Broadening the Knowledge of Mexican Boletes: Addition of a New Genus, Seven New Species, and Three New Combinations.

Boletes are one of the most common groups of fungi in temperate, subtropical, and tropical ecosystems. In Mexico, the northern region has mainly been explored in terms of bolete diversity. This study describes a new genus and seven new species based on macromorphological, micromorphological, molecular, phylogenetic, and ecological data. Garcileccinum gen. nov. is typified with G. salmonicolor based on multigene phylogenetic analysis of nrLSU, RPB2, and TEF1, and it is closely related to Leccinum and Leccinellum. Garcileccinum viscosum and G. violaceotinctum are new combinations. Boletellus minimatenebris (ITS, nrLSU, and RPB2), Cacaoporus mexicanus (RPB2 and ATP6), Leccinum oaxacanum, Leccinum juarenzense (nrLSU, RPB2, and TEF1), Tylopilus pseudoleucomycelinus (nrLSU and RPB2), and Xerocomus hygrophanus (ITS, nrLSU, and RPB2) are described as new species. Boletus neoregius is reclassified as Pulchroboletus neoregius comb. nov. based on morphological and multigene phylogenetic analysis (ITS and nrLSU), and its geographic distribution is extended to Central Mexico, since the species was only known from Costa Rica. Furthermore, T. leucomycelinus is a new record from Mexico. This study contributes to increasing our knowledge of boletes and expands the diversity found in Mexican forests.

Five New Species of Aureoboletus and Chalciporus (Boletaceae, Boletales) and Their Ethnomycological Aspects.

Among Boletales, the family Boletaceae has the highest diversity worldwide. Additionally, this fungal group has great ecological relevance because it not only includes mainly ectomycorrhizal but also saprotrophic species. Furthermore, some species are used as food and have sociocultural and economic importance worldwide. In Mexico, the Boletaceae family boasts a substantial number of species, yet our understanding of these species remains far from comprehensive. In this work, by using macro- and micromorphological and phylogenetic analyses of DNA sequences from multi-gene analyses based on ITS, nrLSU, rpb1, rpb2, and tef1, we report five new species belonging to the genera Aureoboletus and Chalciporus: A. ayuukii and A. elvirae from a Quercus scytophylla forest, A. readii from a mixed forest, C. perezsilvae from cloud forest, and C. piedracanteadensis from both a mixed coniferous forest and a Quercus-Pinus forest. In Mexico, four species of Aureoboletus are used as a food source, and in this work, we add another one, A. readii, which is traditionally consumed by members of the Tlahuica-Pjiekakjoo culture, who are located in the central part of the country. This work contributes to our knowledge of two genera of Boletaceae in a geographical area that is scarcely studied, and thus, our understanding of its biocultural relevance is enriched.

New Ascomycetes from the Mexican Tropical Montane Cloud Forest.

The tropical montane cloud forest is the most diverse and threatened vegetation type in Mexico. In the last decade, the number of described Ascomycetes species has notably increased, reaching more than 1300 species. This study describes six new species based on their molecular and morphological characteristics. Our results suggest that Mexico has the highest number of described species in the Neotropics. However, many other Mexican lineages still need to be described.

The genetic architecture and evolution of the human skeletal form.

The human skeletal form underlies bipedalism, but the genetic basis of skeletal proportions (SPs) is not well characterized. We applied deep-learning models to 31,221 x-rays from the UK Biobank to extract a comprehensive set of SPs, which were associated with 145 independent loci genome-wide. Structural equation modeling suggested that limb proportions exhibited strong genetic sharing but were independent of width and torso proportions. Polygenic score analysis identified specific associations between osteoarthritis and hip and knee SPs. In contrast to other traits, SP loci were enriched in human accelerated regions and in regulatory elements of genes that are differentially expressed between humans and great apes. Combined, our work identifies specific genetic variants that affect the skeletal form and ties a major evolutionary facet of human anatomical change to pathogenesis.

High-resolution ultrasound tendon-to-bone distances in partial and complete finger flexor A2 pulley ruptures simulated in human cadaver dissection: toward understanding imaging of partial pulley ruptures.

