bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic significance of inferior vena cava volume defined by initial polytrauma CT-imaging: single-center experience of a level-1 trauma center
Authors: Meyer Hans-Jonas , Sotikova Veronika , Hetz Michael , Osterhoff Georg , Kleber Christian , Denecke Timm , Werdehausen Robert , Hempel Gunther , Struck Manuel F.
Published: October 2024

Background

The significance of computed tomography (CT)-based volume measurement of the inferior vena cava (IVC) in the treatment and prognosis of trauma patients is not yet fully understood. The conflicting results that have been reported may be attributable to differences in injury severity and the use of different measurement methods, including IVC index and volumetry. The purpose of this study was to determine the relationship between IVC volume and red blood cell (RBC) transfusion and mortality in intubated trauma patients who were stable enough for initial CT imaging.

Methods

A retrospective analysis was conducted on all consecutive trauma patients who underwent emergency tracheal intubation and mechanical ventilation before initial whole-body CT imaging at a level-1 trauma center over a 12-year period (2008–2019). The IVC volume was determined on initial trauma CT and included in multivariable models with demographic and diagnostic data. Associations of overall RBC transfusion, massive transfusion, 24-h mortality, and 30-day mortality were assessed using logistic regression analyses and Cox proportional hazard models.

Results

A total of 438 patients (75.3% male) with a median age of 50 years, and a median injury severity score (ISS) of 26 points were included in the analysis. Most of the patients (97.5%) had suffered from blunt trauma mechanisms. Median IVC volume was 36.25 cm3, and RBC transfusion and massive transfusion were performed in 197 and 90 patients, respectively. The 24-h and 30-day mortality rates were 7.3% and 23.3%, respectively. VCI volume was found to be independently associated with the necessity of RBC transfusion and 24-h mortality (OR 0.98, 95% CI 0.96–0.99, p = 0.01 and HR 0.96, 95% CI 0.93–0.99, p = 0.025, respectively), while associations with massive transfusion and 30-day mortality were not statistically significant in multivariable analyses.

Conclusion

Initial IVC volume may serve as a predictor of patients at risk for overall RBC transfusion requirements and 24-h mortality, suggesting the possibility of its diagnostic efficacy in short-term outcomes. Further studies are needed to confirm these findings.
The adequacy of residential parking requirements: a comparison of demand and required supply in European cities
Authors: Merten Laura , Kuhnimhof Tobias
Published: October 2024

Minimum residential parking requirements exist in most European cities to regulate the number of off-street parking spaces built for new or converted residential buildings. As minimum parking requirements can have various negative impacts, they are controversially discussed and increasingly complemented or replaced by maximum requirements in several cities around the world. This paper evaluates the adequacy of residential minimum and maximum parking requirements in 12 mid-sized cities in Germany, the Netherlands and Switzerland. By calculating the number of required parking spaces and by comparing this required supply to the estimated parking demand, we evaluate the impacts and possible steering effects of parking standards. We base our estimations on a hypothetical scenario, in which all existing residential buildings comply with the requirements and use the number of registered cars as a proxy for residential parking demand.

Our results reveal great differences between the cities’ parking standards. Some cities have minimum requirements, which would lead to a parking supply exceeding the current parking demand in large, mainly densely-populated and centrally located areas. These requirements would result in an oversupply of off-street parking at the place of residence of more than 50% of all residents, which in some areas would even exceed the parking demand by a factor of 2. In contrast to that, other cities have quite stringent requirements, which fall well below the current parking demand at the place of residence of 64 to 81% of all residents. Some of these restrictive cities complement their minimum parking requirements with additional measures by enforcing maximum requirements, limiting access to parking permits or reducing the overall parking capacity. Based on these findings, we discuss the adequacy of the parking requirements, their likely underlying objectives and their possible impacts on future urban development.
The complete mitochondrial genome of Castanopsis carlesii and Castanea henryi reveals the rearrangement and size differences of mitochondrial DNA molecules
Authors: Tu Xiong-De , Xin Ya-Xuan , Fu Hou-Hua , Zhou Cheng-Yuan , Liu Qing-Long , Tang Xing-Hao , Zou Long-Hai , Liu Zhong-Jian , Chen Shi-Pin , Lin Wen-Jun , Li Ming-He
Published: October 2024

Background

Castanopsis carlesii is a dominant tree species in subtropical evergreen broad-leaved forests and holds significant ecological value. It serves as an excellent timber tree species and raw material for cultivating edible fungi. Henry Chinquapin (Castanea henryi) wood is known for its hardness and resistance to water and moisture, making it an exceptional timber species. Additionally, its fruit has a sweet and fruity taste, making it a valuable food source. However, the mitogenomes of these species have not been previously reported. To gain a better understanding of them, this study successfully assembled high-quality mitogenomes of C. carlesii and Ca. henryi for the first time.

