bluuebunny/crossref_metadata_2025 huggingface dataset:
Musculoskeletal patients’ preferences for care from physiotherapists or support workers: a discrete choice experiment
Authors: Sarigiovannis Panos , Loría-Rebolledo Luis Enrique , Foster Nadine E. , Jowett Sue , Saunders Benjamin
Published: September 2024

Background

Delegation of clinical tasks from physiotherapists to physiotherapy support workers is common yet varies considerably in musculoskeletal outpatient physiotherapy services, leading to variation in patient care. This study aimed to explore patients’ preferences and estimate specific trade-offs patients are willing to make in treatment choices when treated in musculoskeletal outpatient physiotherapy services.

Methods

A discrete choice experiment was conducted using an efficient design with 16 choice scenarios, divided into two blocks. Adult patients with musculoskeletal conditions recruited from a physiotherapy service completed a cross-sectional, online questionnaire. Choice data analyses were conducted using a multinomial logit model. The marginal rate of substitution for waiting time to first follow-up physiotherapy appointment and distance from the physiotherapy clinic was calculated and a probability model was built to estimate the probability of choosing between two distinct physiotherapy service options under different scenarios.

Results

382 patient questionnaires were completed; 302 participants were treated by physiotherapists and 80 by physiotherapists and support workers. There was a significant preference to be seen by a physiotherapist, have more follow-up treatments, to wait less time for the first follow-up appointment, to be seen one-to-one, to see the same clinician, to travel a shorter distance to get to the clinic and to go to clinics with ample parking. Participants treated by support workers did not have a significant preference to be seen by a physiotherapist and it was more likely that they would choose to be seen by a support worker for clinic scenarios where the characteristics of the physiotherapy service were as good or better.

Conclusions

Findings highlight that patients treated by support workers are likely to choose to be treated by support workers again if the other service characteristics are as good or better compared to a service where treatment is provided only by physiotherapists. Findings have implications for the design of physiotherapy services to enhance patient experience when patients are treated by support workers. The findings will contribute to the development of “best practice” recommendations to guide physiotherapists in delegating clinical work to physiotherapy support workers for patients with musculoskeletal conditions.
Enhanced anti-tumor efficacy of S3I-201 in breast cancer mouse model through Wharton jelly- exosome
Authors: Hosseini Masoomeh , Ezzeddini Rana , Hashemi Seyed Mahmoud , Soudi Sara , Salek Farrokhi Amir
Published: September 2024

Objective

Exosomes, membrane-enveloped vesicles found in various cell types, including Wharton’s jelly mesenchymal stem cells, play a crucial role in intercellular communication and regulation. Their use as a cell-free nanotechnology and drug delivery system has attracted attention. Triple-negative breast cancer (TNBC) is a major global health problem and is characterized by a high mortality rate. This study investigates the potential of Wharton’s Jelly mesenchymal stem cell-derived exosomes (WJ-Exo) as carriers of S3I-201 and their effects on STAT3 expression in breast cancer cell lines, and evaluates whether these exosomes can enhance the anti-tumor effect of S3I-201.

Methods

The filtered WJ-Exos were analyzed by Transmission Electron Microscopy (TEM), Scanning electron microscopy (SEM), Dynamic Light Scattering (DLS), flow cytometry, and Western blotting. These exosomes were then used for loading with S3I-201, resulting in the nano-formulation WJ-Exo(S3I-201). The effect of WJ-Exo(S3I-201) on 4T1 cancer cells was investigated in vitro using MTT assay, flow cytometry, wound healing assay, Western blotting and Quantitative Real-Time Polymerase chain reaction (qPCR) analysis. Finally, the therapeutic efficacy of the nano-formulation was investigated in vivo using a tumor-bearing mouse model.

Results

In vitro experiments showed that co-incubation of 4T1 cells with the nano-formulation resulted in a significant reduction in p-STAT3 levels, induction of apoptosis, modulation of Bcl-2, Bax and caspase-3 protein and gene expression, and inhibition of migration. In vivo, treatment of tumor-bearing mice with WJ-Exo(S3I-201) showed a strong antitumor effect that exceeded the efficacy observed in the S3I-201 group.

Conclusion

Our results demonstrate that WJ-Exo is an effective carrier for targeting S3I-201 to tumor cells and enhances the therapeutic efficacy of S3I-201 in tumor-bearing mice.
Associations of daily eating frequency and nighttime fasting duration with biological aging in National Health and Nutrition Examination Survey (NHANES) 2003–2010 and 2015–2018
Authors: Wang Xuanyang , Zhang Jia , Xu Xiaoqing , Pan Sijia , Cheng Licheng , Dang Keke , Qi Xiang , Li Ying
Published: September 2024

Background

Information on the influences of daily eating frequency (DEF) and nighttime fasting duration (NFD) on biological aging is minimal. Our study investigated the potential associations of DEF and NFD with accelerated aging.

Methods

Out of 24212 participants in NHANES 2003–2010 and 2015–2018, 4 predicted age metrics [homeostatic dysregulation (HD), Klemera–Doubal method (KDM), phenoAge (PA), and allostatic load (AL)] were computed based on 12 blood chemistry parameters. Utilizing 24-h dietary recall, DEF was measured by the frequency of eating occurrences, while NFD was determined by assessing the timing of the initial and final meals throughout the day. Weighted multivariate linear regression models and restricted cubic spline (RCS) were utilized to examine the associations.

