bluuebunny/crossref_metadata_2025 huggingface dataset:
The significance of finerenone as a novel therapeutic option in diabetic kidney disease: a scoping review with emphasis on cardiorenal outcomes of the finerenone phase 3 trials
Authors: Arici Mustafa , Altun Bulent , Araz Mustafa , Atmaca Aysegul , Demir Tevfik , Ecder Tevfik , Guz Galip , Gogas Yavuz Dilek , Yildiz Alaattin , Yilmaz Temel
Published: June 2024

This scoping review prepared by endocrinology and nephrology experts aimed to address the significance of finerenone, as a novel therapeutic option, in diabetic kidney disease (DKD), based on the biological prospect of cardiorenal benefit due to non-steroidal mineralocorticoid receptor antagonist (MRA) properties, and the recent evidence from the finerenone phase 3 program clinical trials. The importance of finerenone in slowing DKD progression was critically reviewed in relation to the role of MR overactivation in the pathogenesis of cardiorenal disease and unmet needs in the current practice patterns. The efficacy and safety outcomes of finerenone phase III study program including FIDELIO-DKD, FIGARO-DKD and FIDELITY were presented. Specifically, perspectives on inclusion of patients with preserved estimated glomerular filtration rate (eGFR) or high albuminuria, concomitant use of sodium-glucose co-transporter-2 inhibitor (SGLT2i) or glucagon-like peptide 1 receptor agonist (GLP-1 RA), baseline glycated hemoglobin (HbA1c) level and insulin treatment, clinically meaningful heart failure outcomes and treatment-induced hyperkalemia were addressed. Finerenone has emerged as a new therapeutic agent that slows DKD progression, reduces albuminuria and risk of cardiovascular complications, regardless of the baseline HbA1c levels and concomitant treatments (SGLT2i, GLP-1 RA, or insulin) and with a favorable benefit-risk profile. The evolving data on the benefit of SGLT2is and non-steroidal MRAs in slowing or reducing cardiorenal risk seem to provide the opportunity to use these pillars of therapy in the management of DKD, after a long-period of treatment scarcity in this field. Along with recognition of the albuminuria as a powerful marker to detect those patients at high risk of cardiorenal disease, these important developments would likely to impact standard-of-care options in the setting of DKD.
Genomes and secondary metabolomes of Streptomyces spp. isolated from Leontopodium nivale ssp. alpinum
Authors: Malfent Fabian , Zehl Martin , Kirkegaard Rasmus H. , Oberhofer Martina , Zotchev Sergey B.
Published: June 2024

Bacterial endophytes dwelling in medicinal plants represent an as yet underexplored source of bioactive natural products with the potential to be developed into drugs against various human diseases. For the first time, several Streptomyces spp. were isolated from the rare and endangered traditional medicinal plant Leontopodium nivale ssp. alpinum, also known as Edelweiss. In the search for novel natural products, nine endophytic Streptomyces spp. from Edelweiss were investigated via genome sequencing and analysis, followed by fermentation in different media and investigation of secondary metabolomes. A total of 214 secondary metabolite biosynthetic gene clusters (BGCs), of which 35 are presumably unique, were identified by the bioinformatics tool antiSMASH in the genomes of these isolates. LC-MS analyses of the secondary metabolomes of these isolates revealed their potential to produce both known and presumably novel secondary metabolites, whereby most of the identified molecules could be linked to their cognate BGCs. This work sets the stage for further investigation of endophytic streptomycetes from Edelweiss aimed at the discovery and characterization of novel bioactive natural products.
Modeling the contribution of theta-gamma coupling to sequential memory, imagination, and dreaming
Authors: Pirazzini Gabriele , Ursino Mauro
Published: June 2024

Gamma oscillations nested in a theta rhythm are observed in the hippocampus, where are assumed to play a role in sequential episodic memory, i.e., memorization and retrieval of events that unfold in time. In this work, we present an original neurocomputational model based on neural masses, which simulates the encoding of sequences of events in the hippocampus and subsequent retrieval by exploiting the theta-gamma code. The model is based on a three-layer structure in which individual Units oscillate with a gamma rhythm and code for individual features of an episode. The first layer (working memory in the prefrontal cortex) maintains a cue in memory until a new signal is presented. The second layer (CA3 cells) implements an auto-associative memory, exploiting excitatory and inhibitory plastic synapses to recover an entire episode from a single feature. Units in this layer are disinhibited by a theta rhythm from an external source (septum or Papez circuit). The third layer (CA1 cells) implements a hetero-associative net with the previous layer, able to recover a sequence of episodes from the first one. During an encoding phase, simulating high-acetylcholine levels, the network is trained with Hebbian (synchronizing) and anti-Hebbian (desynchronizing) rules. During retrieval (low-acetylcholine), the network can correctly recover sequences from an initial cue using gamma oscillations nested inside the theta rhythm. Moreover, in high noise, the network isolated from the environment simulates a mind-wandering condition, randomly replicating previous sequences. Interestingly, in a state simulating sleep, with increased noise and reduced synapses, the network can “dream” by creatively combining sequences, exploiting features shared by different episodes. Finally, an irrational behavior (erroneous superimposition of features in various episodes, like “delusion”) occurs after pathological-like reduction in fast inhibitory synapses. The model can represent a straightforward and innovative tool to help mechanistically understand the theta-gamma code in different mental states.
Design and evaluation of a global workspace agent embodied in a realistic multimodal environment
Authors: Dossa Rousslan Fernand Julien , Arulkumaran Kai , Juliani Arthur , Sasai Shuntaro , Kanai Ryota
Published: June 2024

