bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term safety and tolerability of ambrisentan treatment for pediatric patients with pulmonary arterial hypertension: An open-label extension study
Authors: Ivy Dunbar , Beghetti Maurice , Juaneda-Simian Ernesto , Ravindranath Ramiya , Lukas Mary Ann , Machlitt-Northen Sandra , Scott Nicola , Narita Jun , Berger Rolf M. F.
Published: February 2024

This open-label, extension study assessed long-term safety, tolerability, and efficacy of ambrisentan in a pediatric population (age 8– < 18 years) with pulmonary arterial hypertension (PAH). Following completion of a 6-month, randomized study, participants entered the long-term extension at individualized ambrisentan dosages (2.5/5/7.5 or 10 mg/day). Safety assessments included adverse events (AEs), AEs of special interest, and serious AEs (SAEs); efficacy outcomes included 6-min walking distance (6MWD) and World Health Organization functional class (WHO FC). Thirty-eight of 41 (93%) randomized study participants entered the extension; 21 (55%) completed (reaching age 18 years). Most participants received concomitant phosphodiesterase-5 inhibitors (n = 25/38, 66%). Median ambrisentan exposure was 3.5 years. Most participants experienced ≥ 1 AE (n = 34/38, 89%), and 21 (55%) experienced SAEs, most commonly worsening PAH (n = 3/38, 8%), acute cardiac failure, pneumonia, or anemia (n = 2/38; 5% each); none considered ambrisentan-related. Seven participants (18%) died, with recorded reasons (MedDRA preferred term): cardiac failure (n = 2), PAH (n = 2), COVID-19 (n = 1), acute right ventricular failure (n = 1), and failure to thrive (n = 1); median time to death: 5.2 years. Anemia and hepatotoxicity AEs were generally mild to moderate and did not require ambrisentan dose adjustment. Assessed at study end in 29 participants (76%), mean 6MWD improved by 17% (standard deviation: 34.3%), and all (29/29, 100%) had improved or unchanged WHO FC.

   Conclusion: Long-term weight-based ambrisentan dosing, alone or combined with other PAH therapies in children with PAH aged 8– < 18 years, exhibited tolerability and clinical improvements consistent with prior randomized study results.

   Trial registration: NCT01342952, April 27, 2011.

What is Known:•The endothelin receptor antagonist, ambrisentan, is indicated for treatment of pulmonary arterial hypertension (PAH). Previous studies have shown similar efficacy and tolerability in pediatric patients as in adults.

What is New:• This open-label extension study assessed the long-term use of ambrisentan in pediatric patients (8–<18 years) with PAH, most of whom were also receiving recommended background PAH treatment. • Weight-based dosing of ambrisentan, given alone or in combination with other PAH therapies, was well tolerated with clinical improvements consistent with prior randomized study results.
Optimal sequence of LT for symptomatic BM in EGFR-mutant NSCLC: a comparative study of first-line EGFR-TKIs with/without upfront LT
Authors: Niu Lishui , Wu Honghua , Gao Ruihuan , Chen Liu , Wang Jiangtao , Duan Hexin , Long Yujiao , Xie Yi , Zhou Qin , Zhou Rongrong
Published: February 2024

Background

The third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) can penetrate blood–brain barrier and are effective for brain metastases (BMs). There is no consensus on the optimal sequence of local therapy (LT) and EGFR-TKIs for symptomatic BM patients because patients suffering neurological symptoms were not enrolled in most clinical trials.

Methods

Non-small cell lung cancer (NSCLC) patients with EGFR mutation (EGFRm) and symptomatic BM receiving first-line osimertinib and aumolertinib from two medical centers were collected. All participants were allocated into the third-generation EGFR-TKIs (TKIs) group and the upfront LT (uLT) plus third-generation EGFR-TKIs (TKIs + uLT) group. Demographic data, survival outcomes, treatment failure patterns, and adverse events were evaluated between the two groups. We also conducted subgroup analyses to explore the impact of BM number on survival outcomes.

Results

86 patients were enrolled, 44 in the TKIs group and 42 in the TKIs + uLT group. There were no significant differences in the short-term response between the groups. TKIs + uLT was associated with significantly longer overall survival (OS) (43 vs. 28 months; hazard ratio [HR], 0.36, 95% confidence interval [CI], 0.17–0.77; p = .011). No differences in progression-free survival (PFS), intracranial PFS (iPFS), failure patterns, or safety were observed. In subgroup analyses of oligo-BM patients, TKIs + uLT could prolong OS (43 vs. 31 months; HR 0.22; 95% CI 0.05–0.92; p = .015).

Conclusions

EGFRm NSCLC patients with symptomatic BM might benefit from uLT, particularly oligo-BM patients. However, larger prospective cohort studies should be carried out to confirm the responses of the TKIs + uLT scheme.
Tumor-to-stroma cd8+ t cells ratio combined with cancer-associated fibroblasts: an innovative approach to predicting lymph node metastases of cervical cancer
Authors: Guo Shuangshuang , Chen Peiyu , Yang Yang , Wei Wenfei , Pan YuHua , Zeng Fanke , Fan Liangsheng , Wang Wei
Published: February 2024

Purpose

Precise identification of lymph node metastases is vital for the management of cervical cancer. However, the existing diagnostic methods for lymph node metastases have certain drawbacks. In this study, we aim to explore the expression of cancer-associated fibroblasts (CAFs) and tumor-to-stroma CD8+ T cells ratio (CD8+ T cells T:S ratio) and its association with lymph node metastases of cervical cancer.

