bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic biomarkers and aortic dissection: a systematic review and meta-analysis
Authors: Chen Hongjian , Li Yunjie , Li Zheqian , Shi Yanli , Zhu Haobo
Published: October 2023

Background

Aortic dissection (AD) is a serious and fatal vascular disease. The earlier the condition of AD patients can be assessed precisely, the more scientifically controlled the patient’s condition will be. Therefore, timely and accurate diagnosis is significant for AD. Blood biomarker testing as a method of liquid biopsy can improve the diagnostic efficiency of AD. This study conducted a systematic review of the current blood diagnostic biomarkers of AD.

Methods

The PubMed, Cochrane Library, Web of Science, and Embase electronic databases were systematically searched from inception to January 1, 2023, using the terms “aortic dissection”, “serum”, “plasma” and “diagnosis”. Stata 12.0 software was used to perform Random effects meta-analysis was performed using Stata 12.0 software to determine the effect sizes and corresponding 95% confidence intervals. Then, a summary receiver operator characteristic (SROC) curve was drawn, and the area under the ROC curve (AUC) was calculated.

Results

D-dimer had the best sensitivity and AUC for AD, with values of 0.96 (95% CI: 0.93–0.98) and 0.95 (95% CI: 0.93–0.97), respectively. The sensitivity and AUC values for D-dimer with a cut-off value of 500 ng/mL were 0.97 (95% CI: 0.95–0.99) and 0.94 (95% CI: 0.92–0.96), respectively. In contrast, microRNA had a better specificity value for AD, at 0.79 (95% CI: 0.73–0.83).

Conclusions

D-dimer and microRNA have good accuracy in the diagnosis of AD, but the specificity of D-dimer is worse, and studies of microRNA are insufficient. The combination of different biomarkers can improve the diagnostic accuracy. Other blood biomarkers are related to the pathological progression of AD and can be selected according to pathological progress.
Knowledge, practice of cervical cancer screening and associated factors among women police members of Addis Ababa police commission Ethiopia
Authors: Misgun Tangut , Demissie Dereje Bayissa
Published: October 2023

Background

Cervical cancer is a public health problem. It is one of the leading causes of death in women worldwide and the second leading cause of female cancer-related deaths. Cervical cancer screening enables the detection of abnormal cervical cells, including precancerous cervical lesions, as well as early-stage cervical cancer. Routine cervical screening has been shown to reduce both the incidence and mortality of the disease.

Objective

The aim of this study was to assess knowledge, practice of cervical cancer screening and associated factors among women police members at Addis Ababa police commission Ethiopia 2022.

Method

An institutional-based cross-sectional study was conducted at the Addis Ababa police commission in the Lidet Sub-city police department from December 1st to January 30th, 2022. The data were collected through a structured, self-administered questionnaire from 361 randomly selected police officers. The collected data were analyzed using SPSS version 26 software in descriptive statistics, binary, and multivariable logistic regression analysis to identify factors associated with the outcome variable at PV = 0.05 with an AOR and 95% CI. Results: The complete response rate was 97.57% (361/371). This found that 59.5% of the total study participants were aged between 18 and 29 years old, and 47.3% were married in marital status. This study determined knowledge status of police commission towards cervical cancer screening revealed that 183(49.5%) had good knowledge, with identified factors which increases likelihood of good knowledge were attitude [AOR = 2.03, 95%CI;( 1.25–3.3)] and cervical cancer screening practice [AOR = 2.0, 95%CI (1.15–3.53)] respectively.

This is determined the prevalence of cervical cancer screening practice was 68(18.4%)with 95% CI(14.3–22.4) with identified factors which increases likelihood of cervical cancer screening practice were age, [AOR = 3.24, 95% CI;( 1.08–9.75)], marital status [AOR = 3.88,95%CI,(1.55–9.73)] monthly income [AOR = 4.82,95%CI;(1.44–16.12)],religion[AOR = 8.65,95%CI,( 1.65–45.46)] and knowledge [AOR = 2.35,95%CI;( 1.22–4.52)] respectively. The main reason reported for not practice of cervical cancer screening was feeling healthy.

Conclusion and recommendation

This study identified that the knowledge status of female police commissioners were poor and practice of cervical cancer screening were found to be very low. Some of the factors associated with the cervical cancer screening practice were age, marital status, monthly income and knowledge of the women. In addition, feeling being health was associated poor practice of cervical cancer screening. To alleviate this problem the health authorities at different level of the health system should take massive awareness creation activities through various communication channels about screening service prepare screening campaign.
Proximal hip fractures in 71,920 elderly patients: incidence, epidemiology, mortality and costs from a retrospective observational study
Authors: Viganò Marco , Pennestrì Federico , Listorti Elisabetta , Banfi Giuseppe
Published: October 2023

Background

The risk of proximal femoral fractures increases with aging, causing significant morbidity, disability, mortality and socioeconomic pressure. The aims of the present work are (1) to investigate the epidemiology and incidence of these fractures among the elderly in the Region of Lombardy; (2) to identify the factors influencing survival; (3) to identify the factors influencing hospitalization and post-operative costs.

Methods

The Region of Lombardy provided anonymized datasets on hospitalized patients with a femoral neck fracture between 2011 and 2016, and anonymized datasets on extra-hospital treatments to track the patient history between 2008 and 2019. Statistical evaluations included descriptive statistics, survival analysis, Cox regression and multiple linear models.

