Long-Term Outcomes Following Definitive or Adjuvant Proton Radiotherapy for Adenoid Cystic Carcinoma.

Purpose: Adenoid cystic carcinoma (ACC) is a rare malignancy accounting for 1% of all head and neck cancers. Treatment for ACC has its challenges and risks, yet few outcomes studies exist. We present long-term outcomes of patients with ACC of the head and neck treated with proton therapy (PT). Materials and Methods: Under an institutional review board-approved, single-institutional prospective outcomes registry, we reviewed the records of 56 patients with de novo, nonmetastatic ACC of the head and neck treated with PT with definitive (n = 9) or adjuvant PT (n = 47) from June 2007 to December 2021. The median dose to the primary site was 72.6 gray relative biological equivalent (range, 64-74.4) delivered as either once (n = 19) or twice (n = 37) daily treatments. Thirty patients received concurrent chemotherapy. Thirty-one patients received nodal radiation, 30 electively and 1 for nodal involvement. Results: With a median follow-up of 6.2 years (range, 0.9-14.7), the 5-year local-regional control (LRC), disease-free survival, cause-specific survival, and overall survival rates were 88%, 85%, 89%, and 89%, respectively. Intracranial extension (P = .003) and gross residual tumor (P = .0388) were factors associated with LRC rates. While the LRC rate for those with a gross total resection was 96%, those with subtotal resection or biopsy alone were 81% and 76%, respectively. The 5-year cumulative incidence of clinically significant grade ≥3 toxicity was 15%, and the crude incidence at the most recent follow-up was 23% (n = 13). Conclusion: This is the largest sample size with the longest median follow-up to date of patients with ACC treated with PT. PT can provide excellent disease control for ACC of the head and neck with acceptable toxicity. T4 disease, intracranial involvement, and gross residual disease at the time of PT following either biopsy or subtotal resection were significant prognostic features for worse outcomes.

Hyperargininemia: A Rare Diagnosis in Adulthood.

Background: Hyperargininemia is a rare inherited metabolic disorder of the urea cycle with an autosomal recessive transmission. It occurs due to a deficiency of the enzyme arginase I and causes progressive neurological damage. Very few cases are diagnosed in adulthood, with the majority being diagnosed before the age of 4. Currently, this condition is diagnosed by a mass spectrometry technique in neonatal screening, which has been implemented in Portugal since 2007; births before that were not screened for this entity. Case description: We present a case of a 23-year-old woman referred to the internal medicine and neurology departments with a history of two hospital admissions for rhabdomyolysis at the age of 18, consanguineous parents, learning difficulties and multiple falls since the age of 8. In addition, the patient also had behavioural changes so she had psychological counselling at school, but lacked family support. Neurological examination showed mild proximal paraparesis, and spastic and paraparetic gait. The aetiological study revealed a pathological variant in homozygosity ARG1 and increased blood levels of arginine. Therefore, the diagnosis of hyperargininemia was confirmed. Conclusions: Compared to other urea cycle disorders, hyperargininemia is the rarest one. It is important to recognise the characteristic clinical features and diagnose it early because a favourable outcome can be achieved with appropriate treatment. This case shows a delayed diagnosis of hyperargininemia and highlights the importance of the internist's role in diagnosing rare diseases. LEARNING POINTS: Hyperargininemia is a rare hereditary metabolic disease of the urea cycle and the rarest of the disorders affecting this cycle.The diagnosis is almost always made within the first four years of life and very few are diagnosed in adulthood.Early diagnosis is essential to reduce the progression of neurological damage, through appropriate treatment.

Can the Malnutrition Universal Screening Tool (MUST) Predict Healing Complications Following Microvascular Reconstruction of the Head and Neck?

