bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine learning models predicting risk of revision or secondary knee injury after anterior cruciate ligament reconstruction demonstrate variable discriminatory and accuracy performance: a systematic review
Authors: Blackman Benjamin , Vivekanantha Prushoth , Mughal Rafay , Pareek Ayoosh , Bozzo Anthony , Samuelsson Kristian , de SA Darren
Published: January 2025

Background

To summarize the statistical performance of machine learning in predicting revision, secondary knee injury, or reoperations following anterior cruciate ligament reconstruction (ACLR), and to provide a general overview of the statistical performance of these models.

Methods

Three online databases (PubMed, MEDLINE, EMBASE) were searched from database inception to February 6, 2024, to identify literature on the use of machine learning to predict revision, secondary knee injury (e.g. anterior cruciate ligament (ACL) or meniscus), or reoperation in ACLR. The authors adhered to the PRISMA and R-AMSTAR guidelines as well as the Cochrane Handbook for Systematic Reviews of Interventions. Demographic data and machine learning specifics were recorded. Model performance was recorded using discrimination, area under the curve (AUC), concordance, calibration, and Brier score. Factors deemed predictive for revision, secondary injury or reoperation were also extracted. The MINORS criteria were used for methodological quality assessment.

Results

Nine studies comprising 125,427 patients with a mean follow-up of 5.82 (0.08–12.3) years were included in this review. Two of nine (22.2%) studies served as external validation analyses. Five (55.6%) studies reported on mean AUC (strongest model range 0.77–0.997). Four (44.4%) studies reported mean concordance (strongest model range: 0.67–0.713). Two studies reported on Brier score, calibration intercept, and calibration slope, with values ranging from 0.10 to 0.18, 0.0051–0.006, and 0.96–0.97 amongst highest performing models, respectively. Four studies reported calibration error, with all four studies demonstrating significant miscalibration at either two or five-year follow-ups amongst 10 of 14 models assessed.

Conclusion

Machine learning models designed to predict the risk of revision or secondary knee injury demonstrate variable discriminatory performance when evaluated with AUC or concordance metrics. Furthermore, there is variable calibration, with several models demonstrating evidence of miscalibration at two or five-year marks. The lack of external validation of existing models limits the generalizability of these findings. Future research should focus on validating current models in addition to developing new multimodal neural networks to improve accuracy and reliability.
Comparison between relining of ill-fitted maxillary complete denture versus CAD/CAM milling of new one regarding patient satisfaction, denture retention and adaptation
Authors: Kamal Maha Nagy Mohamed
Published: January 2025

Purpose

This study aimed to compare different treatment modalities to correct ill-fitted maxillary complete denture either by the conventional relining method or by scanning the relining impression and digitally construct a new denture regarding patient satisfaction, denture retention, and adaptation.

Materials and methods

Twelve edentulous patients suffering from loose maxillary complete dentures were selected, dentures’ borders and fitting surfaces were prepared, and relining impressions were taken, the impressions were scanned and the STL files were used for CAD/CAM milling ( computer aided designing/ computer aided manufacturing) of new maxillary dentures (Group A), then the relining impression went through the conventional laboratory steps to fabricate (Group B) maxillary dentures. Both groups were evaluated regarding patient satisfaction by a specially designed questionnaire, retention values were measured by a digital force gauge at denture insertion appointment and two weeks later, geomagic software was used to evaluate dentures adaptation to oral tissues.

Results

Both groups (A and B) were completely satisfied with their dentures except regarding esthetics, all group A and 50% of group B were satisfied. Both groups showed a statistically significant increase in retention values at the two-week follow-up period compared to those at denture insertion time, with higher values were for group B. Finally, the relined dentures showed better oral tissue adaptation than digitally constructed dentures.

Conclusion

Relined maxillary dentures showed better retention, esthetics, and denture adaptation with lower cost than digitally constructed maxillary dentures which showed acceptable retention and adaptation, with better time and data saving.

Trial registration

Clinical trials number: NCT06366321. With registration date on ClinicalTrials.gov public website: 13/ 4/ 2024.
A novel stable biomimetic adhesive coating for functionalization of orthodontic brackets against bacterial colonization and white spot lesions
Authors: Singer Lamia , Karačić Sabina , Bierbaum Gabriele , Palmer Brianne , Kirschneck Christian , Bourauel Christoph
Published: January 2025

Background

This study aimed to evaluate the efficacy of polydopamine (PDA) functionalization on orthodontic brackets in inhibiting biofilm formation and promoting surface bioactivity to buffer the acidity of caries-causing bacteria around orthodontic brackets and prevent demineralization. The stability of the coating in artificial saliva (AS) and distilled water was evaluated, along with its effect on pH changes in simulated body fluid (SBF) and distilled water.

Methods

Maxillary incisor orthodontic brackets underwent PDA functionalization using a dopamine hydrochloride solution following a specific protocol. Biofilm formation on both control (Br-0) and coated (Br-PDA) brackets was assessed immediately after coating and after two months of aging (Aged Br-PDA) in artificial saliva. The adherent biofilm bacteria on brackets were quantified with colony count assessment and optical density. Surface morphology, Bioactivity, and coating stability were analyzed using Scanning Electron Microscopy (SEM). Coated and uncoated samples were immersed in SBF and deionized water, and pH changes were monitored over 7 days using a pH meter.

