bluuebunny/crossref_metadata_2025 huggingface dataset:
Mental Health and String Education: Identifying Key Concerns Within the American String Teachers Association Community
Authors: Dirks Rachel L. , Smith Tawnya D. , González-Moreno Patricia A. , Phelps Allyn
Published: August 2023

At the 2020 American String Teachers Association (ASTA) Conference held in Orlando Florida, an attendee of the Wellness Committee Listening Session recommended that a study be conducted to determine the prevalence and awareness of mental health concerns among students and teachers within the organization. Members agreed that there is more needed to be understood so that ASTA could provide professional development webinars, resources, as well as local, state, and national conference sessions. In response to this request and the clear need for more information, a survey was developed and deployed to the ASTA membership in the fall of 2020. Follow-up interviews with members who volunteered in response to an invitation on the survey were conducted in the spring and early summer of 2021. Teachers reported a high prevalence of student mental health issues prior to and during the pandemic and reported concerning levels of work overload, compassion fatigue/burnout, and mental health issues. Generational differences in mental health perceptions were noted, as were opportunities to provide targeted professional development and community-level services.
Has smart city transition elevated the provision of healthcare services? Evidence from China's Smart City Pilot Policy
Authors: Guo Lin , Chai Yulin , Yang Chunxiao , Zhang Linlin , Guo Hongwei , Yang Honglv
Published: August 2023

This paper endeavors to identify the causal effects between the smart city transition and the provision of healthcare services while uncovering potential pathways of influence. This study first constructs a logical analytical framework and posits five hypotheses for examination. Subsequently, leveraging the quasi-natural experiment of the China Smart City Pilot Policy (CSCPP), empirical tests are conducted utilizing a Difference-in-Differences (DD) two-way fixed effects model. The findings suggest that the CSCPP has significantly enhanced the provision of healthcare services. Even after addressing the formidable challenges of endogeneity, sample self-selection, and spatial spillovers, the conclusion remains robust. Mechanism tests indicate that the CSCPP primarily operates through two avenues: augmenting human resources and institutional services. Heterogeneity tests reveal that the efficacy of CSCPP is heightened in cities boasting administrative approval service centers, experiencing diminished financial constraints, and exhibiting elevated healthcare provision levels and situated in the eastern region. The theoretical and empirical analysis of this paper demonstrates that smart city transitions can facilitate the enhancement of healthcare services. The potential contribution of this paper is to enrich the conceptualization of governance frameworks for smart city transition while providing empirical evidence from China.
Understanding Life-Practice Pedagogics—A Distinctively Educational Way of Thinking and Theorizing With Chinese Characteristics
Authors: Deng (邓宗怡) Zongyi
Published: August 2023

Purpose

This article provides an interpretation of the construction of Life-Practice pedagogics by locating it within the Chinese pedagogic tradition and within the context of China's social and economic transition at the turn of the 21st century.

Design/Approach/Methods

As a theoretical essay, the article focuses on interpreting Lan Ye’s Return and Breakthrough: The Outline of Life-Practice Pedagogics, with reference to her other related writings. It draws on theoretical sources from continental Pädagogik and Anglo-American educational theory.

Findings

Squarely in the tradition of Pädagogik, Life-Practice pedagogics exhibits a distinctively educational way of thinking and theorizing—in terms of education as self-formation ( Bildung), education as purposeful activities or practice ( Erziehung), and the dignity of practice. It is also a distinctive Chinese construction rooted in the reality of China and nourished by Chinese educational traditions, with its own unique research methodology.

Originality/Value

The construction of Life-Practice pedagogics provides a powerful case of how education can be established as distinctive discipline in the 21st century and of how pedagogics in China can be revitalized in today's context. This article calls for a rediscovery of the essence of education in the current context of the “learnification” of educational discourse and a multiplicity of educational fads.
Stephen Neill: A Colonial Scholar in an Independent Kenya (1969–1973)
Authors: Daughrity Dyron
Published: August 2023

This article focuses on Bishop Stephen Neill’s years (1969–1973) as the founding chairman of the Department of Philosophy and Religious Studies at the University of Nairobi. While he succeeded in his goal of establishing a fine academic program, almost nobody lamented his departure. While chiefly about Neill, the article touches upon larger issues related to Anglicanism and colonialism in a newly independent Kenya. It features a summary of interviews with Professor Jesse Mugambi, a longtime professor at the university, who worked with Neill during this era. It also includes a brief assessment of Neill’s time in Nairobi from the missionary-demographer David Barrett. A shorter version of this article was given in January 2023 to the American Society of Church History.
The Legacy of Hildegard Prozell
Authors: Ece Kristina
Published: August 2023

Hildegard Prozell (1869–1948) was the first female missionary from the territory of Latvia (then the Russian Empire), who went to India to serve through Leipzig Mission. During her thirteen-year ministry there she established multiple schools for girls, was the school principal, developed zenana mission work in Mayavaram, and trained Bible women in India. Because of her ministry, a female mission support association was established in Riga, as well as mission nights and conferences. Her writing gave people back home a window to sharing the Good News to children in Eastern India.
Pandemonium, Pandemethics, Pantopia: What’s in a Word?
Authors: Küster Volker
Published: August 2023

