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Background Insufficient or excessive respiratory effort during acute hypoxemic respiratory failure (AHRF) increases the risk of lung and diaphragm injury. We sought to establish whether respiratory effort can be optimized to achieve lung- and diaphragm-protective (LDP) targets (esophageal pressure swing − 3 to − 8 cm H 2 O; dynamic transpulmonary driving pressure ≤ 15 cm H 2 O) during AHRF. Methods In patients with early AHRF, spontaneous breathing was initiated as soon as passive ventilation was not deemed mandatory. Inspiratory pressure, sedation, positive end-expiratory pressure (PEEP), and sweep gas flow (in patients receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO)) were systematically titrated to achieve LDP targets. Additionally, partial neuromuscular blockade (pNMBA) was administered in patients with refractory excessive respiratory effort. Results Of 30 patients enrolled, most had severe AHRF; 16 required VV-ECMO. Respiratory effort was absent in all at enrolment. After initiating spontaneous breathing, most exhibited high respiratory effort and only 6/30 met LDP targets. After titrating ventilation, sedation, and sweep gas flow, LDP targets were achieved in 20/30. LDP targets were more likely to be achieved in patients on VV-ECMO (median OR 10, 95% CrI 2, 81) and at the PEEP level associated with improved dynamic compliance (median OR 33, 95% CrI 5, 898). Administration of pNMBA to patients with refractory excessive effort was well-tolerated and effectively achieved LDP targets. Conclusion Respiratory effort is frequently absent  under deep sedation but becomes excessive when spontaneous breathing is permitted in patients with moderate or severe AHRF. Systematically titrating ventilation and sedation can optimize respiratory effort for lung and diaphragm protection in most patients. VV-ECMO can greatly facilitate the delivery of a LDP strategy. Trial registration : This trial was registered in Clinicaltrials.gov in August 2018 (NCT03612583).

In recent decades, the use of nanomaterials has received much attention in industrial and medical fields. However, some reports have mentioned adverse effects of these materials on the biological systems and cellular components. There are several major mechanisms for cytotoxicity of nanoparticles (NPs) such as physicochemical properties, contamination with toxic element, fibrous structure, high surface charge and radical species generation. In this review, a brief key mechanisms involved in toxic effect of NPs are given, followed by the in vitro toxicity assays of NPs and prooxidant effects of several NPs such as carbon nanotubes, titanium dioxide NPs, quantum dots, gold NPs and silver NPs.

With the rapid growth of population and the increasing demand for food worldwide, improving productivity in farming procedures is essential. Smart farming is a concept that emphasizes the use of modern technologies such as the Internet of Things (IoT) and artificial intelligence (AI) to enhance productivity in farming practices. In a smart farming scenario, large amounts of data are collected from diverse sources such as wireless sensor networks, network-connected weather stations, monitoring cameras, and smartphones. These data are valuable resources to be used in data-driven services and decision support systems (DSS) in farming applications. However, one of the major challenges with these large amounts of agriculture data is their immense diversity in terms of format and meaning. Moreover, the different services and technologies in a smart farming ecosystem have limited capability to work together due to the lack of standardized practices for data and system integration. These issues create a significant challenge in cooperative service provision, data and technology integration, and data-sharing practices. To address these issues, in this paper, we propose the platform approach, a design approach intended to guide building effective, reliable, and robust smart farming systems. The proposed platform approach considers six requirements for seamless integration, processing, and use of farm data. These requirements in a smart farming platform include interoperability, reliability, scalability, real-time data processing, end-to-end security and privacy, and standardized regulations and policies. A smart farming platform that considers these requirements leads to increased productivity, profitability, and performance of connected smart farms. In this paper, we aim at introducing the platform approach concept for smart farming and reviewing the requirements for this approach.

Background Global prevalence of osteoporosis and fragility fractures is increasing due to the aging population. Proximal femoral fractures are among the most common orthopedic conditions in elderly that significantly cause health deterioration and mortality. Here, we aimed to evaluate the mortality rates and risk factors, besides the functional outcomes after these injuries. Methods In a retrospective cohort study, all patients admitted with a femoral neck or intertrochanteric fracture between 2016 and the end of 2018 were enrolled in this study. Medical records were reviewed to include patients over 60 years of age who had a proximal femoral fracture and had a complete medical record and radiographs. Exclusion criteria included patients with pathological fractures, cancer under active treatment, follow-up loss, and patient access loss. Demographic and clinical features of patients alongside the details of fracture and patient management were recorded and analyzed. In-hospital and post-discharge mortalities due to included types of fractures at one and 12 months were the primary outcome. Modified Harris Hip Scores (mHHS) was the measure of functional outcome. Results A total of 788 patients including 412 females (52.3%) and 376 males (47.7%) with a mean age of 76.05 ± 10.01 years were included in this study. Among patients, 573 (72.7%) had an intertrochanteric fracture, while 215 (27.3%) had a femoral neck fracture, and 97.1% of all received surgical treatment. With a mean follow-up of 33.31 months, overall mortality rate was 33.1%, and 5.7% one-month and 20.2% 12-months rates. Analysis of 1-month mortality showed a significant mortality difference in patients operated after 48 h of fracture (p = 0.01) and in patients with American Society of Anesthesiologists (ASA) scores of 3–4 compared to ASA scores of 1–2 (p = 0.001). One-year mortality data showed that the mortality rate in femoral neck fractures was lower compared to other types of fracture. Surgical delay of > 48 h, ASA scores of 3–4, and treatment by proximal femoral plate were associated with shorter survival. The overall mean mHHS score was 53.80 ± 20.78. Conclusion We found several risk factors of mortality, including age ≥ 80 years, a > 48-hour delay to surgery, and pre-operative ASA scores of 3–4 in patients with proximal femoral fracture. Furthermore, the use of a proximal femoral plate was a significant risk factor for mortality and lower mHHS scores.

