bluuebunny/crossref_metadata_2025 huggingface dataset:
Hsa_circ_0005397 promotes hepatocellular carcinoma progression through EIF4A3
Authors: Yuan Liu-Xia , Luo Mei , Liu Ruo-Yu , Wang Hui-Xuan , Ju Lin-Ling , Wang Feng , Cao Ya-Li , Wang Zhong-Cheng , Chen Lin
Published: February 2024

Purpose

The purpose of this study was to explore the expression and potential mechanism of hsa_circ_0005397 in hepatocellular carcinoma progression.

Methods

Quantitative reverse transcription-polymerase chain reaction(qRT-PCR) was used to measure the expression level of hsa_circ_0005397 and EIF4A3 from paired HCC tissues and cell lines. Western Blot (WB) and immunohistochemistry (IHC) were used to verify the protein level of EIF4A3. The specificity of primers was confirmed by agarose gel electrophoresis. Receiver Operating Characteristic (ROC) Curve was drawn to analyze diagnostic value. Actinomycin D and nuclear and cytoplasmic extraction assays were utilized to evaluate the characteristics of hsa_circ_0005397. Cell Counting kit-8 (CCK-8) and colony formation assays were performed to detect cell proliferation. Flow cytometry analysis was used to detect the cell cycle. Transwell assay was performed to determine migration and invasion ability. RNA-binding proteins (RBPs) of hsa_circ_0005397 in HCC were explored using bioinformatics websites. The relationship between hsa_circ_0005397 and Eukaryotic Translation Initiation Factor 4A3 (EIF4A3) was verified by RNA Binding Protein Immunoprecipitation (RIP) assays, correlation and rescue experiments.

Results

In this study, hsa_circ_0005397 was found to be significantly upregulated in HCC, and the good diagnostic sensitivity and specificity shown a potential diagnostic capability. Upregulated expression of hsa_circ_0005397 was significantly related to tumor size and stage. Hsa_circ_0005397 was circular structure which more stable than liner mRNA, and mostly distributed in the cytoplasm. Upregulation of hsa_circ_0005397 generally resulted in stronger proliferative ability, clonality, and metastatic potency of HCC cells; its downregulation yielded the opposite results. EIF4A3 is an RNA-binding protein of hsa_circ_0005397, which overexpressed in paired HCC tissues and cell lines. In addition, expression of hsa_circ_0005397 decreased equally when EIF4A3 was depleted. RIP assays and correlation assay estimated that EIF4A3 could interacted with hsa_circ_0005397. Knockdown of EIF4A3 could reverse hsa_circ_0005397 function in HCC progression.

Conclusions

Hsa_circ_0005397 promotes progression of hepatocellular carcinoma through EIF4A3. These research findings may provide novel clinical value for hepatocellular carcinoma.
Results of the Cologne Corona Surveillance (CoCoS) project– a cross-sectional study: survey data on risk factors of SARS-CoV-2 infection, and moderate-to-severe course in primarily immunized adults
Authors: Oberste Max , Asenova Teodora , Ernst Angela , Shah-Hosseini Kija , Schnörch Nadja , Buess Michael , Rosenberger Kerstin Daniela , Kossow Annelene , Dewald Felix , Neuhann Florian , Hellmich Martin
Published: February 2024

Background

Amidst the COVID-19 pandemic, vaccination has been a crucial strategy for mitigating transmission and disease severity. However, vaccine-effectiveness may be influenced by various factors, including booster vaccination, as well as personal factors such as age, sex, BMI, smoking, and comorbidities. To investigate the potential effects of these factors on SARS-CoV-2 infection and disease severity, we analyzed data from the third round of the Cologne Corona Surveillance (CoCoS) project, a large cross-sectional survey.

Methods

The study was conducted mid-February to mid-March 2022 in Cologne, Germany. A random sample of 10,000 residents aged 18 years and older were invited to participate in an online survey. Information on participants’ demographics (age, sex), SARS-CoV-2 infections, vaccination status, smoking, and preexisting medical conditions were collected. The outcomes of the study were: (1) the occurrence of SARS-CoV-2 infection despite vaccination (breakthrough infection) and (2) the occurrence of moderate-to-severe disease as a result of a breakthrough infection. Cox proportional-hazards regression was used to investigate possible associations between the presence/absence of booster vaccination, personal factors and the occurrence of SARS-CoV-2 infection. Associations with moderate-to-severe infection were analyzed using the Fine and Gray subdistribution hazard model.

Results

A sample of 2,991 residents responded to the questionnaire. A total of 2,623 primary immunized participants were included in the analysis of breakthrough infection and 2,618 in the analysis of SARS-CoV-2 infection severity after exclusions due to incomplete data. The multivariable results show that booster vaccination (HR = 0.613, 95%CI 0.415–0.823) and older age (HR = 0.974, 95%CI 0.966–0.981) were associated with a reduced hazard of breakthrough infection. Regarding the severity of breakthrough infection, older age was associated with a lower risk of moderate-to-severe breakthrough infection (HR = 0.962, 95%CI0.949–0.977). Female sex (HR = 2.570, 95%CI1.435–4.603), smoking (HR = 1.965, 95%CI1.147–3.367) and the presence of chronic lung disease (HR = 2.826, 95%CI1.465–5.450) were associated with an increased hazard of moderate-to-severe breakthrough infection.