As the apparent intelligence of artificial neural networks (ANNs) advances, they are increasingly likened to the functional networks and information processing capabilities of the human brain. Such comparisons have typically focused on particular modalities, such as vision or language. The next frontier is to use the latest advances in ANNs to design and investigate scalable models of higher-level cognitive processes, such as conscious information access, which have historically lacked concrete and specific hypotheses for scientific evaluation. In this work, we propose and then empirically assess an embodied agent with a structure based on global workspace theory (GWT) as specified in the recently proposed “indicator properties” of consciousness. In contrast to prior works on GWT which utilized single modalities, our agent is trained to navigate 3D environments based on realistic audiovisual inputs. We find that the global workspace architecture performs better and more robustly at smaller working memory sizes, as compared to a standard recurrent architecture. Beyond performance, we perform a series of analyses on the learned representations of our architecture and share findings that point to task complexity and regularization being essential for feature learning and the development of meaningful attentional patterns within the workspace.
18F-FDG PET/CT semi-quantitative parameters combined with SCC-Ag in predicting lymph node metastasis in stage I-II cervical cancer
Authors: Jiang Cheng-Zhi , Zheng Kai , Zhang Yan-Yin , Yang Jian , Ye Hui , Peng Xiang
Published: June 2024

Objective

To explore the value of 18F-fluordeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) semi-quantitative parameters of primary tumor combined with squamous cell carcinoma antigen (SCC-Ag) in predicting lymph node metastasis (LNM) of cervical cancer (FIGO 2018 stage I-II).

Materials and Methods

A total of 65 patients with stage I-II cervical cancer underwent 18F-FDG PET/CT were included in our study. Comparing the primary tumor 18F-FDG PET/CT semi-quantitative parameters and SCC-Ag between the LNM group and the non-LNM group. Logistic regression and receiver operating characteristic (ROC) were used to analyze the value of 18F-FDG PET/CT metabolic parameters and SCC-Ag in predicting LNM.

Results

There were 14 and 51 patients were classified as having LNM and NLNM. The semi-quantitative parameters, including the maximum standardized uptake value (SUVmax), the mean standardized uptake value (SUVmean), the peak standardized uptake value (SUVpeak), the total lesion glycolysis (TLG), the metabolic tumor volume (MTV) of the tumor and SCC-Ag were all significantly higher in LNM than in NLNM (SUVmax, 16.07 ± 7.81 vs 11.19 ± 4.73, SUVmean, 9.16 ± 3.48 vs 6.29 ± 2.52, SUVpeak, 12.70 ± 5.26 vs 7.65 ± 3.26, MTV, 22.77 ± 12.36 vs 7.09 ± 5.21, TLG, 211.01 ± 154.25 vs 43.38 ± 36.17, SCC-Ag, 5.39 ± 4.56 vs 2.13 ± 2.50, all p<0.01). Logistic regression analysis showed that TLG was an independent predictor of LNM in stage I-II cervical cancer (OR 1.032, 95% CI 1.013–1.052, p<0.01). Moreover, the predictive value of TLG combined with SUVpeak and SCC-Ag increased and the area under the curve increased compared SUVpeak and SCC-Ag.

Conclusion

18F-FDG PET/CT semi-quantitative parameters and SCC-Ag have promise for assessing LNM in stage I-II cervical cancer. TLG of primary tumor provides independent and increasing values in predicting LNM in stage I-II cervical cancer.
T2DM may exert a protective effect against digestive system tumors in East Asian populations: a Mendelian randomization analysis
Authors: An Ni , Zhang Yu , Sha Zhilin , Xu Zhen , Liu Xiuzhen
Published: June 2024

Introduction

Type 2 diabetes mellitus (T2DM) was associated with digestive system tumors. We analyzed publicly available data from GWAS studies using Mendelian randomization methods to clarify its causal relationship and mechanisms. Five common digestive system tumors and four diabetes-related phenotypes were included.

Methods

Inverse variance weighted method was the main analytical method. Meta-analysis was used to summarize results of multiple data sources. Horizontal pleiotropy was tested using Egger-intercept method and validated by MRPRESSO method. Heterogeneity and sensitivity analysis were conducted by Cochran’s Q test and leave-one-out method, respectively.

Results

T2DM is associated with a reduced risk of esophageal (OR: 0.77, 95% CI: 0.71 to 0.83, P< 0.001), gastric (OR: 0.87, 95% CI: 0.84 to 0.90, P< 0.001) and colorectal cancer (OR: 0.88, 95% CI: 0.85 to 0.91, P< 0.001) and hepatocellular carcinoma (OR: 0.92, 95% CI: 0.86 to 0.97, P = 0.005) and an increased risk of pancreatic cancer (OR: 1.92, 95% CI: 1.47 to 2.50, P< 0.001) in East Asian population. T2DM causes decreased fasting insulin levels (OR = 0.966, 95% CI: 0.95 to 0.98, P< 0.001) and increased glycated hemoglobin levels (OR=1.41, 95% CI: 1.39 to 1.44, P<0.001). Elevated fasting insulin levels increase the risk of esophageal cancer (OR = 10.35, 95% CI: 1.10 to 97.25, P = 0.041), while increased glycated hemoglobin levels increase pancreatic cancer risk (OR=2.33, 95% CI: 1.37 to 3.97, P=0.002) but decrease gastric cancer risk (OR=0.801, 95% CI: 0.65 to 0.99, P=0.044).