Results

PDA-functionalized brackets, both freshly coated (1.08 OD) and aged for two months (1.6 OD), showed significantly reduced biofilm formation compared to non-functionalized control brackets (2.07 OD), with p-value < 0.05. This reduction was confirmed through optical density measurements and colony-forming unit (CFU) counts (1.63E + 06, 4.53E + 07, and 7.56E + 07 respectively, p-value < 0.05). SEM analysis revealed alterations in surface morphology and composition, suggesting enhanced biointeraction in the coated brackets. Stability assessments in artificial saliva and deionized water demonstrated the durability of the coating. pH measurements indicated minimal changes in SBF and water, with PDA-functionalized brackets showing slight alterations.

Conclusions

Our research findings suggest that PDA-functionalized brackets possess promising antimicrobial properties and stability, offering potential applications in orthodontic treatment to mitigate biofilm formation and prevent white spot lesions around orthodontic brackets. Further investigation is required to optimize the coating formulation and explore its long-term efficacy in clinical settings.
A lack of sexual autonomy is associated with increased loneliness in young mothers
Authors: Bunke Chelsea , Keck Tara
Published: January 2025

Background

Loneliness is a significant risk factor for both mental and physical health issues, including depression and increased mortality. Loneliness is reported at higher levels during life transitions, such as the transition to motherhood. Loneliness in mothers has far-reaching detrimental impacts on both mother and child, such as an increased risk of maternal depression and child abuse. Understanding the impact of different risk factors for loneliness, specifically in young mothers, may inform potential interventions for this at-risk group. The aim of this study was to determine whether mothers were lonelier than childfree women, and whether there are different risk factors for loneliness in mothers relative to childfree women, both for gender-associated and established risk factors for loneliness.

Methods

This cross-sectional study included partnered mothers and partnered childfree women between the ages of 20 and 29 from the 2020 Generations and Gender Survey (GGS) in the Republic of Moldova. The De Jong Gierveld Loneliness Scale was used to assess overall, emotional, and social loneliness. A total of 11 potential risk factors were considered, across gender, well-being, relationships, and household status. Depending on the nature of the variables and their distributions, Wilcoxon rank-sum tests or Spearman correlation coefficients were used to assess loneliness risk factors for partnered mothers and childfree women.

Results

Data from 396 mothers and 113 childfree women in the Republic of Moldova were analysed in this study. There was no significant difference between the mean overall, emotional, or social loneliness scores in partnered mothers and childfree women. A lack of sexual autonomy was a risk factor associated with social loneliness in young mothers, but not in childfree women. This was the only gendered risk factor that differed between populations. Other gendered risk factors were not significant for any types of loneliness in either population. There were differences between mothers and childfree women in several established risk factors for loneliness.

Conclusion

Mothers were not lonelier than childfree women in this study, but a lack of sexual autonomy was a risk factor associated with loneliness only in mothers.
Facilitators and barriers affecting the implementation of e-health for chronic respiratory diseases in remote settings: a qualitative evidence synthesis
Authors: Salmi Emil Matias , Basile Francesca Wanda , Khan Faiz Ahmad , Watt Larry , Song Rinn , Bijker Else Margreet
Published: January 2025

Background

Chronic respiratory diseases are important causes of disability and mortality globally. Their incidence may be higher in remote locations where healthcare is limited and risk factors, such as smoking and indoor air pollution, are more prevalent. E-health could overcome some healthcare access obstacles in remote locations, but its utilisation has been limited. An improved understanding of barriers and facilitators to the implementation of e-health in remote locations could aid enhanced application of these approaches.

Methods

We performed a qualitative evidence synthesis to explore factors affecting the successful implementation of e-health interventions in remote locations for patients with chronic respiratory diseases. We searched PubMed, CINAHL, Embase, Web of Science and PsycINFO databases for qualitative and mixed-methods studies. Studies were assessed by two researchers, and 41 studies were included in the synthesis. Quality was assessed via the CASP-tool. Findings were coded with Atlas.ti software and categorised based on an adapted Digital Health Equity Framework.

Results

Nineteen themes were identified across five levels (individual, interpersonal, community, society and technology), with associated facilitators and barriers for implementation. An important facilitator of e-health was its role as a tool to overcome obstacles of distance and to increase access to care and patients’ self-efficacy. Potential barriers included the reduction of in-person interactions and an increased burden of work for healthcare providers. Good quality, usability, adaptability and efficacy of e-health interventions were important for implementation to be successful, as were adaptation to the local setting — including culture and language —and involvement of relevant stakeholders throughout the process.