At the margins of the Covid-19 pandemic, religious groups aroused a pandemonium fueled by racism and discrimination against the poor and vulnerable with references to apocalyptic thought patterns. Imagining pantopia versus the “new normal” brings realized eschatology to the dialogue table. God’s option for the poor and the whole of creation is a critique of the neoliberal Anthropocene. It is not only we who try to interpret the virus, the virus is also interpreting us. The hermeneutical circle was suddenly interrupted by a contraflow. The injustices of global neoliberal capitalism and the intersectionality of different forms of discrimination revealed by the virus may not be covered up again but must be tackled by an intercultural pandemethics.
Utilization of street-based COVID-19 vaccination clinics in Phoenix’s homeless population
Authors: Zeien Justin , Vieira Jaime , Hanna Jeffery , Ramirez Alma , Miller Catherine , Hartmark-Hill Jennifer , Rosales Cecilia
Published: August 2023

The novel Coronavirus (COVID-19) is a highly contagious viral illness that has caused the most significant global health crisis in recent human history. Individuals experiencing homelessness represent one of the more vulnerable populations for COVID-19 infection and morbidity. Amongst individuals experiencing homelessness in Phoenix, a student-led interprofessional organization called Street Medicine Phoenix (SMP) sought to both reduce the risk of COVID-19 transmission and morbidity/mortality related to infection. Through collaborations with the Maricopa County Department of Public Health and various community organizations, SMP developed a format for street-based vaccination clinics. SMP deployed these clinics on numerous occasions to the streets directly surrounding the community homeless shelter, allowing SMP to vaccinate individuals directly in their encampments. Through SMP’s efforts starting in February 2021, 400 individuals experiencing homelessness have received at least one COVID-19 vaccine. Challenges encountered included low health literacy, lack of established rapport and trust, low vaccine confidence, difficulty verifying patients’ vaccination status, difficulty obtaining sufficient information from patients to create a record in the Arizona State Immunization Information System (ASIIS), monitoring patients post-vaccination, transporting vaccine supplies from encampment to encampment, and lack of patient awareness of the mobile vaccine clinic services. Despite challenges, SMP’s outreach efforts have demonstrated the feasibility and importance of mobile public health services to reach homeless encampments, particularly mobile vaccination clinics in response to disease outbreaks, and the necessity of strategic partnerships with community agencies to effectively meet the needs of underserved populations.
High temperature influences DNA methylation and transcriptional profiles in sea urchins (Strongylocentrotus intermedius)
Authors: Liu Anzheng , Zeng Fanshuang , Wang Luo , Zhen Hao , Xia Xinglong , Pei Honglin , Dong Changkun , Zhang Yanmin , Ding Jun
Published: August 2023

Background

DNA methylation plays an important role in life processes by affecting gene expression, but it is still unclear how DNA methylation is controlled and how it regulates gene transcription under high temperature stress conditions in Strongylocentrotus intermedius. The potential link between DNA methylation variation and gene expression changes in response to heat stress in S. intermedius was investigated by MethylRAD-seq and RNA-seq analysis. We screened DNA methylation driver genes in order to comprehensively elucidate the regulatory mechanism of its high temperature adaptation at the DNA/RNA level.

Results

The results revealed that high temperature stress significantly affected not only the DNA methylation and transcriptome levels of S. intermedius (P < 0.05), but also growth. MethylRAD-seq analysis revealed 12,129 CG differential methylation sites and 966 CWG differential methylation sites, and identified a total of 189 differentially CG methylated genes and 148 differentially CWG methylated genes. Based on KEGG enrichment analysis, differentially expressed genes (DEGs) are mostly enriched in energy and cell division, immune, and neurological damage pathways. Further RNA-seq analysis identified a total of 1968 DEGs, of which 813 genes were upregulated and 1155 genes were downregulated. Based on the joint MethylRAD-seq and RNA-seq analysis, metabolic processes such as glycosaminoglycan degradation, oxidative phosphorylation, apoptosis, glutathione metabolism, thermogenesis, and lysosomes are regulated by DNA methylation.

Conclusions

High temperature affected the DNA methylation and expression levels of genes such as MOAP-1, GGT1 and RDH8, which in turn affects the metabolism of HPSE, Cox, glutathione, and retinol, thereby suppressing the immune, energy metabolism, and antioxidant functions of the organism and finally manifesting as stunted growth. In summary, the observations in the present study improve our understanding of the molecular mechanism of the response to high temperature stress in sea urchin.
Microbiota profiles in the saliva, cancerous tissues and its companion paracancerous tissues among Chinese patients with lung cancer
Authors: Zhou Yuhan , Zeng Hongfen , Liu Kai , Pan Hui , Wang Baohui , Zhu Minghua , Wang Jiawei , Wang Haoyi , Chen Hongwei , Shen Dan , Wang Yue , Yu Zhaonan
Published: August 2023

Background

Despite the growing interest in the impact of the gut microbiome on cancer, the relationship between the lung microbiome and lung cancer has received limited investigation. Additionally, the composition of the oral microbiome was found to differ from that of individuals with lung cancer, indicating that these microorganisms may serve as potential biomarkers for the detection of lung cancer.

Methods

Forty-three Chinese lung cancer patients were enrolled in the current retrospective study and 16 S rRNA sequencing was performed on saliva, cancerous tissue (CT) and paracancerous tissue (PT) samples.

Results

Diversity and species richness were significantly different between the oral and lung microbiota. Lung microbiota were largely composed of the phyla Proteobacteria, Firmicutes, Bacteroidetes and Actinobacteria. The relative abundance of Promicromonosporacea and Chloroflexi increased in CT, while Enterococcaceae and Enterococcus were enriched in PT (p<0.05). A cancer-related microbiota model was constructed and produced an area under the curve of 0.74 in the training set, indicating discrimination between subjects with and without cancer.