Conclusion

T2DM is associated with a reduced risk of esophageal, gastric and colorectal cancer and hepatocellular carcinoma in East Asian populations. The causal relationships between T2DM with esophageal and gastric cancer are partially mediated by decreased fasting insulin and increased glycated hemoglobin levels, respectively. T2DM indirectly increases the risk of pancreatic cancer by increasing glycated hemoglobin levels.
Long-term, 13-year survival after immune cell therapy combined with chemotherapy for extensive-stage small-cell lung cancer: a case report
Authors: Liu Tong , Wang Heshuang , Kong Qinglong , Wang Haoyu , Wei Haodong , Sun Pengda
Published: June 2024

While the incidence of small-cell lung cancer is low, it has a poor prognosis. Patients with extensive small-cell lung cancer account for about 70% of all cases of small-cell lung cancer, with a median overall survival duration of 8–13 months and a 5-year overall survival rate of only 1%–5%. Herein, we report small-cell lung cancer diagnosed by bronchoscopic biopsy in an adult male patient in 2011. The patient had a clinical stage of cT2N2M1 and stage IV disease (i.e., extensive small-cell lung cancer). Still, he survived for 13 years through a combination of chemotherapy, radiotherapy, and cytokine-induced killer (CIK) immunocell thera. Comprehensive tumor markers, lymphocyte subsets, and lung CT images were obtained through long-term follow-up. After 12 cycles of chemotherapy (CE/IP regimen) and 5940cgy/33f radiotherapy, we found that the patient was in an immunosuppressive state, so the patient was given CIK cell therapy combined with chemotherapy. After 2 years of immunocell-combined chemotherapy, there were no significant changes in the primary lesion or other adverse events. In the 13 years since the patient’s initial diagnosis, we monitored the changes in the patient’s indicators such as CEA, NSE, CD4/CD8 ratio, and CD3+CD4+ lymphocytes, suggesting that these may be the factors worth evaluating regarding the patient’s immune status and the effectiveness of combination therapy. In this case, CIK cell immunotherapy combined with chemotherapy was applied to control tumor progression. With a good prognosis, we concluded that CIK cell immunotherapy combined with chemotherapy can prolong patient survival in cases of extensive small-cell lung cancer, and the advantages of combined therapy are reflected in improving the body’s immune capacity and enhancing the killing effect of immune cells.
Development and validation of AI models using LR and LightGBM for predicting distant metastasis in breast cancer: a dual-center study
Authors: Zhang Wen-hai , Tan Yang , Huang Zhen , Tan Qi-xing , Zhang Yue-mei , Chen Bin-jie , Wei Chang-yuan
Published: June 2024

Objective

This study aims to develop an artificial intelligence model utilizing clinical blood markers, ultrasound data, and breast biopsy pathological information to predict the distant metastasis in breast cancer patients.

Methods

Data from two medical centers were utilized, Clinical blood markers, ultrasound data, and breast biopsy pathological information were separately extracted and selected. Feature dimensionality reduction was performed using Spearman correlation and LASSO regression. Predictive models were constructed using LR and LightGBM machine learning algorithms and validated on internal and external validation sets. Feature correlation analysis was conducted for both models.

Results

The LR model achieved AUC values of 0.892, 0.816, and 0.817 for the training, internal validation, and external validation cohorts, respectively. The LightGBM model achieved AUC values of 0.971, 0.861, and 0.890 for the same cohorts, respectively. Clinical decision curve analysis showed a superior net benefit of the LightGBM model over the LR model in predicting distant metastasis in breast cancer. Key features identified included creatine kinase isoenzyme (CK-MB) and alpha-hydroxybutyrate dehydrogenase.

Conclusion

This study developed an artificial intelligence model using clinical blood markers, ultrasound data, and pathological information to identify distant metastasis in breast cancer patients. The LightGBM model demonstrated superior predictive accuracy and clinical applicability, suggesting it as a promising tool for early diagnosis of distant metastasis in breast cancer.
Jingqianshu granules mitigates premenstrual depression by regulating orexin signaling
Authors: Dong Ping , Dai Weibo , Zhao Tingting , Gong Yuandong , Weng Ning , Lv Shimeng , Zhao Yifan , Du Chunyu , Ma Yuexiang , Zhang Zhen , He Shuhua , Zheng Feng , Sun Peng
Published: June 2024

Introduction: Premenstrual dysphoric disorder (PMDD), a severe form of premenstrual syndrome (PMS), is a serious health disorder that affects patient moods. It is caused by cyclic psychological symptoms and its pathogenesis is still unclear. Abnormalities in the basolateral amygdala (BLA) orexin system, which are important causes of the development of depressive mood, have not been reported in PMDD, so exploring its intrinsic mechanisms is meaningful for enriching the pathomechanisms of PMDD.

Methods: High performance liquid chromatography was used for the determination of the active ingredients of Jingqianshu granules. Developing a rat model of premenstrual depression using the forced swimming test (FST). The experiment consisted of two parts. In Part 1, the rats were divided into the control group, the model group, the model + Jingqianshu group, and the model + fluoxetine group. The FST, open field test, and elevated plus maze test, were used to assess the behavior of the rats as well as to evaluate the effect of drug intervention. Immunofluorescence and RT-qPCR were used to detect the expression of orexin and its receptors OX1R and OX2R genes and proteins. The expression of Toll-like receptor 4, nuclear factor kappa-B, tumor necrosis factor-α, interleukin 6, and interleukin-1β in the BLA brain region was detected by Western-Blot. In part 2, the rats were injected intracerebrally with orexin-A. Observe the behavioral activities of rats in the control group, model group, and model+orexin-A group. Immunofluorescence was used to detect microglia in the BLA area of rats, and the expression levels of the above inflammatory factors were detected by Western-Blot.

