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Introduction: Benzodiazepines are frequently prescribed and misused therefore urine drug screening (UDS) is performed in many patient populations. Most current benzodiazepine immunoassays have poor sensitivity, particularly for detecting the metabolites of newer benzodiazepines such as lorazepam in urine. Objectives: We aimed to verify the clinical performance of the new qualitative Roche Benzodiazepines II (BNZ2) immunoassay, as well as compare its performance to the Roche Benzodiazepines Plus (BENZ) assay in two patient populations: UDS in the emergency department (ED) and compliance monitoring. Methods: An initial verification study was performed, selecting for samples containing clonazepam and lorazepam metabolites. Performance of the BNZ2 and BENZ assays was compared to liquid chromatography-tandem mass spectrometry (LC-MS/MS) as the reference method. Sensitivity, specificity, false positive rate (FPR) and false negative rate (FNR) were determined. Results: We verified the performance claims in the initial verification and demonstrated similar precision, with coefficient of variations (CVs) of 12.8% and 7.7% for negative and positive controls, respectively. Furthermore, we observed higher clinical sensitivity and lower FNR with the BNZ2 assay in both the ED and compliance monitoring populations due to improved cross-reactivity for lorazepam and clonazepam metabolites. Despite these improvements, the BNZ2 assay was unable to detect 27% of specimens positive by LC-MS/MS, including specimens from patients using benzodiazepines without prescription. Discussion: Due to its improved performance and rapid turnaround time, the BNZ2 assay should be implemented for UDS in the ED. However, the assay should not replace LC-MS/MS testing for compliance monitoring, as unsuspected benzodiazepine use may go undetected.

La ciudad india de Fatehpur Sikri presenta una configuración urbana y territorial que entra en conflicto geométrico con el promontorio rocoso donde se asienta. Sin embargo, esta disposición, heredera de la tradición cultural islámica e hindú, es capaz también de crear un brillante recorrido espacial alejado de la configuración axial donde el giro y la sorpresa producen un interesante itinerario al atravesar sus palacios y sus edificios de arenisca roja. Asimismo, los edificios de la ciudad no son ajenos a este particular ordenamiento, y una serie de pabellones individuales organizan el recorrido por el espacio urbano actuando como puntos de referencia. Este artículo propone un estudio en cuanto al espacio urbano y arquitectónico de la ciudad manifestando cómo uno depende del otro indefectiblemente. De este modo, analiza cómo las ideas espaciales de los pabellones están entrelazadas con la idea madre de la ciudad. Para ello, los autores redibujan los planos de emplazamiento de Fatehpur Sikri y los planos de planta y sección de los pabellones con medidas y levantamientos tomados in situ.

Abstract Background Pulmonary ionocytes have been identified in the airway epithelium as a small population of ion transporting cells expressing high levels of CFTR (cystic fibrosis transmembrane conductance regulator), the gene mutated in cystic fibrosis. By providing an infinite source of airway epithelial cells (AECs), the use of human induced pluripotent stem cells (hiPSCs) could overcome some challenges of studying ionocytes. However, the production of AEC epithelia containing ionocytes from hiPSCs has proven difficult. Here, we present a platform to produce hiPSC-derived AECs (hiPSC-AECs) including ionocytes and investigate their role in the airway epithelium. Methods hiPSCs were differentiated into lung progenitors, which were expanded as 3D organoids and matured by air-liquid interface culture as polarised hiPSC-AEC epithelia. Using CRISPR/Cas9 technology, we generated a hiPSCs knockout (KO) for FOXI1, a transcription factor that is essential for ionocyte specification. Differences between FOXI1 KO hiPSC-AECs and their wild-type (WT) isogenic controls were investigated by assessing gene and protein expression, epithelial composition, cilia coverage and motility, pH and transepithelial barrier properties. Results Mature hiPSC-AEC epithelia contained basal cells, secretory cells, ciliated cells with motile cilia, pulmonary neuroendocrine cells (PNECs) and ionocytes. There was no difference between FOXI1 WT and KO hiPSCs in terms of their capacity to differentiate into airway progenitors. However, FOXI1 KO led to mature hiPSC-AEC epithelia without ionocytes with reduced capacity to produce ciliated cells. Conclusion Our results suggest that ionocytes could have role beyond transepithelial ion transport by regulating epithelial properties and homeostasis in the airway epithelium.