Results

71,920 older adults suffered a femoral fracture in Lombardy between 2011 and 2016. 76.3% of patients were females and the median age was 84. The raw incidence of fractures was stable from year 2011 to year 2016, while the age-adjusted incidence diminished. Pertrochanteric fractures were more spread than transcervical fractures. In patients treated with surgery, receiving treatment within 48 h reduced the hazard of death within the next 24 months. Combined surgical procedures led to increased hazard in comparison with arthroplasty alone, while no differences were observed between different arthroplasties and reduction or fixation. In patients treated conservatively, age and male gender were associated with higher hazard of death. All patients considered, the type of surgery was the main factor determining primary hospitalization costs. A higher number of surgeries performed by the index hospital in the previous year was associated with financial savings. The early intervention significantly correlated with minor costs.

Conclusions

The number of proximal femoral fractures is increasing even if the age-adjusted incidence is decreasing. This is possibly due to prevention policies focused on the oldest cohort of the population. Two policies proved to be significantly beneficial in clinical and financial terms: the centralization of patients in high-volume hospitals and a time limit of 48 h from fracture to surgery.

Trial registration

Non applicable.
Frailty as a predictor of mortality: a comparative cohort study of older adults in Costa Rica and the United States
Authors: Santamaría-Ulloa Carolina , Lehning Amanda J. , Cortés-Ortiz Mónica V. , Méndez-Chacón Ericka
Published: October 2023

Background

Frailty is a common condition among older adults that results from aging-related declines in multiple systems. Frailty increases older adults’ vulnerability to negative health outcomes, including loss of mobility, falls, hospitalizations, and mortality. The aim of this study is to examine the association between frailty and mortality in older adults from Costa Rica and the United States.

Methods

This prospective cohort study uses secondary nationally-representative data of community-dwelling older adults from the Costa Rican Longevity and Healthy Aging Study (CRELES, n = 1,790) and the National Health & Aging Trends Study (NHATS, n = 6,680). Frailty status was assessed using Physical Frailty Phenotype, which includes the following five criteria: shrinking, exhaustion, low physical activity, muscle weakness, and slow gait. We used Cox proportional hazard models to examine the association between frailty and all-cause mortality, including sociodemographic characteristics and health behaviors as covariates in the models. Mortality follow-up time was right censored at 8 years from the date at baseline interview.

Results

The death hazard for frail compared to non-frail older adults was three-fold in Costa Rica (HR = 3.14, 95% CI: 2.13–4.62) and four-fold in the White US (HR = 4.02, 95% CI: 3.04–5.32). Older age, being male, and smoking increased mortality risk in both countries. High education was a protective factor in the US, whereas being married/in union was a protective factor in Costa Rica. In the US, White older adults had a lower risk of death compared to all other races and ethnicities.

Conclusions

Results indicate that frailty can have a differential impact on mortality depending on the country. Access to universal health care across the life course in Costa Rica and higher levels of stress and social isolation in the US may explain differences observed in end-of-life trajectories among frail older adults.
Association of rs2282679 polymorphism in vitamin D binding protein gene (GC) with the risk of vitamin D deficiency in an iranian population: season-specific vitamin D status
Authors: Asghari Golaleh , Yuzbashian Emad , Najd-Hassan-Bonab Leila , Mirmiran Parvin , Daneshpour Maryam S. , Azizi Fereidoun
Published: October 2023

Background

Genome-wide association studies in Western countries indicate a considerable impact of variations in vitamin D binding protein (GC) genes on serum concentrations of 25-hydroxyvitamin D (25(OH)D). We aimed to investigate an association between rs2282679 polymorphism in GC and vitamin D deficiency.

Methods

A cross-sectional study conducted in the framework of the Tehran Cardio-Metabolic Genetic Study (TCGS) cohort. A total of 1568 participants aged > 18 years were randomly selected, and their 25(OH) D concentration was measured. Vitamin D deficiency was assessed concerning rs2282679 by descriptive and multivariate analysis, odds ratio (OR), and 95% confidence intervals (95%CI) calculated. Since the interaction term between rs2282679 and recruitment season was significant, we performed regression analysis separately for individuals whose blood was taken in high sunny and those whose blood was drawn in the low sunny season.

Results

The rs2282679 polymorphism was in Hardy-Weinberg equilibrium (P > 0.05) in the studied population. The serum concentration of 25(OH) D median was 15.0 ng/mL, and the prevalence of VDD was 27.8%. The presence of the G allele in rs2282679 increases the risk of VDD in additive (OR = 1.35, 95% CI: 1.06–1.73) and dominant (OR = 1.33, 95% CI: 1.06–1.68) genetic models. After separating participants based on the recruitment season, the unfavorable association was observed in the additive and dominant only in the low sunny season.

Conclusion

The finding of the current study indicates that the GC rs2282679 SNP is associated with vitamin D deficiency. It seems that the impact of risk allele increased in the low sunny season when UV exposure has been declined.
Toxic leadership behaviour of nurse managers and turnover intentions: the mediating role of job satisfaction
Authors: Ofei Adelaide Maria Ansah , Poku Collins Atta , Paarima Yennuten , Barnes Theresa , Kwashie Atswei Adzo
Published: October 2023

Introduction

Globally, hospitals are confronted with major challenges of turnover of nurses. Knowledge of the factors that account for the turnover of nurses will aid in creating strategies that will enhance nurse managers’ leadership behaviour and job satisfaction to reduce turnover. The study, therefore, investigated the mediating role of job satisfaction on toxic leadership and turnover intentions of nurses.