Results: The five components of Jingqianshu granules are: paeoniflorin, erulic acid, liquiritin, hesperidin, and paeonol. During the estrous cycle, rats exhibited depressive-like behavior during the non-receptive phase of the behavioral test, which disappeared during the receptive phase. Immunofluorescence and RT-qPCR showed reduced gene and protein expression of orexin, OX1R, and OX2R in the BLA region of rats in the model group.WB showed elevated levels of inflammatory factors. All returned to control levels after drug treatment. In part 2, injection of orexin-A into the BLA brain region of model rats resulted in reduced immunoreactivity of microglia and decreased expression levels of inflammatory factors.

Discussion: Jianqianshu granules can achieve the purpose of treating premenstrual depression by regulating orexin-mediated inflammatory factors, which provides a new idea for further research on the pathogenesis of PMDD. However, the current study is still preliminary and the pathogenesis of PMDD is complex. Therefore, more in-depth exploration is needed.
Preclinical pharmacokinetic characterization of amdizalisib, a novel PI3Kδ inhibitor for the treatment of hematological malignancies
Authors: Jiang Shuwen , Li Xiangkun , Xue Weifang , Xia Sumei , Wang Jian , Sai Yang , Dai Guangxiu , Su Weiguo
Published: June 2024

Amdizalisib, also named HMPL-689, a novel selective and potent PI3Kδ inhibitor, is currently under Phase II clinical development in China for treating hematological malignancies. The preclinical pharmacokinetics (PK) of amdizalisib were extensively characterized in vitro and in vivo to support the further development of amdizalisib. We characterized the plasma protein binding, blood-to-plasma partition ratio, cell permeability, hepatic microsomal metabolic stability, and drug–drug interaction potential of amdizalisib using in vitro experiments. In vivo PK assessment was undertaken in mice, rats, dogs, and monkeys following a single intravenous or oral administration of amdizalisib. The tissue distribution and excretion of amdizalisib were evaluated in rats. The PK parameters (CL and Vss) of amdizalisib in preclinical species (mice, rats, dogs, and monkeys) were utilized for the human PK projection using the allometric scaling (AS) approach. Amdizalisib was well absorbed and showed low-to-moderate clearance in mice, rats, dogs, and monkeys. It had high cell permeability without P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) substrate liability. Plasma protein binding of amdizalisib was high (approximately 90%). It was extensively distributed but with a low brain-to-plasma exposure ratio in rats. Amdizalisib was extensively metabolized in vivo, and the recovery rate of the prototype drug was low in the excreta. Amdizalisib and/or its metabolites were primarily excreted via the bile and urine in rats. Amdizalisib showed inhibition potential on P-gp but not on BCRP and was observed to inhibit CYP2C8 and CYP2C9 with IC50 values of 30.4 and 10.7 μM, respectively. It exhibited induction potential on CYP1A2, CYP2B6, CYP3A4, and CYP2C9. The preclinical data from these ADME studies demonstrate a favorable pharmacokinetic profile for amdizalisib, which is expected to support the future clinical development of amdizalisib as a promising anti-cancer agent.
Assessing the development of primary English education based on CIPP model—a case study from primary schools in China
Authors: Chang Xiao , Wang Zhe
Published: June 2024

This article examines the development of primary English education from teachers’ and students’ perspectives; this is done by investigating environment, curriculum and teacher and students’ information. The study was carried out with 42 primary English teachers and 404 primary students from 90 urban and rural primary schools in 13 regions in the Hunan Province, China, the participants engaged in the questionnaire tasks to investigate the present status and problems with primary English education in the Hunan Province. Based on the assessment indicators through CIPP model, combining educational theory and sustainable development theory, the present study develops a primary school English education evaluation model and conducts a practical investigation of primary school English education in the Hunan Province, based on the established model. The findings indicate that the quality of teachers has improved, teaching methods and teaching equipment have become diversified, and student interests and English proficiencies have increased. However, there are still deficiencies in the implementation of Primary English Education in the Hunan Province. For instance, certain schools improperly implement national policies, resulting in imbalanced education. Additionally, educational inequality persists due to disparities in family economic status and importance. Moreover, regional, ideological, and management factors contribute to uneven allocation of educational resources. Furthermore, significant disparities exist between urban and rural areas in terms of teacher qualifications, teaching quality, and school operating hours. The article proposes enhancing awareness of sustainable development, strengthening supervision, and seeking educational and policy support to facilitate the sustainable development of primary English education.
Infants show systematic rhythmic motor responses while listening to rhythmic speech
Authors: Boll-Avetisyan Natalie , Shandala Arina , Langus Alan
Published: June 2024

