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Study designRetrospective cohort study of prospectively accrued data.ObjectiveTo evaluate a large, prospective, multicentre dataset of surgically treated degenerative cervical myelopathy (DCM) cases on the contemporary risk of C5 palsy with surgical approach.Summary of background dataThe influence of surgical technique on postoperative C5 palsy after decompression for DCM is intensely debated. Comprehensive, covariate-adjusted analyses are needed using contemporary data.MethodsPatients with moderate to severe DCM were prospectively enrolled in the multicenter, randomized, Phase III CSM-Protect clinical trial and underwent either anterior or posterior decompression between Jan 31, 2012 and May 16, 2017. The primary outcome was the incidence of postoperative C5 palsy, defined as the onset of muscle weakness by at least one grade in manual muscle test at the C5 myotome with slight or absent sensory disruption after cervical surgery. Two comparative cohorts were made based on the anterior or posterior surgical approach. Multivariate hierarchical mixed-effects logistic regression was used to estimate odds ratios (OR) with 95% confidence intervals (CI) for C5 palsy.ResultsA total of 283 patients were included, and 53.4% underwent posterior decompression. The total incidence of postoperative C5 palsy was 7.4% and was significantly higher in patients who underwent posterior decompression compared with anterior decompression (11.26% vs. 3.03%, P =0.008). After multivariable regression, the posterior approach was independently associated with greater than four times the likelihood of postoperative C5 palsy ( P =0.017). Rates of C5 palsy recovery were comparable between the two surgical approaches.ConclusionThe odds of postoperative C5 palsy are significantly higher after posterior decompression compared to anterior decompression for DCM. This may influence surgical decision-making when there is equipoise in deciding between anterior and posterior treatment options for DCM.Level of evidenceTherapeutic Level-II.

The density of wood is a key indicator of the carbon investment strategies of trees, impacting productivity and carbon storage. Despite its importance, the global variation in wood density and its environmental controls remain poorly understood, preventing accurate predictions of global forest carbon stocks. Here we analyse information from 1.1 million forest inventory plots alongside wood density data from 10,703 tree species to create a spatially explicit understanding of the global wood density distribution and its drivers. Our findings reveal a pronounced latitudinal gradient, with wood in tropical forests being up to 30% denser than that in boreal forests. In both angiosperms and gymnosperms, hydrothermal conditions represented by annual mean temperature and soil moisture emerged as the primary factors influencing the variation in wood density globally. This indicates similar environmental filters and evolutionary adaptations among distinct plant groups, underscoring the essential role of abiotic factors in determining wood density in forest ecosystems. Additionally, our study highlights the prominent role of disturbance, such as human modification and fire risk, in influencing wood density at more local scales. Factoring in the spatial variation of wood density notably changes the estimates of forest carbon stocks, leading to differences of up to 21% within biomes. Therefore, our research contributes to a deeper understanding of terrestrial biomass distribution and how environmental changes and disturbances impact forest ecosystems.

BACKGROUND: The incidence of breast and colorectal cancer (CRC) in younger-than-average-age patients is rising and poorly understood. This is the largest study on patients with both cancers who are less than 60 years old and aims to characterize demographic, clinicopathologic, and genetic features and describe therapeutic dilemmas and management strategies. MATERIALS AND METHODS: This is a retrospective medical records review of patients at the University of California San Francisco with both primary breast and CRC before age 60. RESULTS: Fifty-one patients were identified; 41 had detailed medical records. Median age of diagnosis with breast cancer was 43 (range 27-59) and CRC was 50 (28-59). Most were Caucasian (38, 74.5%) and never smokers (23, 56.1%); about half were current alcohol consumers (20, 48.8%) and about one-third had sedentary jobs (14, 34.1%). Average BMI was 25.8 (range: 14-49), and 30% were overweight or obese. Breast was the first cancer diagnosed in 36 patients (70.6%) and 44 (86.3%) had a metachronous CRC diagnosis. Breast cancer was early stage (0-2) in 32 (78.0%) patients whereas CRC was split between early stage (1-2) in 14 (34.1%) and later stage (3-4) in 19 (46.2%). Ten patients (24.3%) had a known germline mutation, although 23 (56.1%) had a family history of cancer in a first-degree relative. CONCLUSION: Younger patients with both breast and CRC are a unique cohort, often without known risk factors. Alcohol consumption and sedentary jobs were the most common risk factors, and about one-quarter had a known genetic predisposition. Comanagement of both cancers requires individualized, multidisciplinary care.

In many animal species, the oocyte meiotic spindle, which is required for chromosome segregation, forms without centrosomes. In some systems, Ran-GEF on chromatin initiates spindle assembly. We found that in Caenorhabditis elegans oocytes, endogenously-tagged Ran-GEF dissociates from chromatin during spindle assembly but re-associates during meiotic anaphase. Meiotic spindle assembly occurred after auxin-induced degradation of Ran-GEF, but anaphase I was faster than controls and extrusion of the first polar body frequently failed. In search of a possible alternative pathway for spindle assembly, we found that soluble tubulin concentrates in the nuclear volume during germinal vesicle breakdown. We found that the concentration of soluble tubulin in the metaphase spindle region is enclosed by ER sheets which exclude cytoplasmic organelles including mitochondria and yolk granules. Measurement of the volume occupied by yolk granules and mitochondria indicated that volume exclusion would be sufficient to explain the concentration of tubulin in the spindle volume. We suggest that this concentration of soluble tubulin may be a redundant mechanism promoting spindle assembly near chromosomes.

ImportanceBefore surgery, the best strategy for managing patients who are taking renin-angiotensin system inhibitors (RASIs) (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) is unknown. The lack of evidence leads to conflicting guidelines.ObjectiveTo evaluate whether a continuation strategy vs a discontinuation strategy of RASIs before major noncardiac surgery results in decreased complications at 28 days after surgery.Design, setting, and participantsRandomized clinical trial that included patients who were being treated with a RASI for at least 3 months and were scheduled to undergo a major noncardiac surgery between January 2018 and April 2023 at 40 hospitals in France.InterventionPatients were randomized to continue use of RASIs (n = 1107) until the day of surgery or to discontinue use of RASIs 48 hours prior to surgery (ie, they would take the last dose 3 days before surgery) (n = 1115).Main outcomes and measuresThe primary outcome was a composite of all-cause mortality and major postoperative complications within 28 days after surgery. The key secondary outcomes were episodes of hypotension during surgery, acute kidney injury, postoperative organ failure, and length of stay in the hospital and intensive care unit during the 28 days after surgery.ResultsOf the 2222 patients (mean age, 67 years [SD, 10 years]; 65% were male), 46% were being treated with angiotensin-converting enzyme inhibitors at baseline and 54% were being treated with angiotensin receptor blockers. The rate of all-cause mortality and major postoperative complications was 22% (245 of 1115 patients) in the RASI discontinuation group and 22% (247 of 1107 patients) in the RASI continuation group (risk ratio, 1.02 [95% CI, 0.87-1.19]; P = .85). Episodes of hypotension during surgery occurred in 41% of the patients in the RASI discontinuation group and in 54% of the patients in the RASI continuation group (risk ratio, 1.31 [95% CI, 1.19-1.44]). There were no other differences in the trial outcomes.Conclusions and relevanceAmong patients who underwent major noncardiac surgery, a continuation strategy of RASIs before surgery was not associated with a higher rate of postoperative complications than a discontinuation strategy.Trial registrationClinicalTrials.gov Identifier: NCT03374449.

