Impact of Tricuspid Repair on Surgical Death in Patients Undergoing Mitral Valve Surgery Due to Rheumatic Disease.

Background: Tricuspid valve repair during mitral valve replacement surgery remains a controversial topic. The risk-benefit ratio in some populations remains uncertain, especially in rheumatic heart disease patients. Therefore, we aimed to evaluate the impact of concomitant tricuspid repair on surgical mortality in patients undergoing cardiac surgery due to rheumatic mitral valve disease who have moderate to severe functional tricuspid regurgitation. Methods: This is a prospective cohort study from January 1, 2017, to December 30, 2022. All patients over 18 years of age who underwent cardiac surgery to correct rheumatic mitral valve disease with concomitant moderate to severe tricuspid regurgitation were included. The primary outcome was a surgical death. In an exploratory analysis, clinical and echocardiographic data were obtained 2 years after the procedure. Results: Of the 144 patients included, 83 (57.6%) underwent tricuspid valve repair. The mean age was 46.2 (±12.3) years with 107 (74.3%) female individuals, the median left ventricular ejection fraction was 61.0% (55-67), and systolic pulmonary artery pressure (sPAP) was 55.0 mmHg (46-74), with 45 (31.3%) individuals with right ventricular dysfunction. The total in-hospital mortality was 15 (10.4%) individuals, and there was no difference between the groups submitted or not to tricuspid repair: 10 (12.0%) vs. 5 (7.5%); p = 0.46, respectively. There was an association with one variable independently: the sPAP value, relative risk 1.04 (1.01-1.07), p = 0.01. The estimated cut-off value of sPAP that indicates higher early mortality through the receiver operating characteristic curve (area 0.70, p = 0.012) was 73.5 mmHg. Conclusions: Performing tricuspid repair in individuals who were undergoing cardiac surgery to correct rheumatic mitral valve disease was not associated with increased surgical mortality. Our results suggest the safety of tricuspid repair even in this high-risk population, reinforcing the recommendations in current guidelines.

Single-cell resolution characterization of myeloid-derived cell states with implication in cancer outcome.

Tumor-associated myeloid-derived cells (MDCs) significantly impact cancer prognosis and treatment responses due to their remarkable plasticity and tumorigenic behaviors. Here, we integrate single-cell RNA-sequencing data from different cancer types, identifying 29 MDC subpopulations within the tumor microenvironment. Our analysis reveals abnormally expanded MDC subpopulations across various tumors and distinguishes cell states that have often been grouped together, such as TREM2+ and FOLR2+ subpopulations. Using deconvolution approaches, we identify five subpopulations as independent prognostic markers, including states co-expressing TREM2 and PD-1, and FOLR2 and PDL-2. Additionally, TREM2 alone does not reliably predict cancer prognosis, as other TREM2+ macrophages show varied associations with prognosis depending on local cues. Validation in independent cohorts confirms that FOLR2-expressing macrophages correlate with poor clinical outcomes in ovarian and triple-negative breast cancers. This comprehensive MDC atlas offers valuable insights and a foundation for futher analyses, advancing strategies for treating solid cancers.

A soluble model for synchronized rhythmic activity in ant colonies.

Synchronization is one of the most striking instances of collective behavior, occurring in many natural phenomena. For example, in some ant species, ants are inactive within the nest most of the time, but their bursts of activity are highly synchronized and involve the entire nest population. Here we revisit a simulation model that generates this synchronized rhythmic activity through autocatalytic behavior, i.e., active ants can activate inactive ants, followed by a period of rest. We derive a set of delay differential equations that provide an accurate description of the simulations for large ant colonies. Analysis of the fixed-point solutions, complemented by numerical integration of the equations, indicates the existence of stable limit-cycle solutions when the rest period is greater than a threshold and the event of spontaneous activation of inactive ants is very unlikely, so that most of the arousal of ants is done by active ants. Furthermore, we argue that the persistent oscillations observed in the simulations for colonies of finite size are due to resonant amplification of demographic noise.