Methods

Hundred and ten cervical cancer tissues and 39 biopsy tissues from patients were investigated immunocytochemically for the expression of CAFs and CD8+ T cells. The statistical correlation analysis was carried out using the SPSS system.

Results

A strong and statistically significant negative correlation (r= − 0.690; P < 0.001) was observed between CAF density and CD8+ T cells T:S ratio. Not only were CAFs density and CD8+ T cells T:S ratio correlated with lymph node metastases respectively (P < 0.001), but the combination of them also significantly correlated with lymph node metastases (P < 0.001). Then, we constructed the combined diagnosis model (Logit (P) = − 4.446 + 0.300 × CAFs + 0.752 × CD8+ T cells T:S Ratio) of cervical cancer lymph node metastases. ROC curves analysis showed that the ROC curves areas for CAFs, CD8+ T cells T:S ratio, and a combination of both are 0.879, 0.747, and 0.951. Then, the prediction model was verified by biopsy specimens and consistent results were obtained.

Conclusions

The combination of CAF density and CD8+ T cells T:S ratio has a significant predictive value for lymph node metastases in patients with cervical cancer.
TEP RNA: a new frontier for early diagnosis of NSCLC
Authors: Wang Yuan , Dong Aiping , Jin Minhan , Li Shirong , Duan Yang
Published: February 2024

Background

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer (LC), which is the leading cause of tumor mortality. In recent years, compared with tissue biopsy, which is the diagnostic gold standard for tumor diagnosis, Liquid biopsy (LB) is considered to be a more minimally invasive, sensitive, and safer alternative or auxiliary diagnostic method. However, the current value of LB in early diagnosis of LC is not ideal, so it is particularly important to study the changes in blood composition during the process of tumorigenesis and find more sensitive biomarkers.

Purpose

Platelets are a type of abundant blood cells that carry a large amount of RNA. In the LC regulatory network, activated platelets play an important role in the process of tumorigenesis, development, and metastasis. In order to identify predictive liquid biopsy biomarkers for the diagnosis of NSCLC, we summarized the development and function of platelets, the interaction between platelets and tumors, the value of TEP RNA in diagnosis, prognosis, and treatment of NSCLC, and the method for detecting TEP RNA of NSCLC in this article.

Conclusion

The application of platelets in the diagnosis and treatment of NSCLC remains at a nascent stage. In addition to the drawbacks of low platelet count and complex experimental processes, the diagnostic accuracy of TEP RNA-seq for cancer in different populations still needs to be improved and validated. At present, a large number of studies have confirmed significant differences in the expression of TEP RNA in platelets between NSCLC patients and healthy individuals. Continuous exploration of the diagnostic value of TEP RNA in NSCLC is of utmost importance. The integration of NSCLC platelet-related markers with other NSCLC markers can improve current tumor diagnosis and prognostic evaluation systems, providing broad prospects in tumor screening, disease monitoring, and prognosis assessment.
Current look at the most promising proteomic and glycomic biomarkers of bladder cancer
Authors: Harsanyi Stefan , Kianickova Kristina , Katrlik Jaroslav , Danisovic Lubos , Ziaran Stanislav
Published: February 2024

Background

Bladder cancer (BC) belongs to the most frequent cancer types. The diagnostic process is still long and costly, with a high percentage of false-positive or -negative results. Due to the cost and lack of effectiveness, older methods need to be supplemented or replaced by a newer more reliable method. In this regard, proteins and glycoproteins pose high potential.

Methods

We performed an online search in PubMed/Medline, Scopus, and Web of Science databases to find relevant studies published in English up until May 2023. If applicable, we set the AUC threshold to 0.90 and sensitivity/specificity (SN/SP) to 90%.

Findings

Protein and glycoprotein biomarkers are a demonstrably viable option in BC diagnostics. Cholinesterase shows promise in progression-free survival. BLCA-4, ORM-1 along with HTRA1 in the detection of BC. Matrix metallopeptidase 9 exhibits potential for stratification of muscle-invasive subtypes with high negative predictive value for aggressive phenotypes. Distinguishing non-muscle invasive subtypes benefits from Keratin 17. Neu5Gc-modified UMOD glycoproteins pose potential in BC diagnosis, while fibronectin, laminin-5, collagen type IV, and lamprey immunity protein in early detection of BC.
Pilot Study of Intensive Trismus Intervention Using Restorabite™ During Unilateral Adjuvant Radiation for Head and Neck Cancer
Authors: Charters Emma , Loy Jamie , Wu Raymond , Cheng Kai , Dunn Masako , Davies Sarah , Clark Jonathan
Published: February 2024

Trismus commonly arises after surgery for head and neck cancer (HNC) and its severity is potentiated by postoperative radiotherapy. While the benefit of trismus rehabilitation after surgery and radiotherapy is well established, the evidence during radiotherapy is less clear. This may be due to poor adherence to trismus exercises secondary to acute mucositis. This study assessed the feasibility of using a novel trismus device during adjuvant radiotherapy for HNC in patients with acute postoperative trismus. Prospective single-arm cohort feasibility study. Eligible patients had undergone surgery with curative intent for HNC, planned for adjuvant radiotherapy, and were suitable for trismus rehabilitation. Participants completed a 10-week exercise program using a novel jaw stretching device. Study outcomes were adherence, maximal incisal opening (MIO), and trismus-related function and quality of life scores, assessed at baseline, 10 weeks, and 6 months after commencing exercises. Nine patients diagnosed with trismus after primary surgery were recruited. The mean increase in MIO at 10 weeks was 7.8 mm (range −4 to 15 mm, p = 0.03), and at 6 months was 10.6 mm (range 1–26 mm, p = 0.03). Significant improvements were observed in trismus-related quality of life (Gothenburg Trismus Questionnaire; p = 0.04). Adherence to the exercises was 100% in week 1–2, 67% in weeks 3–6, and 100% at 10 weeks (1 month post radiation). This study demonstrates the feasibility of using a novel jaw stretching device during adjuvant radiotherapy. Further evaluation is warranted to assess the effectiveness of early intervention and prevention of trismus during HNC radiotherapy.