The Mississippian-era site of Cahokia was the largest Native American city north of Mexico. Archaeologists have long speculated about possible astronomic alignments and spatial relationships in the layout of its 100+ earthen mounds. In this paper LiDAR imagery, historic documents, ethnohistoric and archaeologic data are used to assess the site relative to astronomic and landscape alignments. New findings show how Monks, Rattlesnake, Powell and other mounds are aligned to the Sun, Moon, and Milky Way. Additionally, these alignments intersect prominent bluffs to the east and southeast that appear to have been used as horizon markers.

The Cahokia Mound Group in Illinois, USA, is acknowledged as the largest Native American city north of Mexico. It flourished during the Mississippian Period. Cahokia, however, was only one of three complexes in the immediate area. Located across the Mississippi River from Cahokia, the St. Louis Mound Group was part of the larger complex.The St. Louis Mound Group featured at least 25 earthen mounds including the so-called Big Mound that contained dozens of human burials.In the 1800s the St. Louis Mound Group was leveled to allow for urban expansion. Few records are in existence documenting the location or other details concerning the group. As a result, an important part of prehistory seems lost.  In this paper the likely location for the St. Louis Mound Group is identified using survey plats from the 1850s, early lithographs and other data. Findings are assessed for astronomical alignments and landscape relationships, with possible cosmological implications noted.

BACKGROUND AND AIMS: Home treatment is considered safe in acute pulmonary embolism (PE) patients selected by a validated triage tool (e.g. simplified PE severity index score or Hestia rule), but there is uncertainty regarding the applicability in underrepresented subgroups. The aim was to evaluate the safety of home treatment by performing an individual patient-level data meta-analysis. METHODS: Ten prospective cohort studies or randomized controlled trials were identified in a systematic search, totalling 2694 PE patients treated at home (discharged within 24 h) and identified by a predefined triage tool. The 14- and 30-day incidences of all-cause mortality and adverse events (combined endpoint of recurrent venous thromboembolism, major bleeding, and/or all-cause mortality) were evaluated. The relative risk (RR) for 14- and 30-day mortalities and adverse events is calculated in subgroups using a random effects model. RESULTS: The 14- and 30-day mortalities were 0.11% [95% confidence interval (CI) 0.0-0.24, I2 = 0) and 0.30% (95% CI 0.09-0.51, I2 = 0). The 14- and 30-day incidences of adverse events were 0.56% (95% CI 0.28-0.84, I2 = 0) and 1.2% (95% CI 0.79-1.6, I2 = 0). Cancer was associated with increased 30-day mortality [RR 4.9; 95% prediction interval (PI) 2.7-9.1; I2 = 0]. Pre-existing cardiopulmonary disease, abnormal troponin, and abnormal (N-terminal pro-)B-type natriuretic peptide [(NT-pro)BNP] at presentation were associated with an increased incidence of 14-day adverse events [RR 3.5 (95% PI 1.5-7.9, I2 = 0), 2.5 (95% PI 1.3-4.9, I2 = 0), and 3.9 (95% PI 1.6-9.8, I2 = 0), respectively], but not mortality. At 30 days, cancer, abnormal troponin, and abnormal (NT-pro)BNP were associated with an increased incidence of adverse events [RR 2.7 (95% PI 1.4-5.2, I2 = 0), 2.9 (95% PI 1.5-5.7, I2 = 0), and 3.3 (95% PI 1.6-7.1, I2 = 0), respectively]. CONCLUSIONS: The incidence of adverse events in home-treated PE patients, selected by a validated triage tool, was very low. Patients with cancer had a three- to five-fold higher incidence of adverse events and death. Patients with increased troponin or (NT-pro)BNP had a three-fold higher risk of adverse events, driven by recurrent venous thromboembolism and bleeding.

BackgroundBrain-computer interfaces can enable communication for people with paralysis by transforming cortical activity associated with attempted speech into text on a computer screen. Communication with brain-computer interfaces has been restricted by extensive training requirements and limited accuracy.MethodsA 45-year-old man with amyotrophic lateral sclerosis (ALS) with tetraparesis and severe dysarthria underwent surgical implantation of four microelectrode arrays into his left ventral precentral gyrus 5 years after the onset of the illness; these arrays recorded neural activity from 256 intracortical electrodes. We report the results of decoding his cortical neural activity as he attempted to speak in both prompted and unstructured conversational contexts. Decoded words were displayed on a screen and then vocalized with the use of text-to-speech software designed to sound like his pre-ALS voice.ResultsOn the first day of use (25 days after surgery), the neuroprosthesis achieved 99.6% accuracy with a 50-word vocabulary. Calibration of the neuroprosthesis required 30 minutes of cortical recordings while the participant attempted to speak, followed by subsequent processing. On the second day, after 1.4 additional hours of system training, the neuroprosthesis achieved 90.2% accuracy using a 125,000-word vocabulary. With further training data, the neuroprosthesis sustained 97.5% accuracy over a period of 8.4 months after surgical implantation, and the participant used it to communicate in self-paced conversations at a rate of approximately 32 words per minute for more than 248 cumulative hours.ConclusionsIn a person with ALS and severe dysarthria, an intracortical speech neuroprosthesis reached a level of performance suitable to restore conversational communication after brief training. (Funded by the Office of the Assistant Secretary of Defense for Health Affairs and others; BrainGate2 ClinicalTrials.gov number, NCT00912041.).

Repeated exposure to Subject Island violations can lead to increased acceptability ratings and faster reading times (Chaves & Dery, 2014, 2019; Clausen, 2011; Francom, 2009; Hiramatsu, 2000; Lu et al. 2021; Lu et al., 2022). However, it remains unclear what the nature of this effect and the driving mechanism is. The present paper describes a longitudinal investigation to test whether the effect of repeated exposure to Subject Island constructions is short-lived or whether it can spread over three weeks’ time, as measured by offline measures (Likert acceptability ratings) and online measures (self-paced reading). Using more observations and more sensitive methodologies, our work builds and improves on the only previous longitudinal study on such islands, Snyder (2022). We uncover evidence suggestive of gradual and strategic (by-construction and by-region) adaptation to Subject Island violations, indicated by faster response times, as well as higher acceptability ratings following repeated exposure, most consistent with a syntactic adaptation effect over and above task adaptation.