Characterization of the Edge States in Colloidal Bi2Se3 Platelets.

The remarkable development of colloidal nanocrystals with controlled dimensions and surface chemistry has resulted in vast optoelectronic applications. But can they also form a platform for quantum materials, in which electronic coherence is key? Here, we use colloidal, two-dimensional Bi2Se3 crystals, with precise and uniform thickness and finite lateral dimensions in the 100 nm range, to study the evolution of a topological insulator from three to two dimensions. For a thickness of 4-6 quintuple layers, scanning tunneling spectroscopy shows an 8 nm wide, nonscattering state encircling the platelet. We discuss the nature of this edge state with a low-energy continuum model and ab initio GW-Tight Binding theory. Our results also provide an indication of the maximum density of such states on a device.

In vivo chronic exposure to inorganic mercury worsens hypercholesterolemia, oxidative stress and atherosclerosis in the LDL receptor knockout mice.

Heavy metal exposure leads to multiple system dysfunctions. The mechanisms are likely multifactorial and involve inflammation and oxidative stress. The aim of this study was to evaluate markers and risk factors for atherosclerosis in the LDL receptor knockout mouse model chronically exposed to inorganic mercury (Hg) in the drinking water. Results revealed that Hg exposed mice present increased plasma levels of cholesterol, without alterations in glucose. As a major source and target of oxidants, we evaluated mitochondrial function. We found that liver mitochondria from Hg treated mice show worse respiratory control, lower oxidative phosphorylation efficiency and increased H2O2 release. In addition, Hg induced mitochondrial membrane permeability transition. Erythrocytes from Hg treated mice showed a 50% reduction in their ability to take up oxygen, lower levels of reduced glutathione (GSH) and of antioxidant enzymes (SOD, catalase and GPx). The Hg treatment disturbed immune system cells counting and function. While lymphocytes were reduced, monocytes, eosinophils and neutrophils were increased. Peritoneal macrophages from Hg treated mice showed increased phagocytic activity. Hg exposed mice tissues present metal impregnation and parenchymal architecture alterations. In agreement, increased systemic markers of liver and kidney dysfunction were observed. Plasma, liver and kidney oxidative damage indicators (MDA and carbonyl) were increased while GSH and thiol groups were diminished by Hg exposure. Importantly, atherosclerotic lesion size in the aorta root of Hg exposed mice were larger than in controls. In conclusion, in vivo chronic exposure to Hg worsens the hypercholesterolemia, impairs mitochondrial bioenergetics and redox function, alters immune cells profile and function, causes several tissues oxidative damage and accelerates atherosclerosis development.

Microglial phagolysosome dysfunction and altered neural communication amplify phenotypic severity in Prader-Willi Syndrome with larger deletion.

Prader-Willi Syndrome (PWS) is a rare neurodevelopmental disorder of genetic etiology, characterized by paternal deletion of genes located at chromosome 15 in 70% of cases. Two distinct genetic subtypes of PWS deletions are characterized, where type I (PWS T1) carries four extra haploinsufficient genes compared to type II (PWS T2). PWS T1 individuals display more pronounced physiological and cognitive abnormalities than PWS T2, yet the exact neuropathological mechanisms behind these differences remain unclear. Our study employed postmortem hypothalamic tissues from PWS T1 and T2 individuals, conducting transcriptomic analyses and cell-specific protein profiling in white matter, neurons, and glial cells to unravel the cellular and molecular basis of phenotypic severity in PWS sub-genotypes. In PWS T1, key pathways for cell structure, integrity, and neuronal communication are notably diminished, while glymphatic system activity is heightened compared to PWS T2. The microglial defect in PWS T1 appears to stem from gene haploinsufficiency, as global and myeloid-specific Cyfip1 haploinsufficiency in murine models demonstrated. Our findings emphasize microglial phagolysosome dysfunction and altered neural communication as crucial contributors to the severity of PWS T1's phenotype.

