Randomized Trial of Facilitated Adherence to Screening Colonoscopy vs Sequential Fecal-Based Blood Test.

BACKGROUND & AIMS: Colorectal cancer (CRC) screening guidelines include screening colonoscopy and sequential high-sensitivity fecal occult blood testing (HSgFOBT), with expectation of similar effectiveness based on the assumption of similar high adherence. However, adherence to screening colonoscopy compared with sequential HSgFOBT has not been reported. In this randomized clinical trial, we assessed adherence and pathology findings for a single screening colonoscopy vs sequential and nonsequential HSgFOBTs. METHODS: Participants aged 40-69 years were enrolled at 3 centers representing different clinical settings. Participants were randomized into a single screening colonoscopy arm vs sequential HSgFOBT arm composed of 4-7 rounds. Initial adherence to screening colonoscopy and sequential adherence to HSgFOBT, follow-up colonoscopy for positive HSgFOBT tests, crossover to colonoscopy, and detection of advanced neoplasia or large serrated lesions (ADN-SERs) were measured. RESULTS: There were 3523 participants included in the trial; 1761 and 1762 participants were randomized to the screening colonoscopy and HSgFOBT arms, respectively. Adherence was 1473 (83.6%) for the screening colonoscopy arm vs 1288 (73.1%) for the HSgFOBT arm after 1 round (relative risk [RR], 1.14; 95% CI, 1.10-1.19; P ≤ .001), but only 674 (38.3%) over 4 sequential HSgFOBT rounds (RR, 2.19; 95% CI, 2.05-2.33). Overall adherence to any screening increased to 1558 (88.5%) in the screening colonoscopy arm during the entire study period and 1493 (84.7%) in the HSgFOBT arm (RR, 1.04; 95% CI, 1.02-1.07). Four hundred thirty-six participants (24.7%) crossed over to screening colonoscopy during the first 4 rounds. ADN-SERs were detected in 121 of the 1473 participants (8.2%) in the colonoscopy arm who were adherent to protocol in the first 12 months of the study, whereas detection of ADN-SERs among those who were not sequentially adherent (n = 709) to HSgFOBT was subpar (0.6%) (RR, 14.72; 95% CI, 5.46-39.67) compared with those who were sequentially adherent (3.3%) (n = 647) (RR, 2.52; 95% CI, 1.61-3.98) to HSgFOBT in the first 4 rounds. When including colonoscopies from HSgFOBT patients who were never positive yet crossed over (n = 1483), 5.5% of ADN-SERs were detected (RR, 1.50; 95% CI, 1.15-1.96) in the first 4 rounds. CONCLUSIONS: Observed adherence to sequential rounds of HSgFOBT was suboptimal compared with a single screening colonoscopy. Detection of ADN-SERs was inferior when nonsequential HSgFOBT adherence was compared with sequential adherence. However, the greatest number of ADN-SERs was detected among those who crossed over to colonoscopy and opted to receive a colonoscopy. The effectiveness of an HSgFOBT screening program may be enhanced if crossover to screening colonoscopy is permitted. CLINICALTRIALS: gov, Number: NCT00102011.

Projected Colorectal Cancer Incidence and Mortality Based on Observed Adherence to Colonoscopy and Sequential Stool-Based Screening.

INTRODUCTION: Modeling supporting recommendations for colonoscopy and stool-based colorectal cancer (CRC) screening tests assumes 100% sequential participant adherence. The impact of observed adherence on the long-term effectiveness of screening is unknown. We evaluated the effectiveness of a program of screening colonoscopy every 10 years vs annual high-sensitivity guaiac-based fecal occult blood testing (HSgFOBT) using observed sequential adherence data. METHODS: The MIcrosimulation SCreening ANalysis (MISCAN) model used observed sequential screening adherence, HSgFOBT positivity, and diagnostic colonoscopy adherence in HSgFOBT-positive individuals from the National Colonoscopy Study (single-screening colonoscopy vs ≥4 HSgFOBT sequential rounds). We compared CRC incidence and mortality over 15 years with no screening or 10 yearly screening colonoscopy vs annual HSgFOBT with 100% and differential observed adherence from the trial. RESULTS: Without screening, simulated incidence and mortality over 15 years were 20.9 (95% probability interval 15.8-26.9) and 6.9 (5.0-9.2) per 1,000 participants, respectively. In the case of 100% adherence, only screening colonoscopy was predicted to result in lower incidence; however, both tests lowered simulated mortality to a similar level (2.1 [1.6-2.9] for screening colonoscopy and 2.5 [1.8-3.4] for HSgFOBT). Observed adherence for screening colonoscopy (83.6%) was higher than observed sequential HSgFOBT adherence (73.1% first round; 49.1% by round 4), resulting in lower simulated incidence and mortality for screening colonoscopy (14.4 [10.8-18.5] and 2.9 [2.1-3.9], respectively) than HSgFOBT (20.8 [15.8-28.1] and 3.9 [2.9-5.4], respectively), despite a 91% adherence to diagnostic colonoscopy with FOBT positivity. The relative risk of CRC mortality for screening colonoscopy vs HSgFOBT was 0.75 (95% probability interval 0.68-0.80). Findings were similar in sensitivity analyses with alternative assumptions for repeat colonoscopy, test performance, risk, age, and projection horizon. DISCUSSION: Where sequential adherence to stool-based screening is suboptimal and colonoscopy is accessible and acceptable-as observed in the national colonoscopy study, microsimulation, comparative effectiveness, screening recommendations.

