bluuebunny/crossref_metadata_2025_split huggingface dataset:
A meta-validated immune infiltration-related gene model predicts prognosis and immunotherapy sensitivity in HNSCC
Authors: Ding Yinghe , Chu Ling , Cao Qingtai , Lei Hanyu , Li Xinyu , Zhuang Quan 
Published: January 2023

Abstract
Background
Tumor microenvironment (TME) is of great importance to regulate the initiation and advance of cancer. The immune infiltration patterns of TME have been considered to impact the prognosis and immunotherapy sensitivity in Head and Neck squamous cell carcinoma (HNSCC). Whereas, specific molecular targets and cell components involved in the HNSCC tumor microenvironment remain a twilight zone.

Methods
Immune scores of TCGA-HNSCC patients were calculated via ESTIMATE algorithm, followed by weighted gene co-expression network analysis (WGCNA) to filter immune infiltration-related gene modules. Univariate, the least absolute shrinkage and selection operator (LASSO), and multivariate cox regression were applied to construct the prognostic model. The predictive capacity was validated by meta-analysis including external dataset GSE65858, GSE41613 and GSE686. Model candidate genes were verified at mRNA and protein levels using public database and independent specimens of immunohistochemistry. Immunotherapy-treated cohort GSE159067, TIDE and CIBERSORT were used to evaluate the features of immunotherapy responsiveness and immune infiltration in HNSCC.

Results
Immune microenvironment was significantly associated with the prognosis of HNSCC patients. Total 277 immune infiltration-related genes were filtered by WGCNA and involved in various immune processes. Cox regression identified nine prognostic immune infiltration-related genes (MORF4L2, CTSL1, TBC1D2, C5orf15, LIPA, WIPF1, CXCL13, TMEM173, ISG20) to build a risk score. Most candidate genes were highly expressed in HNSCC tissues at mRNA and protein levels. Survival meta-analysis illustrated high prognostic accuracy of the model in the discovery cohort and validation cohort. Higher proportion of progression-free outcomes, lower TIDE scores and higher expression levels of immune checkpoint genes indicated enhanced immunotherapy responsiveness in low-risk patients. Decreased memory B cells, CD8+ T cells, follicular helper T cells, regulatory T cells, and increased activated dendritic cells and activated mast cells were identified as crucial immune cells in the TME of high-risk patients.

Conclusions
The immune infiltration-related gene model was well-qualified and provided novel biomarkers for the prognosis of HNSCC.
Subcuticular suture and incisional surgical-site infection in elective hepatobiliary and pancreatic surgery: an open-label, pragmatic randomized clinical trial (CLOSKIN trial)
Authors: Aguirre-Allende Ignacio , Alkorta-Zuloaga Maialen , Iglesias-Gaspar Maria Teresa , Urreta-Ballobre Iratxe , García-Domínguez Amaia , Arteaga-Martin Xabier , Beguiristain-Gómez Adolfo , Medrano-Gómez Miguel Ángel , Ruiz-Montesinos Inmaculada , Riverola-Aso Ana Paula , Jiménez-Agüero Raúl , Enríquez-Navascués José María 
Published: January 2023

Abstract
Background
Subcuticular suture has proven to reduce superficial incisional SSI (si-SSI) in clean surgery. However, question remains regarding clean-contaminated procedures. The aim of this study is to assess if subcuticular suture is superior to staples in reducing si-SSI incidence in elective HBP surgery.

Methods
Single-centre, open-label, parallel, pragmatic randomized clinical trial conducted at a referral tertiary Hospital between January 2020 and April 2022. Patients eligible for elective HBP surgery were randomly assigned (1:1) to subcuticular suture or surgical staples wound closure using a minimisation method based on previously confirmed risk factors. The primary endpoint was the incidence of si-SSI. Considered secondary endpoints were major postoperative morbidity in both groups, additional wound complications, median hospital length of stay and need for re-hospitalisation.

