bluuebunny/crossref_metadata_2025 huggingface dataset:
The practice and evaluation of antifungal stewardship programs at a tertiary first-class hospital in China
Authors: Zhang Huiyuan , Wang Yinglin , Diao Ruigang , Huo Xuechen , Zhao Quan
Published: May 2024

Background

The sharp increase in fungal infections, insufficient diagnostic and treatment capabilities for fungal infections, poor prognosis of patients with fungal infections as well as the increasing drug resistance of fungi are serious clinical problems. It is necessary to explore the implementation and evaluation methods of antifungal stewardship (AFS) to promote the standardized use of antifungal drugs.

Methods

The AFS programme was implemented at a tertiary first-class hospital in China using a plan-do-check-act (PDCA) quality management tool. A baseline investigation was carried out to determine the utilization of antifungal drugs in pilot hospitals, analyse the existing problems and causes, and propose corresponding solutions. The AFS programme was proposed and implemented beginning in 2021, and included various aspects, such as team building, establishment of regulations, information construction, prescription review and professional training. The management effectiveness was recorded from multiple perspectives, such as the consumption of antifungal drugs, the microbial inspection rate of clinical specimens, and the proportion of rational prescriptions. The PDCA management concept was used for continuous improvement to achieve closed-loop management.

Results

In the first year after the implementation of the AFS programme, the consumption cost, use intensity and utilization rate of antifungal drugs decreased significantly (P < 0.01). The proportion of rational antifungal drug prescriptions markedly increased, with the proportion of prescriptions with indications increasing from 86.4% in 2019 to 97.0% in 2022, and the proportion of prescriptions with appropriate usage and dosage increased from 51.9 to 87.1%. In addition, after the implementation of the AFS programme, physicians’ awareness of the need to complete microbial examinations improved, and the number of fungal cultures and serological examinations increased substantially. Statistics from drug susceptibility tests revealed a decrease in the resistance rate of Candida to fluconazole.

Conclusion

This study indicated that the combination of AFS and the PDCA cycle could effectively reduce antifungal consumption and promote the rational use of antifungal drugs, providing a reference for other health care systems to reduce the overuse of antifungal drugs and delay the progression of fungal resistance.
Diagnostic performance of rapid antigen tests (RAT) for COVID-19 and factors associated with RAT-negative results among RT-PCR-positive individuals during Omicron BA.2, BA.5 and XBB.1 predominance
Authors: Tan Celine Y. , Zeng Kangwei , Cui Lin , Lin Raymond T P , Chen Mark
Published: May 2024

Background

While numerous studies have evaluated the real-world performance of rapid antigen tests (RATs), data on the effect of Omicron sublineages such as XBB and reinfections on RAT performance is limited. We assessed the performance of RATs and factors associated with RAT-negative results among individuals who tested SARS-CoV-2-positive by reverse transcription-polymerase chain reaction (RT-PCR).

Methods

We conducted a retrospective study among Singapore residents who underwent testing for SARS-CoV-2 with RAT (Acon Flowflex or SD Biosensor) and RT-PCR in the same clinical encounter between 9 May 2022 and 21 November 2022. RT-PCR served as a reference standard for RAT performance. Logistic regression was used to estimate the odds ratios (OR) of factors associated with negative RAT results among RT-PCR-positive cases.

Results

Of 8,620 clinical encounters analysed, 3,519 (40.8%) were SARS-CoV-2-positive on RT-PCR. Overall sensitivity and specificity of RAT was 84.6% (95% CI 83.3–85.7%) and 99.4% (95% CI 99.1–99.6%) respectively. Acon Flowflex consistently achieved higher sensitivity and specificity than SD Biosensor test kit. Among RT-PCR-positive cases, individuals who had a previous documented SARS-CoV-2 infection, coinfection with another respiratory pathogen or tested ≥ 6 days from symptom onset had higher odds of testing RAT-negative, but the associations were attenuated after adjustment for cycle threshold values (proxy for viral load). There was no significant difference in RAT performance between Omicron sublineages BA.2, BA.5 and XBB.1.

Conclusion

Diagnostic performance of RAT was not affected by changes in predominant circulating Omicron sublineages. However, reinfection cases may be under ascertained by RAT. In individuals with a previous SARS-CoV-2 infection episode or symptom onset ≥ 6 days prior to testing, a confirmatory RT-PCR may be considered if there is high clinical suspicion.
Awareness and associated factors of venous thromboembolism in breast cancer surgical patients: a cross-sectional study
Authors: Wang Qiuzhou , Chen Hongxiu , Yang Qingyu , Qiu Jiajia , Guo Sijin , Zhou Yi , Huang Lihong , Li Chen , Zhang Xiaoxia
Published: May 2024

Background

Venous thromboembolism (VTE) is a major complication of breast cancer surgical patients. Assessing VTE awareness enables medical staff to tailor educational programs that improve patient self-management and reduce VTE risk. Therefore, this study aimed to assess VTE awareness among breast cancer surgical patients and identify factors influencing their awareness level.

Methods

A multicenter cross-sectional study was conducted on breast cancer patients scheduled for surgery from May 2023 to November 2023. Data were collected using a general information form and a validated self-assessment questionnaire on VTE awareness for breast cancer surgical patients. Univariate analysis and multiple linear regression analysis were used to analyze the data.