Study Design: Retrospective cohort study. Objective: Malnutrition has been found to have negative effects on the immune system and inflammatory responses, impairing the wound healing process. Free flap failure is a serious complication in patients undergoing microvascular reconstruction, as it increases patient morbidity, length of stay in the hospital, patient, and hospital costs, as well as causes the need for further surgical interventions1. Malnutrition is estimated to be present in 35-50% of head and neck cancer patients with higher rates in those experiencing hypo-oropharyngeal disease. This is often caused by functional and pain limitations from due to disease burden causing odynophagia and dysphagia. The Malnutrition Universal Screening Tool (MUST) is recommended for risk screening and provides three scores for risk classification: high, intermediate, and low2. We argue that the use of MUST as a preoperative assessment tool is useful to predict postoperative surgical site infection and delayed wound healing in patients that will undergo reconstruction with free flaps for head and neck defects. Methods: A retrospective cohort study was designed to include all subjects who underwent head and neck microvascular free tissue transfer at a single institution between 2013 and 2019. Primary and secondary reconstructions were included, for benign or malignant pathology, osteonecrosis, osteomyelitis, congenital defects, and trauma. The nutritional risk was evaluated using MUST, which analyzes body mass index, weight loss, and acute disease effect, to classify patients as low, intermediate, and high risk. We further divided the subjects into two comparison groups- low-intermediate and high risk. The primary outcome was surgical site complications and delayed wound healing. Data was analyzed as frequencies and means with standard deviations, as well as Fisher's exact test and t-test. P-values <0.05 were considered statistically significant. Analyses were done utilizing IBM SPSS Statistics Version 29. Results: 131 subjects were included for data analysis, with 54 being considered low MUST risk, 12 intermediate risk (66 low-intermediate), and 65 were high risk. The mean BMI overall was 25.5 ±5.3, and 27.2 in the low-intermediate group, and 23.7 in the high-risk group. Eighty-two subjects experienced <5-pound weight loss in the preceding 6 months to surgery, while 17 lost between 5-10 pounds, and 23 lost 10< pounds. Cancer/osteonecrosis was the etiology for 54 (82%) subjects of the low-intermediate group, and 61 (92%) of the high-risk group (P = .089). The subjects classified in High-risk group according to the MUST score had 11% more surgical site complications (P = .120) and 13.7% more delayed wound healing and dehiscence(P = .09); only 3 subjects in the study presented total flap loss and they were all in the High-risk group. Surgical site complication, delayed wound healing rates and partial or total flap loss were not increased by any specific medical comorbidity or history such as radiation or chemotherapy. Conclusions: In conclusion, Subjects with high MUST score had increased complications and poor wound healing, and subjects with acute disease effect that induces a phase of nil per os for > 5 day have higher risk of total flap loss and surgical site complication.

Iridescence Mimicking in Fabrics: A Ultraviolet/Visible Spectroscopy Study.

Poly(styrene-methyl methacrylate-acrylic acid) photonic crystals (PCs), with five different sizes (170, 190, 210, 230 and 250 nm), were applied onto three plain fabrics, namely polyamide, polyester and cotton. The PC-coated fabrics were analyzed using scanning electronic microscopy and two UV/Vis reflectance spectrophotometric techniques (integrating sphere and scatterometry) to evaluate the PCs' self-assembly along with the obtained spectral and colors characteristics. Results showed that surface roughness of the fabrics had a major influence on the color produced by PCs. Polyamide-coated fabrics were the only samples having an iridescent effect, producing more vivid and brilliant colors than polyester and cotton samples. It was observed that as the angle of incident light increases, a hypsochromic shift in the reflection peak occurs along with the formation of new reflection peaks. Furthermore, color behavior simulations were performed with an illuminant A light source on polyamide samples. The illuminant A simulation showed greener and yellower structural colors than those illuminated with D50. The polyester and cotton samples were analyzed using scatterometry to check for iridescence, which was unseen upon ocular inspection and then proven to be present in these samples. This work allowed a better comprehension of how structural colors and their iridescence are affected by the textile substrate morphology and fiber type.

Association between tonsillectomy and oropharyngeal cancer risk: a retrospective cohort study.

