bluuebunny/crossref_metadata_2025 huggingface dataset:
Is there any relationship between nurses’ perceived organizational justice, moral sensitivity, moral courage, moral distress and burnout?
Authors: Lotfi-Bejestani Sara , Atashzadeh-Shoorideh Foroozan , Ghafouri Raziyeh , Nasiri Malihe , Ohnishi Kayoko , Ghadirian Fataneh
Published: October 2023

Aim

The present study is an attempt to investigate the relationship between Corley’s model variables in mental health nurses.

Background

Based on Corley’s model, burnout and moral distress in nurses are, in retrospect, the consequences of the interplay of organizational and individual factors such as perceived organizational justice, moral sensitivity, and moral courage. The relationship between two variables or three variables of Corley’s moral distress model has been investigated, but the test of Corley’s moral distress model with more variables has not been done. Therefore, this research was proposed with the aim of investigating the relationship between the variables of moral courage and moral sensitivity (as characteristics of nurses), perceived organizational justice (as an antecedent), moral distress, and job burnout (as consequences of moral distress).

Methods

The study was conducted as a descriptive correlational study involving 500 nurses working in the mental health wards of hospitals. Data collection was conducted using perceived organizational justice scale, moral sensitivity scale, moral courage scale, moral distress scale, and burnout inventory.

Results

The results showed a significant relationship between perceived organizational justice, moral sensitivity, moral courage, and moral distress (< 0.05). Moreover, perceived organizational justice and moral distress had an inverse relationship. Moral sensitivity and moral courage had a direct relationship with moral distress (< 0.05). Furthermore, the results showed inadequate model fitness.

Conclusions

This study adds to the existing knowledge about the experiences of mental health nurses and their interactions with both organizational and individual factors. It highlights that the connections between perceived organizational justice, moral sensitivity, moral courage, moral distress, and burnout are intricate and multifaceted. As we deepen our understanding of these relationships, it opens the door for the development of interventions and strategies to enhance nurses’ well-being and the quality of care they deliver in mental health settings. Moreover, future research and ongoing refinement and expansion of Corley’s model will be crucial in addressing the complex challenges within the healthcare sector.
The early impacts of primary HPV cervical screening implementation in Australia on the pathology sector: a qualitative study
Authors: Bavor Claire , Brotherton Julia ML , Smith Megan A , Prang Khic-Houy , McDermott Tracey , Rankin Nicole M , Zammit Claire M , Jennett Chloe J , Sultana Farhana , Machalek Dorothy A , Nightingale Claire E ,   on behalf of the STORIES team
Published: October 2023

Background

The transition of Australia’s National Cervical Screening Program from cytology to a molecular test for human papillomavirus (HPV) (locally referred to as the ‘Renewal’), including a longer five-year interval and older age at commencement, significantly impacted all sectors of program delivery. The Renewal had major implications for the roles and requirements of pathology laboratories providing services for the Program. This study aimed to understand the early impacts of the Renewal and its implementation on the pathology sector.

Methods

Semi-structured qualitative interviews were conducted with key stakeholders (N = 49) involved in the STakeholder Opinions of Renewal Implementation and Experiences Study (STORIES), 11–20 months after the program transition. A subset of interviews (N = 24) that discussed the pathology sector were analysed using inductive thematic analysis.

Results

Four overarching themes were identified: implementation enablers, challenges, missed opportunities, and possible improvements. Participants believed that the decision to transition to primary HPV screening was highly acceptable and evidence-based, but faced challenges due to impacts on laboratory infrastructure, resources, staffing, and finances. These challenges were compounded by unfamiliarity with new information technology (IT) systems and the new National Cancer Screening Register (‘Register’) not being fully functional by the date of the program transition. The limited availability of self-collection and lack of standardised fields in pathology forms were identified as missed opportunities to improve equity in the Program. To improve implementation processes, participants suggested increased pathology sector involvement in planning was needed, along with more timely and transparent communication from the Government, and clearer clinical management guidelines.

Conclusion

The transition to primary HPV screening had a significant and multifaceted impact on the Australian pathology sector reflecting the magnitude and complexity of the Renewal. Strategies to support the pathology sector through effective change management, clear, timely, and transparent communication, as well as adequate funding sources will be critical for other countries planning to transition cervical screening programs.
One size does not fit all: an application of stochastic modeling to estimating primary healthcare needs in Ethiopia at the sub-national level
Authors: Hagedorn Brittany L. , Han Rui , McCarthy Kevin A.
Published: October 2023

Background

Primary healthcare systems require adequate staffing to meet the needs of their local population. Guidelines typically use population ratio targets for healthcare workers, such as Ethiopia’s goal of two health extension workers for every five thousand people. However, fixed ratios do not reflect local demographics, fertility rates, disease burden (e.g., malaria endemicity), or trends in these values. Recognizing this, we set out to estimate the clinical workload to meet the primary healthcare needs in Ethiopia by region.

Methods

We utilize the open-source R package PACE-HRH for our analysis, which is a stochastic Monte Carlo simulation model that estimates workload for a specified service package and population. Assumptions and data inputs for region-specific fertility, mortality, disease burden were drawn from literature, DHS, and WorldPop. We project workload until 2035 for seven regions and two charted cities of Ethiopia.

