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Abstract Prostate cancer treatment resistance is a significant challenge facing the field. Genomic and transcriptomic profiling have partially elucidated the mechanisms through which cancer cells escape treatment, but their relation toward the tumor microenvironment (TME) remains elusive. Here we present a comprehensive transcriptomic landscape of the prostate TME at multiple points in the standard treatment timeline employing single-cell RNA-sequencing and spatial transcriptomics data from 120 patients. We identify club-like cells as a key epithelial cell subtype that acts as an interface between the prostate and the immune system. Tissue areas enriched with club-like cells have depleted androgen signaling and upregulated expression of luminal progenitor cell markers. Club-like cells display a senescence-associated secretory phenotype and their presence is linked to increased polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) activity. Our results indicate that club-like cells are associated with myeloid inflammation previously linked to androgen deprivation therapy resistance, providing a rationale for their therapeutic targeting.

Introduction: Spine fractures occur commonly in the geriatric population. Super-elderly individuals (i.e., those 80 years of age and older) represent a growing segment of the population and are especially prone to these fractures. The contemporary epidemiology of spine fractures in the super-elderly population is incompletely described in the literature. MATERIALS AND METHODS: This descriptive epidemiology study used the National Electronic Injury Surveillance System to examine the incidence and recent trends of spine fractures occurring among super-elderly individuals in the United States (US) from 2011 to 2020. Annual, overall, and age-/sex-specific incidence rates (IRs) were analyzed. Average annual percent change (AAPC) estimates were calculated to indicate the magnitude/direction of trends in annual injury rates. Results: An estimated n = 385,375 super-elderly patients sustained spine fractures over the 10-year study period for an overall IR of 31.5 per 10,000 person-years at-risk. Lumbar fractures (IR = 16.3) were the most common, followed by thoracic (IR = 9.4) and cervical (IR = 6.9) fractures. Incidence was significantly higher in super-elderly females (IR = 35.6) than in males (IR = 24.8). Incidence was significantly higher in nonagenarians (IR = 50.7) and centenarians (IR = 42.6) than in octogenarians (IR = 26.8). Accounting for population growth yielded a significantly increasing incidence over the study period from 20.8 in 2011 to 40.3 in 2020 (AAPC = 8, P < 0.0001). Conclusions: This study suggests that the annual incidence of spine fractures in the oldest cohort of patients in the US (80 + years of age) increased significantly during the recent decade from 2011 to 2020. Increased IRs highlight the need for future research aimed at optimizing outcomes and quality of life in this frail and ever-growing segment of the population.

Abstract Microtubules are essential for various cellular processes. The functional diversity of microtubules is attributed to the incorporation of various α- and β-tubulin isotypes encoded by different genes. In this work, we investigated the functional role of β4B-tubulin isotype (TUBB4B) in hearing and vision as mutations in TUBB4B are associated with sensorineural disease. Using a Tubb4b knockout mouse model, our findings demonstrate that TUBB4B is essential for hearing. Mice lacking TUBB4B are profoundly deaf due to defects in the inner and middle ear. Specifically, in the inner ear, the absence of TUBB4B lead to disorganized and reduced densities of microtubules in pillar cells, suggesting a critical role for TUBB4B in providing mechanical support for auditory transmission. In the middle ear, Tubb4b −/− mice exhibit motile cilia defects in epithelial cells, leading to the development of otitis media. However, Tubb4b deletion does not affect photoreceptor function or cause retinal degeneration. Intriguingly, β6-tubulin levels increase in retinas lacking β4B-tubulin isotype, suggesting a functional compensation mechanism. Our findings illustrate the essential roles of TUBB4B in hearing but not in vision in mice, highlighting the distinct functions of tubulin isotypes in different sensory systems.

This study is the first systematic review of research on outdoor learning occurring in all disciplines and interdisciplinary areas of study at higher education institutions in the United States and published in refereed English language journals. The article describes characteristics of outdoor learning research (OLR) and outdoor learning (OL). It discusses similarities, differences, challenges and trends as well as recommending additional research. The research protocol consists of a systematic search of 10 bibliographic databases using 18 keywords and 5 structural criteria to identify articles. This yielded 183 refereed articles published between 1996 and 2020 for analysis. Results and discussion are presented in seven categories. Outdoor learning research (OLR) publication frequency is growing, but is diffused among many journals resulting in limited communication of results. OLR is not a primary focus for most authors, limiting progress in understanding and development. OLR occurs at doctoral institutions and is distributed across disciplines and interdisciplinary areas. OLR is mostly descriptive, often case studies. Theory testing and inferential research is less common. Outdoor learning (OL) occurs in many academic areas with agriculture and social sciences, sustainability and adventure being most frequent. Learning methods use constructivist theory and experiential methods. Venues are diverse. OL drivers and barriers are generic and need elaboration. Enhanced learning and improved practices are stated outcomes. OL is a growing, but disjointed component of U.S. higher education. OLR demonstrates that OL addresses changing academic and participant interests. Recommendations to enhance OL practice are provided. Suggestions are made for future outdoor learning research.

BackgroundExisting interventions for co-occurring depression and cannabis use often do not treat both disorders simultaneously and can result in higher rates of symptom relapse. Traditional in-person interventions are often difficult to obtain due to financial and time limitations, which may further prevent individuals with co-occurring depression and cannabis use from receiving adequate treatment. Digital interventions can increase the scalability and accessibility for these individuals, but few digital interventions exist to treat both disorders simultaneously. Targeting transdiagnostic processes of these disorders with a digital intervention—specifically positive valence system dysfunction—may yield improved access and outcomes. ObjectiveRecent research has highlighted a need for the inclusion of individuals with lived experiences to assist in the co-design of interventions to enhance scalability and relevance of an intervention. Thus, the purpose of this study is to describe the process of eliciting feedback from individuals with elevated depressed symptoms and cannabis use and co-designing a digital intervention, Amplification of Positivity—Cannabis Use Disorder (AMP-C), focused on improving positive valence system dysfunction in these disorders. MethodsTen individuals who endorsed moderate to severe depressive symptoms and regular cannabis use (2-3×/week) were recruited online via Meta ads. Using a mixed methods approach, participants completed a 1-hour mixed methods interview over Zoom (Zoom Technologies Inc) where they gave their feedback and suggestions for the development of a mental health app, based on an existing treatment targeting positive valence system dysfunction, for depressive symptoms and cannabis use. The qualitative approach allowed for a broader investigation of participants’ wants and needs regarding the engagement and scalability of AMP-C, and the quantitative approach allowed for specific ratings of intervention components to be potentially included. ResultsParticipants perceived the 13 different components of AMP-C as overall helpful (mean 3.9-4.4, SD 0.5-1.1) and interesting (mean 4.0-4.9, SD 0.3-1.1) on a scale from 1 (not at all) to 5 (extremely). They gave qualitative feedback for increasing engagement in the app, including adding a social component, using notifications, and being able to track their symptoms and progress over time. ConclusionsThis study highlights the importance of including individuals with lived experiences in the development of interventions, including digital interventions. This inclusion resulted in valuable feedback and suggestions for improving the proposed digital intervention targeting the positive valence system, AMP-C, to better match the wants and needs of individuals with depressive symptoms and cannabis use.