Conclusion

The results provide a first indication of which factors may be associated with SARS-CoV-2 breakthrough infection and moderate-to-severe course of infection despite vaccination. However, the retrospective nature of the study and risk of bias in the reporting of breakthrough infection severity limit the strength of the results.

Trial registration

DRKS.de, German Clinical Trials Register (DRKS), Identifier: DRKS00024046, Registered on 25 February 2021.
Relations between the levels of moderate to vigorous physical activity, BMI, dietary habits, cognitive functions and attention problems in 8 to 9 years old pupils: network analysis (PACH Study)
Authors: Raudeniece Jelena , Vanags Edmunds , Justamente Ilze , Skara Dana , Fredriksen Per Morten , Brownlee Iain , Reihmane Dace
Published: February 2024

Background

Physical activity (PA) and dietary habits (DH) play a crucial role on quality of life and health outcomes from various aspects.

Methods

This study aims to investigate the relations between recommended daily levels of moderate to vigorous physical activity (MVPA) in 8 to 9 year old pupils, and their body mass index (BMI), DH, cognitive functions and attention problem scores by network analysis. Study participants were split into two groups based on their MVPA levels on weekdays.

Results

Our findings suggest that children who reach recommended MVPA levels consume more vegetables and fruits, eat breakfast more frequently, have better motor speed and lower impulsivity score.

Conclusions

The number of interlinkages between various parameters in network structure for children who do not reach recommended MVPA levels is greater and more intense, highlighting the differences between the groups and suggesting that different interventions and approaches to improve/change lifestyle habits might be used.
Are there any benefits for post-operative splinting after carpal tunnel release? A systematic review and meta-analysis
Authors: Peter-Okaka Uchenna I. , Shiri Samira , Owodunni Oluwafemi , Bagheri Seyed Reza , Jalilian Amir , Uzoukwu Cynthia , Eden Sonia , Alimohammadi Ehsan
Published: February 2024

Background

There is a controversy on the effectiveness of post-operating splinting in patients with carpal tunnel release (CTR) surgery. This study aimed to systematically evaluate various outcomes regarding the effectiveness of post-operating splinting in CTR surgery.

Methods

Multiple databases, including PubMed, EMBASE, CINAHL, Web of Science, and Cochrane, were searched for terms related to carpal tunnel syndrome. A total of eight studies involving 596 patients were included in this meta-analysis. The quality of studies was evaluated, and their risk of bias was calculated using the methodological index for non‐randomized studies (MINORS) and Cochrane’s collaboration tool for assessing the risk of bias in randomized controlled trials. Data including the visual analogue scale (VAS), pinch strength, grip strength, two-point discrimination, symptom severity score (SSS), and functional status scale (FSS) were extracted.

Results

Our analysis showed no significant differences between the splinted and non-splinted groups based on the VAS, SSS, FSS, grip strength, pinch strength, and two-point discrimination. The calculated values of the standardized mean difference (SMD) or the weighted mean difference (WMD) and a 95% confidence interval (CI) for different variables were as follows: VAS [SMD = 0.004, 95% CI (-0.214, 0.222)], pinch strength [WMD = 1.061, 95% CI (-0.559, 2.681)], grip strength [SMD = 0.178, 95% CI (-0.014, 0.369)], SSS [WMD = 0.026, 95% CI (- 0.191, 0.242)], FSS [SMD = 0.089, 95% CI (-0.092, 0.269)], and the two-point discrimination [SMD = 0.557, 95% CI (-0.140, 1.253)].

Conclusions

Our findings revealed no statistically significant differences between the splinted and non-splinted groups in terms of the VAS, SSS, FSS, grip strength, pinch strength, and two-point discrimination. These results indicate that there is no substantial evidence supporting a significant advantage of post-operative splinting after CTR.
Communication strategies for adults in palliative care: the speech-language therapists’ perspective
Authors: Dias Cátia , Rodrigues Inês Tello , Gonçalves Hernâni , Duarte Ivone
Published: February 2024

Background

Communication disorders are a challenge that many patients in palliative care (PC) may encounter. This intervention area is emerging for the speech-language therapist (SLT), the professional who works in preventing, assessing, diagnosing, and treating human communication disorders. This study aims to identify and classify the communication strategies considered most important by SLTs for use in PC and evaluate whether there are any differences in perception regarding the importance of strategies between SLTs with and without PC experience.

Methods

This cross-sectional quantitative study was conducted using a survey, which employed a well-structured, self-completion questionnaire previously validated by a panel of experts with over six years of PC experience.

Results

The strategies rated as most important within each group were the following: (i) adjust the patient’s position and minimise environmental noise; (ii) establish eye contact and adjust the pace of speech; (iii) adjust the language level and raise one topic at a time; (iv) use images of the patient’s interests and their personal objects; (v) use orality and multimodal form; (vi) use simplified language and structured pauses; and (vii) use tables with images and books with pictures.

