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.

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.

Impact of Ceftazidime-Avibactam Treatment in the Emergence of Novel KPC Variants in the ST307-Klebsiella pneumoniae High-Risk Clone and Consequences for Their Routine Detection.

The emergence of Klebsiella pneumoniae isolates carrying novel blaKPC variants conferring ceftazidime-avibactam (CAZ/AVI) resistance is being increasingly reported. We evaluated the accuracy of phenotypic methods commonly used in routine clinical laboratories in the detection of novel K. pneumoniae carbapenemase (KPC) enzymes. Additionally, we characterized by whole-genome sequencing (WGS) the KPC-ST307-K. pneumoniae isolates recovered in our hospital before and after CAZ/AVI therapy. Rectal colonization or infection by carbapenem-resistant KPC-3 K. pneumoniae isolates (imipenem MIC, 16 mg/L; meropenem MIC, 8 to >16 mg/L) and CAZ/AVI-susceptible isolates (CAZ/AVI MIC, 1 to 2 mg/L) were first detected in three intensive care unit (ICU) patients admitted between March 2020 and July 2020. KPC K. pneumoniae isolates with increased CAZ/AVI MICs (8 to 32 mg/L) and carbapenem susceptibility (imipenem and meropenem MIC, <1 mg/L) were recovered within 6 to 24 days after CAZ/AVI treatment. WGS confirmed that all KPC K. pneumoniae isolates belonged to the sequence type 307 (ST307) high-risk clone and carried identical antimicrobial resistance genes and virulence factors. The presence of the novel blaKPC-46, blaKPC-66, and blaKPC-92 genes was confirmed in the K. pneumoniae isolates with increased CAZ/AVI MICs and restored carbapenem activity. KPC production was confirmed by immunochromatography, the eazyplex Superbug CRE system, and the Xpert Carba-R assay in all KPC K. pneumoniae isolates, but not in any isolate using chromogenic agar plates for carbapenemase producers (ChromID-CARBA), the KPC/MBL/OXA-48 Confirm kit, and the ß-CARBA test. Nevertheless, all grew in chromogenic agar plates for extended-spectrum ß-lactamase (ESBL) producers (ChromID-ESBL). We report the failure of the most common phenotypic methods used for the detection of novel KPC carbapenemases but not of rapid molecular or immunochromatography assays, thus highlighting their relevance in microbiology laboratories.

The EFSUMB Guidelines and Recommendations for Musculoskeletal Ultrasound - Part I: Extraarticular Pathologies.

The first part of the guidelines and recommendations for musculoskeletal ultrasound, produced under the auspices of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB), provides information about the use of musculoskeletal ultrasound for assessing extraarticular structures (muscles, tendons, entheses, ligaments, bones, bursae, fasciae, nerves, skin, subcutaneous tissues, and nails) and their pathologies. Clinical applications, practical points, limitations, and artifacts are described and discussed for every structure. After an extensive literature review, the recommendations have been developed according to the Oxford Centre for Evidence-based Medicine and GRADE criteria and the consensus level was established through a Delphi process. The document is intended to guide clinical users in their daily practice.

The EFSUMB Guidelines and Recommendations for Musculoskeletal Ultrasound - Part II: Joint Pathologies, Pediatric Applications, and Guided Procedures.

The second part of the Guidelines and Recommendations for Musculoskeletal Ultrasound (MSUS), produced under the auspices of EFSUMB, following the same methodology as for Part 1, provides information and recommendations on the use of this imaging modality for joint pathology, pediatric applications, and musculoskeletal ultrasound-guided procedures. Clinical application, practical points, limitations, and artifacts are described and discussed for every joint or procedure. The document is intended to guide clinical users in their daily practice.

Combination of arterial lactate levels and Cv-aCO2/Da-vO2 ratio to predict early allograft dysfunction after liver transplantation.