Abstract One of the great diagnostic challenges for children with pulmonary arterial hypertension is the need for general anesthesia (GA) to enable successful right heart catheterization. Here, for the first time, we describe how echocardiographic estimates of right ventricular function and pulmonary pressures change in pediatric patients during GA.

Abstract Critical loads (CLs) are frequently used to quantify terrestrial ecosystem impacts from nitrogen (N) deposition using ecological responses such as the growth and mortality of tree species. Typically, CLs are reported as a single value, with uncertainty, for an indicator across a species' entire range. Mediating factors such as climate and soil conditions can influence species' sensitivity to N, but the magnitudes of these effects are rarely calculated explicitly. Here, we quantify the spatial variability and estimation error in N CLs for the growth and survival of 10 different tree species while accounting for key environmental factors that mediate species sensitivity to N (e.g., soil characteristics). We used a bootstrapped machine learning approach to determine the level of N deposition at which a 1% decrease occurs in growth rate or survival probability at forest plot locations across the United States. We found minimal differences (8.5 kg N ha−1 year−1) within these regimes. We also evaluated the most important factors for predicting tree growth rates and mortality and found that climate, competition, and air pollution generally have the greatest influence on growth rates and survival probability. Lastly, we developed a new probability of exceedance metric for each species and found high likelihoods of exceedance across large portions (46%) of some species' ranges. Our analysis demonstrates that machine learning approaches provide a unique capability to: (1) quantify mediating factor influences on N sensitivity of trees, (2) estimate the error in local N CL estimates, and (3) generate localized N CLs with probabilities of exceedance for tree species.

Abstract The diets of the eight species of ursids range from carnivory (e.g., polar bears, Ursus maritimus) to insectivory (e.g., sloth bears, Melursus ursinus), omnivory (e.g., brown bears, U. arctos), and herbivory (e.g., giant pandas, Ailuropoda melanoleuca). Dietary energy availability ranges from the high-fat, highly digestible, calorically dense diet of polar bears (~ 6.4 kcal digestible energy/g fresh weight) to the high-fiber, poorly digestible, calorically restricted diet (~ 0.7) of giant pandas. Thus, ursids provide the opportunity to examine the extent to which dietary energy drives evolution of energy metabolism in a closely related group of animals. We measured the daily energy expenditure (DEE) of captive brown bears in a relatively large, zoo-type enclosure and compared those values to previously published results on captive brown bears, captive and free-ranging polar bears, and captive and free-ranging giant pandas. We found that all three species have similar mass-specific DEE when travel distances and energy intake are normalized even though their diets differ dramatically and phylogenetic lineages are separated by millions of years. For giant pandas, the ability to engage in low-cost stationary foraging relative to more wide-ranging bears likely provided the necessary energy savings to become bamboo specialists without greatly altering their metabolic rate.

Abstract Declining Arctic sea ice is increasing polar bear land use. Polar bears on land are thought to minimize activity to conserve energy. Here, we measure the daily energy expenditure (DEE), diet, behavior, movement, and body composition changes of 20 different polar bears on land over 19–23 days from August to September (2019–2022) in Manitoba, Canada. Polar bears on land exhibited a 5.2-fold range in DEE and 19-fold range in activity, from hibernation-like DEEs to levels approaching active bears on the sea ice, including three individuals that made energetically demanding swims totaling 54–175 km. Bears consumed berries, vegetation, birds, bones, antlers, seal, and beluga. Beyond compensating for elevated DEE, there was little benefit from terrestrial foraging toward prolonging the predicted time to starvation, as 19 of 20 bears lost mass (0.4–1.7 kg•day−1). Although polar bears on land exhibit remarkable behavioral plasticity, our findings reinforce the risk of starvation, particularly in subadults, with forecasted increases in the onshore period.

Abstract Background Cellulose degradation by cellulases has been studied for decades due to the potential of using lignocellulosic biomass as a sustainable source of bioethanol. In plant cell walls, cellulose is bonded together and strengthened by the polyphenolic polymer, lignin. Because lignin is tightly linked to cellulose and is not digestible by cellulases, is thought to play a dominant role in limiting the efficient enzymatic degradation of plant biomass. Removal of lignin via pretreatments currently limits the cost-efficient production of ethanol from cellulose, motivating the need for a better understanding of how lignin inhibits cellulase-catalyzed degradation of lignocellulose. Work to date using bulk assays has suggested three possible inhibition mechanisms: lignin blocks access of the enzyme to cellulose, lignin impedes progress of the enzyme along cellulose, or lignin binds cellulases directly and acts as a sink. Results We used single-molecule fluorescence microscopy to investigate the nanoscale dynamics of Cel7A from Trichoderma reesei, as it binds to and moves along purified bacterial cellulose in vitro. Lignified cellulose was generated by polymerizing coniferyl alcohol onto purified bacterial cellulose, and the degree of lignin incorporation into the cellulose meshwork was analyzed by optical and electron microscopy. We found that Cel7A preferentially bound to regions of cellulose where lignin was absent, and that in regions of high lignin density, Cel7A binding was inhibited. With increasing degrees of lignification, there was a decrease in the fraction of Cel7A that moved along cellulose rather than statically binding. Furthermore, with increasing lignification, the velocity of processive Cel7A movement decreased, as did the distance that individual Cel7A molecules moved during processive runs. Conclusions In an in vitro system that mimics lignified cellulose in plant cell walls, lignin did not act as a sink to sequester Cel7A and prevent it from interacting with cellulose. Instead, lignin both blocked access of Cel7A to cellulose and impeded the processive movement of Cel7A along cellulose. This work implies that strategies for improving biofuel production efficiency should target weakening interactions between lignin and cellulose surface, and further suggest that nonspecific adsorption of Cel7A to lignin is likely not a dominant mechanism of inhibition.

ABSTRACT: The legalization of industrial hemp by the 2018 Farm Bill in the United States has driven a sharp increase in its cultivation, including for cannabinoid extraction. Spent hemp biomass (SHB), produced from the extraction of cannabinoids, can potentially be used as feed for dairy cows; however, it is still illegal to do so in the United States, according to the US Food and Drug Administration Center for Veterinary Medicine, due to the presence of cannabinoids and the lack of data on the effect on animals. To assess the safety of this byproduct as feed for dairy cows, late-lactation Jersey cows (245 ± 37 d in milk; 483 ± 38 kg body weight; 10 multiparous and 8 primiparous) received a basal total mixed ration (TMR) diet plus 13% alfalfa pellet (CON) or 13% pelleted SHB for 4 wk (intervention period [IP]) followed by 4 wk of withdrawal period (WP), where all cows received only the basal TMR during WP. The dry matter intake (DMI), body weight, body condition score, milk yield, milk components, and fatty acid profile, blood parameters, N metabolism, methane emission, and activity were measured. Results indicated that feeding SHB decreased DMI mainly due to the low palatability of the SHB pellet, as the cows consumed only 7.4% of the total TMR with 13.0% SHB pellet offered in the ration. However, milk yield was not affected during the IP and was higher than CON during the WP, leading to higher milk yield/DMI. Milk components were not affected, except for a tendency in decreased fat percentage. Milk fat produced by cows fed SHB had a higher proportion of oleate and bacteria-derived fatty acids than CON. The activity of the cows was not affected, except for a shorter overall lying time in SHB versus CON cows during the IP. Blood parameters related to immune function were not affected. Compared with CON, cows fed SHB had a lower cholesterol concentration during the whole experiment and higher β-hydroxybutyric acid during the WP, while a likely low-grade inflammation during the IP was indicated by higher ceruloplasmin and reactive oxidative metabolites. Other parameters related to liver health and inflammatory response were unaffected, except for a tendency for higher activity of alkaline phosphatase during IP and a lower activity of gamma-glutamyl transferase during WP in the SHB group versus CON. The bilirubin concentration was increased in cows fed SHB, suggesting a possible decrease in the clearance ability of the liver. Digestibility of the dry matter and protein and methane emission were not affected by feeding SHB. The urea, purine derivatives, and creatinine concentration in urine was unaffected, but cows fed SHB had higher N use efficiency and lower urine volume. Altogether, our data revealed a relatively low palatability of SHB affecting DMI with minimal biological effects, except for a likely low-grade inflammation, a higher N use efficiency, and a possible decrease in liver clearance. Overall, the data support the use of SHB as a safe feed ingredient for lactating dairy cows.