Methods

A multi-centre cross-sectional study was undertaken to assess 943 nurses using the Toxic-leadership Behaviour of Nurse Managers scale, Minnesota Satisfaction Questionnaire and Turnover Intention scale. Descriptive statistics was used to assess the prevalence of toxic leadership, job satisfaction and turnover and Pearson’s correlation examined the relationships between the variables. Hayes’ PROCESS macro approach of mediation was used to determine the effect of toxic leadership behaviour on the turnover intention on the possible influence of job satisfaction.

Results

The response rate for the study was 76.0%. Mean scores for turnover intentions and toxic leadership behaviour were 3.71 and 2.42 respectively. Nurses who work with toxic managers showed a higher propensity to leave their jobs. Job satisfaction acted as a mediator between the toxic leadership practices of managers and turnover intentions. The total effect of toxic leadership behaviour on turnover intention comprised its direct effect (β = 0.238, SE = 0.017, 95% CI [0.205, 0.271]) and its indirect effect (β = -0.020, SE = 0.017).

Conclusions

Job satisfaction acted as a mediating factor for toxic leadership behaviour and nurses’ turnover intentions. As part of nurse retention initiatives, avoiding toxic leadership behaviours will be the ultimate agenda. Nurse administrators should recognize the value of excellent leadership and develop a structured training programme through the use of evidence-based professional development plans for nurse managers.
Polyautoimmunity manifest as inflammatory myopathy, uveitis, and progressive cutaneous depigmentation in a mixed breed dog: a case report
Authors: Lee Mary Ann , Hulsebosch Sean E. , Affolter Verena K. , Dear Jonathan D. , Knipe Marguerite F. , Maggs David J. , Moore Bret A. , Outerbridge Catherine A. , Marsilio Sina
Published: October 2023

Background

Polyautoimmunity is the expression of more than one autoimmune disease in a single patient. This report documents polyautoimmunity in a mixed breed dog with concurrent uveitis, cutaneous depigmentation, and inflammatory myopathy.

Case presentation

A 1-year-old male neutered mixed breed dog was presented for progressive generalized leukotrichia and leukoderma, bilateral panuveitis, and masticatory muscle atrophy. The latter progressed to myositis of lingual, pharyngeal, and masticatory muscles confirmed by biopsy. Temporalis muscle was completely replaced by adipose and fibrous tissue, and necrotic myofibers with extensive infiltration of mononuclear cells indicated active myositis of lingual muscle. Skin biopsies showed severe melanin clumping in epidermis, hair follicles, and hair shafts, and perifollicular pigmentary incontinence. Uveitis, depigmentation, and myositis affecting the masticatory, pharyngeal, and tongue muscles were diagnosed based on clinical, histological, and laboratory findings.

Conclusions

To the authors’ knowledge, this is the first report of concurrent uveitis, progressive cutaneous depigmentation, and inflammatory myopathy in a dog.
Awareness of the public charge, confidence in knowledge, and the use of public healthcare programs among Mexican-origin Oregon Latino/as
Authors: Wolwowicz-Lopez Edlyn , Boniface Emily , Díaz-Anaya Sara , Cornejo-Torres Yareli , Darney Blair G.
Published: October 2023

Objective

We describe awareness about the modified “public charge” rule among Oregon’s Mexican-origin Latino/a population and whether concerns about the rule influenced disenrollment from state-funded programs, which do not fall under the public charge.

Methods

We conducted a cross-sectional survey of adults (ages 18–59) recruited at the Mexican consulate and living in the state of Oregon. Our outcomes were awareness (of the public charge, source of knowledge, and confidence in knowledge of the public charge) and disenrolling self or family members from state-funded public healthcare programs due to concerns about the rule. We described outcomes and used logistic regression and calculated adjusted probabilities to identify factors associated with awareness of the public charge.

Results

Of 498 Latino/a respondents, 48% reported awareness of the public charge. Among those who knew about the public charge, 14.6% had disenrolled themselves or family members from public healthcare programs and 12.1% were hesitant to seek care due to concerns about the public charge. Younger respondents had a lower adjusted probability of awareness of the public charge (18–24 years: 15.6% (95% CI 3.1–28.2); 30–39 years 54.9% (95% CI 47.7–62.0). Higher education was associated with a higher adjusted probability of awareness of the public charge; ability to speak English was not associated with awareness of the public charge.

Conclusion

Our study reveals limited awareness about the public charge among Mexican-origin Oregon Latino/as. Outreach and advocacy are essential to ensure Latino/as know their rights to access available state-funded healthcare programs.
The mechanism of oleic acid inhibiting platelet activation stimulated by collagen
Authors: Zhou Xianghui , Zhou Xin , Zhu Ruirui , Ming Zhangyin , Cheng Zhipeng , Hu Yu
Published: October 2023

Background

Abnormal platelet activation is a key factor in the occurrence and development of thrombotic diseases. However, the physiological mechanisms that underlie platelet homeostasis remain unclear. Oleic acid, one of the most abundant lipids in the human diet, has potential antithrombotic effects. This study aimed to investigate the effects of oleic acid on platelet activation and thrombosis.