Conclusions

Characterization of microbiota in saliva, CT and PT from Chinese lung cancer patients revealed little difference between CT and PT, indicating that the tumor and its microenvironment might influence the local microbiome. A model to distinguish between CT and PT was constructed, which has the potential to enhance our comprehension of the involvement of microbiota in the pathogenesis of lung cancer and identify novel therapeutic targets.
Comparative efficacy of 24 exercise types on postural instability in adults with Parkinson’s disease: a systematic review and network meta-analysis
Authors: Qian Yujia , Fu Xueying , Zhang Haoyang , Yang Yong , Wang Guotuan
Published: August 2023

Objective

To compare, rank and evaluate the 24 exercise types that improve postural instability in patients with Parkinson’s disease (PD).

Methods

We searched the data in PubMed, MEDLINE, Embase, PsycINFO, Cochrane library, and Web of Science from their inception date to January 23, 2023. Randomized controlled trials (RCTs) that aimed at determining the effectiveness of physical activity interventions on postural instability in adults with PD. This review focused on different balance outcome categories: (a) balance test batteries (BBS); (b) static steady-state balance (sSSB); (c) dynamic steady-state balance (dSSB); (d) proactive balance (PB); (e) reactive balance (RB).

Results

Among 10,474 records, 199 studies (patients = 9523) were eligible for qualitative synthesis. The random-effects NMA model revealed that the following exercise training modalities had the highest p score of being best when compared with control group: body-weight support treadmill training (BWS_TT) for BBS (p score = 0.97; pooled standardised mean difference (95% CI): 1.56 (0.72 to 2.39)) and dSSB (1.00; 1.53 (1.07 to 2.00)), aquatic exercise (AQE) for sSSB (0.85; 0.94 (0.33 to 1.54)), Pilates for PB (0.95; 1.42 (0.59 to 2.26)). Balance and gait training with the external cue or attention (BGT_ECA) and robotic assisted gait balance (RA_GT) had similar superior effects in improving RB. The confidence in evidence was often low according to Confidence in Network Meta-Analysis.

Conclusions

There is low quality evidence that BWS_TT, AQE, Pilates, BGT_ECA and RA_GT are possibly the most effective treatments, pending outcome of interest, for adults with PD.
Mycobacterium abscessus pulmonary disease presenting with spontaneous pneumomediastinum and subcutaneous emphysema in childhood acute lymphoblastic leukemia: a case report and literature review
Authors: Liu Wenyuan , Chu Jinhua , Xie Zhiwei , Yang Linhai , Huang Lingling , Tu Songji , Cai Huaju , Wu Zhengyu , Wei Anbang , Liu Chengzhu , Cheng Yan , Zhang Kunlong , Wang Ningling
Published: August 2023

Introduction

Mycobacterium abscessus is a rapidly growing mycobacterium commonly identified in adults with underlying pulmonary diseases but is rarely observed in children. A better understanding of this pathogen in children is essential.

Case presentation

We report the case of a 49-month-old female child without previous underlying pulmonary diseases but with acute lymphoblastic leukemia (ALL). The patient was complicated with pneumonia during chemotherapy, which was primarily characterized by spontaneous pneumomediastinum and subcutaneous emphysema on chest computed tomography (CT). M. abscessus sequences were detected by metagenomic next-generation sequencing in bronchoalveolar lavage fluid. With mechanical ventilation, closed thoracic drainage, and anti-infective therapy for 6 months, the patient’s infection was controlled. The patient completed 2.5 years of treatment for ALL, and the drugs were discontinued. The patient currently remains in complete hematologic remission.

Discussion

We reviewed the literature on 33 children with M. abscessus pulmonary disease. These children mostly had underlying immunodeficiency. Chest CT most often showed nodular shadows, consolidation, and bronchiectasis. Spontaneous pneumomediastinum and subcutaneous emphysema were not reported as major manifestations.

Conclusion

Spontaneous pneumomediastinum and subcutaneous emphysema were our patient's main characteristics on chest CT, and this study enriches the knowledge regarding possible imaging changes in M. abscessus pulmonary disease in children. This case report reflects good clinical experience in maintaining the balance between chemotherapy and anti-infective therapy in childhood ALL.
Performance of different colorectal cancer screening strategies: a long-term passive follow-up population-based screening program in Beijing, China
Authors: Zhang Xi , Yang Lei , Liu Shuo , Li Huichao , Li Qingyu , Li Haoxin , Wang Ning , Ji Jiafu
Published: August 2023

Background

We aimed to assess the performance of the risk assessment questionnaire and fecal immunochemical test (FIT) in a population-based colorectal cancer (CRC) screening program to provide timely evidence for tailored screening strategies in China.

Methods

This analysis was conducted using data from Beijing Cancer Screening Prospective Cohort Study (BCSPCS). A risk assessment questionnaire and FIT were selected as the primary screening methods, and participants with any positive results were referred to undergo a diagnostic colonoscopy.

Results

From 2015 to 2020, 148,636 Beijing residents aged 40–69 years were invited from designated communities, with 147,807 finishing the risk assessment questionnaire and 115,606 (78.2%) completing the FIT. Among the 42,969 (29.1%) high-risk CRC participants, 23,824 (55.4%) underwent colonoscopy. One year after enrollment, all subjects were linked to the Beijing Cancer Registry (BCR) database and 241 cases of CRC were confirmed. The CRC incidence rate was 58.2/100,000 for the low-risk arm and 418.9/100,000 for the high-risk arm. For participants who underwent colonoscopy, 91 CRC cases were detected, with a detection rate of 91.9% and 63.7% of them were early-stage cases. Furthermore, the sensitivities of utilizing the risk assessment questionnaire alone, FIT alone, combined risk assessment questionnaire and FIT were 75.7%, 50.1%, and 95.1%, and the specificities were 75.3%, 87.3%, and 70.7%, respectively.

