bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutrophil elastase as a versatile cleavage enzyme for activation of αvβ3 integrin-targeted small molecule drug conjugates with different payload classes in the tumor microenvironment
Authors: Rebstock Anne-Sophie , Wiedmann Mareike , Stelte-Ludwig Beatrix , Wong Harvey , Johnson Amy J. , Izumi Raquel , Hamdy Ahmed , Lerchen Hans-Georg 
Published: March 2024

Introduction: The development of bioconjugates for the targeted delivery of anticancer agents is gaining momentum after recent success of antibody drug conjugates (ADCs) in the clinic. Smaller format conjugates may have several advantages including better tumor penetration; however, cellular uptake and trafficking may be substantially different from ADCs. To fully leverage the potential of small molecule drug conjugates (SMDCs) with potent binding molecules mediating tumor homing, novel linker chemistries susceptible for efficient extracellular activation and payload release in the tumor microenvironment (TME) need to be explored.Methods: We designed a novel class of SMDCs, which target αvβ3 integrins for tumor homing and are cleaved by neutrophil elastase (NE), a serine protease active in the TME. A peptidomimetic αvβ3 ligand was attached via optimized linkers composed of substrate peptide sequences of NE connected to different functional groups of various payload classes, such as camptothecins, monomethyl auristatin E, kinesin spindle protein inhibitors (KSPi) and cyclin-dependent kinase 9 inhibitors (CDK-9i).Results: NE-mediated cleavage was found compatible with the diverse linker attachments via hindered ester bonds, amide bonds and sulfoximide bonds. Efficient and traceless release of the respective payloads was demonstrated in biochemical assays. The newly designed SMDCs were highly stable in buffer as well as in rat and human plasma. Cytotoxicity of the SMDCs in cancer cell lines was clearly dependent on NE. IC50 values were in the nanomolar or sub-nanomolar range across several cancer cell lines reaching similar potencies as compared to the respective payloads only in the presence of NE. In vivo pharmacokinetics evaluating SMDC and free payload exposures in rat and particularly the robust efficacy with good tolerability in triple negative breast and small cell lung cancer murine models demonstrate the utility of this approach for selective delivery of payloads to the tumor.Discussion: These results highlight the broad scope of potential payloads and suitable conjugation chemistries paving the way for future SMDCs harnessing the safety features of targeted delivery approaches in combination with NE cleavage in the TME.
Anti-neuroinflammatory effect of hydroxytyrosol: a potential strategy for anti-depressant development
Authors: Li Shuaiguang , Shao Huarong , Sun Ting , Guo Xinyan , Zhang Xiaoyuan , Zeng Qingkai , Fang Shaoying , Liu Xiaoyu , Wang Fan , Liu Fei , Ling Peixue 
Published: March 2024

Introduction: Depression is a complex psychiatric disorder with substantial societal impact. While current antidepressants offer moderate efficacy, their adverse effects and limited understanding of depression’s pathophysiology hinder the development of more effective treatments. Amidst this complexity, the role of neuroinflammation, a recognized but poorly understood associate of depression, has gained increasing attention. This study investigates hydroxytyrosol (HT), an olive-derived phenolic antioxidant, for its antidepressant and anti-neuroinflammatory properties based on mitochondrial protection.Methods:In vitro studies on neuronal injury models, the protective effect of HT on mitochondrial ultrastructure from inflammatory damage was investigated in combination with high-resolution imaging of mitochondrial substructures. In animal models, depressive-like behaviors of chronic restraint stress (CRS) mice and chronic unpredictable mild stress (CUMS) rats were examined to investigate the alleviating effects of HT. Targeted metabolomics and RNA-Seq in CUMS rats were used to analyze the potential antidepressant pathways of HT.Results: HT protected mitochondrial ultrastructure from inflammatory damage, thus exerting neuroprotective effects in neuronal injury models. Moreover, HT reduced depressive-like behaviors in mice and rats exposed to CRS and CUMS, respectively. HT’s influence in the CRS model included alleviating hippocampal neuronal damage and modulating cytokine production, mitochondrial dysfunction, and brain-derived neurotrophic factor (BDNF) signaling. Targeted metabolomics in CUMS rats revealed HT’s effect on neurotransmitter levels and tryptophan-kynurenine metabolism. RNA-Seq data underscored HT’s antidepressant mechanism through the BDNF/TrkB signaling pathways, key in nerve fiber functions, myelin formation, microglial differentiation, and neural regeneration.Discussion: The findings underscore HT’s potential as an anti-neuroinflammatory treatment for depression, shedding light on its antidepressant effects and its relevance in nutritional psychiatry. Further investigations are warranted to comprehensively delineate its mechanisms and optimize its clinical application in depression treatment.
Functionality, muscular strength and cardiorespiratory capacity in the elderly: relationships between functional and physical tests according to sex and age
Authors: Toro-Román Víctor , Ferrer-Ramos Pau , Illera-Domínguez Víctor , Pérez-Chirinos Carla , Fernández-Valdés Bruno 
Published: March 2024