Methods

Platelet aggregation, ATP release, and fibrinogen spread were evaluated to determine the role of oleic acid in platelet activation. A ferric chloride-induced carotid injury model was used to establish the effect of oleic acid on thrombus formation in vivo. Western blotting analysis and transfection experiments were performed to determine the mechanisms involved in this process.

Results

Oleic acid inhibited platelet aggregation, granule release, and calcium mobilization. Furthermore, it inhibited the spread of platelets on fibrinogen. We also found that oleic acid delayed arterial thrombosis in mice, as demonstrated in a murine model of ferric chloride-induced carotid artery thrombosis. The molecular mechanism of its inhibition of platelet activity may be through the Syk-PLCγ2 and CaMKKβ/AMPKα/VASP pathways. In addition, we demonstrated that the phosphorylation of AMPK at Ser496 was an important mechanism of platelet activation.

Conclusions

Our study showed that oleic acid inhibits platelet activation and reduces thrombogenesis by inhibiting the phosphorylation of multiple signaling molecules, offering new insights into the research and development of antiplatelet drugs.
Carbon dioxide and MAPK signalling: towards therapy for inflammation
Authors: Gałgańska Hanna , Jarmuszkiewicz Wieslawa , Gałgański Łukasz
Published: October 2023

Inflammation, although necessary to fight infections, becomes a threat when it exceeds the capability of the immune system to control it. In addition, inflammation is a cause and/or symptom of many different disorders, including metabolic, neurodegenerative, autoimmune and cardiovascular diseases. Comorbidities and advanced age are typical predictors of more severe cases of seasonal viral infection, with COVID-19 a clear example. The primary importance of mitogen-activated protein kinases (MAPKs) in the course of COVID-19 is evident in the mechanisms by which cells are infected with SARS-CoV-2; the cytokine storm that profoundly worsens a patient’s condition; the pathogenesis of diseases, such as diabetes, obesity, and hypertension, that contribute to a worsened prognosis; and post-COVID-19 complications, such as brain fog and thrombosis. An increasing number of reports have revealed that MAPKs are regulated by carbon dioxide (CO2); hence, we reviewed the literature to identify associations between CO2 and MAPKs and possible therapeutic benefits resulting from the elevation of CO2 levels. CO2 regulates key processes leading to and resulting from inflammation, and the therapeutic effects of CO2 (or bicarbonate, HCO3−) have been documented in all of the abovementioned comorbidities and complications of COVID-19 in which MAPKs play roles. The overlapping MAPK and CO2 signalling pathways in the contexts of allergy, apoptosis and cell survival, pulmonary oedema (alveolar fluid resorption), and mechanical ventilation–induced responses in lungs and related to mitochondria are also discussed.
Allergen-induced CD11c + dendritic cell pyroptosis aggravates allergic rhinitis
Authors: Qiao Yue-Long , Zhu Ming-Wan , Xu Shan , Jiao Wo-Er , Ni Hai-Feng , Tao Ze-Zhang , Chen Shi-Ming
Published: October 2023

Background

Pyroptosis is crucial for controlling various immune cells. However, the role of allergen-induced CD11c + dendritic cell (DC) pyroptosis in allergic rhinitis (AR) remains unclear.

Methods

Mice were grouped into the control group, AR group and necrosulfonamide-treated AR group (AR + NSA group). The allergic symptom scores, OVA-sIgE titres, serum IL-1β/IL-18 levels, histopathological characteristics and T-helper cell-related cytokines were evaluated. CD11c/GSDMD-N-positive cells were examined by immunofluorescence analysis. Murine CD11c + bone marrow-derived DCs (BMDCs) were induced in vitro, stimulated with OVA/HDM, treated with necrosulfonamide (NSA), and further cocultured with lymphocytes to assess BMDC function. An adoptive transfer murine model was used to study the role of BMDC pyroptosis in allergic rhinitis.

Results

Inhibiting GSDMD-N-mediated pyroptosis markedly protected against Th1/Th2/Th17 imbalance and alleviated inflammatory responses in the AR model. GSDMD-N was mainly coexpressed with CD11c (a DC marker) in AR mice. In vitro, OVA/HDM stimulation increased pyroptotic morphological abnormalities and increased the expression of pyroptosis-related proteins in a dose-dependent manner; moreover, inhibiting pyroptosis significantly decreased pyroptotic morphology and NLRP3, C-Caspase1 and GSDMD-N expression. In addition, OVA-induced BMDC pyroptosis affected CD4 + T-cell differentiation and related cytokine levels, leading to Th1/Th2/Th17 cell imbalance. However, the Th1/Th2/Th17 cell immune imbalance was significantly reversed by NSA. Adoptive transfer of OVA-loaded BMDCs promoted allergic inflammation, while the administration of NSA to OVA-loaded BMDCs significantly reduced AR inflammation.

