bluuebunny/crossref_metadata_2025 huggingface dataset:
Healthcare professionals’ perception on emergence of security threat using digital health technologies in healthcare delivery
Authors: Kissi Jonathan , Azakpah Godwin , Mensah Nathan Kumasenu , Dzamvivie Kennedy , Bosompem Twisty Ampofowaa , Wireko Victor Adu , Amoah-Anomah Grace
Published: June 2024

Background

The advancement of digital health technologies (DHTs) in the healthcare industry has revolutionized healthcare by improving efficiency and accessibility. The shift from paper-based records to electronic health records (EHRs) as a result of modern technologies introduced various security threats, endangering patient data privacy and system reliability. This study explores intricate security threats among healthcare professionals affecting DHT utilization.

Methodology

A structured questionnaire was designed to solicit for data from healthcare professionals on the existence of possible security threats, magnitude of physical and technical threats, and the extent to which the activities of staff and vendors affect the current DHTs being utilized in Cape Coast Teaching Hospital and Directorate of University Health Services at the University of Cape Coast. Purposive and convenience sampling techniques were employed to select healthcare professionals from various medical fields, and their views were captured for the study.

Results

Findings and data analyzed from the study revealed that technical threats, such as hacking, phishing, malware, and encryption weaknesses, pose more substantial dangers to DHTs compared to physical threats. The study explored viable strategies to prevent unauthorized access to DHTs and safeguard patient information. Encouraging measures, such as encryption, multi-factor authentication, regular security training, and periodic password changes, emerged as promising methods in addressing DHT security threats.

Conclusion

The study emphasizes the necessity of robust security measures and regular updates to effectively counter the emerging security threats. It underscores the critical necessity for a comprehensive protocol to enhance DHT security, addressing physical, technical, and personnel-related threats.
Psychometric Evaluation of the Trauma-Informed Care Provider Assessment Tool
Authors: Hanson Carl L. , Crandall Ali , Novilla M. Lenneth B. , Bird Kaitlyn Tan
Published: June 2024

The increasing recognition of adverse childhood experiences as a significant factor in adult health outcomes underscores the need for trauma-informed care (TIC) in healthcare settings. The purpose of this study was to assess the psychometric properties of the TIC Provider Assessment Tool (TIC-PAT) designed for primary care providers. The TIC-PAT aligns with the TIC Pyramid framework and assesses both universal trauma precautions and trauma-specific care. A total of 176 primary care providers in the United States completed the TIC-PAT through an anonymous online survey. Findings through exploratory and confirmatory factor analyses revealed a unidimensional (one-factor) model, consolidating questions into a concise 10-item measure. This study contributes an efficient assessment tool for the provision of TIC by primary care providers in healthcare settings, promoting better patient–provider interactions and enhancing provider awareness of trauma's impact on health.
Leaving post-anything urban studies behind?
Authors: Emery Jay
Published: June 2024

Luger and Schwarze's critical unsettling of postindustrial is a presciently welcome one. For some years now, I—and others—have become increasingly uncomfortable with referring to and describing the locations of our research as “postindustrial.” The main focus of this commentary is on the facets of Luger and Schwarze's (2024) arguments as they relate to nonmetropolitan deindustrializing urbanisms in the North Atlantic in an attempt to develop how we better conceptualize, understand and do justice to and with such spaces. The main thrust of the contribution is for the affective intensities and traumas of deindustrialization to be brought into closer analytical dialog with the profusion of processes associated with, in particular, “organized abandonment” and “neoliberal urbanism.” If classed experiences and knowledge shape these dialogs, there remains hope for urban studies to contribute to an emergent multiethnic class politics around commonalities of contemporary as well as historical class violence.
PhyloNext: a pipeline for phylogenetic diversity analysis of GBIF-mediated data
Authors: Mikryukov Vladimir , Abarenkov Kessy , Laffan Shawn , Robertson Tim , McTavish Emily Jane , Jeppesen Thomas Stjernegaard , Waller John , Blissett Matthew , Kõljalg Urmas , Miller Joseph T.
Published: June 2024

Background

Understanding biodiversity patterns is a central topic in biogeography and ecology, and it is essential for conservation planning and policy development. Diversity estimates that consider the evolutionary relationships among species, such as phylogenetic diversity and phylogenetic endemicity indices, provide valuable insights into the functional diversity and evolutionary uniqueness of biological communities. These estimates are crucial for informed decision-making and effective global biodiversity management. However, the current methodologies used to generate these metrics encounter challenges in terms of efficiency, accuracy, and data integration.

Results

We introduce PhyloNext, a flexible and data-intensive computational pipeline designed for phylogenetic diversity and endemicity analysis. The pipeline integrates GBIF occurrence data and OpenTree phylogenies with the Biodiverse software. PhyloNext is free, open-source, and provided as Docker and Singularity containers for effortless setup. To enhance user accessibility, a user-friendly, web-based graphical user interface has been developed, facilitating easy and efficient navigation for exploring and executing the pipeline. PhyloNext streamlines the process of conducting phylogenetic diversity analyses, improving efficiency, accuracy, and reproducibility. The automated workflow allows for periodic reanalysis using updated input data, ensuring that conservation strategies remain relevant and informed by the latest available data.