Introduction: There are several tests that provide information about physical fitness and functionality in older adults. The aims of this study were: (i) to analyze the differences between sex and age in functional, strength and cardiorespiratory tests; and (ii) to study the correlations between functional, strength and cardiorespiratory tests according to sex and age.Methods: A total of 171 older adults (72.09 ± 13.27 kg; 1.59 ± 0.09 m; 72.72 ± 6.05 years) were divided according to sex (men: n = 63; women: n = 108) and age (≥60 &lt;70: n = 65; ≥70 &lt;80: n = 89; ≥80: n = 18). Anthropometry, body composition, upper limb strength (hand grip; HG), lower limb strength (countermovement jump; CMJ), cardiorespiratory capacity (6 min walking test; 6MWT), timed up and go test (TUG) and Short Physical Performance Battery (SPPB) were assessed.Results: Men showed higher values in CMJ height, HG and expired volume (VE) (p &lt; 0.05). There were no significant differences between sexes in TUG and SPPB. Regarding age, there were significant differences in CMJ, VE and peak oxygen uptake (VO2peak), TUG, gait speed, chair and stand test and SPPB total (p &lt; 0.05). The test times were higher in older people. Regarding correlations, the TUG showed significant correlations in all strength and cardiorespiratory tests, regardless of sex and age. The CMJ correlated more significantly with functional tests compared to HG.Discussion: There were sex and age differences in functional, strength, and cardiorespiratory tests. The execution of quick and low-cost tests such as the CMJ and TUG could provide information on overall physical fitness in older adults.
Biocontrol efficacy of cajeput oil against Anopheles stephensi L. mosquito and its effect on non-target species
Authors: Vivekanandhan Perumal , Alahmadi Tahani Awad , Ansari Mohammad Javed , Subala S. P. 
Published: March 2024

Chemical insecticides are effective at controlling mosquito populations, but their excessive use can pollute the environment and harm non-target organisms. Mosquitoes can also develop resistance to these chemicals over time, which makes long-term mosquito control efforts challenging. In this study, we assessed the phytochemical, biochemical, and insecticidal properties of the chemical constituents of cajeput oil. Results show that Melaleuca cajuputi essential oil may exhibit mosquito larvicidal properties against Anopheles stephensi larvae (second-fourth instar) at 24 h post-treatment. At 24 h post-exposure, the essential oil resulted in a significant decrease in detoxifying enzymes. All of these findings indicate that cajeput oil infects An. stephensi larvae directly affect the immune system, leading to decreased immune function. Cajeput oil significantly affects the second, third, and fourth instar larvae of An. stephensi, according to the bioassay results. Cajeput oil does not induce toxicity in non-target Eudrilus eugeniae earthworm species, as indicated by a histological study of earthworms. Phytochemical screening and GC-MS analysis of the essential oil revealed the presence of several major phytochemicals that contribute to mosquito larvicidal activity. The importance of cajeput oil as an effective candidate for biological control of the malarial vector An. stephensi is supported by this study.
Effects of cell morphology, physiology, biochemistry and CHS genes on four flower colors of Impatiens uliginosa
Authors: Zhao Lu-Qiu , Liu Yang , Huang Qi , Gao Shan , Huang Mei-Juan , Huang Hai-quan 
Published: March 2024