Results

All regions and charted cities are expected to experience increased workload between 2021 and 2035 for a starting catchment of five thousand people. The expected (mean) annual clinical workload varied from 2,930 h (Addis) to 3,752 h (Gambela) and increased by 19–28% over fifteen years. This results from a decline in per capita workload (due to declines in fertility and infectious diseases), overpowered by total population growth. Pregnancy, non-communicable diseases, sick child care, and nutrition remain the largest service categories, but their priority shifts substantially in some regions by 2035. Sensitivity analysis shows that fertility assumptions have major implications for workload. We incorporate seasonality and estimate monthly variation of up to 8.9% (Somali), though most services with high variability are declining.

Conclusions

Regional variation in demographics, fertility, seasonality, and disease trends all affect the workload estimates. This results in differences in expected clinical workload, the level of uncertainty in those estimates, and relative priorities between service categories. By showing these differences, we demonstrate the inadequacy of a fixed population ratio for staffing allocation. Policy-makers and regulators need to consider these factors in designing their healthcare systems, or they risk sub-optimally allocating workforce and creating inequitable access to care.
Hemodynamic changes in late advanced pregnant Zaraibi goats during the peripartum period
Authors: Madbouly Hager , El-Shahat K. H. , Fathi Mohamed , Abdelnaby Elshymaa A.
Published: October 2023

The objective of the present study was to demonstrate the blood flow velocities, blood flow rate (BFR; bpm) with the accurate ratio of both systolic and diastolic velocities points (S/D) in addition to Doppler indices (resistive and pulsatility index [RI and PI]) in both fetal [fetal heart (FH), fetal abdominal aorta (Ab. A), and umbilical artery (UM.A)] and maternal [Middle uterine artery (MU.A)] sides during the last month of gestation. Ten Zaraibi (Egyptian Nubian) goats weighing 40-50kg and aged from 5–7 years were examined twice per month till reached the last month of pregnancy. Then all females were examined every 5 days starting from day -35 till day -1 before kidding.The pregnant goats were examined by ultrasonic and Doppler indices were recorded with Doppler scanning (7.5 -12 MHz, with colored and spectral graph to form the perfect wave to assess Doppler measurements). The obtained data were analyzed using analysis of variance. Results indicated that on the fetal side; the maximum point of velocity (MSV; cm/sec) in the FH and BFRwere elevated from day -35 till day -10 with a slight decline at days -5 and -1 at the peripartum period (P < 0.05), while FH.PI and S/D ratio declined till day -1(P < 0.05). In addition, the fetal Ab. A, and UM.A PI, RI, and S/D ratio declined from day -35 till day -1 at the peripartum period with a significant increase in the peak systolic velocity (PSV) and BFR(P < 0.05). However, non-significant changes in the end diastolic velocity (EDV) were detected. On the maternal side, the MU.A PI and S/D declined from day -35 till day -1 with an elevation of both PSV and BFRat the same time points (P < 0.05). In conclusion, the Doppler evaluation of fetal and maternal blood flow vessels is important to give complete information that directly affects the health status of the mother and fetus.
Clinical significance and immune infiltration analyses of a novel coagulation-related signature in ovarian cancer
Authors: Yang Jiani , Wang Chao , Zhang Yue , Cheng Shanshan , Wu Meixuan , Gu Sijia , Xu Shilin , Wu Yongsong , Sheng Jindan , Voon Dominic Chih-Cheng , Wang Yu
Published: October 2023

Ovarian cancer (OV) is the most lethal gynecological malignancies worldwide. The coagulation cascade could induce tumor cell infiltration and contribute to OV progression. However, coagulation-related gene (CRG) signature for OV prognosis hasn’t been determined yet. In this study, we evaluated the prognostic value of coagulation scores through receiver operating characteristics (ROC) analysis and K-M curves, among OV patients at our institution. Based on the transcriptome data of TCGA-OV cohort, we stratified two coagulation-related subtypes with distinct differences in prognosis and tumor immune microenvironment (p < 0.05). Moreover, from the 6406 differentially-expressed genes (DEGs) between the GTEx (n = 180) and TCGA-OV cohorts (n = 376), we identified 138 potential CRGs. Through LASSO-Cox algorithm, we finally distinguished a 3-gene signature (SERPINA10, CD38, and ZBTB16), with promising prognostic ability in both TCGA (p < 0.001) and ICGC cohorts (p = 0.040). Stepwise, we constructed a nomogram based on the clinical features and coagulation-related signature for overall survival prediction, with the C-index of 0.6761, which was evaluated by calibration curves. Especially, based on tissue microarrays analysis, Quantitative real-time fluorescence PCR (qRT-PCR), and Western Blot, we found that aberrant upregulation of CRGs was related to poor prognosis in OV at both mRNA and protein level (p < 0.05). Collectively, the coagulation-related signature was a robust prognostic biomarker, which could provide therapeutic benefits for chemotherapy/immunotherapy and assist clinical decision in OV patients.
Barriers and facilitators to health care access for people experiencing homelessness in four European countries: an exploratory qualitative study
Authors: Carmichael Christina , Schiffler Tobias , Smith Lee , Moudatsou Maria , Tabaki Ioanna , Doñate-Martínez Ascensión , Alhambra-Borrás Tamara , Kouvari Matina , Karnaki Pania , Gil-Salmeron Alejandro , Grabovac Igor
Published: October 2023

Background

People experiencing homelessness (PEH) are known to be at higher risk of adverse health outcomes and premature mortality when compared to the housed population and often face significant barriers when attempting to access health services. This study aimed to better understand the specific health care needs of PEH and the barriers and facilitators associated with their timely and equitable access to health services in the European context.