Results

Our research reveals that the mitochondrial DNA (mtDNA) of C. carlesii exhibits a unique multi-branched conformation, while Ca. henryi primarily exists in the form of two independent molecules that can be further divided into three independent molecules through one pair of long repetitive sequences. The size of the mitogenomes of C. carlesii and Ca. henryi are 592,702 bp and 379,929 bp respectively, which are currently the largest and smallest Fagaceae mitogenomes recorded thus far. The primary factor influencing mitogenome size is dispersed repeats. Comparison with published mitogenomes from closely related species highlights differences in size, gene loss patterns, codon usage preferences, repetitive sequences, as well as mitochondrial plastid DNA segments (MTPTs).

Conclusions

Our study enhances the understanding of mitogenome structure and evolution in Fagaceae, laying a crucial foundation for future research on cell respiration, disease resistance, and other traits in this family.
Carotid intima-media thickness, fibroblast growth factor 23, and mineral bone disorder in children with chronic kidney disease
Authors: Palupi-Baroto Retno , Hermawan Kristia , Murni Indah Kartika , Nurlita Tiara , Prihastuti Yuli , Puspitawati Ira , Tandri Chika Carnation , Ambarsari Cahyani Gita
Published: October 2024

Background

Carotid intima-media thickness (cIMT) is a measure of atherosclerotic vascular disease and a surrogate biomarker for cardiovascular risk in patients with chronic kidney disease (CKD). Mineral and bone disorders (MBD) are complications of CKD, contributing to vascular calcification and accelerated atherosclerosis. Increased fibroblast growth factor 23 (FGF23)—the earliest detectable serum abnormality associated with CKD-MBD—has been linked with cardiovascular disease in patients with CKD. This study aimed to identify factors and analyze the relationship associated with high cIMT, high FGF23, and poor MBD control in children with CKD.

Methods

A cross-sectional study was conducted in Yogyakarta, Indonesia recruiting children with CKD. The correlations and factors between cIMT, FGF23, and MBD were explored.

Results

We recruited 42 children aged 2–18 years old with CKD stages 2 to 5D. There were no significant correlations between cIMT and factors including advanced CKD, use of dialysis, body mass index, hypertension, anemia, MBD, FGF23 levels, and left ventricular mass index (LVMI). Patients with advanced CKD had poorly controlled anemia, hypertension, and higher LVMI. In multivariate analysis, CKD stages, hypertension stages, the presence of MBD, and LVMI were associated with FGF23 levels (p < 0.05).

Conclusions

FGF23 levels increased with CKD progression, and MBD was more prevalent in advanced kidney disease. Elevated FGF23 is potentially associated with increased MBD prevalence in late-stage CKD. A larger study is needed to confirm the factors affecting cIMT in children with CKD.
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

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

The 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

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

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

Background

Adults 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).

Methods

Ambulatory 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.

Results

The 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.

Conclusions

Young 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 registration

ISRCTN69044459; 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

Cybersecurity 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

This 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

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

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

Hypertension 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
The pathways of unaccompanied foreign minors evaluated by the social workers: a case study in Italy
Authors: Terzera Laura , Bonomi Paolo
Published: October 2024