Conclusions

PhyloNext provides researchers, conservationists, and policymakers with a powerful tool to facilitate a broader understanding of biodiversity patterns, supporting more effective conservation planning and policy development. This new pipeline simplifies the creation of reproducible and easily updatable phylogenetic diversity analyses. Additionally, it promotes increased interoperability and integration with other biodiversity databases and analytical tools.
Transcriptome analysis of the Japanese eel (Anguilla japonica) during larval metamorphosis
Authors: Sudo Ryusuke , Asakura Taiga , Ishikawa Takashi , Hatakeyama Rui , Fujiwara Atushi , Inoue Komaki , Mochida Keiichi , Nomura Kazuharu
Published: June 2024

Background

Anguillid eels spend their larval period as leptocephalus larvae that have a unique and specialized body form with leaf-like and transparent features, and they undergo drastic metamorphosis to juvenile glass eels. Less is known about the transition of leptocephali to the glass eel stage, because it is difficult to catch the metamorphosing larvae in the open ocean. However, recent advances in rearing techniques for the Japanese eel have made it possible to study the larval metamorphosis of anguillid eels. In the present study, we investigated the dynamics of gene expression during the metamorphosis of Japanese eel leptocephali using RNA sequencing.

Results

During metamorphosis, Japanese eels were classified into 7 developmental stages according to their morphological characteristics, and RNA sequencing was used to collect gene expression data from each stage. A total of 354.8 million clean reads were generated from the body and 365.5 million from the head, after the processing of raw reads. For filtering of genes that characterize developmental stages, a classification model created by a Random Forest algorithm was built. Using the importance of explanatory variables feature obtained from the created model, we identified 46 genes selected in the body and 169 genes selected in the head that were defined as the “most characteristic genes” during eel metamorphosis. Next, network analysis and subsequently gene clustering were conducted using the most characteristic genes and their correlated genes, and then 6 clusters in the body and 5 clusters in the head were constructed. Then, the characteristics of the clusters were revealed by Gene Ontology (GO) enrichment analysis. The expression patterns and GO terms of each stage were consistent with previous observations and experiments during the larval metamorphosis of the Japanese eel.

Conclusion

Genome and transcriptome resources have been generated for metamorphosing Japanese eels. Genes that characterized metamorphosis of the Japanese eel were identified through statistical modeling by a Random Forest algorithm. The functions of these genes were consistent with previous observations and experiments during the metamorphosis of anguillid eels.
The nuclear and mitochondrial genome assemblies of Tetragonisca angustula (Apidae: Meliponini), a tiny yet remarkable pollinator in the Neotropics
Authors: Ferrari Rafael Rodrigues , Ricardo Paulo Cseri , Dias Felipe Cordeiro , de Souza Araujo Natalia , Soares Dalliane Oliveira , Zhou Qing-Song , Zhu Chao-Dong , Coutinho Luiz Lehmann , Arias Maria Cristina , Batista Thiago Mafra
Published: June 2024

Background

The field of bee genomics has considerably advanced in recent years, however, the most diverse group of honey producers on the planet, the stingless bees, are still largely neglected. In fact, only eleven of the ~ 600 described stingless bee species have been sequenced, and only three using a long-read (LR) sequencing technology. Here, we sequenced the nuclear and mitochondrial genomes of the most common, widespread and broadly reared stingless bee in Brazil and other neotropical countries—Tetragonisca angustula (popularly known in Brazil as jataí).

Results

A total of 48.01 Gb of DNA data were generated, including 2.31 Gb of Pacific Bioscience HiFi reads and 45.70 Gb of Illumina short reads (SRs). Our preferred assembly comprised 683 contigs encompassing 284.49 Mb, 62.84 Mb of which (22.09%) corresponded to 445,793 repetitive elements. N50, L50 and complete BUSCOs reached 1.02 Mb, 91 contigs and 97.1%, respectively. We predicted that the genome of T. angustula comprises 17,459 protein-coding genes and 4,108 non-coding RNAs. The mitogenome consisted of 17,410 bp, and all 37 genes were found to be on the positive strand, an unusual feature among bees. A phylogenomic analysis of 26 hymenopteran species revealed that six odorant receptor orthogroups of T. angustula were found to be experiencing rapid evolution, four of them undergoing significant contractions.

Conclusions

Here, we provided the first nuclear and mitochondrial genome assemblies for the ecologically and economically important T. angustula, the fourth stingless bee species to be sequenced with LR technology thus far. We demonstrated that even relatively small amounts of LR data in combination with sufficient SR data can yield high-quality genome assemblies for bees.
Comprehensive identification and systematical characterization of BRX gene family and the functional of GhBRXL5A in response to salt stress
Authors: Zhu Shouhong , Li Yan , Chen Wei , Yao Jinbo , Fang Shengtao , Pan Jingwen , Wan Wenting , Tabusam Javaria , Lv Youjun , Zhang Yongshan
Published: June 2024

Background

BRVIS RADIX (BRX) family is a small gene family with the highly conserved plant-specific BRX domains, which plays important roles in plant development and response to abiotic stress. Although BRX protein has been studied in other plants, the biological function of cotton BRX-like (BRXL) gene family is still elusive.

Result

In this study, a total of 36 BRXL genes were identified in four cotton species. Whole genome or segmental duplications played the main role in the expansion of GhBRXL gene family during evolutionary process in cotton. These BRXL genes were clustered into 2 groups, α and β, in which structural and functional conservation within same groups but divergence among different groups were found. Promoter analysis indicated that cis-elements were associated with the phytohormone regulatory networks and the response to abiotic stress. Transcriptomic analysis indicated that GhBRXL2A/2D and GhBRXL5A/5D were up/down-regulated in response to the different stress. Silencing of GhBRXL5A gene via virus-induced gene silencing (VIGS) improved salt tolerance in cotton plants. Furthermore, yeast two hybrid analysis suggested homotypic and heterotypic interactions between GhBRXL1A and GhBRXL5D.