This scenario was designed to investigate the protein corona pattern on the pillar-layer surface of a Cu-based metal–organic framework (MOF) in human plasma. The [Cu(L)(L / )].1.3DMA (MOF-1) {L = 4, 4 / -bipyridine and L /  = 5-aminoisophthalic acid}, was synthesized through the sonochemical irradiation approach as well as characterized by various techniques like scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray powder diffraction and single-crystal X-ray diffraction. The space group was determined to be an orthorhombic space group ( Pbam ) by single-crystal X-ray diffraction. Single-crystal X-ray analyses on MOF-1 showed that Cu +2 ion was 6-coordinated. Besides, to study and clarify interactions between MOFs and biological milieu, human whole blood plasma was selected as a model. Fluorescence spectroscopy and SDS-PAGE techniques were employed to explore quantitative and qualitative in situ characterization of protein corona as well. Furthermore, cell viability in a cancerous cell lines was evaluated by MTT assay in the presence and absence of the corona. The results from SDS-PAGE illustrated that the most adsorbed quantity among plasma proteins belongs to fibrinogen (α, β and γ chains), and this protein showed the maximum frequency on the MOF-1s surface, so the possible interactions of MOF-1s with fibrinogen also studied using fluorescence spectroscopy and corresponding data were plotted. According to the obtained data from MTT assay, these structures have concentration-dependent toxicity. In brief, based on the obtained data in the current study, the designed MOF can be introduced as a new desirable carrier for drug/gen delivery after further prerequisite assessments.

Triple-negative breast cancer (TNBC), which affects 15-20% of cases, lacks targeted therapies and poses challenges in treatment. MicroRNAs (miRNAs) are potential biomarkers and therapeutic targets in breast cancer. To unravel its unique regulatory role, this study focused on miRNA microarray analysis, particularly miR-548F-3p, in TNBC samples. Using the GSE76275 dataset, gene expression profiles were analyzed using the Affymetrix Human Genome U133 Plus 2.0 Array. Differentially expressed genes (DEGs) were identified using robust preprocessing. Weighted gene co-expression network analysis (WGCNA) explored gene modules and identified hub genes co-expressed with miR-548F-3p. Functional enrichment and protein-protein interaction (PPI) network analyses were conducted. Survival analysis was used to assess the prognostic impact of the identified genes. The study found 224 up-regulated DEGs, with miR-548F-3p exhibiting significant down-regulation. MultimiR identified 400 genes that were targeted by miR-548F-3p. WGCNA revealed a blue co-expression module, with 356 genes targeted by miR-548F-3p. A Venn diagram identified common genes, including VANGL2, BRCC3, ANP32E, and ANLN. Functional enrichment highlighted crucial pathways in TNBC pathogenesis, including mitotic spindle organization, spindle assembly checkpoint signaling, cell cycle, and amino acid (serine) metabolism. PPI network analysis identified hub genes, including FOXM1, KIF23, and CDC20. VANGL2, BRCC3, ANP32E, and ANLN were significantly associated with patient outcomes in survival analysis. This analysis highlighted TNBC's molecular landscape, emphasizing miR-548F-3p's regulatory role. The identified genes, VANGL2, BRCC3, ANP32E, and ANLN, offer insights into TNBC pathogenesis and potential therapeutic targets, laying the foundation for understanding their clinical implications in the intricate landscape of TNBC.

Bone tissue engineering aims to produce bone substitutes that are crucial for tissue repair. In this study, a three-dimensional (3D) host-guest scaffold model was developed. A porous polylactic acid (PLA) framework (host) was fabricated using a 3D printing technique to provide mechanical stability. The pores in the framework were subsequently occupied with nano-hydroxyapatite (HA), gelatin (G), and blueberry extract (BB) mixed with different ratios (guest). The physicochemical, mechanical, and biological behavior of the scaffolds were investigated. The results exhibited that all fabricated scaffolds degraded gradually as time progressed, with less than 20% degradation occurring within 56 days. The host-guest scaffolds favorably influenced the viability and attachment of MC3T3-E1 cells in vitro. Based on the MTT assay results, all scaffolds showed excellent cell viability, particularly HA10-BB40. Furthermore, the cell attachment increased on the surfaces of scaffolds with increasing HA and BB content. Specifically, high number of cells were observed on HA10-BB20 and HA10-BB40. Meanwhile, the best cell mineralization was detected in HA10-BB40 group. Additionally, the scratch assay also showed the ability of BB to enhance cell migration. According to these findings, HA10-BB40 was identified as the best scaffold composition and further analyzed for mechanical properties, wettability, apatite formation ability, and gene expression. The compressive strength of HA10-BB40 was 4.92 MPa, and its surface demonstrated hydrophilic characteristic. This scaffold formed a uniform apatite layer on its surface after 7 days of immersion in SBF. In addition, the expression of Runx2, Col1α1, and VEGF genes in HA10-BB40 significantly enhanced compared to the control group. This study showed the potential of the fabricated host-guest scaffolds, particularly HA10-BB40, as a favorable substrate for engineered bone replacements.