Abstract We revisit the Next-to-Leading Order (two-loop) contributions to the Anomalous Dimensions of ∆F = 1 four-quark operators in QCD. We devise a test for anomalous dimensions, that we regard as of general interest, and by means of which we detect a problem in the results available in the literature. Deconstructing the steps leading to the available result, we identify the source of the problem, which is related to the operator known as Q 11. We show how to fix the problem and provide the corrected anomalous dimensions. With the insight of our findings, we propose an alternative approach to the one used in the literature which does not suffer from the identified disease, and which confirms our corrected results. We assess the numerical impact of our corrections, which happens to be in the ballpark of 5% in certain entries of the evolution matrix. Our results are important for the correct resummation of Next-to-Leading Logarithms in analyses of physics beyond the Standard Model in ∆F = 1 processes, such as the decays of Kaons and B-mesons.

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft‐tissue sarcomas with a poor survival rate, presenting either sporadically or in the context of neurofibromatosis type 1 (NF1). The histological diagnosis of MPNSTs can be challenging, with different tumors exhibiting great histological and marker expression overlap. This heterogeneity could be partly responsible for the observed disparity in treatment response due to the inherent diversity of the preclinical models used. For several years, our group has been generating a large patient‐derived orthotopic xenograft (PDOX) MPNST platform for identifying new precision medicine treatments. Herein, we describe the expansion of this platform using six primary tumors clinically diagnosed as MPNSTs, from which we obtained six additional PDOX mouse models and three cell lines, thus generating three pairs of in vitro–in vivo models. We extensively characterized these tumors and derived preclinical models, including genomic, epigenomic, and histological analyses. Tumors were reclassified after these analyses: three remained as MPNSTs (two being classic MPNSTs), one was a melanoma, another was a neurotrophic tyrosine receptor kinase (NTRK)‐rearranged spindle cell neoplasm, and, finally, the last was an unclassifiable tumor bearing neurofibromin‐2 (NF2) inactivation, a neuroblastoma RAS viral oncogene homolog (NRAS) oncogenic mutation, and a SWI/SNF‐related matrix‐associated actin‐dependent regulator of chromatin (SMARCA4) heterozygous truncated variant. New cell lines and PDOXs faithfully recapitulated histology, marker expression, and genomic characteristics of the primary tumors. The diversity in tumor identity and their specific associated genomic alterations impacted treatment responses obtained when we used the new cell lines for testing compounds against known altered pathways in MPNSTs. In summary, we present here an extension of our MPNST precision medicine platform, with new PDOXs and cell lines, including tumor entities confounded as MPNSTs in a real clinical scenario. This platform may constitute a useful tool for obtaining correct preclinical information to guide MPNST clinical trials.

While the impact of authentic research experiences in STEM on student engagement and interest in science has been documented, less is known about the role of peer communities in fostering this interest and engagement. This research explores the idea that a strong peer community can catalyze deep learning and engagement in scientific research among high school students. The program engaged 20 high school students in a year-long community-based participatory research project in public health each year. The study used a mixed methods approach, combining data from focus group discussions, observations, and surveys to describe the program's impact on participants. Analysis across three years reveals that (a) the program was associated with a statistically significant shift in students' identity as researchers, with a medium growth effect size (Cohen's d) for the second and third years, which moderated by the end of the program, and (b) the peer community played a central role in the participants' engagement in the program, on their identity as researchers, and strengthened their interest in STEM. These findings convey the importance of designing STEM experiences that build strong peer communities around science practices and how such communities can have profound impacts on students' identities in STEM.