Conclusions

Overall, these results provide useful and valuable information for understanding the evolution of cotton GhBRXL genes and their functions in salt stress.
The challenges associated with the prevention of smuggling and counterfeiting health goods in Iran
Authors: Mahmoudi Meymand Farzaneh , Takian Amirhossein , Jaafaripooyan Ebrahim
Published: June 2024

Background

Smuggling health goods given the importance and critical nature of health services should be undeniably addressed and controlled by all countries. This issue is especially more widespread in developing countries with more damaging consequences. This paper therefore aims to identify and analyze the challenges of preventing smuggling of health goods in Iran.

Method

Within this qualitative study, we conducted face-to-face, semi-structured interviews with 30 purposefully recruited key informants and stakeholders in the detection, prevention, and combating of health goods smuggling. Each interview was analyzed thematically, using an inductive approach to generate codes, then categorized and presented in the form of main themes and sub-themes. Maxqda 11 assisted in coding, analysis, and data management.

Results

Three main themes emerged representing the challenges of prevention of smuggling in Iran in the areas of anti-smuggling policy development, including categories of inefficient policy and plan, and failure to reach agenda; policy implementation; categorized into actors, resources and instruments, and implementation guarantee; and finally monitoring and evaluation; including, procedures and practices, and the role of surveyors.

Conclusion

Prevention of smuggling health goods proves to be a highly complex, challenging, and multi-faceted practice. Therefore, strengthening policy-making, regulatory frameworks, and facilitation functions about smuggling, counterfeiting, and corruption should be promoted in parallel.
Effectiveness of cognitive rehearsal programs for the prevention of workplace bullying among hospital nurses: a systematic review and meta-analysis
Authors: Jeong Yulliana , Jung Hye Sun , Baek Eun Mi
Published: June 2024

Background

To solve the problem of workplace bullying among nurses, it is necessary to review the effects of interventions and generalize the findings. We conducted a systematic literature review and meta-analysis to evaluate the effects of cognitive rehearsal programs on workplace bullying among hospital nurses.

Methods

Data were collected from March 30 to April 11, 2021, and 11,048 journal articles published in South Korea and internationally were examined across eight databases. Nine articles were selected for inclusion in the systematic literature review; five of the nine studies were included in the meta-analysis. For randomized controlled trials, the risk of bias was evaluated, and for non-randomized controlled trials, the study quality was evaluated using the Risk of Bias for Non-randomized Studies version 2.0. Egger’s regression test was performed to determine publication bias.

Results

Of the nine articles selected for this study, two were randomized controlled trials and seven were non-randomized controlled trials. The I2 value was 18.9%, indicating non-significant heterogeneity. The overall effect size of the cognitive rehearsal programs was -0.40 (95% confidence interval: -0.604 to -0.196; Z = -3.85; p = .0001) in a random-effects model, indicating a large effect size with statistical significance.

Conclusions

Therefore, cognitive rehearsal programs that address workplace bullying among hospital nurses are effective. Health policymakers must implement cognitive rehearsal programs in a policy manner to address the problems of bullying in the workplace.
Risk of breakthrough infection and hospitalisation after COVID-19 primary vaccination by HIV status in four Italian regions during 2021
Authors: Mateo-Urdiales Alberto , Fabiani Massimo , Mayer Flavia , Sacco Chiara , Belleudi Valeria , Da Cas Roberto , Fotakis Emmanouil Alexandros , De Angelis Luigi , Cutillo Maria , Petrone Daniele , Morciano Cristina , Cannone Andrea , Del Manso Martina , Riccardo Flavia , Bella Antonino , Menniti-Ippolito Franscesca , Pezzotti Patrizio , Spila Alegiani Stefania , Massari Marco
Published: June 2024

Background

As of 2024, vaccination remains the main mitigation measure against COVID-19, but there are contradictory results on whether people living with HIV (PLWH) are less protected by vaccines than people living without HIV (PLWoH). In this study we compared the risk of SARS-CoV-2 infection and COVID-19 hospitalisation following full vaccination in PLWH and PLWoH.

Methods

We linked data from the vaccination registry, the COVID-19 surveillance system and from healthcare/pharmacological registries in four Italian regions. We identified PLWH fully vaccinated (14 days post completion of the primary cycle) and matched them at a ratio of 1:4 with PLWoH by week of vaccine administration, age, sex, region of residence and comorbidities. Follow-up started on January 24, 2021, and lasted for a maximum of 234 days. We used the Kaplan-Meier estimator to calculate the cumulative incidence of infection and COVID-19 hospitalisation in both groups, and we compared risks using risk differences and ratios taking PLWoH as the reference group.

Results

We matched 42,771 PLWH with 171,084 PLWoH. The overall risk of breakthrough infection was similar in both groups with a rate ratio (RR) of 1.10 (95% confidence interval (CI):0.80–1.53). The absolute difference between groups at the end of the study period was 8.28 events per 10,000 person-days in the PLWH group (95%CI:-18.43-40.29). There was a non-significant increase the risk of COVID-19 hospitalisation among PLWH (RR:1.90; 95%CI:0.93–3.32) which corresponds to 6.73 hospitalisations per 10,000 individuals (95%CI: -0.57 to 14.87 per 10,000).