BACKGROUND: The purpose of this retrospective cohort study is to describe the association between the history of tonsillectomy and the risk of oropharyngeal squamous cell carcinoma (OPSSC), using a large cohort of patients. MATERIALS AND METHODS: We performed a retrospective cohort study with 3620 patients diagnosed with OPٍSCC from 2010 to 2021. We utilized the University of Florida patients' registry i2b2 system. Three subsets of OPSSC were defined, base of tongue(BOT) cancer, tonsillar cancer, and other OPSSC. Tumor demographics and history of tonsillectomy were collected. Odds ratio for OPSSC were assessed utilizing a logistic regression model with adjusting for gender, race, and age. P < 0.05 was deemed significant. RESULTS: Of the 3620 OPSSC patients were BOT cancer (N = 964), tonsillar cancer (N = 995), and other OPSSC (N = 1661). There was a statistically significant reduction in tonsillar cancer and BOT cancer odds ratio in patients with a history of tonsillectomy vs. patients without tonsillectomy (0.086 and 0.117), respectively, with a P value < .0001. The odds ratio of OPSSC in patients with a history of tonsillectomy vs. patients without tonsillectomy is 1.031. CONCLUSION: This study showed that the OPSSC and previous history of tonsillectomy are associated. Our results showed a significant reduction in BOT and tonsillar cancer risk in patients with a history of tonsillectomy and an insignificant decrease in other OPSSC. This study could emphasize the importance of the development of future clinical trials to investigate the role of prophylactic tonsillectomy as a secondary preventive strategy to reduce OPSSC.

Comparison of the outcomes of split thickness skin graft versus thickness skin graft for closure of the radial forearm free flap donor site: A systematic review.

BACKGROUND: Radial forearm free flap (RFFF) donor site closure is traditionally performed with split thickness skin grafts (STSG), which can be associated with poor aesthetics, wrist stiffness, paresthesia, reduced strength, and tendon exposure. Full thickness skin grafts (FTSG) are potentially beneficial as they provide a more durable coverage, and the skin graft donor site can be closed primarily, which is more aesthetic. The aim of this systematic review is to compare the outcomes of STSG versus FTSG for closure of the RFFF donor site. METHODS: A systematic review was performed, following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The primary objective was to answer: do subjects undergoing RFFF harvest, utilizing FTSG to close the RFFF donor site, compared to STSG, achieve superior aesthetics at the RFFF donor site? Included papers compared FTSG and STSG with statistical data. Means were compared with t-test and proportions with Fisher's exact test. RESULTS: The initial search resulted in 1851 studies. After applying the inclusion/exclusion criteria, the search resulted in eight studies, with 366 total skin grafts, 197 STSG and 169 FTSG. Six studies evaluated aesthetics utilizing a Likert scale, with the scaled average aesthetic score for FTSG being 7.9/10 compared to 6.9/10 for STSG (p < .001). Tendon exposure was measured in five studies, with a rate of 13.1% for STSG versus 10.6% for FTSG (p = .555). No significant difference in function was observed, however, methods to quantify function were heterogeneous. CONCLUSION: FTSG compared to STSG, resulted in statistically significant improved aesthetics, with comparable rates of tendon exposure and function.

Lichen planus after COVID-19 infection and vaccination.

BACKGROUND: Lichen planus is one of the common adverse reactions after COVID-19 infection and vaccination. Despite it being reported in several case reports, the literature including a large sample of the studied population is lacking. The current study was performed to assess the risk of LP after COVID-19 infection as well as COVID-19 vaccination. METHODS: The current study was designed as a retrospective cross-sectional hospital-based study of registered patients at the University of Florida (UF) health centers. The diagnoses of LP, COVID-19 infection, and COVID-19 vaccines were detected. The logistic regression model was used to assess the risk of developing LP after COVID-19 infection and vaccination. RESULTS: A total hospital patient of 684,110 attended UF Health centers were included in this study. 181 patients reported LP after COVID-19 vaccination and 24 patients developed LP after COVID-19 infection. The risk of developing LP after COVID-19 vaccination was 1.573 while the risk of developing LP after COVID-19 infection was 1.143. CONCLUSION: The odds of getting LP after COVID-19 vaccination are significantly developed. The current study showed that COVID-19 infection and vaccination are associated with LP. So, healthcare practitioners should be aware of this reaction for rapid recognition and treatment.