The mobilization and transport of newly fixed carbon are driven by plant water use in an experimental rainforest under drought.

Non-structural carbohydrates (NSCs) are building blocks for biomass and fuel metabolic processes. However, it remains unclear how tropical forests mobilize, export, and transport NSCs to cope with extreme droughts. We combined drought manipulation and ecosystem 13CO2 pulse-labeling in an enclosed rainforest at Biosphere 2, assessed changes in NSCs, and traced newly assimilated carbohydrates in plant species with diverse hydraulic traits and canopy positions. We show that drought caused a depletion of leaf starch reserves and slowed export and transport of newly assimilated carbohydrates below ground. Drought effects were more pronounced in conservative canopy trees with limited supply of new photosynthates and relatively constant water status than in those with continual photosynthetic supply and deteriorated water status. We provide experimental evidence that local utilization, export, and transport of newly assimilated carbon are closely coupled with plant water use in canopy trees. We highlight that these processes are critical for understanding and predicting tree resistance and ecosystem fluxes in tropical forest under drought.

Bornean tropical forests recovering from logging at risk of regeneration failure.

Active restoration through silvicultural treatments (enrichment planting, cutting climbers and liberation thinning) is considered an important intervention in logged forests. However, its ability to enhance regeneration is key for long-term recovery of logged forests, which remains poorly understood, particularly for the production and survival of seedlings in subsequent generations. To understand the long-term impacts of logging and restoration we tracked the diversity, survival and traits of seedlings that germinated immediately after a mast fruiting in North Borneo in unlogged and logged forests 30-35 years after logging. We monitored 5119 seedlings from germination for ~1.5 years across a mixed landscape of unlogged forests (ULs), naturally regenerating logged forests (NR) and actively restored logged forests via rehabilitative silvicultural treatments (AR), 15-27 years after restoration. We measured 14 leaf, root and biomass allocation traits on 399 seedlings from 15 species. Soon after fruiting, UL and AR forests had higher seedling densities than NR forest, but survival was the lowest in AR forests in the first 6 months. Community composition differed among forest types; AR and NR forests had lower species richness and lower evenness than UL forests by 5-6 months post-mast but did not differ between them. Differences in community composition altered community-weighted mean trait values across forest types, with higher root biomass allocation in NR relative to UL forest. Traits influenced mortality ~3 months post-mast, with more acquisitive traits and relative aboveground investment favoured in AR forests relative to UL forests. Our findings of reduced seedling survival and diversity suggest long time lags in post-logging recruitment, particularly for some taxa. Active restoration of logged forests recovers initial seedling production, but elevated mortality in AR forests lowers the efficacy of active restoration to enhance recruitment or diversity of seedling communities. This suggests current active restoration practices may fail to overcome barriers to regeneration in logged forests, which may drive long-term changes in future forest plant communities.