Conclusion

The Beijing CRC screening program can effectively detect early-onset CRC; however, the compliance with colonoscopy still needs to be improved.
Effects of sleep pattern, duration, and quality on premenstrual syndrome and primary dysmenorrhea in korean high school girls
Authors: Jeong Daye , Lee Heakyong , Kim Jaehee
Published: August 2023

Background

Sleep deprivation is known to be a risk factor for premenstrual syndrome and primary dysmenorrhea in adults. However, it has rarely been investigated in adolescents. The aim of this study was to investigate whether sleep pattern, duration, and quality independently affect premenstrual syndrome and primary dysmenorrhea in adolescent girls. An additional purpose was to investigate the sleep status in Korean adolescent girls during the COVID-19 pandemic.

Methods

A cross-sectional survey study was conducted in 519 high school girls aged 15 to 18 years in Gyeonggido, South Korea, in 2021 during the COVID-19 lockdown. Menstrual pain intensity and menstrual symptoms were assessed using the visual analogue scale (VAS) and Cox menstrual symptom scale (CMSS), respectively. Premenstrual syndrome was assessed by the premenstrual symptoms screening tool (PSST). Sleep was assessed by the Pittsburgh Sleep Quality Index (PSQI). The known risk factors of dysmenorrhea, including menstrual and lifestyle characteristics and stress, were assessed as covariates.

Results

During the pandemic, approximately 68% of girls slept 7 h or less, while about 60% reported poor sleep quality. Additionally, 64% of participants had a bedtime later after 1AM, and 34% woke up later after 8AM. Late bedtime significantly affected VAS (P = 0.05), CMSS severity and frequency (both P < 0.01), and PSST symptom (P < 0.01). Waking up late affected CMSS severity (P < 0.05), PSST symptom (P = 0.05), and PSST function (P < 0.05). However, the significance of these effects disappeared after controlling for covariates. Sleeping less than 5 h affected CMSS frequency (P < 0.05) and PSST symptoms (P < 0.001). After controlling for covariates, the significance of the effect on PSST symptom remained (P < 0.05). General sleep quality and PSQI components, including subjective sleep quality, sleep latency, sleep disturbance, use of sleeping medication, and daytime dysfunction, significantly affected CMSS frequency and severity and PSST symptom after controlling for covariates (P < 0.05, P < 0.01, or P < 0.001). The multiple regression analysis revealed that among sleep characteristics, sleep quality was the most important risk factor of premenstrual syndrome and dysmenorrhea.

Conclusion

Our study result heightens the importance of healthy sleep hygiene, especially sleep quality in the management of premenstrual syndrome and dysmenorrhea in adolescent girls.
Does the ‘Educational Alliance’ conceptualize the student - supervisor relationship when conducting a master thesis in medicine? An interview study
Authors: Brenner Michael , Weiss-Breckwoldt Anja Nikola , Condrau Flurin , Breckwoldt Jan
Published: August 2023

Background

Completing a master thesis (MT) is mandatory in many undergraduate curricula in medicine but a specific educational framework to guide the supervisor-student relationship during the MT has not been published. This could be helpful to facilitate the MT process and to more effectively reach the learning objectives related to science education in medicine. An attractive model for this purpose is the ‘Educational Alliance’ (EA), which focusses on the three components ‘clarity and agreement on (a) goals, (b) tasks and (c) relationship & roles’. This study investigated factors that can either facilitate or hinder the process of MTs, and related these to the components of the EA.

Methods

We conducted semi-structured face-to-face interviews with 20 students and – separately – with their 20 corresponding supervisors, after the MT had been accepted. The interviews included open questions on factors facilitating or hindering the success of the MT. Audio recordings of the interviews were anonymized and transcribed, and then analysed by qualitative content analysis. Also, quantitative data were gathered on satisfaction with the MT process and the supervisory quality (using Likert-type questions).

Results

We were able to analyse all 40 interviews, related to 20 MTs. From the transcripts, we extracted 469 comments related to the research question and categorized these into the four main categories (a) ‘Preparation’, (b) ‘Process’, (c) ‘Atmosphere’, (d) ‘Value of the MT’. Interviewees highlighted the importance of a careful preparation phase, clear expectations, a clear research plan, thorough and timely feedback, mutual agreement on timelines, and a positive working atmosphere. Each of these factors could be brought in line with the three components of the EA framework: agreement and clarity of goals, tasks, relationships & roles. Satisfaction with the MT process was rated 8.75 ± 1.22 SD (of 10) points by supervisors, and 7.80 ± 1.61 SD points by students, while supervision quality was rated + 1.51 ± 0.63 SD (scale from − 2 to + 2) by supervisors, and + 1.26 ± 0.93 SD by students.

Conclusion

We propose the EA framework as a useful guidance for students, supervisors, and the university towards conducting successful MTs in medicine. Based on the findings, we provide specific recommendations for students, supervisors, and university.
Pilot study of an interprofessional pediatric mechanical ventilation educational initiative in two intensive care units
Authors: Mehrzai Pazun , Höfeler Thormen , Ebenebe Chinedu Ulrich , Moll-Khosrawi Parisa , Demirakça Süha , Vettorazzi Eik , Bergers Marlies , Lange Mandy , Dreger Sabine , Maruhn Hanna , Singer Dominique , Deindl Philipp
Published: August 2023

Introduction

Inappropriate ventilator settings, non-adherence to a lung-protective ventilation strategy, and inadequate patient monitoring during mechanical ventilation can potentially expose critically ill children to additional risks. We set out to improve team theoretical knowledge and practical skills regarding pediatric mechanical ventilation and to increase compliance with treatment goals.