Mathematical Modeling of Vessel Geometry and Circumference in Microvascular Surgery.

Introduction: Microvascular anastomosis has traditionally been executed with a perpendicular transection through the vessel at the widest diameter to increase circumference and thus increase blood flow while decreasing resistance. In Chen's 2015 article, it was suggested that an "open Y" would improve vessel size match, and Wei and Mardini discuss angled transections of the vessels. This project aims to explore the geometric configurations feasible at the anastomotic transection and mathematically model the resulting hypothetical increases in circumference. Materials and Methods: The mathematical models were theoretically developed by our team. The formulas model increases in circumference of the transection at different distances in relation to the bifurcation of a blood vessel, as well as changes in circumference at different transection angulations. An in vitro exploration as to the anastomotic feasibility of each geometric cut was completed on ten poultry tissue specimens. Results: The mathematical models demonstrated the change in vessel circumference, with multiple geometric designs calculated, best shown through diagrams. For example, if the vessel width is 1 mm, the distance from the increasing vessel diameter to the final bifurcation is 1 mm, and the bifurcation angle is 45°, the circumference of the transected vessel increases by 82.8%. Models of transections at different angulations, for instance 30°, 45°, and 60°, yield an increase in elliptical circumference of 8.0%, 22.5%, and 58.1%, respectively. Additional derivations calculate the elliptical circumference at any angle in a single vessel, and at any angle in a bifurcating vessel. Conclusion: The theoretical and clinical aim of this project is to increase awareness of the anastomotic creativity and mathematically demonstrate the optimal anastomotic geometry, which has not been objectively explored to our knowledge. An in vivo study would further support clinical improvements, with the aim to map postoperative fluid dynamics through the geometric anastomoses.

Exosomes modified with anti-MEK1 siRNA lead to an effective silencing of triple negative breast cancer cells.

Triple negative breast cancer (TNBC) is a highly heterogenous disease not sensitive to endocrine or HER2 therapy and standardized treatment regimens are still missing. Therefore, development of novel TNBC treatment approaches is of utmost relevance. Herein, the potential of MAPK/ERK downregulation by RNAi-based therapeutics in a panel of mesenchymal stem-like TNBC cell lines was uncovered. Our data revealed that suppression of one of the central nodes of this signaling pathway, MEK1, affects proliferation, migration, and invasion of TNBC cells, that may be explained by the reversion of the epithelial-mesenchymal transition phenotype, which is facilitated by the MMP-2/MMP-9 downregulation. Moreover, an exosome-based system was successfully generated for the siRNA loading (iExoMEK1). Our data suggested absence of modification of the physical properties and general integrity of the iExoMEK1 comparatively to the unmodified counterparts. Such exosome-mediated downregulation of MEK1 led to a tumor regression accompanied by a decrease of angiogenesis using the chick chorioallantoic-membrane model. Our results highlight the potential of the targeting of MAPK/ERK cascade as a promising therapeutic approach against TNBC.

Undiagnosed Primary Sjögren's Syndrome With Pleural Involvement.

Sjögren's syndrome (SS) is a systemic autoimmune disorder characterized by the lymphocytic infiltration of the exocrine glands, primarily the salivary and lacrimal glands, resulting in the dryness of the eyes and mouth. However, Sjögren's syndrome is not limited to glandular involvement, as it can also affect various other organ systems, leading to a wide range of extraglandular manifestations and delaying the diagnosis. In this scenario, a high level of suspicion is required.

Eosinophilic Variant of Granulomatosis With Polyangiitis.

Granulomatosis with polyangiitis (GPA) is a multisystemic necrotizing vasculitis with a special tropism to the respiratory tract and the kidneys. Although uncommon, GPA may be associated with hypereosinophilia and limited organ involvement. In these cases, American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria may be insufficient to establish the diagnosis. We described a limited form of GPA, hypereosinophilia, and predominant skin involvement.

Comparative Assessment of Total Versus Hemi Glossectomy Defects Reconstructed With Anterolateral Thigh Free Flap.