Introduction: The A2 pulley tear is the most common injury in rock climbing. Whereas complete A2 pulley ruptures have been extensively researched, studies focused on partial A2 pulley ruptures are lacking. A2 pulleys rupture distally to proximally. High-resolution ultrasound imaging is considered the gold-standard tool for diagnosis and the most relevant ultrasound measurement is the tendon-to-bone distance (TBD), which increases when the pulley ruptures. The purpose of this study was to establish tendon-to-bone distance values for different sizes of partial A2 pulley ruptures and compare these values with those of complete ruptures. Material and methods: The sample consisted of 30 in vitro fingers randomly assigned to 5 groups: G1, no simulated tear (control); G2, simulated 5 mm tear (low-grade partial rupture); G3, simulated 10 mm tear (medium-grade partial rupture); G4, simulated 15 mm tear (high-grade partial rupture); and G5, simulated 20 mm or equivalent tear (complete rupture). A highly experienced sonographer blinded to the randomization process and dissections examined all fingers. Results: The tendon-to-bone distance measurements (medians and interquartile ranges) were as follows: G1, 0.95 mm (0.77-1.33); G2, 2.11 mm (1.78-2.33); G3, 2.28 mm (1.95-2.42); G4, 3.06 mm (2.79-3.28); and G5, 3.66 mm (3.55-4.76). Significant differences were found between non-torn pulleys and simulated partial and complete pulley ruptures. Discussion: In contrast, and inconsistent with other findings, no significant differences were found among the different partial rupture groups. In conclusion, the longer the partial pulley rupture, the higher the tendon-to-bone distance value. The literature is inconsistent regarding the tendon-to-bone distance threshold to diagnose a partial A2 pulley rupture. The minimum tendon-to-bone distance value for a partial rupture was 1.6 mm, and tendon-to-bone distance values above 3 mm suggest a high-grade partial pulley rupture (15 mm incision) or a complete pulley rupture.

Real-world effectiveness and factors associated with increased mortality in non-critically ill patients with COVID-19 pneumonia receiving remdesivir.

OBJECTIVES: Evidence on the effectiveness of remdesivir when used in real-life clinical practice is controversial. This study aims to analyse its effectiveness and the factors associated with increased mortality in non-critically ill patients with COVID-19 pneumonia who require supplemental low-flow oxygen and received remdesivir. METHODS: A retrospective cohort study was conducted at Ramón y Cajal University Hospital (Madrid, Spain) which included all patients treated with remdesivir in our institution during the second pandemic breakout in Spain, from August to November 2020. Treatment with remdesivir was limited to non-critically ill patients with COVID-19 pneumonia requiring low-flow supplemental oxygen, with a treatment duration of 5 days. RESULTS: A total of 1757 patients were admitted with COVID-19 pneumonia during the study period, of which 281 non-critically ill patients were treated with remdesivir and included in the analysis. Mortality at 28 days after initiation of treatment was 17.1%. The median (IQR) time to recovery was 9 days (6-15). 104 (37.0%) patients had complications during hospitalisation, with renal failure being the most frequent (31 patients; 36.5%). After adjustment for confounding factors, high-flow oxygen therapy was associated with increased 28-day mortality (HR 2.77; 95% CI 1.39 to 5.53; p=0.004) and decreased 28-day clinical improvement (HR 0.54; 95% CI 0.35 to 0.85; p=0.008). A significant difference in survival and clinical improvement was identified between patients treated with high and low-flow oxygen. CONCLUSION: The 28-day mortality rate in patients treated with remdesivir needing low-flow oxygen therapy was higher than that published in clinical trials. Age and increased oxygen therapy needed after the beginning of treatment were the main risk factors associated with mortality.

Masseteric nerve ultrasound identification for dynamic facial reanimation purposes.