Conclusions

Verbal and non-verbal strategies were rated as highly important. There was no evidence of differences in perception in terms of importance between the SLTs with or without experience in PC, but more studies are needed to support this aspect. The patient’s communication ability is one of the cornerstones of PC quality. Through their actions, speech-language professionals could empower the patient with strategies so that they can autonomously and self-determinedly express their experiences and most significant needs.
Validation of the Collett-Lester fear of death scale in occupational therapy students: psychometric testing and implications for palliative care education
Authors: Gutiérrez-Sánchez Daniel , López-Leiva Inmaculada , Martín-de-las-Heras Stella , Rubio Leticia , Martín-Martín Jaime
Published: February 2024

Background

The fear of death is a common experience among healthcare students and professionals that may impact the quality of care provided to patients, particularly those receiving palliative care. The Collett-Lester Fear of Death Scale is a widely used instrument to assess this fear, although its psychometric properties have not been extensively studied in Occupational Therapy students. The present study aimed to validate the Collett-Lester Fear of Death Scale (CL-FODS) in a sample of Occupational Therapy students and to explore its implications for palliative care education.

Method

A cross-sectional study was conducted to perform psychometric testing of the CL-FODS in Occupational Therapy undergraduate students. Structural validity, internal consistency, and test-retest reliability were analysed. A total of 195 Occupational Therapy students were included in this study. Additionally, the participants completed a brief survey on their experiences and attitudes towards palliative care.

Results

The internal consistency was satisfactory (α = 0.888). The exploratory factor analysis to evaluate the internal structure yielded four factors. The model fit indices were: comparative fit index = 0.89, and root mean square error of approximation = 0.06). The test–retest reliability was satisfactory and demonstrated an intraclass correlation coefficient of 0.939.

Conclusion

The Spanish version of the CL-FODS showed satisfactory psychometric properties; therefore, assessing fear of death in Occupational Therapy students is helpful. This study highlights the importance of addressing fear of death and palliative care education in Occupational Therapy undergraduates to improve future professional attitudes and, consequently, the quality of patient care at the end of life.
Chili pepper extracts, capsaicin, and dihydrocapsaicin as potential anticancer agents targeting topoisomerases
Authors: Hudáková Terézia , Šemeláková Martina , Očenáš Peter , Kožurková Mária , Krochtová Kristína , Sovová Simona , Tóthová Zuzana , Guľášová Zuzana , Popelka Peter , Solár Peter
Published: February 2024

DNA topoisomerases regulate conformational changes in DNA topology during normal cell growth, such as replication, transcription, recombination, and repair, and may be targeted for anticancer drugs. A DNA topology assay was used to investigate DNA-damaging/protective activities of extracts from Habanero Red (HR), Habanero Maya Red (HMR), Trinidad Moruga Scorpion (TMS), Jalapeno (J), Serrano pepper (SP), Habanero Red Savina (HRS), Bhut Jolokia (BJ), and Jamaica Rosso (JR) peppers, demonstrating their inhibitory effect on the relaxation of pBR by Topo I. DNA topoisomerase II (Topo II) is proven therapeutic target of anticancer drugs. Complete inhibition of Topo II was observed for samples TMS, HR, and HMR. Extracts J and SP had the lowest capsaicin and dihydrocapsaicin content compared to other peppers. HR, HMR, TMS, J, S, HRS, BJ, JR extracts showed the anticancer effect, examined by MTS and xCell assay on the in vitro culture of human colon carcinoma cell line HCT116.
Exploring the current state of clinical and practical teaching in obstetrics and gynecology in the era of competency-based education: a nationwide survey among German teaching coordinators
Authors: Meyer Bastian , Riedel Fabian , Amann Niklas , Graf Anna , Stuehrenberg Antonia , Ritter Viktoria , Wallwiener Markus , Heublein Sabine , Recker Florian , Weiss Martin , Riedel Maximilian
Published: February 2024

Background

Obstetrics and gynecology (OB/GYN) is an essential medical field that focuses on women’s health. Universities aim to provide high-quality healthcare services to women through comprehensive education of medical students. In Germany, medical education is undergoing a phase of restructuring towards the implementation of competency-based learning. The objective of the current survey was to gain insights into the teaching methods, resources, and challenges at German medical universities in the field OB/GYN. This aims to document the current state of medical education and derive potential suggestions for improvements in the era of competency-based learning. The survey was conducted with teaching coordinators from the majority of OB/GYN departments at German universities.

Methods

A questionnaire was sent to the teaching coordinators in all 41 OB/GYN departments at German university hospitals. The survey was delivered via email with a link to an online survey platform.

Results

The study received 30 responses from 41 universities. Differences were observed in the work environment of teaching coordinators concerning release from clinical duties for teaching purposes and specialized academic training. Overall, medical education and student motivation were perceived positively, with noticeable gaps, particularly in practical gynecological training. Deficiencies in supervision and feedback mechanisms were also evident. Subfields such as urogynecology and reproductive medicine appear to be underrepresented in the curriculum, correlating with poorer student performance. E-learning was widely utilized and considered advantageous.

Conclusion

The present study provides valuable insights into the current state of medical education in OB/GYN at German universities from the perspective of teaching experts. We highlight current deficits, discuss approaches to overcome present obstacles, and provide suggestions for improvement.
Quality indicators for collaborative care networks in persistent somatic symptoms and functional disorders: a modified delphi study
Authors: Mamo Nick , Tak Lineke M. , van de Klundert Manouk A. W. , Olde Hartman Tim C. , Rosmalen Judith G. M. , Hanssen Denise J. C.
Published: February 2024

Background

Care for persistent somatic symptoms and functional disorders (PSS/FD) is often fragmented. Collaborative care networks (CCNs) may improve care quality for PSS/FD. Effectiveness likely depends on their functioning, but we lack a straightforward quality evaluation system. We therefore aimed to develop quality indicators to evaluate CCNs for PSS/FD.