A restauração ativa por meio de tratamentos silviculturais (plantio de enriquecimento, corte de trepadeiras e desbaste) é considerada uma intervenção importante em florestas com exploração de madeira. No entanto, sua capacidade de melhorar a regeneração, essencial para a recuperação de longo prazo das florestas exploradas, permanece pouco compreendida, especialmente no que diz respeito à produção e sobrevivência de mudas em gerações subsequentes. Para compreender os impactos de longo prazo da exploração madeireira e da restauração, acompanhamos a diversidade, sobrevivência e características de plântulas que germinaram imediatamente após uma frutificação em massa no norte de Bornéu, em florestas com e sem exploração de madeira, 30-35 anos após o fim da extração. Monitoramos 5119 mudas desde a germinação por aproximadamente 1,5 anos em uma paisagem mista de florestas não exploradas (UL), florestas exploradas em regeneração natural (NR) e florestas exploradas restauradas ativamente por meio de tratamentos silviculturais de reabilitação (AR), 15-27 anos após a restauração. Medimos 14 traços funcionais de folhas, raízes e alocação de biomassa em 399 mudas de 15 espécies. Logo após a frutificação, as florestas UL e AR apresentaram densidades de mudas mais altas do que as florestas NR, mas a sobrevivência foi mais baixa nas florestas AR nos primeiros seis meses. A composição da comunidade diferiu entre os tipos de floresta; as florestas AR e NR teviram menor riqueza de espécies e menor equidade do que as florestas UL 5-6 meses após a frutificação, mas não diferiram entre si. As diferenças na composição da comunidade alteraram os valores de média ponderada pela comunidade das características entre os tipos de floresta com maior alocação de biomassa radicular nas florestas NR em relação às florestas UL. As características influenciaram a mortalidade aproximadamente 3 meses após a frutificação, com traços mais aquisitivos maior investimento em biomassa relativa acima do solo nas florestas AR em relação às florestas UL. Nossas descobertas de redução na sobrevivência e diversidade de plântulas sugerem que há longos retardos no recrutamento após o fim da exploração de madeira, particularmente para alguns táxons. A restauração ativa de florestas exploradas recupera a produção inicial de plântulas, mas a mortalidade elevada nas florestas AR diminui a eficácia da restauração ativa no melhorio do recrutamento e da diversidade das comunidades de mudas. Isso sugere que as práticas atuais de restauração ativa podem não superar as barreiras à regeneração em florestas exploradas, o que pode levar a mudanças de longo prazo nas comunidades florestais no futuro.

Punctuated equilibrium at 50: Anything there for evolutionary anthropology? Yes; definitely.

The theory of punctuated equilibrium (PE) was developed a little over 50 years ago to explain long-term, large-scale appearance and disappearance of species in the fossil record. A theory designed specifically for that purpose cannot be expected, out of the box, to be directly applicable to biocultural evolution, but in revised form, PE offers a promising approach to incorporating not only a wealth of recent empirical research on genetic, linguistic, and technological evolution but also large databases that document human biological and cultural diversity across time and space. Here we isolate the fundamental components of PE and propose which pieces, when reassembled or renamed, can be highly useful in evolutionary anthropology, especially as humanity faces abrupt ecological challenges on an increasingly larger scale.

Global Run-On sequencing to measure nascent transcription in Saccharomyces cerevisiae.

Global Run-On sequencing is a reliable and widely used approach for monitoring nascent transcription on a genomewide scale. The assay has been successfully used for studying global transcription in humans, plants, worms, flies, and fission yeast. Here we describe a GRO-seq protocol for studying transcription in budding yeast, Saccharomyces cerevisiae. Briefly, the technique involves permeabilization of actively growing yeast cells, allowing transcription to proceed in permeabilized cells in the presence of brominated UTP, affinity purification of bromo-UMP incorporated nascent transcripts followed by cDNA library construction, deep sequencing, and mapping against the reference genome. The approach maps the position of transcriptionally active RNA polymerase on a genomewide basis. In addition to identifying the complete set of transcriptionally active genes in a cell under a given set of conditions, the method can be used to determine elongation rate, termination defect and promoter directionality at the genomewide level. The approach is especially useful in identifying short-lived unstable transcripts that are rapidly degraded even before they leave the nucleus.

Vergence and accommodation deficits in paediatric and adolescent patients during sub-acute and chronic phases of concussion recovery.