Conclusions

Several factors affecting the implementation of e-health in remote and rural locations for patients with chronic respiratory disease were identified. Intervention objectives, target population, geographical location, local culture, and available resources should be carefully considered when designing an e-health intervention. These findings can be used to inform the successful design and implementation of future e-health interventions.
Role of extracellular vesicles in the pathogenesis of mosquito-borne flaviviruses that impact public health
Authors: Martínez-Rojas Pedro Pablo , Monroy-Martínez Verónica , Ruiz-Ordaz Blanca H.
Published: January 2025

Mosquito-borne flaviviruses represent a public health challenge due to the high-rate endemic infections, severe clinical outcomes, and the potential risk of emerging global outbreaks. Flavivirus disease pathogenesis converges on cellular factors from vectors and hosts, and their interactions are still unclear. Exosomes and microparticles are extracellular vesicles released from cells that mediate the intercellular communication necessary for maintaining homeostasis; however, they have been shown to be involved in disease establishment and progression. This review focuses on the roles of extracellular vesicles in the pathogenesis of mosquito-borne flavivirus diseases: how they contribute to viral cycle completion, cell-to-cell transmission, and cellular responses such as inflammation, immune suppression, and evasion, as well as their potential use as biomarkers or therapeutics (antiviral or vaccines). We highlight the current findings concerning the functionality of extracellular vesicles in different models of dengue virus, Zika virus, yellow fever virus, Japanese encephalitis virus, and West Nile virus infections and diseases. The available evidence suggests that extracellular vesicles mediate diverse functions between hosts, constituting novel effectors for understanding the pathogenic mechanisms of flaviviral diseases.
Unravelling the outcome of L-glutaminase produced by Streptomyces sp. strain 5 M as an anti-neoplasm activity
Authors: Hassan Mervat G. , El-Sayyad Gharieb S. , Abdel-Monem Mohamed O. , Malash Mohamed N. , Kishk Mona A. , El Awady Mohamed E. , El-khonezy Mohamed I.
Published: January 2025

Background

Actinomycetes are a well-known example of a microbiological origin that may generate a wide variety of chemical structures. As excellent cell factories, these sources are able to manufacture medicines, agrochemicals, and enzymes that are crucial.

Results

In this study, about 34 randomly selected Streptomyces isolates were discovered in soil, sediment, sea water, and other environments. Using a qualitative fast plate assay, they were tested for L-glutaminase production, and nine of them produced a significant amount of pink L-glutamine. Streptomyces sp. strain 5 M was identified by examining the 16S rRNA gene in the promising strain G8. A pH of 7.5, an incubation temperature of 40 °C, and the use of glucose and peptone as the carbon and nitrogen sources, respectively, produced the highest quantities of L-glutaminase. The molecular weight of the isolated L-glutaminase was estimated to be 52 kDa using SDS-PAGE analysis. At pH 7.5 and Temp., 40 °C, the isolated enzyme exhibited its highest levels of stability and activity. The isolated enzyme’s Km and Vmax values were 2.62 mM and 10.20 U/ml, respectively. Strong toxicity against HepG-2, HeLa, and MCF-7 was observed due to the anticancer properties of the isolated L-glutaminase.

Conclusion

Our findings include the discovery of Streptomyces sp. strain 5 M, which yields a free L-glutaminase and maybe a possible applicant for extra pharmacological investigation as an antineoplastic drug.
Significance of siderophore-producing cyanobacteria on enhancing iron uptake potentiality of maize plants grown under iron-deficiency
Authors: Brick Mandees Bakr , Hussein Mervat H. , Mowafy Amr M. , Hamouda Ragaa A. , Ayyad Amr M. , Refaay Dina A.
Published: January 2025

Background

In response to iron deficiency and other environmental stressors, cyanobacteria producing siderophores can help in ameliorating plant stress and enhancing growth physiological and biochemical processes. The objective of this work was to screen the potential of Arthrospira platensis, Pseudanabaena limnetica, Nostoc carneum, and Synechococcus mundulus for siderophore production to select the most promising isolate, then to examine the potentiality of the isolated siderophore in promoting Zea mays seedling growth in an iron-limited environment.

Results

Data of the screening experiment illustrated that Synechococcus mundulus significantly recorded the maximum highest siderophore production (78 ± 2%) while the minimum production was recorded by Nostoc carneum (24.67 ± 0.58%). Therefore, Synechococcus mundulus was chosen for the beneficiary study and the intended agricultural application. Siderophore-type identification tests proved that Synechococcus mundulus produced hydroxamate-type. The response surface approach was successful in optimizing the conditions of siderophore production in Synechococcus mundulus with actual values for maximum biomass (387.11 mg L− 1) and siderophore production (91.84%) higher than the predicted values. The proton nuclear magnetic resonance (1H NMR) analysis data and the Fourier transformer-infrared spectrum analysis (FT-IR) signify the hydroxamate nature of Synechococcus mundulus isolated siderophore. Zea mays seedlings’ growth response in the hydroponic system was significantly stimulated in response to supplementation with Synechococcus mundulus siderophore in the absence of iron compared to plants grown without iron and the positive controls. Additionally, the contents of chlorophyll a, chlorophyll b, carotenoids, total carbohydrates, and total protein were all surpassed in siderophore-treated plants, which is expected due to the increased iron content.

Conclusions

The results introduced in this study highlighted the significant potential of Synechococcus mundulus-derived siderophore in stimulating Zea mays physicochemical growth parameters and iron uptake. Findings of this study present novel visions of cyanobacteria producing siderophores as an ecofriendly alternative candidate to synthetic iron chelators and their role in plant stress management.
The effect of an app-based dietary education on dietary intake and cardiometabolic risk markers in people with type 2 diabetes: results from a randomized controlled trial
Authors: Sjöblom Linnea , Hantikainen Essi , Dahlgren Anna , Trolle Lagerros Ylva , Bonn Stephanie E.
Published: January 2025

Background

mHealth, i.e. mobile-health, strategies may be used as a complement to regular care to support healthy dietary habits in primary care patients. We evaluated the effect of a 12-week smartphone-based dietary education on overall diet quality (primary outcome), and dietary intake and cardiometabolic risk markers (secondary outcomes) in people with type 2 diabetes.