Conclusions

Our findings suggest PLWH were not at increased risk of breakthrough SARS-CoV-2 infection or COVID-19 hospitalisation following a primary cycle of mRNA vaccination.
Predictive significance of systemic immune-inflammation index combined with prealbumin for postoperative pneumonia following lung resection surgery
Authors: Miao Haihang , Ge Dingying , Wang Qianwen , Zhou Lulu , Chen Hongsheng , Qin Yibin , Zhang Faqiang
Published: June 2024

Background

We aimed to determine whether systemic immune-inflammation index (SII) combined with prealbumin can provide better predictive power for postoperative pneumonia in patients undergoing lung resection surgery.

Methods

We identified eligible patients undergoing lung resection surgery at the Affiliated Hospital of Nantong University from March 2021 to March 2022. Demographic characteristics, clinical data, and laboratory information were collected and reviewed from the electronic medical records of the patients. To test the effect of the combined detection of SII and prealbumin, we made an equation using logistic regression analysis. The receiver operating characteristic curve (ROC) was plotted to evaluate the predictive powers, sensitivity, and specificity of prealbumin, SII, and SII combined with prealbumin. Decision curve analysis (DCA) was used to determine the clinical validity and net benefit of different methods of detection.

Results

Totally 386 eligible patients were included with a median age of 62.0 years (IQR: 55.0, 68.0), and 57 (14.8%) patients presented with postoperative pneumonia within 7 days after surgery. The multivariate regression analysis showed that preoperative SII as continuous variable was associated with an increased risk of postoperative pneumonia (OR: 1.38, 95% CI: 1.19–2.83, P = 0.011), whereas the prealbumin as continuous variable remained as an independent protective predictor of postoperative pneumonia in the adjusted analysis (OR: 0.80, 95% CI: 0.37–0.89, P = 0.023). Compared to SII or prealbumin, the combined detection of preoperative SII and prealbumin showed a higher predictive power with area under curve of 0.79 (95% CI: 0.71–0.86, P < 0.05 for all). Additionally, DCA indicated that the combined detection was superior over preoperative SII or prealbumin alone in clinical validity and net benefit.

Conclusion

Both preoperative SII and prealbumin are independent influencing factors for postoperative pneumonia after lung resection surgery. The combined detection of preoperative SII and prealbumin can significantly improve prediction capability to identify potential postoperative pneumonia-susceptible patients, facilitating early interventions to improve postoperative quality of life for surgical lung resection patients.
The potential of organoids in renal cell carcinoma research
Authors: Chen Qiuyang , Sun Xuan , Li Yubei , Yang Xinyue , Yang Xuejian , Xu Haifei , Cai Hongzhou , Hu Jun
Published: June 2024

Renal cell carcinoma, a leading cause of death in urological malignancies, arises from the nephron. Its characteristics include diversity in disease biology, varied clinical behaviors, different prognoses, and diverse responses to systemic therapies. The term ‘organoids’ is used to describe structures resembling tissues created through the three-dimensional cultivation of stem cells in vitro. These organoids, when derived from tumor tissues, can retain the diversity of the primary tumor, mirror its spatial tissue structure, and replicate similar organ-like functions. In contrast to conventional two-dimensional cell cultures and the transplantation of tumor tissues into other organisms, organoids derived from tumors maintain the complexity and microenvironment of the original tumor tissue. This fidelity makes them a more reliable model for the development of cancer drugs, potentially accelerating the translation of these drugs to clinical use and facilitating personalized treatment options for patients. This review aims to summarize the recent advancements in the use of organoids for studying renal cell carcinoma, focusing on their cultivation, potential applications, and inherent limitations.
Benefit finding among family caregivers of patients with advanced cancer in a palliative treatment: a qualitative study
Authors: Song Yuanyi , Wang Min , Zhu Meina , Wang Na , He Ting , Wu Xu , Shi Zhihui , Chen Mengye , Ji Tian , Shen Ying
Published: June 2024

Background

Benefit finding is the search for positive meaning from traumatic events, such as cancer. It can help caregivers have a positive experience in the caregiving process, relieve negative emotions, and reduce caregiving stress. The aim of this study was to explore benefit finding among caregivers of patients with advanced cancer in their palliative caregiving journey.

Methods

An exploratory qualitative design of phenomenology was used. Semistructured interviews were conducted with 19 caregivers of palliative care patients with advanced cancer. The Colaizzi 7-step analysis was used to analyse, summarize, and extract themes from the interview data.

Results

The study identified five themes of caregiver benefit finding in the caregiving process: personal growth, strengthened relationships with patients, adjustment and adaptation, perceived social support, and perceived meaning in life. Most caregivers reported a closer, more dependent relationship with the patient, and only one caregiver did not report any positive changes.

Conclusions

Caregivers of palliative care patients with advanced cancer can have positive experiences in their care. Healthcare professionals should focus on supporting caregivers and helping them find positive experiences to cope with the challenges of caregiving and improve their quality of life.
Knowledge and associated factors of healthcare professionals in detecting patient-ventilator asynchrony using waveform analysis at intensive care units of the federal public hospitals in Addis Ababa, Ethiopia, 2023
Authors: Zelalem Habtamu , Sibhat Migbar Mekonnen , Yeshidinber Abate , Kehali Habtamu
Published: June 2024

Background

The interaction between the patient and the ventilator is often disturbed, resulting in patient-ventilator asynchrony (PVA). Asynchrony can lead to respiratory failure, increased artificial ventilation time, prolonged hospitalization, and escalated healthcare costs. Professionals’ knowledge regarding waveform analysis has significant implications for improving patient outcomes and minimizing ventilation-related adverse events. Studies investigating the knowledge of healthcare professionals on patient-ventilator asynchrony and its associated factors in the Ethiopian context are limited. Therefore, this study aimed to assess the knowledge of healthcare professionals about using waveform analysis to detect asynchrony.