Results

Of 1969 patients included, the term awareness rates for deep vein thrombosis and pulmonary embolism were 42.5% and 26.1%, respectively. Information about VTE was primarily obtained from doctors (30.4%), nurses (24.0%), and social media (23.3%). The overall average VTE awareness score was 1.55 ± 0.53, with the dimension of VTE preventive measures scoring highest, and VTE clinical symptoms/signs scoring lowest. Multivariate analysis identified education level, personal VTE history, chemotherapy and surgical history, and the hospital’s regional location as significant factors associated with VTE awareness level (p < 0.05).

Conclusion

This study highlights a critical need for improved VTE awareness among breast cancer surgical patients, particularly regarding clinical symptoms/signs. Health education programs are recommended especially tailored for patients with lower education levels, no history of VTE, or without prior surgery or chemotherapy, to improve their understanding of VTE.
mRNA markers for survival prediction in glioblastoma multiforme patients: a systematic review with bioinformatic analyses
Authors: Azimi Parisa , Yazdanian Taravat , Ahmadiani Abolhassan
Published: May 2024

Background

Glioblastoma multiforme (GBM) is a type of fast-growing brain glioma associated with a very poor prognosis. This study aims to identify key genes whose expression is associated with the overall survival (OS) in patients with GBM.

Methods

A systematic review was performed using PubMed, Scopus, Cochrane, and Web of Science up to Journey 2024. Two researchers independently extracted the data and assessed the study quality according to the New Castle Ottawa scale (NOS). The genes whose expression was found to be associated with survival were identified and considered in a subsequent bioinformatic study. The products of these genes were also analyzed considering protein-protein interaction (PPI) relationship analysis using STRING. Additionally, the most important genes associated with GBM patients’ survival were also identified using the Cytoscape 3.9.0 software. For final validation, GEPIA and CGGA (mRNAseq_325 and mRNAseq_693) databases were used to conduct OS analyses. Gene set enrichment analysis was performed with GO Biological Process 2023.

Results

From an initial search of 4104 articles, 255 studies were included from 24 countries. Studies described 613 unique genes whose mRNAs were significantly associated with OS in GBM patients, of which 107 were described in 2 or more studies. Based on the NOS, 131 studies were of high quality, while 124 were considered as low-quality studies. According to the PPI network, 31 key target genes were identified. Pathway analysis revealed five hub genes (IL6, NOTCH1, TGFB1, EGFR, and KDR). However, in the validation study, only, the FN1 gene was significant in three cohorts.

Conclusion

We successfully identified the most important 31 genes whose products may be considered as potential prognosis biomarkers as well as candidate target genes for innovative therapy of GBM tumors.
Multimodal imaging observation of primary vitreous cysts
Authors: Lu Siduo , Cai Ning , Yang Di
Published: May 2024

Background

Primary vitreous cyst is a clinical variant delineated by the existence of a vesicle within the vitreous cavity from birth. This particular disease tends to be uncommon, and the underlying mechanisms contributing to its pathogenesis remain obscure.

Case presentation

A 37-year-old male patient manifested blurry vision and floaters in his right eye, a symptomology first noticed three months prior. Upon slit-lamp examination, a pigmented, round, 1 papilla diameter-sized mass was discerned floating in the vitreous. A meticulous examination of the floaters was conducted using an array of multimodal imaging techniques. Other potential conditions, including cysticercosis, toxoplasmosis, and tumors, were conclusively excluded through comprehensive diagnostic tests such as blood examinations, liver ultrasound, and cranial magnetic resonance imaging (MRI), resulting in the diagnosis of a primary vitreous cyst. The patient did not report any other discomforts and did not receive any subsequent interventions or treatments.

Conclusion

We furnish an exhaustive case report of a patient diagnosed with a primary vitreous cyst. The incorporation of multimodal images in the characterization of the disease anticipates facilitating an enriched comprehension by medical practitioners.
Convergence of the dimensional assessment of personality pathology (DAPP-BQ) and the five-factor personality inventory for the international classification of diseases 11th edition (FFiCD) in the context of the five-factor model and personality disorders
Authors: Aluja Anton , Balada Ferran , Atitsogbe Kokou A. , Rossier Jérôme , García Luis F.
Published: May 2024

The current manuscript presents the convergence of the Dimensional Assessment of Personality Pathology (DAPP-BQ), using its short form the DAPP-90, and the Five-Factor Personality Inventory for International Classification of Diseases (ICD-11), the FFiCD, in the context of the five-factor personality model and the categorical approach of personality disorders (PDs). The current manuscript compares the predictive validity of both the FFiCD and the DAPP-90 regarding personality disorder scales and clusters. Results demonstrate a very high and meaningful convergence between the DAPP-90 and the FFiCD personality pathology models and a strong alignment with the FFM. The DAPP-90 and the FFiCD also present an almost identical predictive power of PDs. The DAPP-90 accounts for between 18% and 47%, and the FFiCD between 21% and 47% of PDs adjusted variance. It is concluded that both DAPP-90 and FFiCD questionnaires measure strongly similar pathological personality traits that could be described within the frame of the FFM. Additionally, both questionnaires predict a very similar percentage of the variance of personality disorders.
Elevated thyroid stimulating hormone and metabolic syndrome risk in patients with first-episode and drug-naïve major depressive disorder: a large-scale cross-sectional study
Authors: Zhang Qiaoyang , Dong Guanzhong , Zhu Xuanyan , Cao Yin , Zhang Xiangyang
Published: May 2024

Background

Metabolic syndrome (MetS) is common in major depressive disorder (MDD), but its relationship with thyroid hormones remains unclear. We aimed to examine the association of thyroid hormones and MetS in first-episode drug-naïve (FEDN) MDD patients.