In response to the SARS-CoV-2 pandemic, the United States declared a state of emergency and implemented large-scale shutdowns and public health initiatives to prevent overwhelming public resources. The success of these prevention methods remains unresolved as restrictions and implementation varied from national, state, and local levels. Despite national and local regulations, individual adherence to preventative guidelines presented an additional layer of variability. Cases of COVID-19 continued to rise and fall over a two-year period on a national level, despite masking recommendations, ease of testing, and availability of vaccines. The Ysleta del Sur Pueblo is a Native American tribal community and sovereign nation located in El Paso, Texas. Speaking Rock Entertainment Center is a major business operated by the tribe, employing many tribal and non-tribal members from the El Paso area. Following nationwide re-openings of non-essential businesses, Speaking Rock implemented an infection control program with strict adherence to recommendations provided by the Center for Disease Control and Prevention (CDC) and additional disease control. This response would result in a fully vaccinated workforce within the wider community of El Paso, where the vaccination rate was less than 80%. Herein, we examine the efficacy of these measures and report on the success of the program resulting in zero hospitalizations or deaths compared with rates of 1 in 250 and 1 in 40, respectively, in the surrounding community.

The viscoelasticity of monoclonal antibodies (mAbs) is important during their production, formulation, and drug delivery. High concentration mAbs can provide higher efficacy therapeutics (e.g., during immunotherapy) and improved efficiency during their production (economy of scale during processing). Two humanized mAbs were studied (mAb-1 and mAb-2) with differing isoelectric points. Using high speed particle tracking microrheology, we demonstrated that the mAb solutions have significant viscoelasticities above concentrations of 40 mg/ml. Power law viscoelasticity was observed over the range of time scales ( 10 − 4–1 s) probed for the high concentration mAb suspensions. The terminal viscosity demonstrated an exponential dependence on mAb concentration (a modified Mooney relationship) as expected for charged stabilized Brownian colloids. Gelation of the mAbs was explored by lowering the pH of the buffer and a power law scaling of the gelation transition was observed, i.e., the exponent of the anomalous diffusion of the probe particles scaled inversely with the gelation time.

IntroductionChronic cancer-related pain from locally recurrent infiltrative cancers within the bony confines of the pelvis is a devastating and hard to manage condition that can be refractory to many conventional pain management methods. Spinal cord stimulation (SCS) is an evolving and safe method of pain management and can be trialled in a quick and well-tolerated operation under local anaesthesia. To date, this has not been reported in the setting of locally recurrent inoperable pelvic cancers.Case descriptionIn the present study, we report two cases of patients with severe back and lower limb pain resulting from recurrent anal and rectal cancers involving the right lumbar and sacral nerve roots as well as the bony sacrum, which severely affected quality of life and daily functioning.DiscussionFollowing successful SCS, effective pain relief was observed.ConclusionSCS could represent an effective supplementary or alternative technique to conventional pain management in this challenging group of patients, especially if other available methods have been exhausted.

BackgroundElectronic health record–based clinical decision support (CDS) tools can facilitate the adoption of evidence into practice. Yet, the impact of CDS beyond single-site implementation is often limited by dissemination and implementation barriers related to site- and user-specific variation in workflows and behaviors. The translation of evidence-based CDS from initial development to implementation in heterogeneous environments requires a framework that assures careful balancing of fidelity to core functional elements with adaptations to ensure compatibility with new contexts. ObjectiveThis study aims to develop and apply a framework to guide tailoring and implementing CDS across diverse clinical settings. MethodsIn preparation for a multisite trial implementing CDS for pediatric overweight or obesity in primary care, we developed the User-Centered Framework for Implementation of Technology (UFIT), a framework that integrates principles from user-centered design (UCD), human factors/ergonomics theories, and implementation science to guide both CDS adaptation and tailoring of related implementation strategies. Our transdisciplinary study team conducted semistructured interviews with pediatric primary care clinicians and a diverse group of stakeholders from 3 health systems in the northeastern, midwestern, and southeastern United States to inform and apply the framework for our formative evaluation. ResultsWe conducted 41 qualitative interviews with primary care clinicians (n=21) and other stakeholders (n=20). Our workflow analysis found 3 primary ways in which clinicians interact with the electronic health record during primary care well-child visits identifying opportunities for decision support. Additionally, we identified differences in practice patterns across contexts necessitating a multiprong design approach to support a variety of workflows, user needs, preferences, and implementation strategies. ConclusionsUFIT integrates theories and guidance from UCD, human factors/ergonomics, and implementation science to promote fit with local contexts for optimal outcomes. The components of UFIT were used to guide the development of Improving Pediatric Obesity Practice Using Prompts, an integrated package comprising CDS for obesity or overweight treatment with tailored implementation strategies. Trial RegistrationClinicalTrials.gov NCT05627011; https://clinicaltrials.gov/study/NCT05627011

Abstract Cell walls surround all plant cells, and their composition and structure are tightly regulated to maintain cellular and organismal homeostasis. In response to wall damage, the cell wall integrity (CWI) system is engaged to ameliorate effects on plant growth. Despite the central role CWI plays in plant development, our current understanding of how this system functions at the molecular level is limited. Here, we investigated the transcriptomes of etiolated seedlings of mutants of Arabidopsis thaliana with defects in three major wall polysaccharides, pectin (quasimodo2), cellulose (cellulose synthase3je5), and xyloglucan (xyloglucan xylosyltransferase1 and 2), to probe whether changes in the expression of cell wall‐related genes occur and are similar or different when specific wall components are reduced or missing. Many changes occurred in the transcriptomes of pectin‐ and cellulose‐deficient plants, but fewer changes occurred in the transcriptomes of xyloglucan‐deficient plants. We hypothesize that this might be because pectins interact with other wall components and/or integrity sensors, whereas cellulose forms a major load‐bearing component of the wall; defects in either appear to trigger the expression of structural proteins to maintain wall cohesion in the absence of a major polysaccharide. This core set of genes functioning in CWI in plants represents an attractive target for future genetic engineering of robust and resilient cell walls.