Results

Compared to DEF of ≤ 3.0 times, subjects with DEF ≥ 4.6 times demonstrated lower KDM residual [β: -0.57, 95% confidence-interval (CI): (-0.97, -0.17)] and PA residual [β: -0.47, 95% CI: (-0.69, -0.25)]. In comparison to NFD between 10.1 and 12.0 h, individuals with NFD ≤ 10.0 h were at higher HD [β: 0.03, 95% CI: (0.01, 0.04)], KDM residual [β: 0.34, 95% CI: (0.05, 0.63)], and PA residual [β: 0.38, 95% CI: (0.18, 0.57)]. Likewise, those with NFD ≥ 14.1 h also had higher HD [β: 0.02, 95% CI: (0.01, 0.04)] and KDM residual [β: 0.33, 95% CI: (0.03, 0.62)]. The results were confirmed by the dose–response relationships of DEF and NFD with predicted age metrics. Lactate dehydrogenase (LDH) and globulin (Glo) were acknowledged as implicated in and mediating the relationships.

Conclusions

DEF below 3.0 times and NFD less than 10.0 or more than 14.1 h were independently associated with higher predicted age metrics.
Socioecologies in shaping migrants and refugee youths’ sexual and reproductive health and rights: a participatory action research study
Authors: Aibangbee Michaels , Micheal Sowbhagya , Liamputtong Pranee , Pithavadian Rashmi , Hossain Syeda Zakia , Mpofu Elias , Dune Tinashe
Published: September 2024

Objective

This study explores socioecological factors facilitating the sexual and reproductive health and rights (SRHR) experiences of migrant and refugee youth (MRY) in Greater Western Sydney, Australia. MRY may be at higher risk for poorer SRH outcomes due to cultural, linguistic, and systemic barriers.

Methods

Using participatory action research, 17 focus groups were conducted with 87 MRY aged 15–29 from diverse cultural backgrounds. Data were analysed thematically, using socioecological framework.

Results

Key facilitators of MRY's SRHR were identified at the microsystem and exosystem levels, including (1) Peer dynamics and support, with friends serving as trusted confidants and sources of advice; (2) Safety and contraceptive choices, highlighting the importance of access to contraception and STI prevention; and (3) Digital platforms for SRHR information access, with online resources filling knowledge gaps.

Conclusion

Findings suggest the need for SRHR interventions to leverage peer support networks, expand access to contraceptive options, and develop culturally appropriate digital resources for MRY. Further research is needed to identify and enhance facilitators across all socioecological levels to comprehensively support MRY's SRHR needs.
Gynecological violence and its resonance in female gynaecologist–client interactions
Authors: Sherafat Shamim
Published: September 2024

Aim

Women must seek regular gynecological care for their checkups, childbirth, or gynecological diseases. Given the critical responsibility of obstetricians and gynecologists in safeguarding the health and lives of both mother and baby, this profession is highly sensitive and stressful. Structural factors may complicate the relationship between the doctor and client and lead to gynecological violenceA study in Iran sheds light on the violence between female gynecologists and their clients.

Methods

The research is done through semi-structured interviews with clients, residents, and female gynecologists in Iran to examine the lived experiences of both.

Results

Based on the WHO’s definition of gynecological violence and its categories, verbal, physical, and psychological violence, social discrimination, neglect of care, and failure to maintain client confidentiality were the main themes found in gynecological violence in Iran.

Conclusion

The relationship between the gynecologist and the client suffers due to differences in religious and cultural beliefs, as well as the stressful nature of the job. Female gynecologists go through a challenging training course at university and also medical practice, and the significance of maternal mortality contributes to the stressfulness of their job. Working in public hospitals with a high workload and facing conflicts of interest between financial benefits and patient health complicates the relationship between the gynecologist and the client, creating the conditions for violence between them.
The chemical composition of secondary organic aerosols regulates transcriptomic and metabolomic signaling in an epithelial-endothelial in vitro coculture
Authors: Offer Svenja , Di Bucchianico Sebastiano , Czech Hendryk , Pardo Michal , Pantzke Jana , Bisig Christoph , Schneider Eric , Bauer Stefanie , Zimmermann Elias J. , Oeder Sebastian , Hartner Elena , Gröger Thomas , Alsaleh Rasha , Kersch Christian , Ziehm Till , Hohaus Thorsten , Rüger Christopher P. , Schmitz-Spanke Simone , Schnelle-Kreis Jürgen , Sklorz Martin , Kiendler-Scharr Astrid , Rudich Yinon , Zimmermann Ralf
Published: September 2024

Background

The formation of secondary organic aerosols (SOA) by atmospheric oxidation reactions substantially contributes to the burden of fine particulate matter (PM2.5), which has been associated with adverse health effects (e.g., cardiovascular diseases). However, the molecular and cellular effects of atmospheric aging on aerosol toxicity have not been fully elucidated, especially in model systems that enable cell-to-cell signaling.

Methods

In this study, we aimed to elucidate the complexity of atmospheric aerosol toxicology by exposing a coculture model system consisting of an alveolar (A549) and an endothelial (EA.hy926) cell line seeded in a 3D orientation at the air‒liquid interface for 4 h to model aerosols. Simulation of atmospheric aging was performed on volatile biogenic (β-pinene) or anthropogenic (naphthalene) precursors of SOA condensing on soot particles. The similar physical properties for both SOA, but distinct differences in chemical composition (e.g., aromatic compounds, oxidation state, unsaturated carbonyls) enabled to determine specifically induced toxic effects of SOA.