Methods

We recruited 1718 unmedicated MDD patients in this cross-sectional study. MetS was defined based on the 2004 Chinese Diabetes Society Criteria. Serum thyroid hormones including free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), thyroid peroxidase antibodies (TPOAb), and anti-thyroglobulin (TGAb) were examined. We used the logistic regression model to determine risk factors for MetS and examined the performance of the regression model by using the Area Under the Curve (AUC). In addition, we performed the trend test to test whether the results were robust.

Results

The prevalence of MetS in unmedicated MDD patients was 34.4%. MDD patients with MetS had higher levels of serum TSH, TGAb, and TPOAb (all P < 0.001). Concurrently, serum TSH levels were independent risk factors for MetS in MDD patients (OR:1.49, 95%CI: 1.40–1.58), which could also distinguish MDD patients with and without MetS (AUC was 0.77). Additionally, in the trend test, the results also indicated a similar trend when TSH was used as a categorical variable (P for trend < 0.001).

Conclusions

This study suggests that TSH levels were independent risk factors for MetS in FEDN MDD patients (OR:1.49). The examination of thyroid function may contribute to the early detection of MetS.
Metaverse, virtual reality and augmented reality in total shoulder arthroplasty: a systematic review
Authors: Longo Umile Giuseppe , Lalli Alberto , Gobbato Bruno , Nazarian Ara
Published: May 2024

Purpose

This systematic review aims to provide an overview of the current knowledge on the role of the metaverse, augmented reality, and virtual reality in reverse shoulder arthroplasty.

Methods

A systematic review was performed using the PRISMA guidelines. A comprehensive review of the applications of the metaverse, augmented reality, and virtual reality in in-vivo intraoperative navigation, in the training of orthopedic residents, and in the latest innovations proposed in ex-vivo studies was conducted.

Results

A total of 22 articles were included in the review. Data on navigated shoulder arthroplasty was extracted from 14 articles: seven hundred ninety-three patients treated with intraoperative navigated rTSA or aTSA were included. Also, three randomized control trials (RCTs) reported outcomes on a total of fifty-three orthopedics surgical residents and doctors receiving VR-based training for rTSA, which were also included in the review. Three studies reporting the latest VR and AR-based rTSA applications and two proof of concept studies were also included in the review.

Conclusions

The metaverse, augmented reality, and virtual reality present immense potential for the future of orthopedic surgery. As these technologies advance, it is crucial to conduct additional research, foster development, and seamlessly integrate them into surgical education to fully harness their capabilities and transform the field. This evolution promises enhanced accuracy, expanded training opportunities, and improved surgical planning capabilities.
Bacterial sealing ability of calcium silicate-based sealer for endodontic surgery: an in-vitro study
Authors: Mansour Mai M. , Moussa Sybel M. , Meheissen Marwa A. , Aboelseoud Mahmoud R.
Published: May 2024

Background

Apical surgery with standard retrograde maneuvers may be challenging in certain cases. Simplifying apical surgery to reduce operating time and streamline retrograde manipulation is an emerging need in clinical endodontics.

Aim of the study

The aim of the study was to compare the bacterial sealing ability of a calcium silicate-based sealer with the single cone technique combined with root end resection only, and calcium silicate-based sealer as a retrograde filling versus MTA retrofilling, and to analyze bacterial viability using confocal laser scanning microscope (CLSM).

Materials and methods

In this in vitro experimental study, 50 extracted human maxillary incisor teeth were instrumented and randomly divided into five groups: three experimental groups, a positive control group, and a negative control group (n = 10/group). In the experimental groups, the roots were obturated using the single cone technique (SCT) and a calcium silicate-based sealer. In group 1, the roots were resected 3 mm from the apex with no further retrograde preparation or filling. In groups 2 and 3, the roots were resected, retroprepared, and retrofilled with either a calcium silicate-based sealer or MTA, respectively. Group 4 (positive control) was filled with a single gutta-percha cone without any sealer. In group 5 (negative control), the canals were left empty, and the roots were sealed with wax and nail varnish. A bacterial leakage model using Enterococcus faecalis was employed to assess the sealing ability over a 30-day period, checking for turbidity and analyzing colony forming units (CFUs) per milliliter. Five specimens from each group were examined using CLSM for bacterial viability. Data for the bacterial sealing ability were statistically analyzed using chi-squared and Kruskal-Wallis tests.

Results

The three experimental groups did not show significant differences in terms of bacterial leakage, or bacterial counts (CFUs) (P > 0.05). However, significant differences were observed when comparing the experimental groups to the positive control group. Notably, the calcium silicate-based sealer, when used as a retrofilling, yielded the best sealing ability. CLSM imaging revealed viable bacterial penetration in all the positive control group specimens while for the experimental groups, dead bacteria was the prominent feature seen.