Social workers, who are responsible for unaccompanied minors (UAM), have in-depth knowledge of those minors’ backgrounds and the reception pathways they follow. The social workers support key aspects of UAM integration such as learning the host country’s language, school integration and vocational training. Via 566 interviews collected through a survey carried out in collaboration with the Municipality of Milan, we asked social workers to provide an overall evaluation of the progress of each reception path, to test a synthetic indicator capable of effectively measuring UAM progress. We confirmed the reliability of this indicator, as the results correlated with outcomes used in the literature to assess UAM pathways, such as learning the host country's language, uninterrupted schooling and training, and deviant behaviour related to crime and drug abuse. We used ordinal logistic regression to identify the UAM characteristics associated with the overall operator’s evaluation. Our analysis showed that the duration of stay in Italy before and after the start of the reception process had an impact on the social workers’ evaluations, as did certain pre-arrival characteristics such as country of origin, years of study in the home country and underlying motivations for migrating. Finally, the psychological vulnerability of a significant number of UAM, often linked to traumatic experiences leading to migration or experienced during the journey, significantly penalises the success of reception pathways.
Novel EXT1 variants cause divergent symptom severity in multiple cartilaginous exostoses: a family report
Authors: Atasever Yildirim Gozde , Anlas Ozlem , Kisla Ekinci Rabia Miray
Published: October 2024

Background

Multiple cartilaginous exostoses (MCE) are a rare genetic disorder characterized by multiple osteochondromas in the metaphysis of long bones.

Case Presentation.

We report a 15-year-old male patient, his father, and his brother, all presenting varied severity of the same symptom. The patient exhibited symptoms since infancy, with osteochondromas affecting mobility and causing joint deformities. Whole exome sequencing identified a pathogenic NM_000127.3(EXT1):c.1056 + 2 T > G and a likely pathogenic NM_000127.3(EXT1):c.1047G > T variant in the EXT1 gene, both novel.

Conclusions

Despite three decades since the discovery of the EXT1 gene, MCE diagnosis may be delayed until adolescence or adulthood. This report contributes to clinical understanding, emphasizing the importance of early diagnosis, genetic analysis, and potential treatment approaches, to mitigate long-term deformities and complications in MCE patients.
Intercoronary communication: a rare coronary anomaly
Authors: Adimoulame Seenu Prasanth , Palakshachar Anand , Ramalingam Rangaraj , Moorthy Nagaraja , Kumbhalkar Anushree
Published: October 2024

Background

Intercoronary communication also known as coronary arcade or coronary cascade is a rare coronary artery anomaly with an incidence of only 0.002% in patients undergoing angiography. This case emphasizes the importance of recognizing this rare anomaly and highlights its clinical significance.

Case presentation

We report a case of intercoronary communication in a 56-year-old female who presented with acute chest pain and ST-segment depression in the lateral leads. High-sensitivity troponin-T was elevated and transthoracic echocardiography revealed normal left ventricular function with no regional wall motion abnormality. Hence, the diagnosis of acute coronary syndrome – non-st-elevation myocardial infarction was considered. Coronary angiography revealed a 95% focal stenosis in the major obtuse marginal artery (OM). The right coronary artery (RCA) angiogram revealed a single abnormal channel communicating the right posterolateral branch (PLV) and the distal left circumflex artery (LCX) with retrograde opacification of the proximal LCX, left main coronary artery (LMCA) and left aortic sinus. After she underwent revascularization with the drug-eluting stent to the OM. CT-coronary angiography confirmed the presence of intercoronary communication (ICC) between the right posterolateral branch and the distal LCX artery. No active intervention was done for the ICC. Over a year of follow-up, our patient remained asymptomatic.

Conclusions

Angiographically and anatomically, collaterals and intercoronary communications should be differentiated. Obstructive coronary artery disease leads to the development of collaterals, which are typically less than 1 mm in diameter, multiple and tortuous. However, ICC tends to be single and straight, usually seen without obstructive disease with unidirectional or bidirectional flow. Histologically, collaterals consist of endothelium supported by poorly organized collagen, muscle and elastic fibers. Meanwhile, ICCs resemble epicardial vessels in that they have a well-defined muscular layer. This case emphasizes the importance of recognizing this rare coronary anomaly and distinguishing it from collaterals to help in accurate diagnosis. Although they can provide an efficient blood supply to the jeopardized myocardium and can aid as a channel during coronary interventions, they can also cause myocardial ischemia by coronary steal.
Early structural valve deterioration following transcatheter aortic valve implantation in a patient with Scheie syndrome: a case report
Authors: Yanagino Yusuke , Kainuma Satoshi , Toda Koichi , Kawamura Ai , Kawamura Takuji , Yoshioka Daisuke , Taira Masaki , Shimamura Kazuo , Miyagawa Shigeru
Published: October 2024