Method

Using an online three-round modified Delphi process, an expert panel provided, selected and ranked quality indicators for CCNs in PSS/FD. Recruited experts were diverse healthcare professionals with relevant experience in PSS/FD care in the Netherlands.

Results

The expert panel consisted of 86 professionals representing 15 disciplines, most commonly physiotherapists, psychologists and medical specialists. 58% had more than 10 years experience in PSS/FD care. Round one resulted in 994 quotations, which resulted in 46 unique quality indicators. These were prioritised in round two and ranked in round three by the panel, resulting in a final top ten. The top three indicators were: “shared vision of care for PSS/FD”, “pathways tailored to the individual patient”, and “sufficiently-experienced caregivers for PSS/FD”.

Conclusions

The identified quality indicators to evaluate CCNs in the field of PSS/FD can be implemented in clinical practice and may be useful in improving services and when assessing effectiveness.
Facilitators and barriers for implementing screening brief intervention and referral for health promotion in a rural hospital in Alberta: using consolidated framework for implementation research
Authors: Mah Sharon S. , Teare Gary F. , Law Jessica , Adhikari Kamala
Published: February 2024

Background

Screening, brief intervention, and referral (SBIR) is an evidence-based, comprehensive health promotion approach commonly implemented to reduce alcohol and substance use. Implementation research on SBIR demonstrate that patients find it acceptable, reduces hospital costs, and it is effective. However, SBIR implementation in hospital settings for multiple risk factors (fruit and vegetable consumption, physical activity, alcohol and tobacco use) is still emergent. More evidence is needed to guide SBIR implementation for multiple risk factors in hospital settings.

Objective

To explore the facilitators and barriers of SBIR implementation in a rural hospital using the Consolidated Framework for Implementation Research (CFIR).

Methods

We conducted a descriptive qualitative investigation consisting of both inductive and deductive analyses. We conducted virtual, semi-structured interviews, guided by the CFIR framework. All interviews were audio-recorded, and transcribed verbatim. NVivo 12 Pro was used to organize and code the raw data.

Results

A total of six key informant semi-structured interviews, ranging from 45 to 60 min, were carried out with members of the implementation support team and clinical implementers. Implementation support members reported that collaborating with health departments facilitated SBIR implementation by helping (a) align health promotion risk factors with existing guidelines; (b) develop training and educational resources for clinicians and patients; and (c) foster leadership buy-in. Conversely, clinical implementers reported several barriers to SBIR implementation including, increased and disrupted workflow due to SBIR-related documentation, a lack of knowledge on patients’ readiness and motivation to change, as well as perceived patient stigma in relation to SBIR risk factors.

Conclusion

The CFIR provided a comprehensive framework to gauge facilitators and barriers relating to SBIR implementation. Our pilot investigation revealed that future SBIR implementation must address organizational, clinical implementer, and patient readiness to implement SBIR at all phases of the implementation process in a hospital.
Analysis of heterologous expression of phaCBA promotes the acetoin stress response mechanism in Bacillus subtilis using transcriptomics and metabolomics approaches
Authors: Li Tao , Li Haixiang , Zhong Lei , Qin Yufei , Guo Gege , Liu Zhaoxing , Hao Ning , Ouyang Pingkai
Published: February 2024

Acetoin, a versatile platform chemical and popular food additive, poses a challenge to the biosafety strain Bacillus subtilis when produced in high concentrations due to its intrinsic toxicity. Incorporating the PHB synthesis pathway into Bacillus subtilis 168 has been shown to significantly enhance the strain’s acetoin tolerance. This study aims to elucidate the molecular mechanisms underlying the response of B. subtilis 168-phaCBA to acetoin stress, employing transcriptomic and metabolomic analyses. Acetoin stress induces fatty acid degradation and disrupts amino acid synthesis. In response, B. subtilis 168-phaCBA down-regulates genes associated with flagellum assembly and bacterial chemotaxis, while up-regulating genes related to the ABC transport system encoding amino acid transport proteins. Notably, genes coding for cysteine and d-methionine transport proteins (tcyB, tcyC and metQ) and the biotin transporter protein bioY, are up-regulated, enhancing cellular tolerance. Our findings highlight that the expression of phaCBA significantly increases the ratio of long-chain unsaturated fatty acids and modulates intracellular concentrations of amino acids, including l-tryptophan, l-tyrosine, l-leucine, l-threonine, l-methionine, l-glutamic acid, l-proline, d-phenylalanine, l-arginine, and membrane fatty acids, thereby imparting acetoin tolerance. Furthermore, the supplementation with specific exogenous amino acids (l-alanine, l-proline, l-cysteine, l-arginine, l-glutamic acid, and l-isoleucine) alleviates acetoin’s detrimental effects on the bacterium. Simultaneously, the introduction of phaCBA into the acetoin-producing strain BS03 addressed the issue of insufficient intracellular cofactors in the fermentation strain, resulting in the successful production of 70.14 g/L of acetoin through fed-batch fermentation. This study enhances our understanding of Bacillus’s cellular response to acetoin-induced stress and provides valuable insights for the development of acetoin-resistant Bacillus strains.
Rapid systematic review on risks and outcomes of sepsis: the influence of risk factors associated with health inequalities
Authors: Bladon Siân , Ashiru-Oredope Diane , Cunningham Neil , Pate Alexander , Martin Glen P , Zhong Xiaomin , Gilham Ellie L , Brown Colin S , Mirfenderesky Mariyam , Palin Victoria , van Staa Tjeerd P
Published: February 2024