Spontaneous reporting of adverse reactions associated with the COVID-19 vaccine in health care professionals: A descriptive observational study conducted in a Portuguese hospital.

Background: The coronavirus disease 2019 (COVID-19) was classified as a pandemic in March 2020 by the World Health Organization. The Pfizer-BioNTech COVID-19 vaccine was the first to be authorized in the European Union, based on data from phase 1, 2, and 3 clinical trials of limited duration. Concerns have been raised regarding the vaccine's safety profile. Some of the adverse drug reactions (ADRs) associated with vaccines may not have been identified during clinical trials. This study aimed to identify ADRs associated with the Pfizer-BioNTech vaccine in health care professionals at a Portuguese tertiary university hospital. Methods: The data used in this analysis consist of ADRs reported through a spontaneous notification system from vaccines administered between December 27, 2020, and January 31, 2021. ADRs were categorized according to the MedDRA terminology. Results: A total of 8,605 Pfizer-BioNTech vaccines were administered to 4568 health care professionals. ADRs were reported among 520 of the vaccines, with an incidence of 13.56% in women and 5.31% in men. The mean age of the population reporting ADRs was 41.52 years, with a standard deviation of 9.83 years. The most frequent ADRs were myalgia (n = 274), headache (n = 199), pyrexia (n = 164), injection site pain (n = 160), fatigue (n = 84), nausea (n = 81), chills (n = 65), lymphadenopathy (n = 64), and arthralgia (n = 53). Hypersensitivity reactions occurred in 15 health care professionals, with no anaphylactic reactions observed. A total of four Important Medical Events were observed, which consisted of two cases of syncope, one case of sudden hearing loss, and one case of transverse myelitis. Conclusion: The vaccine was well-tolerated among the study participants. Reactogenicity was greater after the second dose. The incidence of ADRs was higher in women and individuals aged between 40 to 49 years. Systemic adverse reactions were most frequently reported. Systematic monitoring of ADRs of COVID-19 vaccines in real-life context is essential for a more robust establishment of its safety profile.

Impact of Microbiota Depletion by Antibiotics on SARS-CoV-2 Infection of K18-hACE2 Mice.

Clinical and experimental data indicate that severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection is associated with significant changes in the composition and function of intestinal microbiota. However, the relevance of these effects for SARS-CoV-2 pathophysiology is unknown. In this study, we analyzed the impact of microbiota depletion after antibiotic treatment on the clinical and immunological responses of K18-hACE2 mice to SARS-CoV-2 infection. Mice were treated with a combination of antibiotics (kanamycin, gentamicin, metronidazole, vancomycin, and colistin, Abx) for 3 days, and 24 h later, they were infected with SARS-CoV-2 B lineage. Here, we show that more than 80% of mice succumbed to infection by day 11 post-infection. Treatment with Abx had no impact on mortality. However, Abx-treated mice presented better clinical symptoms, with similar weight loss between infected-treated and non-treated groups. We observed no differences in lung and colon histopathological scores or lung, colon, heart, brain and kidney viral load between groups on day 5 of infection. Despite some minor differences in the expression of antiviral and inflammatory markers in the lungs and colon, no robust change was observed in Abx-treated mice. Together, these findings indicate that microbiota depletion has no impact on SARS-CoV-2 infection in mice.

The impact of an enhanced health surveillance system for COVID-19 management in Serrana, Brazil.