Results
Of the 379 patients, 346 patients were randomly assigned to receive skin closure with staples (n = 173) or subcuticular suture (n = 173). After further exclusion of 11 participants, 167 and 168 patients, respectively in the control and the experimental group received their allocated intervention. For the primary endpoint, no significant differences in si-SSI rate were found: 17 (9.82%) staples group vs. 8 (4.62%) in subcuticular suture group (p = 0.062). Subset analysis confirmed absence of significant differences. As for secondary endpoints, overall wound complications did not differ significantly between two procedures: 19 (10.98%) vs. 10 (6.35%) (p = 0.127). There were no treatment related adverse events. However, occurrence of si-SSI contributed to major postoperative morbidity in both groups (p < 0.001 and p = 0.018) and to a substantially prolonged postoperative hospitalization (p = 0.015).

Conclusions
Subcuticular suture might offer a relative benefit for skin closure reducing incidence of si-SSI after elective HBP surgery, although this was found not to be clinically relevant. Yet, this should not be interpreted as equivalence among both treatments. Therefore, wound closure strategy should not be based only on these grounds.
Trial registration number: ISRCTN Registry number ISRCTN37315612 (registration date: 14/01/2020).
Advanced neonatal procedural skills: a simulation-based workshop: impact and skill decay
Authors: Stritzke Amelie , Murthy Prashanth , Fiedrich Elsa , Assaad Michael-Andrew , Howlett Alexandra , Cheng Adam , Vickers David , Amin Harish 
Published: January 2023

Abstract
Background
Trainees aiming to specialize in Neonatal Perinatal Medicine (NPM), must be competent in a wide range of procedural skills as per the Royal College of Canada. While common neonatal procedures are frequent in daily clinical practice with opportunity to acquire competence, there are substantial gaps in the acquisition of advanced neonatal procedural skills. With the advent of competency by design into NPM training, simulation offers a unique opportunity to acquire, practice and teach potentially life-saving procedural skills. Little is known on the effect of simulation training on different areas of competence, and on skill decay.

Methods
We designed a unique simulation-based 4-h workshop covering 6 advanced procedures chosen because of their rarity yet life-saving effect: chest tube insertion, defibrillation, exchange transfusion, intra-osseus (IO) access, ultrasound-guided paracentesis and pericardiocentesis. Direct observation of procedural skills (DOPS), self-perceived competence, comfort level and cognitive knowledge were measured before (1), directly after (2), for the same participants after 9–12 months (skill decay, 3), and directly after a second workshop (4) in a group of NPM and senior general pediatric volunteers.

Results
The DOPS for all six procedures combined for 23 participants increased from 3.83 to 4.59. Steepest DOPS increase pre versus post first workshop were seen for Defibrillation and chest tube insertion. Skill decay was evident for all procedures with largest decrease for Exchange Transfusion, followed by Pericardiocentesis, Defibrillation and Chest Tube. Self-perceived competence, comfort and cognitive knowledge increased for all six procedures over the four time points. Exchange Transfusion stood out without DOPS increase, largest skill decay and minimal impact on self-assessed competence and comfort. All skills were judged as better by the preceptor, compared to self-assessments.

Conclusions
The simulation-based intervention advanced procedural skills day increased preceptor-assessed directly observed procedural skills for all skills examined, except exchange transfusion. Skill decay affected these skills after 9–12 months. Chest tube insertions and Defibrillations may benefit from reminder sessions, Pericardiocentesis may suffice by teaching once. Trainees’ observed skills were better than their own assessment. The effect of a booster session was less than the first intervention, but the final scores were higher than pre-intervention.

Trial Registration
Not applicable, not a health care intervention.
Ethics and governance of trustworthy medical artificial intelligence
Authors: Zhang Jie , Zhang Zong-ming 
Published: January 2023

Abstract
Background
The growing application of artificial intelligence (AI) in healthcare has brought technological breakthroughs to traditional diagnosis and treatment, but it is accompanied by many risks and challenges. These adverse effects are also seen as ethical issues and affect trustworthiness in medical AI and need to be managed through identification, prognosis and monitoring.

Methods
We adopted a multidisciplinary approach and summarized five subjects that influence the trustworthiness of medical AI: data quality, algorithmic bias, opacity, safety and security, and responsibility attribution, and discussed these factors from the perspectives of technology, law, and healthcare stakeholders and institutions. The ethical framework of ethical values-ethical principles-ethical norms is used to propose corresponding ethical governance countermeasures for trustworthy medical AI from the ethical, legal, and regulatory aspects.

