bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pre-post trial to examine biological mechanisms of the effects of time-restricted eating on symptoms and quality of life in bipolar disorder
Authors: Johnson Sheri L. , Murray Greg , Manoogian Emily N. C. , Mason Liam , Allen J. D. , Berk Michael , Panda Satchidananda , Rajgopal Nandini A. , Gibson Jake C. , Bower Carter D. , Berle Eline F. , Joyner Keanan , Villanueva Robert , Michalak Erin E. , Kriegsfeld Lance J. 
Published: October 2024

Abstract
Background
The primary objective of this trial is to examine the mechanisms of time-restricted eating (TRE) as an adjunct to psychiatric care for people with bipolar disorder (BD) with sleep or circadian disruptions. This study builds on prior studies of circadian disruption in BD as well as growing evidence that TRE improves circadian functioning.

Methods
One-hundred fifty participants diagnosed with BD 1 or II will be recruited via advertising in the local community. Main inclusion criteria include: obtaining medical treatment for BD; current sleep or circadian problems; self-reported eating period of ≥ 12 h; no eating disorder or other health conditions that would hinder or limit the safety of following TRE; and not currently experiencing a mood episode, acute suicidality, psychosis, alcohol or substance use disorder. Participants will be asked to complete a baseline period in which daily food intake is logged online for two weeks. After baseline, participants will be asked to follow TRE for 8 weeks and to continue to complete daily food logging during this time. Symptom severity interviews will be conducted by phone or videoconference at baseline, mid-intervention (6 weeks post-baseline), end of intervention (10 weeks post-baseline), and 6 months post-baseline. Self-rated symptom severity and quality of life data will be gathered online at the same time points as symptom severity interviews, and at 16 weeks post-baseline (6 weeks after the TRE period ends). To assess potential mechanisms of change, we will examine the change in diurnal amplitude of ‘clock’ gene expression as a primary mediator at 8 weeks compared to baseline. We will further test whether diurnal amplitude of clock gene expression is predictive above and beyond the role of two covariate potential mediators, glucose tolerance and inflammation at 8 weeks relative to baseline. To provide an index of whether TRE successfully decreases emotional lability, participants will be asked to complete 5 mood assessments per day for 7 days at baseline and at 10 weeks. These mood assessments will be optional.

Discussion
The planned research will provide novel and important information on whether TRE improves sleep/circadian rhythm problems, along with reductions in mood symptoms and improvements in quality of life, for individuals with BD.

Trial registration
ClinicalTrials.gov ID: NCT06555406.
Alleviating rheumatoid arthritis with a photo-pharmacotherapeutic glycan-integrated nanogel complex for advanced percutaneous delivery
Authors: Weng Pei-Wei , Lu Hsien-Tsung , Rethi Lekshmi , Liu Chia-Hung , Wong Chin-Chean , Rethi Lekha , Wu Kevin C.-W. , Jheng Pei-Ru , Nguyen Hieu T. , Chuang Andrew E.-Y. 
Published: October 2024

AbstractThe prospective of percutaneous drug delivery (PDD) mechanisms to address the limitations of oral and injectable treatment for rheumatoid arthritis (RA) is increasing. These limitations encompass inadequate compliance among patients and acute gastrointestinal side effects. However, the skin’s intrinsic layer can frequently hinder the percutaneous dispersion of RA medications, thus mitigating the efficiency of drug delivery. To circumvent this constraint, we developed a strontium ranelate (SrR)-loaded alginate (ALG) phototherapeutic hydrogel to assess its effectiveness in combating RA. Our studies revealed that this SrR-loaded ALG hydrogel incorporating photoelectrically responsive molybdenum disulfide nanoflowers (MoS2 NFs) and photothermally responsive polypyrrole nanoparticles (Ppy NPs) to form ALG@SrR-MoS2 NFs-Ppy NPs demonstrated substantial mechanical strength, potentially enabling delivery of hydrophilic therapeutic agents into the skin and significantly impeding the progression of RA. Comprehensive biochemical, histological, behavioral, and radiographic analyses in an animal model of zymosan-induced RA demonstrated that the application of these phototherapeutic ALG@SrR-MoS2 NFs-Ppy NPs effectively reduced inflammation, increased the presence of heat shock proteins, regulatory cluster of differentiation M2 macrophages, and alleviated joint degeneration associated with RA. As demonstrated by our findings, treating RA and possibly other autoimmune disorders with this phototherapeutic hydrogel system offers a distinctive, highly compliant, and therapeutically efficient method.
A process study of early achievements and challenges in countries engaged with the WHO Special Initiative for Mental Health
Authors: Ager Alastair , Hermosilla Sabrina , Schafer Alison , Kestel Dévora 
Published: October 2024