Results

In A549 cells, exposure to naphthalene-derived SOA induced stress-related airway remodeling and an early type I immune response to a greater extent. Transcriptomic analysis of EA.hy926 cells not directly exposed to aerosol and integration with metabolome data indicated generalized systemic effects resulting from the activation of early response genes and the involvement of cardiovascular disease (CVD) -related pathways, such as the intracellular signal transduction pathway (PI3K/AKT) and pathways associated with endothelial dysfunction (iNOS; PDGF). Greater induction following anthropogenic SOA exposure might be causative for the observed secondary genotoxicity.

Conclusion

Our findings revealed that the specific effects of SOA on directly exposed epithelial cells are highly dependent on the chemical identity, whereas non directly exposed endothelial cells exhibit more generalized systemic effects with the activation of early stress response genes and the involvement of CVD-related pathways. However, a greater correlation was made between the exposure to the anthropogenic SOA compared to the biogenic SOA. In summary, our study highlights the importance of chemical aerosol composition and the use of cell systems with cell-to-cell interplay on toxicological outcomes.

Graphical Abstract
Clinical variability of equine asthma phenotypes and analysis of diagnostic steps in phenotype differentiation
Authors: Meiseberg Lia Kristin , Delarocque Julien , de Buhr Nicole , Ohnesorge Bernhard
Published: September 2024

Background

Equine asthma is a common, non-infectious, chronic lung disease that affects up to 80% of the horse population. Strict phenotyping and identification of subclinically asthmatic horses can be challenging. The aim of this study was to describe equine asthma phenotypes (mild, moderate, and severe asthma) defined by BALF cytology and occurrence of clinical signs in a population of privately owned horses and to identify the variables and examination steps with best discriminative potential. The standardised examination protocol included clinical examinations, blood work, airway endoscopy with bronchoalveolar lavage fluid analysis, arterial blood gas analysis and radiography under clinical conditions performed by one veterinarian.

Results

Out of 26 horses, four were diagnosed with mild (subclinical), seven with moderate, and seven with severe asthma based on clinical examination and BALF cytology. Eight horses served as controls. Cough with history of coughing was the strongest variable in phenotype differentiation. Factor analysis revealed an increasing clinical variability with disease severity and an overlapping of clinical presentations between phenotypes. Elevated mast cell (4/4 horses) and neutrophil counts (3/4 horses) in bronchoalveolar lavage cytology differentiated mild asthmatic horses from healthy horses. Moderate and severe asthmatic horses were characterised by clinical signs and neutrophil counts.

Conclusions

The results indicate that medical history, clinical examination and bronchoalveolar lavage cytology are minimum indispensable steps to diagnose equine asthma and that phenotypes are clinically overlapping. A differentiation of three phenotypes without neutrophil and mast cell counts in bronchoalveolar lavage cytology is not sufficient for clinical diagnostics. A comparably exact diagnosis cannot be achieved by relying on alternative examinations used in this study. Screenings of inconspicuous horses with bronchoalveolar lavage can aid in diagnosing subclinically affected animals, however, group size was small, the procedure is invasive and clinical relevance of slightly elevated cells in bronchoalveolar lavage remains unclear. Clinical relevance could not be clarified in this study, since follow-up examinations or lung function testing were not performed.
Eco-friendly electrochemical assay of oxytetracycline and flunixin in their veterinary injections and spiked milk samples
Authors: Trabik Yossra A. , Ayad Miriam F. , Mahmoud Amr M. , Abdullatif Hind A. , Michael Adel M.
Published: September 2024

Two solid-contact electrochemical sensors were developed for detection of each of oxytetracycline HCl (OXY), and the co-formulated non-steroidal anti-inflammatory drug flunixin meglumine (FLU) in veterinary formulations and animal-derived food products. The designed sensors were based on a glassy carbon electrode as the substrate material and high molecular weight polyvinyl chloride (PVC) polymeric ion-sensing membranes doped with multiwalled carbon nanotubes (MWCNTs) to improve the potential stability and minimize signal drift. For determination of OXY, the sensing membrane was modified with potassium tetrakis (4-chlorophenyl) borate (K-TCPB), which was employed as a cation exchanger, and 2-hydroxypropyl-β-cyclodextrin (HP-ßCD), which was used as an ionophore. A linear response within a concentration range of 1 × 10− 6-1 × 10− 2 M with a slope of 59.47 mV/decade over a pH range of 1–5 was recorded. For the first time, two potentiometric electrodes were developed for determination of FLU, where the sensing membrane was modified with tetra dodecyl ammonium chloride (TDDAC) as an anion exchanger. A linear response within a concentration range of 1 × 10− 5-1 × 10− 2 M and a slope of -58.21 mV/decade over a pH range of 6–11 was observed. The suggested sensors were utilized for the selective determination of each drug in pure powder form, in veterinary formulations, and in spiked milk samples, with mean recoveries ranging from 98.50 to 102.10, and without any observed interference. The results acquired by the proposed sensors were statistically analyzed and compared with those acquired by the official methods, and the results showed no significant difference.

Graphical Abstract
Effectiveness and safety of Arecae Semen compounds for patients with depression: a systematic review and meta-analysis
Authors: Lin Tong , Zang Xiaoyu , Chen Yi , Zhao Linhua , Zhang Ying
Published: September 2024

Background

Arecae Semen is a traditional herbal medicine widely used in the medical service and food industry, but in recent years, the carcinogenesis of edible Arecae Semen chewing has aroused comprehensive attention, therefore it is necessary to evaluate its medicinal properties. Increasing evidence has shown that Arecae Semen Compounds (ASC) possess antidepressant ability. This study aimed to evaluate the effectiveness and safety of ASC in the treatment of depression.