Background

Scheie syndrome, an attenuated subtype of mucopolysaccharidosis type I, is a rare storage disease that causes progressive glycosaminoglycans (GAGs) accumulation. Cardiovascular disorders determine the prognosis, and cardiac valve abnormalities are the most common cause. The patients are usually young so mechanical valve replacement is often performed, but because of the features of this disease, the surgical treatment is very risky. Recently, transcatheter aortic valve implantation (TAVI) has been reported as an alternative choice for aortic stenosis, but optimal choice is still unclear. Here, we introduce a patient that underwent TAVI and refer to the histological finding of a biological valve extracted in relation to GAGs accumulation.

Case presentation

A 54-year-old woman with Scheie syndrome underwent valve surgeries three times throughout her whole life. At age 41, she received a mitral valve replacement with a mechanical valve for mitral stenosis. She promptly developed severe diastolic dysfunction and low output syndrome after the release of aortic clamping, thus requiring temporary mechanical circulatory support4. At age 51, she suffered from heart failure due to severe aortic stenosis and underwent TAVI because conventional aortic valve replacement (AVR) was deemed too risky. Three years later, her heart failure relapsed, and an echocardiogram unexpectedly revealed thickened bioprosthetic valve leaflets and a significant pressure gradient across the valve, consistent with early structural valve deterioration. AVR was performed via median sternotomy with a mechanical valve. As with the first operation, she presented refractory heart failure requiring mechanical circulatory support and was meticulously managed. However, she steadily showed worsening of multiple organ systems and died 9 days after the operation. Pathological autopsy and histological examination revealed accumulation of tissue with GAGs on the leaflets of the bioprosthetic valve of TAVI, which may have been the cause of early structural valve deterioration.

Conclusion

For patients with Scheie syndrome, a biological valve can be compromised by the accumulation of GAGs, thereby causing early SVD. These findings may support valve selection for these high-risk patients.
Towards democratised psychiatry: building metacommunities for inclusive and equitable global mental health
Authors: Reba Yansen Alberth , Muttaqin M. Zaenul , Prasetya Yovian Yustiko
Published: October 2024

Through their study, George Ikkos & Nick Bouras reveal that the responsibilities of the psychiatric community are increasingly complex, especially amid the onslaught of globalisation and the confines of neoliberalism. ‘Metacommunity’ in this context refers not only to the history of psychiatrists but their role in strengthening and influencing mental health policies. A number of challenges continue to emerge in the public sphere, highlighting the need for psychiatry to adapt to society's evolving demands for inclusivity, equity and ethical governance. These challenges emphasise the importance of shaping the future of psychiatry that is responsive to the complexities of mental health care and aligned with democratic principles that prioritise transparency and social accountability. We have added several aspects that could complement psychiatrists' future theory and practice, including a more collaborative and evidence-based approach to dealing with increasingly complex mental health issues.
Self-Nanoemulsifying/ Self-Assembled Cubic Nanoparticles Lyophilized Tablet: A Novel Biphasic Release Approach to Enhance the Bioavailability of a Lipophilic Drug
Authors: Farag Michael M. , El-Sebaie Wessam , Basalious Emad B. , El-Gazayerly Omaima N.
Published: October 2024

This study aimed to prepare a combined self-nanoemulsifying and self-assembled cubic nanoparticles (SNE/SAC) lyophilized tablet eliciting biphasic release pattern escorted with enhanced bioavailability for drugs hampered with slow dissolution and poor absorption. The antimuscarinic Darifenacin hydrobromide (DRF) was selected as a model drug used to treat overactive bladder-associated nocturia. The DRF-SNE/SAC lyophilized tablet was prepared so that upon reconstitution a mixture of DRF-loaded cubic nanoparticles and nanoemulsion dispersion is obtained. The nanoemulsion portion is responsible for the fast release followed by controlled release of the remaining dose loaded in cubic nanoparticles. A comparative pharmacokinetic study adopting randomized crossover design in male albino rabbits versus marketed product Frequefenacine® tablet was performed. Half of the dose (52.05% ± 4.21%) was rapidly released in the first 4 h followed by sustained release of the remaining drug where (90.16% ± 8.85%) was released in 24 h. The tested system showed 2.45 folds higher % relative bioavailability and 1.57 folds higher Cmax with 1.62 longer residence time relative to reference product. The results endow the ability of the developed DRF-SNE/SAC lyophilized tablet to be considered as a propitious approach for the treatment of overactive bladder-associated nocturia without midnight dose administration.