Abstract
Background
There is increasing awareness of the importance of the transformation of mental health systems. Launched in 2019, the WHO Special Initiative for Mental Health seeks to accelerate access to quality and affordable care for mental health conditions as an integral component of Universal Health Coverage. Nine countries are currently engaged with the initiative.

Methods
This study reviewed processes of implementation—and progress achieved—across all settings by late 2022. It involved review of 158 documents provided by WHO relating to Special Initiative activities and 42 interviews with country-level stakeholders, WHO Regional and HQ personnel engaged with the initiative, and core donors. Documents were thematically coded using a template based upon the WHO framework of health system building blocks. Responses to structured interviews were coded based on an emergent thematic framework.

Results
Documentation reported similar achievements across all domains; however challenges were reported most frequently in relation to service delivery, leadership and governance, and workforce. Issues of financing were notable in being twice as likely to be reported as a challenge than a success. Interviews indicated four major areas of perceived achievement: establishing a platform and profile to address mental health issues; convening a multi-stakeholder, participatory engagement process; new, appropriate services being developed; and key developments in law, policy, or governance around mental health. The planning process followed for the initiative, senior country-level buy-in and the quality of key personnel were the factors considered most influential in driving progress. Ambivalent political commitment and competing priorities were the most frequently cited challenges across all interviewees.

Conclusions
The role of the Special Initiative in raising the profile of mental health on national agendas through a participatory and inclusive process has been widely valued, and there are indications of the beginnings of transformational shifts in mental health services. To secure these benefits, findings suggest three strategic priorities: increasing political prioritisation and funding for systems-level change; clearly articulating sustainable, transformed models of care; and promoting feasible and contextualised measures to support accountability and course correction. All are of potential relevance in informing global strategies for mental health systems transformation in other settings.
MCPIP1 modulates the miRNA‒mRNA landscape in keratinocyte carcinomas
Authors: Lichawska-Cieslar Agata , Szukala Weronika , Ylla Guillem , Machaj Gabriela , Ploskonka Faustyna , Chlebicka Iwona , Szepietowski Jacek C. , Jura Jolanta 
Published: October 2024

Abstract
Background
Monocyte Chemotactic Protein 1-Induced Protein 1 (MCPIP1, also called Regnase-1) is a negative modulator of inflammation with tumor-suppressive properties. Mice with keratinocyte-specific deletion of the Zc3h12a gene, encoding MCPIP1, (Mcpip1eKO mice) are more susceptible to the development of epidermal papillomas initiated by 7,12-dimethylbenz[a]-anthracene (DMBA) and promoted by 2-O-tetradecanoylphorbol-13-acetate (TPA).

Methods
The aim of this study was to investigate the MCPIP1 RNase-dependent microRNA (miRNA)‒mRNA regulatory network in chemically induced squamous cell carcinoma (SCC)-like skin papillomas. Next-generation sequencing (NGS) coupled with bioinformatic analysis was used to shortlist the MCPIP1-dependent changes in protein-coding genes and miRNAs. The expression levels of the selected miRNAs were analyzed by quantitative PCR in human keratinocytes with MCPIP1 silencing. Functional studies were performed in human keratinocytes transfected with appropriate miRNA mimics. The DIANA-microT-CDS algorithm and DIANA-TarBase v7 database were used to predict potential target genes and identify the experimentally validated targets of differentially expressed (DE) miRNAs.

Results
RNA sequencing (RNA-Seq) analysis of control and Mcpip1eKO DMBA/TPA-induced papillomas revealed transcriptome changes, with 2400 DE protein-coding genes and 33 DE miRNAs. The expression of miR-223-3p, miR-376c-3p, and miR-139-5p was confirmed to be dependent on MCPIP1 activity in both murine and human models. We showed that MCPIP1 directly regulates the expression of miR-376c-3p via direct cleavage of the corresponding precursor miRNA. The pro-proliferative activity of miR-223-3p, miR-376c-3p, and miR-139-5p was experimentally confirmed in SCC-like keratinocytes. Bioinformatic prediction of the mRNA targets of the DE-miRNAs revealed 416 genes as putative targets of the 18 upregulated miRNAs and 425 genes as putative targets of the 15 downregulated miRNAs. Further analyses revealed the murine interactions that are conserved in humans. Functional analysis indicated that during the development of cutaneous SCC, the most important pathways/processes mediated by the miRNA‒mRNA MCPIP1-dependent network are the regulation of inflammatory processes, epithelial cell proliferation, Wnt signaling, and miRNA transcription.