Results
Medical data are primarily unstructured, lacking uniform and standardized annotation, and data quality will directly affect the quality of medical AI algorithm models. Algorithmic bias can affect AI clinical predictions and exacerbate health disparities. The opacity of algorithms affects patients’ and doctors’ trust in medical AI, and algorithmic errors or security vulnerabilities can pose significant risks and harm to patients. The involvement of medical AI in clinical practices may threaten doctors ‘and patients’ autonomy and dignity. When accidents occur with medical AI, the responsibility attribution is not clear. All these factors affect people’s trust in medical AI.

Conclusions
In order to make medical AI trustworthy, at the ethical level, the ethical value orientation of promoting human health should first and foremost be considered as the top-level design. At the legal level, current medical AI does not have moral status and humans remain the duty bearers. At the regulatory level, strengthening data quality management, improving algorithm transparency and traceability to reduce algorithm bias, and regulating and reviewing the whole process of the AI industry to control risks are proposed. It is also necessary to encourage multiple parties to discuss and assess AI risks and social impacts, and to strengthen international cooperation and communication.
The impact of distance education on nursing students course performance in a sino-foreign cooperative program during the onset of COVID-19: a quasi-experimental study
Authors: Zhang Yu , Zhang Ning , Liu Hongyuan , Kan Yinshi , Zou Yan 
Published: January 2023

Abstract
Background
The outbreak of COVID-19 changed many studies’ teaching mode in higher education profoundly, including nursing. This study evaluated the impact of distance education on the course performance of nursing students in a nursing fundamentals course during the epidemic of COVID-19.

Methods
This is a comparative prospective and retrospective quasi-experimental study. Nursing students in a Sino-foreign cooperative program were allocated to either an intervention group (distance education, n = 48) or control group (face-to-face teaching, n = 36). A self-efficacy questionnaire, an academic engagement scale and grades of the final written examination were used to evaluate the students’ self-efficacy, academic engagement and academic performance, respectively. The data in this study were analyzed by two independent sample t-tests and the Chi-square test.
Students experiencing distance teaching had worse academic performance (p = 0.001) and lower levels of learning behavior self-efficacy (p<0.05). The total score of academic engagement (p = 0.04) for students experiencing distance teaching were significantly lower than the scores of those students in the control group.

Conclusions
In the context of COVID-19, nursing students conducted using distance education had poor course performance.
Unravelling the impact of insecticide-treated bed nets on childhood malaria in Malawi
Authors: Tangena Julie-Anne A. , Mategula Donnie , Sedda Luigi , Atkinson Peter M. 
Published: January 2023

Abstract
Background
To achieve malaria elimination it is essential to understand the impact of insecticide-treated net (ITNs) programmes. Here, the impact of ITN access and use on malaria prevalence in children in Malawi was investigated using Malaria Indicator Survey (MIS) data.

Methods
MIS data from 2012, 2014 and 2017 were used to investigate the relationship between malaria prevalence in children (6–59 months) and ITN use. Generalized linear modelling (GLM), geostatistical mixed regression modelling and non-stationary GLM were undertaken to evaluate trends, spatial patterns and local dynamics, respectively.

Results
Malaria prevalence in Malawi was 27.1% (95% CI 23.1–31.2%) in 2012 and similar in both 2014 (32.1%, 95% CI 25.5–38.7) and 2017 (23.9%, 95% CI 20.3–27.4%). ITN coverage and use increased during the same time period, with household ITN access growing from 19.0% (95% CI 15.6–22.3%) of households with at least 1 ITN for every 2 people sleeping in the house the night before to 41.7% (95% CI 39.1–44.4%) and ITN use from 41.1% (95% CI 37.3–44.9%) of the population sleeping under an ITN the previous night to 57.4% (95% CI 55.0–59.9%). Both the geostatistical and non-stationary GLM regression models showed child malaria prevalence had a negative association with ITN population access and a positive association with ITN use although affected by large uncertainties. The non-stationary GLM highlighted the spatital heterogeneity in the relationship between childhood malaria and ITN dynamics across the country.