Abstract: —J. Blunden and T. Boyer In 2023, La Niña conditions that generally prevailed in the eastern Pacific Ocean from mid-2020 into early 2023 gave way to a strong El Niño by October. Atmospheric concentrations of Earth’s major greenhouse gases—carbon dioxide, methane, and nitrous oxide—all increased to record-high levels. The annual global average carbon dioxide concentration in the atmosphere rose to 419.3±0.1 ppm, which is 50% greater than the pre-industrial level. The growth from 2022 to 2023 was 2.8 ppm, the fourth highest in the record since the 1960s. The combined short-term effects of El Niño and the long-term effects of increasing levels of heat-trapping gases in the atmosphere contributed to new records for many essential climate variables reported here. The annual global temperature across land and oceans was the highest in records dating as far back as 1850, with the last seven months (June–December) having each been record warm. Over land, the globally averaged temperature was also record high. Dozens of countries reported record or near-record warmth for the year, including China and continental Europe as a whole (warmest on record), India and Russia (second warmest), and Canada (third warmest). Intense and widespread heatwaves were reported around the world. In Vietnam, an all-time national maximum temperature record of 44.2°C was observed at Tuong Duong on 7 May, surpassing the previous record of 43.4°C at Huong Khe on 20 April 2019. In Brazil, the air temperature reached 44.8°C in Araçuaí in Minas Gerais on 20 November, potentially a new national record and 12.8°C above normal. The effect of rising temperatures was apparent in the cryosphere, where snow cover extent by June 2023 was the smallest in the 56-year record for North America and seventh smallest for the Northern Hemisphere overall. Heatwaves contributed to the greatest average mass balance loss for Alpine glaciers around the world since the start of the record in 1970. Due to rapid volume loss beginning in 2021, St. Anna Glacier in Switzerland and Ice Worm Glacier in the United States disappeared completely. In August, as a direct result of glacial thinning over the past 20 years, a glacial lake on a tributary of the Mendenhall Glacier in Alaska burst through its ice dam and caused unprecedented flooding on Mendenhall River near Juneau. Across the Arctic, the annual surface air temperature was the fourth highest in the 124-year record, and summer (July–September) was record warm. Smaller-than-normal snow cover extent in May and June contributed to the third-highest average peak tundra greenness in the 24-year record. In September, Arctic minimum sea ice extent was the fifth smallest in the 45-year satellite record. The 17 lowest September extents have all occurred in the last 17 years. In Antarctica, temperatures for much of the year were up to 6°C above average over the Weddell Sea and along coastal Dronning Maud Land. The Antarctic Peninsula also experienced well-above-average temperatures during the 2022/23 melt season, which contributed to its fourth consecutive summer of above-average surface melt. On 21 February, Antarctic sea ice extent and sea ice area both reached all-time lows, surpassing records set just a year earlier. Over the course of the year, new daily record-low sea ice extents were set on 278 days. In some instances, these daily records were set by a large margin, for example, the extent on 6 July was 1.8 million km2 lower than the previous record low for that day. Across the global oceans, the annual sea surface temperature was the highest in the 170-year record, far surpassing the previous record of 2016 by 0.13°C. Daily and monthly records were set from March onward, including an historic-high daily global mean sea surface temperature of 18.99°C recorded on 22 August. Approximately 94% of the ocean surface experienced at least one marine heatwave in 2023, while 27% experienced at least one cold spell. Globally averaged ocean heat content from the surface to 2000-m depth was record high in 2023, increasing at a rate equivalent to ∼0.7 Watts per square meter of energy applied over Earth’s surface. Global mean sea level was also record high for the 12th consecutive year, reaching 101.4 mm above the 1993 average when satellite measurements began, an increase of 8.1±1.5 mm over 2022 and the third highest year-over-year increase in the record. A total of 82 named tropical storms were observed during the Northern and Southern Hemispheres’ storm seasons, below the 1991–2020 average of 87. Hurricane Otis became the strongest landfalling hurricane on record for the west coast of Mexico at 140 kt (72 m s−1), causing at least 52 fatalities and $12–16 billion U.S. dollars in damage. Freddy became the world’s longest-lived tropical cyclones on record, developing into a tropical cyclone on 6 February and finally dissipating on 12 March. Freddy crossed the full width of the Indian Ocean and made one landfall in Madagascar and two in Mozambique. In the Mediterranean Sea—outside of traditional tropical cyclone basins—heavy rains and flooding from Storm Daniel killed more than 4300 people and left more than 8000 missing in Libya. The record-warm temperatures in 2023 created conditions that helped intensify the hydrological cycle. Measurements of total-column water vapor in the atmosphere were the highest on record, while the fraction of cloud area in the sky was the lowest since records began in 1980. The annual global mean precipitation total over land surfaces for 2023 was among the lowest since 1979, but global one-day maximum totals were close to average, indicating an increase in rainfall intensity. In July, record-high areas of land across the globe (7.9%) experienced extreme drought, breaking the previous record of 6.2% in July 2022. Overall, 29.7% of land experienced moderate or worse categories of drought during the year, also a record. Mexico reported its driest (and hottest) year since the start of its record in 1950. In alignment with hot and prolonged dry conditions, Canada experienced its worst national wildfire season on record. Approximately 15 million hectares burned across the country, which was more than double the previous record from 1989. Smoke from the fires were transported far into the United States and even to western European countries. August to October 2023 was the driest three-month period in Australia in the 104-year record. Millions of hectares of bushfires burned for weeks in the Northern Territory. In South America, extreme drought developed in the latter half of the year through the Amazon basin. By the end of October, the Rio Negro at Manaus, a major tributary of the Amazon River, fell to its lowest water level since records began in 1902. The transition from La Niña to El Niño helped bring relief to the prolonged drought conditions in equatorial eastern Africa. However, El Niño along with positive Indian Ocean dipole conditions also contributed to excessive rainfall that resulted in devastating floods over southeastern Ethiopia, Somalia, and Kenya during October to December that displaced around 1.5 million people. On 5 September, the town of Zagora, Greece, broke a national record for highest daily rainfall (754 mm in 21 hours, after which the station ceased reporting) due to Storm Daniel; this one-day accumulation was close to Zagora’s normal annual total.

OBJECTIVE: To determine the feasibility, efficacy, and safety of early cold stored platelet transfusion compared with standard care resuscitation in patients with hemorrhagic shock. BACKGROUND: Data demonstrating the safety and efficacy of early cold stored platelet transfusion are lacking following severe injury. METHODS: A phase 2, multicenter, randomized, open label, clinical trial was performed at 5 US trauma centers. Injured patients at risk of large volume blood transfusion and the need for hemorrhage control procedures were enrolled and randomized. The intervention was the early transfusion of a single apheresis cold stored platelet unit, stored for up to 14 days versus standard care resuscitation. The primary outcome was feasibility and the principal clinical outcome for efficacy and safety was 24-hour mortality. RESULTS: Mortality at 24 hours was 5.9% in patients who were randomized to early cold stored platelet transfusion compared with 10.2% in the standard care arm (difference, -4.3%; 95% CI, -12.8% to 3.5%; P =0.26). No significant differences were found for any of the prespecified ancillary outcomes. Rates of arterial and/or venous thromboembolism and adverse events did not differ across treatment groups. CONCLUSIONS AND RELEVANCE: In severely injured patients, early cold stored platelet transfusion is feasible, safe and did not result in a significant lower rate of 24-hour mortality. Early cold stored platelet transfusion did not result in a higher incidence of arterial and/or venous thrombotic complications or adverse events. The storage age of the cold stored platelet product was not associated with significant outcome differences. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04667468.

As on land, oceans exhibit high temporal and spatial temperature variation. This ocean weather contributes to the physiological and ecological processes that ultimately determine the patterns of species distribution and abundance, yet is often unrecognized, especially in tropical oceans. Here, we tested the paradigm of temperature stability in shallow waters (

Virus-like particles (VLPs) from bacteriophage MS2 provide a platform to study protein self-assembly and create engineered systems for drug delivery. Here, we aim to understand the impact of intersubunit interface mutations on the local and global structure and function of MS2-based VLPs. In previous work, our lab identified locally supercharged double mutants [T71K/G73R] that concentrate positive charge at capsid pores, enhancing uptake into mammalian cells. To study the effects of particle size on cellular internalization, we combined these double mutants with a single point mutation [S37P] that was previously reported to switch particle geometry from T = 3 to T = 1 icosahedral symmetry. These new variants retained their enhanced cellular uptake activity and could deliver small-molecule drugs with efficacy levels similar to our first-generation capsids. Surprisingly, these engineered triple mutants exhibit increased thermostability and unexpected geometry, producing T = 3 particles instead of the anticipated T = 1 assemblies. Transmission electron microscopy revealed various capsid assembly states, including wild-type (T = 3), T = 1, and rod-like particles, that could be accessed using different combinations of these point mutations. Molecular dynamics experiments recapitulated the structural rationale in silico for the single point mutation [S37P] forming a T = 1 virus-like particle and showed that this assembly state was not favored when combined with mutations that favor rod-like architectures. Through this work, we investigated how interdimer interface dynamics influence VLP size and morphology and how these properties affect particle function in applications such as drug delivery.