BACKGROUND: the masseteric nerve is one of the main options to neurotize free muscle flaps in irreversible long-term facial paralysis. Several preoperative skin marking techniques for the masseteric nerve have been proposed to limit the surgical dissection area, shorten the surgical time, and enable a safer dissection. However, these have shown variability amongst them and cannot preoperatively visualize the nerve. Thus, we aim to design an observational study to validate a high-frequency ultrasound (HFUS) nerve identification technique. METHODS: a systematic HFUS examination was designed and performed to visualize the masseteric nerve in 64 hemifaces of healthy volunteers. One-third were randomly selected to undergo an additional HFUS-guided needle electrostimulation to validate the HFUS image. RESULTS: the masseteric nerve was identified by HFUS in 96,9% of hemifaces (95% CI 0.89 to >0.99) and showed almost perfect agreement with direct needle stimulation as calculated with Cohen's kappa coefficient; 0.95 (CI 0.85 to 1.00). It was found within the masseter muscle, in between the deeper muscle bellies, at 18,3 mm (SD ±2,2) from the skin. Only in 12,9% of cases (95 CI 0.06 to 0.24) its course became adjacent to the mandible periosteum. Other important features, such as disposition in relation to the parotid gland or whether the nerve was directly covered by a thick intramuscular aponeurosis, could be well observed by HFUS. CONCLUSIONS: HFUS enables masseteric nerve identification and can give the surgeon specific information on anatomical relations for each examined individual prior to surgery.

Elaphomycescastilloi (Elaphomycetaceae, Ascomycota) and Entolomasecotioides (Entolomataceae, Basidiomycota), two new sequestrate fungi from tropical montane cloud forest from south Mexico.

Two new species of sequestrate fungi are described from south Mexico based on morphological and molecular evidences. Here we describe Elaphomycescastilloi characterized by the yellowish mycelial mat, dull blue gleba and ascospores of 9.7-11.5 µm; Entolomasecotioides is characterized by the secotioid basidiomata, sulcate, pale cream pileus, and basidiospores of 7-13 × 5-9 µm. Both species grow in montane cloud forest under Quercus sp. in the state of Chiapas, Mexico. Descriptions, photographs, and multilocus phylogeny for both species are presented.

Genetic contributions of noncognitive skills to academic development.

Noncognitive skills such as motivation and self-regulation, predict academic achievement beyond cognitive skills. However, the role of genetic and environmental factors and of their interplay in these developmental associations remains unclear. We provide a comprehensive account of how cognitive and noncognitive skills contribute to academic achievement from ages 7 to 16 in a sample of >10,000 children from England and Wales. Results indicated that noncognitive skills become increasingly predictive of academic achievement across development. Triangulating genetic methods, including twin analyses and polygenic scores (PGS), we found that the contribution of noncognitive genetics to academic achievement becomes stronger over development. The PGS for noncognitive skills predicted academic achievement developmentally, with prediction nearly doubling by age 16, pointing to gene-environment correlation (rGE). Within-family analyses indicated both passive and active/evocative rGE processes driven by noncognitive genetics. By studying genetic effects through a developmental lens, we provide novel insights into the role of noncognitive skills in academic development.

Genetic contributions of noncognitive skills to academic development.

Noncognitive skills such as motivation and self-regulation, are partly heritable and predict academic achievement beyond cognitive skills. However, how the relationship between noncognitive skills and academic achievement changes over development is unclear. The current study examined how cognitive and noncognitive skills contribute to academic achievement from ages 7 to 16 in a sample of over 10,000 children from England and Wales. Noncognitive skills were increasingly predictive of academic achievement across development. Twin and polygenic scores analyses found that the contribution of noncognitive genetics to academic achievement became stronger over the school years. Results from within-family analyses indicated that associations with noncognitive genetics could not simply be attributed to confounding by environmental differences between nuclear families and are consistent with a possible role for evocative/active gene-environment correlations. By studying genetic effects through a developmental lens, we provide novel insights into the role of noncognitive skills in academic development.

Novelties in Macrofungi of the Tropical Montane Cloud Forest in Mexico.

The tropical montane cloud forest in Mexico is the most diverse and threatened ecosystem. Mexican macrofungi numbers more than 1408 species. This study described four new species of Agaricomycetes (Bondarzewia, Gymnopilus, Serpula, Sparassis) based on molecular and morphological characteristics. Our results support that Mexico is among the most biodiverse countries in terms of macrofungi in the Neotropics.

General dimensions of human brain morphometry inferred from genome-wide association data.