Introduction: Angiolipomatosis is a rare benign condition involving subcutaneous fat and blood vessels, particularly uncommon in pediatric patients. Case presentation: An 11-year-old male presented with multiple firm, non-tender masses in the right gluteal and perianal regions, the largest measuring 8 cm for approximately 8 months duration. The patient underwent staged surgical excisions under general anesthesia due to extensive disease burden. In the first stage, perianal and medial gluteal masses were excised. Lipomatous masses were carefully dissected from the external anal sphincter to the posterior superior iliac spine (PSIS) with preservation of the external anal sphincter. The procedure was well tolerated, but the patient developed a postoperative wound infection, requiring intravenous antibiotics, debridement, and the creation of a loop colostomy to control wound contamination. Six weeks later, a second-stage excision removed the remaining gluteal masses, including a palpable mass measuring 8 x 4 × 2.5 cm. Hemostasis was achieved, and a Jackson-Pratt drain was placed to manage post-op wound fluid accumulation. The patient recovered well after both surgeries and at the 3-month follow-up, there were no complications. Pathological analysis confirmed angiolipomatosis in the gluteal region and diffuse lipomatosis in the perianal region. No recurrence was observed over a 3-year follow-up period. Conclusion: Angiolipomatosis should be considered as a differential diagnosis for pediatric soft tissue masses in uncommon locations like the gluteal and perianal regions. Atypical presentations can be successfully managed with careful surgical planning helping to avoid unnecessary radical procedures. A staged approach is recommended when encountering diffuse disease, as in this case, and consideration should be given to diverting ostomy if wound contamination is a concern.

We employ numerical models to explore the connection between subduction zone coupling or megathrust rupture and upper plate faults in the northern Cascadia forearc. Active forearc faults north of the Olympic Peninsula exhibit similar characteristics: west-northwest strike, oblique right-lateral slip senses, and low slip rates (

Summary: A diet lacking dietary fibers promotes the expansion of gut microbiota members that can degrade host glycans, such as those on mucins. The microbial foraging on mucin has been associated with disruptions of the gut-protective mucus layer and colonic inflammation. Yet, it remains unclear how the co-utilization of mucin and dietary fibers affects the microbiota composition and metabolic activity. Here, we used 14 dietary fibers and porcine colonic and gastric mucins to study the dynamics of mucin and dietary fiber utilization by the human fecal microbiota in vitro. Combining metaproteome and metabolites analyses revealed the central role of the Bacteroides genus in the utilization of complex fibers together with mucin while Akkermansia muciniphila was the main utilizer of sole porcine colonic mucin but not gastric mucin. This study gives a broad overview of the colonic environment in response to dietary and host glycan availability.

IntroductionScarce real-life data exists for COVID-19 management in hematologic disease (HD) patients in the Omicron era.PurposeTo assess the current clinical management and outcome of SARS-CoV-2 infection diagnosed, identify the risk factors for severe outcomes according to the HD characteristics and cell therapy procedures in a real-world setting.MethodsA retrospective observational registry led by the Spanish Transplant Group (GETH-TC) with 692 consecutive patients with HD from December 2021 to May 2023 was analyzed.ResultsNearly one-third of patients (31%) remained untreated and presented low COVID-19-related mortality (0.9%). Nirmatrelvir/ritonavir was used mainly in mild COVID-19 cases in the outpatient setting (32%) with a low mortality (1%), while treatment with remdesivir was preferentially administered in moderate-to-severe SARS-CoV-2 infection cases during hospitalization (35%) with a mortality rate of 8.6%. The hospital admission rate was 23%, while 18% developed pneumonia. COVID-19-related mortality in admitted patients was 14%. Older age, autologous hematopoietic stem cell transplantation (SCT), chimeric antigen receptor T-cell therapy, corticosteroids and incomplete vaccination were factors independently associated with COVID-19 severity and significantly related with higher rates of hospital admission and pneumonia. Incomplete vaccination status, treatment with prior anti-CD20 monoclonal antibodies, and comorbid cardiomyopathy were identified as independent risk factors for COVID-19 mortality.ConclusionsThe results support that, albeit to a lower extent, COVID-19 in the Omicron era remains a significant problem in HD patients. Complete vaccination (3 doses) should be prioritized in these immunocompromised patients. The identified risk factors may help to improve COVID-19 management to decrease the rate of severe disease, ICU admissions and mortality.