Conclusion

Within the limitations of this study, it could be concluded that the bacterial sealing ability of calcium silicate-based sealer with the single cone technique combined with root end resection only and calcium silicate-based sealer as a retrograde filling were comparable with MTA retrofilling during endodontic surgical procedures.
Knowledge, attitude, and practice of Iranian adults toward Persian Medicine: a national survey
Authors: Abbassian Alireza , Abbaassi Mohammad Hossein , Pouraskari Zahra , Alaedini Farshid , Abbasi-Ghahramanloo Abbas , Emaratkar Elham , Ayati Mohammad Hossein , Khadem Ebrahim , Shirzad Meysam , Tabarrai Malihe , Choopani Rasool , Tansaz Mojgan , Sadighi Jila , Rezaeizadeh Hossein , Akhondzadeh Shahin , Khodadoost Mahmood
Published: May 2024

Background

Previous researches conducted in both developed and developing countries have demonstrated a rising trend in the utilization of complementary and alternative medicine. The World Health Organization has underscored the importance of studying the prevalence and determinants of such alternative practices. This study delves into the knowledge, attitudes, and practices of Iranian adults towards Persian medicine, a distinct form of complementary and alternative medicine, through a national survey for the first time.

Methods

A total of 2882 Iranian adults (aged ≥ 15 years) were randomly chosen from all regions. Data were gathered through structured door-to-door interviews using a survey questionnaire, wherein cases were selected randomly based on postal codes, and interviewers completed the forms at the participants’ residences.

Results

Approximately 46% of the subjects exhibited familiarity with Persian Medicine. The study revealed that the primary sources of knowledge about Persian Medicine were family, relatives, and friends, with only 2.9% indicating medical staff as their source of information. Furthermore, the study indicated that 21% of participants expressed a strong interest in using Persian Medicine, while 30.3% did not. When comparing Persian medicine to modern medicine, respondents indicated that Persian medicine is more cost-effective and has fewer side effects, yet modern medicine is more widely used globally; although, the majority responded “I don’t know” to other questions. The results also demonstrated that approximately 37% of the participants had a history of Persian Medicine utilization in their lifetime.

Conclusion

This study revealed that Iranian adults have low reliable knowledge (from medical staff, Persian medicine books and other publications) and limited familiarity with Persian medicine, with about one third of the participants expressing disinterest (attitude) and over half of them having not utilized this form of medicine (practice).
Evaluation of usability and user feedback to guide telepharmacy application development in Indonesia: a mixed-methods study
Authors: Alfian Sofa D. , Sania Jihan A. , Aini Dzulfah Q. , Khoiry Qisty A. , Griselda Meliana , Ausi Yudisia , Zakiyah Neily , Puspitasari Irma M. , Suwantika Auliya A. , Mahfud Mariska , Aji Saktian , Abdulah Rizky , Kassianos Angelos P.
Published: May 2024

Background

In Indonesia, the adoption of telepharmacy was propelled by the COVID-19 pandemic, prompting the need for a user-friendly application to support both the general population and pharmacists in accessing healthcare services. Therefore, this study aimed to evaluate usability and user feedback of a pioneering telepharmacy application known as Tanya Obat (translating to “Ask about Medications”) in Indonesia, from the perspectives of the general population and pharmacists.

Methods

A mixed-methods sequential study was conducted with the early-stage Tanya Obat application in Bandung City. Participants, including the general population and pharmacists, were instructed to use the application for a week. Questionnaires for the general population and pharmacists were distributed from March to May and February to June 2023, respectively. The System Usability Scale questionnaire was adopted to describe usability of the developed application. Further exploration of the quantitative results required collecting open-ended feedback to assess the impressions of the participants, difficulties encountered, and desired features for enhanced user-friendliness. The collected statements were summarized and clustered using thematic analysis. Subsequently, the association between the characteristics of participants and perceived usability was determined with the Chi-square test.

Result

A total of 176 participants, comprising 100 individuals from the general population and 76 pharmacists, engaged in this study. In terms of usability, the questionnaire showed that Tanya Obat application was on the borderline of acceptability, with mean scores of 63.4 and 64.1 from the general population and pharmacists, respectively. Additionally, open-ended feedback targeted at achieving a more compelling user experience was categorized into two themes, including concerns regarding the functionality of certain features and recommendations for improved visual aesthetics and bug fixes. No significant associations were observed between the characteristics of participants and perceived usability (p-value > 0.05).

Conclusion

The results showed that the perceived usability of Tanya Obat developed for telepharmacy was below average. Therefore, feature optimizations should be performed to facilitate usability of this application in Indonesia.
Automatic segmentation of 15 critical anatomical labels and measurements of cardiac axis and cardiothoracic ratio in fetal four chambers using nnU-NetV2
Authors: Liang Bocheng , Peng Fengfeng , Luo Dandan , Zeng Qing , Wen Huaxuan , Zheng Bowen , Zou Zhiying , An Liting , Wen Huiying , Wen Xin , Liao Yimei , Yuan Ying , Li Shengli
Published: May 2024

Background

Accurate segmentation of critical anatomical structures in fetal four-chamber view images is essential for the early detection of congenital heart defects. Current prenatal screening methods rely on manual measurements, which are time-consuming and prone to inter-observer variability. This study develops an AI-based model using the state-of-the-art nnU-NetV2 architecture for automatic segmentation and measurement of key anatomical structures in fetal four-chamber view images.