INTRODUCTION: Visual function deficits have been reported in adolescents following concussion. We compared vergence and accommodation deficits in paediatric and adolescent patients at a tertiary medical centre in the sub-acute (15 days to 12 weeks) and chronic (12 weeks to 1 year) phases of concussion recovery. METHODS: The study included patients aged 7 to <18 years seen between 2014 and 2021, who had a binocular vision (BV) examination conducted within 15 days and 1 year of their concussion injury. Included patients had to have 0.10 logMAR monocular best-corrected vision or better in both eyes and be wearing a habitual refractive correction. BV examinations at near included measurements of near point of convergence, convergence and divergence amplitudes, vergence facility, monocular accommodative amplitude and monocular accommodative facility. Vergence and accommodation deficits were diagnosed using established clinical criteria. Group differences were assessed using nonparametric statistics and ANCOVA modelling. RESULTS: A total of 259 patients were included with 111 in the sub-acute phase and 148 in the chronic phase of concussion recovery. There was no significant difference in the rates of vergence deficits between the two phases of concussion recovery (sub-acute = 48.6%; chronic = 49.3%). There was also no significant difference in the rates of accommodation deficits between the two phases of concussion recovery (sub-acute = 82.0%; chronic = 77.0%). CONCLUSION: Patients in both the sub-acute and chronic phases of concussion recovery exhibited a high frequency of vergence and accommodation deficits, with no significant differences between groups. Results indicate that patients exhibiting vision deficits in the sub-acute phase may not resolve without intervention, though a prospective, longitudinal study is required to test the hypothesis.

Medial Ulnar Collateral Ligament Reconstruction With Allograft Provides Excellent Clinical Outcomes, High Rates of Return to Play, and a Low Incidence of Postoperative Complications: A Systematic Review.

PURPOSE: To perform a systematic review evaluating clinical outcomes in patients undergoing medial ulnar collateral ligament reconstruction (MUCLR) with soft-tissue allograft. METHODS: A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The primary outcomes evaluated were patient-reported outcome scores, return to play (RTP) rates, incidence of postoperative complications, and rates of graft rupture or mechanical failure. RESULTS: The literature search identified 395 articles, and 5 studies met final inclusion criteria after full-text review. A total of 274 patients were analyzed in the included studies and follow-up ranged from 3.0 to 7.6 years. Two studies (number of patients = 141) reported outcomes exclusively of MUCLR with allograft, whereas 3 studies (number of patients = 133) reported outcomes in patients undergoing MUCLR with either allograft or autograft. Allograft sources included gracilis, semitendinosus, plantaris, peroneus longus, and palmaris longus. Level of patient athletic competition ranged from recreational athletes to the professional level; however, nonathletes in the setting of trauma were also included. The RTP rate after MUCLR with soft-tissue allograft was 95.3%, and 89.3% of patients returned to a similar or greater level of play postoperatively. The Timmerman-Andrews score was reported in 2 studies, and the means postoperatively ranged from 94.55 to 97. Postoperative complication rates were low (range, 0% to 20%), and there were no reported incidences of allograft rupture or mechanical failure. CONCLUSIONS: Based on the available data, soft-tissue allograft for MUCLR in athletic patient populations provides excellent clinical outcomes, high rates of RTP, and low rates of postoperative complications and graft failure at short-term follow-up. There remains a lack of high-quality evidence directly comparing autograft versus allograft outcomes in elite overhead-throwing athletes to support allograft as an acceptable alternative for MUCLR in this patient population. LEVEL OF EVIDENCE: Level IV, systematic review of Level III-IV studies.

Medial elbow injuries in the throwing athlete.

There has been an epidemic increase in injuries to the elbow in our youth sports over the past 15 years. Initially, career-ending elbow injuries occurred almost exclusively in the professional population. The landmark procedure developed by Dr. Frank Jobe, colloquially termed "Tommy John surgery" after the initial player in whom he performed the surgical procedure, allowed roughly two-thirds of professional athletes to return to play at or near the same level. As the surgical procedure became more widespread, modifications of the technique by Jobe and many other contributors raised the return-to-play level to 85%-94% of players regaining the ability to return to sport at the preinjury level. Almost simultaneously, the emphasis on velocity in the professional ranks led to an unintentional increase in stress on the throwing elbow. This was magnified in our athletes by the advent of year-round sports, as well as the formation of "showcase" events to demonstrate skills and measure velocity. This, unfortunately, has resulted in an increase in both repetitive stress injuries and acute traumatic injuries in our young athletes. The purpose of this article is to discuss age-related injuries from both a preventative standpoint and a treatment standpoint.

TFIIB-Termination Factor Interaction Affects Termination of Transcription on Genome-Wide Scale.