IntroductionFlower color is one of the important ornamental traits in the plants, which plays an active role in attracting pollinators to pollinate plants and reproduce their offspring. The flower color of Impatiens uliginosa is rich, there are four main flower colors in nature: deep red, red, pink, and white. However, it remains unclear whether on four different flower colors mechanism of I. uliginosa.MethodsWe investigate colorimetric measurement, observation of epidermal cells, cellular pH determination, extraction and determination of total anthocyanins and flavonoid, semi-quantitative determination of pigment components, and gene cloning and qRT-PCR of CHS genes to study four flower colors of I. uliginosa.ResultsThe L* and b* values were the highest in white flower, while the a* values were the highest in pink flower. The same shape of epidermal cells was observed in different flower colors, which was all irregular flat polygons, and there were partial lignification. Their cellular pH values were weakly acidic, while the pH values of the deep red flower was the highest and the white flower was the lowest. The highest pigment content of the four flower colors was total anthocyanin content. And malvidin-3-galactosidechloride (C23H25ClO12), cyanidin-3-O-glucoside (C21H21O11) and delphinidin (C15H11O7) were the main pigment components affecting the color of four different flower colors. The anthocyanin synthesis gene IuCHS was expressed in four flowers, and all three copies of it had the highest expression level in pink flower and the lowest expression level in white flower.DiscussionThese results revealed the influence of main internal factors on four different flower colors of I. uliginosa, and provided a basis for further understanding of the intracellular and molecular regulatory mechanisms of flower color variation, and laid a foundation for the improvement of flower color breeding of Impatiens.
Workplace trauma and professional quality of Life in clinical and forensic psychiatry: the CRITIC study
Authors: Bloemendaal Anthony F. T. , Kamperman Astrid M. , Bonebakker Annette E. , Kool N. , Olff M. , Mulder C. L. 
Published: March 2024

BackgroundFrontline staff in psychiatry need to perform at a very high professional level in order to ensure patient and community safety. At the same time they are exposed to high levels of stress and workplace trauma. This may have severe consequences for their professional quality of life. In addition, health care workers in general have higher incidence levels of childhood adversity than the general population. The CRITIC (CRITical Incidents and aggression in Caregivers) Study aims to improve increased understanding of the interaction between personal life history (childhood adversity and benevolence), individual capabilities, exposure to trauma and violence at work and Professional Quality of Life (ProQOL).MethodThe Critic Study is a cross-sectional survey of these aspects in frontline, treatment and administrative staff in clinical and forensic psychiatry. We aim to include 360 participants. Participants will be asked to complete questionnaires on childhood adversity and childhood benevolence (assessing personal life history), professional quality of life, current trauma and violence exposure, current mental health (depression, anxiety and stress), coping, social support, work engagement and resilience. In this study we will examine the moderating role of adverse and benevolent childhood experiences in the association between workplace trauma exposure and professional quality of life. Finally, a theoretical model on the relationships between trauma, stress and coping in the context of professional functioning will be tested using structural equation modelling.DiscussionThe CRITIC study examines which factors influence the complex relationship between childhood adversity and benevolence, and ProQOL in healthcare workers. It also aims to provide insight into the complex relationship between personal life history, individual characteristics, exposure to trauma and violence at work and ProQOL. The results can be used for designing interventions to increase resilience to trauma and to improve professional quality of life among health care professionals.Trial registrationThe CRITIC study has been approved by the Medical Ethical Committee of the Erasmus Medical Centre, under trial registration number NL73417.078.20
Awareness and willingness to use pre-exposure prophylaxis for HIV prevention among men who have sex with men in Rwanda: findings from a web-based survey
Authors: Munyaneza Athanase , Patel Viraj V. , Gutierrez Nataly Rios , Shi Qiuhu , Muhoza Benjamin , Kubwimana Gallican , Ross Jonathan , Nsereko Etienne , Murenzi Gad , Nyirazinyoye Laetitia , Mutesa Leon , Anastos Kathryn , Adedimeji Adebola 
Published: March 2024