Rhythm is known to play an important role in infant language acquisition, but few infant language development studies have considered that rhythm is multimodal and shows strong connections between speech and the body. Based on the observation that infants sometimes show rhythmic motor responses when listening to auditory rhythms, the present study asked whether specific rhythm cues (pitch, intensity, or duration) would systematically increase infants’ spontaneous rhythmic body movement, and whether their rhythmic movements would be associated with their speech processing abilities. We used pre-existing experimental and video data of 148 German-learning 7.5- and 9.5-month-old infants tested on their use of rhythm as a cue for speech segmentation. The infants were familiarized with an artificial language featuring syllables alternating in pitch, intensity, duration, or none of these cues. Subsequently, they were tested on their recognition of bisyllables based on perceived rhythm. We annotated infants’ rhythmic movements in the videos, analyzed whether the rhythmic moving durations depended on the perceived rhythmic cue, and correlated them with the speech segmentation performance. The result was that infants’ motor engagement was highest when they heard a duration-based speech rhythm. Moreover, we found an association of the quantity of infants’ rhythmic motor responses and speech segmentation. However, contrary to the predictions, infants who exhibited fewer rhythmic movements showed a more mature performance in speech segmentation. In sum, the present study provides initial exploratory evidence that infants’ spontaneous rhythmic body movements while listening to rhythmic speech are systematic, and may be linked with their language processing. Moreover, the results highlight the need for considering infants’ spontaneous rhythmic body movements as a source of individual differences in infant auditory and speech perception.
Delirium management in perioperative geriatric services: a narrative review of non-pharmaceutical strategies
Authors: Travers Rozenn , Gagliardi Geoffroy , Ramseyer Maximilian
Published: June 2024

Delirium, a common complication in elderly surgical patients, poses significant challenges in perioperative care. Perioperative geriatric services (PGS) aim at managing comorbidities, postoperative complications, and initiating early recovery of mobility to enhance elderly patients’ prognosis in the perioperative period. Studies have shown that patients with preoperative cognitive disorders are at a significantly increased risk of postoperative delirium. While postoperative delirium affects up to 70% of people over 60 and 90% of people with neurodegenerative diseases, it remains underdiagnosed in many cases. Postoperative delirium can lead to functional decline, prolonged hospitalization, increased healthcare costs, cognitive impairment, and psychological malaise. This article briefly summarizes the literature on delirium, its risk factors, and its non-pharmaceutical management strategies within the perioperative period. It highlights the importance of integrating cognitive and psychological assessments into perioperative care protocols to provide baseline data, improve patient outcomes, reduce hospital stays, and minimize complications associated with delirium. By embracing evidence-based delirium management protocols, healthcare professionals can better identify and manage delirium, ultimately improving the quality of care for elderly surgical patients, which would also benefit healthcare staff and healthcare institutions.
Regional insights on tobacco-related tweets: unveiling user opinions and usage patterns
Authors: Castillo-Toledo Consuelo , Fernandez-Lazaro Cesar I. , Lara-Abelenda Francisco J. , Molina-Ruiz Rosa M. , Ortega Miguel Angel , Mora Fernando , Alvarez-Mon Melchor , Quintero Javier , Alvarez-Mon Miguel Angel
Published: June 2024

Introduction

Tobacco consumption and its impact on health remain high worldwide. Additionally, it is a contentious issue generating significant controversy. Twitter has proven to be a useful platform for evaluating public health topics related to population health behaviors, and tobacco consumption.

Objective

The objective of this study is to analyze the content of tweets related to tobacco. Moreover, geolocation data will be considered to understand regional differences.

Methods

Tweets published between 2018 and 2022, in both English and Spanish, containing the keyword “tobacco,” were analyzed. A total of 56,926 tweets were obtained. The tweets were classified into different categories. 550 tweets were manually analyzed, and an automated and computerized classification was performed for the remaining and largest subset of tweets.

Results

The analysis yielded 30,812 classifiable tweets. Healthcare professionals were the most frequent contributors to the topic (50.2%), with the most common theme being general information about the toxic effects of tobacco. 57.9% of the tweets discussed the harmful effects of tobacco on health, with fear being the predominant emotion. The largest number of tweets were located in America.

Conclusions

Our study revealed a substantial number of tweets highlighting the health risks and negative perceptions of tobacco consumption. Africa showed the lowest percentage of tweets discussing the health risks associated with tobacco, coinciding with the continent having the least developed anti-tobacco policies. Healthcare professionals emerged as the most prominent users discussing the topic, which is encouraging as they play a crucial role in disseminating accurate and scientific health information.
Sex-related differences in young binge drinkers on the neurophysiological response to stress in virtual reality
Authors: Moreno-Fernández Román D. , Bernabéu-Brotons Elena , Carbonell-Colomer Myriam , Buades-Sitjar Francisco , Sampedro-Piquero Patricia
Published: June 2024

Background

Stress is one of the main environmental factors involved in the onset of different psychopathologies. In youth, stressful life events can trigger inappropriate and health-damaging behaviors, such as binge drinking. This behavior, in turn, can lead to long-lasting changes in the neurophysiological response to stress and the development of psychological disorders late in life, e.g., alcohol use disorder. Our aim was to analyze the pattern of neurophysiological responses triggered with the exposition to a stressful virtual environment in young binge drinkers.

Methods

AUDIT-3 (third question from the full AUDIT) was used to detect binge drinking (BD) in our young sample (age 18–25 years). According to the score, participants were divided into control (CO) and BD group. Next, a standardized virtual reality (VR) scenario (Richie’s Plank) was used for triggering the stress response while measuring the following neurophysiological variables: brain electrical activity by electroencephalogram (EEG) and cortisol levels through saliva samples both measurements registered before and after the stressful situation. Besides, heart rate (HR) with a pulsometer and electrodermal response (EDA) through electrodes placed on fingers were analyzed before, during and after the VR task.