Methods

We conducted an exploratory cross-national qualitative study involving people with lived experience of homelessness and health and social care professionals in Austria, Greece, Spain, and the UK. A total of 69 semi-structured interviews comprising 15 social care professionals, 19 health care professionals, and 35 PEH were completed, transcribed, and analysed thematically.

Results

Findings were organised into three overarching themes relating to the research question: (a) Health care needs of PEH, (b) Barriers to health care access, and (c) Facilitators to health care access. Overall, the general health of PEH was depicted as extremely poor, and mainstream health services were portrayed as ill-equipped to respond to the needs of this population. Adopting tailored approaches to care, especially involving trusted professionals in the delivery of care, was identified as a key strategy for overcoming existing barriers.

Conclusions

The results of this study indicate there to be a high degree of consistency in the health care needs of PEH and the barriers and facilitators associated with their access to health care across the various European settings. Homelessness in itself is recognized to represent an essential social determinant of health, with PEH at risk of unequal access to health services. Changes are thus required to facilitate PEH’s access to mainstream primary care. This can also be further complemented by investment in ‘in-reach’ services and other tailored and person-centred forms of health care.

Trial registration

This study was registered retrospectively on June 6, 2022, in the registry of ClinicalTrials.gov under the number NCT05406687.
Skin cancer: understanding the journey of transformation from conventional to advanced treatment approaches
Authors: Hasan Nazeer , Nadaf Arif , Imran Mohammad , Jiba Umme , Sheikh Afsana , Almalki Waleed H. , Almujri Salem Salman , Mohammed Yousuf Hussain , Kesharwani Prashant , Ahmad Farhan Jalees
Published: October 2023

Skin cancer is a global threat to the healthcare system and is estimated to incline tremendously in the next 20 years, if not diagnosed at an early stage. Even though it is curable at an early stage, novel drug identification, clinical success, and drug resistance is another major challenge. To bridge the gap and bring effective treatment, it is important to understand the etiology of skin carcinoma, the mechanism of cell proliferation, factors affecting cell growth, and the mechanism of drug resistance. The current article focusses on understanding the structural diversity of skin cancers, treatments available till date including phytocompounds, chemotherapy, radiotherapy, photothermal therapy, surgery, combination therapy, molecular targets associated with cancer growth and metastasis, and special emphasis on nanotechnology-based approaches for downregulating the deleterious disease. A detailed analysis with respect to types of nanoparticles and their scope in overcoming multidrug resistance as well as associated clinical trials has been discussed.

Graphical Abstract
Liquid biopsy techniques and pancreatic cancer: diagnosis, monitoring, and evaluation
Authors: Wang Kangchun , Wang Xin , Pan Qi , Zhao Bei
Published: October 2023

Pancreatic cancer (PC) is one of the most common malignancies. Surgical resection is a potential curative approach for PC, but most patients are unsuitable for operations when at the time of diagnosis. Even with surgery, some patients may still experience tumour metastasis during the operation or shortly after surgery, as precise prognosis evaluation is not always possible. If patients miss the opportunity for surgery and resort to chemotherapy, they may face the challenging issue of chemotherapy resistance. In recent years, liquid biopsy has shown promising prospects in disease diagnosis, treatment monitoring, and prognosis assessment. As a noninvasive detection method, liquid biopsy offers advantages over traditional diagnostic procedures, such as tissue biopsy, in terms of both cost-effectiveness and convenience. The information provided by liquid biopsy helps clinical practitioners understand the molecular mechanisms underlying tumour occurrence and development, enabling the formulation of more precise and personalized treatment decisions for each patient. This review introduces molecular biomarkers and detection methods in liquid biopsy for PC, including circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), noncoding RNAs (ncRNAs), and extracellular vesicles (EVs) or exosomes. Additionally, we summarize the applications of liquid biopsy in the early diagnosis, treatment response, resistance assessment, and prognostic evaluation of PC.
Periodontitis is associated with stroke
Authors: Zheng Xiaodan , Li Xin , Zhen Juanying , Xue Dai , Hu Jun , Cao Qing , Xu Aimin , Cheung Bernard Man Yung , Wu Jun , Li Chao
Published: October 2023

Background

Periodontitis is considered as a risk factor for cardiovascular diseases and atherosclerosis. However, the relationship between periodontitis and stroke is rarely studied. Therefore, we aimed to explore the relationship between periodontitis and stroke.

Methods

Statistical analysis was performed using the complex sampling design. We analyzed data on 6,460 participants, representing 92,856,028 American citizens aged 30 years or older, who had valid data on periodontitis and stroke from the National Health and Nutrition Examination Survey 2009–2014. We used clinical attachment level and probing pocket depth precisely to determine periodontitis and it is the first time to use such a precise method for exploring the relationship between periodontitis and stroke.