Methods

An educational initiative was conducted from August 2019 to July 2021 in a neonatal and pediatric intensive care unit of the University Children’s Hospital, Hamburg-Eppendorf, Germany. We tested baseline theoretical knowledge using a multiple choice theory test (TT) and practical skills using a practical skill test (PST), consisting of four sequential Objective Structured Clinical Examinations of physicians and nurses. We then implemented an educational bundle that included video self-training, checklists, pocket cards, and reevaluated team performance. Ventilators and monitor settings were randomly checked in all ventilated patients. We used a process control chart and a mixed-effects model to analyze the primary outcome.

Results

A total of 47 nurses and 20 physicians underwent assessment both before and after the implementation of the initiative using TT. Additionally, 34 nurses and 20 physicians were evaluated using the PST component of the initiative. The findings revealed a significant improvement in staff performance for both TT and PST (TT: 80% [confidence interval (CI): 77.2–82.9] vs. 86% [CI: 83.1–88.0]; PST: 73% [CI: 69.7–75.5] vs. 95% [CI: 93.8–97.1]). Additionally, there was a notable increase in self-confidence among participants, and compliance with mechanical ventilation treatment goals also saw a substantial rise, increasing from 87.8% to 94.5%.

Discussion

Implementing a pediatric mechanical ventilation education bundle improved theoretical knowledge and practical skills among interprofessional pediatric intensive care staff and increased treatment goal compliance in ventilated children.
NANDA nursing diagnoses associated with the occurrence of psychomotor agitation in patients with severe mental disorder: a cross-sectional study
Authors: Garrote-Cámara María-Elena , Juárez-Vela Raúl , Rodríguez-Muñoz Pedro-Manuel , Pérez Jesús , Sánchez-González Juan-Luis , Rubinat-Arnaldo Esther , Navas-Echazarreta Noelia , Sufrate-Sorzano Teresa , Santolalla-Arnedo Iván
Published: August 2023

Background

Psychomotor agitation is increased psychomotor activity, restlessness and irritability. People with psychomotor agitation respond by overreacting to intrinsic and extrinsic stimuli, experiencing stress and/or cognitive impairment. the aim was to analyse the association of nursing diagnoses with the disinhibition dimension, the aggressiveness dimension and the lability dimension of the Corrigan Agitated Behaviour Scale.

Methods

This study was conducted in Spain using a multicentre cross-sectional convenience sample of 140 patients who had been admitted to psychiatric hospital units and had presented an episode of psychomotor agitation between 2018 and 2021.

Results

The Corrigan Agitated Behaviour Scale was used to assess psychomotor agitation. Associated nursing diagnoses, violence directed at professionals and the environment are shown to be predictive values for the severity of the agitation episode. Moderate-severe psychomotor agitation episodes are shown as predictors of violence directed mainly at professionals and the environment.

Conclusions

There is an urgent need for mental health nurses to have knowledge of the extended clinic in order to care for users and improve their health conditions in dealing with people, with their social, subjective and biological dimension.
Tryptophan metabolite norharman secreted by cultivated Lactobacillus attenuates acute pancreatitis as an antagonist of histone deacetylases
Authors: Zhou Qi , Tao Xufeng , Guo Fangyue , Wu Yu , Deng Dawei , Lv Linlin , Dong Deshi , Shang Dong , Xiang Hong
Published: August 2023

Background

Patients with acute pancreatitis (AP) exhibit specific phenotypes of gut microbiota associated with severity. Gut microbiota and host interact primarily through metabolites; regrettably, little is known about their roles in AP biological networks. This study examines how enterobacterial metabolites modulate the innate immune system in AP aggravation.

Methods

In AP, alterations in gut microbiota were detected via microbiomics, and the Lactobacillus metabolites of tryptophan were identified by liquid chromatography-tandem mass spectrometry (LC–MS/MS). By culturing Lactobacillus with tryptophan, differential metabolites were detected by LC–MS/MS. Lipopolysaccharide (LPS)-stimulated RAW264.7 cells and mice with cerulein plus LPS-induced AP were used to evaluate the biological effect of norharman on M1 macrophages activation in AP development. Further, RNA sequencing and lipid metabolomics were used for screening the therapeutic targets and pathways of norharman. Confocal microscopy assay was used to detect the structure of lipid rafts. Molecular docking was applied to predict the interaction between norharman and HDACs. Luciferase reporter assays and chromatin immunoprecipitation (ChIP) were used to explore the direct mechanism of norharman promoting Rftn1 expression. In addition, myeloid-specific Rftn1 knockout mice were used to verify the role of Rftn1 and the reversed effect of norharman.

Results

AP induced the dysfunction of gut microbiota and their metabolites, resulting in the suppression of Lactobacillus-mediated tryptophan metabolism pathway. The Lactobacillus metabolites of tryptophan, norharman, inhibited the release of inflammatory factor in vitro and in vivo, as a result of its optimal inhibitory action on M1 macrophages. Moreover, norharman blocked multiple inflammatory responses in AP exacerbation due to its ability to maintain the integrity of lipid rafts and restore the dysfunction of lipid metabolism. The mechanism of norharman’s activity involved inhibiting the enzyme activity of histone deacetylase (HDACs) to increase histone H3 at lysine 9/14 (H3K9/14) acetylation, which increased the transcription level of Rftn1 (Raftlin 1) to inhibit M1 macrophages’ activation.