OBJECTIVE: We report findings from a U.S. mixed-methods pilot study of the Person-Centered Care in Fetal Care Centers (PCC-FCC) Scale. METHODS: Participants, who received care at a U.S. Fetal Care Center (FCC) between 2017 and 2021, completed an online questionnaire providing sociodemographic details, specifics about the care received, qualitative experiences, and scores from the PCC-FCC Scale. RESULTS: Participants (n = 247) PCC-FCC scores and qualitative feedback indicate high perceived person-centered care (PCC), particularly in areas of care coordination, respectful care, and patient education. However, 8% scored below the midpoint, and 38% of comments were negative, especially regarding expectation setting, preparation for post-intervention maternal health, and psychosocial support. Public insurance was associated with higher total PCC-FCC (p = 0.03) and Factor 2 scores (p = 0.02) compared to those with private insurance. The qualitative themes trust, clarity, comprehensive care, compassion, and belonging further elucidate the concept of PCC in FCCs. CONCLUSION: The PCC-FCC Scale pilot study revealed strong overall PCC in FCCs, yet variability in patient experiences suggests areas needing improvement, including expectation setting, preparation for post-intervention maternal health, and psychosocial support. Future research must prioritize diverse samples and continued mixed methodologies to better understand the role of insurance and identify other potential disparities, ensuring comprehensive representation of the FCC patient population.

Van der Waals (vdW) stacking is a powerful technique to achieve desired properties in condensed matter systems through layer-by-layer crystal engineering. A remarkable example is the control over the twist angle between artificially-stacked vdW crystals, enabling the realization of unconventional phenomena in moiré structures ranging from superconductivity to strongly correlated magnetism. Here, we report the appearance of unusual 120° twisted faults in vdW magnet CrI3 crystals. In exfoliated samples, we observe vertical twisted domains with a thickness below 10 nm. The size and distribution of twisted domains strongly depend on the sample preparation methods, with as-synthesized unexfoliated samples showing tenfold thicker domains than exfoliated samples. Cooling induces changes in the relative populations among different twisting domains, rather than the previously assumed structural phase transition to the rhombohedral stacking. The stacking disorder induced by sample fabrication processes may explain the unresolved thickness-dependent magnetic coupling observed in CrI3.

Mycena s.s. is a ubiquitous mushroom genus whose members degrade multiple dead plant substrates and opportunistically invade living plant roots. Having sequenced the nuclear genomes of 24 Mycena species, we find them to defy the expected patterns for fungi based on both their traditionally perceived saprotrophic ecology and substrate specializations. Mycena displayed massive genome expansions overall affecting all gene families, driven by novel gene family emergence, gene duplications, enlarged secretomes encoding polysaccharide degradation enzymes, transposable element (TE) proliferation, and horizontal gene transfers. Mainly due to TE proliferation, Arctic Mycena species display genomes of up to 502 Mbp (2-8× the temperate Mycena), the largest among mushroom-forming Agaricomycetes, indicating a possible evolutionary convergence to genomic expansions sometimes seen in Arctic plants. Overall, Mycena show highly unusual, varied mosaic-like genomic structures adaptable to multiple lifestyles, providing genomic illustration for the growing realization that fungal niche adaptations can be far more fluid than traditionally believed.

BACKGROUND: Serum AFP-L3%, AFP, and DCP are useful biomarkers for HCC detection, but their utility in assessing treatment response remains unknown. We aim to evaluate the accuracy of a biomarker model in the detection of posttreatment viable tumors. METHODS: For model derivation, recipients with HCC undergoing liver transplant from 2018 to 2022 who had biomarkers collected within 3 months before transplant were included. We developed a generalized linear model for detecting posttreatment viable tumors with the 3 biomarkers as covariates, which we termed the LAD Score. An independent cohort of 117 patients with HCC was used for external validation. RESULTS: Among 205 recipients of transplant, 70.2% had evidence of viable tumor on explant. The median LAD score was higher among patients with viable versus nonviable tumors (1.06 vs. 0.465, p < 0.001). The LAD score had a sensitivity of 55.6% and a specificity of 85.1% at the cutoff of 0.927, which was more accurate than imaging for detecting posttreatment viable tumors (AUROC 0.736 vs. 0.643, respectively; p = 0.045). The superior performance of the LAD score over imaging is primarily driven by its greater accuracy in detecting tumors

In an ultrafast nonlinear optical interaction, the electric field of the emitted nonlinear signal provides direct access to the induced nonlinear transient polarization or transient currents and thus carries signatures of ultrafast dynamics in a medium. Measurement of the electric field of such signals offers sensitive observables to track ultrafast electron dynamics in various systems. In this work, we resolve the real-time phase of the electric field of a femtosecond third-order nonlinear optical signal in the molecular frame. The electric field emitted from impulsively pre-aligned gas-phase molecules at room temperature, in a degenerate four-wave mixing scheme, is measured using a spectral interferometry technique. The nonlinear signal is measured around a rotational revival to extract its molecular-frame angle dependence from pump-probe time-delay scans. By comparing these measurements for two linear molecules, carbon dioxide and nitrogen, we show that the measured second-order phase parameter (temporal chirp) of the signal is sensitive to the valence electronic symmetry of the molecules, whereas the amplitude of the signal does not show such sensitivity. We compare measurements to theoretical calculations of the chirp observable in the molecular frame. This work is an important step towards using electric field measurements in nonlinear optical spectroscopy to study ultrafast dynamics of electronically excited molecules in the molecular frame.

Introduction: Patients experiencing an out-of-hospital cardiac arrest (OHCA) frequently do not receive bystander cardiopulmonary resuscitation (CPR), especially in low- and middle-income countries (LMIC). In this study we sought to determine the prevalence of OHCA patients in Vietnam who received bystander CPR and its effects on survival outcomes.Methods: We performed a multicenter, retrospective observational study of patients (≥18 years) presenting with OHCA at three major hospitals in an LMIC from February 2014–December 2018. We collected data on the hospital and patient characteristics, the cardiac arrest events, the emergency medical services (EMS) system, the therapy methods, and the outcomes and compared these data, before and after pairwise 1:1 propensity score matching, between patients who received bystander CPR and those who did not. Upon admission, we assessed factors associated with good neurological survival at hospital discharge in univariable and multivariable logistic models.Results: Of 521 patients, 388 (74.5%) were men, and the mean age was 56.7 years (SD 17.3). Although most cardiac arrests (68.7%, 358/521) occurred at home and 78.8% (410/520) were witnessed, a low proportion (22.1%, 115/521) of these patients received bystander CPR. Only half of the patients were brought by EMS (8.1%, 42/521) or private ambulance (42.8%, 223/521), 50.8% (133/262) of whom had resuscitation attempts. Before matching, there was a significant difference in good neurological survival between patients who received bystander CPR (12.2%, 14/115) and patients who did not (4.7%, 19/406; P < .001). After matching, good neurological survival was absent in all OHCA patients who did not receive CPR from a bystander. The multivariable analysis showed that bystander CPR (adjusted odds ratio: 3.624; 95% confidence interval 1.629–8.063) was an independent predictor of good neurological survival.Conclusion: In our study, only 22.1% of total OHCA patients received bystander CPR, which contributed significantly to a low rate of good neurological survival in Vietnam. To improve the chances of survival with good neurological functions of OHCA patients, more people should be trained to perform bystander CPR and teach others as well. A standard program for emergency first-aid training is necessary for this purpose.