Results

39.9% of participants had periodontitis and 2.1% of participants had a record of stroke diagnosis. Stroke was associated with severity levels of periodontitis (p for trend = 0.018). The odds ratio for stroke was significantly elevated in the severe periodontitis and moderate periodontitis participants compared to participants without periodontitis (OR for severe periodontitis: 2.55, 95% CI 1.25–5.21; OR for moderate periodontitis: 1.71, 95% CI 1.17–2.50). After adjusting for race/ethnicity and sex, the association remained significant (p for trend = 0.009). After further adjusting for BMI, hypercholesterolemia, diabetes, alcohol consumption and physical activity, the association still existed (p for trend = 0.027). The association was significant consistently after further adjusting for age (p for trend = 0.033).

Conclusions

In this nationally representative study, we found an association between periodontitis and stroke. The risk of stroke in participants with severe periodontitis and moderate periodontitis was 2.55 times and 1.71times as high as those without periodontitis. Dental health management may be of benefit to stroke prevention.
Proteasome inhibition protects blood–brain barrier P-glycoprotein and lowers Aβ brain levels in an Alzheimer’s disease model
Authors: Vulin Milica , Zhong Yu , Maloney Bryan J. , Bauer Björn , Hartz Anika M. S.
Published: October 2023

Background

Loss of P-glycoprotein (P-gp) at the blood–brain barrier contributes to amyloid-β (Aβ) brain accumulation in Alzheimer’s disease (AD). Using transgenic human amyloid precursor protein (hAPP)-overexpressing mice (Tg2576), we previously showed that Aβ triggers P-gp loss by activating the ubiquitin–proteasome pathway, which leads to P-gp degradation. Furthermore, we showed that inhibiting the ubiquitin-activating enzyme (E1) prevents P-gp loss and lowers Aβ accumulation in the brain of hAPP mice. Based on these data, we hypothesized that repurposing the FDA-approved proteasome inhibitor, bortezomib (Velcade®; BTZ), protects blood–brain barrier P-gp from degradation in hAPP mice in vivo.

Methods

We treated hAPP mice with the proteasome inhibitor BTZ or a combination of BTZ with the P-gp inhibitor cyclosporin A (CSA) for 2 weeks. Vehicle-treated wild-type (WT) mice were used as a reference for normal P-gp protein expression and transport activity. In addition, we used the opioid receptor agonist loperamide as a P-gp substrate in tail flick assays to indirectly assess P-gp transport activity at the blood–brain barrier in vivo. We also determined P-gp protein expression by Western blotting, measured P-gp transport activity levels in isolated brain capillaries with live cell confocal imaging and assessed Aβ plasma and brain levels with ELISA.

Results

We found that 2-week BTZ treatment of hAPP mice restored P-gp protein expression and transport activity in brain capillaries to levels found in WT mice. We also observed that hAPP mice displayed significant loperamide-induced central antinociception compared to WT mice indicating impaired P-gp transport activity at the blood–brain barrier of hAPP mice in vivo. Furthermore, BTZ treatment prevented loperamide-induced antinociception suggesting BTZ protected P-gp loss in hAPP mice. Further, BTZ-treated hAPP mice had lower Aβ40 and Aβ42 brain levels compared to vehicle-treated hAPP mice.

Conclusions

Our data indicate that BTZ protects P-gp from proteasomal degradation in hAPP mice, which helps to reduce Aβ brain levels. Our data suggest that the proteasome system could be exploited for a novel therapeutic strategy in AD, particularly since increasing Aβ transport across the blood–brain barrier may prove an effective treatment for patients.
Advancements of radiotherapy for recurrent head and neck cancer in modern era
Authors: Zhang Shu , Zeng Ni , Yang Jiangping , He Jinlan , Zhu Fubin , Liao Wenjun , Xiong Maoqi , Li Yan
Published: October 2023

Head and neck cancer is a kind of cancer which can be eradicated from radical radiation therapy. However, with best efforts, nearly 40% patients will experience locoregional recurrence. Locoregional recurrence is the main cause of cancer-related death in head and neck cancers, so local treatments play a key role in improving progression free survival. In the last decades, radiation techniques have been tremendously developed, highly conformal radiation techniques such as intensity-modulated radiotherapy, stereotactic body radiation therapy, brachytherapy and proton or heavy ion radiation therapy have their unique radiobiological advances. Although reirradiation is widely used in clinical practice, but little is known when comparing the different techniques. In this review, we will provide a comprehensive overview of the role of reirradiation in recurrent head and neck cancers including radiation techniques, patient selection, overall clinical benefits, and toxicities.
Towards deep-learning (DL) based fully automated target delineation for rectal cancer neoadjuvant radiotherapy using a divide-and-conquer strategy: a study with multicenter blind and randomized validation
Authors: Geng Jianhao , Zhu Xianggao , Liu Zhiyan , Chen Qi , Bai Lu , Wang Shaobin , Li Yongheng , Wu Hao , Yue Haizhen , Du Yi
Published: October 2023

Purpose

Manual clinical target volume (CTV) and gross tumor volume (GTV) delineation for rectal cancer neoadjuvant radiotherapy is pivotal but labor-intensive. This study aims to propose a deep learning (DL)-based workflow towards fully automated clinical target volume (CTV) and gross tumor volume (GTV) delineation for rectal cancer neoadjuvant radiotherapy.