ObjectivePhenytoin has been shown to reduce the peripapillary retinal nerve fiber layer (pRNFL) loss in optic neuritis (ON). We evaluated the effects of phenytoin on retinal ganglion layers and visual outcomes of newly diagnosed acute ON.MethodsA randomized, placebo-controlled trial was conducted in a tertiary referral eye hospital and patients with the first episode of typical demyelinating ON, without any history of multiple sclerosis were randomly assigned to phenytoin or placebo. The thickness of ganglion cell-inner plexiform layer (GCIPL) measured by optical coherence tomography (OCT) was considered as the primary outcome.ResultsOne patient in the phenytoin group developed severe cutaneous rashes that progressed to Stevens-Johnson syndrome (SJS)/toxic epidermal necrosis (TEN), and further allocation of patients to the phenytoin group was stopped, and finally fifteen participants were included in the phenytoin group. Fifty-one patients were enrolled to the placebo group, from which four were excluded. Both visual acuity and field were not significantly different between the control and phenytoin groups after 1 and 6 months. Mean 3- and 6-mm macular GCIPL thicknesses decreased after 6 months to 73.6 ± 14.1 and 57.9 ± 7.5 μm, respectively, in the phenytoin group and to 71.6 ± 15.7 and 55.6 ± 6.6 μm, respectively, in the placebo group with no significant differences between the two groups (P = 0.77 and P = 0.26, respectively, linear multilevel model).ConclusionPhenytoin is not probably safe and effective as neuroprotection after acute ON. Further investigation with other sodium channel inhibitors could be considered.

Acute myeloid leukemia (AML) is an aggressive blood cancer with frequently poor clinical outcomes. This heterogeneous malignancy encompasses genetically, molecularly, and even clinically different subgroups. This makes it difficult to develop therapeutic agents that are effective for all subtypes of the disease. Therefore, a selective, universal, and adaptable delivery platform capable of carrying various types of anti-neoplastic agents is an unmet requirement in this area. Two multifunctional fusion proteins were designed for the delivery of biotinylated cargoes to human myeloid leukemia cells by fusing an anti-IL-1RAP single-chain antibody with streptavidin (tetramer or monomer), a cell-penetrating peptide (CPP), and an endosomolytic peptide in a single biomacromolecule. The designed fusions were analyzed primarily in silico, and the biofunctionality of the selected fusion was fully characterized via several binding assays, hemolysis assay, confocal microscopy and cell cytotoxicity assay after production via the Escherichia coli ( E. coli ) system. The refolded protein exhibited desirable binding activity to leukemic cells, pure antigen and biotinylated BSA. Further analyses revealed efficient cellular uptake, endosomolytic activity, and nuclear penetration without any detectable cytotoxicity toward normal epithelial cells. The described platform seems to have great potential for targeted delivery of different therapeutics to malignant myeloid cells.

Multiples of the normal median (MoM) of free βHCG is a valuable parameter in evaluation of risk of adverse pregnancy outcomes. In the current retrospective study, we assessed the maternal and fetal outcomes in pregnant women having free βHCG MoM levels < 0.2 or > 5 in their first trimester screening (FTS). Relative risk of trisomy 21 was significantly higher in patients having free βHCG MoM > 5. On the other hand, relative risk of trisomies 13 and 18 and Turner syndrome were higher in those having free βHCG MoM < 0.2. Other chromosomal abnormalities were nearly equally detected between those having free βHCG MoM < 0.2 or > 5. Relative risk of hydrocephaly and hydrops fetalis was higher when free βHCG MoM was below 0.2. On the other hand, relative risk of low birth weight was higher when free βHCG MoM was above 5. Moreover, frequency of gestational diabetes mellitus, preeclampsia, preterm delivery and vaginal bleeding increased with levels of free βHCG MoM. However, polyhydramnios had the opposite trend. Frequencies of premature rupture of membranes and pregnancy induced hypertension were highest among pregnant women having levels of free βHCG MoM < 0.2. The current study indicates importance of free βHCG MoM in identification of at-risk pregnancies in terms of both fetal and maternal outcomes. In fact, βHCG MoM < 0.2 or > 5 can be regarded as risk factors for adverse maternal or fetal outcomes irrespective of the presence of other abnormalities in the FTS results.