Level of Evidence: IV
Alternative prioritization for mitigating urban transportation challenges using a Fermatean fuzzy-based intelligent decision support model
Authors: Bouraima Mouhamed Bayane , Ayyildiz Ertugrul , Ozcelik Gokhan , Tengecha Nyamatari Anselem , Stević Željko
Published: February 2024

Practitioners and decision-makers often face difficulties in selecting and prioritizing effective strategies to address challenges to sustainable urban transportation development. Although there has been considerable research conducted on the subject, the Tanzanian context, which is greatly affected by social and environmental problems, has received inadequate attention. Therefore, this study intends to bridge this gap by pinpointing the obstacles to sustainable urban transportation and proposing the most appropriate strategies to tackle them. The study proposes seven strategies and determines five criteria to prioritize them. To accomplish this, the study proposes a novel Fermatean fuzzy-based intelligent decision support model to assess the criteria weights and prioritizes strategies based on the weighted criteria. The study validates the proposed methodology by conducting a sensitivity analysis, which indicates that restricting car use (A5), improving sector coordination (A1), and conducting extensive research on transportation issues (A7) are the top three strategies for promoting sustainable urban transportation. The study’s findings hold significant value in providing urban transportation planners with helpful guidance to develop optimization techniques that can improve transportation systems.
Adapting transfer learning models to dataset through pruning and Avg-TopK pooling
Authors: OZDEMIR Cuneyt
Published: February 2024

This study focuses on efficiently adapting transfer learning models to address the challenges of creating customized deep learning models for specific datasets. Designing a model from scratch can be time-consuming and complex due to factors like model complexity, size, and dataset structure. To overcome these obstacles, a novel approach is proposed using transfer learning models. The proposed method involves identifying relevant layers in transfer learning models and removing unnecessary ones using a layer-based variance pruning technique. This results in the creation of new models with improved computational efficiency and classification performance. By streamlining the models through layer-based variance pruning, the study achieves enhanced accuracy and faster computation. Experiments were conducted using the COVID-19 dataset and well-known transfer learning models, including InceptionV3, ResNet50V2, DenseNet201, VGG16, and Xception to validate the approach. Among these models, the variance-based layer pruning technique was applied to InceptionV3 and DenseNet201, yielding the best results. When these pruned models were combined with the new pooling layer, Avg-TopK, the proposed method achieved an outstanding image classification accuracy of 99.3%. Comparisons with previous models and literature studies indicate that the proposed approach outperforms existing methods, showcasing state-of-the-art performance. This high-performance approach provides great potential for diagnosing COVID-19 and monitoring disease progression, especially on hardware-limited devices. By leveraging transfer learning models, pruning, and efficient pooling techniques, the study presents a promising strategy for tackling challenges in custom model design, leading to exceptional results in such as image classification and segmentation tasks. The proposed methodology holds the potential to yield exceptional outcomes across a spectrum of tasks, encompassing disciplines such as image classification and segmentation.
Lateral fenestration of lumbar intervertebral discs in rabbits: development and characterisation of an in vivo preclinical model with multi-modal endpoint analysis
Authors: Crowley James D. , Oliver Rema A. , Wang Tian , Pelletier Matthew H. , Walsh William R.
Published: February 2024

Purpose

To evaluate the biological and biomechanical effects of fenestration/microdiscectomy in an in vivo rabbit model, and in doing so, create a preclinical animal model of IVDD.

Methods

Lateral lumbar IVD fenestration was performed in vivo as single- (L3/4; n = 12) and multi-level (L2/3, L3/4, L4/5; n = 12) fenestration in skeletally mature 6-month-old New Zealand White rabbits. Radiographic, micro-CT, micro-MRI, non-destructive robotic range of motion, and histological evaluations were performed 6- and 12-weeks postoperatively. Independent t tests, one-way and two-way ANOVA and Kruskal–Wallis tests were used for parametric and nonparametric data, respectively. Statistical significance was set at P < 0.05.

Results

All rabbits recovered uneventfully from surgery and ambulated normally. Radiographs and micro-CT demonstrated marked reactive proliferative osseous changes and endplate sclerosis at fenestrated IVDs. Range of motion at the fenestrated disc space was significantly reduced compared to intact controls at 6- and 12-weeks postoperatively (P < 0.05). Mean disc height index percentage for fenestrated IVDs was significantly lower than adjacent, non-operated IVDs for both single and multi-level groups, at 6 and 12 weeks (P < 0.001). Pfirrmann MRI IVDD and histological grading scores were significantly higher for fenestrated IVDs compared to non-operated adjacent and age-matched control IVDs for single and multi-level groups at 6 and 12 weeks (P < 0.001).