OBJECTIVE: Realignment osteotomy performed concomitantly with cartilage restoration typically requires early restricted weightbearing and can add significant morbidity, potentially leading to an increased risk of early perioperative complications. The purpose of this study was to compare the 30-day complication rates after isolated cartilage restoration (ICR) versus concomitant cartilage restoration and osteotomy (CRO) using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. DESIGN: NSQIP registries between 2006 and 2019 were queried using Current Procedural Terminology codes to identify patients undergoing ICR (autologous chondrocyte implantation, osteochondral autograft transfer, or osteochondral allograft transplantation) and CRO (with concomitant high tibial osteotomy, distal femoral osteotomy, and/or tibial tubercle osteotomy). Complications rates between treatment groups were compared using multivariate logistic regression analyses adjusted for sex, age, steroid use, and respiratory status. RESULTS: A total of 773 ICR and 97 CRO surgical procedures were identified. Mean patient ages were 35.9 years for the ICR group and 31.2 years for the CRO group. Operative time was significantly longer in the CRO group (170.8 min) compared with the ICR group (97.8 min). Multivariate analysis demonstrated no significant differences in rates of PE, VTE, and all-cause readmission between the ICR and CRO groups. No events of wound disruption, SSI and reoperation were found in the CRO group, while the ICR group was characterized by low rates of wound disruption, reoperation, and SSI (

PurposeTo develop a patient-reported outcome measure to assess the impact of glaucoma and treatment, including minimally invasive glaucoma surgery (MIGS).DesignObservational study before and after concomitant cataract and Food and Drug Administration-approved implantable MIGS device surgery.SettingSurvey administration was on a computer, iPad, or similar device.Patient population184 adults completed the baseline survey, 124 a survey 3 months after surgery, and 106 the 1-month test-retest reliability survey. The age range was 37 to 89 (average age = 72). Most were female (57%), non-Hispanic White (81%), and had a college degree (56%).Main outcome measuresThe Glaucoma Outcomes Survey (GOS) assesses functional limitations (27 items), vision-related symptoms (7 items), psychosocial issues (7 items), and satisfaction with microinvasive glaucoma surgery (1 item). These multiple-item scales were scored on a 0 to 100 range, with a higher score indicating worse health.ResultsInternal consistency reliability estimates ranged from 0.75 to 0.93, and 1-month test-retest intraclass correlations ranged from 0.83 to 0.92 for the GOS scales. Product-moment correlations among the scales ranged from 0.56 to 0.60. Improvement in visual acuity in the study eye from baseline to the 3-month follow-up was significantly related to improvements in GOS functional limitations (r = 0.18, P = .0485), vision-related symptoms (r = 0.19, P = .0386), and psychosocial concerns (r = 0.18, P = .0503). Responders to treatment ranged from 17% for vision-related symptoms to 48% for functional limitations.ConclusionsThis study supports using the GOS for ophthalmic procedures such as MIGS. Further evaluation of the GOS in different patient subgroups and clinical settings is needed.

Standard diagnostics used in longitudinal antimalarial studies are unable to characterize the complexity of submicroscopic parasite dynamics, particularly in high transmission settings. We use molecular markers and amplicon sequencing to characterize post-treatment stage-specific malaria parasite dynamics during a 42 day randomized trial of 3- versus 5 day artemether-lumefantrine in 303 children with and without HIV (ClinicalTrials.gov number NCT03453840). The prevalence of parasite-derived 18S rRNA is >70% in children throughout follow-up, and the ring-stage marker SBP1 is detectable in over 15% of children on day 14 despite effective treatment. We find that the extended regimen significantly lowers the risk of recurrent ring-stage parasitemia compared to the standard 3 day regimen, and that higher day 7 lumefantrine concentrations decrease the probability of ring-stage parasites in the early post-treatment period. Longitudinal amplicon sequencing reveals remarkably dynamic patterns of multiclonal infections that include new and persistent clones in both the early post-treatment and later time periods. Our data indicate that post-treatment parasite dynamics are highly complex despite efficacious therapy, findings that will inform strategies to optimize regimens in the face of emerging partial artemisinin resistance in Africa.

Vitamin A deficiency remains prevalent on a global scale, including in regions where maize constitutes a high percentage of human diets. One solution for alleviating this deficiency has been to increase grain concentrations of provitamin A carotenoids in maize (Zea mays ssp. mays L.)-an example of biofortification. The International Maize and Wheat Improvement Center (CIMMYT) developed a Carotenoid Association Mapping panel of 380 inbred lines adapted to tropical and subtropical environments that have varying grain concentrations of provitamin A and other health-beneficial carotenoids. Several major genes have been identified for these traits, 2 of which have particularly been leveraged in marker-assisted selection. This project assesses the predictive ability of several genomic prediction strategies for maize grain carotenoid traits within and between 4 environments in Mexico. Ridge Regression-Best Linear Unbiased Prediction, Elastic Net, and Reproducing Kernel Hilbert Spaces had high predictive abilities for all tested traits (β-carotene, β-cryptoxanthin, provitamin A, lutein, and zeaxanthin) and outperformed Least Absolute Shrinkage and Selection Operator. Furthermore, predictive abilities were higher when using genome-wide markers rather than only the markers proximal to 2 or 13 genes. These findings suggest that genomic prediction models using genome-wide markers (and assuming equal variance of marker effects) are worthwhile for these traits even though key genes have already been identified, especially if breeding for additional grain carotenoid traits alongside β-carotene. Predictive ability was maintained for all traits except lutein in between-environment prediction. The TASSEL (Trait Analysis by aSSociation, Evolution, and Linkage) Genomic Selection plugin performed as well as other more computationally intensive methods for within-environment prediction. The findings observed herein indicate the utility of genomic prediction methods for these traits and could inform their resource-efficient implementation in biofortification breeding programs.

The beamline optics and endstations at branch B of the Versatile Soft X-ray (VerSoX) beamline B07 at Diamond Light Source are described. B07-B provides medium-flux X-rays in the range 45-2200 eV from a bending magnet source, giving access to local electronic structure for atoms of all elements from Li to Y. It has an endstation for high-throughput X-ray photoelectron spectroscopy (XPS) and near-edge X-ray absorption fine-structure (NEXAFS) measurements under ultrahigh-vacuum (UHV) conditions. B07-B has a second endstation dedicated to NEXAFS at pressures from UHV to ambient pressure (1 atm). The combination of these endstations permits studies of a wide range of interfaces and materials. The beamline and endstation designs are discussed in detail, as well as their performance and the commissioning process.