Methods

We retrieved articles in eight databases from their inception to May 2024. Randomized controlled trials (RCTs) comparing the effects of ASC alone or combined with routine treatment in patients with depression were identified. The Cochrane risk of bias (ROB) tool (ROB 2) was used for assessing the ROB in the included trials. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to assess the certainty of the evidence for the review outcomes. The outcomes included Hamilton depression rating scale (HAMD) scores, depression-related symptoms, serum dopamine levels, and adverse events. Stata 14.0 was used for data analysis calculating standardized mean difference (SMD) for continuous outcomes and relative risk (RR) for binary outcomes, both with 95% confidence intervals (CI).

Results

Nine RCTs involving 787 patients were included in this review. ASC lowered HAMD scores (SMD − 3.43, 95% CI − 5.24 to − 1.61; I2 = 95.2%, P < 0.001), alleviated depression-related symptoms, increased serum dopamine levels, and reduced the incidence of adverse events slightly (RR 0.18, 95% CI 0.04 to 0.77; I2 = 0, P = 0.775) compared with the control group. Publication bias might account for the asymmetrical presentation of funnel plots. Meta-regression analysis revealed that regarding HAMD scores, there was no significant relationship with duration, sample size, or treatment strategy. The evidence of the outcomes was of very low certainty.

Conclusions

ASC may achieve better therapeutic effects, alleviate depression-related symptoms with a lower incidence of adverse events, and provide a potentially effective and safe complementary therapy for patients with depression. However, the evidence is very uncertain so further researches are required to validate our results and explore clinical implications of Arecae Semen in depth.

Systematic review registration

PROSPERO CRD42022361150.
The relationship between food insecurity, purchasing patterns and perceptions of the food environment in urban slums in Ibadan, Nigeria
Authors: Ilori Temitope , Christofides Nicola , Baldwin-Ragaven Laurel
Published: September 2024

Background

Rapid urbanisation without concomitant infrastructure development has led to the creation of urban slums throughout sub-Saharan Africa. People living in urban slums are particularly vulnerable to food insecurity due to the lack of physical and economic accessibility to food. Hence, it is important to explore how vulnerable groups living in slums interact with the food environment. This study assessed the relationships between food insecurity, including restrictive coping strategies, food purchasing patterns and perceptions about the food environment among dwellers of selected urban slums in Ibadan, Nigeria.

Methods

This community-based cross-sectional study was conducted with people responsible for food procurement from 590 randomly selected households in two urban slums in Ibadan. Food insecurity and restrictive coping strategies were assessed using the Household Food Insecurity Access Scale and the Coping Strategy Index, respectively. We examined purchasing patterns of participants by assessing the procurement of household foodstuffs in different categories, as well as by vendor type. Participants’ perceptions of the food environment were derived through a five-item composite score measuring food availability, affordability and quality. Chi-square tests and logistic regression models analysed associations between food insecurity, purchasing patterns and perceptions of the food environment.

Results

The prevalence of food insecurity in the sample was 88%, with 40.2% of the households experiencing severe food insecurity. Nearly a third (32.5%) of the households used restrictive coping strategies such as limiting the size of food portions at mealtimes, while 28.8% reduced the frequency of their daily meals. Participants purchased food multiple times a week, primarily from formal and informal food markets rather than from wholesalers and supermarkets. Only a few households grew food or had livestock (3.2%). Food insecure households had a lower perceived access to the food environment, with an approximate 10% increase in access score per one-unit decrease in food insecurity (AOR = 0.90, 95% CI: 0.84, 0.96). The most procured foods among all households were fish (72.5%), bread (60.3%), rice (56.3%), yam and cassava flours (50.2%). Food-secure households procured fruit, dairy and vegetable proteins more frequently.

Conclusion

Food insecurity remains a serious public health challenge in the urban slums of Ibadan. Perceptions of greater access to the food environment was associated with increasing food security. Interventions should focus on creating more robust social and financial protections, with efforts to improve livelihoods to ensure food security among urban slum-dwellers.
PARP-1 negatively regulates nucleolar protein pool and mitochondrial activity: a cell protective mechanism
Authors: Ghorai Atanu , Saha Soumajit , Rao Basuthkar J.
Published: September 2024

Background

Poly(ADP-ribose) polymerase-1 (PARP-1) is a pan nuclear protein that utilizes NAD+ as a substrate for poly(ADP-ribosyl)ation reaction (PARylation), resulting in both auto-modification and the modification of its accepter proteins. Earlier reports suggested that several nucleolar proteins interact and colocalize with PARP-1, leading to their PARylation. However, whether PARP-1 has any role in nucleolar biogenesis and the functional relevance of such a role is still obscure.

Results

Using PARP-1 depleted cells, we investigated the function of PARP-1 in maintaining the nucleolar morphology and protein levels under normal physiological conditions. Our results revealed that several nucleolar proteins like nucleolin, fibrillarin, and nucleophosmin get up-regulated when PARP-1 is depleted. Additionally, in line with the higher accumulation of nucleolin, stably depleted PARP-1 cells show lower activation of caspase-3, lesser annexin-V staining, and reduced accumulation of AIF in the nucleus upon induction of oxidative stress. Concurrently, PARP-1 silenced cells showed higher mitochondrial oxidative phosphorylation and more fragmented and intermediate mitochondria than the parental counterpart, suggesting higher metabolic activity for better survival.