Results

Regarding the behavior assessed during the VR task, BD group spent significantly less amount of time walking forward the table and a tendency toward more time walking backwards. There was no statistically significant difference between the BD and the CO group regarding time looking down, but when we controlled the variable sex, the BD women group displayed higher amount of time looking down than the rest of the groups. Neurophysiological measurements revealed that there was not any statistically significant difference between groups in any of the EEG registered measures, EDA response and cortisol levels. Sex-related differences were found in HR response to VR scenario, in which BD women displayed the highest peak of response to the stressor. Also, the change in heartbeat was higher in BD women than men.

Conclusion

Unveiling the neurophysiological alterations associated with BD can help us to prevent and detect early onset of alcohol use disorder. Also, from our data we conclude that participants’ sex can modulate some stress responses, especially when unhealthy behaviors such as BD are present. Nevertheless, the moment of registration of the neurophysiological variables respect to the stressor seems to be a crucial variable.
Pharmacokinetic/pharmacodynamic issues for optimizing treatment with beta-lactams of Gram-negative infections in critically ill orthotopic liver transplant recipients: a comprehensive review
Authors: Gatti Milo , Pea Federico
Published: June 2024

Orthotopic liver transplant (OLT) represents the standard of care for managing patients affected by end-stage and life-threatening liver diseases. Although a significant improvement in surgical techniques, immunosuppressant regimens, and prompt identification of early post-transplant complications resulted in better clinical outcome and survival in OLT recipients, the occurrence of early bacterial infections still represents a remarkable cause of morbidity and mortality. In this scenario, beta-lactams are the most frequent antimicrobials used in critical OLT recipients. The aim of this narrative review was to provide a comprehensive overview of the pathophysiological issues potentially affecting the pharmacokinetics of beta-lactams and to identify potential strategies for maximizing the likelihood of attaining adequate pharmacokinetic/pharmacodynamic (PK/PD) targets of beta-lactams in critically ill OLT recipients. A literature search was carried out on PubMed-MEDLINE database (until 31st March 2024) in order to retrieve clinical trials, real-world observational evidence, and/or case series/reports evaluating the PK/PD of traditional and novel beta-lactams in settings potentially involving critically ill OLT recipients. Retrieved evidence were categorized according to the concepts of the so-called “antimicrobial therapy puzzle”, specifically assessing a) beta-lactam PK/PD features, with specific regard to aggressive PK/PD target attainment; b) site of infection, with specific regard to beta-lactam penetration in the lung, ascitic fluid, and bile; and c) pathophysiological alterations, focusing mainly on those specifically associated with OLT. Overall, several research gaps still exist in assessing the PK behavior of beta-lactams in critical OLT recipients. The impact of specific OLT-associated pathophysiological alterations on the attainment of optimal PK/PD targets may represent an important field in which further studies are warranted. Assessing the relationship between aggressive beta-lactam PK/PD target attainment and clinical outcome in critical OLT recipients will represent a major challenge in the next future.
Aberrant immunity in the oral cavity—a link with rheumatoid arthritis?
Authors: Malcolm Jennifer , Culshaw Shauna
Published: June 2024

There are well established epidemiological links between rheumatoid arthritis and periodontitis. Recent data have started to shed light on the mechanisms that might underlie the relationship between these two complex diseases. Unravelling the roles of distinct pathways involved in these mechanisms has the potential to yield novel preventative and therapeutic strategies for both diseases. Perhaps most intriguingly, this represents an area where understanding the biology in the oral cavity might reveal fundamental advances in understanding immune regulation and the relationships between the host and microbiome. Here we seek to discuss aspects of the adaptive immune response that might link periodontitis and rheumatoid arthritis.
Inclusion effect of jack mackerel meal in diets substituting fish meal with corn gluten meal on growth and feed utilization of olive flounder (Paralichthys olivaceus)
Authors: Islam Md. Rabiul , Cho Sung Hwoan , Kim Taeho
Published: June 2024

Inclusion effect of different amount of jack mackerel meal (JMM) in the diets substituting 50% fish meal (FM) with corn gluten meal (CGM) on growth, feed availability, biochemical composition, plasma, and serum chemistry of olive flounder (Paralichthys olivaceus) was elucidated. Seven experimental diets were formulated. The control (Con) diet contained 60% FM. Fifty percent of FM in the Con diet was substituted with CGM, and then 5, 10, 20, 30, 40, and 50% JMM were added at the expense of FM to formulate the CJ5, CJ10, CJ20, CJ30, CJ40, and CJ50 diets, respectively. All formulated feeds were assigned to triplicate groups of fish. A total of 420 juvenile fish averaging 18 ± 0.01 g (mean ± SEM) was uniformly divided into 21, 50-L tanks, with 20 fish per tank. Fish were carefully hand-fed to satiation for 8 weeks. The weight gain of olive flounder fed the Con diet was significantly (p < 0.001) higher than that of fish fed the CJ5, CJ10, and CJ20 diets, but not significantly (p > 0.05) different from that of fish fed the CJ30, CJ40, and CJ50 diets. Olive flounder fed the Con diet achieved significantly (p < 0.001 and p < 0.04) greater specific growth rates (SGR) and feed consumption than those of fish fed the CJ5 and CJ10 diets, but not significantly (p > 0.05) different from those of fish fed the CJ20, CJ30, CJ40, and CJ50 diets. However, there were no significant (p > 0.05) differences in feed utilization, proximate composition, amino acid profiles, and plasma and serum parameters of olive flounder. In conclusion, incorporation of 30, and 20% JMM are the most desirable treatments in the olive flounder diets replacing 50% FM with CGM based on weight gain, and SGR and feed consumption, respectively. This study will be very helpful to develop low-FM diets for sustainable olive flounder culture.
Süreyya-Dani technique, a new technique to address notching of soft triangle and opening external nasal valve
Authors: Omer Goran Latif , Şeneldir Süreyya , Di Girolamo Stefano , Habibullah Imad J. , Ahmed Avar F. , Ali Sahand S. , Abdullah Aland S. , Mustafa Ayman M. , Abdalla Berun A. , Hassan Hemin Noori , Mohammed Shvan H. , Kakamad Fahmi H.
Published: June 2024