RATIONALE: The causal relationship between undernutrition and response to anti-tuberculosis (TB) treatment and TB treatment outcomes among people with retreatment TB is understudied. OBJECTIVE: To evaluate the effect of undernutrition on treatment success and sputum smear conversion among people with retreatment drug-susceptible TB in Kampala, Uganda. METHODS: We conducted a quasi-experimental study utilizing propensity score weighting among people with retreatment drug-susceptible TB aged ≥ 15 years treated between 2012 and 2022 in Kampala. The primary exposure was undernutrition assessed using the mid-upper arm circumference at the time of TB diagnosis. The primary outcome was treatment success defined as cure or treatment completion at month 6. Sputum smear conversion was the secondary outcome and was measured as a change in sputum smear status from positive to negative at months 2, 5, and 6. We estimated the causal effect of undernutrition on the outcomes using a propensity-score weighted modified Poisson regression model with robust error variance. MEASUREMENTS AND MAIN RESULTS: Of the 605 participants, 432 (71.4 %) were male, 215 (35.5 %) were aged 25-34 years, 427 (70.6 %) had bacteriologically confirmed pulmonary TB, 133 (22.0 %) were undernourished and 398 (65.8 %) achieved treatment success. Of participants with bacteriologically confirmed pulmonary TB, 232 (59.0 %), 327 (59.3 %), and 360 (97.6 %) achieved sputum smear conversion at months 2, 5, and 6, respectively. Undernutrition reduced treatment success (RR 0.42, 95 % CI 0.32-0.55) as well as sputum smear conversion at months 2 (RR 0.45, 95 % CI 0.42-0.49) and 5 (RR 0.46, 95 % CI 0.43-0.51) but not month 6 (RR 0.99, 95 % CI 0.97-1.02). CONCLUSION: Undernutrition negatively impacts treatment outcomes. Therefore, nutritional assessment should be an integral component of TB care, with nutritional counseling and support offered to those undernourished to optimize their TB treatment response and outcomes.

Soil fungi belonging to different functional guilds, such as saprotrophs, pathogens, and mycorrhizal symbionts, play key roles in forest ecosystems. To date, no study has compared the actual gene expression of these guilds in different forest soils. We used metatranscriptomics to study the competition for organic resources by these fungal groups in boreal, temperate, and Mediterranean forest soils. Using a dedicated mRNA annotation pipeline combined with the JGI MycoCosm database, we compared the transcripts of these three fungal guilds, targeting enzymes involved in C- and N mobilization from plant and microbial cell walls. Genes encoding enzymes involved in the degradation of plant cell walls were expressed at a higher level in saprotrophic fungi than in ectomycorrhizal and pathogenic fungi. However, ectomycorrhizal and saprotrophic fungi showed similarly high expression levels of genes encoding enzymes involved in fungal cell wall degradation. Transcripts for N-related transporters were more highly expressed in ectomycorrhizal fungi than in other groups. We showed that ectomycorrhizal and saprotrophic fungi compete for N in soil organic matter, suggesting that their interactions could decelerate C cycling. Metatranscriptomics provides a unique tool to test controversial ecological hypotheses and to better understand the underlying ecological processes involved in soil functioning and carbon stabilization.

BACKGROUND: Injectable cabotegravir (CAB)/rilpivirine (RPV) is the only combination long-acting (LA) antiretroviral regimen approved for HIV. RPV may not be effective among individuals with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, which has >10% prevalence in many countries. Lenacapavir (LEN) is an LA capsid inhibitor given every 6 months, but has not been studied in combination with other LA agents. METHODS: We assembled a case series from 4 US academic medical centers where patients with adherence challenges were prescribed LEN subcutaneously every 26 weeks/CAB (+/- RPV) intramuscularly every 4 or 8 weeks. Descriptive statistics, including viral load (VL) outcomes, were summarized. RESULTS: All patients (n = 34: 76% male; 24% cis/trans female; 41% Black; 38% Latino/a; median age [range], 47 [28-75] years; 29% and 71% on CAB every 4 or 8 weeks) reported challenges adhering to oral ART. The reasons for using LEN/CAB with or without RPV were documented or suspected NNRTI mutations (n = 21, 59%), integrase mutations (n = 5, 15%), high VL (n = 6, 18%), or continued viremia on CAB/RPV alone (n = 4, 12%). Injection site reactions on LA LEN were reported in 44% (32% grade I, 12% grade 2). All patients but 2 (32/34; 94%) were suppressed (VL

Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine as interpreted by individual family physicians and medical educators in the USA and elsewhere around the world. In 'X: standing up for diversity, equity and inclusion', authors address the following themes: 'The power of diversity-why inclusivity is essential to equity in healthcare', 'Medical education for whom?', 'Growing a diverse and inclusive workforce', 'Therapeutic judo-an inclusive approach to patient care', 'Global family medicine-seeing the world "upside down"', 'The inverse care law', 'Social determinants of health as a lens for care', 'Why family physicians should care about human rights' and 'Toward health equity-the opportunome'. May the essays that follow inspire readers to promote change.

Tobacco use remains a leading preventable cause of morbidity and mortality, with pharmacotherapy and counseling recognized as effective cessation aids. Yet, the potential role of pharmacists and pharmacy technicians in tobacco cessation services is underutilized. This study explores the integration of such services in community pharmacies, identifying facilitators and barriers to their implementation. A qualitative study was conducted across seven community pharmacies in California that were affiliated with the Community Pharmacy Enhanced Services Network. Participants included 22 pharmacists and 26 pharmacy technicians/clerks who completed tobacco cessation training. Data were collected through semi-structured interviews, focusing on experiences with implementing cessation services. The analysis was guided by Rogers’ Diffusion of Innovations Theory. MAXQDA software was used for data management and thematic analysis. Sixteen pharmacy personnel participated in the study, highlighting key themes around the integration of cessation services. Compatibility with existing workflows, the importance of staff buy-in, and the crucial role of pharmacy technicians emerged as significant facilitators. Challenges included the complexity of billing for services, software limitations for documenting tobacco use and cessation interventions, and gaps in training for handling complex patient cases. Despite these barriers, pharmacies successfully initiated cessation services, with variations in service delivery and follow-up practices. Community pharmacies represent viable settings for delivering tobacco cessation services, with pharmacists and technicians playing pivotal roles. However, systemic changes are needed to address challenges related to billing, documentation, and training. Enhancing the integration of cessation services in community pharmacies could significantly impact public health by increasing access to effective cessation support.

Methods to access chiral sulfur(VI) pharmacophores are of interest in medicinal and synthetic chemistry. We report the desymmetrization of unprotected sulfonimidamides via asymmetric acylation with a cinchona-phosphinate catalyst. The desired products are formed in excellent yield and enantioselectivity with no observed bis-acylation. A data-science-driven approach to substrate scope evaluation was coupled to high throughput experimentation (HTE) to facilitate statistical modeling in order to inform mechanistic studies. Reaction kinetics, catalyst structural studies, and density functional theory (DFT) transition state analysis elucidated the turnover-limiting step to be the collapse of the tetrahedral intermediate and provided key insights into the catalyst-substrate structure-activity relationships responsible for the origin of the enantioselectivity. This study offers a reliable method for accessing enantioenriched sulfonimidamides to propel their application as pharmacophores and serves as an example of the mechanistic insight that can be gleaned from integrating data science and traditional physical organic techniques.