Conclusions

The enterobacterial metabolite norharman can decrease HDACs activity to increase H3K9/14 acetylation of Rftn1, which inhibits M1 macrophage activation and restores the balance of lipid metabolism to relieve multiple inflammatory responses. Therefore, norharman may be a promising prodrug to block AP aggravation.

Graphical Abstract
Adverse associations between maternal deoxynivalenol exposure and birth outcomes: a prospective cohort study in China
Authors: Tan Tianqi , Chen Tingting , Zhu Wenwen , Gong Lin , Yan Yizhong , Li Qian , Chen Li , Li Yiling , Liu Jialin , Li Yanan , Yang Xuefeng , Hao Liping , Wang Huaiji , Yang Nianhong , Wei Sheng
Published: August 2023

Background

Deoxynivalenol (DON), one of the most prevalent mycotoxins, has been found to cause fetal growth retardation in animals. However, limited evidence exists regarding its effects on pregnant women.

Methods

Maternal urinary concentration of total DON (tDON) and free DON (fDON) in the second trimester was measured using liquid chromatography with tandem mass spectrometry. Provisional daily intake (PDI) of DON was calculated based on tDON concentration. Linear and logistic regression models were used to evaluate the association between DON exposure levels and birth weight, birth length, and the risk of small for gestational age (SGA).

Results

Among 1538 subjects, the median concentrations of tDON and fDON were 12.1 ng/mL and 5.1 ng/mL, respectively. The PDI values revealed that the median DON intake was 0.7 µg/kg bw, and 35.9% of the total population exceeded the provisional maximum tolerable daily intake (PMTDI) of 1 µg/kg bw. Compared with the lowest tertile, birth weight decreased by 81.11 g (95% CI: -127.00, -35.23) for tDON (P-trend < 0.001) and 63.02 g (95% CI: -108.72, -17.32) for fDON (P-trend = 0.004) in the highest tertile. Each unit increase in Ln-tDON and Ln-fDON was also inversely associated with birth weight. Furthermore, compared to those who did not exceed PMTDI, pregnant women whose PDI exceeded PMTDI had lower birth weight (β = -79.79 g; 95% CI: -119.09, -40.49) and birth length (β = -0.21 cm; 95% CI: -0.34, -0.07), and a higher risk of SGA (OR = 1.48; 95% CI: 1.02, 2.15) in their offspring. Similar associations with birth weight, birth length, and SGA were found when comparing the highest tertile of PDI to the lowest tertile (all P-trend < 0.05).

Conclusions

Maternal DON exposure is related to decreased birth weight. Our findings implicate that DON exposure during pregnancy may cause fetal growth faltering, and measures should be taken to reduce DON exposure in pregnant women.
Targeted delivery of a PD-1-blocking scFv by CD133-specific CAR-T cells using nonviral Sleeping Beauty transposition shows enhanced antitumour efficacy for advanced hepatocellular carcinoma
Authors: Yang Chaopin , You Jinqi , Pan Qiuzhong , Tang Yan , Cai Liming , Huang Yue , Gu Jiamei , Wang Yizhi , Yang Xinyi , Du Yufei , Ouyang Dijun , Chen Hao , Zhong Haoran , Li Yongqiang , Yang Jieying , Han Yulong , Sun Fengze , Chen Yuanyuan , Wang Qijing , Weng Desheng , Liu Zhongqiu , Xiang Tong , Xia Jianchuan
Published: August 2023

Background

CD133 is considered a marker for cancer stem cells (CSCs) in several types of tumours, including hepatocellular carcinoma (HCC). Chimeric antigen receptor-specific T (CAR-T) cells targeting CD133-positive CSCs have emerged as a tool for the clinical treatment of HCC, but immunogenicity, the high cost of clinical-grade recombinant viral vectors and potential insertional mutagenesis limit their clinical application.

Methods

CD133-specific CAR-T cells secreting PD-1 blocking scFv (CD133 CAR-T and PD-1 s cells) were constructed using a sleeping beauty transposon system from minicircle technology, and the antitumour efficacy of CD133 CAR-T and PD-1 s cells was analysed in vitro and in vivo.

Results

A univariate analysis showed that CD133 expression in male patients at the late stage (II and III) was significantly associated with worse progression-free survival (PFS) (P = 0.0057) and overall survival (OS) (P = 0.015), and a multivariate analysis showed a trend toward worse OS (P = 0.041). Male patients with advanced HCC exhibited an approximately 20-fold higher PD-L1 combined positive score (CPS) compared with those with HCC at an early stage. We successfully generated CD133 CAR-T and PD-1 s cells that could secrete PD-1 blocking scFv based on a sleeping beauty system involving minicircle vectors. CD133 CAR-T and PD-1 s cells exhibited significant antitumour activity against HCC in vitro and in xenograft mouse models. Thus, CD133 CAR-T and PD-1 s cells may be a therapeutically tractable strategy for targeting CD133-positive CSCs in male patients with advanced HCC.

Conclusions

Our study provides a nonviral strategy for constructing CAR-T cells that could also secrete checkpoint blockade inhibitors based on a Sleeping Beauty system from minicircle vectors and revealed a potential benefit of this strategy for male patients with advanced HCC and high CD133 expression (median immunohistochemistry score > 2.284).
Molecular characterization of Glaesserella parasuis strains circulating in North American swine production systems
Authors: Mugabi Robert , Silva Ana Paula S. Poeta , Hu Xiao , Gottschalk Marcelo , Aragon Virginia , Macedo Nubia R. , Sahin Orhan , Harms Perry , Main Rodger , Tucker Alexander W. , Li Ganwu , Clavijo Maria J.
Published: August 2023

Background

Glaesserella parasuis is the causative agent of Glässer’s disease in pigs. Serotyping is the most common method used to type G. parasuis isolates. However, the high number of non-typables (NT) and low discriminatory power make serotyping problematic. In this study, 218 field clinical isolates and 15 G. parasuis reference strains were whole-genome sequenced (WGS). Multilocus sequence types (MLST), serotypes, core-genome phylogeny, antimicrobial resistance (AMR) genes, and putative virulence gene information was extracted.

