (MFCs) can remove antibiotics and antibiotic resistance genes (ARGs) simultaneously, but their removal mechanism is unclear. In this study, metagenomic analysis was employed to reveal the functional genes involved in degradation, electron transfer and the nitrogen cycle in the soil MFC.

Results

The results showed that the soil MFC effectively removed tetracycline in the overlapping area of the cathode and anode, which was 64% higher than that of the control. The ARGs abundance increased by 14% after tetracycline was added (54% of the amplified ARGs belonged to efflux pump genes), while the abundance decreased by 17% in the soil MFC. Five potential degraders of tetracycline were identified, especially the species Phenylobacterium zucineum, which could secrete the 4-hydroxyacetophenone monooxygenase encoded by EC 1.14.13.84 to catalyse deacylation or decarboxylation. Bacillus, Geobacter, Anaerolinea, Gemmatirosa kalamazoonesis and Steroidobacter denitrificans since ubiquinone reductase (encoded by EC 1.6.5.3), succinate dehydrogenase (EC 1.3.5.1), Coenzyme Q-cytochrome c reductase (EC 1.10.2.2), cytochrome-c oxidase (EC 1.9.3.1) and electron transfer flavoprotein-ubiquinone oxidoreductase (EC 1.5.5.1) served as complexes I, II, III, IV and ubiquinone, respectively, to accelerate electron transfer. Additionally, nitrogen metabolism-related gene abundance increased by 16% to support the microbial efficacy in the soil MFC, and especially EC 1.7.5.1, and coding the mutual conversion between nitrite and nitrate was obviously improved.

Conclusions

The soil MFC promoted functional bacterial growth, increased functional gene abundance (including nitrogen cycling, electron transfer, and biodegradation), and facilitated antibiotic and ARG removal. Therefore, soil MFCs have expansive prospects in the remediation of antibiotic-contaminated soil. This study provides insight into the biodegradation mechanism at the gene level in soil bioelectrochemical remediation.
Dual-game based UAV swarm obstacle avoidance algorithm in multi-narrow type obstacle scenarios
Authors: Lin Ye , Na Zhenyu , Feng Zilong , Lin Bin , Lin Yun
Published: November 2023

Due to the advantages of rapid deployment, flexible response and strong invulnerability, unmanned aerial vehicle (UAV) swarm has been widely applied in collaborative warfare and emergency communication. However, UAV swarm in complex environments is prone to chaotic collapse due to obstructions. A UAV swarm obstacle avoidance system model for multi-narrow type obstacles is established. Due to the fact that only one UAV is allowed to pass through each small hole at any given moment, addressing the issue of congestion caused by swarming effects becomes crucial in addition to managing the competitive allocation of multiple UAVs to multiple holes. Aiming at this problem, a dual-game real-time obstacle avoidance scheme is proposed for UAV swarm with multi-narrow type obstacle scenarios, which divides the flight process of the UAV swarm into two stages: maintaining the flight state of the UAV swarm unchanged when no obstacles are encountered, and implementing matching separation and motion state switching by means of dual-game strategy when facing multi-narrow type obstacles, ultimately achieving orderly passage after multiple rounds of games. For the proposed scheme, a dual-game based Flocking (DGF) obstacle avoidance algorithm is proposed. Specifically, the motion state of each UAV obtained from the game is parameterized and integrated with the Flocking algorithm to calculate the motion control input for each UAV. The solution is iteratively obtained until the UAV swarm completes the obstacle avoidance. Simulation results demonstrate that the proposed DGF algorithm not only enables smooth obstacle avoidance for the UAV swarm in multi-narrow type obstacle scenarios, but also effectively resolves the internal chaos problem in the UAV swarm, thereby preventing rigid collisions.
Identification of hub genes and their correlation with immune infiltrating cells in membranous nephropathy: an integrated bioinformatics analysis
Authors: Han Miaoru , Wang Yi , Huang Xiaoyan , Li Ping , Liang Xing , Wang Rongrong , Bao Kun
Published: November 2023

Background

Membranous nephropathy (MN) is a chronic glomerular disease that leads to nephrotic syndrome in adults. The aim of this study was to identify novel biomarkers and immune-related mechanisms in the progression of MN through an integrated bioinformatics approach.

Methods

The microarray data were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between MN and normal samples were identified and analyzed by the Gene Ontology analysis, the Kyoto Encyclopedia of Genes and Genomes analysis and the Gene Set Enrichment Analysis (GSEA) enrichment. Hub The hub genes were screened and identified by the weighted gene co-expression network analysis (WGCNA) and the least absolute shrinkage and selection operator (LASSO) algorithm. The receiver operating characteristic (ROC) curves evaluated the diagnostic value of hub genes. The single-sample GSEA analyzed the infiltration degree of several immune cells and their correlation with the hub genes.