Apart from its well-established role in the initiation of transcription, the general transcription factor TFIIB has been implicated in the termination step as well. The ubiquity of TFIIB involvement in termination as well as mechanistic details of its termination function, however, remain largely unexplored. Using GRO-seq analyses, we compared the terminator readthrough phenotype in the sua7-1 mutant (TFIIBsua7-1) and the isogenic wild type (TFIIBWT) strains. Approximately 74% of genes analyzed exhibited a 2-3-fold increase in readthrough of the poly(A)-termination signal in the TFIIBsua7-1 mutant compared to TFIIBWT cells. To understand the mechanistic basis of TFIIB's role in termination, we performed the mass spectrometry of TFIIB-affinity purified from chromatin and soluble cellular fractions-from TFIIBsua7-1 and TFIIBWT cells. TFIIB purified from the chromatin fraction of TFIIBWT cells exhibited significant enrichment of CF1A and Rat1 termination complexes. There was, however, a drastic decrease in TFIIB interaction with CF1A and Rat1 complexes in the TFIIBsua7-1 mutant. ChIP assays revealed about a 90% decline in the recruitment of termination factors in the TFIIBsua7-1 mutant compared to wild type cells. The overall conclusion of these results is that TFIIB affects the termination of transcription on a genome-wide scale, and the TFIIB-termination factor interaction plays a crucial role in the process.

How do the top 10 known offending drug classes associated with decreased bone mineral density affect total shoulder arthroplasty outcomes?

BACKGROUND: Many regularly prescribed classes of drugs are known to negatively impact bone health. However, it is unclear if perioperative use of these drugs impacts total shoulder arthroplasty (TSA) outcomes. The purpose of this study was to analyze the impact of perioperative use of 10 drug classes with known negative effects on bone health on prosthesis-related outcomes of TSA. METHODS: Patients who underwent primary TSA were retrospectively identified in the PearlDiver database. Within this population, patients prescribed proton pump inhibitors (PPIs), thiazolidinediones (TZDs), loop diuretics, glucocorticoids, aromatase inhibitors, calcineurin inhibitors, selective serotonin reuptake inhibitors (SSRIs), antiepileptic drugs (AEDs), first-generation antipsychotics (FGAs), and second-generation antipsychotics (SGAs) within 6 months before or 6 months after primary TSA were identified (n = 23,748). These patients were propensity score matched 1:1 with controls (n = 23,748) on age, sex, and several comorbidities. After matching, patients with perioperative drug exposure were divided into 10 subgroups (ie, 1 for each drug class). Rates of prosthesis-related complications among patients taking each medication class vs. controls were compared with multivariable logistic regression. RESULTS: Relative to controls, SGA exposure was associated with significantly higher rates of all-cause revision (odds ratio [OR] 1.68) and aseptic revision (OR 1.57). Loop diuretic exposure was associated with significantly higher rates of all-cause revision (OR 1.44) and aseptic revision (OR 1.43). Glucocorticoid exposure was associated with significantly higher rates of all-cause revision (OR 1.32) and aseptic revision (OR 1.30). SSRI exposure was associated with significantly higher rates of all-cause revision (OR 1.27) and aseptic revision (OR 1.24). Periprosthetic fracture, aseptic loosening, and septic revision was comparable for all drug cohorts compared to matched controls (all P > .05). Patients with perioperative exposure to PPIs, TZDs, FGAs, AEDs, aromatase inhibitors, and calcineurin inhibitors displayed comparable rates of all queried complications compared with controls (all P > .05). CONCLUSION: Compared with matched controls, patients with perioperative exposure to SGAs, loop diuretics, glucocorticoids and SSRIs exhibited significantly higher rates of all-cause and aseptic revisions following primary TSA. Several other medications that are risk factors for osteoporosis and fragility fractures did not demonstrate significant associations with any complications, including periprosthetic fracture. These results highlight the need for a thorough review of patients' medical history and current medication usage prior to preoperative risk counseling for patients seeking TSA.

Hip Muscle Strength, Range of Motion, and Functional Performance in Young Elite Male Australian Football Players.