Objective: To describe the successful implementation of an enhanced public health surveillance system based on early detection, tracing contacts, and patient follow-up and support. Study design: A prospective observational cohort study conducted in Serrana, São Paulo State, Brazil. Methods: The implementation was based on four axes: increasing the access to SARS-CoV-2 testing; correct swab collection; testing patients with mild symptoms; and patient follow-up. Positivity rate, patient demographic and clinical characteristics, dynamics of disease severity, SARS-CoV-2 genome evolution, and the impact on COVID-19 research were assessed from August 23, 2020 to February 6, 2021 (between epidemiological week 35/2020 and 5/2021, a total of 24 weeks). Results: The number of sites collecting rt-PCR for SARS-CoV-2 was increased from one to seven points and staff was trained in the correct use of personal protective equipment and in the swab collection technique. During the study period, 6728 samples were collected from 6155 participants vs. 2770 collections in a similar period before. SARS-CoV-2 RNA was detected in 1758 (26.1%) swabs vs. 1117 (36.7%) before the implementation of the surveillance system (p < 0.001). Positivity rates varied widely between epidemiological weeks 35/2020 and 5/2021 (IQR, 12.8%-31.3%). Out of COVID-19 patients, 91.1% were adults at a median age of 35 years (IQR, 25-50 years), 42.6% were men and 57.4% were women, with a SARS-CoV-2 positivity rate of 28.6% and 24.4% (p < 0.001), respectively. The most common symptoms were headache (72.6%), myalgia (65.0%), and cough (61.7%). Comorbidities were found in 20.8% of patients, the most common being hypertension and diabetes. According to the World Health Organization clinical progression scale, 93.5% of patients had mild disease, 1.6% were hospitalized with moderate disease, 3.2% were hospitalized with severe disease, and 1.4% died. The enhanced surveillance system led to the development of COVID-19 related research. Conclusions: The enhanced surveillance system in Serrana improved COVID-19 understanding and management. By integrating community and academic institutions, it was possible to monitor SARS-CoV-2 positive cases and variants, follow the epidemic trend, guide patients, and develop relevant research projects.

Development of a New Integrated System for Vital Sign Monitoring in Small Animals.

Monitoring the vital signs of mice is an essential practice during imaging procedures to avoid populational losses and improve image quality. For this purpose, a system based on a set of devices (piezoelectric sensor, optical module and thermistor) able to detect the heart rate, respiratory rate, body temperature and arterial blood oxygen saturation (SpO2) in mice anesthetized with sevoflurane was implemented. Results were validated by comparison with the reported literature on similar anesthetics. A new non-invasive electrocardiogram (ECG) module was developed, and its first results reflect the viability of its integration in the system. The sensors were strategically positioned on mice, and the signals were acquired through a custom-made printed circuit board during imaging procedures with a micro-PET (Positron Emission Tomography). For sevoflurane concentration of 1.5%, the average values obtained were: 388 bpm (beats/minute), 124 rpm (respirations/minute) and 88.9% for the heart rate, respiratory rate and SpO2, respectively. From the ECG information, the value obtained for the heart rate was around 352 bpm for injectable anesthesia. The results compare favorably to the ones established in the literature, proving the reliability of the proposed system. The ECG measurements show its potential for mice heart monitoring during imaging acquisitions and thus for integration into the developed system.

High-Dose Convalescent Plasma for Treatment of Severe COVID-19.

To assess whether high-dose coronavirus disease (COVID-19) convalescent plasma (CCP) transfusion may benefit patients with severe COVID-19, we conducted a multicenter randomized trial in Brazil. Patients with severe COVID-19 who were within 10 days of initial symptom onset were eligible. Patients in the CCP group received 3 daily doses of CCP (600 mL/d) in addition to standard treatment; control patients received standard treatment only. Primary outcomes were death rates at days 30 and 60 of study randomization. Secondary outcomes were ventilator-free days and hospital-free days. We enrolled 107 patients: 36 CCP and 71 control. At day 30, death rates were 22% for CCP and 25% for the control group; at day 60, rates were 31% for CCP and 35% for control. Needs for invasive mechanical ventilation and durations of hospital stay were similar between groups. We conclude that high-dose CCP transfused within 10 days of symptom onset provided no benefit for patients with severe COVID-19.