PURPOSE: We examined the ability of the P(v-a)CO2/Da-vO2 ratio combined with elevated lactate levels to predict early allograft dysfunction (EAD). MATERIALS AND METHODS: Patients were classified into four groups according to lactate levels and P(v-a)CO2/Da-vO2 ratio: Group 1; lactate >2.0 mmol/L and P(v-a)CO2/Da-vO2 ratio >1.0; Group 2; lactate >2.0 mmol/L and P(v-a)CO2/Da-vO2 ratio <1.0; group 3; lactate<2.0 mmol/L and P(v-a)CO2/Da-vO2 ratio >1.0; group 4; lactate<2.0 mmol/L and P(v-a)CO2/Da-vO2 ratio <1.0. We defined EAD according to Olthoff criteria. RESULTS: One-hundred and fifty patients were included. EAD occurred in 41 patients (27.3%), and was associated with worse graft survival at 1 year (92% vs. 73%; P = ,003) as well as a higher re-transplantation rate (4,6% vs. 17,1%; P = ,019). The multivariate analysis revealed that P(v-a)CO2/Da-vO2 ratio at T6 [OR 7.05(CI95% 2.77-19.01, P<.001)] was an independent predictor for EAD. Belonging to group 1 at 6 h was associated with worse clinical outcomes but no association was found with 1-year graft survival or 1-year patient survival. CONCLUSIONS: In this single center, prospective, observational study in patients who received an OLT, we found that elevated lactate levels combined with a high Cv-aCO2/Da-vO2 after 6 h was associated with the development of EAD and worse clinical outcomes in the early postoperative period.

Mediators of the socioeconomic status and life satisfaction relationship in older adults: a multi-country structural equation modeling approach.

OBJECTIVES: Socioeconomic status (SES) relates to life satisfaction in old age, although the underlying mechanisms remain unclear. Health and subjective social status have shown to be related to both SES and life satisfaction. This study aims to test the mediating role of health and subjective social status in old age, and to analyze if these potential mediations vary among three European countries with different socioeconomic characteristics and welfare regimes. METHOD: The sample comprised 7,272 participants aged 50+ from COURAGE in Europe study, a household survey carried out in 2011-2012 on nationally representative samples from Finland, Poland, and Spain. A Multiple Indicators, Multiple Causes approach based on multi-group Structural Equation Modeling was implemented to test mediating effects. RESULTS: The structural invariance model showed an adequate fit (CFI = 0.971, RMSEA = 0.061). Health and subjective social status invariantly mediated the relationship between SES and life satisfaction across countries with different socioeconomic characteristics and welfare regimes. SES direct effects explained 0.83-0.85% of life satisfaction variance, whilst indirect effects explained 2.29-2.36% of life satisfaction variance via health, 3.30-3.42% via subjective social status, and 0.06% via both mediating variables. CONCLUSION: Policies aimed at increasing the SES of the older adults may entail multiple benefits, resulting in better subjective social status, health, and life satisfaction outcomes, thus fostering healthy aging of the population.

Minimally invasive ultrasound-guided vs open release for carpal tunnel syndrome in working population: A randomized controlled trial.

PURPOSE: To compare the clinical effectiveness of minimally invasive ultrasound (US)-guided vs open release for carpal tunnel syndrome. METHODS: In an open randomized controlled trial, 47 employed patients were allocated to US-guided carpal tunnel release (USCTR) and 42 to an open carpal tunnel release (OCTR) procedure. The main outcome was symptom severity measured by the Boston Carpal Tunnel Syndrome Questionnaire (BCTQ-S). Secondary outcomes were hand functionality (BCTQ-F), nerve conduction, two-point discrimination, handgrip and pinch strength, pain (visual analog scale), work leave and complications. For BCTQ-S and BCTQ-F, minimal clinically important differences (MCID) were also considered. Follow-up duration was 12 months. RESULTS: Mixed model analyses detected no significant differences between the two treatment arms in BCTQ-S (P = .098) while BCTQ-F scores were significantly better in the USCTR group (P = .007). This benefit was, however, not supported by the MCID data. Remaining variables were similar in the two groups except pain which was lower in USCTR at 3 months follow-up. All variables but two-point discrimination showed significant improvement after 3 months. CONCLUSIONS: Our findings reveal similar symptom relief benefits following OCTR or USCTR in these patients. The patients in our USCTR group, however, reported better hand functional status and less pain.

Longer Tendon-Bone Distances of the A2 and A4 Annular Pulleys in Experienced High-Level Sport Climbers: Injury or Adaptation?