CONTEXT: Hip and groin injuries are common in field sports such as football, with measurement of hip strength and range of motion (ROM) recommended for assessment of these conditions. We aimed to report hip strength, hip ROM, and functional task performance in young elite Australian football athletes. DESIGN: Cross-sectional study. METHODS: Fifty-eight newly drafted Australian Football League athletes completed hip abduction, adduction, internal rotation, external rotation, and flexion strength testing with an adjustable stabilized or hand-held dynamometer. Hip internal rotation and external rotation, bent knee fall out, and ankle dorsiflexion ROM were also measured. Players completed hop for distance, side bridge, and star excursion balance functional tests. We compared findings between the dominant and nondominant limbs. RESULTS: We found small deficits unlikely to be clinically meaningful in the dominant limb for hip abduction and adduction strength, and a small deficit in the nondominant limb for external rotation strength and side bridge time. Athletes had lower hip internal rotation (mean difference 2.56°; 95% confidence interval, 0.87 to 4.26) and total rotation ROM (2.03°; 95% confidence interval, 0.06 to 4.01) on the dominant limb. CONCLUSIONS: There were no meaningful differences between dominant and nondominant limbs for hip strength, ROM, or functional tests. Our results may be used for benchmarking young male Australian football athletes when targeting optimal strength and returning from injury.

Beyond the canonical role of TFIIB in eukaryotic transcription.

The role of general transcription factor TFIIB in transcription extends well beyond its evolutionarily conserved function in initiation. Chromatin localization studies demonstrating binding of TFIIB to both the 5' and 3' ends of genes in a diverse set of eukaryotes strongly suggested a rather unexpected role of the factor in termination. TFIIB indeed plays a role in termination of transcription. TFIIB occupancy of the 3' end is possibly due to its interaction with the termination factors residing there. Interaction of the promoter-bound TFIIB with factors occupying the 3' end of a gene may be the basis of transcription-dependent gene looping. The proximity of the terminator-bound factors with the promoter in a gene loop has the potential to terminate promoter-initiated upstream anti-sense transcription thereby conferring promoter directionality. TFIIB, therefore, is emerging as a factor with pleiotropic roles in the transcription cycle. This could be the reason for preferential targeting of TFIIB by viruses. Further studies are needed to understand the critical role of TFIIB in viral pathogenesis in the context of its newly identified roles in termination, gene looping and promoter directionality.

Demographic consequences of heterogeneity in conspecific density dependence among mast-fruiting tropical trees.

The role of conspecific density dependence (CDD) in the maintenance of species richness is a central focus of tropical forest ecology. However, tests of CDD often ignore the integrated effects of CDD over multiple life stages and their long-term impacts on population demography. We combined a 10-year time series of seed production, seedling recruitment and sapling and tree demography of three dominant Southeast Asian tree species that adopt a mast-fruiting phenology. We used these data to construct individual-based models that examine the effects of CDD on population growth rates (λ) across life-history stages. Recruitment was driven by positive CDD for all species, supporting the predator satiation hypothesis, while negative CDD affected seedling and sapling growth of two species, significantly reducing λ. This negative CDD on juvenile growth overshadowed the positive CDD of recruitment, suggesting the cumulative effects of CDD during seedling and sapling development has greater importance than the positive CDD during infrequent masting events. Overall, CDD varied among positive, neutral and negative effects across life-history stages for all species, suggesting that assessments of CDD on transitions between just two stages (e.g. seeds seedlings or juveniles mature trees) probably misrepresent the importance of CDD on population growth and stability.

Distribution of biomass dynamics in relation to tree size in forests across the world.

Tree size shapes forest carbon dynamics and determines how trees interact with their environment, including a changing climate. Here, we conduct the first global analysis of among-site differences in how aboveground biomass stocks and fluxes are distributed with tree size. We analyzed repeat tree censuses from 25 large-scale (4-52 ha) forest plots spanning a broad climatic range over five continents to characterize how aboveground biomass, woody productivity, and woody mortality vary with tree diameter. We examined how the median, dispersion, and skewness of these size-related distributions vary with mean annual temperature and precipitation. In warmer forests, aboveground biomass, woody productivity, and woody mortality were more broadly distributed with respect to tree size. In warmer and wetter forests, aboveground biomass and woody productivity were more right skewed, with a long tail towards large trees. Small trees (1-10 cm diameter) contributed more to productivity and mortality than to biomass, highlighting the importance of including these trees in analyses of forest dynamics. Our findings provide an improved characterization of climate-driven forest differences in the size structure of aboveground biomass and dynamics of that biomass, as well as refined benchmarks for capturing climate influences in vegetation demographic models.

Fake or not? Automated detection of COVID-19 misinformation and disinformation in social networks and digital media.