Conclusions

Fenestration, akin to microdiscectomy, demonstrated significant biological, and biomechanical effects in this in vivo rabbit model and warrants consideration by veterinary and human spine surgeons. This described model may be suitable for preclinical in vivo evaluation of therapeutic strategies for IVDD in veterinary and human patients.
Secular trends in mental health problems among young people in Norway: a review and meta-analysis
Authors: Potrebny Thomas , Nilsen Sondre Aasen , Bakken Anders , von Soest Tilmann , Kvaløy Kirsti , Samdal Oddrun , Sivertsen Børge , Aase Heidi , Bang Lasse
Published: February 2024

There is a growing concern that the mental health of recent generations of youth is deteriorating, yet the etiology of these secular changes is not fully understood. We aimed to review the evidence on trends in mental health problems among young people in Norway. Seven large-scale repeated cross-sectional studies were included in this study, comprising 35 cross-sectional data collections between 1992 and 2019, with a total sample of 776,606 young people. Our study found a clear increase in mental health problems among young females in Norway over the past few decades, while the trends were less marked for males. The proportion of individuals scoring above the problematic symptom score threshold increased on average by 11.2% (range 2.2% to 21.9%) for females and 5.2% (range − 0.9% to 11.1%) for males, based on data from the individual studies. The results from a meta-regression analysis showed that across all surveys, mean symptom scores increased by 17% (95% CI 12 to 21%) among females and 5% (95% CI 1 to 9%) among males from 1992 to 2019. Overall, mental health problems have increased continually since the early 1990s among young people, especially among young females. The cause of these secular changes remains unknown but likely reflect the interplay of several factors at the individual and societal level.

Protocol registration: Open science framework, November 8, 2021 (https://osf.io/g7w3v).
Rural farmers’ perceptions of and adaptations to climate change in Sub-Saharan Africa: Does climate-smart agriculture (CSA) matter in Nigeria and Ethiopia?
Authors: Alhassan Usman , Haruna Emmanuel Umoru
Published: February 2024

The available literature has ignored farmers’ perceptions on the benefits and drawbacks of adopting climate-smart agriculture (CSA) in favor of focusing primarily on profitability and economic constraints. We use the Ethiopian Socioeconomic Survey (ESS) and the General Household Survey from 2018 and 2019 to compare Nigeria and Ethiopia, both of which have sizable rural populations to assess farmers’ climate change perception and their adaptation options in promoting CSA. We first hypothesize that farmers with high tolerance for risk and stable financial resources are more likely to adopt CSA techniques, relying on the adopter perception theory of agricultural innovations and technologies. We address potential selection bias using the Heckman selection model, and estimate our data using multinomial logistic estimator, as well as standard logistic regression for robustness checks. We find that in both Ethiopia and Nigeria, household income and plot size influence farmers’ adaptations to climate change mitigation practices. However, farmers with bigger plots who run the risk of massive production loss tend to adopt measures of coping with climate change. We show that in both Ethiopia and Nigeria, rural farmers’ adaptation decisions are heavily influenced by agricultural extension programs and community social networks. Overall, our work highlights the important role of income, farm size, and climate-related information for investing in climate-smart agricultural methods to curb food insecurity in Sub-Saharan Africa.
Electroantennographic and Behavioral Responses of the Melon fly, Zeugodacus cucurbitae (Coquillett), to Volatile Compounds of Ridge Gourd, Luffa acutangular L.
Authors: Wang Jing jing , Ma Chao , Tian Zhen ya , Zhou Yong ping , Yang Jin fang , Gao Xuyuan , Chen Hong song , Ma Wei hua , Zhou Zhong shi
Published: February 2024

The melon fly, Zeugodacus cucurbitae (Coquillett), is a major invasive pest, widely distributed in the Asia–Pacific region and some parts of Africa. Melon fly attractants could improve the effectiveness of current pest management measures. Previous studies have shown that some host fruits are attractive to melon flies but few have investigated the chemical compounds responsible for their attraction. In this study, we aimed to identify the volatile compounds from Luffa acutangula L that attract Z. cucurbitae. In headspace trapping, chemical profiling identified 19 compounds from ridge gourds, with 1-pentadecene being the major component. EAG results revealed that seven compounds elicited antennal responses in Z. cucurbitae, and significant differences in antennal responses between male and female Z. cucurbitae adults were recorded to p-xylene, alpha-pinene, and 1-octadecene. Behavioral experiments demonstrated that the EAG-active compounds methyl isovalerate and methyl myristate had either attractive or repellent effects on Z. cucurbitae at different concentrations, and 1-octadecene attracted Z. cucurbitae. Our findings provide a theoretical basis producing repellents or attractants for effective Integrated Pest Management of Z. cucurbitae.
GLP-1(7–36) protected against oxidative damage and neuronal apoptosis in the hippocampal CA region after traumatic brain injury by regulating ERK5/CREB
Authors: Wang Shuwei , Liu Aijun , Xu Chaopeng , Hou Jingxuan , Hong Jun
Published: February 2024

Background

Glucagon-like peptide-1 (GLP-1) (7–36) amide, an endogenous active form of GLP-1, has been shown to modulate oxidative stress and neuronal cell survival in various neurological diseases.

Objective

This study investigated the potential effects of GLP-1(7–36) on oxidative stress and apoptosis in neuronal cells following traumatic brain injury (TBI) and explored the underlying mechanisms.

Methods

Traumatic brain injury (TBI) models were established in male SD rats for in vivo experiments. The extent of cerebral oedema was assessed using wet-to-dry weight ratios following GLP-1(7–36) intervention. Neurological dysfunction and cognitive impairment were evaluated through behavioural experiments. Histopathological changes in the brain were observed using haematoxylin and eosin staining. Oxidative stress levels in hippocampal tissues were measured. TUNEL staining and Western blotting were employed to examine cell apoptosis. In vitro experiments evaluated the extent of oxidative stress and neural apoptosis following ERK5 phosphorylation activation. Immunofluorescence colocalization of p-ERK5 and NeuN was analysed using immunofluorescence cytochemistry.