Methods

In this two-armed randomized clinical trial, people with type 2 diabetes were recruited within a primary care setting and randomized 1:1 to a smartphone-delivered dietary education for 12 weeks or a control group receiving regular care only. Dietary intake and cardiometabolic risk markers were measured at baseline and after 3 months. Diet was assessed using a 4-day dietary record and a food frequency questionnaire (FFQ). Overall diet quality was estimated with a Nordic Nutrition Recommendation (NNR) score and specific dietary intake was estimated for 13 food groups/nutrients. We used linear regression models to examine differences in change from baseline to the 3-month follow-up between the intervention and control group, adjusted for baseline values of each outcome variable.

Results

The study included 129 participants (67 in the intervention group and 62 controls), of whom 61% were men. At baseline, mean age was 63.0 years and mean body mass index was 29.8 kg/m2. When analyzing dietary record data, we found no effect of the intervention on diet quality or intake, however, the control group had increased their score by 1.6 points (95%CI: -2.9, -0.26) compared to the intervention group. In the analyses of FFQ data, the intervention group had lowered their daily intake in grams of saturated (β = -4.1, 95%CI: -7.9, -0.2) and unsaturated (mono- and polyunsaturated) (β = -6.9, 95%CI: -13.5, -0.4) fat more than the control group. The intervention group also presented lower serum triglycerides levels than the controls (β = -0.33, 95%CI: -0.60, -0.05). No statistical differences were found in any other dietary variables or cardiometabolic risk markers.

Conclusion

While we found no effect on overall diet quality, our findings suggest that a smartphone-based dietary education might impact dietary fat intake and corresponding cardiometabolic risk markers in people with type 2 diabetes. Our results should be considered hypothesis-generating and need to be confirmed in future studies.

Trial registration

Registered at ClinicalTrials.gov (NCT03784612). Registered 24 December 2018.
Managing xylazine-involved overdoses in a community harm reduction setting: lessons from Tijuana, Mexico
Authors: Bufanda Lilia Pacheco , Montoya Alejando González , Carrillo Brenda Torres , Tejeda Mariana Alejandra Gonzalez , Segovia Luis A. , Calderón-Villarreal Alhelí , Friedman Joseph R.
Published: January 2025

Background

Xylazine is a α2-adrenergic receptor agonist, used for sedation in veterinary contexts. Although it is increasingly found in overdose deaths across North America, the clinical management of xylazine-involved overdoses has not been extensively studied, especially in community-based harm reduction settings. Here we present a clinical series of xylazine-involved overdose and share the clinical approach and lessons learned by a community overdose response team in Tijuana, Mexico amidst the arrival of xylazine.

Case Presentation

We present three cases describing the clinical management of patients with xylazine-involved overdoses that occurred in close proximity to the Prevencasa community harm reduction clinic. The long period of post-naloxone sedation in xylazine overdoses is a unique clinical feature. The first case is a 61-year-old man with longstanding opioid and methamphetamine use disorder found hypoxic, who received 4.0 mg of intranasal naloxone, and quickly began respirating well. He remained unconscious for 20 min, and upon awakening, experienced withdrawal symptoms, agitation and confusion, and exposed himself to considerable physical danger by entering a local roadway. The second is a 28-year-old man who primarily uses stimulants, who overdosed while trying “China White”. His oxygen saturation improved from 81 to 100% with supplemental oxygen and field management, and he did not require naloxone administration. He recovered consciousness after 40 min. The third patient is a 36-year-old male who was found down, saturating at 20%, who received 0.4 mg intramuscular naloxone, was placed in recovery position, and remained unconscious for 12 min before making a complete recovery. The first and third patients provided urine and drug samples that tested positive for xylazine and fentanyl.

Conclusions

We describe insights about the clinical management of combined xylazine-fentanyl involved overdoses in the field, from a community harm reduction context where xylazine arrived suddenly spurring a large number of overdoses. In response to the long period of post-naloxone sedation inherent to xylazine overdoses, the clinical team learned to center oxygenation—not consciousness—as the key parameter of interest for the titration of naloxone, increase emphasis on field airway management, portable oxygen administration, and scene safety, and employ xylazine testing strips for urine and direct substance analysis to educate the patient population about health risks.
Uterus didelphys: the first case report on molecular profiling of endometrial tissue from both uterine cavities
Authors: Sola-Leyva Alberto , Romero Bárbara , Canha-Gouveia Analuce , Pérez-Prieto Inmaculada , Molina Nerea M. , Vargas Eva , Mozas-Moreno Juan , Chamorro Clara , Saare Merli , Salumets Andres , Altmäe Signe
Published: January 2025

Background

A didelphic uterus represents a unique and infrequent congenital condition in which a woman possesses two distinct uteri, each with its own cervix. This anomaly arises due to partial or incomplete merging of the Müllerian ducts during the developmental stages in the womb. Accounting for uterine malformations, a didelphic uterus is a relatively rare condition, affecting approximately 0.5–2% of the population and is considered one of the more uncommon types of uterine abnormalities.