Background and aims

Sepsis is a serious and life-threatening condition caused by a dysregulated immune response to an infection. Recent guidance issued in the UK gave recommendations around recognition and antibiotic treatment of sepsis, but did not consider factors relating to health inequalities. The aim of this study was to summarise the literature investigating associations between health inequalities and sepsis.

Methods

Searches were conducted in Embase for peer-reviewed articles published since 2010 that included sepsis in combination with one of the following five areas: socioeconomic status, race/ethnicity, community factors, medical needs and pregnancy/maternity.

Results

Five searches identified 1,402 studies, with 50 unique studies included in the review after screening (13 sociodemographic, 14 race/ethnicity, 3 community, 3 care/medical needs and 20 pregnancy/maternity; 3 papers examined multiple health inequalities). Most of the studies were conducted in the USA (31/50), with only four studies using UK data (all pregnancy related). Socioeconomic factors associated with increased sepsis incidence included lower socioeconomic status, unemployment and lower education level, although findings were not consistent across studies. For ethnicity, mixed results were reported. Living in a medically underserved area or being resident in a nursing home increased risk of sepsis. Mortality rates after sepsis were found to be higher in people living in rural areas or in those discharged to skilled nursing facilities while associations with ethnicity were mixed. Complications during delivery, caesarean-section delivery, increased deprivation and black and other ethnic minority race were associated with post-partum sepsis.

Conclusion

There are clear correlations between sepsis morbidity and mortality and the presence of factors associated with health inequalities. To inform local guidance and drive public health measures, there is a need for studies conducted across more diverse setting and countries.
Fatigue and symptom-based clusters in post COVID-19 patients: a multicentre, prospective, observational cohort study
Authors: Cornelissen Merel E. B. , Bloemsma Lizan D. , Vaes Anouk W. , Baalbaki Nadia , Deng Qichen , Beijers Rosanne J. H. C. G. , Noij Lieke C. E. , Houweling Laura , Bazdar Somayeh , Spruit Martijn A. , Maitland-van der Zee Anke H. ,   on behalf of the P4O2 Consortium
Published: February 2024

Background

In the Netherlands, the prevalence of post COVID-19 condition is estimated at 12.7% at 90–150 days after SARS-CoV-2 infection. This study aimed to determine the occurrence of fatigue and other symptoms, to assess how many patients meet the Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) criteria, to identify symptom-based clusters within the P4O2 COVID-19 cohort and to compare these clusters with clusters in a ME/CFS cohort.

Methods

In this multicentre, prospective, observational cohort in the Netherlands, 95 post COVID-19 patients aged 40–65 years were included. Data collection at 3–6 months after infection included demographics, medical history, questionnaires, and a medical examination. Follow-up assessments occurred 9–12 months later, where the same data were collected. Fatigue was determined with the Fatigue Severity Scale (FSS), a score of ≥ 4 means moderate to high fatigue. The frequency and severity of other symptoms and the percentage of patients that meet the ME/CFS criteria were assessed using the DePaul Symptom Questionnaire-2 (DSQ-2). A self-organizing map was used to visualize the clustering of patients based on severity and frequency of 79 symptoms. In a previous study, 337 Dutch ME/CFS patients were clustered based on their symptom scores. The symptom scores of post COVID-19 patients were applied to these clusters to examine whether the same or different clusters were found.

Results

According to the FSS, fatigue was reported by 75.9% of the patients at 3–6 months after infection and by 57.1% of the patients 9–12 months later. Post-exertional malaise, sleep disturbances, pain, and neurocognitive symptoms were also frequently reported, according to the DSQ-2. Over half of the patients (52.7%) met the Fukuda criteria for ME/CFS, while fewer patients met other ME/CFS definitions. Clustering revealed specific symptom patterns and showed that post COVID-19 patients occurred in 11 of the clusters that have been observed in the ME/CFS cohort, where 2 clusters had > 10 patients.

Conclusions

This study shows persistent fatigue and diverse symptomatology in post COVID-19 patients, up to 12–18 months after SARS-CoV-2 infection. Clustering showed that post COVID-19 patients occurred in 11 of the clusters that have been observed in the ME/CFS cohort.
A proteomic classifier panel for early screening of colorectal cancer: a case control study
Authors: Hua Hanju , Wang Tingting , Pan Liangxuan , Du Xiaoyao , Xia Tianxue , Fa Zhenzhong , Gu Lei , Gao Fei , Yu Chaohui , Gao Feng , Liao Lujian , Shen Zhe
Published: February 2024

Background

Diagnosis of colorectal cancer (CRC) during early stages can greatly improve patient outcome. Although technical advances in the field of genomics and proteomics have identified a number of candidate biomarkers for non-invasive screening and diagnosis, developing more sensitive and specific methods with improved cost-effectiveness and patient compliance has tremendous potential to help combat the disease.