Results

Rats with TBI exhibited neurological deterioration, increased oxidative stress, and enhanced apoptosis, which were ameliorated by GLP-1(7–36) treatment. Notably, GLP-1(7–36) induced ERK5 phosphorylation in TBI rats. However, upon ERK5 inhibition, oxidative stress and neuronal apoptosis levels were elevated, even in the presence of GLP-1(7–36).

Conclusion

In summary, this study suggested that GLP-1(7–36) suppressed oxidative damage and neuronal apoptosis after TBI by activating ERK5/CREB.
Learning from failure: do narcissists learn?
Authors: Sewaid Ahmed , Silaghi Florina , García-Cestona Miguel
Published: February 2024

We investigate the narcissists’ response to failure and whether narcissists effectively learn from this negative experience. To address this, we leverage data from a leading crowdfunding platform, and analyze 116,981 failed crowdfunding attempts. Our analysis shows a positive relationship between narcissism and the probability of relaunching which is negatively moderated by the degree of failure. Indeed, due to their fragility, narcissistic entrepreneurs are more likely to engage in ego-defensive behavior, and thus, they are less likely to relaunch following high degrees of failure. Moreover, narcissistic entrepreneurs exhibit poorer performance in their subsequent endeavors. This underperformance is driven by external attribution of failure and lower levels of pro-activity. In fact, following failure, narcissistic entrepreneurs are less likely to change internal factors that might contribute to their previous failure and they are more likely to respond to failure by reattempting in a different context. Managerial and policy implications are discussed.
Die Auswirkungen von Feedback auf Lernbereitschaft und Wechseltendenz von Arbeitnehmern und Studierenden
Authors: Genkova Petia , Gassel Gwenda
Published: February 2024

In Zeiten des Fachkräftemangels sind Organisationen gezwungen ihre Mitglieder durch vielfältige Maßnahmen an sich zu binden. Gleichzeitig müssen sie dem schnellen Wandel der modernen Arbeitswelt gerecht werden und das Wissen und die Kompetenzen ihrer Angestellten kontinuierlich weiterentwickeln. Diese Entwicklung ist abhängig von der Lernbereitschaft des jeweiligen Individuums. Aus dieser doppelten Herausforderung ergibt sich die Fragestellung, was Organisationen tun können, um ihre Mitglieder einerseits an sich zu binden und anderseits die Lernbereitschaft zu fördern. In diesem Zusammenhang kann die Bedeutung von Feedback Prozessen für die erfolgreiche Bindung, Motivation und Entwicklung von Mitarbeiter*innen betont werden. Diese Querschnittsstudie untersucht an 186 Studierende und Angestellten, inwiefern Feedback von Vorgesetzten und Kolleg*innen die Lernbereitschaft erhöht und die Wechseltendenz senkt, unter Berücksichtigung der Selbstwirksamkeitserwartung (SWE). Die Ergebnisse zeigen Zusammenhänge zwischen Feedback von Kolleg*innen und der Lernbereitschaft sowie von Vorgesetzten und der Lernbereitschaft, jeweils mediiert von der SWE. Für die Wechseltendenz konnte kein signifikantes Ergebnis nachgewiesen werden.
Unveiling global sustainability boundaries: exploring inner dimensions of human critical determinants for sustainability
Authors: Santos Filipe Duarte , O’Riordan Tim , de Sousa Miguel Rocha , Pedersen Jiesper Tristan Strandsbjerg
Published: February 2024

Greater global awareness and action to implement sustainable development are underway. However, global progress towards sustainability has been slow. Advancing towards some form of sustainability requires greater attention and analysis of the role played by the human inner world. While the scientific analytic tools have focused on external aspects, we present a scientific methodology to identify human critical determinants (HCDs) acquired during the human biological and cultural evolution, which, although crucial for survival, well-being, and economic prosperity, may also currently act as human sustainability boundaries (HSDs). These boundaries can be softened by personal transformations with the capability of spurring resonant institutional and governance transformations. This commentary examines how a definable set of interacting and interdependent HCD provides a complete and coherent explanation of why reaching sustainability is currently an elusive objective.
Assessing the Potential Apoptotic Effects of Different Hydatid Cyst Fluids on Human Healthy Hepatocytes and Hepatocellular Carcinoma Cells
Authors: Baysal İpek , Örsten Serra , Cengiz Görkem , Ünal Emre , Doğrul Ahmet Bülent , Çiftçi Türkmen , Çiftçi Samiye Yabanoğlu , Akinci Devrim , Akhan Okan
Published: February 2024

Cystic Echinococcosis (CE) is a zoonotic infection caused by the larval form of Echinococcus granulosus in humans. Emerging evidence suggests an intriguing inverse association between E. granulosus infection and the occurrence of cancer. This study aimed to investigate the influence of diverse host-derived hydatid cyst fluids (HCF) with distinct genotypes on human liver hepatocytes (HC) and hepatocellular carcinoma cells (HepG2). Specifically, we examined their effects on cell proliferation, apoptosis sensitivity (BAX/BCL-2), apoptosis-related p53 expression, and the expression of cancer-related microRNA (hsa-miR-181b-3p). Cell proliferation assays, real-time PCR, and ELISA studies were conducted to evaluate potential anti-cancer properties. The findings revealed that animal-origin HCF (G1(A)) induced direct cell death by augmenting the susceptibility of HepG2 cells to apoptosis. Treatment with both G1(A) and G1(H) HCF sensitized HepG2 and HC cell lines to apoptosis by modulating the BAX/BCL-2 ratio, accompanied by upregulation of the p53 gene. Additionally, G1(A) HCF and human-derived HCFs (G1(H), G7(H)) reduced the expression of miR-181b-3p in HepG2 cells. Consequently, this study demonstrates the potential anti-cancer effect of HCF in HepG2 cells and provides the first comparative assessment of HCFs from human and animal sources with diverse genotypes, offering novel insights into this field.
The Effects of Sleeve Gastrectomy on the Appetitive Domain of Taste Using the Progressive Ratio Task
Authors: Althukair Noura K. , Abdeen Ghalia N. , le Roux Carel W. , Miras Alex D. , Alqahtani Aayed R.
Published: February 2024