Methods

A dataset, consisting of 1,083 high-quality fetal four-chamber view images, was annotated with 15 critical anatomical labels and divided into training/validation (867 images) and test (216 images) sets. An AI-based model using the nnU-NetV2 architecture was trained on the annotated images and evaluated using the mean Dice coefficient (mDice) and mean intersection over union (mIoU) metrics. The model’s performance in automatically computing the cardiac axis (CAx) and cardiothoracic ratio (CTR) was compared with measurements from sonographers with varying levels of experience.

Results

The AI-based model achieved a mDice coefficient of 87.11% and an mIoU of 77.68% for the segmentation of critical anatomical structures. The model’s automated CAx and CTR measurements showed strong agreement with those of experienced sonographers, with respective intraclass correlation coefficients (ICCs) of 0.83 and 0.81. Bland–Altman analysis further confirmed the high agreement between the model and experienced sonographers.

Conclusion

We developed an AI-based model using the nnU-NetV2 architecture for accurate segmentation and automated measurement of critical anatomical structures in fetal four-chamber view images. Our model demonstrated high segmentation accuracy and strong agreement with experienced sonographers in computing clinically relevant parameters. This approach has the potential to improve the efficiency and reliability of prenatal cardiac screening, ultimately contributing to the early detection of congenital heart defects.
The mediating role of perceived social support on the relationship between lack of occupational coping self-efficacy and implicit absenteeism among intensive care unit nurses: a multicenter cross‑sectional study
Authors: Lin Qin , Fu Mengxue , Sun Kun , Liu Linfeng , Chen Pei , Li Ling , Niu Yanping , Wu Jijun
Published: May 2024

Background

Implicit absenteeism is very common among nurses. Poor perceived social support of intensive care unit nurses has a negative impact on their mental and physical health. There is evidence that lack of occupational coping self-efficacy can promote implicit absenteeism; however, the relationship between lack of occupational coping self-efficacy in perceived social support and implicit absenteeism of intensive care unit nurses is unclear. Therefore, this study aimed to evaluate the role of perceived social support between lack of occupational coping self-efficacy and implicit absenteeism of intensive care unit nurses, and to provide reliable evidence to the management of clinical nurses.

Methods

A cross-sectional study of 517 intensive care unit nurses in 10 tertiary hospitals in Sichuan province, China was conducted, of which 474 were valid questionnaires with a valid recovery rate of 91.6%. The survey tools included the Chinese version of Implicit Absenteeism Scale, the Chinese version of Perceived Social Support Scale, the Chinese version of Occupational Coping Self-Efficacy Scale and the Sociodemographic characteristics. Descriptive analysis and Pearson correlation analysis were performed using SPSS version 22.0, while the mediating effects were performed using AMOS version 24.0.

Results

The average of intensive care unit nurses had a total implicit absenteeism score of (16.87 ± 3.98), in this study, the median of intensive care unit nurses’ implicit absenteeism score was 17, there were 210 intensive care unit nurses with low implicit absenteeism (44.3%) and 264 ICU nurses with high implicit absenteeism (55.7%). A total perceived social support score of (62.87 ± 11.61), and a total lack of occupational coping self-efficacy score of (22.78 ± 5.98). The results of Pearson correlation analysis showed that implicit absenteeism was negatively correlated with perceived social support (r = -0.260, P < 0.001) and positively correlated with lack of occupational coping self-efficacy (r = 0.414, P < 0.001). In addition, we found that perceived social support plays a mediating role in lack of occupational coping self-efficacy and implicit absenteeism [β = 0.049, 95% CI of (0.002, 0.101)].

Conclusions

Intensive care unit nurses had a high level of implicit absenteeism with a moderate level of perceived social support and lack of occupational coping self-efficacy. Nursing managers should pay attention to the nurses those who were within low levels of social support and negative coping strategies, and take measures to reduce intensive care unit nurses’ professional stress, minimize implicit absenteeism.
Comprehensive analysis of KLF family reveals KLF6 as a promising prognostic and immune biomarker in pancreatic ductal adenocarcinoma
Authors: Lin Jiayu , Liu Pengyi , Sun Keyan , Jiang Lingxi , Liu Yang , Huang Yishu , Liu Jia , Shi Minmin , Zhang Jun , Wang Ting , Shen Baiyong
Published: May 2024

Background

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest tumors worldwide, with extremely aggressive and complicated biology. Krüppel-like factors (KLFs) encode a series of transcriptional regulatory proteins and play crucial roles in a variety of processes, including tumor cell differentiation and proliferation. However, the potential biological functions and possible pathways of KLFs in the progression of PDAC remain elusive.

Methods

We systematically evaluated the transcriptional variations and expression patterns of KLFs in pancreatic cancer from the UCSC Xena. Based on difference analysis, the non-negative matrix factorization (NMF) algorithm was utilized to identify the immune characteristics and clinical significance of two different subtypes. The multivariate Cox regression was used to construct the risk model and then explore the differences in tumor immune microenvironment (TIME) and drug sensitivity between high and low groups. Through single-cell RNA sequencing (scRNA-seq) analysis, we screened KLF6 and further investigated its biological functions in pancreatic cancer and pan-cancer.