Methods

A multicenter cross-sectional study was conducted on 237 healthcare professionals (HCPs) working in the intensive care units (ICUs) of federal public hospitals in Addis Ababa, Ethiopia, from December 2022 to May 2023. The data were collected using a structured and pretested interviewer-administered questionnaire. Then, the collected data were cleaned, coded, and entered into Epi data V-4.2.2 and exported to SPSS V-27 for analysis. After description, associations were analyzed using binary logistic regression. Variables with a P-value of < 0.25 in the bivariable analysis were transferred to the multivariable analysis. Statistical significance was declared using 95% confidence intervals, and the strengths of associations were reported using adjusted odds ratios (AORs).

Results

A total of 237 HCPs participated in the study with a response rate of 100%. Half (49.8%) of the participants were females. The mean age of the participants was 29 years (SD = 3.57). Overall, 10.5% (95% CI: 6.9–15.2) of the participants had good knowledge of detecting PVA using waveform analysis. In the logistic regression, the number of MV-specific trainings and the training site had a statistically significant association with knowledge of HCPs. HCPs who attended more frequent MV training were more likely to have good knowledge than their counterparts [AOR = 6.88 (95% CI: 2.61–15.45)]. Additionally, the odds of good knowledge among professionals who attended offsite training were 2.6 times higher than those among professionals trained onsite [AOR = 2.63 (95% CI: 1.36–7.98)].

Conclusion

The knowledge of ICU healthcare professionals about the identification of PVA using waveform analysis is low. In addition, the study also showed that attending offsite MV training and repeated MV training sessions were independently associated with good knowledge. Consequently, the study findings magnify the relevance of providing frequent and specific training sessions focused on waveform analysis to boost the knowledge of HCPs.
The impact of the Covid-19 pandemic on the effectiveness of psychosomatic rehabilitation in Germany
Authors: Kaier Klaus , Knecht Jakob , Nalbach Lukas , Körner Mirjam
Published: June 2024

Background

The aim of the present study is to investigate the impact of the Covid-19 pandemic on the effectiveness of psychosomatic rehabilitation.

Methods

Between April 2019 and March 2022, a total of 18,388 patients from 7 rehabilitation centres could be included in the study. For each patient, score values from the HEALTH-49 and ICF AT-50 Psych questionnaires were calculated at the beginning and at the end of rehabilitation and the effectiveness of the rehabilitation program was determined by comparing the scores at the beginning and at the end of the rehabilitation programme. Using risk adjusted linear mixed models, three time intervals were compared: a pre-pandemic episode (April 2019 to March 2020), the first year of the pandemic (April 2020 to March 2021) and the second year of the pandemic (April 2021 to March 2022).

Results

Overall, it can be stated that the pandemic has substantially impaired the effectiveness of psychosomatic rehabilitation measures. This phenomenon can be observed across a wide range of psychosocial markers and even two years after the start of the pandemic there is no end to the limited effectiveness. With regard to ‘psychological and somatoform disorders’, for example, there was a relative decrease in the effectiveness of the rehabilitation measure by 11.29% in the first year of the pandemic compared to the pre-pandemic episode, p < 0.001. In the second year of the pandemic, the effectiveness of the rehabilitation measure was still decreased by 8.8% compared to the pre-pandemic episode, p < 0.001. In addition, the evaluations show that a division of the pandemic effect into direct effects (on the individual) and indirect effects (via further complication of the occupational problem environment) can be made and that the pandemic-related complication of the occupational problem environment are still prevalent more than two years after the start of the pandemic.

Discussion

The Covid-19 pandemic has had a significant impact on the psychosomatic rehabilitation programs reducing the effectiveness of treatment not only for a short period of time but constantly until March 2022.

Trial Registration Number

DRKS00029669; Date of registration: 02/08/2022.
Hypoxia-induced activation of HIF-1alpha/IL-1beta axis in microglia promotes glioma progression via NF-κB-mediated upregulation of heparanase expression
Authors: Si Jinchao , Guo Jingya , Zhang Xu , Li Wei , Zhang Shen , Shang Shuyu , Zhang Quanwu
Published: June 2024

Background

Glioma is a common tumor that occurs in the brain and spinal cord. Hypoxia is a crucial feature of the tumor microenvironment. Tumor-associated macrophages/microglia play a crucial role in the advancement of glioma. This study aims to illuminate the detailed mechanisms by which hypoxia regulates microglia and, consequently, influences the progression of glioma.

Methods

The glioma cell viability and proliferation were analyzed by cell counting kit-8 assay and 5-ethynyl-2’-deoxyuridine assay. Wound healing assay and transwell assay were implemented to detect glioma cell migration and invasion, respectively. Enzyme-linked immunosorbent assay was conducted to detect protein levels in cell culture medium. The protein levels in glioma cells and tumor tissues were evaluated using western blot analysis. The histological morphology of tumor tissue was determined by hematoxylin-eosin staining. The protein expression in tumor tissues was determined using immunohistochemistry. Human glioma xenograft in nude mice was employed to test the influence of hypoxic microglia-derived interleukin-1beta (IL-1β) and heparanase (HPSE) on glioma growth in vivo.