Methods

This case report aims to study the physical separation in uterine didelphys and its impact on endometrial microbiome and inflammation, and the patterns of endometrial receptivity observed.

Results

Endometrial receptivity analyses revealed a similar receptive state in both uteri, both in the early receptive phase. Differential markers of chronic endometritis, including CD138, and MUM1-positive cells, were observed when comparing endometrial biopsies from both uteri. The right uterus exhibited a higher prevalence of these positive cells. Regarding the microbiome, significant differences were found between the uteri, notably in the right uterus, a clear non-dominance of lactobacilli and the presence of genera such as Staphylococcus, Streptococcus, and Acinetobacter. Additionally, the right uterus presented a less ‘favourable’ microenvironment, a characteristic that was also reflected in the right cervix; both sites presenting less lactobacilli than the left side samples. A distinct metabolomic signature associated with the physical separation of the uteri contributed to the differences in endometrial milieu.

Conclusions

Our study revealed that physical separation, among other factors in uterus didelphys, affects the endometrial microbiome, metabolome, and inflammatory state, with significant microbiome variation observed between the uteri, although similar endometrial receptivity patterns were noted.
Weight cycling exacerbates glucose intolerance and hepatic triglyceride storage in mice with a history of chronic high fat diet exposure
Authors: Bernecker Miriam , Lin Anna , Feuchtinger Annette , Molenaar Anna , Schriever Sonja C. , Pfluger Paul T.
Published: January 2025

Background

Obese subjects undergoing weight loss often fear the Yoyo dieting effect, which involves regaining or even surpassing their initial weight. To date, our understanding of such long-term obesity and weight cycling effects is still limited and often based on only short-term murine weight gain and loss studies. This study aimed to investigate the long-term impacts of weight cycling on glycemic control and metabolic health, focusing on adipose tissue, liver, and hypothalamus.

Methods

Chow-fed mice and mice subjected to prolonged high-fat diet (HFD) consumption for 20 weeks, followed by 24 weeks of dietary interventions to either induce weight gain, weight loss, or weight cycling were monitored for perturbations in feeding efficiency and glucose homeostasis. Post-mortem analyses included qPCR, Western Blotting, biochemical and microscopical assessments for hepatic steatosis and insulin resistance, hypothalamic and adipose tissue inflammation, and circulating lipid, leptin and IL-6 levels.

Results

Weight cycling led to hyperphagia and rapid weight regain, matching the weights of mice continuously on HFD. Despite weight loss, adipose tissue inflammation persisted with elevated pro-inflammatory markers, macrophage infiltration, and impaired Glut4 expression. HFD-induced dysregulation in hypothalamic expression of orexigenic peptides and synaptic plasticity markers persisted also after weight normalization suggesting long-lasting neural alterations. Weight-cycled mice exhibited higher circulating IL-6 and leptin levels, increased hepatic lipid storage, and dysregulated glucose metabolism compared to those with consistent diets, indicating worsened metabolic effects by Yoyo dieting.

Conclusion

In sum, our study highlights significant metabolic risks associated with weight cycling, particularly following prolonged obesity. Persistent adipose tissue inflammation, perturbed neural peptide and plasticity markers and impaired glucose tolerance emphasize the need for effective and sustainable weight loss strategies to mitigate the adverse outcomes of weight regain and improve long-term metabolic health.
From ex vivo to in vivo chimeric antigen T cells manufacturing: new horizons for CAR T-cell based therapy
Authors: Pinto E. , Lione L. , Compagnone M. , Paccagnella M. , Salvatori E. , Greco M. , Frezza V. , Marra E. , Aurisicchio L. , Roscilli G. , Conforti A.
Published: January 2025

In the past decades, Chimeric Antigen Receptor (CAR)-T cell therapy has achieved remarkable success, leading to the approval of six therapeutic products for haematological malignancies. Recently, the therapeutic potential of this therapy has also been demonstrated in non-tumoral diseases. Currently, the manufacturing process to produce clinical-grade CAR-T cells is complex, time-consuming, and highly expensive. It involves multiple steps, including the collection of T cells from patients or healthy donors, in vitro engineering and expansion, and finally reinfusion into patients. Therefore, despite the impressive clinical outcomes, ex vivo manufacturing process makes CAR-T cells out of reach for many cancer patients. Direct in vivo engineering of T cells could be a more rapid solution able to circumvent both the complexity and the costs associated with ex vivo manufactured CAR-T cells. This novel approach allows to completely eliminate ex vivo cell manipulation and expansion while producing therapeutic cell populations directly in vivo. To date, several studies have demonstrated the feasibility of in vivo T cell reprogramming, by employing injectable viral- or nanocarrier-based delivery platforms in tumour animal models. Additionally, in vivo production of CAR-T cells might reduce the incidence, or at least the severity, of systemic toxicities frequently occurring with ex vivo produced CAR-T cells, such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. In this review, we highlight the challenges associated with the current ex vivo manufacturing protocols and review the latest progresses in the emerging field of in vivo CAR-T therapy, by comparing the various platforms so far investigated. Moreover, we offer an overview of the advantages deriving from in vivo reprogramming of other immune cell types, such as Natural Killer and macrophages, with CAR constructs.
Increasing and maintaining rates of standardized depression screening in youth with childhood-onset systemic lupus erythematosus in a pediatric rheumatology clinic
Authors: Datyner Emily , Dingle Jodi , Newsome Victoria , Buckley Lisa H. , Belsky Natasha , Park Seungweon , Mitchell Manda , Fine Brooke , Patterson Barron , Graham T. Brent , Davis Alaina
Published: January 2025