Methods

We enrolled three cohorts of 479 subjects, including 226 CRC cases, 197 healthy controls, and 56 advanced precancerous lesions (APC). In the discovery cohort, we used quantitative mass spectrometry to measure the expression profile of plasma proteins and applied machine-learning to select candidate proteins. We then developed a targeted mass spectrometry assay to measure plasma concentrations of seven proteins and a logistic regression classifier to distinguish CRC from healthy subjects. The classifier was further validated using two independent cohorts.

Results

The seven-protein panel consisted of leucine rich alpha-2-glycoprotein 1 (LRG1), complement C9 (C9), insulin-like growth factor binding protein 2 (IGFBP2), carnosine dipeptidase 1 (CNDP1), inter-alpha-trypsin inhibitor heavy chain 3 (ITIH3), serpin family A member 1 (SERPINA1), and alpha-1-acid glycoprotein 1 (ORM1). The panel classified CRC and healthy subjects with high accuracy, since the area under curve (AUC) of the training and testing cohort reached 0.954 and 0.958. The AUC of the two independent validation cohorts was 0.905 and 0.909. In one validation cohort, the panel had an overall sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 89.9%, 81.8%, 89.2%, and 82.9%, respectively. In another blinded validation cohort, the panel classified CRC from healthy subjects with a sensitivity of 81.5%, specificity of 97.9%, and overall accuracy of 92.0%. Finally, the panel was able to detect APC with a sensitivity of 49%.

Conclusions

This seven-protein classifier is a clear improvement compared to previously published blood-based protein biomarkers for detecting early-stage CRC, and is of translational potential to develop into a clinically useful assay.
Leveraging artificial intelligence to advance implementation science: potential opportunities and cautions
Authors: Trinkley Katy E. , An Ruopeng , Maw Anna M. , Glasgow Russell E. , Brownson Ross C.
Published: February 2024

Background

The field of implementation science was developed to address the significant time delay between establishing an evidence-based practice and its widespread use. Although implementation science has contributed much toward bridging this gap, the evidence-to-practice chasm remains a challenge. There are some key aspects of implementation science in which advances are needed, including speed and assessing causality and mechanisms. The increasing availability of artificial intelligence applications offers opportunities to help address specific issues faced by the field of implementation science and expand its methods.

Main text

This paper discusses the many ways artificial intelligence can address key challenges in applying implementation science methods while also considering potential pitfalls to the use of artificial intelligence. We answer the questions of “why” the field of implementation science should consider artificial intelligence, for “what” (the purpose and methods), and the “what” (consequences and challenges). We describe specific ways artificial intelligence can address implementation science challenges related to (1) speed, (2) sustainability, (3) equity, (4) generalizability, (5) assessing context and context-outcome relationships, and (6) assessing causality and mechanisms. Examples are provided from global health systems, public health, and precision health that illustrate both potential advantages and hazards of integrating artificial intelligence applications into implementation science methods. We conclude by providing recommendations and resources for implementation researchers and practitioners to leverage artificial intelligence in their work responsibly.

Conclusions

Artificial intelligence holds promise to advance implementation science methods (“why”) and accelerate its goals of closing the evidence-to-practice gap (“purpose”). However, evaluation of artificial intelligence’s potential unintended consequences must be considered and proactively monitored. Given the technical nature of artificial intelligence applications as well as their potential impact on the field, transdisciplinary collaboration is needed and may suggest the need for a subset of implementation scientists cross-trained in both fields to ensure artificial intelligence is used optimally and ethically.
Atypical social cognition processing in bulimia nervosa: an fMRI study of patients thinking of others’ mental states
Authors: Kamashita Rio , Setsu Rikukage , Numata Noriko , Koga Yasuko , Nakazato Michiko , Matsumoto Koji , Ando Hiroki , Masuda Yoshitada , Maral Sertap , Shimizu Eiji , Hirano Yoshiyuki
Published: February 2024

Background

Feeding and eating disorders are severe mental disorders that gravely affect patients’ lives. In particular, patients with anorexia nervosa (AN) or bulimia nervosa (BN) appear to have poor social cognition. Many studies have shown the relationship between poor social cognition and brain responses in AN. However, few studies have examined the relationship between social cognition and BN. Therefore, we examined which brain regions impact the ability for social cognition in patients with BN.

Methods

We used task-based functional magnetic resonance imaging (fMRI) to examine brain responses during a social cognition task and the Reading Mind in the Eyes Test (RMET). During the fMRI, 22 women with BN and 22 healthy women (HW) took the RMET. Participants also completed the eating disorder clinical measures Bulimic Investigatory Test, Edinburgh (BITE) and Eating Disorders Examination Questionnaire (EDE-Q), the Patient Health Questionnaire (PHQ-9) measure of depression; and the Generalized Anxiety Disorder (GAD-7) measure of anxiety.