Topiramate treatment in Wistar rats during childhood induces sex-specific vascular dysfunction in adulthood.

The present study determined whether treatment during childhood with topiramate (TPM), a new generation antiepileptic drug, results in altered aortic reactivity in adult male and female rats. We also sought to understand the role of endothelium-derived contractile factors in TPM-induced vascular dysfunction. Male and female Wistar rats were treated with TPM (41 mg/kg/day) or water (TPM vehicle) by gavage during childhood (postnatal day, 16-28). In adulthood, thoracic aorta reactivity to phenylephrine (phenyl), as well as aortic thickness and expression of cyclooxygenases (COX-1 and COX-2), NOX2, and p47phox were evaluated. The aortic response to phenyl was increased in male and female rats from the TPM group when compared with the control group. In TPM male rats, the hyperreactivity to phenyl was abrogated by the inhibition of NADPH oxidase and COX-2, while in female rats, responses were restored only by inhibition of COX-2. In addition, TPM male rats presented aortic hypertrophy and increased expression of NOX-2 and p47phox, while TPM female rats showed increased COX-2 aortic expression. Taken together, for the first-time, the present study provides evidence that treatment with TPM during childhood causes vascular dysfunction in adulthood, and that the mechanism underlying the vascular effects of TPM is sex-specific.

Introduction of SARS-CoV-2 C.37 (WHO VOI lambda) in the Sao Paulo State, Southeast Brazil.

The Lambda variants of interest (VOI) (C37/GR/452Q.V1/21G) was initially reported in Lima, Peru but has gained rapid dissemination through other Latin American countries. Nevertheless, the dissemination and molecular epidemiology of the Lambda VOI in Brazil is unknown apart from a single case report. In this respect, we characterized the circulation of the SARS-CoV-2 Lambda VOI (C37/GR/452Q.V1/21G) in Sao Paulo State, Brazil. From March to June 2021, we identified seven Lambda isolates in a set of approximately 8000 newly sequenced genomes of the Network for Pandemic Alert of Emerging SARS-CoV-2 variants from Sao Paulo State. Interestingly, in three of the positive patients, the Lambda VOI infection was probably related to a contact transmission. These individuals were fully vaccinated to COVID-19 and presented mild symptoms. The remaining positive for Lambda VOI individuals showed different levels of COVID-19 symptoms and one of them needed hospitalization (score 5, WHO). In our study, we present a low level of Lambda VOI circulation in the Sao Paulo State. This reinforces the essential role of molecular surveillance for the effective SARS-CoV-2 pandemic response, especially in regard to circulating variants.

Melanoma classification using light-Fields with morlet scattering transform and CNN: Surface depth as a valuable tool to increase detection rate.

Medical image classification through learning-based approaches has been increasingly used, namely in the discrimination of melanoma. However, for skin lesion classification in general, such methods commonly rely on dermoscopic or other 2D-macro RGB images. This work proposes to exploit beyond conventional 2D image characteristics, by considering a third dimension (depth) that characterises the skin surface rugosity, which can be obtained from light-field images, such as those available in the SKINL2 dataset. To achieve this goal, a processing pipeline was deployed using a morlet scattering transform and a CNN model, allowing to perform a comparison between using 2D information, only 3D information, or both. Results show that discrimination between Melanoma and Nevus reaches an accuracy of 84.00, 74.00 or 94.00% when using only 2D, only 3D, or both, respectively. An increase of 14.29pp in sensitivity and 8.33pp in specificity is achieved when expanding beyond conventional 2D information by also using depth. When discriminating between Melanoma and all other types of lesions (a further imbalanced setting), an increase of 28.57pp in sensitivity and decrease of 1.19pp in specificity is achieved for the same test conditions. Overall the results of this work demonstrate significant improvements over conventional approaches.

Histo-blood group A is a risk factor for severe COVID-19.