Abstract Impact Bronchopulmonary dysplasia has multiple definitions that are currently based on phenotypic characteristics. Using an unsupervised machine learning approach, we created BPD subclasses (e.g., endotypes) by clustering whole microarray data. T helper 17 cell differentiation was the most significant pathway differentiating the BPD endotypes. Introduction Bronchopulmonary dysplasia (BPD) is the most common complication of extreme prematurity. Discovery of BPD endotypes in an unbiased format, derived from the peripheral blood transcriptome, may uncover patterns underpinning this complex lung disease. Methods An unsupervised agglomerative hierarchical clustering approach applied to genome-wide expression of profiling from 62 children at day of life five was used to identify BPD endotypes. To identify which genes were differentially expressed across the BPD endotypes, we formulated a linear model based on least-squares minimization with empirical Bayes statistics. Results Four BPD endotypes (A, B,C,D) were identified using 7,319 differentially expressed genes. Across BPD endotypes, 5,850 genes had a p value

Abstract Two-dimensional materials have unusual properties and promise applications in nanoelectronics, spintronics, photonics, (electro)catalysis, separations, and elsewhere. Most are inorganic and their properties are difficult to tune. Here we report the preparation of Zn porphene, a member of the previously only hypothetical organic metalloporphene family. Similar to graphene, these also are fully conjugated two-dimensional polymers, but are composed of fused metalloporphyrin rings. Zn porphene is synthesized on water surface by two-dimensional oxidative polymerization of a Langmuir layer of Zn porphyrin with K2IrCl6, reminiscent of known one-dimensional polymerization of pyrroles. It is transferable to other substrates and bridges μm-sized pits. Contrary to previous theoretical predictions of metallic conductivity, it is a p-type semiconductor due to a predicted Peierls distortion of its unit cell from square to rectangular, analogous to the appearance of bond-length alternation in antiaromatic molecules. The observed reversible insertion of various metal ions, possibly carrying a fifth or sixth ligand, promises tunability and even patterning of circuits on an atomic canvas without removing any π centers from conjugation.

Abstract Benign idiopathic neonatal seizures (BINS), colloquially referred to as the “fifth‐day fits,” is a clinical neonatal epilepsy syndrome associated with early, spontaneous resolution of seizures and favorable developmental outcome. Although this disease entity was first described over four decades ago, the etiopathogenesis remains unknown, and it is unclear if the syndrome represents a single, cohesive disorder or a common manifestation of various unrelated neonatal neurological disturbances. As such, there are no standardized approaches to diagnostic workup and management. Benign familial neonatal seizures (BFNS) is a well‐characterized genetic syndrome associated with KCNQ2 and KCNQ3 pathogenic variants, which also manifests clinically with self‐resolving seizures in the neonatal period. While it remains unclear if there is any shared pathogenesis between these two disorders, the exceedingly similar phenotypic presentations and natural history raise the question of whether consensus management approaches used in genetic BFNS can also be applied to BINS. Here, we present a topical and historical review of BINS and BFNS literature and propose specific treatment recommendations based on extrapolation of limited existing clinical data.

Bronchopulmonary dysplasia (BPD) is a complex, multifactorial lung disease affecting preterm neonates that can result in long-term pulmonary and non-pulmonary complications. Current therapies mainly focus on symptom management after the development of BPD, indicating a need for innovative approaches to predict and identify neonates who would benefit most from targeted or earlier interventions. Clinical informatics, a subfield of biomedical informatics, is transforming healthcare by integrating computational methods with patient data to improve patient outcomes. The application of clinical informatics to develop and enhance clinical therapies for BPD presents opportunities by leveraging electronic health record data, applying machine learning algorithms, and implementing clinical decision support systems. This review highlights the current barriers and the future potential of clinical informatics in identifying clinically relevant BPD phenotypes and developing clinical decision support tools to improve the management of extremely preterm neonates developing or with established BPD. However, the full potential of clinical informatics in advancing our understanding of BPD with the goal of improving patient outcomes cannot be achieved unless we address current challenges such as data collection, storage, privacy, and inherent data bias.

Introduction: Aseptic tibial loosening following total knee arthroplasty (TKA) can be challenging to diagnose radiographically. Surgeons often face the clinical scenario of determining implant fixation in patients that do not have serial radiographs and only subtle radiographic features of loosening. Therefore, the purpose of our study was to determine how accurately attendings and trainees are at identifying aseptic tibial loosening. Methods: Two cohorts of patients were identified for this study. Cohort one consisted of twenty patients with aseptic tibial loosening. Cohort two consisted of twenty patients with well-fixed pain-free total knee replacements at one-year follow-up. Surgeons were then given a clinical scenario that all patients are returning with pain at follow-up. The surgeon then reviewed each patient's radiographs and determined whether the tibial component was loose or well-fixed. Results: Overall, surgeons were significantly more likely to correctly identify well-fixed implants than loose implants (p

ABSTRACT People with cystic fibrosis (pwCF) commonly test positive for the pathogenic fungus Aspergillus fumigatus, which is associated with a decline in lung function. Trikafta is a recently approved therapy for pwCF that improves quantity and function of the CFTR protein; however, it is not known how Trikafta affects microbial communities in the lung. Therefore, the aim of this study was to determine whether Trikafta directly affects A. fumigatus growth and biology. While Trikafta did not impact the viability of A. fumigatus conidia, treatment of A. fumigatus biofilms with Trikafta reduced overall biofilm biomass. This finding was associated with increased membrane permeability, decreased viability, and reduced metabolic activity following long-term treatment of biofilms. Trikafta-induced membrane permeability, and biomass reduction was partially blocked with the calcium channel inhibitor verapamil and fully blocked by the mammalian CFTR inhibitor GlyH-101. Trikafta-induced biomass reduction and metabolic activity was shown to be regulated by the high-osmolarity glycerol pathway gene sakA. Trikafta treatment also induced resistance to the cell wall stressor calcofluor white, susceptibility to the anti-fungal drug caspofungin, and decreased inflammatory responses from murine bone marrow cells. Collectively, these results reveal that Trikafta affects infection-relevant A. fumigatus biology and host-microbial interactions. IMPORTANCE PwCF commonly test positive for pathogenic fungi, and more than 90% of the cystic fibrosis patient population is approved for the modulator treatment, Trikafta. Therefore, it is critical to understand how fungal communities, specifically A. fumigatus, respond to Trikafta exposure. Therefore, we sought to determine whether Trikafta impacted the biology of A. fumigatus biofilms. Our data demonstrate that Trikafta reduces biomass in several laboratory strains as well as clinical strains isolated from the expectorated sputum of pwCF. Furthermore, Trikafta reduces fungal viability and the capacity of biofilms to recover following treatment. Of particular importance, Trikafta affects how A. fumigatus biofilms respond to cell wall stressors, suggesting that Trikafta modulates components of the cell wall. Since the cell wall directly affects how a host immune system will respond to and effectively neutralize pathogens, our work, demonstrating that Trikafta impacts the A. fumigatus cell wall, is potentially highly relevant to fungal-induced disease pathogenesis.