Conclusions
Loss of MCPIP1 modulates the expression profiles of 33 miRNAs in chemically induced Mcpip1eKO papillomas, and these changes directly affect the miRNA‒mRNA network and the modulation of pathways and processes related to carcinogenesis.
Effects of multicomponent exercise intervention on cardiometabolic risk factors in children and young adults with cerebral palsy: a multiple-baseline trial
Authors: Savikangas Tiina , Valadão Pedro , Haapala Eero A. , Finni Taija 
Published: October 2024

AbstractBackgroundAdults with cerebral palsy (CP) have a high risk of cardiometabolic diseases. It is unknown whether this risk is elevated in young people with CP and whether exercise can reduce this risk. Therefore, we investigated the effects of the EXErcise for Cerebral Palsy (EXECP) intervention on cardiometabolic risk in children and young adults with CP and compared this risk to typically developing children and young adults (TDs).MethodsAmbulatory male and female participants with spastic CP, aged 9–24 years, and age- and sex-matched TDs without musculoskeletal disorders were recruited. Participants with CP were measured at baseline, after a three-month control period manifesting normal development, and after the three-month strength, gait, and flexibility training intervention. TDs were measured at baseline and after the control period. They did not attend the intervention. Cardiometabolic risk factors included body weight, body fat percentage, and skeletal muscle mass index assessed with bioimpedance; resting systolic and diastolic blood pressure and aortic pulse wave velocity assessed with a non-invasive oscillometric device; fasting plasma high-density and low-density lipoprotein cholesterol, triglyceride, and glucose levels. Data were analyzed with independent samples t-tests and linear mixed-effects models adjusted for sex and age.ResultsThe study involved 18 participants with CP (13 males, 9–22 year, mean 14.2 ± 4.4) and 17 TDs (12 males, 9–22 year, mean 14.6 ± 4.3). At baseline, participants with CP had a 1.0 (95% confidence interval (CI) [-2.0, -0.0]) kg/m2lower skeletal muscle mass index than TDs. During the control period, no statistically significant between-group differences were observed in the change of any outcome. In the CP group, body weight (β = 1.87, 95% CI [1.04, 2.70]), fat percentage (β = 1.22 [0.07, 2.37], and blood glucose (β = 0.19, 95% CI [0.01, 0.37]) increased, while diastolic blood pressure (β=-2.31, 95% CI [-4.55, -0.06]) and pulse wave velocity (β=-0.44, 95% CI [-0.73, -0.16]) decreased. In the TD group, only body weight increased (β = 0.85, 95% CI [0.01, 1.68]) statistically significantly. In the CP group, no changes were observed during the intervention.ConclusionsYoung people with and without CP do not exhibit significant differences in most cardiometabolic risk factors. EXECP intervention may attenuate some adverse development trajectories occurring without the intervention but greater volume and intensity of aerobic exercise may be needed to reduce cardiometabolic risk.Trial registrationISRCTN69044459; Registration date 21/04/2017.
Explainable AI-based innovative hybrid ensemble model for intrusion detection
Authors: Ahmed Usman , Jiangbin Zheng , Almogren Ahmad , Khan Sheharyar , Sadiq Muhammad Tariq , Altameem Ayman , Rehman Ateeq Ur 
Published: October 2024