BACKGROUND: Free tissue transfers for reconstruction following tongue resection has become standard practice. PURPOSE: This study sought to evaluate volume shrinkage of the anterolateral thigh free (ALTF) reconstructing tongue defects at 6 months postoperative. The aim was to estimate a shrinkage factor for ALTF reconstructing hemi and total glossectomy. STUDY DESIGN, SETTING, SAMPLE: This was an IRB-approved retrospective cohort study conducted at the head and neck service at the University of Florida, College of Medicine, Jacksonville (FL). This study targeted patients with tongue cancer from January 2018 to April 2022. INCLUSION CRITERIA: patients with tongue squamous cell carcinoma (SCC) who were surgically treated by either hemi or total glossectomy and reconstructed with ALTF. Patients had to have a postoperative computer tomography scans at 1 and 6 months post-surgery. Patients with constant body mass index during 6 months postreconstruction. Additionally, the patients were to have been treated with adjuvant radiotherapy. EXCLUSION CRITERIA: patients with recurrent tongue cancer and those who weren't reconstructed or managed with other treatment modalities. PREDICTOR VARIABLE: Type of tongue resection hemi versus total glossectomy for treatment of tongue SCC. MAIN OUTCOME VARIABLE: Shrinkage percentage of ALTF reconstructing tongue defects at 6 months postoperatively. COVARIATES: Age and gender. ANALYSES: Paired t-test and student t-test with level of significance P ≤ .05 were used to statistically analyze ALTF volume changes at 1 and 6 months postoperatively and ALTF shrinkage percentage at 6 months postreconstruction, respectively. RESULTS: We identified 85 patients who were treated for tongue SCC during the time period of study. Out of the 85 patients, 11 patients were reconstructed with an ALTF. Eight males and 3 females with a mean age of 62.3 years old. Six patients had total glossectomy and 5 had hemi glossectomy. Patients with hemi glossectomy had a significant difference in mean average flap shrinkage of 39.6%, while in those with total glossectomy had 17.7% (P = .004). CONCLUSION AND RELEVANCE: According to our results, we recommend that the flap size should be larger than the defect to adjust for volume shrinkage (1.4 times and 1.2 times for cases of hemi and total glossectomy, respectively).

It takes two to remyelinate: A bioengineered platform to study astrocyte-oligodendrocyte crosstalk and potential therapeutic targets in remyelination.

The loss of the myelin sheath insulating axons is the hallmark of demyelinating diseases. These pathologies often lead to irreversible neurological impairment and patient disability. No effective therapies are currently available to promote remyelination. Several elements contribute to the inadequacy of remyelination, thus understanding the intricacies of the cellular and signaling microenvironment of the remyelination niche might help us to devise better strategies to enhance remyelination. Here, using a new in vitro rapid myelinating artificial axon system based on engineered microfibres, we investigated how reactive astrocytes influence oligodendrocyte (OL) differentiation and myelination ability. This artificial axon culture system enables the effective uncoupling of molecular cues from the biophysical properties of the axons, allowing the detailed study of the astrocyte-OL crosstalk. Oligodendrocyte precursor cells (OPCs) were cultured on poly(trimethylene carbonate-co-ε-caprolactone) copolymer electrospun microfibres that served as surrogate axons. This platform was then combined with a previously established tissue engineered glial scar model of astrocytes embedded in 1 % (w/v) alginate matrices, in which astrocyte reactive phenotype was acquired using meningeal fibroblast conditioned medium. OPCs were shown to adhere to uncoated engineered microfibres and differentiate into myelinating OL. Reactive astrocytes were found to significantly impair OL differentiation ability, after six and eight days in a co-culture system. Differentiation impairment was seen to be correlated with astrocytic miRNA release through exosomes. We found significantly reduction on the expression of pro-myelinating miRNAs (miR-219 and miR-338) and an increase in anti-myelinating miRNA (miR-125a-3p) content between reactive and quiescent astrocytes. Additionally, we show that OPC differentiation inhibition could be reverted by rescuing the activated astrocytic phenotype with ibuprofen, a chemical inhibitor of the small rhoGTPase RhoA. Overall, these findings show that modulating astrocytic function might be an interesting therapeutic avenue for demyelinating diseases. The use of these engineered microfibres as an artificial axon culture system will enable the screening for potential therapeutic agents that promote OL differentiation and myelination while providing valuable insight on the myelination/remyelination processes.