Results

In silico WGS serotyping identified 11 of 15 serotypes. The most frequently detected serotypes were 7, 13, 4, and 2. MLST identified 72 sequence types (STs), of which 66 were novel. The most predominant ST was ST454. Core-genome phylogeny depicted 3 primary lineages (LI, LII, and LIII), with LIIIA sublineage isolates lacking all vtaA genes, based on the structure of the phylogenetic tree and the number of virulence genes. At least one group 1 vtaA virulence genes were observed in most isolates (97.2%), except for serotype 8 (ST299 and ST406), 15 (ST408 and ST552) and NT (ST448). A few group 1 vtaA genes were significantly associated with certain serotypes or STs. The putative virulence gene lsgB, was detected in 8.3% of the isolates which were predominantly of serotype 5/12. While most isolates carried the bcr, ksgA, and bacA genes, the following antimicrobial resistant genes were detected in lower frequency;  blaZ (6.9%), tetM (3.7%), spc (3.7%), tetB (2.8%), bla-ROB-1 (1.8%), ermA (1.8%), strA (1.4%), qnrB (0.5%), and aph3''Ia (0.5%).  

Conclusion

This study showed the use of WGS to type G. parasuis isolates and can be considered an alternative to the more labor-intensive and traditional serotyping and standard MLST. Core-genome phylogeny provided the best strain discrimination. These findings will lead to a better understanding of the molecular epidemiology and virulence in G. parasuis that can be applied to the future development of diagnostic tools, autogenous vaccines, evaluation of antibiotic use, prevention, and disease control.
Unravelling factors associated with malaria parasitaemia among children 6–24 months to inform malaria interventions in Nigeria: evidence from 2021 Malaria Indicator Survey
Authors: Ujuju Chinazo N. , Mokuolu Olugbenga A. , Nwafor-Okoli Chinyere , Nnamani Kenechi O.
Published: August 2023

Background

As an additional two million malaria cases were reported in 2021 compared to the previous year, concerted efforts toward achieving a steady decline in malaria cases are needed to achieve malaria elimination goals. This work aimed at determining the factors associated with malaria parasitaemia among children 6–24 months for better targeting of malaria interventions.

Methods

A cross-sectional study analysed 2021 Nigeria Malaria Indicator Survey dataset. Data from 3058 children 6–24 months were analyzed. The outcome variable was children 6–24 months whose parasitaemia was determined using a rapid diagnostic test (RDT). Independent variables include child age in months, mothers’ age, mothers’ education, region, place of residence, household ownership and child use of insecticide-treated net (ITN), exposure to malaria messages and knowledge of ways to prevent malaria. Logistic regression analysis was conducted to examine possible factors associated with malaria parasitaemia in children 6–24 months.

Results

Findings revealed that 28.7% of the 3058 children aged 6–24 months tested positive for malaria by RDT. About 63% of children 12–17 months (aOR = 1.63, 95% CI 1.31–2.03) and 91% of children 18 to 24 months (aOR = 1.91, 95% CI 1.51–2.42) were more likely to have a positive malaria test result. Positive malaria test result was also more likely in rural areas (aOR = 1.79, 95% CI 2.02–24.46), northeast (aOR = 1.54, 95% CI 1.02–2.31) and northwest (aOR = 1.63, 95% CI 1.10–2.40) region. In addition, about 39% of children who slept under ITN had a positive malaria test result (aOR = 1.39 95% CI 1.01–1.90). While children of mothers with secondary (aOR = 0.40, 95% CI 0.29–0.56) and higher (aOR = 0.26, 95% CI 0.16–0.43) levels of education and mothers who were aware of ways of avoiding malaria (aOR = 0.69, 95% CI 0.53–0.90) were less likely to have a malaria positive test result.

Conclusion

As older children 12 to 24 months, children residing in the rural, northeast, and northwest region are more likely to have malaria, additional intervention should target them in an effort to end malaria.
Prognostic value of peritoneal scar-like tissue in patients with peritoneal metastases of ovarian origin presenting for curative-intent cytoreductive surgery
Authors: El Asmar Antoine , Pop Florin , Helou Etienne El , Demetter Pieter , Veys Isabelle , Polastro Laura , Bohlok Ali , Liberale Gabriel
Published: August 2023

Background

Complete cytoreductive surgery (CRS), remain the gold standard in the treatment of peritoneal metastases of ovarian cancer (PMOC). Given the increasing rate of neoadjuvant chemotherapy in patients with high PCI, prior abdominal surgeries, inflammation and fibrotic changes, the benefit of removing any “peritoneal scar-like tissues” (PST) during CRS, hasn’t been thoroughly investigated. Our objective in this retrospective cohort was to identify the proportion of malignant cells positivity in PST of patients with PMOC, undergoing curative-intent CRS ± HIPEC.

Methods

This is a retrospective study, conducted at our comprehensive cancer center, including patients with PMOC, presenting for curative-intent CRS. During CRS, benign-looking peritoneal lesions, lacking the typical hard nodular, aggressive, and invasive morphology, were systematically resected or electro fulgurated. PSTs were analyzed for the presence of tumoral cells by our pathologist. Correlations between the presence of PST and their positivity, and the different patients’ variables, were studied.