AbstractCybersecurity threats have become more worldly, demanding advanced detection mechanisms with the exponential growth in digital data and network services. Intrusion Detection Systems (IDSs) are crucial in identifying illegitimate access or anomalous behaviour within computer network systems, consequently opposing sensitive information. Traditional IDS approaches often struggle with high false positive rates and the ability to adapt embryonic attack patterns. This work asserts a novel Hybrid Adaptive Ensemble for Intrusion Detection (HAEnID), an innovative and powerful method to enhance intrusion detection, different from the conventional techniques. HAEnID is composed of a string of multi-layered ensemble, which consists of a Stacking Ensemble (SEM), a Bayesian Model Averaging (BMA), and a Conditional Ensemble method (CEM). HAEnID combines the best of these three ensemble techniques for ultimate success in detection with a considerable cut in false alarms. A key feature of HAEnID is an adaptive mechanism that allows ensemble components to change over time as network traffic patterns vary and new threats appear. This way, HAEnID would provide adequate protection as attack vectors change. Furthermore, the model would become more interpretable and explainable using Shapley Additive Explanations (SHAP) and Local Interpretable Model-agnostic Explanations (LIME). The proposed Ensemble model for intrusion detection on CIC-IDS 2017 achieves excellent accuracy (97-98%), demonstrating effectiveness and consistency across various configurations. Feature selection further enhances performance, with BMA-M (20) reaching 98.79% accuracy. These results highlight the potential of the ensemble model for accurate and reliable intrusion detection and, hence, is a state-of-the-art choice for accuracy and explainability.
Experimental, Numerical, and Analytical Investigation of the Reinforced Concrete Hidden and Wide Beams
Authors: Mahmoud Ahmed A. , El Gani Belal K. , Mustafa Tarek S. , Khater Ahmed N. M. 
Published: October 2024

AbstractThis research presents an experimental, analytical, and numerical study to predict the flexural behavior of reinforced concrete hidden and wide beams embedded in slabs. The experimentally studied parameters of testing eight specimens include beam depth, beam width, and beam eccentricity from the column. The obtained test results were compared to the predictions of finite element analysis using the ANSYS program. A numerical parametric study was conducted by the ANSYS program to explore other parameters affecting the ultimate flexural strength of beams. The studied parameters encompass concrete compressive strength, steel reinforcement strength, bottom reinforcement ratio, top-to-bottom reinforcement ratio, and web reinforcement ratio. The results revealed that an increase in beam depth led to higher ultimate load and secant stiffness, along with a decrease in deflection. The increase in beam width significantly affected beam depth, resulting in increased ultimate load and secant stiffness and a slight decrease in deflection. The increase in beam eccentricity from the column resulted in a decrease in ultimate load and secant stiffness while increasing the deflection. Comparisons between experimental and numerical results were made against calculations based on the ECP 203-2017 and ACI 318-19 codes, and the comparison yielded satisfactory results.
Balancing the scales: assessing the impact of irrigation and pathogen burden on potato blackleg disease and soil microbial communities
Authors: Keating Ciara , Kilbride Elizabeth , Stalham Mark A. , Nellist Charlotte , Milner Joel , Humphris Sonia , Toth Ian , Mable Barbara K. , Ijaz Umer Zeeshan 
Published: October 2024

Abstract
Background
Understanding the interaction between environmental conditions, crop yields, and soil health is crucial for sustainable agriculture in a changing climate. Management practices to limit disease are a balancing act. For example, in potato production, dry conditions favour common scab (Streptomyces spp.) and wet conditions favour blackleg disease (Pectobacterium spp.). The exact mechanisms involved and how these link to changes in the soil microbiome are unclear. Our objectives were to test how irrigation management and bacterial pathogen load in potato seed stocks impact: (i) crop yields; (ii) disease development (blackleg or common scab); and (iii) soil microbial community dynamics.

Methods
We used stocks of seed potatoes with varying natural levels of Pectobacterium (Jelly [high load], Jelly [low load] and Estima [Zero – no Pectobacterium]). Stocks were grown under four irrigation regimes that differed in the timing and level of watering. The soil microbial communities were profiled using amplicon sequencing at 50% plant emergence and at harvest. Generalised linear latent variable models and an annotation-free mathematical framework approach (ensemble quotient analysis) were then used to show the interacting microbes with irrigation regime and Pectobacterium pathogen levels.

Results
Irrigation increased blackleg symptoms in the plots planted with stocks with low and high levels of Pectobacterium (22–34%) but not in the zero stock (2–6%). However, withholding irrigation increased common scab symptoms (2–5%) and reduced crop yields. Irrigation did not impact the composition of the soil microbiome, but planting stock with a high Pectobacterium burden resulted in an increased abundance of Planctomycetota, Anaerolinea and Acidobacteria species within the microbiome. Ensemble quotient analysis highlighted the Anaerolinea taxa were highly associated with high levels of Pectobacterium in the seed stock and blackleg symptoms in the field.