Conclusion

Based on our findings, we demonstrate that PARP-1 may have a role in regulating nucleolar protein levels and mitochondrial activity, thus maintaining the homeostasis between cell protective and cell death pathways, and such cell-protective mechanism could be implicated as the priming state of a pre-cancerous condition or tumour dormancy.
Glutamine metabolism-related genes predict the prognostic risk of acute myeloid leukemia and stratify patients by subtype analysis
Authors: Zhou Jie , Zhang Na , Zuo Yan , Xu Feng , Cheng Lihua , Fu Yuanyuan , Yang Fudong , Shu Min , Zhou Mi , Zou Wenting , Zhang Shengming
Published: September 2024

Background

Acute myeloid leukemia (AML) is a genetically heterogeneous disease in which glutamine (Gln) contributes to AML progression. Therefore, this study aimed to identify potential prognostic biomarkers for AML based on Gln metabolism-related genes.

Methods

Gln-related genes that were differentially expressed between Cancer Genome Atlas-based AML and normal samples were analyzed using the limma package. Univariate, least absolute shrinkage, selection operators, and stepwise Cox regression analyses were used to identify prognostic signatures. Risk score-based prognostic and nomogram models were constructed to predict the prognostic risk of AML. Subsequently, consistent cluster analysis was performed to stratify patients into different subtypes, and subtype-related module genes were screened using weighted gene co-expression network analysis.

Results

Through a series of regression analyses, HGF, ANGPTL3, MB, F2, CALR, EIF4EBP1, EPHX1, and PDHA1 were identified as potential prognostic biomarkers of AML. Prognostic and nomogram models constructed based on these genes could significantly differentiate between high- and low-risk AML with high predictive accuracy. The eight-signature also stratified patients with AML into two subtypes, among which Cluster 2 was prone to a high risk of AML prognosis. These two clusters exhibited different immune profiles. Of the subtype-related module genes, the HOXA and HOXB family genes may be genetic features of AML subtypes.

Conclusion

Eight Gln metabolism-related genes were identified as potential biomarkers of AML to predict prognostic risk. The molecular subtypes clustered by these genes enabled prognostic risk stratification.
Proteomics of blood extracellular vesicles in inflammatory respiratory diseases for biomarker discovery and new insights into pathophysiology
Authors: Kawasaki Takahiro , Takeda Yoshito , Kumanogoh Atsushi
Published: September 2024

Background

Inflammatory respiratory diseases, such as interstitial lung disease (ILD), bronchial asthma (BA), chronic obstructive pulmonary disease (COPD), and respiratory infections, remain significant global health concerns owing to their chronic and severe nature. Emerging as a valuable resource, blood extracellular vesicles (EVs) offer insights into disease pathophysiology and biomarker discovery in these conditions.

Main body

This review explores the advancements in blood EV proteomics for inflammatory respiratory diseases, highlighting their potential as non-invasive diagnostic and prognostic tools. Blood EVs offer advantages over traditional serum or plasma samples. Proteomic analyses of blood EVs have revealed numerous biomarkers that can be used to stratify patients, predict disease progression, and identify candidate therapeutic targets. Blood EV proteomics has identified proteins associated with progressive fibrosis in ILD, offering new avenues of treatment. In BA, eosinophil-derived EVs harbor biomarkers crucial for managing eosinophilic inflammation. Research on COPD has also identified proteins that correlate with lung function. Moreover, EVs play a critical role in respiratory infections such as COVID-19, and disease-associated proteins are encapsulated. Thus, proteomic studies have identified key molecules involved in disease severity and immune responses, underscoring their role in monitoring and guiding therapy.

Conclusion

This review highlights the potential of blood EV proteomics as a non-invasive diagnostic and prognostic tool for inflammatory respiratory diseases, providing a promising avenue for improved patient management and therapeutic development.
Hydroxytyrosol in cancer research: recent and historical insights on discoveries and mechanisms of action
Authors: Kumar Ajay , Singh Brahmjot , Paul Kapil , Bakshi Palak , Bajaj Payal , Kumar Manoj , Dhiman Sukhvinder , Jasrotia Shivam , Kumar Parveen , Dutta Ranjan
Published: September 2024

Background

Cancer is a persistent global health challenge, demanding continuous exploration of innovative therapeutic strategies. Hydroxytyrosol (HT), derived from olive oil, has garnered attention for its potent antioxidant and anti-inflammatory properties, revitalizing interest due to recent breakthroughs in comprehending its intricate anticancer mechanisms.

Main Body

This review conducts a detailed analysis of hydroxytyrosol’s molecular mechanisms in cancer. Delve into the complex pathways and processes underlying its anticancer properties, including its impact on critical cellular events such as inhibiting cancer cell growth, proliferation, metastasis, and apoptosis. We meticulously evaluate HT efficacy and safety through scrutiny of preclinical and clinical studies. Additionally, we explore the potential synergistic effects of combining HT with conventional cancer therapies to improve treatment outcomes while reducing side effects, offering a comprehensive approach to cancer management.

Conclusion

This review stands as a valuable resource for researchers, clinicians, and policymakers, providing profound insights into HT potent anticancer activity at the molecular level. It underscores the immense potential of natural compounds in the intricate realm of cancer management and highlights the urgent need for further research to translate these discoveries into effective clinical applications. Ultimately, it fosters the development of targeted and personalized therapeutic approaches, reigniting hope in the ongoing battle against cancer and enhancing the quality of life for those afflicted by this relentless disease.
Effect of morningness-eveningness chronotype on academic performance of undergraduate students
Authors: Imam Haider , Singla Deepika , Basista Ruchi
Published: September 2024

Background

Circadian rhythms are crucial for physiological functioning, and they vary among people. There are three distinct chronotypes: morning, evening, and neither type. Morning types experience their highest level of activation during the early part of the day and tend to be more conscientious and focused on achieving their goals. Evening types, on the other hand, reach their peak performance during the latter portion of the day and exhibit a higher level of intelligence. University class schedules may occasionally clash with evening-type individuals’ circadian preferences, potentially impacting their academic performance in comparison to their morning-type peers. Therefore, this study was done to investigate if morningness-eveningness can affect college students’ academic performance as sleeping late or sleep deprivation can lead to disease in the young population.