Materials & methods

We retrospectively included 141 patients with Stage II-III mid-low rectal cancer and randomly grouped them into training (n = 121) and testing (n = 20) cohorts. We adopted a divide-and-conquer strategy to address CTV and GTV segmentation using two separate DL models with DpuUnet as backend-one model for CTV segmentation in the CT domain, and the other for GTV in the MRI domain. The workflow was validated using a three-level multicenter-involved blind and randomized evaluation scheme. Dice similarity coefficient (DSC) and 95th percentile Hausdorff distance (95HD) metrics were calculated in Level 1, four-grade expert scoring was performed in Level 2, and head-to-head Turing test in Level 3.

Results

For the DL-based CTV contours over the testing cohort, the DSC and 95HD (mean ± SD) were 0.85 ± 0.06 and 7.75 ± 6.42 mm respectively, and 96.4% cases achieved clinical viable scores (≥ 2). The positive rate in the Turing test was 52.3%. For GTV, the DSC and 95HD were 0.87 ± 0.07 and 4.07 ± 1.67 mm respectively, and 100% of the DL-based contours achieved clinical viable scores (≥ 2). The positive rate in the Turing test was 52.0%.

Conclusion

The proposed DL-based workflow exhibited promising accuracy and excellent clinical viability towards automated CTV and GTV delineation for rectal cancer neoadjuvant radiotherapy.
Changes in vital signs during adrenaline administration for hemostasis in intracordal injection: an observational study with a hypothetical design of endotracheal adrenaline administration in cardiopulmonary arrest
Authors: Hasegawa Tomohiro , Watanabe Yusuke
Published: October 2023

Background

The background is that intravenous adrenaline administration is recommended for advanced cardiovascular life support in adults and endotracheal administration is given low priority. The reason is that the optimal dose of adrenaline in endotracheal administration is unknown, and it is ethically difficult to design studies of endotracheal adrenaline administration with non-cardiopulmonary arrest. We otolaryngologists think so because we administered adrenaline to the vocal folds for hemostasis after intracordal injection under local anesthesia, but have had few cases of vital changes. We hypothesized that examining vital signs before and after adrenaline administration for hemostasis would help determine the optimal dose of endotracheal adrenaline.

Methods

We retrospectively examined the medical records of 79 patients who visited our hospital from January 2018 to December 2020 and received adrenaline in the vocal folds and trachea for hemostasis by intracordal injection under local anesthesia to investigate changes in heart rate and systolic blood pressure before and after the injection.

Results

The mean heart rates before and after injection were 83.96 ± 18.51 (standard deviation) beats per minute (bpm) and 81.50 ± 15.38 (standard deviation) bpm, respectively. The mean systolic blood pressure before and after the injection were 138.13 ± 25.33 (standard deviation) mmHg and 135.72 ± 22.19 (standard deviation) mmHg, respectively. Heart rate and systolic blood pressure had P-values of 0.136, and 0.450, respectively, indicating no significant differences.

Conclusions

Although this study was an observational, changes in vital signs were investigated assuming endotracheal adrenaline administration. The current recommended dose of adrenaline in endotracheal administration with cardiopulmonary arrest may not be effective. In some cases of cardiopulmonary arrest, intravenous and intraosseous routes of adrenaline administration may be difficult and the opportunity for resuscitation may be missed. Therefore, it is desirable to have many options for adrenaline administration. Therefore, if the optimal dose and efficacy of endotracheal adrenaline administration can be clarified, early adrenaline administration will be possible, which will improve return of spontaneous circulation (ROSC) and survival discharge rates.
Effects of multimodal low-opioid anesthesia protocol during on-pump coronary artery bypass grafting: a prospective cohort study
Authors: Stepan Maruniak , Oleh Loskutov , Oleksandr Druzhyna , Justyna Swol
Published: October 2023

Background

The most favorable anesthesia protocol during on-pump coronary artery bypass grafting (CABG) in patients with coronary heart disease remains unclear, despite previous publications regarding the interaction between anesthesia protocol and postoperative complications. The aim of the study was to compare the effect of a multimodal low-opioid anesthesia protocol (MLOP) on early postoperative complications during on-pump CABG.

Methods

A single-center prospective cohort study including 120 patients undergoing on-pump CABG aged 18 to 65 years, divided into two groups according to undergoing MLOP or routine-opioid anesthesia protocol (ROP). The analyzed parameters were plasma IL-6 levels, complications, duration of mechanical ventilation, length of intensive care unit stay, and hospitalization.

Results

In the MLOP group, the levels of IL-6 at the end of the surgery were 25.6% significantly lower compared to the ROP group (33.4 ± 9.4 vs. 44.9 ± 15.9, p < 0.0001), the duration of mechanical ventilation was significantly shorter (2.0 (2.0; 3.0) h vs. 4.0 (3.0; 5.0) h, p < 0.001), the incidence of low cardiac output syndrome was almost two and half times lower (7 (11.7%) vs. 16 (26.7%), p = 0.037), and also the incidence of postoperative atrial fibrillation was significantly lower (9 (15.0%) vs. 19 (31.7%), p = 0.031).

Conclusion

Our study confirms that using MLOP was characterized by significantly lower levels of IL-6 at the end of surgery and a lower incidence of low cardiac output syndrome and postoperative atrial fibrillation than ROP.