Graphical Abstract
Effect of Liquid Load Level and Binder Type on the Tabletability of Mesoporous Silica Based Liquisolids
Authors: Appelhaus Jan , Steffens Kristina E. , Wagner Karl G.
Published: October 2024

Mesoporous silica offers an easy way to transform liquids into solids, due to their high loading capacity for liquid or dissolved active ingredients and the resulting enhanced dissolution properties. However, the compression of both unloaded and loaded mesoporous silica bulk material into tablets is challenging, due to poor/non-existing binding capacity. This becomes critical when high drug loads are to be achieved and the fraction of additional excipients in the final tablet formulation needs to be kept at a minimum. Our study aimed to investigate the mechanism of compression and tabletability dependent on the Liquid Load Level of the silica and type of filler/binder in binary tabletting mixtures. To this end, Vivapur® 101, FlowLac® 90, Pearlitol® 200 SD and tricalcium citrate tetrahydrate were selected and mixed with Syloid® XDP 3050 at various Liquid Load Levels. Compaction characteristics were analysed using the StylOne® Classic 105 ML compaction simulator. Additionally, the Overall Liquid Load (OLL) was defined as a new critical quality attribute for liquisolid tablets. The Overall Liquid Load allows straightforward, formulation-relevant comparisons between various fillers/binders, liquid components, and silica types. Results indicate strong binding capacity and high plasticity of the fillers/binders as key components for successful high liquid load silica tablet formulation. A volumetric combination of 30% Vivapur® 101 and 70% 0.75 mL/g loaded Syloid® XDP 3050 proved to be the most effective mixture, achieving an Overall Liquid Load of 36–41% [v/v] and maintaining a tensile strength of 1.5 N/mm2 with various liquid vehicles.

Graphical Abstract
Breakfast Habits in Patients Using Levothyroxine: Patient Experiences and Preferences
Authors: Willems Jeresa I A , van Twist Daan J L , Luu Inge H Y , Bianchi Rutgert , Peeters Robin P , Tummers-de Lind van Wijngaarden Roderick F A
Published: October 2024

Background

Levothyroxine (LT4) is recommended to be ingested in a fasting state, 30-60 minutes before breakfast to avoid interactions with food and drugs. In clinical practice, we noticed that this instruction may be inconvenient for patients. Therefore, we aimed to evaluate patient experiences and preferences concerning the recommended fasting administration of LT4.

Methods

Patients using LT4 were invited to complete a questionnaire. Regression analyses were performed to identify patient characteristics associated with taking LT4 close to or together with food and/or interfering drugs, feeling burdened with postponing breakfast, and preferring nonfasting LT4 ingestion.

Results

Of 463 invited patients, 410 completed the questionnaire (88.6%). Of these, 76.8% was female and median age was 57 years (interquartile range: 43-67). Nearly all patients (97.3%) reported to have received instruction on fasting LT4 ingestion, but only 30% adhered to this. Nonfasting LT4 intake was associated with use of co-medication (odds ratio [OR], 2.82; 95% CI, 1.77-4.47), treatment duration >1 year (OR, 1.76; 95% CI, 1.02-3.04), and male sex (OR, 1.67; 95% CI, 1.03-2.70). Approximately half of the patients reported being burdened with postponing breakfast and the majority (60.5%) expressed their preference for nonfasting LT4 ingestion. Interestingly, 25% omitted breakfast and 13.4% forgot their medication because of the fasting requirement. Furthermore, the majority (68.2%) of patients that used interfering drugs stated not to be instructed to separate these drugs from LT4.

Conclusion

This study highlights the burden associated with fasting LT4 ingestion, leading to nonadherence, irregular LT4 intake, and omitting breakfast. Given the clear preferences towards nonfasting LT4 ingestion, further research into alternative nonfasting administration methods is warranted.