OBJECTIVES: Evaluate the impact of ABO histo-blood group type on COVID-19 severity. BACKGROUND: ABO histo-blood type has been associated with different outcomes in infectious diseases. It has also shown a higher proportion of type A patients with SARS-CoV-2. In this observational study, extracted from an ongoing clinical trial on the efficacy of convalescent plasma transfused in COVID-19 patients, we describe the impact of ABO blood type on the risk of developing severe COVID-19. MATERIALS AND METHODS: Seventy-two consecutive patients (37 type A, 23 type O, 11 type B, 1 type AB) with severe (respiratory failure) COVID-19 were included. Control group was composed of 160 individuals randomly selected from the same populational basis. RESULTS: Blood group A was overrepresented (51.39%) in the patient group in relation to the control group (30%), whereas blood group O was less represented (31.94%) in patient than in control group (48%). Odds ratio (A vs. O) was 2.581 (1.381-4.817), CI 95%; p = 0.004. Also, blood group A patients appeared to have more severe disease, given by the scores of the Sequential Organ Failure Assessment and Simplified Acute Physiologic Score 3 (p = 0.036 and p = 0.058, respectively). CONCLUSION: Histo-blood type A is associated with a higher risk of developing severe COVID-19 in relation to blood type O.

The impact of an enhanced health surveillance system for COVID-19 management in Serrana - Brazil

Objective To describe the successful implementation of an enhanced public health surveillance system based on early detection, tracing contacts, and patient follow-up and support. Study design A prospective observational cohort study conducted in Serrana, São Paulo State, Brazil. Methods The implementation was based on four axes: increasing the access to SARS-CoV-2 testing; correct swab collection; testing patients with mild symptoms; and patient follow-up. Positivity rate, patient demographic and clinical characteristics, dynamics of disease severity, SARS-CoV-2 genome evolution, and the impact on COVID-19 research were assessed from August 23, 2020 to February 6, 2021 (between epidemiological week 35/2020 and 5/2021, a total of 24 weeks). Results The number of sites collecting rt-PCR for SARS-CoV-2 was increased from one to seven points and staff was trained in the correct use of personal protective equipment and in the swab collection technique. During the study period, 6728 samples were collected from 6155 participants vs. 2770 collections in a similar period before. SARS-CoV-2 RNA was detected in 1758 (26.1%) swabs vs. 1117 (36.7%) before the implementation of the surveillance system (p < 0.001). Positivity rates varied widely between epidemiological weeks 35/2020 and 5/2021 (IQR, 12.8%–31.3%). Out of COVID-19 patients, 91.1% were adults at a median age of 35 years (IQR, 25–50 years), 42.6% were men and 57.4% were women, with a SARS-CoV-2 positivity rate of 28.6% and 24.4% (p < 0.001), respectively. The most common symptoms were headache (72.6%), myalgia (65.0%), and cough (61.7%). Comorbidities were found in 20.8% of patients, the most common being hypertension and diabetes. According to the World Health Organization clinical progression scale, 93.5% of patients had mild disease, 1.6% were hospitalized with moderate disease, 3.2% were hospitalized with severe disease, and 1.4% died. The enhanced surveillance system led to the development of COVID-19 related research. Conclusions The enhanced surveillance system in Serrana improved COVID-19 understanding and management. By integrating community and academic institutions, it was possible to monitor SARS-CoV-2 positive cases and variants, follow the epidemic trend, guide patients, and develop relevant research projects.

Skin lesion classification using features of 3D border lines.

Machine learning algorithms are progressively assuming important roles as computational tools to support clinical diagnosis, namely in the classification of pigmented skin lesions using RGB images. Most current classification methods rely on common 2D image features derived from shape, colour or texture, which does not always guarantee the best results. This work presents a contribution to this field, by exploiting the lesions' border line characteristics using a new dimension - depth, which has not been thoroughly investigated so far. A selected group of features is extracted from the depth information of 3D images, which are then used for classification using a quadratic Support Vector Machine. Despite class imbalance often present in medical image datasets, the proposed algorithm achieves a top geometric mean of 94.87%, comprising 100.00% sensitivity and 90.00% specificity, using only depth information for the detection of Melanomas. Such results show that potential gains can be achieved by extracting information from this often overlooked dimension, which provides more balanced results in terms of sensitivity and specificity than other settings.