Results

The KLFs exhibited differential expression and mutations in the transcriptomic profile of PDAC. According to the expression of KLFs, patients were classified into two distinct subtypes, each exhibiting significant differences in prognosis and TIME. Moreover, the KLF signature was developed using univariate Cox and Lasso regression, which proved to be a reliable and effective prognostic model. Furthermore, the KLF_Score was closely associated with immune infiltration, response to immunotherapy, and drug sensitivity and we screened small molecule compounds targeting prognostic genes separately. Through scRNA-seq analysis, KLF6 was selected to further demonstrate its role in the malignance of PC in vitro. Finally, pan-cancer analysis emphasized the biological significance of KLF6 in multiple types of tumors and its clinical utility in assessing cancer prognosis.

Conclusion

This study elucidated the pivotal role of KLF family genes in the malignant development of PC through comprehensive analysis and revealed that KLF6 would be a novel diagnostic biomolecule marker and potential therapeutic target for PDAC.
Field testing of user-friendly perennial malaria chemoprevention packaging in Benin, Côte d’Ivoire and Mozambique
Authors: Faye Sylvain Landry Birane , Lugand Maud Majeres , Offianan André Touré , Dossou-Yovo Aurélie , Kouadio Dieudonné Kouakou M’Bra , Pinto Felix
Published: May 2024

Background

Perennial malaria chemoprevention (PMC) aims to protect children at risk from severe malaria by the administration of anti-malarial drugs to children of defined ages throughout the year. Sulfadoxine-pyrimethamine (SP) has been widely used for chemoprevention in Africa and a child-friendly dispersible tablet formulation has recently become available.

Methods

This qualitative non-interventional observational study was conducted in Benin, Côte d’Ivoire, and Mozambique between February and June 2022. Prototype blister packs, dispensing boxes and job aids designed to support dispersible SP deployment for PMC were evaluated using focus group discussions (FGD) and semi-structured in-depth individual interviews (IDI) with health authorities, health personnel, community health workers (CHWs) and caregivers. The aim was to evaluate knowledge and perceptions of malaria and chemoprevention, test understanding of the tools and identify gaps in understanding, satisfaction, user-friendliness and acceptability, and assess the potential role of CHWs in PMC implementation. Interviews were transcribed and imported to ATLAS.ti for encoding and categorization. Thematic content analysis used deductive and inductive coding with cross-referencing of findings between countries and participants to enrich data interpretation. Continuous comparison across the IDI and FGD permitted iterative, collaborative development of materials.

Results

Overall, 106 participants completed IDIs and 70 contributed to FGDs. Malaria was widely recognised as the most common disease affecting children, and PMC was viewed as a positive intervention to support child health. The role of CHWs was perceived differently by the target groups, with caregivers appreciating their trusted status in the community, whereas health authorities preferred clinic-based deployment of PMC by health professionals. Empirical testing of the prototype blister packs, dispensing boxes and job aids highlighted the context-specific expectations of respondents, such as familiar situations and equipment, and identified areas of confusion or low acceptance. A key finding was the need for a clear product identity reflecting malaria.

Conclusion

Simple modifications profoundly affected the perception of PMC and influenced acceptability. Iterative quantitative investigation resulted in PMC-specific materials suited to the local context and socio-cultural norms of the target population with the aim of increasing access to chemoprevention in children most at risk of severe malaria.
Outer membrane vesicles generated by an exogenous bacteriophage lysin and protection against Acinetobacter baumannii infection
Authors: Li Changchang , Xue Heng , Du Xinjing , Nyaruaba Raphael , Yang Hang , Wei Hongping
Published: May 2024

Background

The outer membrane vesicles (OMVs) produced by Gram-negative bacteria can modulate the immune system and have great potentials for bacterial vaccine development.

Results

A highly active Acinetobacter baumannii phage lysin, LysP53, can stimulate the production of OMVs after interacting with A. baumannii, Escherichia coli, and Salmonella. The OMVs prepared by the lysin (LOMVs) from A. baumannii showed better homogeneity, higher protein yield, lower endotoxin content, and lower cytotoxicity compared to the naturally produced OMVs (nOMVs). The LOMVs contain a significantly higher number of cytoplasmic and cytoplasmic membrane proteins but a smaller number of periplasmic and extracellular proteins compared to nOMVs. Intramuscular immunization with either LOMVs or nOMVs three times provided robust protection against A. baumannii infections in both pneumonia and bacteremia mouse models. Intranasal immunization offered good protection in the pneumonia model but weaker protection (20–40%) in the bacteremia model. However, with a single immunization, LOMVs demonstrated better protection than the nOMVs in the pneumonia mouse model.

Conclusions

The novel lysin approach provides a superior choice compared to current methods for OMV production, especially for vaccine development.

Graphical Abstract
D-dimer and fibrinogen indicate ischemic risk in patients with atrial fibrillation after percutaneous coronary intervention
Authors: Gjermeni Diona , Anfang Viktoria , Szabó Sofia , Vetter Hannah , Venhoff Ana C. , Leggewie Stefan , Hesselbarth David , Trenk Dietmar , Buechsel Martin , Westermann Dirk , Olivier Christoph B.
Published: May 2024

Background

This study aimed to evaluate the association of antiphospholipid antibodies (aPL) and conventional markers of coagulation with ischemic and bleeding risk in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI).