Results

No difference was observed in the RMET scores between women with BN and HW. Both groups showed activation in brain regions specific to social cognition. During the task, no differences were shown between the groups in the BOLD signal (p < 0.05, familywise error corrected for multiple comparisons). However, there was a tendency of more robust activation in the right angular gyrus, ventral diencephalon, thalamus proper, temporal pole, and middle temporal gyrus in BN (p < 0.001, uncorrected for multiple comparisons). Moreover, HW showed a positive correlation between RMET scores and the activation of two regions: medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC); however, no significant correlation was observed in women with BN.

Conclusions

While activation in the mPFC and ACC positively correlated to the RMET scores in HW, no correlation was observed in BN patients. Therefore, women with BN might display modulated neural processing when thinking of others’ mental states. Further examination is needed to investigate neural processing in BN patients to better understand their social cognition abilities.

Trial registration

UMIN, UMIN000010220. Registered 13 March 2013, https://rctportal.niph.go.jp/s/detail/um?trial_id=UMIN000010220
A tumor suppressor protein encoded by circKEAP1 inhibits osteosarcoma cell stemness and metastasis by promoting vimentin proteasome degradation and activating anti-tumor immunity
Authors: Zhang Ying , Liu Zhaoyong , Zhong Zhigang , Ji Yanchen , Guo Huancheng , Wang Weidong , Chen Chuangzhen
Published: February 2024

Background

Osteosarcoma (OS) is one of most commonly diagnosed bone cancer. Circular RNAs (circRNAs) are a class of highly stable non-coding RNA, the majority of which have not been characterized functionally. The underlying function and molecular mechanisms of circRNAs in OS have not been fully demonstrated.

Method

Microarray analysis was performed to identify circRNAs that are differentially-expressed between OS and corresponding normal tissues. The biological function of circKEAP1 was confirmed in vitro and in vivo. Mass spectrometry and western blot assays were used to identify the circKEAP1-encoded protein KEAP1-259aa. The molecular mechanism of circKEAP1 was investigated by RNA sequencing and RNA immunoprecipitation analyses.

Results

Here, we identified a tumor suppressor circKEAP1, originating from the back-splicing of exon2 of the KEAP1 gene. Clinically, circKEAP1 is downregulated in OS tumors and associated with better survival in cancer patients. N6-methyladenosine (m6A) at a specific adenosine leads to low expression of circKEAP1. Further analysis revealed that circKEAP1 contained a 777 nt long ORF and encoded a truncated protein KEAP1-259aa that reduces cell proliferation, invasion and tumorsphere formation of OS cells. Mechanistically, KEAP1-259aa bound to vimentin in the cytoplasm to promote vimentin proteasome degradation by interacting with the E3 ligase ARIH1. Moreover, circKEAP1 interacted with RIG-I to activate anti-tumor immunity via the IFN-γ pathway.

Conclusion

Taken together, our findings characterize a tumor suppressor circKEAP1 as a key tumor suppressor regulating of OS cell stemness, proliferation and migration, providing potential therapeutic targets for treatment of OS.
Extracorporeal cardiopulmonary resuscitation versus conventional CPR in cardiac arrest: an updated meta-analysis and trial sequential analysis
Authors: Low Christopher Jer Wei , Ling Ryan Ruiyang , Ramanathan Kollengode , Chen Ying , Rochwerg Bram , Kitamura Tetsuhisa , Iwami Taku , Ong Marcus Eng Hock , Okada Yohei
Published: February 2024

Background

Extracorporeal cardiopulmonary resuscitation (ECPR) may reduce mortality and improve neurological outcomes in patients with cardiac arrest. We updated our existing meta-analysis and trial sequential analysis to further evaluate ECPR compared to conventional CPR (CCPR).

Methods

We searched three international databases from 1 January 2000 through 1 November 2023, for randomised controlled trials or propensity score matched studies (PSMs) comparing ECPR to CCPR in both out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA). We conducted an updated random-effects meta-analysis, with the primary outcome being in-hospital mortality. Secondary outcomes included short- and long-term favourable neurological outcome and survival (30 days–1 year). We also conducted a trial sequential analysis to evaluate the required information size in the meta-analysis to detect a clinically relevant reduction in mortality.

Results

We included 13 studies with 14 pairwise comparisons (6336 ECPR and 7712 CCPR) in our updated meta-analysis. ECPR was associated with greater precision in reducing overall in-hospital mortality (OR 0.63, 95% CI 0.50–0.79, high certainty), to which the trial sequential analysis was concordant. The addition of recent studies revealed a newly significant decrease in mortality in OHCA (OR 0.62, 95% CI 0.45–0.84). Re-analysis of relevant secondary outcomes reaffirmed our initial findings of favourable short-term neurological outcomes and survival up to 30 days. Estimates for long-term neurological outcome and 90-day–1-year survival remained unchanged.

Conclusions

We found that ECPR reduces in-hospital mortality, improves neurological outcome, and 30-day survival. We additionally found a newly significant benefit in OHCA, suggesting that ECPR may be considered in both IHCA and OHCA.
Modelling the dynamic basic reproduction number of dengue based on MOI of Aedes albopictus derived from a multi-site field investigation in Guangzhou, a subtropical region
Authors: Guo Xiang , Li Li , Ren Wenwen , Hu Minling , Li Ziyao , Zeng Shu , Liu Xiaohua , Wang Yuji , Xie Tian , Yin Qingqing , Wei Yuehong , Luo Lei , Shi Benyun , Wang Chunmei , Wu Rangke , Yang Zhicong , Chen Xiao-Guang , Zhou Xiaohong
Published: February 2024

Background

More than half of the global population lives in areas at risk of dengue (DENV) transmission. Developing an efficient risk prediction system can help curb dengue outbreaks, but multiple variables, including mosquito-based surveillance indicators, still constrain our understanding. Mosquito or oviposition positive index (MOI) has been utilized in field surveillance to monitor the wild population density of Aedes albopictus in Guangzhou since 2005.