Materials and methods

A sample of 100 collegiate students aged 18–30 years were recruited via convenience sampling from Jamia Hamdard, Delhi, and informed consent was obtained from the subjects. The morningness-eveningness questionnaire (MEQ) was used to assess students’ chronotype, and the mean of the last three academic years percentage was used to assess the academic performance of the students.

Results

The total academic performance score was better in the morning category (75.53 ± 7.28) as compared to the evening (66.42 ± 10.08) and intermediate (73.72 ± 6.46) categories. There was a low degree of positive correlation between total academic performance and TMEQ (total morning-evening questionnaire) score (ρ = 0.204).

Conclusion

The academic performance of morning chronotype students was better than that of evening chronotype students.
Randomized Phase III SIERRA Trial of
131
I-Apamistamab Before Allogeneic Hematopoietic Cell Transplantation Versus Conventional Care for Relapsed/Refractory AML
Authors: Gyurkocza Boglarka , Nath Rajneesh , Seropian Stuart , Choe Hannah , Litzow Mark R. , Abboud Camille , Koshy Nebu , Stiff Patrick , Tomlinson Benjamin , Abhyankar Sunil , Foran James , Hari Parameswaran , Chen George , Al-Kadhimi Zaid , Kebriaei Partow , Sabloff Mitchell , Orozco Johnnie J. , Jamieson Katarzyna , Silverman Margarida , Van Besien Koen , Schuster Michael , Law Arjun Datt , Larkin Karilyn , Pandit-Taskar Neeta , Rowley Scott D. , Munshi Pashna , Cook Rachel , Levy Moshe Y. , Lazarus Hillard M. , Sandmaier Brenda M. , Pagel John M. , Reddy Vijay , MacDougall James , McNamara Kathleen , Spross Jennifer , Haeuber Elaina , Vusirikala Madhuri , Nahar Akash , Desai Avinash , Giralt Sergio
Published: September 2024

PURPOSE

Older patients with relapsed or refractory AML (RR AML) have dismal prognoses without allogeneic hematopoietic cell transplantation (alloHCT). SIERRA compared a targeted pretransplant regimen involving the anti-CD45 radioconjugate
131
I-apamistamab with conventional care.

METHODS

SIERRA (ClinicalTrials.gov identifier:
NCT02665065
) was a phase III open-label trial. Patients age ≥55 years with active RR AML were randomly assigned 1:1 to either an
131
I-apamistamab–led regimen before alloHCT or conventional care followed by alloHCT if initial complete remission (CR)/CR with incomplete platelet recovery (CRp) occurred. Initial response was assessed 28-56 days after alloHCT in the
131
I-apamistamab group and 28-42 days after salvage chemotherapy initiation; patients without CR/CRp or with AML progression could cross over to receive
131
I-apamistamab followed by alloHCT. The primary end point was durable complete remission (dCR) lasting 180 days after initial CR/CRp. Secondary end points were overall survival (OS) and event-free survival (EFS), assessed hierarchically in the intention-to-treat (ITT) population.

RESULTS

The ITT population included 153 patients (
131
I-apamistamab [n = 76]; conventional care [n = 77]). In total, 44/77 conventional care arm patients crossed over and 40/77 (52%) received
131
I-apamistamab and alloHCT, with six patients (13.6%) experiencing a dCR. In the ITT population, the dCR rate was significantly higher with
131
I-apamistamab (17.1% [95% CI, 9.4 to 27.5]) than conventional care (0% [95% CI, 0 to 4.7];
P
< .0001). The OS hazard ratio (HR) was 0.99 (95% CI, 0.70 to 1.41;
P
= .96), and the EFS HR was 0.23 (95% CI, 0.15 to 0.34), with HR <1 favoring
131
I-apamistamab. Grade ≥3 treatment-related adverse events occurred in 59.7% and 59.2% of the
131
I-apamistamab and conventional care groups, respectively.

CONCLUSION

The
131
I-apamistamab–led regimen was associated with a higher dCR rate than conventional care in older patients with RR AML.
131
I-apamistamab was well tolerated and could address an unmet need in this population.
Ups and downs of fossorial life: migration restlessness and geotaxis may explain overwintering emergence in the spotted salamander
Authors: Giacometti Danilo , Moldowan Patrick D. , Tattersall Glenn J.
Published: September 2024

To decide whether to remain underground or to emerge from overwintering, fossorial ectotherms simultaneously process environmental, gravitational and circannual migratory cues. Here, we provide an experimental framework to study the behaviour of fossorial ectotherms during soil temperature inversion – a phenomenon that marks the transition between winter and spring – based on three non-mutually exclusive hypotheses (thermoregulation, negative geotaxis and migration restlessness). Using a vertical thermal gradient, we evaluated how temperature selection (Tsel), activity and vertical position selection differed under simulated soil temperature inversion (contrasting the active versus overwintering thermal gradients) in the spotted salamander (Ambystoma maculatum). Salamanders had different Tsel and activity levels between gradients, but selected similar heights regardless of thermal gradient orientation. Negative geotaxis may explain responses to changes in vertical thermal gradient orientation, with migratory restlessness contributing to differences in activity levels. Ultimately, our work should benefit those who aim to better understand the biology of fossorial ectotherms.
Effects of Cannabidiol Ingestion on Thermoregulatory and Inflammatory Responses to Treadmill Exercise in the Heat in Recreationally Active Males
Authors: JOHNSON DRUSUS A. , CABLE THOMAS G. , FUNNELL MARK P. , PEDEN DONALD L. , THORLEY JOSH , FERREIRA DA CUNHA MAFALDA , REYNOLDS KIRSTY M. , HARRIS LUKE , WOOD MATT , CHAVEZ-O’REILLY TOM , CARRINGTON JOE , BAILEY STEPHEN J. , CLIFFORD TOM , HEANEY LIAM M. , JAMES LEWIS J.
Published: September 2024