Octadecylphosphonic acid self-assembled monolayers were used as a combined carbon and hydrogen source to grow graphene films on sapphire substrates via hot filament chemical vapor deposition. The functionalized substrates were sealed with a thin Cu film and heated to 950°C under Ar flow. After synthesis, the Cu was etched away. The graphene samples then underwent a hydrogenation treatment in the same reactor setup, exposed to a CH4/H2 gas mixture at 820°C for 2 hours. The structure and properties of the graphene films before and after hydrogenation were characterized. Raman spectroscopy was employed to probe the defect-related bands and C-H bonding. X-ray diffraction provided insights into the crystalline structure and interlayer spacing. The ferromagnetic response was measured using a PPMS system across a range of temperatures and magnetic fields. XPS was used to assess the chemical composition and bonding. This multi-step process enabled a detailed evaluation of the novel synthesis protocol and its effects on the resulting hydrogenated graphene material.

Introduction: chronic kidney disease is an aggravating condition for the public health system. The detection and timely monitoring of the triggering and progression factors of the disease are a priority in each health system. Objective: to characterize chronic kidney disease in patients with type 2 diabetes mellitus with poor metabolic control. Method: a descriptive, cross-sectional study was carried out on patients with type 2 diabetes mellitus who entered the chronic kidney disease program of the Hospital “Dr. Miguel Enríquez” from October 2021 to January 2023. The population was made up of 175 patients; the sample selected was of 74 patients, who met the inclusion criteria after signing the informed consent. Results: there was a predominance of chronic kidney disease in young patients (64% in 18 to 49 years olds); likewise, the female sex represented a 65.3%; and a duration of type 2 diabetes mellitus of 1 to 5 years in 49.3%; the most frequent comorbidities were: dyslipidemia, arterial hypertension and heart failure with a prevalence of 89.3%, 79.3% and 41.3% respectively. The predominant kidney damage stage was grade 2 in a 20.0%; 4% of patients required renal replacement treatment. Conclusions: kidney disease usually progresses more in women and in patients with multiple cardiovascular risk factors. Inadequate glycemic control is associated with the progression of kidney disease. Damage to kidney function largely depends on metabolic control.

Fundamento: La educación con enfoque inclusivo en Cuba es prioridad, ella está en el centro de los estudios que realizan psicólogos, pedagogos y especialistas; por ello es necesaria la preparación de profesores en esta dirección. En el caso del profesor de Educación Física en los distintos niveles educativos debe aprovechar las posibilidades que ofrece el deporte para la estimulación de potencialidades en los escolares con situación de discapacidad, lo que ayudaría a mejorar este proceso en la escuela primaria contemporánea. Objetivo: Proponer un sistema de actividades para la preparación de los profesores de Educación Física de manera que favorezca el desarrollo de habilidades, conocimientos y motivaciones para la dirección del Deporte para Todos con enfoque inclusivo. Metodología: Se trabajó con los 20 profesores de Educación Física que pertenecen a las 8 escuelas generales que están inmersas en el proceso de inclusión y la escuela especial en el municipio Cabaiguán, específicamente en el sector urbano. Se emplearon diferentes métodos de investigación, como la observación, análisis de documentos, entrevista y criterio de especialistas. Resultado: La propuesta de actividades de preparación para los profesores de Educación Física permite un eficiente trabajo en la organización, desarrollo y dirección del Deporte para Todos en un contexto deportivo inclusivo y sostenible, incentiva la creatividad e innovación, mejora el nivel de preparación del profesor permitiendo transformar la práctica educativa. Los especialistas consideraron las actividades como bastante adecuado para la preparación del profesor de Educación Física, pues sus perspectivas inclusivas ofrecen respuestas a la necesidad de organizar y desarrollar el Deporte para Todos con escolares en situación de discapacidad en las escuelas. Conclusiones: El sistema de actividades para la preparación de los profesores de Educación Física puede incidir de manera favorable, permitiendo el desarrollo de habilidades, conocimientos y nuevas motivaciones en la dirección del Deporte para Todos con enfoque inclusivo.