Conclusion

Allergen-induced dendritic cell pyroptosis promotes the development of allergic rhinitis through GSDMD-N-mediated pyroptosis, which provides a clue to allergic disease interventions.
Genomic communication via circulating extracellular vesicles and long-term health consequences of COVID-19
Authors: Nair Soumyalekshmi , Nova-Lamperti Estefania , Labarca Gonzalo , Kulasinghe Arutha , Short Kirsty R. , Carrión Flavio , Salomon Carlos
Published: October 2023

COVID-19 continues to affect an unprecedented number of people with the emergence of new variants posing a serious challenge to global health. There is an expansion of knowledge in understanding the pathogenesis of Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the impact of the acute disease on multiple organs. In addition, growing evidence reports that the impact of COVID-19 on different organs persists long after the recovery phase of the disease, leading to long-term consequences of COVID-19. These long-term consequences involve pulmonary as well as extra-pulmonary sequelae of the disease. Noteably, recent research has shown a potential association between COVID-19 and change in the molecular cargo of extracellular vesicles (EVs). EVs are vesicles released by cells and play an important role in cell communication by transfer of bioactive molecules between cells. Emerging evidence shows a strong link between EVs and their molecular cargo, and regulation of metabolism in health and disease. This review focuses on current knowledge about EVs and their potential role in COVID-19 pathogenesis, their current and future implications as tools for biomarker and therapeutic development and their possible effects on long-term impact of COVID-19.
A dual role for adeno-associated virus in human health
Authors: Araujo Natalia M
Published: October 2023

Adeno-associated virus (AAV) differs from most other viruses, as it requires the simultaneous presence of a helper virus for an active infection. Up to 80% of the human population is seropositive for AAV antibodies. AAV has been known to be a non-pathogenic virus and an inhibitor of carcinogenesis caused by coinfecting viruses. However, the recent reports associating AAV infection with hepatocellular carcinoma development and the mysterious cases of acute severe hepatitis in children have challenged the idea that AAV is a harmless virus. Herein, we explore the usefulness of AAV in gene therapy and the importance of AAV as a protector or perpetrator in human carcinogenesis, ultimately reflecting on the dual role of AAV in human health.
Large mesenchymal cystic and chondroid pulmonary hamartoma mimicking lung cancer: Case report
Authors: Ahn Seha , Lee Heejin , Kang Joon Kyu , Kim In Sub , Moon Youngkyu , Choi Jung Suk , Choi Si Young
Published: October 2023

Pulmonary hamartoma is the most commonly resected benign neoplasm of lung. The mesenchymal cystic subtype is a rare and often bilaterally occurring variant composed of multiple cysts and nodules. Herein, we present an asymptomatic 70-year-old woman with a large and mostly cystic growth of right hilar region. Computed tomography of the chest and fluorodeoxyglucose positron emission tomography/computed tomography imaging traced its origins to right middle lobe. Overall features suggested primary lung cancer or perhaps other cystic lung disease.

Because transbronchial lung biopsy failed to establish a histologic diagnosis, right middle lobectomy was undertaken by video-assisted thoracoscopic surgery. The gross surgical specimen harbored a single and sizeable (8.0 × 4.0 cm) cystic lesion containing multiple yellow-white nodules. A diagnosis of mesenchymal cystic and chondroid hamartoma was ultimately rendered. This particular case is noteworthy, given the initial clinical resemblance to primary lung cancer.
Cost-effectiveness and budget impact analysis of lisdexamfetamine versus methylphenidate for patients under 18 with attention-deficit/hyperactivity disorder in Iran
Authors: Tajik Amirmohammad , Nikfar Shekoufeh , Elyasi Sepideh , Rajabi Omid , Varmaghani Mehdi
Published: October 2023

Background

Lisdexamfetamine (LDX) and Methylphenidate (MPH) are stimulant agents that have been shown to provide significant benefits in the management of attention-deficit/hyperactivity disorder (ADHD) in patients.

Aim

This study aimed to assess the cost-effectiveness and the budget impact of LDX compared to MPH as the first-line treatment for ADHD.

Methods

A one-year cost-effectiveness analysis (CEA) was conducted to compare the effects of LDX and MPH in reducing disease symptoms and patient costs and improving quality of life (QoL) from a social perspective. Clinical data were obtained using the EQ-5D questionnaire. In contrast, economic data were sourced from the official website of the Iranian Food and Drug Association (FDA), the national book of tariffs, and specific questionnaires designed to evaluate patients' direct and indirect costs. 197 patients were included in the study, including individuals who sought psychiatric evaluation at a hospital in Mashhad and those who obtained ADHD medications from governmental pharmacies. The cost-effectiveness of the study medicine was assessed using the decision tree method, and the results were presented as the Incremental Cost-Effectiveness Ratio (ICER). Deterministic Sensitivity Analysis (DSA) and Probabilistic Sensitivity Analysis (PSA) were performed to assess the robustness of the findings. Additionally, a Budget Impact Analysis (BIA) was conducted over five years, considering three different scenarios, to evaluate the financial implications of incorporating LDX into the national pharmaceutical system.

Results

The ICER for LDX therapy compared to MPH was estimated at USD 264.28 (with an incremental cost of USD 54.9, incremental effectiveness of 0.208, and Quality-Adjusted Life Years (QALYs) gained of 0.765). The PSA indicated a 0.994% probability of LDX being cost-effective, considering a threshold of USD 2450 per QALY. Furthermore, the DSA revealed that the acquisition cost of LDX influenced the model's sensitivity. The BIA demonstrated that incorporating LDX into Iran's healthcare system would result in a financial burden of approximately $368,566 in the first year, representing an additional cost of $11,154 compared to the non-availability of this medicine and the use of previous medications. It is projected that by 2027, the financial burden of treating ADHD with LDX will reach approximately USD 443,879 over five years, amounting to an increase of $71,154 compared to the absence of this medicine.