Introduction

Sleeve gastrectomy (SG) is an effective treatment for obesity in adolescents. The underlying weight loss mechanism may impact the peripheral and central gustatory system along with reward circuits in the brain. This study aims to assess changes in appetitive behavior in short-, medium-, and long-term follow-up.

Methods

In this prospective observational study, a total of 8 adolescents with obesity who underwent SG and 9 comparator unoperated participants were studied. Appetitive behaviour towards fat and sweet taste stimuli was assessed using the Progressive Ratio Task (PRT) over a 6 year period.

Results

Mean body mass index (BMI) of the surgical patients dropped from 51.5 ± 2.8 kg/m2 to 31.4 ± 1.9 and 30.9 ± 2.3 kg/m2 at 1 and 6 years follow-up, respectively. (p < 0.001). The median (interquartile range) total rewards earned during the PRT was 6 (5–7) pre-surgery, 5 (3–6) after one year and 4 (2–4) after six years from surgery (p = 0.007).

Conclusion

SG reduced appetitive behaviour at 1 year with maintained the benefit over 6 years as measured by the progressive ratio task.

Graphical Abstract
Hematopoiesis Revolves Around the Primordial Evolutional Rhythm of Purinergic Signaling and Innate Immunity – A Journey to the Developmental Roots
Authors: Ratajczak Mariusz Z. , Bujko Kamila , Brzezniakiewicz-Janus Katarzyna , Ratajczak Janina , Kucia Magdalena
Published: February 2024

A cell's most significant existential task is to survive by ensuring proper metabolism, avoiding harmful stimuli, and adapting to changing environments. It explains why early evolutionary primordial signals and pathways remained active and regulate cell and tissue integrity. This requires energy supply and a balanced redox state. To meet these requirements, the universal intracellular energy transporter purine nucleotide-adenosine triphosphate (ATP) became an important signaling molecule and precursor of purinergic signaling after being released into extracellular space. Similarly, ancient proteins involved in intracellular metabolism gave rise to the third protein component (C3) of the complement cascade (ComC), a soluble arm of innate immunity. These pathways induce cytosol reactive oxygen (ROS) and reactive nitrogen species (RNS) that regulate the redox state of the cells. While low levels of ROS and RNS promote cell growth and differentiation, supra-physiological concentrations can lead to cell damage by pyroptosis. This balance explains the impact of purinergic signaling and innate immunity on cell metabolism, organogenesis, and tissue development. Subsequently, along with evolution, new regulatory cues emerge in the form of growth factors, cytokines, chemokines, and bioactive lipids. However, their expression is still modulated by both primordial signaling pathways. This review will focus on the data that purinergic signaling and innate immunity carry on their ancient developmental task in hematopoiesis and specification of hematopoietic stem/progenitor cells (HSPCs). Moreover, recent evidence shows both these regulatory pathways operate in a paracrine manner and inside HSPCs at the autocrine level.

Graphical Abstract
A comparative study in elective repair of large incisional hernias using on-lay mesh vs. sub-lay mesh: a meta-analysis
Authors: Hassan Basma Hussein Abdelaziz , Kamel Kirollos Adel Louiz , Awad Philobater Bahgat Adly , Awad Kerolos Bahgat Adly , Maaty Sameh Abdallah , Fawzi Fawzi Salah , El-Shayeb Bassem Helmy
Published: February 2024

Ventral abdominal wall incisional hernia is defined as a defect in the musculo-fascial layers of the abdominal wall in the region of the postoperative scar. There is a slight increase in the incidence of incisional hernia in the female gender. The higher percentage of incisional hernia in females might be due to laxity of abdominal wall muscles after multiple pregnancies and also an increased incidence of obesity in females. To assess incisional hernia repair using two different techniques: on-lay mesh and sub-lay mesh, as regards operative time, postoperative recurrence, wound infection, seroma, hematoma, and flap necrosis. Pubmed, Web of Science, and Scopus were searched on 15 March 2022. The keywords incisional hernia, sub-lay mesh on-lay mesh, retromuscular mesh, and polypropylene. According to our results, there is a statistical difference between onlay and sublay regarding intra-operative time as sublay mesh is more time-consuming. Regarding postoperative complications, there is no statistical difference in recurrence, seroma, hematoma, flap necrosis, and infection but there is a statistical difference regarding in hospital stay as patients with sub-lay repair stays less than only.
Solution theory to semilinear stochastic equations of Schrödinger type on curved spaces I: operators with uniformly bounded coefficients
Authors: Ascanelli Alessia , Coriasco Sandro , Süss André
Published: February 2024