INTRODUCTION: Experienced high-level climbers are subject to a number of bone and soft tissue changes over the years and are also among the most exposed to pulley injuries. One of the main consequences of pulley rupture is the separation of the flexor tendons from the subjacent phalanges, also known as bowstringing. The purpose of this study was to determine whether this population has asymptomatic bowstringing of the A2 and/or A4 pulleys as determined by tendon-bone distance (TBD) values when compared to nonclimbers. METHODS: High-resolution ultrasound TBD measurements in active forced flexion were made for the A2 and A4 pulley of the ring finger bilaterally. Participants were 21 asymptomatic sport climbers who had 21 consecutive years of climbing at a level above 9.66 in the International Mountaineering and Climbing Federation difficulty metric scale. Control subjects were 21 age-matched nonclimbers. RESULTS: A significantly longer TBD-25% (0.3 mm) and 35% (0.4 mm) for the A2 and A4 pulleys, respectively-was found in the experienced climbers group (experienced climbers group: A2 1.6±0.5 mm and A4 1.6±0.4 mm; nonclimbers group: A2 1.2±0.1 mm and A4 1.2±0.2 mm). CONCLUSIONS: Our results suggest that bowstringing of A2 and A4 pulleys occurs in asymptomatic experienced high-level climbers, which could be interpreted as either an adaptive mechanism to workloads endured over years of climbing or a consequence of underdiagnosed pulley ruptures.

Ultrasound classification of medial gastrocnemious injuries.

High-resolution ultrasound (US) has helped to characterize the "tennis leg injury" (TL). However, no specific classifications with prognostic value exist. This study proposes a medial head of the gastrocnemius injury classification based on sonographic findings and relates this to the time to return to work (RTW) and return to sports (RTS) to evaluate the prognostic value of the classification. 115 subjects (64 athletes and 51 workers) were retrospectively reviewed to asses specific injury location according to medial head of the gastrocnemius anatomy (myoaponeurotic junction; gastrocnemius aponeurosis (GA), free gastrocnemius aponeurosis (FGA)), presence of intermuscular hematoma, and presence of gastrocnemius-soleus asynchronous movement. Return to play (RTP; athletes) and return to work (RTW; occupational) days were recorded by the treating physician. This study proposes 5 injury types with a significant relation to RTP and RTW (P < .001): Type 1 (myoaponeurotic injury), type 2A (gastrocnemius aponeurosis injury with a <50% affected GA width), type 2B (gastrocnemius aponeurosis with >50% affected GA width), type 3 (free gastrocnemius aponeurosis (FGA) tendinous injury), and type 4 (mixed GA and FGA injury). The longest RTP/RTW periods were associated with injuries with FGA involvement. Intermuscular hematoma and Gastrocnemius-soleus asynchronous motion during dorsiflexion and plantarflexion were observed when the injury affected >50% of the GA width, with or without associated FGA involvement, and this correlated with a worse prognosis. The proposed classification can be readily applied in the clinical setting although further studies on treatment options are required.

Ultrasound classification of traumatic distal biceps brachii tendon injuries.

OBJECTIVE: The present work is aimed at analysing ultrasound findings in patients with distal biceps brachii tendon (DBBT) injuries to assess the sensitivity of ultrasound in detecting the different forms of injury, and to compare ultrasound results with magnetic resonance imaging (MRI) and surgical results. MATERIALS AND METHODS: A total of 120 patients with traumatic DBBT injuries examined between 2011 and 2015 were analysed. We compared ultrasound results with MRI results when surgery was not indicated and with MRI and surgical results when surgery was indicated. RESULTS: For major DBBT injuries (complete tears and high-grade partial tears), the concordance study between exploration methods and surgical results found that ultrasound presented a slight statistically significant advantage over MRI (ultrasound: κ = 0.95-very good-95% CI 0.88 to 1.01, MRI: κ = 0.63-good-95% CI 0.42 to 0.84, kappa difference p < 0.01). Minor injuries, in which most tendon fibres remain intact (tendinopathies, elongations and low-grade partial tears), are the most difficult to interpret, as ultrasound and MRI reports disagreed in 12 out of 39 cases and no surgical confirmation could be obtained. CONCLUSIONS: Based on present results and previous MRI classifications, we establish a traumatic DBBT injury ultrasound classification. The sensitivity and ultrasound-surgery correlation results in the diagnosis of major DBBT injuries obtained in the present study support the recommendation that ultrasound can be used as a first-line imaging modality to evaluate DBBT injuries.

Cross-cultural Adaptation and Validation of the Medication Regimen Complexity Index Adapted to Spanish.