Trial registration

The study is registered in clinicaltrials.gov №NCT05514652.
Acute myeloid leukemia: from NGS, through scRNA-seq, to CAR-T. dissect cancer heterogeneity and tailor the treatment
Authors: Peroni Edoardo , Randi Maria Luigia , Rosato Antonio , Cagnin Stefano
Published: October 2023

Acute myeloid leukemia (AML) is a malignant blood cancer with marked cellular heterogeneity due to altered maturation and differentiation of myeloid blasts, the possible causes of which are transcriptional or epigenetic alterations, impaired apoptosis, and excessive cell proliferation. This neoplasm has a high rate of resistance to anticancer therapies and thus a high risk of relapse and mortality because of both the biological diversity of the patient and intratumoral heterogeneity due to the acquisition of new somatic changes. For more than 40 years, the old gold standard “one size fits all” treatment approach included intensive chemotherapy treatment with anthracyclines and cytarabine.

The manuscript first traces the evolution of the understanding of the pathology from the 1970s to the present. The enormous strides made in its categorization prove to be crucial for risk stratification, enabling an increasingly personalized diagnosis and treatment approach.

Subsequently, we highlight how, over the past 15 years, technological advances enabling single cell RNA sequencing and T-cell modification based on the genomic tools are affecting the classification and treatment of AML. At the dawn of the new millennium, the advent of high-throughput next-generation sequencing technologies has enabled the profiling of patients evidencing different facets of the same disease, stratifying risk, and identifying new possible therapeutic targets that have subsequently been validated. Currently, the possibility of investigating tumor heterogeneity at the single cell level, profiling the tumor at the time of diagnosis or after treatments exist. This would allow the identification of underrepresented cellular subclones or clones resistant to therapeutic approaches and thus responsible for post-treatment relapse that would otherwise be difficult to detect with bulk investigations on the tumor biopsy. Single-cell investigation will then allow even greater personalization of therapy to the genetic and transcriptional profile of the tumor, saving valuable time and dangerous side effects. The era of personalized medicine will take a huge step forward through the disclosure of each individual piece of the complex puzzle that is cancer pathology, to implement a “tailored” therapeutic approach based also on engineered CAR-T cells.
The therapeutic landscape of tauopathies: challenges and prospects
Authors: Cummings Jeffrey L. , Gonzalez M. Isabel , Pritchard Martyn C. , May Patrick C. , Toledo-Sherman Leticia M. , Harris Glenn A.
Published: October 2023

Tauopathies are a group of neurodegenerative disorders characterized by the aggregation of the microtubule-associated protein tau. Aggregates of misfolded tau protein are believed to be implicated in neuronal death, which leads to a range of symptoms including cognitive decline, behavioral change, dementia, and motor deficits. Currently, there are no effective treatments for tauopathies. There are four clinical candidates in phase III trials and 16 in phase II trials. While no effective treatments are currently approved, there is increasing evidence to suggest that various therapeutic approaches may slow the progression of tauopathies or improve symptoms. This review outlines the landscape of therapeutic drugs (indexed through February 28, 2023) that target tau pathology and describes drug candidates in clinical development as well as those in the discovery and preclinical phases. The review also contains information on notable therapeutic programs that are inactive or that have been discontinued from development.
Using the canadian egg ladder in children with food protein-induced enterocolitis syndrome: a case series
Authors: Ye Linlei , Wong Tiffany , Lavine Elana , Cook Victoria E. , Erdle Stephanie C.
Published: October 2023

Background

Current management of food protein-induced enterocolitis syndrome (FPIES) involves strict avoidance of the offending food for 12–18 months, followed by oral food challenge (OFC) under physician supervision. OFCs are resource-intensive and there is a lack of a universal standardized protocol for FPIES. Prolonged avoidance may increase the risk of IgE-mediated allergy, particularly in atopic patients. Food ladders have shown success in promoting accelerated tolerance in patients with IgE-mediated allergy. Our case series evaluated the safety of use of the Canadian Egg Ladder in patients with mild-to-moderate FPIES to egg.

Methods

From May 2020 to November 2021, patients with mild-to-moderate FPIES to egg, defined as no history of lethargy or intravenous fluid administration, were started on the Canadian Egg Ladder. Instructions for advancing up the ladder were identical to using the Canadian Egg Ladder in patients with IgE-mediated allergy. Patients were followed every 3–6 months, at which time information was collected regarding progression up the ladder, symptoms while on treatment and interventions required. Treating allergists completed a survey to capture baseline demographic characteristics and prior tolerance to egg. Descriptive statistics were analyzed using MS Excel.

Results

Twenty-one patients with mild-to-moderate FPIES were started on the Canadian Egg Ladder. Median age at initiation of the ladder was 10 months (IQR, 9–11). Nineteen (90.5%) patients completed the ladder, tolerating a serving size amount of cooked egg, over a median duration of 7 month (IQR, 4–9 months). Four patients (19.0%) had mild symptoms including vomiting (9.5%), pallor (9.5%), belching (4.8%), irritability (4.8%) and small spit up (4.8%). In three of the four patients, symptoms were the result of accidental exposure to a higher step of the ladder. There were no reports of lethargy. No patients required health care presentation or intravenous fluid administration. No patients discontinued the ladder.