Results

Hypoxic HMC3 cells promoted proliferation, migration, and invasion abilities of U251 and U87 cells by secreting IL-1β, which was upregulated by hypoxia-induced activation of hypoxia inducible factor-1alpha (HIF-1α). Besides, IL-1β from HMC3 cells promoted glioma progression and caused activation of nuclear factor-κB (NF-κB) and upregulation of HPSE in vivo. We also confirmed that IL-1β facilitated HPSE expression in U251 and U87 cells by activating NF-κB. Hypoxic HMC3 cells-secreted IL-1β facilitated the proliferation, migration, and invasion of U251 and U87 cells via NF-κB-mediated upregulation of HPSE expression. Finally, we revealed that silencing HPSE curbed the proliferation and metastasis of glioma in mice.

Conclusion

Hypoxia-induced activation of HIF-1α/IL-1β axis in microglia promoted glioma progression via NF-κB-mediated upregulation of HPSE expression.
Development of novel lysosome-related signatures and their potential target drugs based on bulk RNA-seq and scRNA-seq for diabetic foot ulcers
Authors: Tan Longhai , Qu Junjun , Wang Junxia
Published: June 2024

Background

Diabetic foot ulcers (DFU) is the most serious complication of diabetes mellitus, which has become a global health problem due to its high morbidity and disability rates and the poor efficacy of conventional treatments. Thus, it is urgent to identify novel molecular targets to improve the prognosis and reduce disability rate in DFU patients.

Results

In the present study, bulk RNA-seq and scRNA-seq associated with DFU were downloaded from the GEO database. We identified 1393 DFU-related DEGs by differential analysis and WGCNA analysis together, and GO/KEGG analysis showed that these genes were associated with lysosomal and immune/inflammatory responses. Immediately thereafter, we identified CLU, RABGEF1 and ENPEP as DLGs for DFU using three machine learning algorithms (Randomforest, SVM-RFE and LASSO) and validated their diagnostic performance in a validation cohort independent of this study. Subsequently, we constructed a novel artificial neural network model for molecular diagnosis of DFU based on DLGs, and the diagnostic performance in the training and validation cohorts was sound. In single-cell sequencing, the heterogeneous expression of DLGs also provided favorable evidence for them to be potential diagnostic targets. In addition, the results of immune infiltration analysis showed that the abundance of mainstream immune cells, including B/T cells, was down-regulated in DFUs and significantly correlated with the expression of DLGs. Finally, we found latamoxef, parthenolide, meclofenoxate, and lomustine to be promising anti-DFU drugs by targeting DLGs.

Conclusions

CLU, RABGEF1 and ENPEP can be used as novel lysosomal molecular signatures of DFU, and by targeting them, latamoxef, parthenolide, meclofenoxate and lomustine were identified as promising anti-DFU drugs. The present study provides new perspectives for the diagnosis and treatment of DFU and for improving the prognosis of DFU patients.
Predictors of the quality of the relationship between informal caregiver and care recipient in informal caregiving of older people: presentation and evaluation of a new item
Authors: Becker Linda , Graessel Elmar , Pendergrass Anna
Published: June 2024

Background

An important factor that has not been directly addressed very often in caregiver (CG) counseling to date is the quality of the relationship between the CG and the care recipient (CR). One reason is the lack of availability of a suitable assessment tool that is not strongly influenced by social desirability. Here, we present and evaluate a new item for the assessment of relationship quality (RQ) in the context of informal caregiving of older people.

Methods

N = 962 informal caregivers of older people participated. Our item assessed RQ by providing three answer categories (positive, neutral, and negative) that were presented through the use of smiley faces. For evaluation, and to avoid bias due to social desirability, the neutral and negative categories were combined. We calculated a stepwise binary logistic regression.

Results

Expected associations with the variables care burden, perceived positive aspects, and care motivation were found (all p values < 0.01). An exploratory analysis revealed that additional predictors of RQ consisted of the CR’s age as well as whether the CR’s diagnosis was dementia, CG’s amount of dysfunctional coping, and whether the CG was caring for more than one CR.

Conclusions

We conclude that our item is well-suited for the assessment of RQ in the context of informal caregiving of older people. Because it uses language-free answer categories by means of smiley faces, our item can be applied easily. Bias due to social desirability can be minimized by dichotomization (i.e., combining the negative and neural answer categories). In future research, our tool should be evaluated in other contexts.
Reconstitution of peripheral blood T cell receptor β immune repertoire in immune checkpoint inhibitors associated myocarditis
Authors: Yan Peng , Liu Yanan , Zhang Mingyan , Liu Ning , Zheng Yawen , Zhang Haiqin , Zhou Hao , Sun Meili
Published: June 2024

Purpose

Immune checkpoint inhibitors (ICIs)-associated myocarditis was a rare yet severe complication observed in individuals undergoing immunotherapy. This study investigated the immune status and characteristics of patients diagnosed with ICIs- associated myocarditis.

Methods

A total of seven patients diagnosed with ICIs-associated myocarditis were included in the study, while five tumor patients without myocarditis were recruited as reference controls. Additionally, 30 healthy individuals were recruited as blank controls. Biochemical indices, electrocardiogram, and echocardiography measurements were obtained both prior to and following the occurrence of myocarditis. High-throughput sequencing of T cell receptor (TCR) was employed to assess the diversity and distribution characteristics of TCR CDR3 length, as well as the diversity of variable (V) and joining (J) genes of T lymphocytes in peripheral blood.

Results

In the seven patients with ICIs-associated myocarditis, Troponin T (TNT) levels exhibited a significant increase following myocarditis, while other parameters such as brain natriuretic peptide (BNP), QTc interval, and left ventricular ejection fraction (LVEF) did not show any significant differences. Through sequencing, it was observed that the diversity and uniformity of CDR3 in the ICIs-associated myocarditis patients were significantly diminished. Additionally, the distribution of CDR3 nucleotides deviated from normality, and variations in the utilization of V and J gene segments.