Introduction

While different methods are employed for fixing narrowed nasal valves and preventing the notching of soft triangles, this study aims to demonstrate the effectiveness of a new technique called Süreyya-Dani Technique.

Methods

This prospective study composed 100 patients who underwent rhinoplasty using the Süreyya-Dani technique. All patients presented with either notching of the soft triangle and/or external nasal valve dysfunction. Patients with the absence of soft triangle notching and external nasal valve dysfunction were excluded from this study. Facial analysis was conducted for all patients to identify any asymmetry in the face, and all nasal defects were identified. Descriptive statistics were calculated for different variables. Analytical statistics, namely Chi-Square test, was conducted with a significance level set at P < 0.05.

Results

In the current study, 100 patients were involved, out of which 63 (63%) were female and 37 (37%) were male. The participants' ages ranged from 18 to 46 years, with a mean age of 30 years. various chief complaints were found among patients, with the majority 37(37%) expressing cosmetic concerns. A statistically significant difference was found for the association of nasal tip defects with genders, intraoperative findings, and chef complaints, and the association between the degree of external valve insufficiency and crural weakness (P-value < 0.05).

Conclusion

Despite many techniques that have been put forward to fix narrowed nasal valves and prevent notching of the soft triangle, the Süreyya-Dani Technique could work to prevent its occurrence successfully.
Antibacterial activity and mechanism of chelerythrine against Streptococcus agalactiae
Authors: Xin Jige , Pu Qiqi , Wang Ruiying , Gu Yeqing , He Lin , Du Xuan , Tang Guowen , Han Diangang
Published: June 2024

Streptococcus agalactiae (S.agalactiae), also known as group B Streptococcus (GBS), is a highly infectious pathogen. Prolonged antibiotic usage leads to significant issues of antibiotic residue and resistance. Chelerythrine (CHE) is a naturally occurring benzophenidine alkaloid and chelerythrine chloride (CHEC) is its hydrochloride form with diverse biological and pharmacological activities. However, the antibacterial mechanism of CHEC against GBS remains unclear. Thus, this study aims to investigate the in vitro antibacterial activity of CHEC on GBS and elucidate its underlying mechanism. The antibacterial effect of CHEC on GBS was assessed using inhibitory zone, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) assays, as well as by constructing a time-kill curve. The antibacterial mechanism of CHEC was investigated through techniques such as scanning electron microscopy (SEM) and transmission electron microscopy (TEM), measurement of alkaline phosphatase (AKP) activity, determination of Na+ K+, Ca2+ Mg2+—adenosine triphosphate (ATP) activity, observation of membrane permeability, and analysis of intracellular reactive oxygen species (ROS) and mRNA expression levels of key virulence genes. The results demonstrated that the inhibition zone diameters of CHEC against GBS were 14.32 mm, 12.67 mm, and 10.76 mm at concentrations of 2 mg/mL, 1 mg/mL, and 0.5 mg/mL, respectively. The MIC and MBC values were determined as 256 μg/mL and 512 μg/mL correspondingly. In the time-kill curve, 8 × MIC, 4 × MIC and 2 × MIC CHEC could completely kill GBS within 24 h. SEM and TEM analyses revealed significant morphological alterations in GBS cells treated with CHEC including shrinkage, collapse, and leakage of cellular fluids. Furthermore, the antibacterial mechanism underlying CHEC’s efficacy against GBS was attributed to its disruption of cell wall integrity as well as membrane permeability resulting in extracellular release of intracellular ATP, AKP, Na+ K+, Ca2+ Mg2+. Additionally CHEC could increase the ROS production leading to oxidative damage and downregulating mRNA expression levels of key virulence genes in GBS cells. In conclusion, CHEC holds potential as an antimicrobial agent against GBS and further investigations are necessary to elucidate additional molecular mechanisms.
Using Lie Sphere Geometry to Study Dupin Hypersurfaces in Rn
Authors: Cecil Thomas E.
Published: June 2024

A hypersurface M in Rn or Sn is said to be Dupin if along each curvature surface, the corresponding principal curvature is constant. A Dupin hypersurface is said to be proper Dupin if each principal curvature has constant multiplicity on M, i.e., the number of distinct principal curvatures is constant on M. The notions of Dupin and proper Dupin hypersurfaces in Rn or Sn can be generalized to the setting of Lie sphere geometry, and these properties are easily seen to be invariant under Lie sphere transformations. This makes Lie sphere geometry an effective setting for the study of Dupin hypersurfaces, and many classifications of proper Dupin hypersurfaces have been obtained up to Lie sphere transformations. In these notes, we give a detailed introduction to this method for studying Dupin hypersurfaces in Rn or Sn, including proofs of several fundamental results. We also give a survey of the results in the field that have been obtained using this approach.
Risk of Tumor Progression after Microsurgery for Parasellar Meningioma Invading the Cavernous Sinus
Authors: Nowak Arkadiusz , Maj Edyta , Marchel Andrzej , Kunert Przemysław
Published: June 2024