Conclusion

From a social perspective, the inclusion of LDX in the treatment regimen for ADHD is associated with higher costs and an increased financial burden. However, based on our analysis, LDX appears to be a cost-effective choice for managing ADHD in Iran when compared to MPH.
Facile synthesis and eco-friendly analytical methods for concurrent estimation of selected pharmaceutical drugs in their solutions: application to quality by design, lean six sigma, and stability studies
Authors: Al-Kadhi Nada S. , Mohamed Mahmoud A. , Ahmed Hoda A. , Nassar Hossam F.
Published: October 2023

Economical, highly robust, selective, precise, and eco-friendly RP-UPLC and spectrophotometric methods were developed and validated for the concurrent estimation of selected pharmaceutical drugs represented in ceftazidime (CFZ) and pyridine (PYD) in their solutions using Agilent Zorbax SB-C18 RRHD (50 × 2.1 mm, 1.8 μm) column at flow rate 0.3 mL/min with wavelength 254 nm. Box-Behnken design (BBD) established Response surface methodology (RSM) to achieve the optimum chromatographic condition with minimal trials conducted. Three independent variables specifically acetonitrile ratio 60–70%, pH 3–7, and temperature 25–35 °C were implemented to evaluate the influences of these variables on the responses as resolution and retention time. Desirability and overlay plots were carried out to adjust the optimal condition that achieved the shortest retention time of less than 2 min and desired resolution of more than 1.5 using a mobile phase consisting of acetonitrile: purified water (70:30, v/v) at pH 5.0 adjusted by 0.1% orthophosphoric acid with the column oven temperature 30 °C and column void volume 0.46 mL. Mean centering of ratio spectra (MCR) and ratio subtraction (RS) methods were effectively applied to resolve drugs' spectral superposition at 220 nm, 255.4 nm, 260.3 nm, and 254.6 nm for CFZ and PYD, respectively. Linearity range was accomplished for UPLC, MCR, and RS methods over the concentration range of 2–100, 1–50,3–30 and 5–30 µg/mL for CFZ and PYD, respectively with correlation coefficient > 0.999 and good recovery results within 98–102%. Six Sigma methodology was achieved using the process capability index (Cpk) to compare the suggested and USP methods showing that both are highly capable with Cpk > 1.33. The proposed method was successfully validated depending on ICH guidelines and ANOVA results and applied for the accelerated stability study.

Graphical Abstract
Genomic, transcriptomic and epigenomic sequencing data of the B-cell leukemia cell line REH
Authors: Lysenkova Wiklander Mariya , Övernäs Elin , Lagensjö Johanna , Raine Amanda , Petri Anna , Wiman Ann-Christin , Ramsell Jon , Marincevic-Zuniga Yanara , Gezelius Henrik , Martin Tom , Bunikis Ignas , Ekberg Sara , Erlandsson Rikard , Larsson Pontus , Mosbech Mai-Britt , Häggqvist Susana , Hellstedt Kerje Susanne , Feuk Lars , Ameur Adam , Liljedahl Ulrika , Nordlund Jessica
Published: October 2023

Objectives

The aim of this data paper is to describe a collection of 33 genomic, transcriptomic and epigenomic sequencing datasets of the B-cell acute lymphoblastic leukemia (ALL) cell line REH. REH is one of the most frequently used cell lines for functional studies of pediatric ALL, and these data provide a multi-faceted characterization of its molecular features. The datasets described herein, generated with short- and long-read sequencing technologies, can both provide insights into the complex aberrant karyotype of REH, and be used as reference datasets for sequencing data quality assessment or for methods development.

Data description

This paper describes 33 datasets corresponding to 867 gigabases of raw sequencing data generated from the REH cell line. These datasets include five different approaches for whole genome sequencing (WGS) on four sequencing platforms, two RNA sequencing (RNA-seq) techniques on two different sequencing platforms, DNA methylation sequencing, and single-cell ATAC-sequencing.
Validity of a multiphase CT-based radiomics model in predicting the Leibovich risk groups for localized clear cell renal cell carcinoma: an exploratory study
Authors: Liu Huayun , Wei Zongjie , Xv Yingjie , Tan Hao , Liao Fangtong , Lv Fajin , Jiang Qing , Chen Tao , Xiao Mingzhao
Published: October 2023

Objective

To develop and validate a multiphase CT-based radiomics model for preoperative risk stratification of patients with localized clear cell renal cell carcinoma (ccRCC).

Methods

A total of 425 patients with localized ccRCC were enrolled and divided into training, validation, and external testing cohorts. Radiomics features were extracted from three-phase CT images (unenhanced, arterial, and venous), and radiomics signatures were constructed by the least absolute shrinkage and selection operator (LASSO) regression algorithm. The radiomics score (Rad-score) for each patient was calculated. The radiomics model was established and visualized as a nomogram by incorporating significant clinical factors and Rad-score. The predictive performance of the radiomics model was evaluated by the receiver operating characteristic curve, calibration curve, and decision curve analysis (DCA).