Lithium–sulfur batteries (LiSBs) offer high energy density, cost-effectiveness, and eco-friendliness, making them promising for future energy storage. This study explores using BiFeO3 (BFO) nanoparticles (NPs) to tackle challenges such as lithium polysulfides (LiPs) and shuttle issues in LiSBs. It employs a solid-state melt diffusion technique, encapsulates sulfur in single-walled carbon nanotubes (SCNTs), and utilizes BFO for effective polysulfide control. Herein, composite cathodes of sulfur (S)/SCNTs (abbr. SCNT) were fabricated, and cells were designed using a BFO-coated separator (SCNT-BFS). In addition, a cathode modification was performed with composite S/SCNTs/BFO (SCNT-BF), and a comparative analysis was conducted to assess the effectiveness of the BFO in the separator and the cathode. Cyclic voltammetry measurements revealed that the increased current peak intensity at lower reduction potential in SCNT-BF and SCNT-BFS indicated control of higher-order LiPs (Li2Sx, where 4 ≤ x ≤ 8), resulting in the generation of more stable lower-order products (Li2S2/Li2S). The charge/discharge analysis revealed controlled LiPs, resulting in high-capacity retention in SCNT-BF (∼75%) and SCNT-BFS (∼88%) over 200 cycles, which yielded capacities of 526 and 700 mAh/g at C/8 (1C = 1675 mA/g). These promising results suggest that incorporating BFO into the cathode and separator can advance the commercialization of durable LiSBs.

El resultado de este trabajo trató sobre los beneficios y riesgos de los sistemas de iluminación LED en el ámbito económico, social y medioambiental y la valoración de las condiciones para su empleo en Cuba. Se profundiza en la relación de las ventajas de esta tecnología con los beneficios que ofrece su aplicación en diferentes sectores de la sociedad y la economía. También, se aborda su impacto en la industria de la iluminación y en las comunidades no conectadas a la red eléctrica en los países en desarrollo. Además, se exponen los principales riesgos que implica su utilización, identificando los campos de investigación abiertos relacionados en esta dirección, y se demuestra la importancia de considerar en los proyectos, los riesgos de la iluminación LED. Finalmente, se exponen las condiciones existentes en Cuba, para el desarrollo de la iluminación LED y su contribución a la sostenibilidad e independencia energética.

La investigación se centró en el proceso de comunicación interna como problemática que incide en la comunicación organizacional de la Facultad de Ciencias Técnicas y Agropecuarias de La Universidad de Las Tunas y que tributa al logro de los objetivos estratégicos de la organización, en la que toman partido los estudiantes de la carrera Licenciatura en Turismo. El objetivo del artículo es fortalecer la comunicación interna en dicha facultad para mejorar la comunicación organizacional y contribuir al cumplimiento de su misión. Para su aplicación se empleó la complementariedad metodológica con métodos y técnicas cualitativas y cuantitativas. Este estudio constituyó el primero de comunicación organizacional efectuado en la facultad, de ahí su importancia y pertinencia. El diseño de la Estrategia de Comunicación Interna contribuye a perfeccionar las prácticas comunicativas basadas en los problemas y potencialidades identificados en el estudio.