Evolutionary dynamics of HIV-1 subtype C in Brazil.

The extensive genetic diversity of HIV-1 is a major challenge for the prevention and treatment of HIV-1 infections. Subtype C accounts for most of the HIV-1 infections in the world but has been mainly localized in Southern Africa, Ethiopia and India. For elusive reasons, South Brazil harbors the largest HIV-1 subtype C epidemic in the American continent that is elsewhere dominated by subtype B. To investigate this topic, we collected clinical data and viral sequences from 2611 treatment-naïve patients diagnosed with HIV-1 in Brazil. Molecular epidemiology analysis supported 35 well-delimited transmission clusters of subtype C highlighting transmission within South Brazil but also from the South to all other Brazilian regions and internationally. Individuals infected with subtype C had lower probability to be deficient in CD4+ T cells when compared to subtype B. The HIV-1 epidemics in the South was characterized by high female-to-male infection ratios and women-to-child transmission. Our results suggest that HIV-1 subtype C probably takes advantage of longer asymptomatic periods to maximize transmission and is unlikely to outcompete subtype B in settings where the infection of women is relatively less relevant. This study contributes to elucidate factors possibly underlying the geographical distribution and expansion patterns of the most spread HIV-1 subtypes.

The impact of climate change in wheat and barley yields in the Iberian Peninsula.

The impact of climate change on wheat and barley yields in two regions of the Iberian Peninsula is here examined. Regression models are developed by using EURO-CORDEX regional climate model (RCM) simulations, forced by ERA-Interim, with monthly maximum and minimum air temperatures and monthly accumulated precipitation as predictors. Additionally, RCM simulations forced by different global climate models for the historical period (1972-2000) and mid-of-century (2042-2070; under the two emission scenarios RCP4.5 and RCP8.5) are analysed. Results point to different regional responses of wheat and barley. In the southernmost regions, results indicate that the main yield driver is spring maximum temperature, while further north a larger dependence on spring precipitation and early winter maximum temperature is observed. Climate change seems to induce severe yield losses in the southern region, mainly due to an increase in spring maximum temperature. On the contrary, a yield increase is projected in the northern regions, with the main driver being early winter warming that stimulates earlier growth. These results warn on the need to implement sustainable agriculture policies, and on the necessity of regional adaptation strategies.

Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil.

The success of antiretroviral treatment (ART) is threatened by the emergence of drug resistance mutations (DRM). Since Brazil presents the largest number of people living with HIV (PLWH) in South America we aimed at understanding the dynamics of DRM in this country. We analyzed a total of 20,226 HIV-1 sequences collected from PLWH undergoing ART between 2008-2017. Results show a mild decline of DRM over the years but an increase of the K65R reverse transcriptase mutation from 2.23% to 12.11%. This increase gradually occurred following alterations in the ART regimens replacing zidovudine (AZT) with tenofovir (TDF). PLWH harboring the K65R had significantly higher viral loads than those without this mutation (p < 0.001). Among the two most prevalent HIV-1 subtypes (B and C) there was a significant (p < 0.001) association of K65R with subtype C (11.26%) when compared with subtype B (9.27%). Nonetheless, evidence for K65R transmission in Brazil was found both for C and B subtypes. Additionally, artificial neural network-based immunoinformatic predictions suggest that K65R could enhance viral recognition by HLA-B27 that has relatively low prevalence in the Brazilian population. Overall, the results suggest that tenofovir-based regimens need to be carefully monitored particularly in settings with subtype C and specific HLA profiles.