Purpose

Exertional heat stress can induce systemic endotoxin exposure and a proinflammatory cascade, likely impairing thermoregulation. Cannabidiol (CBD) is protective in preclinical models of tissue ischemia and inflammation. Therefore, this study examined the effects of CBD ingestion on exercise-induced thermoregulatory and inflammatory responses.

Methods

In a randomized, double-blinded study, 13 active males (age 25 ± 5 yr; peak oxygen uptake (V̇O2peak) 50.4 ± 3.2 mL·kg−1·min−1) ingested 298 mg CBD or placebo 105 min before 1 h treadmill exercise (60%–65% V̇O2peak) in 32°C and 50% relative humidity. Core temperature, skin temperature, heart rate, subjective outcomes, and sweat loss were assessed during/after exercise. Plasma osmolality, plasma volume changes, and plasma markers of intestinal damage (I-FABP), monocyte activation (CD14), and inflammatory cytokine responses (IL-6, IL-8, and TNF-α) were assessed at baseline, pre-exercise, and 20 and 90 min post-exercise.

Results

Core temperature (∆ 1.69°C ± 0.48°C (CBD) and 1.79°C ± 0.53°C (Placebo)) and I-FABP increased during exercise, with no differences between conditions (P > 0.050). Mean (95% confidence interval) CD14 was 1776 (463 to 3090) pg·mL−1 greater 90 min post-exercise in placebo (P = 0.049). Median (interquartile range) peak IL-6 concentration was −0.8 (−1.1 to −0.3) pg·mL−1 less in CBD (P = 0.050), whereas the between-condition difference in IL-6 area under curve was −113 (−172 to 27) (pg·mL−1)·270 min (P = 0.054).

Conclusions

CBD did not affect thermoregulation during exertional heat stress but appeared to elicit minor immunosuppressive effects, reducing CD14 and IL-6 responses, warranting investigation in humans under more severe heat strain and other proinflammatory scenarios.
État des lieux de l’apprentissage des langues étrangères en ligne focalisé sur le français langue étrangère et la didactique des langues dans l’univers virtuel
Authors: Τσιγάρα Παναγιώτα
Published: September 2024

Αυτή η εργασία στοχεύει στον απολογισμό της τρέχουσας κατάστασης της διαδικτυακής μάθησης σε τρεις ευρωπαϊκές χώρες, τη Γερμανία, τη Γαλλία και την Ελλάδα, από μια συγκριτική σκοπιά κατά τη διάρκεια της ερευνητικής περιόδου που εκτείνεται μεταξύ Οκτωβρίου 2011 και Μαρτίου 2015. Η μελέτη επικεντρώνεται στα γαλλικά ως ξένη γλώσσα και την επιστήμη της διδασκαλίας της γλώσσας στο εικονικό σύμπαν και ρίχνει φως στις εκπαιδευτικές και τεχνικές πτυχές αυτού του μοντέλου κατάρτισης. Ένας από τους κύριους σκοπούς του είναι να εξετάσει τη θέση της ηλεκτρονικής μάθησης στις χώρες που μελετήθηκαν προκειμένου να δούμε τι αντίκτυπο μπορούν να έχουν οι διαφορές τους στην κοινωνικοοικονομική κατάσταση και το πολιτιστικό και εκπαιδευτικό πλαίσιο στην εκμάθηση γλωσσών, τη διδακτική της εξ αποστάσεως εκπαίδευσης (FAD) και τις προοπτικές του. Η μικτή μέθοδος έρευνας (ποιοτική και ποσοτική) υιοθετείται με την ανάλυση βάσεων δεδομένων στον τομέα της διδασκαλίας γλωσσών και διεθνών περιοδικών που σχετίζονται με την εξ αποστάσεως εκπαίδευση. Η χρήση ερωτηματολογίων συμπληρώνει την έρευνα που στοχεύει στον εντοπισμό και την ανάλυση των αναγκών FAD*, τον εντοπισμό λόγων που ενθαρρύνουν ή αποθαρρύνουν το κοινό να συμμετάσχει σε ένα διαδικτυακό μάθημα και προτείνει διορθωτικά μέτρα για να προχωρήσει περαιτέρω. Στην έρευνα συμμετείχαν 337 άτομα. Η μελέτη αυτή επιβεβαιώνει ότι σε όλες τις χώρες που μελετήθηκαν, ανεξάρτητα από τους τομείς και τα επίπεδα εκπαίδευσης, η προσφορά ηλεκτρονικών μαθημάτων διευρύνεται συνεχώς. Ωστόσο, υπάρχουν παράμετροι που επιβραδύνουν σημαντικά την ανάπτυξη του πεδίου. Από τους πιο καθοριστικούς, είναι το ζήτημα της κατάρτισης του διδακτικού προσωπικού, παράμετρος που συχνά υποτιμάται από τους υπεύθυνους προγραμμάτων καθιστώντας την ανάγκη ενσωμάτωσης ενός σχετικού αντικειμένου στο πρόγραμμα σπουδών των τμημάτων των μελλοντικών καθηγητών ξένων γλωσσών καίρια.
Is the typical stage of Penicillus capitatus Lamarck (Bryopsidales, Halimedaceae) a possible indicator of climate warming?
Authors: PAGANA ILARIA , PUGLIA GIUSEPPE DIEGO , MARLETTA GIULIANA , ALONGI GIUSEPPINA
Published: September 2024