Abstract Maternal malnutrition increases fetal and neonatal morbidity, partly by affecting placental function and morphology, but its impact on placental hemodynamics are unknown. Our objective was to define the impact of maternal malnutrition on placental oxygen reserve and perfusion in vivo in a rhesus macaque model of protein restriction (PR) using advanced imaging. Animals were fed control (CON, 26% protein), 33% PR diet (17% protein), or a 50% PR diet (13% protein, n = 8/group) preconception and throughout pregnancy. Animals underwent Doppler ultrasound and fetal biometry followed by MRI at gestational days 85 (G85) and 135 (G135; term is G168). Pregnancy loss rates were 0/8 in CON, 1/8 in 33% PR, and 3/8 in 50% PR animals. Fetuses of animals fed a 50% PR diet had a smaller abdominal circumference (G135, p

Abstract Background Immune responses to COVID-19 mRNA vaccines have not been well characterized in frail older adults. We postulated that frailty is associated with impaired antibody and cellular mRNA vaccine responses. Methods We followed older adults in a retirement facility with longitudinal clinical and serological samples from the first Moderna mRNA-1273 vaccine dose starting in February 2021 through their 3rd (booster) vaccine dose. Outcomes were antibody titers, antibody avidity, and AIM+ T cell function and phenotype. Statistical analysis used linear regression with clustered error for antibody titers over multiple timepoints with clinical predictors including, age, sex, prior infection status, and clinical frailty scale (CFS) score. T cell function analysis used linear regression models with clinical predictors and cellular memory phenotype variables. Results Participants (n = 15) had median age of 90 years and mild, moderate, or severe frailty scores (n = 3, 7, or 5 respectively). Over the study time course, anti-spike antibody titers were 10-fold higher in individuals with lower frailty status (p = 0.001 and p = 0.005, unadjusted and adjusted for prior COVID-19 infection). Following the booster, titers to spike protein improved regardless of COVID-19 infection or degree of frailty (p = 0.82 and p = 0.29, respectively). Antibody avidity significantly declined over 6 months in all participants following 2 vaccine doses (p

Richter’s Transformation is a treatment-resistant and fatal progression from Chronic Lymphocytic Leukemia (CLL) to an aggressive lymphoma. Here, the authors show that PRMT5 is upregulated months prior to and after transformation, PRMT5 overexpression in a CLL mouse model leads to increased risk of transformation, and that targeted PRMT5 inhibition prolongs survival and delays disease development.

Abstract Objectives Complex physiological adaptations often involve the coordination of molecular responses across multiple tissues. Establishing transcriptomic resources for non-traditional model organisms with phenotypes of interest can provide a foundation for understanding the genomic basis of these phenotypes, and the degree to which these resemble, or contrast, those of traditional model organisms. Here, we present a one-of-a-kind gene expression dataset generated from multiple tissues of two hibernating brown bears (Ursus arctos). Data description This dataset is comprised of 26 samples collected from 13 tissues of two hibernating brown bears. These samples were collected opportunistically and are typically not possible to attain, resulting in a highly unique and valuable gene expression dataset. In combination with previously published datasets, this new transcriptomic resource will facilitate detailed investigation of hibernation physiology in bears, and the potential to translate aspects of this biology to treat human disease.

Rates of increase in sulfur fertiliser use have outpaced other nutrients to compensate for reductions in atmospheric sulfur deposition due to improved air quality, according to an analysis of fertiliser sales and atmospheric nutrient deposition fluxes in the Midwest USA between 1985 and 2015.

Abstract Despite the biological and therapeutic relevance of CDK4/6 for the treatment of HR+, HER2- advanced breast cancer, the detailed mode of action of CDK4/6 inhibitors is not completely understood. Of particular interest, phosphorylation of CDK4 at T172 (pT172) is critical for generating the active conformation, yet no such crystal structure has been reported to date. We describe here the x-ray structure of active CDK4-cyclin D3 bound to the CDK4/6 inhibitor abemaciclib and discuss the key aspects of the catalytically-competent complex. Furthermore, the effect of CDK4/6 inhibitors on CDK4 T172 phosphorylation has not been explored, despite its role as a potential biomarker of CDK4/6 inhibitor response. We show mechanistically that CDK4/6i stabilize primed (pT172) CDK4-cyclin D complex and selectively displace p21 in responsive tumor cells. Stabilization of active CDK4-cyclin D1 complex can lead to pathway reactivation following alternate dosing regimen. Consequently, sustained binding of abemaciclib to CDK4 leads to potent cell cycle inhibition in breast cancer cell lines and prevents rebound activation of downstream signaling. Overall, our study provides key insights demonstrating that prolonged treatment with CDK4/6 inhibitors and composition of the CDK4/6-cyclin D complex are both critical determinants of abemaciclib efficacy, with implications for this class of anticancer therapy.

Abstract Free-space optical communications are poised to alleviate the data-flow bottleneck experienced by spacecraft as traditional radio frequencies reach their practical limit. While enabling orders-of-magnitude gains in data rates, optical signals impose much stricter pointing requirements and are strongly affected by atmospheric turbulence. Coherent detection methods, which capitalize fully on the available degrees of freedom to maximize data capacity, have the added complication of needing to couple the received signal into single-mode fiber. In this paper we present results from a coherent 1550 nm link across turbulent atmosphere between a deployable optical terminal and a drone-mounted retroreflector. Through 10 Hz machine vision optical tracking with nested 200 Hz tip/tilt adaptive optics stabilisation, we corrected for pointing errors and atmospheric turbulence to maintain robust single mode fiber coupling, resulting in an uninterrupted 100 Gbps optical data link while tracking at angular rates of up to 1.5 deg/s, equivalent to that of spacecraft in low earth orbit. With the greater data capacity of coherent communications and compatibility with extant fiber-based technologies being demonstrated across static links, ground-to-low earth orbit links of Terabits per second can ultimately be achieved with capable ground stations.

Calcium is important for the growth and development of plants. It serves crucial functions in cell wall and cell membrane structure and serves as a secondary messenger in signaling pathways relevant to nutrient and immunity responses. Thus, measuring calcium levels in plants is important for studies of plant biology and for technology development in food, agriculture, energy, and forest industries. Often, calcium in plants has been measured through techniques such as atomic absorption spectrophotometry (AAS), inductively coupled plasma–mass spectrometry (ICP-MS), and electrophysiology. These techniques, however, require large sample sizes, chemical extraction of samples or have limited spatial resolution. Here, we used near-edge X-ray absorption fine structure (NEXAFS) spectroscopy at the calcium L- and K-edges to measure the calcium to carbon mass ratio with spatial resolution in plant samples without requiring chemical extraction or large sample sizes. We demonstrate that the integrated absorbance at the calcium L-edge and the edge jump in the fluorescence yield at the calcium K-edge can be used to quantify the calcium content as the calcium mass fraction, and validate this approach with onion epidermal peels and ICP-MS. We also used NEXAFS to estimate the calcium mass ratio in hypocotyls of a model plant, Arabidopsis thaliana, which has a cell wall composition that is similar to that of onion epidermal peels. These results show that NEXAFS spectroscopy performed at the calcium edge provides an approach to quantify calcium levels within plants, which is crucial for understanding plant physiology and advancing plant-based materials.