Results

The AUC of the triphasic radiomics signature reached 0.862 (95% CI: 0.809–0.914), 0.853 (95% CI: 0.785–0.921), and 0.837 (95% CI: 0.714–0.959) in three cohorts, respectively, which were higher than arterial, venous, and unenhanced radiomics signatures. Multivariate logistic regression analysis showed that Rad-score (OR: 4.066, 95% CI: 3.495–8.790) and renal vein invasion (OR: 12.914, 95% CI: 1.118–149.112) were independent predictors and used to develop the radiomics model. The radiomics model showed good calibration and discrimination and yielded an AUC of 0.872 (95% CI: 0.821–0.923), 0.865 (95% CI: 0.800–0.930), and 0.848 (95% CI: 0.728–0.967) in three cohorts, respectively. DCA showed the clinical usefulness of the radiomics model in predicting the Leibovich risk groups.

Conclusions

The radiomics model can be used as a non-invasive and useful tool to predict the Leibovich risk groups for localized ccRCC patients.

Critical relevance statement

The triphasic CT-based radiomics model achieved favorable performance in preoperatively predicting the Leibovich risk groups in patients with localized ccRCC. Therefore, it can be used as a non-invasive and effective tool for preoperative risk stratification of patients with localized ccRCC.

Key points

• The triphasic CT-based radiomics signature achieves better performance than the single-phase radiomics signature.

• Radiomics holds prospects in preoperatively predicting the Leibovich risk groups for ccRCC.

• This study provides a non-invasive method to stratify patients with localized ccRCC.

Graphical Abstract
Advances in stem cell therapy for peritoneal fibrosis: from mechanisms to therapeutics
Authors: Huang Weiyan , Xia Demeng , Bi Wendi , Lai Xueli , Yu Bing , Chen Wei
Published: October 2023

Peritoneal fibrosis (PF) is a pathophysiological condition caused by a variety of pathogenic factors. The most important features of PF are mesothelial–mesenchymal transition and accumulation of activated (myo-)fibroblasts, which hinder effective treatment; thus, it is critical to identify other practical approaches. Recently, stem cell (SC) therapy has been indicated to be a potential strategy for this disease. Increasing evidence suggests that many kinds of SCs alleviate PF mainly by differentiating into mesothelial cells; secreting cytokines and extracellular vesicles; or modulating immune cells, particularly macrophages. However, there are relatively few articles summarizing research in this direction. In this review, we summarize the risk factors for PF and discuss the therapeutic roles of SCs from different sources. In addition, we outline effective approaches and potential mechanisms of SC therapy for PF. We hope that our review of articles in this area will provide further inspiration for research on the use of SCs in PF treatment.
Regulatory T cells contribute to the immunosuppressive phenotype of neutrophils in a mouse model of chronic lymphocytic leukemia
Authors: Goral Agnieszka , Sledz Marta , Manda-Handzlik Aneta , Cieloch Adrianna , Wojciechowska Alicja , Lachota Mieszko , Mroczek Agnieszka , Demkow Urszula , Zagozdzon Radoslaw , Matusik Katarzyna , Wachowska Malgorzata , Muchowicz Angelika
Published: October 2023

Background

Impaired neutrophil activity is an important issue in chronic lymphocytic leukemia (CLL), as it contributes to a dysfunctional immune response leading to life-threatening infections in patients. Some features typical of CLL neutrophils, e.g., the B-cell-supportive secretion profile, have already been described. However, most of these studies were performed on cells isolated from peripheral blood. It is still unclear which molecular factors and cell types are involved in shaping neutrophil function and phenotype in the CLL microenvironment. Since regulatory T cells (Treg) play an important role in CLL progression and influence the activity of neutrophils, we investigated the crosstalk between Treg and neutrophils in the spleen using a murine model of CLL.

Methods

In this work, we used an Eµ-TCL1 mouse model of human CLL. For our in vivo and ex vivo experiments, we inoculated wild-type mice with TCL1 leukemic cells isolated from Eµ-TCL1 transgenic mice and then monitored disease progression by detecting leukemic cells in peripheral blood. We analyzed both the phenotype and activity of neutrophils isolated from the spleens of TCL1 leukemia-bearing mice. To investigate the interrelation between Treg and neutrophils in the leukemia microenvironment, we performed experiments using TCL1-injected DEREG mice with Treg depletion or RAG2KO mice with adoptively transferred TCL1 cells alone or together with Treg.

Results

The obtained results underline the plasticity of the neutrophil phenotype, observed under the influence of leukemic cells alone and depending on the presence of Treg. In particular, Treg affect the expression of CD62L and IL-4 receptor in neutrophils, both of which are crucial for the function of these cells. Additionally, we show that Treg depletion and IL-10 neutralization induce changes in the leukemia microenvironment, partially restoring the “healthy” phenotype of neutrophils.

Conclusions

Altogether, the results indicate that the crosstalk between Treg and neutrophils in CLL may play an important role in CLL progression by interfering with the immune response.
Advanced numerical techniques for time integration of relativistic equations of motion for charged particles
Authors: Umeda Takayuki , Ozaki Riku
Published: October 2023

Advanced numerical techniques for solving the relativistic equations of motion for charged particles are provided. A new fourth-order integrator is developed by combining the Taylor series expansion of the numerical angle of relativistic gyration and the fourth-order Runge–Kutta method for integrating the Lorentz factor. The new integrator gives the exact relativistic E-cross-B drift velocity, but has a numerical accuracy much higher than the classic fourth-order Runge–Kutta integrator.