Tin dioxide (SnO2) is a low-cost and high-capacity anode material for lithium-ion batteries, but the fast capacity fading significantly limits its practical applications. Current research efforts have focused on preparing sophisticated composite structures or optimizing functional binders, both of which increase material manufacturing costs. Herein, we utilize pristine and commercially available SnO2 nanopowders and enhance their cycling performance by simply narrowing the potential range and optimizing electrolytes. Specifically, a narrower potential range (0–1 V) mitigates the capacity fading associated with the conversion reaction, whereas an ether-based electrolyte further suppresses the volume expansion related to the alloy reaction. Consequently, this SnO2 anode delivers a promising battery performance, with a high capacity of ~650 mAhg−1 and stable cycling for 100 cycles. Our work provides an alternative approach to developing high-capacity and long-cycling metal oxide anode materials.

Transition metal oxides are considered to be highly promising anode materials for high-energy lithium-ion batteries. While carbon matrices have demonstrated effectiveness in enhancing the electrical conductivity and accommodating the volume expansion of transition metal oxide-based anode materials in lithium-ion batteries (LIBs), achieving an optimized utilization ratio remains a challenging obstacle. In this investigation, we have devised a straightforward synthesis approach to fabricate CuO nano powder integrated with carbon matrix. We found that with the use of a sodium carboxymethyl cellulose (CMC) based binder and fluoroethylene carbonate additives, this anode exhibits enhanced performance compared to acrylonitrile multi-copolymer binder (LA133) based electrodes. CuO@CMC electrodes reveal a notable capacity ~1100 mA h g−1 at 100 mA g−1 following 170 cycles, and exhibit prolonged cycling stability, with a capacity of 450 mA h g−1 at current density 300 mA g−1 over 500 cycles. Furthermore, they demonstrated outstanding rate performance and reduced charge transfer resistance. This study offers a viable approach for fabricating electrode materials for next-generation, high energy storage devices.

Sanfilippo syndrome, or mucopolysaccharidosis type III (MPS III), is a rare lysosomal disease caused by congenital enzymatic deficiencies in heparan sulfate (HS) degradation, leading to organ dysfunction. The most severe hallmark of MPS III comprises neurological alterations, although gastrointestinal symptoms (GISs) have also been shown to be relevant in many patients. Here, we explored the contribution of the gut microbiota to MPS III GISs. We analyzed the composition and functionality of the gut microbiota in two MPS III siblings with the same mutation (c.544C > T, c.1080delC, in the SGSH gene) and the same diet, but with differences in their GISs, including recurrent diarrhea in one of them. Using 16S sequencing, we observed that the MPS III patients exhibited decreased alpha diversity and a lower abundance of Lachnospiraceae and Bifidobacteriaceae accompanied by a higher abundance of the Ruminococcaceae and Rikenellaceae families than the healthy control subjects. Comparing siblings, we found an increased abundance of Bacteroidaceae and a lower abundance of Ruminococcaceae and Akkermansiaceae in the GIS-free patient. This patient also had a higher relative abundance of Sus genes (SusA, SusB, SusE, and SusG) involved in glycosaminoglycan metabolism. We found higher HS levels in the stool of the two MPS III patients than in healthy volunteers, particularly in the patient with GISs. Functionally, whole fecal metabolites from the patient with GISs induced oxidative stress in vitro in healthy monocytes. Finally, the Bacteroides thetaiotaomicron strain isolated from MPS III stool samples exhibited HS degradation ability. Overall, our results reveal different microbiota compositions and functionalities in MPS III siblings, who exhibited differential gastrointestinal symptomatology. Our study may serve as a gateway to explore the impact of the gut microbiota and its potential to enhance the quality of life in Sanfilippo syndrome patients.

Background: Periodontal emergencies are characterized by being painful, sudden and short-lasting, requiring emergency stomatological services. Objective: To describe periodontal emergencies in North Area patients in Sancti Spíritus. Methodology: A retrospective longitudinal descriptive study was conducted from January to June 2023. 87 patients who attended the Emergency Department of the Provincial Teaching Stomatology Clinic of Sancti Spíritus during this period were selected, with a periodontal emergency diagnosis. The used variables were age, sex and periodontal emergencies, absolute numbers and percentages were used as indicators. Results: The highest amount of patients were from the 19-34 years age group (33.3 %), female (56.3 %). The highest number was affected by aphthous stomatitis (44.8 %), followed by periodontal abscess (32.1 %) with a high incidence in the 60 and older age group. Conclusions: Aphthous stomatitis followed by periodontal abscess were the most frequent periodontal emergencies in the study.