BACKGROUND: The most widely used validated instrument to assess the complexity of medication regimens is the Medication Regimen Complexity Index (MRCI). OBJECTIVE: This study aimed to translate, adapt, and validate a reliable version of the MRCI adapted to Spanish (MRCI-E). METHODS: The cross-cultural adaptation process consisted of an independent translation by 3 clinical pharmacists and a backtranslation by 2 native English speakers. A reliability analysis was conducted on 20 elderly randomly selected patients. Two clinical pharmacists calculated the MRCI-E from discharge treatments and 2 months later. For the validity analysis, the sample was augmented to 60 patients. Convergent validity was assessed by analyzing the correlation between the number of medications; discriminant validity was stratified by gender; and predictive validity was determined by analyzing the ability to predict readmission and mortality at 3 and 6 months. RESULTS: The MRCI-E retained the original structure of 3 sections. The reliability analysis demonstrated an excellent internal consistency (Cronbach's α=0.83), and the intraclass correlation coefficient exceeded 0.9 in all cases. The correlation coefficient with the number of medications was 0.883 ( P<0.001). No significant differences were found when stratified by gender (3.6; 95%CI=-2.9 to 10.2; P=0.27). Patients who were readmitted at 3 months had a higher MRCI-E score (10.7; 95%CI=4.4 to 17.2; P=0.001). The differences remained significant in patients readmitted at 6 months, but differences in mortality were not detected. CONCLUSIONS: The MRCI-E retains the reliability and validity of the original index and provides a suitable tool to assess the complexity of medication regimens in Spanish.

Multidisciplinary approach to the persistent double distal tendon of the biceps brachii.

PURPOSE: The aim of this study is to correlate the ultrasound (US) appearance of the persistent double or bifid distal tendon of the biceps brachii muscle with anatomical and histological data. This will provide a new model to study the pathological distal biceps brachii tendon (DBBT). METHODS: The DBBT of 20 cadaveric elbows were examined with linear array broadband US transducers (frequency band 14-6 MHz) using an anterior approach. Trypan blue dye was injected underneath the paratenon under US guidance in 16 specimens. After they were dissected, five of them were processed to obtain histological slices stained with hematoxylin-eosin and antiserum to protein S100. RESULTS: At US, the DBBT is a tendon in which the fascicles are organized in two different hyperechoic components separated by a hyperechoic septum related to the endotenon. The endotenon is lax, flexible, and makes folding and gliding of the two portions feasible. The DBBT is surrounded by a hyperechoic paratenon adjacent to the tendon surface, which is only differentiable by US when dye is interposed between such structures. CONCLUSIONS: The connective septum of endotenon located between the two main components of the DBBT is responsible for the US image of two separate tendons and functionally enables it to work as two separate entities, thus allowing respective folding and gliding. The paratenon surrounding the lacertus fibrosus and the DBBT plays an important stabilization role, enabling them to change shape and arrangement during joint motion. It is also an important conduit for nerves and blood vessels.

Eleven New Species of the Genus Tarzetta (Tarzettaceae, Pezizales) from Mexico.

The genus Tarzetta is distributed mainly in temperate forests and establishes ectomycorrhizal associations with angiosperms and gymnosperms. Studies on this genus are scarce in México. A visual, morphological, and molecular (ITS-LSU) description of T. americupularis, T. cupressicola, T. davidii, T. durangensis, T. mesophila, T. mexicana, T. miquihuanensis, T. poblana, T. pseudobronca, T. texcocana, and T. victoriana was carried out in this work, associated with Abies, Quercus, and Pinus. The results of SEM showed an ornamented ascospores formation by Mexican Taxa; furthermore, the results showed that T. catinus and T. cupularis are only distributed in Europe and are not associated with any American host.

Minimally invasive ultrasound-guided carpal tunnel release: a cadaver study.

BACKGROUND: Carpal tunnel syndrome is a common condition frequently requiring surgical intervention. We describe a new minimally invasive surgical technique for carpal tunnel release utilizing ultrasound (US) visualization. METHODS: The technique was performed on 20 fresh frozen cadaver specimens. A surgical metallic probe with a "U"-shaped trough and upward curved distal tip was precisely positioned in the carpal tunnel with US guidance followed by division of the flexor retinaculum (FR) with a "V"-shaped scalpel. RESULTS: Complete division of the FR was confirmed by US. Dissection performed on the specimens confirmed complete release of FR and absence of neurovascular injury. The distance from the division of the FR to these structures, the "safety margins," was measured. CONCLUSIONS: This new technique for carpal tunnel release appears to combine the safety and efficacy of open carpal tunnel surgery with the advantages of the minimally invasive techniques.

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.

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.

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.

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.

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.