A data set of earthquake bulletin and seismic waveforms for Ghana obtained by deep learning.

The Ghana Digital Seismic Network (GHDSN) data, with six broadband sensors, operating in southern Ghana for two years (2012-2014). The recorded dataset is processed for simultaneous event detection and phase picking by a Deep Learning (DL) model, the EQTransformer tool. Here, the detected earthquakes consisting of supporting data, waveforms (including P and S arrival phases), and earthquake bulletin are presented. The bulletin includes the 559 arrival times (292 P and 267 S phases) and waveforms of the 73 local earthquakes in SEISAN format. The supporting data encompasses the preliminary crustal velocity models obtained from the joint inversion analysis of the detected hypocentral parameters. These parameters comprised of a 6- layer model of the crustal velocity (Vp and Vp/Vs ratio), incident time sequence, and statistical analysis of the detected earthquakes and hypocentral parameters analyzed and relocated by the updated crustal velocity and graphic representation of them a 3D live figure enlighting the seismogenic depth of the region. This dataset has a unique appeal for earth science specialists to analyze and reprocess the detected waveforms and characterize the seismogenic sources and active faults in Ghana. The metadata and waveforms have been deposited at the Mendeley Data repository [1].

Potential Biological Properties of Lycopene in a Self-Emulsifying Drug Delivery System.

In recent years, lycopene has been highlighted due to its antioxidant and anti-inflammatory properties, associated with a beneficial effect on human health. The aim of this study was to advance the studies of antioxidant and anti-inflammatory mechanisms on human keratinocytes cells (HaCaT) of a self-emulsifying drug delivery system (SEDDS) loaded with lycopene purified from red guava (nanoLPG). The characteristics of nanoLPG were a hydrodynamic diameter of 205 nm, a polydispersity index of 0.21 and a zeta potential of -20.57, providing physical stability for the nanosystem. NanoLPG demonstrated antioxidant capacity, as shown using the ORAC methodology, and prevented DNA degradation (DNA agarose). Proinflammatory activity was evaluated by quantifying the cytokines TNF-α, IL-6 and IL-8, with only IL-8 showing a significant increase (p < 0.0001). NanoLPG showed greater inhibition of the tyrosinase and elastase enzymes, involved in the skin aging process, compared to purified lycopene (LPG). In vitro treatment for 24 h with 5.0 µg/mL of nanoLPG did not affect the viability of HaCaT cells. The ultrastructure of HaCaT cells demonstrated the maintenance of morphology. This contrasts with endoplasmic reticulum stresses and autophagic vacuoles when treated with LPG after stimulation or not with LPS. Therefore, the use of lycopene in a nanoemulsion may be beneficial in strategies and products associated with skin health.

Silver nanoparticles exert toxic effects in human monocytes and macrophages associated with the disruption of Δψm and release of pro-inflammatory cytokines.

Silver nanoparticles (AgNP) are the most widely produced type of nanoparticles due to their antimicrobial and preservative properties. However, their systemic bioavailability may be considered a potential hazard. When AgNP reach the bloodstream, they interact with the immune cells, contributing to the onset and development of an inflammatory response. Monocytes and macrophages play a pivotal role in our defense system, but the interaction of AgNP with these cells is still not clear. Therefore, the main objective of this work was to assess the cytotoxic and pro-inflammatory effects induced by 5, 10, and 50 nm AgNP coated with polyvinylpyrrolidone (PVP) and citrate, in concentrations that could be attained in vivo (0-25 µg/mL), in human monocytes isolated from human blood and human macrophages derived from a monocytic cell line (THP-1). The effects of PVP and citrate-coated AgNP on cell viability, mitochondrial membrane potential, and cytokines release were evaluated. The results evidenced that AgNP exert strong harmful effects in both monocytes and macrophages, through the establishment of a strong pro-inflammatory response that culminates in cell death. The observed effects were dependent on the AgNP concentration, size and coating, being observed more pronounced cytotoxic effects with smaller PVP coated AgNP. The results showed that human monocytes seem to be more sensitive to AgNP exposure than human macrophages. Considering the increased daily use of AgNP, it is imperative to further explore the adverse outcomes and mechanistic pathways leading to AgNP-induced pro-inflammatory effects to deep insight into the molecular mechanism involved in this effect.