Understanding the neurodegenerative mechanisms underlying cognitive decline in the general population may facilitate early detection of adverse health outcomes in late life. This study investigates genetic links between brain morphometry, ageing and cognitive ability. We develop Genomic Principal Components Analysis (Genomic PCA) to model general dimensions of brain-wide morphometry at the level of their underlying genetic architecture. Genomic PCA is applied to genome-wide association data for 83 brain-wide volumes (36,778 UK Biobank participants) and we extract genomic principal components (PCs) to capture global dimensions of genetic covariance across brain regions (unlike ancestral PCs that index genetic similarity between participants). Using linkage disequilibrium score regression, we estimate genetic overlap between those general brain dimensions and cognitive ageing. The first genetic PCs underlying the morphometric organisation of 83 brain-wide regions accounted for substantial genetic variance (R2  = 40%) with the pattern of component loadings corresponding closely to those obtained from phenotypic analyses. Genetically more central regions to overall brain structure - specifically frontal and parietal volumes thought to be part of the central executive network - tended to be somewhat more susceptible towards age (r = -0.27). We demonstrate the moderate genetic overlap between the first PC underlying each of several structural brain networks and general cognitive ability (rg  = 0.17-0.21), which was not specific to a particular subset of the canonical networks examined. We provide a multivariate framework integrating covariance across multiple brain regions and the genome, revealing moderate shared genetic etiology between brain-wide morphometry and cognitive ageing.

The genetic architecture of the human skeletal form.

The human skeletal form underlies our ability to walk on two legs, but unlike standing height, the genetic basis of limb lengths and skeletal proportions is less well understood. Here we applied a deep learning model to 31,221 whole body dual-energy X-ray absorptiometry (DXA) images from the UK Biobank (UKB) to extract 23 different image-derived phenotypes (IDPs) that include all long bone lengths as well as hip and shoulder width, which we analyzed while controlling for height. All skeletal proportions are highly heritable (∻40-50%), and genome-wide association studies (GWAS) of these traits identified 179 independent loci, of which 102 loci were not associated with height. These loci are enriched in genes regulating skeletal development as well as associated with rare human skeletal diseases and abnormal mouse skeletal phenotypes. Genetic correlation and genomic structural equation modeling indicated that limb proportions exhibited strong genetic sharing but were genetically independent of width and torso proportions. Phenotypic and polygenic risk score analyses identified specific associations between osteoarthritis (OA) of the hip and knee, the leading causes of adult disability in the United States, and skeletal proportions of the corresponding regions. We also found genomic evidence of evolutionary change in arm-to-leg and hip-width proportions in humans consistent with striking anatomical changes in these skeletal proportions in the hominin fossil record. In contrast to cardiovascular, auto-immune, metabolic, and other categories of traits, loci associated with these skeletal proportions are significantly enriched in human accelerated regions (HARs), and regulatory elements of genes differentially expressed through development between humans and the great apes. Taken together, our work validates the use of deep learning models on DXA images to identify novel and specific genetic variants affecting the human skeletal form and ties a major evolutionary facet of human anatomical change to pathogenesis.

Postoperative Blood Pressure Deficit and Acute Kidney Injury After Liver Transplant.

OBJECTIVES: Acute kidney injury is a common cause of morbidity in liver transplant recipients. In critically ill patients who received an orthotopic liver transplant, we examined whether those with acute kidney injury had a greater deficit between pretransplant and posttransplant hemodynamic pressure-related parameters compared with those without acute kidney injury in the early postoperative period. MATERIALS AND METHODS: We included patients who underwent an orthotopic liver transplant during the study period. We obtained premorbid and intensive care unit time-weighted average values for hemodynamic pressure-related parameters (systolic, diastolic, and mean arterial pressure; central venous pressure; mean perfusion pressure; and diastolic perfusion pressure) and calculated deficits in those values. We defined acute kidney injury progression as an increase of ≥1 Kidney Disease: Improving Global Outcomes stage. RESULTS: We included 150 eligible transplantrecipients, with 88 (59%) having acute kidney injury progression. Acute kidney injury was associated with worse clinical outcomes. All achieved pressure-related values were similar between transplant recipients with or without acute kidney injury progression. However, those with acute kidney injury versus those without progression had greater diastolic perfusion pressure deficit at 12 hours (-8.33% vs 1.93%; P = .037) and 24 hours (-7.38% vs 5.11%; P = .002) and increased central venous pressure at 24 hours (46.13% vs 15%; P = .043) and 48 hours (40% vs 20.87%; P = .039). CONCLUSIONS: Patients with acute kidney injury progression had a greater diastolic perfusion pressure deficit and increased central venous pressure compared with patients without progression. Such deficits might be modifiable risk factors for the prevention of acute kidney injury progression.