Abstract Cardiac catheterization remains the gold standard for the diagnosis and management of pediatric pulmonary hypertension (PH). There is lack of consensus regarding optimal anesthetic and airway regimen. This retrospective study describes the anesthetic/airway experience of our single center cohort of pediatric PH patients undergoing catheterization, in which obtaining hemodynamic data during spontaneous breathing is preferential. A total of 448 catheterizations were performed in 232 patients. Of the 379 cases that began with a natural airway, 274 (72%) completed the procedure without an invasive airway, 90 (24%) received a planned invasive airway, and 15 (4%) required an unplanned invasive airway. Median age was 3.4 years (interquartile range [IQR] 0.7–9.7); the majority were either Nice Classification Group 1 (48%) or Group 3 (42%). Vasoactive medications and cardiopulmonary resuscitation were required in 14 (3.7%) and eight (2.1%) cases, respectively; there was one death. Characteristics associated with use of an invasive airway included age

The urgent demand for stable electrode materials, especially for the anode, arises in the pursuit of high-energy Li-ion batteries. This research focuses on bismuth oxide (Bi2O3) and uncovers its performance through a straightforward, commercially viable synthesis route, along with the optimization of binders and electrolytes. By employing a sodium carboxymethyl cellulose binder and fluoroethylene carbonate additives, the Bi2O3 anode demonstrates significantly enhanced performance compared to prior studies. It attains an impressive initial capacity of approximately 750 mA h g−1, exhibits excellent rate capability at 1000 mA g−1 and maintains stable cycling performance over 6000 cycles.

Abstract Ribosomes which can self-replicate themselves practically autonomously in beneficial physicochemical conditions have been recognized as the central organelles of cellular self-reproduction processes. The challenge of cell design is to understand and describe the rates and mechanisms of self-reproduction processes of cells as of coordinated functioning of ribosomes and the enzymatic networks of different functional complexity that support those ribosomes. We show that doubling times of proto-cells (ranging from simplest replicators up to those reaching the size of E. coli) increase rather with the number of different cell component species than with the total numbers of cell components. However, certain differences were observed between cell components in increasing the doubling times depending on the types of relationships between those cell components and ribosomes. Theoretical limits of doubling times of the self-reproducing proto-cells determined by the molecular parameters of cell components and cell processes were in the range between 6–40 min.

Abstract Background There are currently no models for the transition of patients with metabolic bone diseases (MBDs) from paediatric to adult care. The aim of this project was to analyse information on the experience of physicians in the transition of these patients in Spain, and to draw up consensus recommendations with the specialists involved in their treatment and follow-up. Methods The project was carried out by a group of experts in MBDs and included a systematic review of the literature for the identification of critical points in the transition process. This was used to develop a questionnaire with a total of 48 questions that would determine the degree of consensus on: (a) the rationale for a transition programme and the optimal time for the patient to start the transition process; (b) transition models and plans; (c) the information that should be specified in the transition plan; and (d) the documentation to be created and the training required. Recommendations and a practical algorithm were developed using the findings. The project was endorsed by eight scientific societies. Results A total of 86 physicians from 53 Spanish hospitals participated. Consensus was reached on 45 of the 48 statements. There was no agreement that the age of 12 years was an appropriate and feasible point at which to initiate the transition in patients with MBD, nor that a gradual transition model could reasonably be implemented in their own hospital. According to the participants, the main barriers for successful transition in Spain today are lack of resources and lack of coordination between paediatric and adult units. Conclusions The TEAM Project gives an overview of the transition of paediatric MBD patients to adult care in Spain and provides practical recommendations for its implementation.