We study the Cauchy problem for Schrödinger type stochastic semilinear partial differential equations with uniformly bounded variable coefficients, depending on the space variables. We give conditions on the coefficients, on the drift and diffusion terms, on the Cauchy data, and on the spectral measure associated with the noise, such that the Cauchy problem admits a unique function-valued mild solution in the sense of Da Prato and Zabczyc.
Thermal methods of sludge processing—are they suitable for pharmaceuticals and illicit drugs removal from sewage sludge?
Authors: Varjúová Dóra , Staňová Andrea Vojs , Grabicová Kateřina , Zakhar Ronald , Bodík Igor
Published: February 2024

The presented work aimed to investigate the effect of thermal treatment on sludge from wastewater treatment plants (WWTPs) in the Slovak Republic on the content of pharmaceuticals (PhACs) and illicit drugs. Sludge samples from eight WWTPs (total flows of 6900–62,500 m3/day, number of population equivalents over 40,000 for each WWTP, production of sludge 400–3300 tons DM/year) were treated with thermal processes in the temperature range of 80 to 550 °C. More than 100 compounds were studied in the sludge samples, but in this article, we deeply focused on the fate of the thirteen most concentrated and frequently found PhACs (azithromycin, carbamazepine, cetirizine, citalopram and its metabolite N-desmethylcitalopram, diclofenac, fexofenadine, sertraline and its metabolite norsertraline, telmisartan, trazodone, valsartan, and verapamil). The thermal processes used showed a decrease in PhAC concentrations already at 80 °C when the total concentration of selected PhACs decreased to 81%. In thermally treated sludge samples at 250 °C, only telmisartan at all studied WWTPs and diclofenac at WWTP Banská Bystrica stayed above the limits of quantification (LOQs), while the temperature of 550 °C led to a decrease in all thirteen PhACs below LOQs.
Sepsis incidence, suspicion, prediction and mortality in emergency medical services: a cohort study related to the current international sepsis guideline
Authors: Piedmont Silke , Goldhahn Ludwig , Swart Enno , Robra Bernt-Peter , Fleischmann-Struzek Carolin , Somasundaram Rajan , Bauer Wolfgang
Published: February 2024

Purpose

Sepsis suspicion by Emergency Medical Services (EMS) is associated with improved patient outcomes. This study assessed sepsis incidence and recognition by EMS and analyzed which of the screening tools recommended by the Surviving Sepsis Campaign best facilitates sepsis prediction.

Methods

Retrospective cohort study of claims data from health insurances (n = 221,429 EMS cases), and paramedics’ and emergency physicians’ EMS documentation (n = 110,419); analyzed outcomes were: sepsis incidence and case fatality compared to stroke and myocardial infarction, the extent of documentation for screening-relevant variables and sepsis suspicion, tools’ intersections for screening positive in identical EMS cases and their predictive ability for an inpatient sepsis diagnosis.

Results

Incidence of sepsis (1.6%) was similar to myocardial infarction (2.6%) and stroke (2.7%); however, 30-day case fatality rate was almost threefold higher (31.7% vs. 13.4%; 11.8%). Complete vital sign documentation was achieved in 8.2% of all cases. Paramedics never, emergency physicians rarely (0.1%) documented a sepsis suspicion, respectively septic shock. NEWS2 had the highest sensitivity (73.1%; Specificity:81.6%) compared to qSOFA (23.1%; Sp:96.6%), SIRS (28.2%; Sp:94.3%) and MEWS (48.7%; Sp:88.1%). Depending on the tool, 3.7% to 19.4% of all cases screened positive; only 0.8% in all tools simultaneously.

Conclusion

Incidence and mortality underline the need for better sepsis awareness, documentation of vital signs and use of screening tools. Guidelines may omit MEWS and SIRS as recommendations for prehospital providers since they were inferior in all accuracy measures. Though no tool performed ideally, NEWS2 qualifies as the best tool to predict the highest proportion of septic patients and to rule out cases that are likely non-septic.
Low-frequency oscillation of train–network system considering traction power supply mode
Authors: Liu Yuchen , Lyu Xiaoqin , Chang Mingyuan , Yang Qiqi
Published: February 2024

The low-frequency oscillation (LFO) has occurred in the train–network system due to the introduction of the power electronics of the trains. The modeling and analyzing method in current researches based on electrified railway unilateral power supply system are not suitable for the LFO analysis in a bilateral power supply system, where the trains are supplied by two traction substations. In this work, based on the single-input and single-output impedance model of China CRH5 trains, the node admittance matrices of the train–network system both in unilateral and bilateral power supply modes are established, including three-phase power grid, traction transformers and traction network. Then the modal analysis is used to study the oscillation modes and propagation characteristics of the unilateral and bilateral power supply systems. Moreover, the influence of the equivalent inductance of the power grid, the length of the transmission line, and the length of the traction network are analyzed on the critical oscillation mode of the bilateral power supply system. Finally, the theoretical analysis results are verified by the time-domain simulation model in MATLAB/Simulink.
Assimilate Remobilization in Five Spring Grain Legumes Under Mediterranean Conditions
Authors: Koutroubas Spyridon D. , Damalas Christos A. , Fotiadis Sideris
Published: February 2024