IntroductionPre-exposure Prophylaxis (PrEP) is a daily pill aimed at reducing HIV transmission risk when taken as prescribed. It’s highly recommended for high-risk Men who have sex with Men (MSM). This study aimed to assess PrEP awareness and willingness to use it among Rwandan MSM, a critical aspect given PrEP’s proven effectiveness. The findings are expected to inform policy decisions and further advance the implementation of PrEP strategies.MethodsThis is a cross-sectional study design that utilized a web-based survey conducted between April and June 2019 to assess awareness and willingness to use PrEP among sexually active MSM in Rwanda. A snowball sampling technique was used to recruit participants via social media such as WhatsApp and e-mail. Eligibility criteria included being sexually active, aged ≥18 years, self-identifying as MSM, residing in Rwanda, self-reported engagement in receptive or insertive anal sex in the last 12 months, and self-reported HIV-negative serostatus. We assessed two primary outcomes: PrEP awareness (having ever heard of PrEP) and willingness to use PrEP within one month of completing the survey. Multivariable logistic regression was performed to identify participant characteristics associated with PrEP awareness and willingness to use it.ResultsOut of 521 participants, the majority (73%) demonstrated awareness of PrEP. Factors linked to PrEP awareness included residing outside the capital, Kigali, being in the 18–29 age group, having higher education levels, perceiving a benefit from PrEP, and engaging in vaginal sex with a woman while using a condom in the last year. Additionally, 96% of participants expressed a strong willingness to use PrEP.ConclusionRwandan MSM exhibits a high level of PrEP awareness, notably associated with factors like location, age, education, perceived benefits, and condom use. The study also revealed a strong willingness to use PrEP, indicating promising prospects for its adoption among this group. These findings highlight the need for targeted awareness campaigns, personalized interventions, and comprehensive sexual health education to promote PrEP adoption and strengthen HIV prevention efforts among Rwandan MSM.
A pilot study on the global practice of informed consent in paediatric dentistry
Authors: Potgieter Nicoline , Bridge Gemma , Elfrink Marlies , Folayan Morenike Oluwatoyin , Gao Sherry S. , Groisman Sonia , Jawdekar Ashwin , Kemoli Arthur M. , Lim David , Ly Phuong , Mani Shani A. , Masumo Ray , Monteiro Joana , Muasya Marjorie K. , Qureshi Ambrina , Tinanoff Norman 
Published: March 2024

BackgroundConducting oral treatment early in the disease course, is encouraged for better health outcomes. Obtaining informed consent is an essential part of medical practice, protecting the legal rights of patients and guiding the ethical practice of medicine. In practice, consent means different things in different contexts. Silver Diamine Fluoride (SDF) and Silver Fluoride (SF) is becoming popular and cost effective methods to manage carious lesions, however, cause black discolouration of lesions treated. Obtaining informed consent and assent is crucial for any dental treatment—and has specific relevance with SDF/ SF treatments.MethodsThe aim of this paper is to describe informed consent regulations for dental care in a selection of countries, focusing on children and patients with special health care needs. An online survey was shared with a convenience sample of dental professionals from 13 countries. The information was explored and the processes of consent were compared.ResultsFindings suggest that there are variations in terms of informed consent for medical practice. In Tanzania, South Africa, India, Kenya, Malaysia and Brazil age is the determining factor for competence and the ability to give self-consent. In other countries, other factors are considered alongside age. For example, in Singapore, the United Kingdom, and the United States the principle of Gillick Competence is applied. Many countries' laws and regulations do not specify when a dentist may overrule general consent to act in the “best interest” of the patient.ConclusionIt is recommended that it is clarified globally when a dentist may act in the “best interest” of the patient, and that guidance is produced to indicate what constitutes a dental emergency. The insights gathered provide insights on international practice of obtaining informed consent and to identify areas for change, to more efficient and ethical treatment for children and patients with special needs. A larger follow up study is recommended to include more or all countries.
How does the development of rural broadband in China affect agricultural total factor productivity? Evidence from agriculture-related loans
Authors: Li Ying 
Published: March 2024