Summary: Synaptic zinc signaling modulates synaptic activity and is present in specific populations of cortical neurons, suggesting that synaptic zinc contributes to the diversity of intracortical synaptic microcircuits and their functional specificity. To understand the role of zinc signaling in the cortex, we performed whole-cell patch-clamp recordings from intratelencephalic (IT)-type neurons and pyramidal tract (PT)-type neurons in layer 5 of the mouse auditory cortex during optogenetic stimulation of specific classes of presynaptic neurons. Our results show that synaptic zinc potentiates AMPA receptor (AMPAR) function in a synapse-specific manner. We performed in vivo 2-photon calcium imaging of the same classes of neurons in awake mice and found that changes in synaptic zinc can widen or sharpen the sound-frequency tuning bandwidth of IT-type neurons but only widen the tuning bandwidth of PT-type neurons. These results provide evidence for synapse- and cell-type-specific actions of synaptic zinc in the cortex.

The hypothesized electrostatic lofting of individual regolith grains on the Moon and asteroids has been investigated extensively in laboratory studies. Cohesion may dominate how regolith behaves on these small, airless bodies, yet the magnitude of this force remains uncertain. We induce the electrostatic detachment of dust as a mechanism to break cohesive bonds between individual zirconia-silica microspheres in order to measure the interparticle cohesive force between them, likely dominated by capillary bridges. A high-speed camera imaged centroid positions of the lofted microspheres over time. Using the centroids from the initial detachment, we numerically calculated initial accelerations to solve for the cohesion that had been restraining the microspheres. Unexpectedly, the electrostatic lofting of clumps of particles was observed and experimental results showed that clumps were a nonnegligible portion of the lofted object population.

Abstract The eight species of bears world-wide consume a wide variety of diets. Some are specialists with extensive anatomical and physiological adaptations necessary to exploit specific foods or environments [e.g., polar bears (Ursus maritimus), giant pandas (Ailuropoda melanoleuca), and sloth bears (Melursus ursinus)], while the rest are generalists. Even though ursids evolved from a high-protein carnivore, we hypothesized that all have become low-protein macronutrient omnivores. While this dietary strategy has already been described for polar bears and brown bears (Ursus arctos), a recent study on giant pandas suggested their macronutrient selection was that of the ancestral high-protein carnivore. Consumption of diets with inappropriate macronutrient profiles has been associated with increased energy expenditure, ill health, failed reproduction, and premature death. Consequently, we conducted feeding and preference trials with giant pandas and sloth bears, a termite and ant-feeding specialist. Both giant pandas and sloth bears branched off from the ursid lineage a million or more years before polar bears and brown bears. We found that giant pandas are low-protein, high-carbohydrate omnivores, whereas sloth bears are low-protein, high-fat omnivores. The preference for low protein diets apparently occurred early in the evolution of ursids and may have been critical to their world-wide spread.

Abstract Background and Aims Policymakers need data about the burden of respiratory syncytial virus (RSV) lower respiratory tract infections (LRTI) among infants. This study estimates quality of life (QoL) for otherwise healthy term US infants with RSV‐LRTI and their caregivers, previously limited to premature and hospitalized infants, and corrects for selective testing. Methods The study enrolled infants

Abstract High‐entropy (HE) metal chalcogenides are a class of materials that have great potential in applications such as thermoelectrics and electrocatalysis. Layered 2D transition‐metal dichalcogenides (TMDCs) are a sub‐class of high entropy metal chalcogenides that have received little attention to date as their preparation currently involves complicated, energy‐intensive, or hazardous synthetic steps. To address this, a low‐temperature (500 °C) and rapid (1 h) single source precursor approach is successfully adopted to synthesize the hexernary high‐entropy metal disulfide (MoWReMnCr)S2. (MoWReMnCr)S2 powders are characterized by powder X‐ray diffraction (pXRD) and Raman spectroscopy, which confirmed that the material is comprised predominantly of a hexagonal phase. The surface oxidation states and elemental compositions are studied by X‐ray photoelectron spectroscopy (XPS) whilst the bulk morphology and elemental stoichiometry with spatial distribution is determined by scanning electron microscopy (SEM) with elemental mapping information acquired from energy‐dispersive X‐ray (EDX) spectroscopy. The bulk, layered material is subsequently exfoliated to ultra‐thin, several‐layer 2D nanosheets by liquid‐phase exfoliation (LPE). The resulting few‐layer HE (MoWReMnCr)S2 nanosheets are found to contain a homogeneous elemental distribution of metals at the nanoscale by high angle annular dark field‐scanning transmission electron microscopy (HAADF‐STEM) with EDX mapping. Finally, (MoWReMnCr)S2 is demonstrated as a hydrogen evolution electrocatalyst and compared to 2H‐MoS2 synthesized using the molecular precursor approach. (MoWReMnCr)S2 with 20% w/w of high‐conductivity carbon black displays a low overpotential of 229 mV in 0.5 M H2SO4 to reach a current density of 10 mA cm−2, which is much lower than the overpotential of 362 mV for MoS2. From density functional theory calculations, it is hypothesised that the enhanced catalytic activity is due to activation of the basal plane upon incorporation of other elements into the 2H‐MoS2 structure, in particular, the first row TMs Cr and Mn.

Abstract Background Limited data exist on the diagnosis and successful medical management of suspected pancreatic abscessation, and the appropriate terminology of this condition. Hypothesis/Objectives To describe the diagnosis and management of pancreatic fluid accumulations in dogs where pancreatic fluid cytology results were available, to describe those medically and surgically managed at the same institution, and reconsider the terminology describing acute pancreatitis with pancreatic fluid accumulation. Animals Fifteen dogs treated for suspected pancreatic abscessation at a university teaching hospital between January 2010 and March 2020. Methods Retrospective descriptive study. Results Ultrasonographic findings described pancreatic fluid accumulations as hypoechoic in 10/15 and anechoic in 2/15 cases, ranging between 1.6 and 7 cm in diameter (median, 3.5 cm). No complications were documented after ultrasound guided fine‐needle aspiration. Cytologically, all samples revealed a predominantly neutrophilic inflammation. 11/15 samples yielded a negative culture (9/11 received antimicrobials before sampling) and in 4 cases culture was positive. 7/15 were initially managed surgically including all 4 infected cases. 4/7 surgically managed cases were discharged, including 2 infected cases. The remaining 3/7 surgically managed cases were euthanized due poor quality of life. 8/15 cases were managed medically; 7/8 were discharged, 1 died. 3/7 then represented, and underwent successful surgical intervention after recrudescence of clinical signs, and all were discharged. The remaining 4 medically managed cases did not require further therapeutic intervention, with no clinical deterioration on reassessment. Conclusions and Clinical Importance Medical management is a viable treatment option for some dogs with pancreatic fluid accumulation, or as a prequel to surgical management. Subclassifications of pancreatic fluid accumulations using diagnostic findings could enable more tailored management approaches and accurate prognostication.