Conclusion

The reconstitution of the TCR immune repertoire may play a pivotal role in the recognition of antigens in patients with ICIs-associated myocarditis.
Navigating Treatment Options and Communication in Relapsed Pediatric AML
Authors: Graff Zachary , Wachter Franziska , Eapen Mary , Lehmann Leslie , Cooper Todd
Published: June 2024

Despite improved outcomes in newly diagnosed pediatric AML, relapsed disease remains a therapeutic challenge. Factors contributing to slow progress in improving outcomes include inherent challenges in pediatric clinical trial accrual and the scarcity of novel targeted/immunotherapy agents available for pediatric development. This paradigm is changing, however, as international collaboration grows in parallel with the development of promising targeted agents. In this review, we discuss the therapeutic landscape of relapsed pediatric AML, including conventional chemotherapy, targeted therapies, and the challenges of drug approvals in this patient population. We highlight current efforts to improve communication among academia, industry, and regulatory authorities and discuss the importance of international collaboration to improve access to new therapies. Among the therapeutic options, we highlight the approach to second hematopoietic stem cell transplant (HSCT) and discuss which patients are most likely to benefit from this potentially curative intervention. Importantly, we acknowledge the challenges in providing these high-risk interventions to our patients and their families and the importance of shared communication and decision making when considering early-phase clinical trials and second HSCT.
Post-transplant cyclophosphamide-based graft-versus-host disease prophylaxis following mismatched unrelated donor peripheral blood stem cell (PBSC) transplantation.
Authors: Al Malki Monzr M. , Bo-Subait Stephanie , Logan Brent , Olson Janelle , Leckrone Erin , Wu Juan , Stefanski Heather E. , Auletta Jeffery J. , Spellman Stephen R. , Malmberg Craig , Shaffer Brian C. , Modi Dipenkumar , Khimani Farhad , Gooptu Mahasweta , Hamadani Mehdi , Broglie Larisa , Shaw Bronwen E. , Devine Steven Michael , Jimenez Jimenez Antonio Martin
Published: June 2024

6503

Background: Our prior prospective multi-center clinical trial (15-MMUD; NCT02793544) estimated 79% overall survival (OS) at one year in adult patients with hematological malignancies undergoing reduced intensity conditioning (RIC), receiving bone marrow (BM) grafts from HLA-mismatched unrelated donors (MMUD), and post-transplant cyclophosphamide (PTCy)-based graft- versus-host disease (GVHD) prophylaxis (Shaw et al, J Clin Oncol 2021). We sought to determine whether OS in adults receiving mobilized PBSC from MMUD would be comparable. Methods: We conducted a prospective, multi-center Phase II study (ACCESS; NCT04904588) to assess the impact of PTCy-based GVHD prophylaxis on OS following MMUD transplantation in adults and children with advanced hematological malignancies. The study included three strata: two for adults based on conditioning regimen intensity [myeloablative (MAC) or RIC] using PBSC, and one pediatric cohort using MAC and BM. Eligible donors were matched at 4-7/8 HLA-loci (HLA -A, -B, -C, and -DRB1) and < 35 years. The primary endpoint was OS at one year following transplantation. We report the results of a planned interim analysis of the first 70 adult patients enrolled on the RIC PBSC stratum. Results: Thirteen sites enrolled 70 patients with the following demographics: median age of 65 years (range 24-77); 50% male; diagnoses: AML (53%), MDS (26%), ALL (7%), other heme malignancies (14%); and patient race/ethnicity: non-Hispanic white (48%). Donor characteristics included: median age 25y (range 18-35); male (44%); and HLA match level: 7/8: 67%; 6/8: 27%; 5/8: 6%. Conditioning regimens included fludarabine (flu) and melphalan (63%), flu/busulfan (20%), other (17%). OS at one year post HCT was 79% (95% confidence interval (CI): 68-87%). Secondary endpoints are provided in the table. Conclusions: Encouraging OS was observed at one year following MMUD PBSC in patients receiving RIC and PTCy. Notably, half of enrolled patients were people of color. OS was similar to our prior study using BM grafts. Rates of GVHD and other complications appear comparable to those in HLA-matched donor recipients, suggesting MMUD HCT could expand access to a potentially life-saving therapy. Accrual to both adult strata of ACCESS is complete, with over 200 patients in follow-up. Accrual to the pediatric stratum continues. Clinical trial information: NCT04904588 . [Table: see text]
Outcomes of blast-phase MPN and JAK2, MPL, and CALRmutated de novo AML: A propensity score-adjusted cohort study.
Authors: Nurse Daniel Paul , Zabor Emily Craig , Cancilla Daniel , Abdallah Kawther , Adcock Bridget , Batah Heya , Zureigat Hadil , Rauf Asad , Shrivastava Gautam Anand , Nakitandwe Joy , Chen Mark , Younes Ismail Elbaz , Ingraham Austin , Jain Akriti Gupta , Balderman Sophia , Singh Abhay , Advani Anjali S. , Carraway Hetty E , Gerds Aaron Thomas , Mustafa Ali Moaath Khader
Published: June 2024