Methods

In this prospective two-center observational cohort study, patients with AF and an indication for oral anticoagulation (OAC) were enrolled after PCI. Blood was drawn on day 1–3 after PCI. Dilute Russell’s viper venom time was used to determine lupus anticoagulant (LA) in OAC-free plasma. Anti-cardiolipin (aCL) IgG, IgM, and anti-β2-Glycoprotein 1 (aβ2GP1) IgG were analyzed by enzyme-linked immunosorbent assay (ELISA). Fibrinogen (FIB), d-dimer, and prothrombin fragment 1 and 2 (PF 1 + 2) were measured in citrated plasma. The primary ischemic outcome was time to major adverse cardiovascular events (MACE; death, myocardial infarction, or stroke) assessed at 6 months. Bleeding was defined according to International Society on Thrombosis and Haemostasis.

Results

158 patients were enrolled between May 2020 and May 2021 on day 1–3 after PCI. The median age was 78 years (interquartile range [IQR] 72–82), 111 (70%) were male, and 39 (25%) presented with acute coronary syndrome. D-dimer was elevated in 74 (47%) patients, FIB was increased in 40 (25%) and PF1 + 2 in 68 (43%) patients. 32 (20%) patients had ≥ 1 antiphospholipid antibody elevated (aPL; LA: 19 [12%], aCL: 14 [9%], aβ2GP1: 2 [1%]). The presence of aPL was neither significantly associated with MACE (HR 1.46, 95% CI [0.39–5.49], p = 0.579), nor bleeding (HR 1.07 [0.30–3.84], p = 0.917). Elevated d-dimer was significantly associated with higher risk for MACE (HR 5.06 [1.09–23.41], p = 0.038) and major bleeding (HR 7.04 [1.58–31.47], p = 0.011). Elevated D-dimer increased the predictive capacity of HAS-BLED for major bleedings (HAS-BLED: AUC 0.71 [0.60–0.83] vs. HAS-BLED + d-dimer: AUC 0.79 [0.70–0.88]; p = 0.025). Increased levels of FIB were associated with higher risk for MACE (HR 3.65 [1.11–11.96], p = 0.033).

Conclusion

Biomarkers of coagulation might be suitable to assess ischemic and bleeding risk in patients with AF following PCI.
Thyroid papillary carcinoma combined with primary follicular lymphoma: a case report
Authors: Xu Ting , Wu Li , Ye Hua , Luo Shuai , Wang Jinjing
Published: May 2024

Background

Papillary thyroid carcinoma (PTC) stands out as the most prevalent epithelial malignant thyroid tumor. Thyroid primary follicular lymphoma (PFL) represents a rare malignant tumor originating from mesenchymal tissues. The concurrent occurrence of PTC and PFL is exceptionally rare, particularly in the context of Hashimoto’s thyroiditis, presenting significant challenges in clinical diagnosis and treatment.

Case demonstration

A 44-year-old female patient presented with a neck mass persisting for over 1 month. The patient underwent surgery, and the incised tissues were subjected to pathology examinations, along with immunohistochemistry and next-generation sequencing tests suggestive of an EZH2 gene mutation in the tumor cells. The final pathological diagnosis confirmed the presence of PTC combined with PFL. Following a 27-month follow-up, the patient displayed no signs of recurrence or metastasis.

Conclusions

The concurrent occurrence of PTC and PFL poses notable challenges in clinical practice, requiring careful consideration in diagnosis and treatment. Herein, we present a rare case of PTC combined with PFL featuring an EZH2 gene mutation, which can be easily overlooked in the context of Hashimoto’s thyroiditis. The patient’s favorable response to surgical and radiotherapeutic interventions underscores the importance of accurate diagnosis and tailored treatment strategies in similar cases.
Convolutional neural networks combined with conventional filtering to semantically segment plant roots in rapidly scanned X-ray computed tomography volumes with high noise levels
Authors: Teramoto Shota , Uga Yusaku
Published: May 2024

Background

X-ray computed tomography (CT) is a powerful tool for measuring plant root growth in soil. However, a rapid scan with larger pots, which is required for throughput-prioritized crop breeding, results in high noise levels, low resolution, and blurred root segments in the CT volumes. Moreover, while plant root segmentation is essential for root quantification, detailed conditional studies on segmenting noisy root segments are scarce. The present study aimed to investigate the effects of scanning time and deep learning-based restoration of image quality on semantic segmentation of blurry rice (Oryza sativa) root segments in CT volumes.

Results

VoxResNet, a convolutional neural network-based voxel-wise residual network, was used as the segmentation model. The training efficiency of the model was compared using CT volumes obtained at scan times of 33, 66, 150, 300, and 600 s. The learning efficiencies of the samples were similar, except for scan times of 33 and 66 s. In addition, The noise levels of predicted volumes differd among scanning conditions, indicating that the noise level of a scan time ≥ 150 s does not affect the model training efficiency. Conventional filtering methods, such as median filtering and edge detection, increased the training efficiency by approximately 10% under any conditions. However, the training efficiency of 33 and 66 s-scanned samples remained relatively low. We concluded that scan time must be at least 150 s to not affect segmentation. Finally, we constructed a semantic segmentation model for 150 s-scanned CT volumes, for which the Dice loss reached 0.093. This model could not predict the lateral roots, which were not included in the training data. This limitation will be addressed by preparing appropriate training data.