Results

We identified a total of 574 DEGs. The enrichment analysis showed that metabolic and immune-related functions and pathways were significantly enriched. Four co-expression modules were obtained using WGCNA. The candidate signature genes were intersected with DEGs and then subjected to the LASSO analysis, obtaining a total of 6 hub genes. The ROC curves indicated that the hub genes were associated with a high diagnostic value. The CD4+ T cells, CD8+ T cells and B cells significantly infiltrated in MN samples and correlated with the hub genes.

Conclusions

We identified six hub genes (ZYX, CD151, N4BP2L2-IT2, TAPBP, FRAS1 and SCARNA9) as novel biomarkers for MN, providing potential targets for the diagnosis and treatment.
Carpets with visual cues can improve gait in Parkinson’s disease patients: may be independent of executive function
Authors: Hu Ze-Di , Zhu Shi-Guo , Huang Jie-Fan , Chen Jin-Yu , Huang Shi-Shi , Liu Rong-Pei , Chen Zhu-Ling , Ma Lu-Lu , Zhang Xiong , Wang Jian-Yong
Published: November 2023

Background

Gait impairment is common in Parkinson’s disease (PD) patients, which greatly reduces their quality of life. Executive dysfunction is associated with gait impairment. Compensatory strategies, including visual cues, have been shown to be effective in improving PD gait. In this study, we aimed to understand whether carpets with visual cues could improve PD gait, and how the improvement varies across patients with different executive function state.

Methods

We designed carpets with chessboard and stripe cues. A total of 65 Chinese PD patients were recruited. Movement Disorder Society Unified Parkinson’s Disease Rating Scale, L-dopa equivalent daily dosage, Hoehn & Yahr stage, Frontal Assessment Battery, Mini Mental State Examination Scale, Hamilton Anxiety Scale, and Hamilton Depression Scale were evaluated. Gait parameters including stride length, gait speed and fall risk were recorded by a wearable electronic device.

Results

The stride length and gait speed were significantly improved and the fall risk was significantly mitigated when PD patients walked on carpets with chessboard and stripe patterns. Further analysis showed the amelioration of gait parameters was independent of executive dysfunction.

Conclusions

Our study demonstrates that carpets with visual cues can improve the gait of PD patients even in those with mild executive dysfunction.
Relationship between neutrophil to lymphocyte ratio and diabetic peripheral neuropathy: a systematic review and meta-analysis
Authors: Rezaei Shahrabi Armin , Arsenault Gabrielle , Nabipoorashrafi Seyed Ali , Lucke-Wold Brandon , Yaghoobpoor Shirin , Meidani Fatemeh Zari , Rahmati Rahem , Ghaedi Arshin , Khanzadeh Shokoufeh
Published: November 2023

Background

The present study aims to review the existing scientific literature on the role of neutrophil to lymphocyte ratio (NLR) in diabetic peripheral neuropathy (DPN) to perform a meta-analysis on the available data.

Methods

The electronic repositories Web of Science, PubMed, and Scopus were systematically explored starting from their establishment up until June 9, 2022.

Results

Fifteen articles were included in the meta‐analysis after multiple screening according to the PRISMA guidelines. The combined findings indicated that individuals with DPN had higher levels of NLR in comparison to those without DPN (SMD = 0.61; CI 95% = 0.40–0.81, p < 0.001). In the subgroup assessment based on ethnicity, it was observed that diabetic patients with DPN exhibited increased NLR levels in contrast to those without DPN in studies conducted in India (SMD = 1.30; CI 95% = 0.37–2.24, p = 0.006) and East Asia (SMD = 0.53; CI 95% = 0.34–0.73, p < 0.001) but not in studies conducted in Turkey (SMD = 0.30; CI 95% = − 0.06–0.67, p = 0.104) and Egypt (SMD = 0.34; CI 95% = -0.14–0.82, p = 0.165). The pooled sensitivity of NLR was 0.67 (95% CI = 0.49–0.81), and the pooled specificity was 0.70 (95% CI, 0.56–0.81). The pooled positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio (DOR) of NLR were 2.30 (95% CI = 1.71–3.09), 0.45 (95%CI = 0.30–0.67), and 5.06 (95% CI = 3.16–8.12), respectively.

Conclusion

NLR serves as a distinct marker of inflammation, and its rise in cases of DPN suggests an immune system imbalance playing a role in the development of the disease.