Conclusion
Malaria prevalence in children under five had a negative association with ITN population access and a positive association with ITN use, with spatial heterogeneity in these relationships across Malawi. This study presents an important modelling approach that allows malaria control programmes to spatially disentangle the impact of interventions on malaria cases.
Maternal colonization with group B Streptococcus and antibiotic resistance in China: systematic review and meta-analyses
Authors: Wang Jing , Zhang Yan , Lin Miao , Bao Junfeng , Wang Gaoying , Dong Ruirui , Zou Ping , Chen Yuejuan , Li Na , Zhang Ting , Su Zhaoliang , Pan Xiuzhen 
Published: January 2023

Abstract
Background
Maternal rectovaginal colonization with group B Streptococcus (GBS) or Streptococcus agalactiae is the most common pathway for this disease during the perinatal period. This meta-analysis aimed to summarize existing data regarding maternal colonization, serotype profiles, and antibiotic resistance in China.

Methods
Systematic literature reviews were conducted after searching 6 databases. Meta-analysis was applied to analyze colonization rate, serotype, and antimicrobial susceptibility of GBS clinical isolates in different regions of China. Summary estimates are presented using tables, funnel plots, forest plots, histograms, violin plots, and line plots.

Results
The dataset regarding colonization included 52 articles and 195 303 pregnant women. Our estimate for maternal GBS colonization in China was 8.1% (95% confidence interval [CI] 7.2%–8.9%). Serotypes Ia, Ib, III, and V account for 95.9% of identified isolates. Serotype III, which is frequently associated with the hypervirulent clonal complex, accounts for 46.4%. Among the maternal GBS isolates using multilocus sequence typing (MLST), ST19 (25.7%, 289/1126) and ST10 (25.1%, 283/1126) were most common, followed by ST12 (12.4%, 140/1126), ST17 (4.8%, 54/1126), and ST651 (3.7%, 42/1126). GBS was highly resistant to tetracycline (75.1% [95% CI 74.0–76.3%]) and erythromycin (65.4% [95% CI 64.5–66.3%]) and generally susceptible to penicillin, ampicillin, vancomycin, ceftriaxone, and linezolid. Resistance rates of GBS to clindamycin and levofloxacin varied greatly (1.0–99.2% and 10.3–72.9%, respectively). A summary analysis of the bacterial drug resistance reports released by the China Antimicrobial Resistance Surveillance System (CARSS) in the past 5 years showed that the drug resistance rate of GBS to erythromycin, clindamycin, and levofloxacin decreased slowly from 2018 to 2020. However, the resistance rates of GBS to all 3 antibiotics increased slightly in 2021.

Conclusions
The overall colonization rate in China was much lower than the global colonization rate (17.4%). Consistent with many original and review reports in other parts of the world, GBS was highly resistant to tetracycline. However, the resistance of GBS isolates in China to erythromycin and clindamycin was greater than in other countries. This paper provides important epidemiological information, to assist with prevention and treatment of GBS colonization in these women.
Quantifying the direct cost benefits of vestibular telemetry using the CAVA system to diagnose the causes of dizziness
Authors: Phillips John S , Newman Jacob 
Published: January 2023

Abstract
Background
It can be challenging to diagnose the cause of a patient’s dizziness. Patients face significant delays before receiving a correct diagnosis as they will undergo many diagnostic tests under several different medical specialities. As well as prolonging the suffering of patients, these problems place a significant financial burden on health services worldwide. We have developed a wearable medical device which has the potential to diagnose the cause of a patient’s dizziness using vestibular telemetry captured over a thirty-day period. We sought to quantify the potential direct cost savings of an alternative diagnostic pathway using our diagnostic device.

Methods
In this work, we identified the existing diagnostic pathways followed by patients reporting dizziness to their General Practitioner, and modelled the best and worst-case direct costs of providing a patient with a correct diagnosis. We estimated the potential cost of our alternative pathway, and calculated the cost savings this could provide to the NHS.

Results
The results show that our alternative diagnostic pathway could reduce the time and direct cost associated with providing a correct diagnosis. We present a potential indicative cost-saving of between £631 and £1305, per patient.