Methods

Based on the mosquito surveillance data using Mosq-ovitrap collection and human landing collection (HLC) launched at 12 sites in Guangzhou from 2015 to 2017, we established a MOI-based model of the basic dengue reproduction number (R0) using the classical Ross-Macdonald framework combined with a linear mixed-effects model.

Results

During the survey period, the mean MOI and adult mosquito density index (ADI) using HLC for Ae. albopictus were 12.96 ± 17.78 and 16.79 ± 55.92, respectively. The R0 estimated from the daily ADI (ADID) showed a significant seasonal variation. A 10-unit increase in MOI was associated with 1.08-fold (95% CI 1.05, 1.11) ADID and an increase of 0.14 (95% CI 0.05, 0.23) in the logarithmic transformation of R0. MOI-based R0 of dengue varied by month and average monthly temperature. During the active period of Ae. albopictus from April to November in Guangzhou region, a high risk of dengue outbreak was predicted by the MOI-based R0 model, especially from August to October, with the predicted R0 > 1. Meanwhile, from December to March, the estimates of MOI-based R0 were < 1.

Conclusions

The present study enriched our knowledge about mosquito-based surveillance indicators and indicated that the MOI of Ae. albopictus could be valuable for application in estimating the R0 of dengue using a statistical model. The MOI-based R0 model prediction of the risk of dengue transmission varied by month and temperature in Guangzhou. Our findings lay a foundation for further development of a complex efficient dengue risk prediction system.

Graphical Abstract
A smartphone-based crowd-sourced real-time surveillance platform (apple snail inspector) for the invasive snails: a design and development study
Authors: Zhang Qiang , Ding Xin , Zhang Yingshu , Yang Yougui , Mao Fanzhen , Ni Bixian , Liu Yaobao , Culleton Richard , Dai Yang , Cao Jun
Published: February 2024

Background

The large amphibious freshwater apple snail is an important invasive species in China, but there is currently no method available for their surveillance. The development and popularization of smartphones provide a new platform for research on surveillance technologies for the early detection and effective control of invasive species.

Methods

The ASI surveillance system was developed based on the infrastructure of the WeChat platform and Amap. The user can directly enter the game interface through the WeChat port on their mobile phone, and the system automatically obtains their location. The user can then report the location of apple snails. The administrator can audit the reported information, and all information can be exported to Microsoft Excel version 2016 for analysis. The map was generated by ArcGIS 10.2 and was used to characterize the spatial and temporal distribution of apple snails in Jiangsu Province.

Results

The architecture of ASI consists of three parts: a mobile terminal, a server terminal and a desktop terminal. We published more than 10 tweets on the official WeChat account of the system to announce it to the public, and a total of 207 users in 2020 and 2021 correctly reported sightings of apple snails. We identified 550 apple snails breeding sites in 2020 and 2021, featuring ponds (81%), parks (17%) and farmland (2%). In addition, most of the locations contained snail eggs, and the reporting times mainly occurred between May and September.

Conclusions

The ASI is an effective surveillance system that can be used to identify the breeding locations of apple snails and provides the basis of prevention and control for its dispersal. Its successful development and operation provide new potential avenues for surveillance of other public health issues.

Graphical Abstract
Epigenetic regulation and factors that influence the effect of iPSCs-derived neural stem/progenitor cells (NS/PCs) in the treatment of spinal cord injury
Authors: Yang Yubiao , Ma Boyuan , Chen Jinyu , Liu Derong , Ma Jun , Li Bo , Hao Jian , Zhou Xianhu
Published: February 2024

Spinal cord injury (SCI) is a severe neurological disorder that causes neurological impairment and disability. Neural stem/progenitor cells (NS/PCs) derived from induced pluripotent stem cells (iPSCs) represent a promising cell therapy strategy for spinal cord regeneration and repair. However, iPSC-derived NS/PCs face many challenges and issues in SCI therapy; one of the most significant challenges is epigenetic regulation and that factors that influence this mechanism. Epigenetics refers to the regulation of gene expression and function by DNA methylation, histone modification, and chromatin structure without changing the DNA sequence. Previous research has shown that epigenetics plays a crucial role in the generation, differentiation, and transplantation of iPSCs, and can influence the quality, safety, and outcome of transplanted cells. In this study, we review the effects of epigenetic regulation and various influencing factors on the role of iPSC-derived NS/PCs in SCI therapy at multiple levels, including epigenetic reprogramming, regulation, and the adaptation of iPSCs during generation, differentiation, and transplantation, as well as the impact of other therapeutic tools (e.g., drugs, electrical stimulation, and scaffolds) on the epigenetic status of transplanted cells. We summarize our main findings and insights in this field and identify future challenges and directions that need to be addressed and explored.