Prediction of Noninvasive Ventilation Failure in COVID-19 Patients: When Shall We Stop?

INTRODUCTION: In coronavirus disease 2019 (COVID-19), there are no tools available for the difficult task of recognizing which patients do not benefit from maintaining respiratory support, such as noninvasive ventilation (NIV). Identifying treatment failure is crucial to provide the best possible care and optimizing resources. Therefore, this study aimed to build a model that predicts NIV failure in patients who did not progress to invasive mechanical ventilation (IMV). METHODS: This retrospective observational study included critical COVID-19 patients treated with NIV who did not progress to IMV. Patients were admitted to a Portuguese tertiary hospital between October 1, 2020, and March 31, 2021. The outcome of interest was NIV failure, defined as COVID-19-related in-hospital death. A binary logistic regression was performed, where the outcome (mortality) was the dependent variable. Using the independent variables of the logistic regression a decision-tree classification model was implemented. RESULTS: The study sample, composed of 103 patients, had a mean age of 66.3 years (SD=14.9), of which 38.8% (40 patients) were female. Most patients (82.5%) were autonomous for basic activities of daily living. The prediction model was statistically significant with an area under the curve of 0.994 and a precision of 0.950. Higher age, a higher number of days with increases in the fraction of inspired oxygen (FiO2), a higher number of days of maximum expiratory positive airway pressure, a lower number of days on NIV, and a lower number of days from disease onset to hospital admission were, with statistical significance, associated with increased odds of death. A decision-tree classification model was then obtained to achieve the best combination of variables to predict the outcome of interest. CONCLUSIONS: This study presents a model to predict death in COVID-19 patients treated with NIV in patients who did not progress to IMV, based on easily applicable variables that mainly reflect patients' evolution during hospitalization. Along with the decision-tree classification model, these original findings may help clinicians define the best therapeutical approach to each patient, prioritizing life-comforting measures when adequate, and optimizing resources, which is crucial within limited or overloaded healthcare systems. Further research is needed on this subject of treatment failure, not only to understand if these results are reproducible but also, in a broader sense, helping to fill this gap in modern medicine guidelines.

Subcellular compartmentalization of aluminum reduced its hazardous impact on rye photosynthesis.

Aluminum (Al) toxicity limits crops growth and production in acidic soils. Compared to roots, less is known about the toxic effects of Al in leaves. Al subcellular compartmentalization is also largely unknown. Using rye (Secale cereale L.) Beira (more tolerant) and RioDeva (more sensitive to Al) genotypes, we evaluated the patterns of Al accumulation in leaf cell organelles and the photosynthetic and metabolic changes to cope with Al toxicity. The tolerant genotype accumulated less Al in all organelles, except the vacuoles. This suggests that Al compartmentalization plays a role in Al tolerance of Beira genotype. PSII efficiency, stomatal conductance, pigment biosynthesis, and photosynthesis metabolism were less affected in the tolerant genotype. In the Calvin cycle, carboxylation was compromised by Al exposure in the tolerant genotype. Other Calvin cycle-related enzymes, phoshoglycerate kinase (PGK), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), triose-phosphate isomerase (TPI), and fructose 1,6-bisphosphatase (FBPase) activities decreased in the sensitive line after 48 h of Al exposure. Consequentially, carbohydrate and organic acid metabolism were affected in a genotype-specific manner, where sugar levels increased only in the tolerant genotype. In conclusion, Al transport to the leaf and compartmentalization in the vacuoles tolerant genotype's leaf cells provide complementary mechanisms of Al tolerance, protecting the photosynthetic apparatus and thereby sustaining growth.