Development of high yielding cowpea varieties coupled with good taste and rich in essential minerals can promote consumption and thus nutrition and profitability. The sweet taste of cowpea grain is determined by its sugar content, which comprises mainly sucrose and galacto-oligosaccharides (GOS) including raffinose and stachyose. However, GOS are indigestible and their fermentation in the colon can produce excess intestinal gas, causing undesirable bloating and flatulence. In this study, we aimed to examine variation in grain sugar and mineral concentrations, then map quantitative trait loci (QTLs) and estimate genomic-prediction (GP) accuracies for possible application in breeding. Grain samples were collected from a multi-parent advanced generation intercross (MAGIC) population grown in California during 2016-2017. Grain sugars were assayed using high-performance liquid chromatography. Grain minerals were determined by inductively coupled plasma-optical emission spectrometry and combustion. Considerable variation was observed for sucrose (0.6-6.9%) and stachyose (2.3-8.4%). Major QTLs for sucrose (QSuc.vu-1.1), stachyose (QSta.vu-7.1), copper (QCu.vu-1.1) and manganese (QMn.vu-5.1) were identified. Allelic effects of major sugar QTLs were validated using the MAGIC grain samples grown in West Africa in 2017. GP accuracies for minerals were moderate (0.4-0.58). These findings help guide future breeding efforts to develop mineral-rich cowpea varieties with desirable sugar content.

This review explores the application of the conservative management model for pain to sports-related concussions (SRCs), framing concussions as a distinct form of pain syndrome with a pathophysiological foundation in central sensitization. Drawing parallels with proven pain management models, we underscore the significance of a proactive approach to concussion management. Recognizing concussions as a pain syndrome allows for the tailoring of interventions in alignment with conservative principles. This review first covers the epidemiology and controversies surrounding prolonged concussion recovery and persistent post-concussion symptoms (PPCS). Next, the pathophysiology of concussions is presented within the central sensitization framework, emphasizing the need for early intervention to mitigate the neuroplastic changes that lead to heightened pain sensitivity. Five components of the central sensitization process specific to concussion injuries are highlighted as targets for conservative interventions in the acute period: peripheral sensitization, cerebral metabolic dysfunction, neuroinflammation, glymphatic system dysfunction, and pain catastrophizing. These proactive interventions are emphasized as pivotal in accelerating concussion recovery and reducing the risk of prolonged symptoms and PPCS, in line with the philosophy of conservative management.

Circulating cell-free mitochondrial DNA (ccf-mtDNA) is a biomarker of cellular injury or cellular stress and is a potential novel biomarker of psychological stress and of various brain, somatic, and psychiatric disorders. No studies have yet analyzed ccf-mtDNA levels in post-traumatic stress disorder (PTSD), despite evidence of mitochondrial dysfunction in this condition. In the current study, we compared plasma ccf-mtDNA levels in combat trauma-exposed male veterans with PTSD (n = 111) with those who did not develop PTSD (n = 121) and also investigated the relationship between ccf mt-DNA levels and glucocorticoid sensitivity. In unadjusted analyses, ccf-mtDNA levels did not differ significantly between the PTSD and non-PTSD groups (t = 1.312, p = 0.191, Cohens d = 0.172). In a sensitivity analysis excluding participants with diabetes and those using antidepressant medication and controlling for age, the PTSD group had lower ccf-mtDNA levels than did the non-PTSD group (F(1, 179) = 5.971, p = 0.016, partial η2 = 0.033). Across the entire sample, ccf-mtDNA levels were negatively correlated with post-dexamethasone adrenocorticotropic hormone (ACTH) decline (r = -0.171, p = 0.020) and cortisol decline (r = -0.149, p = 0.034) (viz., greater ACTH and cortisol suppression was associated with lower ccf-mtDNA levels) both with and without controlling for age, antidepressant status and diabetes status. Ccf-mtDNA levels were also significantly positively associated with IC50-DEX (the concentration of dexamethasone at which 50% of lysozyme activity is inhibited), a measure of lymphocyte glucocorticoid sensitivity, after controlling for age, antidepressant status, and diabetes status (β = 0.142, p = 0.038), suggesting that increased lymphocyte glucocorticoid sensitivity is associated with lower ccf-mtDNA levels. Although no overall group differences were found in unadjusted analyses, excluding subjects with diabetes and those taking antidepressants, which may affect ccf-mtDNA levels, as well as controlling for age, revealed decreased ccf-mtDNA levels in PTSD. In both adjusted and unadjusted analyses, low ccf-mtDNA levels were associated with relatively increased glucocorticoid sensitivity, often reported in PTSD, suggesting a link between mitochondrial and glucocorticoid-related abnormalities in PTSD.

Human humoral immune responses to SARS-CoV-2 vaccines exhibit substantial inter-individual variability and have been linked to vaccine efficacy. To elucidate the underlying mechanism behind this variability, we conducted a genome-wide association study (GWAS) on the anti-spike IgG serostatus of UK Biobank participants who were previously uninfected by SARS-CoV-2 and had received either the first dose (n = 54,066) or the second dose (n = 46,232) of COVID-19 vaccines. Our analysis revealed significant genome-wide associations between the IgG antibody serostatus following the initial vaccine and human leukocyte antigen (HLA) class II alleles. Specifically, the HLA-DRB1∗13:02 allele (MAF = 4.0%, OR = 0.75, p = 2.34e-16) demonstrated the most statistically significant protective effect against IgG seronegativity. This protective effect was driven by an alteration from arginine (Arg) to glutamic acid (Glu) at position 71 on HLA-DRβ1 (p = 1.88e-25), leading to a change in the electrostatic potential of pocket 4 of the peptide binding groove. Notably, the impact of HLA alleles on IgG responses was cell type specific, and we observed a shared genetic predisposition between IgG status and susceptibility/severity of COVID-19. These results were replicated within independent cohorts where IgG serostatus was assayed by two different antibody serology tests. Our findings provide insights into the biological mechanism underlying individual variation in responses to COVID-19 vaccines and highlight the need to consider the influence of constitutive genetics when designing vaccination strategies for optimizing protection and control of infectious disease across diverse populations.

BackgroundVariations in survival among patients with oligodendroglioma are unexplained by known prognostic factors. To assess the impact of peripheral immune profiles on prognosis, we applied immunomethylomics analyses-DNA methylation of archived whole blood samples, to characterize immune cells.MethodsWe compared the proportions of immune cells from patients with oligodendroglioma to other glioma subtypes and controls. We used recursive partitioning analysis (RPA) within the oligodendrogliomas to correlate with survival.ResultsPatients with oligodendrogliomas (141) were median age at diagnosis of 44 years; 57% male; 75% White; 60% prior chemotherapy; and 25% on dexamethasone at sample collection. Patients with oligodendrogliomas had immune profiles more similar to controls than other glioma subtypes, though with notably lower B-cells. RPA of patients with oligodendrogliomas delineated 2 survival groups based on an interaction between age and B-naïve cells. Patients with longer survival (median 24.2 years) were ≤42 years of age with higher B-naïve cells versus worse survival (median 16.9 years) who were ≤42 years of age with lower B-naïve cells or >42 years of age (P = .00032). Patients with worse survival also had lower CD4- and CD8-naïve T-cells. Similar immune profiles were observed in an independent cohort of oligodendroglioma patients prior to surgery.ConclusionsPeripheral blood immune profiles in oligodendroglioma suggested that younger patients with lower B-naïve cells experienced shorter survival. Though our findings lack of validation cohort and use a heterogenous patient population, they suggest peripheral blood immune profiles may be prognostic for patients with glioma and warrant further investigation.