With the continuous spread of the COVID-19 pandemic, misinformation poses serious threats and concerns. COVID-19-related misinformation integrates a mixture of health aspects along with news and political misinformation. This mixture complicates the ability to judge whether a claim related to COVID-19 is information, misinformation, or disinformation. With no standard terminology in information and disinformation, integrating different datasets and using existing classification models can be impractical. To deal with these issues, we aggregated several COVID-19 misinformation datasets and compared differences between learning models from individual datasets versus one that was aggregated. We also evaluated the impact of using several word- and sentence-embedding models and transformers on the performance of classification models. We observed that whereas word-embedding models showed improvements in all evaluated classification models, the improvement level varied among the different classifiers. Although our work was focused on COVID-19 misinformation detection, a similar approach can be applied to myriad other topics, such as the recent Russian invasion of Ukraine.

Species packing and the latitudinal gradient in beta-diversity.

The decline in species richness at higher latitudes is among the most fundamental patterns in ecology. Whether changes in species composition across space (beta-diversity) contribute to this gradient of overall species richness (gamma-diversity) remains hotly debated. Previous studies that failed to resolve the issue suffered from a well-known tendency for small samples in areas with high gamma-diversity to have inflated measures of beta-diversity. Here, we provide a novel analytical test, using beta-diversity metrics that correct the gamma-diversity and sampling biases, to compare beta-diversity and species packing across a latitudinal gradient in tree species richness of 21 large forest plots along a large environmental gradient in East Asia. We demonstrate that after accounting for topography and correcting the gamma-diversity bias, tropical forests still have higher beta-diversity than temperate analogues. This suggests that beta-diversity contributes to the latitudinal species richness gradient as a component of gamma-diversity. Moreover, both niche specialization and niche marginality (a measure of niche spacing along an environmental gradient) also increase towards the equator, after controlling for the effect of topographical heterogeneity. This supports the joint importance of tighter species packing and larger niche space in tropical forests while also demonstrating the importance of local processes in controlling beta-diversity.

Genes, culture, and the human niche: An overview.

The sharp distinction between biological traits and culturally based traits, which had long been standard in evolutionary approaches to behavior, was blurred in the early 1980s by mathematical models that allowed a co-dependent evolution of genetic transmission and cultural information. Niche-construction theory has since added another contrast to standard evolutionary theory, in that it views niche construction as a cause of evolutionary change rather than simply a product of selection. While offering a new understanding of the coevolution of genes, culture, and human behavior, niche-construction models also invoke multivariate causality, which require multiple time series to resolve. The empirical challenge lies in obtaining time-series data on causal pathways involved in the coevolution of genes, culture, and behavior. This is a significant issue in archeology, where time series are often sparse and causal behaviors are represented only by proxies in the material record.

The extended evolutionary synthesis and human origins: Archaeological perspectives.

Recent developments in evolutionary biology have led to a call for an extension of standard evolutionary theory, with its emphasis on processes such as selection and drift, into a much larger theoretical framework that includes processes such as niche construction, developmental plasticity, inclusive inheritance, and developmental bias. Skeptics argue that these processes are already subsumed within the standard theory and thus an extension is not required. Here, we outline what this evolutionary "rethink" might mean for the study of human origins. Specifically, can paleoanthropologists benefit from an extended theoretical toolkit? The papers in this special issue suggest it can be useful but may not be necessary, depending on the kinds of questions that are being asked.

RNA polymerase II plays an active role in the formation of gene loops through the Rpb4 subunit.

Gene loops are formed by the interaction of initiation and termination factors occupying the distal ends of a gene during transcription. RNAPII is believed to affect gene looping indirectly owing to its essential role in transcription. The results presented here, however, demonstrate a direct role of RNAPII in gene looping through the Rpb4 subunit. 3C analysis revealed that gene looping is abolished in the rpb4Δ mutant. In contrast to the other looping-defective mutants, rpb4Δ cells do not exhibit a transcription termination defect. RPB4 overexpression, however, rescued the transcription termination and gene looping defect of sua7-1, a mutant of TFIIB. Furthermore, RPB4 overexpression rescued the ssu72-2 gene looping defect, while SSU72 overexpression restored the formation of gene loops in rpb4Δ cells. Interestingly, the interaction of TFIIB with Ssu72 is compromised in rpb4Δ cells. These results suggest that the TFIIB-Ssu72 interaction, which is critical for gene loop formation, is facilitated by Rpb4. We propose that Rpb4 is promoting the transfer of RNAPII from the terminator to the promoter for reinitiation of transcription through TFIIB-Ssu72 mediated gene looping.