In this study, through morphological and molecular analysis approaches, we documented the presence of the typical stage (adult stage) of Penicillus capitatus during the coldest seasons of the year, typically periods when this form had never been reported in the Mediterranean. Indeed, the typical stage is common throughout the year in the western Atlantic (native range of the species), whereas it is rare in the Mediterranean, where the Espera stage (juvenile stage) is the main stage. To date, in the Mediterranean, the adult stage has been found only in the warmer months of the year. Therefore, the observation of the typical stage in the Mediterranean Sea during the cold season might suggest a general increase in the seawater temperature in this basin, rendering this stage of P. capitatus a potential climate bioindicator. Furthermore, owing to the molecular analysis methods adopted, it was possible to assess the relationships between the Mediterranean and Atlantic populations of this species.
Opportunistic predatory feeding behaviour of Munida intermedia A. Milne-Edwards & Bouvier, 1899 targeting juveniles of Lepidopus caudatus (Euphrasen, 1788) in the north-western Mediterranean Sea
Authors: GIUSTI MICHELA , ANGIOLILLO MICHELA , CARO ANTHONY , TUNESI LEONARDO
Published: September 2024

The genus Munida, inhabits various marine habitats and exhibits versatile feeding behaviour. This study explored the behavioural patterns of Munida intermedia, shedding light on its opportunistic behaviour and competitive interactions within its ecological niche. In 2018, during an investigation using a remotely operated vehicle (ROV), carried out on the Méjean shoal (north-western Mediterranean Sea), at 397 m depth, specimens were observed engaging in opportunistic predatory feeding, targeting juveniles of the bathypelagic silver scabbardfish Lepidopus caudatus. Our findings underscore the dynamic nature of M. intermedia feeding habits and the significant role of competitive interactions within its habitat, highlighting the role of video technology in capturing real-time information.
Endogenous Merger Decisions Among Competitors: Impact of Limited Capacity and Loyal Segments
Authors: Wang Derui , Wu Xiaole , Tang Christopher S. , Dai Yue
Published: September 2024

We study endogenous merger decisions among three competing firms with asymmetric capacity: one large firm has ample capacity, and two small firms have limited capacity. Each firm can either operate independently or merge with another firm. Because of antitrust laws, all three firms merging is not permitted. When two firms merge, the merged entity and the remaining independent firm use the resulting capacity to capture their own “loyal buyers” and compete in price for price-sensitive “disloyal switchers.” We first consider a base model in which the size of loyal buyers for different firms is symmetric. We find that, in equilibrium, either there is no merger or the large firm will merge with a small firm as a “mixed merger.” We explain how this equilibrium structure is driven by the mergers’ impacts on market competition and firms’ pricing aggressiveness. Specifically, the mixed merger that can most effectively reduce price competition is the equilibrium under relatively competitive market conditions (i.e., the size of loyal buyers is small and capacity is large but limited). We also extend to the case with asymmetric size of loyal segments and show that two small firms merging (“small merger” structure) can be the equilibrium structure when the large firm has a much larger loyal segment than the small firms and the small firms’ capacity is sufficiently large. The impacts of mergers on social welfare and consumer surplus provide practical implications from the antitrust perspective. The antitrust agencies can approve a mixed merger to improve social welfare under certain conditions, but if the agencies pay more attention to consumer surplus, then mixed mergers should not be permitted. Small mergers, though sometimes not the equilibrium structures, can improve social welfare and consumer surplus. In such cases, the government can appropriately promote mergers that are beneficial for society and/or consumers by adopting some restrictive measures or offering incentives.

This paper was accepted by Jeannette Song, operations management.

Funding: The work of D. Wang was supported by the National Natural Science Foundation of China [Grant 72401275]; the work of X. Wu was supported by the National Natural Science Foundation of China [Grants 72025102, 72293560/72293565].

Supplemental Material: The online appendix is available at https://doi.org/10.1287/mnsc.2022.01943 .
Selective serotonin reuptake inhibitors and solitary rectal ulcer syndrome: a bloody relationship
Authors: Moussallem Nicolas , Haddad Gaelle-Christie , Sbeih Sergio , Karam Karam , Fiani Elias
Published: September 2024

Introduction: Solitary rectal ulcer syndrome (SURS) is a poorly understood and uncommon benign disorder of the lower gastrointestinal tract. It presents with various symptoms, often misinterpreted as inflammatory bowel disease. To date, there is no association between the use of selective serotonin reuptake inhibitors (SSRIs) and SURS. Case description: A 29-year-old male on paroxetine for six months and with a non-contributory surgical history presented to the clinic due to three months of haematochezia, abdominal pain and mucoid discharge. Physical examination and a review of systems were unremarkable; a colonoscopy demonstrated a suspicious ulcerated lesion in the rectum, which was identified as SURS on biopsy. The patient was advised lifestyle and dietary modifications. In addition, paroxetine was discontinued, and patient was switched to venlafaxine, a serotonin–norepinephrine reuptake inhibitor. Subsequently, the patient’s symptoms resolved gradually, and he did not report any signs of recurrence on follow-up. Conclusion: Literature confirms that SSRIs can increase the occurrence of GI ulceration yet focuses specifically on upper gastrointestinal bleeding rather than rectal bleeding. This finding raises the need for further research.