Background: Transphyseal humeral separations (TPHS) are rare injuries often associated with non-accidental trauma, necessitating accurate diagnosis. This study aims to assess the accuracy of diagnosis of TPHS. Methods: A retrospective review was conducted at five academic pediatric institutions to identify all surgically treated TPHS in patients up to 4 years of age over a 25-year period. Demographics, misdiagnosis rates, and reported misdiagnoses were noted. Comparative analyses were performed to analyze the effects of patient age and injury mechanism on misdiagnosis rates. Results: Seventy-nine patients (average age: 17.4 months) were identified, with injury mechanisms including accidental trauma (n = 49), non-accidental trauma (n = 21), Cesarean-section (n = 6), and vaginal delivery (n = 3). Neither age nor injury mechanism were significantly associated with diagnostic accuracy in the emergency department (ED)/consulting physician group. ED/consulting physicians achieved an accurate diagnosis 46.7% of the time, while radiologists achieved an accurate diagnosis 26.7% of the time. Diagnostic accuracy did not correlate with Child Protective Services (CPS) involvement or with a delay in surgery of more than 24 h. However, a significant correlation (p = 0.03) was observed between injury mechanism and misdiagnosis rates. Conclusion: This multicenter analysis is the largest study assessing TPHS misdiagnosis rates, highlighting the need for raising awareness and considering advanced imaging or orthopedic consultation for accurate diagnosis. This also reminds orthopedic surgeons to always have vigilant assessment in treating pediatric elbow injuries. Level of Evidence: Level III–Retrospective Cohort Study.

Objective: This study aimed to determine acaricide resistance in Rhipicephalus decoloratus ticks collected from grazing cattle between November 2018 and May 2019 in Elundini, Senqu, and Walter Sisulu Local Municipalities in the northeastern region of the Eastern Cape Province. Materials and Methods: A sample of 20–30 adult engorged female R. decoloratus ticks were collected from at least 10 randomly selected cattle (highly tick-infested) at each dip tank and placed into the labelled plastic collection bottles containing absorbent paper and with a perforated lid at a constant room temperature of ±28°C and >70% relative humidity until resistance testing commenced. The Shaw larval immersion test method was used to determine R. decoloratus larvae resistance to various acaricide concentration levels [amidines, organophosphate (OP), and synthetic pyrethroids (SPs)]. Results: This study found that most ticks were susceptible to exposure to different acaricide field concentrations of amidines (49% at 250 ppm), OPs (33% and 47% at 300 ppm and 500 ppm, respectively), and SPs (44% and 23% at 150 ppm and 300 ppm, respectively). The resistance test¬ing results showed no resistance to amidines at any localities and no resistance to OP in the Senqu region. However, resistance development of the larvae to amines, OPs, and SPs was extensively observed in Senqu (18%, 6%, and 7%), Elundini (15%, 15%, and 17%), and Walter Sisulu (13%, 19%, and 9%) regions, respectively. Conclusions: The larvae's resistance is a cause for worry. Hence, the continuous monitoring of tick resistance to commonly used acaricides will help mitigate widespread acaricidal resistance and sustain livestock productivity. [J Adv Vet Anim Res 2022; 9(1.000): 33-41]

Environmental enteric dysfunction (EED), a subclinical disorder of intestinal function, is associated with malnutrition, infant growth stunting and pathologies in the small intestine. Here the authors report that infant rhesus macaques that are naturally exposed to enteric pathogens commonly linked to human growth stunting present with EED and growth faltering that associates with large intestine pathologies.

The Peruvian Amazon is facing the highest known input of mercury pollution of any ecosystem globally. Intact forests located near artisanal gold mining are particularly at risk from this toxin.

Background High-risk human papillomavirus (HPV) is a primary cause of an increasing number of oropharyngeal squamous cell carcinomas (OPSCCs). The viral etiology of these cancers provides the opportunity for antigen-directed therapies that are restricted in scope compared with cancers without viral components. However, specific virally-encoded epitopes and their corresponding immune responses are not fully defined.Methods To understand the OPSCC immune landscape, we conducted a comprehensive single-cell analysis of HPV16+ and HPV33+ primary tumors and metastatic lymph nodes. We used single-cell analysis with encoded peptide-human leukocyte antigen (HLA) tetramers to analyze HPV16+ and HPV33+ OPSCC tumors, characterizing the ex vivo cellular responses to HPV-derived antigens presented in major Class I and Class II HLA alleles.Results We identified robust cytotoxic T-cell responses to HPV16 proteins E1 and E2 that were shared across multiple patients, particularly in HLA-A*01:01 and HLA-B*08:01. Responses to E2 were associated with loss of E2 expression in at least one tumor, indicating the functional capacity of these E2-recognizing T cells and many of these interactions validated in a functional assay. Conversely, cellular responses to E6 and E7 were limited in quantity and cytotoxic capacity, and tumor E6 and E7 expression persisted.Conclusions These data highlight antigenicity beyond HPV16 E6 and E7 and nominate candidates for antigen-directed therapies.

BackgroundNo distinctive clinical signs of Ebola virus disease (EVD) have prompted the development of rapid screening tools or called for a new approach to screening suspected Ebola cases. New screening approaches require evidence of clinical benefit and economic efficiency. As of now, no evidence or defined algorithm exists.ObjectiveTo evaluate, from a healthcare perspective, the efficiency of incorporating Ebola prediction scores and rapid diagnostic tests into the EVD screening algorithm during an outbreak.MethodsWe collected data on rapid diagnostic tests (RDTs) and prediction scores' accuracy measurements, e.g., sensitivity and specificity, and the cost of case management and RDT screening in EVD suspect cases. The overall cost of healthcare services (PPE, procedure time, and standard-of-care (SOC) costs) per suspected patient and diagnostic confirmation of EVD were calculated. We also collected the EVD prevalence among suspects from the literature. We created an analytical decision model to assess the efficiency of eight screening strategies: 1) Screening suspect cases with the WHO case definition for Ebola suspects, 2) Screening suspect cases with the ECPS at -3 points of cut-off, 3) Screening suspect cases with the ECPS as a joint test, 4) Screening suspect cases with the ECPS as a conditional test, 5) Screening suspect cases with the WHO case definition, then QuickNavi™-Ebola RDT, 6) Screening suspect cases with the ECPS at -3 points of cut-off and QuickNavi™-Ebola RDT, 7) Screening suspect cases with the ECPS as a conditional test and QuickNavi™-Ebola RDT, and 8) Screening suspect cases with the ECPS as a joint test and QuickNavi™-Ebola RDT. We performed a cost-effectiveness analysis to identify an algorithm that minimizes the cost per patient correctly classified. We performed a one-way and probabilistic sensitivity analysis to test the robustness of our findings.ResultsOur analysis found dual ECPS as a conditional test with the QuickNavi™-Ebola RDT algorithm to be the most cost-effective screening algorithm for EVD, with an effectiveness of 0.86. The cost-effectiveness ratio was 106.7 USD per patient correctly classified. The following algorithms, the ECPS as a conditional test with an effectiveness of 0.80 and an efficiency of 111.5 USD per patient correctly classified and the ECPS as a joint test with the QuickNavi™-Ebola RDT algorithm with an effectiveness of 0.81 and a cost-effectiveness ratio of 131.5 USD per patient correctly classified. These findings were sensitive to variations in the prevalence of EVD in suspected population and the sensitivity of the QuickNavi™-Ebola RDT.ConclusionsFindings from this study showed that prediction scores and RDT could improve Ebola screening. The use of the ECPS as a conditional test algorithm and the dual ECPS as a conditional test and then the QuickNavi™-Ebola RDT algorithm are the best screening choices because they are more efficient and lower the number of confirmation tests and overall care costs during an EBOV epidemic.