Transcriptome-wide and stratified genomic structural equation modeling identify neurobiological pathways shared across diverse cognitive traits.

Functional genomic methods are needed that consider multiple genetically correlated traits. Here we develop and validate Transcriptome-wide Structural Equation Modeling (T-SEM), a multivariate method for studying the effects of tissue-specific gene expression across genetically overlapping traits. T-SEM allows for modeling effects on broad dimensions spanning constellations of traits, while safeguarding against false positives that can arise when effects of gene expression are specific to a subset of traits. We apply T-SEM to investigate the biological mechanisms shared across seven distinct cognitive traits (N = 11,263-331,679), as indexed by a general dimension of genetic sharing (g). We identify 184 genes whose tissue-specific expression is associated with g, including 10 genes not identified in univariate analysis for the individual cognitive traits for any tissue type, and three genes whose expression explained a significant portion of the genetic sharing across g and different subclusters of psychiatric disorders. We go on to apply Stratified Genomic SEM to identify enrichment for g within 28 functional categories. This includes categories indexing the intersection of protein-truncating variant intolerant (PI) genes and specific neuronal cell types, which we also find to be enriched for the genetic covariance between g and a psychotic disorders factor.

Machine-learning-derived predictive score for early estimation of COVID-19 mortality risk in hospitalized patients.

The clinical course of COVID-19 is highly variable. It is therefore essential to predict as early and accurately as possible the severity level of the disease in a COVID-19 patient who is admitted to the hospital. This means identifying the contributing factors of mortality and developing an easy-to-use score that could enable a fast assessment of the mortality risk using only information recorded at the hospitalization. A large database of adult patients with a confirmed diagnosis of COVID-19 (n = 15,628; with 2,846 deceased) admitted to Spanish hospitals between December 2019 and July 2020 was analyzed. By means of multiple machine learning algorithms, we developed models that could accurately predict their mortality. We used the information about classifiers' performance metrics and about importance and coherence among the predictors to define a mortality score that can be easily calculated using a minimal number of mortality predictors and yielded accurate estimates of the patient severity status. The optimal predictive model encompassed five predictors (age, oxygen saturation, platelets, lactate dehydrogenase, and creatinine) and yielded a satisfactory classification of survived and deceased patients (area under the curve: 0.8454 with validation set). These five predictors were additionally used to define a mortality score for COVID-19 patients at their hospitalization. This score is not only easy to calculate but also to interpret since it ranges from zero to eight, along with a linear increase in the mortality risk from 0% to 80%. A simple risk score based on five commonly available clinical variables of adult COVID-19 patients admitted to hospital is able to accurately discriminate their mortality probability, and its interpretation is straightforward and useful.

Tetanus, analysis of 29 cases

BackgroundTetanus disease is caused by Clostridium tetani, an anaerobe bacteria found in dust and soil. Once reached human body through damaged tissues, C. tetani releases several neurotoxins which block the inhibitory function, leading to an increased muscle tone, ultimately causing respiratory failure. Severe tetanus is a life-threatening disease, especially in low-income-regions.MethodsThis is a retrospective case-series study, undertaken at two hospitals of Vigo (population area 600,000 inhabitants). Tetanus cases were identified through the discharge databases of both hospitals between the years 1995–2019. Epidemiological and clinical data were obtained from the patient's medical records.ResultsA total of 33 cases were identified; median age was 67 years, and most of patients were women (n=16, 55.2%). Generalized tetanus was the most common clinical course, and neck stiffness was the most frequent symptom. A total of 25 patients (86%) were admitted to the Intensive Care Unit, 21 required invasive ventilation and 2 patients died.DiscussionThe incidence of tetanus was low but most of cases were severe. Mortality was slightly higher than previously reported. Interestingly, the deceased patients were old-women, consistent with previously reported research in high-income-regions, while mortality in low-income-countries concentrates in middle-aged men. (AU)