Here we present the current state of knowledge on the long-term evolution of Saturns moon system due to tides within Saturn. First we provide some background on tidal evolution, orbital resonances and satellite tides. Then we address in detail some of the present and past orbital resonances between Saturns moons (including the Enceladus-Dione and Titan-Hyperion resonances) and what they can tell us about the evolution of the system. We also present the current state of knowledge on the spin-axis dynamics of Saturn: we discuss arguments for a (past or current) secular resonance of Saturns spin precession with planetary orbits, and explain the links of this resonance to the tidal evolution of Titan and a possible recent cataclysm in the Saturnian system. We also address how the moons orbital evolution, including resonances, affects the evolution of their interiors. Finally, we summarize the state of knowledge about the Saturnian systems long-term evolution and discuss prospects for future progress.

A putative male advantage in wayfinding ability is the most widely documented sex difference in human cognition and has also been observed in other animals. The common interpretation, the sex-specific adaptation hypothesis, posits that this male advantage evolved as an adaptive response to sex differences in home range size. A previous study a decade ago tested this hypothesis by comparing sex differences in home range size and spatial ability among 11 species and found no relationship. However, the study was limited by the small sample size, the lack of species with a larger female home range and the lack of non-Western human data. The present study represents an update that addresses all of these limitations, including data from 10 more species and from human subsistence cultures. Consistent with the previous result, we found little evidence that sex differences in spatial navigation and home range size are related. We conclude that sex differences in spatial ability are more likely due to experiential factors and/or unselected biological side effects, rather than functional outcomes of natural selection.

Plants sense abscisic acid (ABA) using chemical-induced dimerization (CID) modules, including the receptor PYR1 and HAB1, a phosphatase inhibited by ligand-activated PYR1. This system is unique because of the relative ease with which ligand recognition can be reprogrammed. To expand the PYR1 system, we designed an orthogonal * module, which harbors a dimer interface salt bridge; X-ray crystallographic, biochemical and in vivo analyses confirm its orthogonality. We used this module to create PYR1*MANDI/HAB1* and PYR1*AZIN/HAB1*, which possess nanomolar sensitivities to their activating ligands mandipropamid and azinphos-ethyl. Experiments in Arabidopsis thaliana and Saccharomyces cerevisiae demonstrate the sensitive detection of banned organophosphate contaminants using living biosensors and the construction of multi-input/output genetic circuits. Our new modules enable ligand-programmable multi-channel CID systems for plant and eukaryotic synthetic biology that can empower new plant-based and microbe-based sensing modalities.

Fertilization occurs before the completion of oocyte meiosis in the majority of animal species and sperm contents move long distances within the zygotes of mouse and C. elegans. If incorporated into the meiotic spindle, paternal chromosomes could be expelled into a polar body resulting in lethal monosomy. Through live imaging of fertilization in C. elegans, we found that the microtubule disassembling enzymes, katanin and kinesin-13 limit long-range movement of sperm contents and that maternal ataxin-2 maintains paternal DNA and paternal mitochondria as a cohesive unit that moves together. Depletion of katanin or double depletion of kinesin-13 and ataxin-2 resulted in the capture of the sperm contents by the meiotic spindle. Thus limiting movement of sperm contents and maintaining cohesion of sperm contents within the zygote both contribute to preventing premature interaction between maternal and paternal genomes.

This case report highlights an uncommon sequelae of chest wall trauma that should be evaluated for patients presenting with similar history and symptoms. A 60-year-old man presented to the emergency department (ED) with swelling, fever, and chest wall pain two days after an assault with blunt chest wall trauma. On exam, there was a suspected chest wall abscess, verified on computed tomography (CT) with associated displaced midsternal fracture. This patient was admitted for abscess incision and drainage. While uncommon, chest wall abscess formation is an important condition that should be considered as a differential diagnosis in any patient presenting with chest wall pain post blunt trauma. With few reported similar presentations in the literature, this case is an important addition in a likely underreported phenomenon that requires prompt evaluation and treatment.

As part of a recent undergraduate seminar on infrastructure, students completed weekly exercises dubbed “infrastructure fieldnotes.” Going beyond conventional discussion board posts or reading responses, exercise prompts incorporated reading analysis, methods practice, writing prompts, and experiments in multimodal representation as students engaged with urban planning and quotidian experiences of infrastructure and made sense of the infrastructures that enable and structure city life. In this research article, the instructor for the course offers a preliminary presentation of the assignment’s structure and pedagogical objectives, followed by an analysis of how some prompts influenced classroom discussions by creating common points of reference and revealing different experiences of the campus and city. This discussion is followed by five student contributions on different aspects of the assignment. Some take up specific prompts to demonstrate how they created openings for engagement with course material, some reflect on how exercises enabled students to cultivate new kinds of awareness or attention to infrastructure, and others extend the fieldnotes project beyond the class to show what kinds of analysis endured after the course ended. Altogether, these student analyses demonstrate and reflect on the utility of sustained, open-ended prompts for student engagement with course material and concepts in an urban campus.

Favolaschia claudopus, a wood-inhabiting basidiomycete of the Mycenaceae family, is considered an invasive species that has recently spread from Oceania to Europe. The CIRM-BRFM 2984 strain of this fungus was originally isolated from a basidiome collected from the fallen limb of a decayed oak tree in Southwest France. The genome sequence of this strain shared characteristics with other Mycenaceae species, including a large genome size and enriched content of protein-coding genes. The genome sequence provided here will facilitate further investigation on the factors that contribute to the successful global dissemination of F. claudopus.

Nuclear power plays a pivotal role in ensuring a scalable, affordable, and reliable low-carbon electricity supply. Along with other low-carbon energy technologies, nuclear energy is essential for reducing our reliance on fossil fuels, addressing climate change and air pollution, and achieving a sustainable economy. Whilst significant progress has been made in reducing the volume of final radioactive waste, its management remains one of the most important challenges when considering the continued use and expansion of nuclear energy. This recently published collection highlights the latest technological and scientific advances aimed to improve the safe, long-term, and sustainable management of wastes produced from nuclear power generation.

Cognitive processes underlie economic relations. In this paper, we develop a conceptual, mathematical, and computational framework for modeling market exchange as a series of dynamically interacting cognitive processes. Specifically, we show how advertisers can build trust and gain confidence in their pricing power to the point that they erode trust and undermine the efficacy of their advertising. Customers conversely orient towards advertisers seeking information or turn away from them as unreliable communicators. These behaviors and the patterns they generate occur inside a state space of unallocated perceived value. They constitute a small subset of the full range of possible strategic and adaptive responses that define cognitive microeconomics.

Whereas principles of communicative efficiency and legal doctrine dictate that laws be comprehensible to the common world, empirical evidence suggests legal documents are largely incomprehensible to lawyers and laypeople alike. Here, a corpus analysis (n=59million words) first replicated and extended prior work revealing laws to contain strikingly higher rates of complex syntactic structures relative to six baseline genres of English.Next, two pre-registered text generation experiments (n=280) tested two leading hypotheses regarding how these complex structures enter into legal documents in the first place. In line with the \textit{magic spell hypothesis}, we found people tasked with writing official laws wrote in a more convoluted manner than when tasked with writing unofficial legal texts of equivalent conceptual complexity. Contrary to the \textit{copy-and-edit hypothesis}, we did not find evidence that people editing a legal document wrote in a more convoluted manner than when writing the same document from scratch.From a cognitive perspective, these results suggest law to be a rare exception to the general tendency in human language towards communicative efficiency. In particular, these findings indicate law's complexity to be derived from its performativity, whereby low-frequency structures may be inserted to signal law's authoritative, world-state-altering nature, at the cost of increased processing demands on readers. From a law and policy perspective, these results suggest that the tension between the ubiquity and impenetrability of the law is not an inherent one, and that laws can be simplified without a loss or distortion of communicative content.