Conclusions

The Canadian Egg Ladder can safely guide the dietary advancement of egg-containing foods in patients with mild-to-moderate FPIES to egg, without the need for prolonged avoidance and resource-intensive OFCs.
Behçet's disease with intestinal involvement: a case report and review of the literature
Authors: Li Lin , Wang Jing , Li Huifang , He Chiyi , Niu Xiaoping
Published: October 2023

Background

Behçet’s disease (BD) is a chronic systemic disease characterized by vasculitis as the basic pathological change. BD is rare, and gastrointestinal involvement occurs in 3% to 25% of affected patients. This article describes a rare case of intestinal BD along with a literature review of intestinal involvement in BD.

Case presentation

A 50-year-old Han woman from China presented with a > 6-month history of distending pain in the right upper abdomen. Because of mechanical obstruction secondary to stricture formation from an ileocecal ulcer, she underwent radical right colon resection, and postoperative pathologic examination indicated an ileocecal ulcer. The patient was readmitted to the hospital 6 months postoperatively for recurrence of the same symptoms. Colonoscopy indicated obvious narrowing of the anastomosis with an oval-shaped deep ulcer that could not be passed by the endoscope. Pathologic examination showed acute and chronic inflammation of the anastomotic mucosa and granulation tissue. In addition, gastroscopy showed a 3.0- × 4.0-cm giant ulcer at the junction of the descending bulb along with a sinus tract. Moreover, total gastrointestinal computed tomography angiography showed significant thickening of the intestinal wall near the transverse colon, forming a sinus tract at the junction of the antrum and duodenum with a length of about 1.3 cm and width of about 0.2 cm. Further inquiry regarding the patient’s medical history revealed that she had developed repeated oral ulcers 3 years previously and repeated eye inflammation 5 years previously. Specimens of the right half of the colon removed 6 months previously were sent to Run Run Shaw Hospital Affiliated to Zhejiang University for consultation. The pathologic examination revealed vasculitis in the submucosa and subserosa, and the patient was finally diagnosed with BD. She began treatment with adalimumab, and repeat gastroenteroscopy revealed that the intestinal ulcer had significantly improved.

Conclusions

An oval-shaped deep intestinal ulcer is a characteristic lesion in patients with BD and may involve the intestinal muscle layer. This case emphasizes that BD is a vasculitis affecting multiple organs and can present with a single, deep, clean-edged intestinal ulcer that penetrates the bowel wall to form a sinus tract. Therefore, careful examination and differential diagnosis should be carried out to prevent a poor prognosis. Adalimumab is effective for patients with intestinal BD.
Exploring the impact of evaluation on learning and health innovation sustainability: protocol for a realist synthesis
Authors: Bird Marissa , Côté-Boileau Élizabeth , Wodchis Walter P. , Jeffs Lianne , MacPhee Maura , Shaw James , Austin Tujuanna , Bruno Frances , Bhalla Megan , Gray Carolyn Steele
Published: October 2023

Background

Within the Learning Health System (LHS) model, learning routines, including evaluation, allow for continuous incremental change to take place. Within these learning routines, evaluation assists in problem identification, data collection, and data transformation into contextualized information, which is then re-applied to the LHS environment. Evaluation that catalyzes learning and improvement may also contribute to health innovation sustainability. However, there is little consensus as to why certain evaluations seem to support learning and sustainability, while others impede it. This realist synthesis seeks to understand the contextual factors and underlying mechanisms or drivers that best support health systems learning and sustainable innovation.

Methods

This synthesis will be guided by Pawson and colleagues’ 2005 and Emmel and colleagues’ 2018 guidelines for conducting realist syntheses. The review process will encompass five steps: (1) scoping the review, (2) building theories, (3) identifying the evidence, (4) evidence selection and appraisal, and (5) data extraction and synthesis. An Expert Committee comprised of leaders in evaluation, innovation, sustainability, and realist methodology will guide this synthesis. Review findings will be reported using the RAMESES guidelines.

Discussion

The use of a realist review will allow for exploration and theorizing about the contextual factors and underlying mechanisms that make evaluations ‘work’ (or ‘not work’) to support learning and sustainability. Depending on results, we will attempt to synthesize findings into a series of recommendations for evaluations with the intention to support health systems learning and sustainability. Finalized results will be presented at national and international conferences, as well as disseminated via a peer-reviewed publication.

Systematic review registration

This realist synthesis protocol has been registered with PROSPERO (https://www.crd.york.ac.uk/prospero/ ID 382690).
Social connectedness and suicidal ideation: the roles of perceived burdensomeness and thwarted belongingness in the distress to suicidal ideation pathway
Authors: Gill Peter Richard , Arena Michael , Rainbow Christopher , Hosking Warwick , Shearson Kim M , Ivey Gavin , Sharples Jenny
Published: October 2023

Background

Suicide is a serious public health issue. Distress has been identified as a common risk factor, with research also suggesting that a lack of social connectedness is involved.

Methods

This quantitative, cross-sectional study investigated the role of perceived burdensomeness and thwarted belongingness in the psychological distress/suicidal ideation pathway in a community sample of 480 Australian adults.