Background

Depression adversely affects health outcomes in patients with childhood-onset systemic lupus erythematous (cSLE). By identifying patients with depressive symptoms, we can intervene early with referrals to mental health resources and improve outcomes. The aim of our quality improvement project was to increase and maintain rates of standardized depression screening for youth with cSLE seen within our pediatric rheumatology clinic.

Methods

Patients with cSLE 12 years of age or older seen for routine follow-up at our pediatric rheumatology clinic from September 16, 2019, through December 30, 2022, were offered the Patient Health Questionnaire-9 modified for adolescents (PHQ-A) to screen for depressive symptoms. A multidisciplinary team developed a key driver diagram to plan potential interventions to improve rates of screening. Plan‒Do‒Study‒Act (PDSA) cycles were used to prepare, implement, and evaluate interventions. Notable interventions focused on accurately identifying eligible patients, facilitating bidirectional communication between staff, and integrating and automating screening within the electronic health record (EHR). Statistical process control (SPC) methods were used for data analysis.

Results

The percentage of eligible patient encounters where depression screening was completed increased from 0 to 81% and was maintained for more than 6 months. This represents special cause variation, as evidenced by data shifts on our statistical process control chart. Among the 592 patients who completed depression screens, 114 (17%) were positive for moderate to severe symptoms, and 59 (9%) were positive for suicidal ideation (SI).

Conclusions

A high rate of standardized depression screening for youth with cSLE was achieved and maintained via integration and automation within our EHR. Establishing a highly reliable screening system is a critical first step in improving mental health care for this vulnerable population of youth.
Electroacupuncture attenuates ferroptosis by promoting Nrf2 nuclear translocation and activating Nrf2/SLC7A11/GPX4 pathway in ischemic stroke
Authors: Yang Xi-chen , Jin Ya-ju , Ning Rong , Mao Qiu-yue , Zhang Peng-yue , Zhou Li , Zhang Cheng-cai , Peng Yi-chen , Chen Na
Published: January 2025

Objective

Electroacupuncture has been shown to play a neuroprotective role following ischemic stroke, but the underlying mechanism remains poorly understood. Ferroptosis has been shown to play a key role in the injury process. In the present study, we wanted to explore whether electroacupuncture could inhibit ferroptosis by promoting nuclear factor erythroid-2-related factor 2 (Nrf2) nuclear translocation.

Methods

The ischemic stroke model was established by middle cerebral artery occlusion/reperfusion (MCAO/R) in adult rats. These rats have been randomly divided into the EA + MCAO/R group, the MCAO/R group, the EA + MCAO/R + Brusatol group (the inhibitor of Nrf2), and the EA + MCAO/R + DMSO group, and the Sham group. The EA + MCAO/R group, EA + MCAO/R + Brusatol group, and the EA + MCAO/R + DMSO group received EA intervention 24 h after modeling for 7 consecutive days. The behavioral function was evaluated by Neurologic severity score (NSS), Garcia score, Foot-fault Test, and Rotarod Test. The infarct volume was detected by TTC staining, and the neuronal damage was observed by Nissl staining. The levels of Fe2+, reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured by ELISA. The immunofluorescence and Western blotting were used to detect the expression of Total Nrf2, p-Nrf2, Nuclear Nrf2, and Cytoplasmic Nrf2, and the essential ferroptosis proteins, including glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11) and ferritin heavy chain 1 (FTH1). The mitochondria were observed by transmission electron microscopy (TEM).

Results

Electroacupuncture improved neurological deficits in rats model of MCAO/R, decreased the brain infarct volume, alleviated neuronal damage, inhibited the Fe2+, ROS, and MDA accumulation, increased SOD levels, increased the expression of GPX4, SLC7A11 and FTH1, and rescued injured mitochondria. Especially, we found that the electroacupuncture up-regulated the expression of Nrf2, and promoted phosphorylation of Nrf2 and nuclear translocation, However, Nrf2 inhibitor Brusatol reversed the neuroprotective effect of electroacupuncture.

Conclusion

Electroacupuncture can alleviate cerebral I/R injury-induced ferroptosis by promoting Nrf2 nuclear translocation. It is expected that these data will provide novel insights into the mechanisms of electroacupuncture protecting against cerebral I/R injury and potential targets underlying ferroptosis in the stroke.

Graphical Abstract
Jianwei Xiaoshi oral liquid attenuates high-calorie diet-induced dyspepsia in immature rats via regulating the pancreatic secretion pathway and maintaining the homeostasis of intestinal microbiota
Authors: Zhang Yan , Wei Xiaolu , Jiang Shan , Gao Wenya , Wang Kun , Wang Hongjie , Wang Huijun , Si Nan , Zhou Yanyan , Luo Keke , Wang Mengxiao , Liu Yuyang , Chen Lihua , Ni Liqi , Zhao Haiyu
Published: January 2025

Background

Jianwei Xiaoshi oral liquid (JWXS), a classical traditional prescription comprising various edible medicinal plants, has demonstrated significant efficacy in treating paediatric indigestion. It originates from Jianpi Pill, which is developed in the Ming Dynasty and nourishes the spleen and regulates gastrointestinal function. However, the specific molecular mechanisms involved remain unclear.