Conclusion
Our alternative diagnostic pathway would reduce the time taken to correctly diagnose patients with vertigo. This in turn would facilitate faster access to targeted treatments, reduce unnecessary interventions, and reduce the suffering of patients. These improvements would also lead to other savings, such as reducing the amount of sick leave taken by patients to attend appointments, and freeing up of NHS time to see other patients.
Proximal tubule-derived exosomes contribute to mesangial cell injury in diabetic nephropathy via miR-92a-1-5p transfer
Authors: Tsai Yi-Chun , Kuo Mei-Chuan , Hung Wei-Wen , Wu Ping-Hsun , Chang Wei-An , Wu Ling-Yu , Lee Su-Chu , Hsu Ya-Ling 
Published: January 2023

Abstract
Background
Diabetic nephropathy (DN) is an increasing threat to human health and regarded to be the leading cause of end-stage renal disease worldwide. Exosomes delivery may play a key role in cross-talk among kidney cells and the progression of DN. However, the mechanisms underlying exosomes in DN remain unclear.

Methods
The cross-disciplinary study, including in vivo, in vitro, and human studies was conducted to explore the cross-talk between proximal tubular epithelial cells (PTECs) and mesangial cells (MCs) in DN. We purified exosome from PTECs treated with high glucose and db/db mice and assessed their influences in the pathologic change of MCs and downstream signal pathway. Healthy individuals and type 2 diabetic patients were enrolled to examine the role of exosomes in clinical applications.

Results
High glucose stimulated PTECs to secrete exosomal miR-92a-1-5p, which was taken-up by glomerular MCs, inducing myofibroblast transdifferentiation (MFT) in vitro and in vivo. PTEC-released exosomal 92a-1-5p decreased reticulocalbin-3 expression, leading to endoplasmic reticulum (ER) stress by downregulating genes essential for ER homeostasis including calreticulin and mesencephalic astrocyte-derived neurotrophic factor. Treatment with miR-92a-1-5p inhibitor ameliorated kidney damage in db/db mice with DN. Urinary miR-92a-1-5p could predict kidney injury in type 2 diabetic patients.

Conclusions
PTEC-derived exosomal miR-92a-1-5p modulated the kidney microenvironment in vivo and in vitro models, which altered ER stress and MFT in MCs resulting in DN progression. Further blocking miR-92a-1-5p epigenetic regulatory network could be a potential therapeutic strategy to prevent the progression of DN.
A drug screening to identify novel combinatorial strategies for boosting cancer immunotherapy efficacy
Authors: Zhang Zongliang , Wang Guoqing , Zhong Kunhong , Chen Yongdong , Yang Nian , Lu Qizhong , Yuan Boyang , Wang Zeng , Li Hexian , Guo Liping , Zhang Ruyuan , Wu Zhiguo , Zheng Meijun , Zhao Shasha , Tang Xin , Shao Bin , Tong Aiping 
Published: January 2023

Abstract
Background
Chimeric antigen receptor (CAR) T cells and immune checkpoint blockades (ICBs) have made remarkable breakthroughs in cancer treatment, but the efficacy is still limited for solid tumors due to tumor antigen heterogeneity and the tumor immune microenvironment. The restrained treatment efficacy prompted us to seek new potential therapeutic methods.

Methods
In this study, we conducted a small molecule compound library screen in a human BC cell line to identify whether certain drugs contribute to CAR T cell killing. Signaling pathways of tumor cells and T cells affected by the screened drugs were predicted via RNA sequencing. Among them, the antitumor activities of JK184 in combination with CAR T cells or ICBs were evaluated in vitro and in vivo.

Results
We selected three small molecule drugs from a compound library, among which JK184 directly induces tumor cell apoptosis by inhibiting the Hedgehog signaling pathway, modulates B7-H3 CAR T cells to an effector memory phenotype, and promotes B7-H3 CAR T cells cytokine secretion in vitro. In addition, our data suggested that JK184 exerts antitumor activities and strongly synergizes with B7-H3 CAR T cells or ICBs in vivo. Mechanistically, JK184 enhances B7-H3 CAR T cells infiltrating in xenograft mouse models. Moreover, JK184 combined with ICB markedly reshaped the tumor immune microenvironment by increasing effector T cells infiltration and inflammation cytokine secretion, inhibiting the recruitment of MDSCs and the transition of M2-type macrophages in an immunocompetent mouse model.

Conclusion
These data show that JK184 may be a potential adjutant in combination with CAR T cells or ICB therapy.