Conclusions

A semantic segmentation model can be constructed even with rapidly scanned CT volumes with high noise levels. Given that scanning times ≥ 150 s did not affect the segmentation results, this technique holds promise for rapid and low-dose scanning. This study offers insights into images other than CT volumes with high noise levels that are challenging to determine when annotating.
Therapies for cutaneous squamous cell carcinoma in recessive dystrophic epidermolysis bullosa: a systematic review of 157 cases
Authors: Hwang Austin , Kwon Andie , Miller Corinne H. , Reimer-Taschenbrecker Antonia , Paller Amy S.
Published: May 2024

Background

Invasive cutaneous squamous cell carcinomas (cSCC) are a leading cause of death in recessive dystrophic epidermolysis bullosa (RDEB), a rare blistering genodermatosis. Outcomes of RDEB-cSCC therapies have primarily been described in case reports. Systematic studies are scarce. This systematic review aims to assess the pathophysiology, clinical characteristics, and outcomes of RDEB-cSCCs, with a focus on results and mechanisms of recent immunotherapies and anti-EGFR treatments.

Results

A systematic literature search of epidermolysis bullosa and cSCC was performed in February 2024, using PubMed, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and EudraCT databases. Cases with administration of systematic therapies and unpublished outcomes regarding death were tracked with corresponding authors. Data extraction and risk of bias assessment was performed by two independent reviewers. Of 1132 references in the original search, 163 relevant articles were identified, representing 59 case reports, 7 cohort studies, 49 abstracts, 47 in-vitro/in-vivo experiments, and 1 bioinformatic study. From these, 157 cases of RDEB-cSCCs were included. The majority of RDEB-cSCCs were well-differentiated (64.1%), ulcerated (59.6%), and at least 2 cm in size (77.6%), with a median age at diagnosis of 30 years old (range 6–68.4). Surgery was the primary form of treatment (n = 128), followed by chemotherapy and radiotherapy. Anti-EGFR therapy and immunotherapy was also reported beginning in 2009 and 2019, respectively. Survival time from first cSCC diagnosis to death was available in 50 cases. When stratified by their treatment regimen, median survival time was 1.85 years (surgery + chemotherapy, n = 6), 2 years (surgery only, n = 19), 4.0 years (+ anti-EFGR therapy, n = 10), 4 years (surgery + radiotherapy, n = 9), 4.6 years (+ immunotherapy, n = 4), and 9.5 years (surgery + chemotherapy + radiotherapy; n = 2). Treatment-related adverse events were primarily limited to impaired wound healing for immunotherapies and nausea and fatigue for anti-EGFR therapies.

Conclusions

Despite the challenges of a limited sample size in a rare disease, this systematic review provides an overview of treatment options for cSCCs in RDEB. When surgical treatment options have been exhausted, the addition of immunotherapy and/or anti-EGFR therapies may extend patient survival. However, it is difficult to attribute extended survival to any single treatment, as multiple therapeutic modalities are often used to treat RDEB-cSCCs.
Brain perfusion changes in beta-thalassemia
Authors: Manara Renzo , Ponticorvo Sara , Contieri Marcella , Canna Antonietta , Russo Andrea Gerardo , Fedele Maria Cristina , Rocco Maria Chiara , Borriello Adriana , Valeggia Silvia , Pennisi Maria , De Angelis Marianna , Roberti Domenico , Cirillo Mario , di Salle Francesco , Perrotta Silverio , Esposito Fabrizio , Tartaglione Immacolata
Published: May 2024

Background

Brain injury in hereditary hemoglobinopathies is commonly attributed to anemia-related relative hypoperfusion in terms of impaired oxygen blood supply. Supratentorial and infratentorial vascular watershed regions seem to be especially vulnerable, but data are very scarce.

Aims

We investigated a large beta-thalassemia sample with arterial spin labeling in order to characterize regional perfusion changes and their correlation with phenotype and anemia severity.

Methods

We performed a multicenter single-scanner cross-sectional 3T-MRI study analyzing non-invasively the brain perfusion in 54 transfusion-dependent thalassemia (TDT), 23 non-transfusion-dependent thalassemia (NTDT) patients and 56 Healthy Controls (HC). Age, hemoglobin levels, and cognitive functioning were recorded.

Results

Both TDT and NTDT patients showed globally increased brain perfusion values compared to healthy controls, while no difference was found between patient subgroups. Using age and sex as covariates and scaling the perfusion maps for the global cerebral blood flow, beta-thalassemia patients showed relative hyperperfusion in supratentorial/infratentorial watershed regions. Perfusion changes correlated with hemoglobin levels (p = 0.013) and were not observed in the less severely anemic patients (hemoglobin level > 9.5 g/dL). In the hyperperfused regions, white matter density was significantly decreased (p = 0.0003) in both patient subgroups vs. HC. In NTDT, white matter density changes correlated inversely with full-scale Intelligence Quotient (p = 0.007) while in TDT no correlation was found.

Conclusion

Relative hyperperfusion of watershed territories represents a hemodynamic hallmark of beta-thalassemia anemia challenging previous hypotheses of brain injury in hereditary anemias. A careful management of anemia severity might be crucial for preventing structural white matter changes and subsequent long-term cognitive impairment.