Methods

To elucidate the material base of JWXS and its underlying mechanism in treating dyspepsia, the UHPLC–Q–Orbitrap HRMS method and network pharmacology were utilized. This was followed by pharmacological experiments, transcriptomics analyses and gut microbiota studies to further investigate the effects of JWXS on dyspepsia.

Results

A total of 105 compounds, mainly flavonoids, alkaloids, organic acids and cyclic peptides, were identified. According to the five principles of generic drug properties, 43 candidate compounds were screened out. Their efficacy was verified through gastric emptying and intestinal propulsion experiments. Transcriptomic analysis revealed that JWXS primarily alleviated dyspepsia symptoms by regulating the secretion of 8 key proteins in the pancreatic secretion pathway. The differences in the gut microbiota, as identified through 16S rRNA and ITS2 sequencing, were subsequently more pronounced than those observed in the bacterial microbiota of the model group. In total, 15 differential bacteria and 16 differential fungi were identified. Targeted metabolomics analysis of SCFAs revealed a significant decrease in valeric acid (VA), acetic acid (AA), and isovaleric acid (IVA) levels in the model group, which were restored to the corresponding levels after the administration of JWXS. Correlation analysis revealed that VA, AA, and IVA were positively correlated with Lactobacillus and Bacteroides, and negatively correlated with Aspergillus and Candida. This further suggested that JWXS might alleviate symptoms of indigestion by regulating the composition of the microbiota, increasing the variety and quantity of beneficial bacteria, reducing fungal contamination, and further increasing the levels of SCFAs in the body.

Conclusion

JWXS improved functional dyspepsia in immature rats via a mechanism involving the regulation of the secretion of 8 key proteins in the pancreatic secretion pathway and the amelioration of flora disorders.

Graphical Abstract
Evaluating the effectiveness of Pisolithus tinctorius in enhancing the Eucalyptus’ resistance to salt stress
Authors: Zayed Mona S. , Ahmed Aya G. A. , Selim Shawky M. , Abd El-Fattah Dalia A.
Published: January 2025

Afforestation projects on saline land, using Eucalyptus trees and ectomycorrhizal fungi, are crucial for restoring affected areas and promoting ecological and economic benefits, particularly in saline-affected areas. This study was conducted to isolate Pisolithus sp. and estimate its potential to improve the growth performance of Eucalyptus globulus seedlings under salt-stress conditions. Pisolithus sp. was isolated from mature sporocarps and identified through 18S rDNA. Pisolithus sp. was evaluated for its response to varying pH values, temperatures, and salinity levels. A pot experiment was conducted to assess the Pisolithus strain’s effectiveness in reducing soil salinity’s impact on the growth of Eucalyptus globulus seedlings in sandy soil. The identified Pisolithus tinctorius with an accession number of OM125275 revealed the highest mycelium dry weight of 0.09 g/100 ml medium at pH 5.8, 0.08 g/100 ml medium at 28 °C, and 0.12 g/100 ml medium at 4% NaCl. Eucalyptus globulus seedlings inoculated with Pisolithus tinctorius demonstrated significant improvement in most parameters compared to non-mycorrhizal (control) seedlings under salt stress. The seedlings inoculated with Pisolithus tinctorius and irrigated with 6 dS/m saline water revealed the highest shoot height (55.670 cm), root length (42.33 cm), shoot fresh weight (6.44 g/plant), root fresh weight (1.84 g/plant), shoot dry weight (2.37 g/plant), and root dry weight (0.810 g/plant) when compared to all treatments. Our findings suggest that selecting appropriate fungal strains is crucial for improving plant performance in saline conditions.

Graphical abstract
Antimicrobial activity of Monascus purpureus-derived red pigments against Salmonella typhimurium, Escherichia coli, and Enterococcus faecalis
Authors: Teiba Islam I. , Mamdouh Islam , Yousef Mokhtar I. , Hussein Ahmed , El-Bilawy Emad H.
Published: January 2025