Conclusions
We conclude that planting seed stocks with a high Pectobacterium burden alters the abundance of specific microbial species within the soil microbiome and suggest that managing pathogen load in seed stocks could substantially affect soil communities, affecting crop health and productivity.
Clinical implementation of advanced respiratory monitoring with esophageal pressure and electrical impedance tomography: results from an international survey and focus group discussion
Authors: Wisse Jantine J. , Scaramuzzo Gaetano , Pellegrini Mariangela , Heunks Leo , Piraino Thomas , Somhorst Peter , Brochard Laurent , Mauri Tommaso , Ista Erwin , Jonkman Annemijn H. 
Published: October 2024

Abstract
Background
Popularity of electrical impedance tomography (EIT) and esophageal pressure (Pes) monitoring in the ICU is increasing, but there is uncertainty regarding their bedside use within a personalized ventilation strategy. We aimed to gather insights about the current experiences and perceived role of these physiological monitoring techniques, and to identify barriers and facilitators/solutions for EIT and Pes implementation.

Methods
Qualitative study involving (1) a survey targeted at ICU clinicians with interest in advanced respiratory monitoring and (2) an expert focus group discussion. The survey was shared via international networks and personal communication. An in-person discussion session on barriers, facilitators/solutions for EIT implementation was organized with an international panel of EIT experts as part of a multi-day EIT meeting. Pes was not discussed in-person, but we found the focus group results relevant to Pes as well. This was confirmed by the survey results and four additional Pes experts that were consulted.

Results
We received 138 survey responses, and 26 experts participated in the in-person discussion. Survey participants had diverse background [physicians (54%), respiratory therapists (19%), clinical researchers (15%), and nurses (6%)] with mostly > 10 year ICU experience. 84% of Pes users and 74% of EIT users rated themselves as competent to expert users. Techniques are currently primarily used during controlled ventilation for individualization of PEEP (EIT and Pes), and for monitoring lung mechanics and lung stress (Pes). EIT and Pes are considered relevant techniques to guide ventilation management and is helpful for educating clinicians; however, 57% of EIT users and 37% of Pes users agreed that further validation is needed. Lack of equipment/materials, evidence-based guidelines, clinical protocols, and/or the time-consuming nature of the measurements are main reasons hampering Pes and EIT application. Identified facilitators/solutions to improve implementation include international guidelines and collaborations between clinicians/researcher and manufacturers, structured courses for training and use, easy and user-friendly devices and standardized analysis pipelines.

Conclusions
This study revealed insights on the role and implementation of advanced respiratory monitoring with EIT and Pes. The identified barriers, facilitators and strategies can serve as input for further discussions to promote the development of EIT-guided or Pes-guided personalized ventilation strategies.
Identification of metabolites from the gut microbiota in hypertension via network pharmacology and molecular docking
Authors: Zhang Wenjie , Zhang Yinming , Li Jun , Tang Jiawei , Wu Ji , Xie Zicong , Huang Xuanchun , Tao Shiyi , Xue Tiantian 
Published: October 2024

AbstractHypertension is the most prevalent cardiovascular disease, affecting one-third of adults. All antihypertensive drugs have potential side effects. Gut metabolites influence hypertension. The objective of this study was to identify antihypertensive gut metabolites through network pharmacology and molecular docking techniques and to validate their antihypertensive mechanisms via in vitro experiments. A total of 10 core antihypertensive targets and 18 gut metabolites that act on hypertension were identified. Four groups of protein metabolites, namely, CXCL8-baicalein, CXCL8-baicalin, CYP1A1-urolithin A, and PTGS2-equol, which have binding energies of − 7.7, − 8.5, − 7.2, and − 8.8 kcal-mol−1, respectively, were found to have relatively high affinities. Based on its drug-likeness properties in silico and toxicological properties, equol was identified as a potential antihypertensive metabolite. On the basis of the results of network pharmacology and molecular docking, equol may exert antihypertensive effects by regulating the IL-17 signaling pathway and PTGS2. A phenylephrine-induced H9c2 cell model was subsequently utilized to verify that equol inhibits cell hypertrophy (P < 0.05) by inhibiting the IL-17 signaling pathway and PTGS2 (P < 0.05). This study demonstrated that equol has the potential to be developed as a novel therapeutic agent for the treatment of hypertension.
Graphical Abstract