6526

Background: Progression to blast phase (BP) occurs in about 10% of patients with BCR-ABL-negative myeloproliferative neoplasms (MPN) and is associated with an extremely poor prognosis with no defined standard of care. The VIALE-A trial, which showed that venetoclax (VEN) improves overall survival (OS) in patients with acute myeloid leukemia (AML) when combined with azacitidine, excluded patients with MPN-BP. Rarely, patients develop de novo AML with a genetic profile like an MPN, harboring JAK2, MPL, or CALR mutations. However, there are a lack of data on the outcomes of these patients. Methods: We conducted a single-center retrospective cohort study to compare composite complete response (CCR), OS and event-free survival (EFS) of patients with MPN-BP or de novo AML with underlying JAK2, MPL, or CALR mutations (AML-D-MPN). CCR was defined as complete response (CR) or CR with incomplete count recovery. Propensity score (PS) modeling was used to adjust for baseline characteristics at AML diagnosis: age, sex, race, comorbidities, ECOG status, cytogenetics, and underlying mutations. Results: Of 750 patients treated from 2015 to 2023, 61 had MPN-BP and 12 had AML-D-MPN. The table describes baseline characteristics. The median time for MPN to BP transformation was 8 years (IQR: 2.8-13.6). With a median follow-up of 8.2 months (mo) (95CI: 1.6-59.6), the median OS for MPN-BP was 4.8 mo (95CI: 2.7-8) and for AML-D-MPN was 6.1 mo (95CI: 1.6-NC). In the MPN-BP, 40 received therapy, which included: intensive regimen [7+3 (n=13); CPX-351 (n=1)], hypomethylating agents (HMA) (n=11), HMA+VEN (n=11) and others (n=4). All AML-D-MPN received therapy, which included 7+3 (n=4), HMA (n=1), HMA+VEN (n=2), and others (n=5). In the whole treated population (n=52), the unadjusted CCR was 60% in intensive regimen, 20% in HMA, 20% in HMA+VEN and 0% in others (p=0.3). The PS-adjusted median (m) OS in mo (95%CI) was: 2.6 (1.4-NC) in intensive regimen, 6.2 (1.2-NC) in HMA, 15 (10-15) in HMA+VEN and 1.7 (0.46-NC) in others (p=0.1). The adjusted m-EFS in the same treatment groups was 1.5 (0.43-NC), 6.2 (1.2-NC), 15 (4.3-15) and 0.92 (0.46-NC) (p=0.16), respectively. In MPN-BP group, the adjusted m-EFS in mo (95%CI) was: 0.62 (0.43-NC) in the intensive regimen, 6.2 (1.2-NC) in HMA, 15 (4.2-15) in HMA+VEN and 0.92 (0.92-NC) in others (p=0.25). Conclusions: Patients with MPN-BP and AML-D-MPN have poor survival with similar responses to therapy. These patients have variable outcomes with different treatments; however, there is a trend toward improved survival with the use of HMA+VEN. [Table: see text]
Olutasidenib for mutated IDH1 acute myeloid leukemia: Final five-year results from the phase 2 pivotal cohort.
Authors: Cortes Jorge E. , Jonas Brian Andrew , Watts Justin M. , Chao Mwe Mwe , De Botton Stéphane
Published: June 2024

6528

Background: Olutasidenib is a potent, selective, oral inhibitor of mIDH1 and is FDA-approved for relapsed/refractory (R/R) acute myeloid leukemia (AML) based on a registrational, Phase 2, open-label, multicenter trial (NCT02719574). We report final five-year results from the pivotal cohort. Methods: In the pivotal cohort of the Phase 2 trial, patients with mIDH1 AML received olutasidenib 150mg BID. Primary endpoint was complete remission (CR) + CR with partial hematologic recovery (CRh) by modified IWG Criteria 2003. Data cutoff: May 15, 2023. Results: Baseline characteristics of 153 enrolled patients are shown in Table. Of 147 efficacy evaluable patients, CR was achieved in 32% (95% CI: 24.5, 40.2) and CR/CRh in 35% (95% CI: 27, 43; P<0.0001). Median time to CR/CRh was 1.9 mo (range: 0.9, 5.6). The median duration of CR/CRh was 25.3 mo (95% CI: 13.5, not reached), with maximum duration 54.6 mo. Overall response rate was 48% (95% CI: 40, 56.7), with median duration 15.5 mo (95% CI: 7.4, 26.2) and maximum duration 54.6 mo. Median overall survival was 11.6 mo (95%CI: 8.9, 15.5). In the 12 patients R/R to prior venetoclax, 33% achieved a CR/CRh; median duration of CR/CRh is not reached (ongoing at 54.3 months), and median overall survival is 16.2 months (95%CI: 2.6, not reached). Transfusion independence from red blood cells and platelets was achieved in 34 of 87 (39%) patients and 28 of 69 (41%) patients, respectively, who were dependent at baseline. 16 (11%) patients proceeded to stem cell transplant. The 5-year safety profile was consistent with what was previously reported. The most common AEs (% reported over 3 years and over the full 5 years) were: febrile neutropenia (22% and 22%), constipation (26% and 27%), diarrhea (20% and 21%), nausea (38% and 39%), fatigue (23% and 23%), pyrexia (24% and 24%), hypokalaemia (20% and 22%), red blood cell count decreased (26% and 26%), white blood cell count increased (25% and 25%). Differentiation syndrome was reported in 14% by Year 3, with no new events by Year 5. The safety profile was stable with long-term follow up. Conclusions: This analysis provides an additional 2 years of data beyond the results that led to FDA approval of olutasidenib. This first report of the five-year data further demonstrates the rapid and durable responses observed with olutasidenib in heavily pretreated patients with mIDH1 AML, including those R/R to prior venetoclax. Clinical trial information: NCT02719574 . [Table: see text]