IntroductionThe construction of digital villages is widely acknowledged as a way to achieve the “dual goals” of high quality of the agricultural and rural economy and common prosperity under the digital China strategy. Studies have explored the socio-economic benefits of different aspects of rural digitization, but few have focused on the productivity role of rural broadband development in the context of the urban-rural broadband divide. The purpose of this paper is to explore the relationship between rural broadband development and agricultural total factor productivity (TFP) and the intrinsic mechanism of action, and to provide empirical evidence on the productivity effect of promoting digital transformation in rural agriculture.MethodsUsing panel data from 31 provinces in China from 2011 to 2020, this paper investigates the impact and mechanism of rural broadband development on agricultural TFP from the perspective of agriculture-related loans by setting up a two-way fixed effects model, a mechanism effects model and a threshold effects model.ResultsThe results find that rural broadband development has a significant role in enhancing agricultural TFP. Heterogeneity analysis indicates that the productivity-enhancing effect of rural broadband development is remarkable only in the central region and the region with higher rural disposable income. Mechanism analysis points out that rural broadband development can increase agricultural TFP by influencing the share of farm-related loans. Threshold analysis further reveals that the role of increasing the share of farm-related loans on agricultural TFP is marked only after rural broadband development reaches a certain level.DiscussionThese findings can provide practical guidance for other developing countries in accelerating the digital transformation of villages and optimizing factor allocation to achieve high-quality agricultural development.
Biliary atresia in preterm infants: a single center experience and review of literature
Authors: Beati Federico , Mosca Antonella , Pietrobattista Andrea , Liccardo Daniela , Ronci Sara , Monti Lidia , Francalanci Paola , Spada Marco , Maggiore Giuseppe , Bagolan Pietro , Fusaro Fabio 
Published: March 2024

IntroductionThe diagnosis of biliary atresia (BA) remains challenging, and there is still uncertainty regarding the optimal time to perform a Kasai portoenterostomy (KPE). Little is known about the difficulties in the diagnosis and outcomes of BA in preterm infants (PBA). This study, which represents the first Italian report of preterm infants with BA, aims to describe a single-center experience of BA in preterm newborns.MethodsWe retrospectively reviewed all infants consecutively diagnosed with BA who underwent a Kasai procedure at the Bambino Gesù Children’s Hospital between January 1998 and December 2021. Prematurity was defined as a gestational age (GA) of &lt;37 weeks. Demographic, laboratory, and histology data were recorded, and the main outcomes considered were clearance of jaundice (COJ), native liver survival, and mortality.ResultsA total of 21 PBA were compared with 117 term BA controls (TBA). The median GA of PBA was 35.1 (32–36.1) weeks, with a mean birth weight of 2,100 (1,897–2,800) g. Age at first presentation was significantly lower in PBA patients: 46 (22–68) vs. 61 (44–72) days; p = 0.02. The median age at KPE was similar between the two groups: 70 days (33 corrected) for PBA vs. 67 in TBA; p = 0.8. At the time of surgery, median serum bilirubin was lower in the PBA group (7.7 vs. 8.6 mg/dl, p = 0.04). Similarly, the median APRi at the time of KPE was lower but not significant in the PBA group: 1.09 vs. 1.16; p = 0.8. No differences were found in terms of COJ between the PBA and TBA groups: n = 9 (43%) vs. 34 (35%); p = 0.2. Overall native liver survival was similar between the two groups: 8.6 (4.8–12.2) for the PBA group vs. 7.6 (5.6–9.5) years for the TBA group with no significant differences; p = 0.45. Post-KPE native liver survival was similar between the two groups: 38% vs. 52% at 5 years for the TBA and PBA groups, respectively;   p = 0.54.ConclusionThe PBA and TBA groups appear to have similar outcomes in terms of COJ, overall native liver survival, and 5-year liver survival. Considering the corrected GA, early KPE is related to lower cholestatic damage. Further multicenter studies are required.