Catastrophes such as a nuclear war would generate atmospheric soot and reduce sunlight, making it difficult to grow crops. Under such conditions, people might turn to inedible plant biomass for nutrition, but the convertibility and nutritional content of this biomass have not been rigorously analyzed. We found that if plant biomass were converted into food at 30% efficiency, 6.7 kg of biomass per day would yield adequate carbohydrates, but contain potentially toxic or insufficient levels of other nutrients for a family of four. Therefore, exploiting biomass with low mineral content for carbohydrates and consuming other sources of protein, fat, and vitamins such as edible insects/single-cell proteins and vitamin supplements could provide a balanced diet in a global catastrophic environment.

As replications of individual studies are resource intensive, techniques for predicting the replicability are required. We introduce the repliCATS (Collaborative Assessments for Trustworthy Science) process, a new method for eliciting expert predictions about the replicability of research. This process is a structured expert elicitation approach based on a modified Delphi technique applied to the evaluation of research claims in social and behavioural sciences. The utility of processes to predict replicability is their capacity to test scientific claims without the costs of full replication. Experimental data supports the validity of this process, with a validation study producing a classification accuracy of 84% and an Area Under the Curve of 0.94, meeting or exceeding the accuracy of other techniques used to predict replicability. The repliCATS process provides other benefits. It is highly scalable, able to be deployed for both rapid assessment of small numbers of claims, and assessment of high volumes of claims over an extended period through an online elicitation platform, having been used to assess 3000 research claims over an 18 month period. It is available to be implemented in a range of ways and we describe one such implementation. An important advantage of the repliCATS process is that it collects qualitative data that has the potential to provide insight in understanding the limits of generalizability of scientific claims. The primary limitation of the repliCATS process is its reliance on human-derived predictions with consequent costs in terms of participant fatigue although careful design can minimise these costs. The repliCATS process has potential applications in alternative peer review and in the allocation of effort for replication studies.

The disadvantage posed by native starch during food application had led to starch modification using physical or chemical techniques. This research therefore, aimed at modelling and optimizing the amylose-amylopectin ratio of modified cooking banana starch using chemometrics approach (response surface methodology). This was done by varying different concentration of octenyl succinate anhydride concentration (3-5%), reaction time (30-60 mins) and pH (8-10) using Box-Behnken design. The result obtained revealed the significance and accuracy of the model in predicting the amylose-amylopectin ratio of the modified starch owing to its low p-value (p < 0.001) and high coefficient of determinant (R2 > 0.97). The adequate precision value greater than 4 was an indication that the model can navigate within the design space. Finally, an optimal value of 3.32% octenyl succinate anhydride concentration, reaction time of 32.04 mins and substrate pH of 8 was obtained which resulted in predicted amylose-amylopectin ratio of 0.806.

Some genes that are part of balanced translocations are reported as drivers for tumourigenesis. Here, the authors report a translocation involving MTCP1 in chronic lymphocytic leukemia and show that MTCP1 overexpression leads to the disease in a murine model.

Abstract Emerging studies are reporting associations between skeletal muscle abnormalities and survival in cancer patients. Cancer prognosis is associated with depletion of essential fatty acids in erythrocytes and plasma in humans. However the relationship between skeletal muscle membrane fatty acid composition and survival is unknown. This study investigates the relationship between fatty acid content of phospholipids in skeletal muscle and survival in cancer patients. Rectus abdominis biopsies were collected during cancer surgery from 35 patients diagnosed with cancer. Thin-layer and gas chromatography were used for quantification of phospholipid fatty acids. Cutpoints for survival were defined using optimal stratification. Median survival was between 450 and 500 days when patients had arachidonic acid (AA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in muscle phospholipid below the cut-point compared to 720–800 days for patients above. Cox regression analysis revealed that low amounts of AA, EPA and DHA are risk factors for death. The risk of death remained significant for AA [HR 3.5 (1.11–10.87), p = 0.03], EPA [HR 3.92 (1.1–14.0), p = 0.04] and DHA [HR 4.08 (1.1–14.6), p = 0.03] when adjusted for sex. Lower amounts of essential fatty acids in skeletal muscle membrane is a predictor of survival in cancer patients. These results warrant investigation to restore bioactive fatty acids in people with cancer.

Rifampicin (RIF), Isoniazid (INH), Ethambutol (EMB), Pyrazinamide (PZA), and/or their fixed-dose combination (FDC) are extensively prescribed in the cure of Tuberculosis (TB) globally. In spite of the beneficial effect, these drugs are capable of inducing cellular toxicity. Existing information on the genotoxic effects of the first-line anti-TB drugs is limited and contentious. Herein, we evaluated the reproductive genotoxicity of RIF, INH, EMB, PZA, and their FDC utilizing the mouse sperm morphology assay. Histological examination of the testes of exposed mice was also performed. Male Swiss albino mice (11–13 weeks old) were intraperitoneally exposed for 5 consecutive days to each of the anti-TB drugs at four different doses of 6.25, 12.5, 25, and 50 mg/kg bw of PZA; 2.5, 5.0, 10, and 20 mg/kg bw of RIF; 1.25, 2.5, 5.0 and 10 mg/kg bw of INH; 3.75, 7.5, 15 and 30 mg/kg bw of EMB; and 7, 14, 28 and 56 mg/kg bw of FDC corresponding respectively to ×0.25, ×0.5, ×1 and ×2.0 of the standard daily dose. In comparison with the negative control (normal saline), there was no significant difference in the testicular weight and organo-somatic index of exposed mice. There was an increase (p > 0.05) in the frequency of abnormal spermatozoa at most of the tested doses of each drug and a dose-dependent decrease with the FDC. Each of the anti-TB drugs except the FDC induced pathological lesions in the testes. These findings suggest that the individual first-line anti-TB drug unlike the FDC has the potential to provoke testicular anomalies in male mice.

In plants, cell adhesion relies on balancing the integrity of the pectin-rich middle lamella with wall loosening during tissue expansion. Mutation of QUASIMODO2 (QUA2), a pectin methyltransferase, causes defective hypocotyl elongation and cell adhesion in Arabidopsis thaliana hypocotyls. However, the molecular function of QUA2 in cell adhesion is obscured by complex genetic and environmental interactions. To dissect the role of QUA2 in cell adhesion, we investigated a qua2 loss-of-function mutant and a suppressor mutant with restored cell adhesion, qua2 esmeralda1, using a combination of imaging and biochemical techniques. We found that qua2 hypocotyls have reductions in middle lamellae integrity, pectin methyl-esterase (PME) activity, pectin content and molecular mass, and immunodetected Ca2+-crosslinking at cell corners, but increased methyl-esterification and polygalacturonase (PG) activity, with qua2 esmd1 having wild type-like or intermediate phenotypes. Our findings suggest that excessive pectin degradation prevents pectin accumulation and the formation of a sufficiently Ca2+-crosslinked network to maintain cell adhesion in qua2 mutants. We propose that PME and PG activities balance tissue-level expansion and cell separation. Together, these data provide insight into the cause of cell adhesion defects in qua2 mutants and highlight the importance of harmonizing pectin modification and degradation during plant growth and development.