Recent advancements in brain stimulation and nanomedicine have ushered in a new era of therapeutic interventions for psychiatric and neurodegenerative disorders. This review explores the cutting-edge innovations in brain stimulation techniques, including their applications in alleviating symptoms of main neurodegenerative disorders and addiction. Deep Brain Stimulation (DBS) is an FDA-approved treatment for specific neurodegenerative disorders, including Parkinson’s Disease (PD), and is currently under evaluation for other conditions, such as Alzheimer’s Disease. This technique has facilitated significant advancements in understanding brain electrical circuitry by enabling targeted brain stimulation and providing insights into neural network function and dysfunction. In reviewing DBS studies, this review places particular emphasis on the underlying main neurotransmitter modifications and their specific brain area location, particularly focusing on the dopaminergic system, which plays a critical role in these conditions. Furthermore, this review delves into the groundbreaking developments in nanomedicine, highlighting how nanotechnology can be utilized to target aberrant signaling in neurodegenerative diseases, with a specific focus on the dopaminergic system. The discussion extends to emerging technologies such as magnetoelectric nanoparticles (MENPs), which represent a novel intersection between nanoformulation and brain stimulation approaches. These innovative technologies offer promising avenues for enhancing the precision and effectiveness of treatments by enabling the non-invasive, targeted delivery of therapeutic agents as well as on-site, on-demand stimulation. By integrating insights from recent research and technological advances, this review aims to provide a comprehensive understanding of how brain stimulation and nanomedicine can be synergistically applied to address complex neuropsychiatric and neurodegenerative disorders, paving the way for future therapeutic strategies.

Although pulmonary embolism (PE) is a frequent complication in COVID-19, its consequences remain unknown. We performed pulmonary function tests, echocardiography and computed tomography pulmonary angiography and identified blood biomarkers in a cohort of consecutive hospitalized COVID-19 patients with pneumonia to describe and compare medium-term outcomes according to the presence of PE, as well as to explore their potential predictors. A total of 141 patients (56 with PE) were followed up during a median of 6 months. Post-COVID-19 radiological lung abnormalities (PCRLA) and impaired diffusing capacity for carbon monoxide (DLCOc) were found in 55.2% and 67.6% cases, respectively. A total of 7.3% had PE, and 6.7% presented an intermediate–high probability of pulmonary hypertension. No significant difference was found between PE and non-PE patients. Univariate analysis showed that age > 65, some clinical severity factors, surfactant protein-D, baseline C-reactive protein, and both peak red cell distribution width and Interleukin (IL)-10 were associated with DLCOc < 80%. A score for PCRLA prediction including age > 65, minimum lymphocyte count, and IL-1β concentration on admission was constructed with excellent overall performance. In conclusion, reduced DLCOc and PCRLA were common in COVID-19 patients after hospital discharge, but PE did not increase the risk. A PCRLA predictive score was developed, which needs further validation.

Adiabatic logic has been proposed as a method for drastically reducing power consumption in specialized low-power circuits. They often require specialized clock drivers that also function as the main power supply, in contrast to standard CMOS logic, and these power clocks are often a point of difficulty in the design process. A novel, stepwise charging driver circuit for four-phase adiabatic logic is proposed and validated through a simulation study. The proposed circuit consists of two identical driver circuits each driving two opposite adiabatic logic phases. Its performance relative to ideal step-charging and a standard CMOS across mismatched phase loads is analyzed, and new best practices are established. It is compared to a reference circuit consisting of one driver circuit for each phase along with a paired on-chip tank capacitor. The proposed driver uses opposite logic phases to act as the tank capacitor for each other in a “self-tanked” fashion. Each circuit was simulated in 15 nm FinFET across a variety of frequencies for an arbitrary logic operation. Both circuits showed comparable power consumption at all frequencies tested, yet the proposed driver uses fewer transistors and control signals and eliminates the explicit tank capacitors entirely, vastly reducing circuit area, complexity, and development time.