Results

In 51% of patients, PST harbored malignant cells. Those were associated with poorly differentiated serous tumors, a high PCI (> 8) and a worse DFS: 17 months in the positive PST group versus 29 months in the negative PST group (p = 0.05), on univariate analysis. Multivariate analysis revealed that PCI > 8 and poorly differentiated primary tumor histology were correlated with a worse DFS, and that higher PCI and advanced FIGO were correlated with a worse OS.

Conclusion

Benign-looking PST harbors malignancy in 51% of cases. The benefit of their systematic resection and their prognostic value should be further investigated in larger cohorts.
Elective nodal irradiation versus involved-field irradiation for stage II–IV cervical esophageal squamous cell carcinoma patients undergoing definitive concurrent chemoradiotherapy: a retrospective propensity study with 8-year survival outcomes
Authors: Wang Jianing , Wu Yajing , Zhang Wei , Chen Yujia , Liu Qing , Jing Shaowu , Zhang Jiandong , Wu Fengpeng , Wang Jun , Qiao Xueying
Published: August 2023

Background

Definitive concurrent chemoradiotherapy (dCCRT) is suggested as the standard treatment for cervical esophageal squamous cell carcinoma (CESCC). This retrospective propensity study compared the 8-year survival outcomes and acute treatment toxicities of these patients treated with elective nodal irradiation (ENI) versus involved-field irradiation (IFI).

Materials and methods

Patients with stage II–IV CESCC treated with dCCRT at the Fourth Hospital of Hebei Medical University between January 1, 2007 and December 31, 2020 were enrolled in the study. All the patients were restaged according to the American Joint Commission 8th edition criteria. The propensity score matching (PSM) was used to minimize the effects of treatment selection bias and potential confounding factors including sex, age, ECOG score, clinical T stage, clinical N stage, clinical TNM stage and radiation dose between the ENI group and IFI group. Survival and the prognostic factors were evaluated.

Results

The 131 eligible patients underwent ENI (60 patients, 45.8%) or IFI (71 patients, 54.2%). The median follow-up time was 91.1 months (range, 23.8–182.0 months) for all the patients. The median OS, 1-, 3-, 5-, and 8-year OS rates were 44.4 months, 87.8%, 55.1%, 38.3%, and 27.2%, respectively. After PSM, there were 49 patients in each group. The median OS, 1-, 3-, 5-, and 8-year OS rates for ENI and IFI group were 32.0 months, 83.7%, 48.5%, 38.5% and 31.1% versus 45.2 months, 89.8%, 52.5%, 37.5%, 26.1%, respectively (P = 0.966; HR 0.99, 95% CI 0.61–1.61). Similar locoregional control was obtained in both groups. The tendency of leukocytopenia and neutropenia was higher in ENI than in IFI (59.2% vs. 38.8%; P = 0.068 and 30.6% vs. 14.3%; P = 0.089) at the end of dCCRT.

Conclusion

Cervical esophageal squamous cell carcinoma patients undergoing definitive concurrent chemoradiotherapy has a satisfactory prognosis with organ conservation. The involved-field irradiation might be a better alternative owing to similar overall survival outcomes and local control with less toxicity of myelosuppression.
A clinical model to predict the progression of knee osteoarthritis: data from Dryad
Authors: Shen Lianwei , Yue Shouwei
Published: August 2023

Background

Knee osteoarthritis (KOA) is a multifactorial, slow-progressing, non-inflammatory degenerative disease primarily affecting synovial joints. It is usually induced by advanced age and/or trauma and eventually leads to irreversible destruction of articular cartilage and other tissues of the joint. Current research on KOA progression has limited clinical application significance. In this study, we constructed a prediction model for KOA progression based on multiple clinically relevant factors to provide clinicians with an effective tool to intervene in KOA progression.

Method

This study utilized the data set from the Dryad database which included patients with Kellgren–Lawrence (KL) grades 2 and 3. The KL grades was determined as the dependent variable, while 15 potential predictors were identified as independent variables. Patients were randomized into training set and validation set. The training set underwent LASSO analysis, model creation, visualization, decision curve analysis and internal validation using R language. The validation set is externally validated and F1-score, precision, and recall are computed.

Result

A total of 101 patients with KL2 and 94 patients with KL3 were selected. We randomly split the data set into a training set and a validation set by 8:2. We filtered “BMI”, “TC”, “Hypertension treatment”, and “JBS3 (%)” to build the prediction model for progression of KOA. Nomogram used to visualize the model in R language. Area under ROC curve was 0.896 (95% CI 0.847–0.945), indicating high discrimination. Mean absolute error (MAE) of calibration curve = 0.041, showing high calibration. MAE of internal validation error was 0.043, indicating high model calibration. Decision curve analysis showed high net benefit. External validation of the metabolic syndrome column-line graph prediction model was performed by the validation set. The area under the ROC curve was 0.876 (95% CI 0.767–0.984), indicating that the model had a high degree of discrimination. Meanwhile, the calibration curve Mean absolute error was 0.113, indicating that the model had a high degree of calibration. The F1 score is 0.690, the precision is 0.667, and the recall is 0.714. The above metrics represent a good performance of the model.

Conclusion

We found that KOA progression was associated with four variable predictors and constructed a predictive model for KOA progression based on the predictors. The clinician can intervene based on the nomogram of our prediction model.

Key information

This study is a clinical predictive model of KOA progression. KOA progression prediction model has good credibility and clinical value in the prevention of KOA progression.