Background: Parasellar meningiomas, which may invade the cavernous sinus, pose a significant challenge to neurosurgeons due to the high risk of postoperative neurological deficits associated with aggressive resection of the intracavernous part of the tumour. Therefore, subtotal tumour removal followed by observation or radiotherapy for the residual meningioma in the cavernous sinus is recommended. This retrospective study aimed to identify prognostic factors influencing recurrence and progression-free survival (PFS) in parasellar meningiomas invading the cavernous sinus after incomplete surgical treatment. Methods: This study included adult patients diagnosed with benign parasellar meningioma (WHO Grade I) invading the cavernous sinus, treated at our institution between 2006 and 2020, and with a postsurgical follow-up of at least 3 years. Surgical treatment involved near-total resection (NTR) with an intracavernous residual tumour or subtotal resection (STR) with additional extracavernous tumour left in place. Kaplan–Meier analysis estimated PFS rates, and Cox regression tested survival time differences between groups. Results: Among the 32 patients, the estimated median PFS was 11 years. Radiotherapy improved 5-year PFS only in patients with STR (p = 0.003). The univariate analysis identified preoperative tumour size, low preoperative Karnofsky Performance Score (KPS), and marked brain oedema as significant factors affecting meningioma progression after surgery. The multivariate analysis confirmed tumour size as an independent factor for progression (p = 0.012). Conclusions: For patients with parasellar meningioma invading the cavernous sinus, extracavernous tumour removal followed by close radiological surveillance of the residual intracavernous meningioma is a safe and appropriate strategy. When an extracavernous tumour component is left, adjuvant stereotactic radiotherapy or radiosurgery is recommended to control tumour growth.
Correction: Sung et al. Linear Tumor Regression of Rectal Cancer in Daily MRI during Preoperative Chemoradiotherapy: An Insight of Tumor Regression Velocity for Personalized Cancer Therapy. Cancers 2022, 14, 3749
Authors: Sung Soo-Yoon , Lee Sea-Won , Hong Ji Hyung , Kang Hye Jin , Lee So Jung , Kim Myungsoo , Kim Ji-Hoon , Kwak Yoo-Kang
Published: June 2024

In the original publication [...]
Mechanisms of the Antineoplastic Effects of New Fluoroquinolones in 2D and 3D Human Breast and Bladder Cancer Cell Lines
Authors: Ferrario Nicole , Marras Emanuela , Vivona Veronica , Randisi Federica , Fallica Antonino Nicolò , Marrazzo Agostino , Perletti Gianpaolo , Gariboldi Marzia Bruna
Published: June 2024

Antibacterial fluoroquinolones have emerged as potential anticancer drugs, thus prompting the synthesis of novel molecules with improved cytotoxic characteristics. Ciprofloxacin and norfloxacin derivatives, previously synthesized by our group, showed higher anticancer potency than their progenitors. However, no information about their mechanisms of action was reported. In this study, we selected the most active among these promising molecules and evaluated, on a panel of breast (including those triple-negative) and bladder cancer cell lines, their ability to induce cell cycle alterations and apoptotic and necrotic cell death through cytofluorimetric studies. Furthermore, inhibitory effects on cellular migration, metalloproteinase, and/or acetylated histone protein levels were also evaluated by the scratch/wound healing assay and Western blot analyses, respectively. Finally, the DNA relaxation assay was performed to confirm topoisomerase inhibition. Our results indicate that the highest potency previously observed for the derivatives could be related to their ability to induce G2/M cell cycle arrest and apoptotic and/or necrotic cell death. Moreover, they inhibited cellular migration, probably by reducing metalloproteinase levels and histone deacetylases. Finally, topoisomerase inhibition, previously observed in silico, was confirmed. In conclusion, structural modifications of progenitor fluoroquinolones resulted in potent anticancer derivatives possessing multiple mechanisms of action, potentially exploitable for the treatment of aggressive/resistant cancers.
The Transition from Pemphigus Foliaceus to Pemphigus Vegetans—An Intriguing Phenomenon within the Spectrum of Autoimmune Blistering Diseases: A Case Report
Authors: Orzan Olguța Anca , Popa Liliana Gabriela , Badiu Iulia , Ion Ana , Giurcăneanu Călin , Bălăceanu-Gurău Beatrice , Tudose Irina
Published: June 2024

Pemphigus vegetans and pemphigus foliaceus are rare autoimmune blistering diseases characterized by the disruption of desmosomal adhesion proteins, particularly desmoglein 3 and desmoglein 1. We report the case of a 62-year-old male who presented initially with scaly red plaques posing several diagnostic challenges. A histopathological examination revealed subcorneal acantholysis, matching the suspected clinical diagnosis of pemphigus foliaceus. The patient progressed, developing vegetating plaques, and a new biopsy was performed. The new histopathological and direct immunofluorescence exams were consistent with pemphigus vegetans. This case highlights the diagnostic challenges posed by the transition of pemphigus foliaceus to its vegetating form. We discuss the role of desmogleins in the pathogenesis of pemphigus and explore potential therapeutic strategies targeting these specific autoantigens.