Graphical Abstract
Resumption of production operations during the silent disposal period of African swine fever outbreaks: a case study
Authors: Hu Zhiqiang , Liu Qingyuan , Tian Xiaogang , Li Lulu , Wu Weisheng , Gao Wenchao , Li Xiaowen
Published: October 2023

Background

Batch production, a widely implemented production model in large-scale pig farms, was characterized by its long-term duration, cost-effectiveness, and efficiency. Nevertheless, the recent occurrence of African swine fever (ASF) outbreaks in China has necessitated the implementation of discreet mating operations within this model, leading to disruptions in production cycles and substantial indirect losses.

Case presentation

This study implemented a novel operational procedure, which involved the division of risk areas for zone management and allowed mating operations, in 12 farms experiencing ASF outbreaks. Another 12 farms were used as a control group, employing the old procedure. Subsequently, the prognoses of both the old and new procedures were calculated and analyzed. The findings indicate that the new method resulted in an enhanced retention rate and reduced non-productive days (NPD), without impacting the positive detection rate and disposal time. Consequently, this approach significantly mitigated economic losses (p < 0.05).

Conclusion

The efficacy of the novel procedure in mitigating the indirect economic losses stemming from ASF outbreaks, through the reduction of NPD while maintaining retention rates and disposition days, has been substantiated. This methodology has demonstrated feasibility in extensive pig farming operations and exhibits promise for broader application.
Inventory analysis of fire effects wrought by wind-driven megafires in relation to weather and pre-fire forest structure in the western Cascades
Authors: Busby Sebastian U. , Klock Angela M. , Fried Jeremy S.
Published: October 2023

Background

Six synchronous, wind-driven, high severity megafires burned over 300,000 hectares of mesic temperate forest in the western Cascades of NW Oregon and SW Washington states in early September 2020. While remote sensing data has been utilized to estimate fire severity across the fires, assessments of fire impacts informed by field observations are missing. We compiled field measurement data, pre- and post-fire, from a statistically representative sample of existing forest inventory analysis (FIA) plots, to estimate stand-level fire effects indices that describe (1) tree survival and its implications for carbon emissions, (2) effects on tree crowns, and (3) effects on soils. Field observations were analyzed in relation to fire weather when plots burned and to evaluate accuracy of remotely sensed burn severity classifications.

Results

Wind speed strongly interacted with tree size and stand age to influence tree survival. Under high fuel aridity but light winds, young stands composed of small trees, found primarily on private lands, exhibited a much lower survival rate than older stands composed of medium to large trees, found primarily on federal lands. Under moderate to high winds, poor tree survival was characteristic of all forest structures and ownerships. Fire impacts on tree crowns were strongly related to wind speed, while fire impacts on soils were not. These fires transferred nearly 70 MMT CO2e from wood in live and growing trees to a combination of immediate smoke and carbon emissions, plus delayed emissions from dead wood, that will release most of the embodied carbon over the next few decades. These emissions will exceed all 2020 anthropogenic emissions in Oregon (64 MMT CO2e). Substantial discrepancies were observed between two remotely sensed burn severity products, BAER-SBS and MTBS-TC, and field observed soil organic matter cover and tree mortality, respectively.

Conclusions

Post-fire FIA plot remeasurements are valuable for understanding fire’s impact on forest ecosystems and as an empirical basis for model validation and hypothesis testing. This continuous forest inventory system will compound the value of these post-fire remeasurements, enabling analysis of post-fire forest ecosystem trajectories in relation to both immediate fire impacts and pre-fire conditions.
Deep structural controls on the distribution of carbonate reservoirs and overburden heterogeneity in Central Luconia province, offshore Borneo revealed by 3D anisotropic inversion of regional controlled-source electromagnetic and magnetotelluric profile data
Authors: Kho Joanna H. W. , Meju Max A. , Miller Roger V. , Saleh Ahmad Shahir
Published: October 2023

Understanding the deep structural controls on reservoir distribution and overburden heterogeneity is important for near-field exploration and green-field development of the Miocene to Holocene carbonate buildups in Central Luconia province in offshore northwest Borneo, Malaysia. Data from 59 stations along an approximately 180 km long controlled-source electromagnetic (CSEM) and magnetotelluric (MT) survey line with three segments recorded using different CSEM transmitter-towing directions were available. We applied three-dimensional (3D) anisotropic resistivity inversion with cross-gradient constraint and verified the resulting models using resistivity logs from nearby wells and the acoustic basement interpreted from seismic data. Our anisotropic resistivity models reveal a fragmented carbonate-rich zone atop a segmented basement comprising electrically resistive horsts coinciding with the northerly Mega-platform, Central and Southern Field Highs, separated by steep conductive zones coinciding with the West, East, and Southeast Troughs previously interpreted from seismic data. The structural highs correlate with the spatial distribution of the known carbonate buildups implying a genetic link. The carbonate bodies are overlain and underlain by persistent layers (C2 and C3) of low resistivity and high anisotropy, which we interpret as indicating compressional deformation or detachment zones. Overburden layer C2 (whose base coincides with the top of a key sedimentary package, Cycle V in seismic data) is thinnest over the East Trough and is discontinuous at the eastern margin of the West Trough, which are locations where drilled wells did not find hydrocarbons implying that the seal rocks are inefficient or breached at those localities. We used these observations to refine the existing seismic-based interpretation of carbonate play-types along our transect indicating how 3D joint CSEM-MT imaging can potentially contribute to derisking or optimizing future exploration and/or development work in this province.