The rise of antimicrobial-resistant microorganisms (AMR) poses a significant global challenge to human health and economic stability. In response, various scientific communities are seeking safe alternatives to antibiotics. This study comprehensively investigates the antibacterial effects of red dye derived from Monascus purpureus against three bacterial pathogens: Salmonella typhimurium ATCC14028, Escherichia coli ATCC8739, and Enterococcus faecalis ATCC25923. The dye was extracted from the Monascus purpureus ATCC16436 strain, using 1 mg of red dye in 1 ml of DMSO to achieve a concentration of 1000 µg/ml. The chemical profile of the red dye extract was analyzed using GC–MS analysis, confirming the presence of several bioactive antimicrobial compounds, including aspidospermidin-17-ol, 1-acetyl-16-methoxy, octanoic acid, and hexadecanoic acid methyl ester. The extract was tested against the bacterial strains at varying concentrations to determine the minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC). The results demonstrated significant antibacterial activity, with the highest MIC and MBC values of 6.25/12.5 µg/ml against S. typhimurium. The antibacterial activity of the red dye was compared to five conventional antibiotics using the disc diffusion method, revealing superior effectiveness, particularly against S. typhimurium, with an inhibition zone measuring 20 ± 0.22 mm. Scanning electron microscopy was employed to explore the mechanism of action of the red dye extract, highlighting its impact on bacterial plasma membrane permeability and its interference with cellular energy production. These findings suggest that the Monascus purpureus-derived red dye extract represents a promising natural alternative to conventional antibiotics, demonstrating potent antibacterial activity and potential as a novel therapeutic agent in combating antimicrobial resistance.
Melatonin improves endometrial receptivity and embryo implantation via MT2/PI3K/LIF signaling pathway in sows
Authors: Qin Xue , Yang Menghao , Yu Yang , Wang Xiaolin , Zheng Yi , Cai Rui , Pang Weijun
Published: January 2025

Background

Increased backfat thickness of sows in early gestation is negative to reproductive performance. Endometrial receptivity is an important determinant of reproductive success, but it is unclear whether the effect of sow backfat thickness on litter size is associated with endometrial receptivity and whether melatonin treatment may have benefits. The present study seeks to answer these questions through in vitro and in vivo investigations.

Results

Excessive lipid deposition and lower melatonin levels in the uterus are detrimental to endometrial receptivity and embryo implantation in high backfat thickness sows. In cells treated with melatonin, the MT2/PI3K/LIF axis played a role in reducing lipid accumulation in porcine endometrial epithelium cells and improved endometrial receptivity. Furthermore, we found a reduction of lipids in the uterus after eight weeks of intraperitoneal administration of melatonin to HFD mice. Notably, melatonin treatment caused a significant reduction in the deposition of endometrial collagen, an increase in the number of glands, and repair of the pinopode structure, ultimately improving endometrial receptivity, promoting embryo implantation, and increasing the number of litter size of mice.

Conclusions

Collectively, the finding reveals the harmful effects of high backfat thickness sows on embryo implantation and highlight the role of melatonin and the MT2/PI3K/LIF axis in improving endometrial receptivity by enhancing metabolism and reducing the levels of uterine lipids in obese animals.
Joint multifractality in cross-correlations between grains & oilseeds indices and external uncertainties
Authors: Shao Ying-Hui , Gao Xing-Lu , Yang Yan-Hong , Zhou Wei-Xing
Published: January 2025

This study investigates the relationships between agricultural spot markets and external uncertainties through multifractal detrending moving-average cross-correlation analysis (MF-X-DMA). The dataset contains the Grains & Oilseeds Index (GOI) and its five subindices for wheat, maize, soyabeans, rice, and barley. Moreover, we use three uncertainty proxies, namely, economic policy uncertainty (EPU), geopolitical risk (GPR), and Volatility Index (VIX). We observe multifractal cross-correlations between agricultural markets and uncertainties. Furthermore, statistical tests reveal that maize has intrinsic joint multifractality with all the uncertainty proxies, highly sensitive to external shocks. Additionally, intrinsic multifractality among GOI-GPR, wheat-GPR, and soyabeans-VIX is illustrated. However, other series have apparent multifractal cross-correlations with high probabilities. Moreover, our analysis suggests that among the three types of external uncertainties, GPR has the strongest association with grain prices, excluding maize and soyabeans.
Modeling the significance of unified theory of acceptance and use of technology in predicting the intention and usage of eCNY
Authors: Ma Yue , Al Mamun Abdullah , Masukujjaman Mohammad , Ja’afar Roslan
Published: January 2025

The introduction of the digital renminbi (eCNY) by the People's Bank of China serves as a means for the central bank to effectively comprehend macroeconomic dynamics and enhance payment infrastructure within the domestic market. Among the pioneering digital currencies, the eCNY is at the forefront of technological research and development, pilot implementation, and the establishment of a robust system. Thus, employing the unified theory of acceptance and use of technology, this study aims to explore the factors shaping the adoption of the eCNY and to determine the mediating effects of intention toward the eCNY and the moderating role of age and gender among various relationships. A cross-sectional survey methodology was deployed to collect data from pilot communities situated within the Yangtze River Delta, Pearl River Delta, and Beijing–Tianjin–Hebei regions. The empirical analysis comprised 809 valid online questionnaires, and the examination was conducted through structural equation modeling employing the partial least squares technique, ultimately subjecting the conceptual model to a comprehensive assessment. The results for intention to use the eCNY indicate that performance expectancy, effort expectancy, social influence, and perceived government policy have significant effects. Facilitating conditions and intentions toward the eCNY positively influenced its actual use. According to the findings of this study, age and sex did not moderate the effect of each hypothesis on the intention to use in the research model. This study breaks new ground by investigating the adoption of the eCNY, a novel form of currency, highlighting its multifaceted nature and providing empirical evidence for a comprehensive model encompassing psychological, social, and contextual factors. This study employs social surveys to identify obstacles in the process of promoting the widespread adoption of the eCNY and offers suggestions to the central bank and government to increase user enthusiasm and decrease user perceptions of risk, thereby promoting its widespread adoption.