Results

As expected, distress was found to be a strong predictor of suicidal ideation. Perceived burdensomeness and thwarted belongingness both moderated and mediated the relationship between distress and suicidal ideation. Specifically, distress was more strongly linked to suicide ideation when burdensomeness or thwarted belongingness were also high. This moderating effect was stronger for thwarted belongingness than it was for burdensomeness. These variables also mediated the pathway, in that higher distress related to higher burdensomeness and thwarted belonging, which in turn related to higher suicide ideation. This mediating effect was stronger for burdensomeness than for thwarted belonging.

Conclusions

Overall, the findings confirm the importance of our social relatedness in suicide. Increasing belongingness and reducing the perception of being a burden on others may be an important intervention strategy for weakening the link between distress and suicide ideation.
Developing and validation of COVID-19 media literacy scale among students during the COVID-19 pandemic
Authors: Jormand Hanieh , Barati Majid , Bashirian Saeed , Khazaei Salman , Jenabi Ensiyeh , Zareian Sepideh
Published: October 2023

Objective

This cross-sectional validation work evaluated the psychometric features of the COVID-19 Media Literacy Scale (C-19MLs) in Students.

Methods

The study was conducted on 530 students from a medical university in Hamadan, Iran, who were recruited through a stratified cluster random sampling process in June-July 2020. Intraclass Correlation Coefficient (ICC) and internal consistency were used to assess the reliability. Moreover, CFA (Confirmatory Factor Analyses) and EFA (Exploratory Factor Analyses) were carried out to examine construction validity. CVR (Content Validity Ratio) and CVI (Content Validity Index) were used to examine the content validity.

Results

According to the factor analysis, it was indicated that the C-19MLs included 21 items measuring five dimensions (constructedness of credible Covid-19 media messages, contractedness of fake media coronavirus messages, fake media coronavirus messages, audience, with three questions in each factor; format, represented lifestyles in fake media coronavirus messages with six questions in each factor) for an explanation of 58.4% of the prevalent variance. The average scores for the CVI and CVR were respectively 0.94 and 0.77. According to confirmatory factor analysis, the studied model had an appropriate fitting to the data; the relative chi-square (x2/df) = 2.706 < 3, RMSEA = 0.093 ≤ 0.1; CFI = 0.893 ≥ 0.9; TLI = 0.874 ≥ 0.9; GFI = 0.816 ≥ 0.9; and SRMR = 0.06 ≤ 0.08. Further analyses represented acceptable findings for internal consistency reliability values with 0.86 of Cronbach’s alpha.

Conclusions

The results proved that the C-19MLs is a reliable and valid tool, and it is suitable and acceptable now and can be utilized in forthcoming investigations. This highlights educators and stakeholders to realize the importance of participating individuals in the new media ecology and new ‘Infomedia’ ecosystems for enabling people in the current digital society.
Determinants of astrocytic pathology in stem cell models of primary tauopathies
Authors: Fiock Kimberly L. , Hook Jordan N. , Hefti Marco M.
Published: October 2023

Astrocytic tau aggregates are seen in several primary and secondary tauopathies, including progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and chronic traumatic encephalopathy (CTE). In all of these diseases, astrocytic tau consists mostly of the longer (4R) tau isoform, even when adjacent neuronal aggregates consist of a mixture of 3- and 4R tau, as in CTE. Even the rare astrocytic tau aggregates seen in Pick’s disease appear to contain both 3R and 4R tau. The reasons for this, and the mechanisms by which astrocytic tau aggregates form, remain unclear. We used a combination of RNA in situ hybridization and immunofluorescence in post-mortem human brain tissue, as well as tau uptake studies in human stem cell-derived astrocytes, to determine the origins of astrocytic tau in 4R tauopathies. We found no differences in tau mRNA expression between diseases or between tau positive and negative astrocytes within PSP. We then found that stem cell-derived astrocytes preferentially take up long isoform (4R) recombinant tau and that this uptake is impaired by induction of reactivity with inflammatory stimuli or nutritional stress. Astrocytes exposed to either 3R or 4R tau also showed downregulation of genes related to astrocyte differentiation. Our findings suggest that astrocytes preferentially take up neuronal 4R tau from the extracellular space, potentially explaining why 4R tau is the predominant isoform in astrocytic tau aggregates.
3D-printing of the elbow in complex posttraumatic elbow-stiffness for preoperative planning, surgery-simulation and postoperative control
Authors: Grunert Ronny , Winkler Dirk , Frank Franziska , Moebius Robert , Kropla Fabian , Meixensberger Juergen , Hepp Pierre , Elze Maria
Published: October 2023

Background

Restoration of mobility of the elbow after post-traumatic elbow stiffening due to osteophytes is often a problem.

Methods

The anatomical structures were segmented within the CT-scan. Afterwards, the Multi Jet Fusion 3D-printing was applied to create the model made of biocompatible and steam-sterilizable plastic. Preoperative simulation of osteophyte resection at the 3D-model was performed as well as the direct comparison with the patient anatomy intraoperatively.

Results

The patient-specific was very helpful for the preoperative simulation of the resection of elbow osteophytes. The 3D anatomical representation improved the preoperative plan its implementation. A high degree of fidelity was found between the 3D Printed Anatomical representation and the actual joint pathology.

Conclusions

Arthrolysis of complex post-traumatic bony changes is an important indication for the use of 3D models for preoperative planning. Due to the use of 3D printing and software simulation, accurate resection planning is feasible and residual bony stiffening can be avoided. 3D printing models can lead to an improvement in surgical quality.