IntroducciónEl tétanos es causado por Clostridium tetani, bacteria anaerobia, ubicada en el suelo. Este microorganismo penetra a través de heridas y libera neurotoxinas que bloquean la función inhibitoria, produciendo espasticidad y fracaso respiratorio. Es una enfermedad grave, especialmente en regiones empobrecidas.MétodosSerie de casos realizada en dos hospitales vigueses (área 600.000 habitantes). Los casos fueron identificados mediante los sistemas de codificación entre 1995-2019. Los datos asistenciales se obtuvieron de la historia clínica.ResultadosSe identificaron 33 casos, mediana de edad, 67 años, la mayoría mujeres (n = 16, 55,2%). El tétanos generalizado fue la forma clínica predominante, la rigidez cervical el síntoma más común. Un total de 25 pacientes requirieron ingreso en UCI, 21 ventilación mecánica, dos fallecieron.DiscusiónEl número de casos fue bajo, pero la mayoría graves. La mortalidad fue ligeramente superior a la informada previamente. La mortalidad se concentró en mujeres ancianas, concordante con otros países desarrollados, mientras que la mortalidad en regiones no-desarrolladas se agrupa en varones de mediana edad. (AU)

Integrated analysis of direct and proxy genome wide association studies highlights polygenicity of Alzheimer's disease outside of the APOE region.

Recent meta-analyses combining direct genome-wide association studies (GWAS) with those of family history (GWAX) have indicated very low SNP heritability of Alzheimer's disease (AD). These low estimates may call into question the prospects of continued progress in genetic discovery for AD within the spectrum of common variants. We highlight dramatic downward biases in previous methods, and we validate a novel method for the estimation of SNP heritability via integration of GWAS and GWAX summary data. We apply our method to investigate the genetic architecture of AD using GWAX from UK Biobank and direct case-control GWAS from the International Genomics of Alzheimer's Project (IGAP). We estimate the liability scale common variant SNP heritability of Clinical AD outside of APOE region at ~7-11%, and we project the corresponding estimate for AD pathology to be up to approximately 23%. We estimate that nearly 90% of common variant SNP heritability of Clinical AD exists outside the APOE region. Rare variants not tagged in standard GWAS may account for additional variance. Our results indicate that, while GWAX for AD in UK Biobank may result in greater attenuation of genetic effects beyond that conventionally assumed, it does not introduce appreciable contamination of signal by genetically distinct traits relative to direct case-control GWAS in IGAP. Genetic risk for AD represents a strong effect of APOE superimposed upon a highly polygenic background.

Dolutegravir plus rilpivirine: benefits beyond viral suppression: DORIPEX retrospective study.

ABSTRACT: Switching dual therapy with dolutegravir (DTG) plus rilpivirine (RPV) was assessed in the SWORD-1 and SWORD-2 studies. Real-life data regarding the immunological impact of this approach on CD4+ and CD8+ T lymphocyte counts and the CD4/CD8 ratio are scarce. We evaluated this strategy on the basis of clinical practice data.A multicentric retrospective cohort study.Treatment-experienced virologically suppressed HIV-1-infected patients who were switched to DTG plus RPV were included. Using different models for paired data, we evaluated the efficacy and immune status in terms of CD4+ and CD8+ T-cell counts and CD4/CD8 ratio at 24 and 48 weeks of treatment.The study population comprised of 524 patients from 34 centers in Spain. Men accounted for 76.9% of patients, with a median age of 53 years. Patients receiving DTG plus RPV reached weeks 24 and 48 in 99.4% and 83.8% of cases, respectively, with only three (0.57%) virological failures. We found a significant decrease in CD8+ T-cell count (log OR -40) at week 24 and an increase in CD4+ T-cell count at week 48 (log OR +22.8). In acquired immunodeficiency syndrome-diagnosed patients, we found a significant increase in the CD4+ T-cell count at week 48 (log OR = 41.7, P = .0038), but no significant changes in the CD8+ T-cell count (log OR = -23.4, P = .54). No differences were found in the CD4/CD8 ratio between the acquired immunodeficiency syndrome subgroup and sex or age.In patients with controlled treatment, dual therapy with DTG plus RPV slightly improved the immune status during the first 48 weeks after switching, not only in terms of CD4+ T-cell count but also in terms of CD8+ T-cell count, with persistently high rates of viral control.