A comparative evaluation of grain legumes is essential for the effective planning of legume-based agricultural systems in a given environment. The goal of this work was to contrast the growth, translocation of assimilates, and grain yield of spring-planted common vetch (Vicia sativa L.), red pea (Lathyrus cicera L.), lentil (Lens culinaris Medik.), chickpea (Cicer arietinum L.), and field pea (Pisum sativa L.) under rainfed Mediterranean conditions. Two cultivars of each species were cultivated on a silty clay soil in northeastern Greece for 2 years (2014 and 2015) with contrasting rainfall patterns. Chickpea and field pea exhibited better early crop growth rate than any other legume. Species differences in assimilates availability prior to grain filling affected the remobilization of assimilates to seed, which increased by 45% for every kg ha−1 rise in early dry matter accumulation. Dry matter translocation efficiency varied from 9 to 51% depending on species and year. Red pea was the best option in terms of seed yield, regardless of the seasonal rainfall. Chickpea in the drier year (2015) and field pea in the wetter year (2014) produced seed yields that were comparable to that of red pea. Lentil and common vetch were generally less productive species in terms of seed yield. Species seed yield was associated with their ability to accumulate biomass either before podding (r = 0.52, P < 0.05) or at maturity (r = 0.51, P < 0.05), but not with harvest index or translocation of dry matter. Findings provide new knowledge regarding growth attributes and reallocation of assimilate in five legume species grown simultaneously in the same environment, which has never been studied before. In addition, results highlight that selecting species with enhanced early or final biomass potential as well as adopting cultural practices that promote biomass accumulation in the growing season appear to be effective management strategies for improving seed yield of the tested grain legumes under Mediterranean conditions.
Rapid detection of tomato spotted wilt virus by real-time RT-LAMP and in-field application
Authors: Caruso A.G. , Ragona A. , Agrò G. , Bertacca S. , Yahyaoui E. , Galipienso L. , Rubio L. , Panno S. , Davino S.
Published: February 2024

Tomato spotted wilt virus (TSWV) is considered one of the most threatening viruses worldwide for different economically important agricultural crops. In this scenario, it is important to perform an early detection by laboratory tests to prevent TSWV spread. A rapid and sensitive TSWV detection protocol based on real time reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed in this work, also using cost-effective and simplified sample preparation procedure, to assess the suitability of the RT-LAMP assay in field conditions on tomato and pepper samples. A set of six primers was designed within the nucleotide sequence region coding for the nucleocapsid protein (N) of segment S, targeting a 220-nucleotide sequence. Sensitivity, specificity, accuracy, and in-field application of the real-time RT-LAMP assay were evaluated. The developed real-time RT-LAMP assay proved to be one thousand and one hundred times more sensitive than end-point RT-PCR and real-time RT-PCR methods, respectively, detecting a total of 9.191 × 101 genome copies as minimum target, and no cross-reactivity were detected with other viruses belonging to Tospoviridae and Bromoviridae families used as outgroup. In addition, the in-field application of the assay using the rapid sample preparation gave adequate and reliable results within 60 minutes, with an acceptable reaction delay when compared to canonical RNA extraction. The in-field analyses showed an increase of TSWV-positive samples (37%) detection compared with end-point RT-PCR and real-time RT-PCR (32% and 29%, respectively), particularly on asymptomatic samples, confirming that the real-time RT-LAMP assay can be implemented as a routine test both in-field and laboratory conditions as a rapid and sensitive technique for TSWV detection.
Host reproduction number as an indicator of reproductive advantage in Bactrocera dorsalis over Bactrocera tryoni – can the concept elucidate the invasive threat in northern Australia?
Authors: Dominiak Bernard Charles
Published: February 2024

Incursions by exotic tephritids continue to threaten Australia. Host suitability for a specific tephritid is ranked by the number of adults which can emerge from one kg of fruit or the Host Reproduction Number (HRN). Bactrocera dorsalis has previously invaded northern Australia but was eradicated. However, Bactrocera dorsalis remains the largest exotic threat and is likely to invade through northern Australia but B. tryoni and other tephritids are already well established. One question is what hosts would likely provide the best early warning for an exotic incursion. Here, the HRN for 40 hosts for Bactrocera dorsalis and B. tryoni were established from the scientific literature. The reproductive advantages of one species over the other were calculated by dividing the higher HRN by the lower HRN. The fruits with the highest reproductive advantage (> 30) favouring B. dorsalis were soursop, mango and capsicum. The reproductive advantage estimate was compared to surveillance data collected during B. dorsalis eradication in north Queensland from 1995 to 1997. Mangoes and capsicum were among the mostly commonly infested hosts. Capsicums provided the second highest number of samples and would seem ideal candidates as sentinel plants for current surveillance programs. Some inconsistencies are identified and discussed. The HRN and reproductive advantage may have the potential to identify hosts and industries for early warning exotic fruit fly surveillance, better-targeted eradication programs and risk assessments for imports/exports.
Formalizing ethical principles within AI systems: experts’ opinions on why (not) and how to do it
Authors: Poszler Franziska , Portmann Edy , Lütge Christoph
Published: February 2024

AI systems are increasingly put into contexts where computed decisions must be guided by ethical considerations. To develop ethically grounded algorithms and technologies, scholars have suggested computational ethics as an essential frontier, which aims to translate ethical principles into computer code. However, computational ethics has received little attention in academic literature so far, with existing work mainly focusing on its technical implementation, while many open questions concerning its (societal and ethical) implications still need to be resolved. Therefore, in this study, we interviewed 12 experts from philosophy, AI and cognitive sciences to shed light on computational ethics beyond a technical perspective. Findings suggest that indicated supporting and opposing arguments can be clustered into pragmatic/practical, societal and epistemic reasons, all of which need to be contemplated when engaging in computational ethics and developing resulting artificial moral agents. Furthermore, the mentioned recommendations for companies’ technological design and development, for industry’s governance measures and academia’s research endeavors are recapitulated and summarized in a holistic framework that aims to facilitate a reflected implementation of ‘ethics in and by design’ in the future.