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Abstract Although DNA methylation primarily represses TEs, it also represses select genes that are methylated in plant body tissues but demethylated by DNA glycosylases (DNGs) in endosperm or pollen. Either one of two DNGs, MATERNAL DEREPRESSION OF R1 (MDR1) or DNG102, is essential for pollen viability in maize. Using single-pollen mRNA sequencing on pollen-segregating mutations in both genes, we identify 58 candidate DNG target genes that account for 11.1% of the wild-type transcriptome but are silent or barely detectable in other tissues. They are unusual in their tendency to lack introns but even more so in their TE-like methylation (teM) in coding DNA. The majority have predicted functions in cell wall modification, and they likely support the rapid tip growth characteristic of pollen tubes. These results suggest a critical role for DNA methylation and demethylation in regulating maize genes with the potential for extremely high expression in pollen but constitutive silencing elsewhere.

Abstract Background Limited treatment options exist for damaged nerves and despite impressive advances in tissue engineering, scientists and clinicians have yet to fully replicate nerve development and recruitment. Innervation is a critical feature for normal organ function. While most organs are innervated prior to birth, a rare example of postnatal nerve recruitment occurs in the natural development of secondary teeth during adolescence. Many animals undergo postnatal shedding of deciduous teeth with development and eruption of secondary teeth, a process requiring recruitment of nerve and vasculature to each tooth pulp for viability. Here, the investigators created a novel model for the study of postnatal innervation by exploiting the natural phenomenon of tooth-driven nerve recruitment. Methods The investigators theorized that developing teeth possess a special capacity to induce innervation which could be harnessed in a clinical setting for nerve regeneration, and hyptothesized that a transplant model could be created to capture this phenomenon. In this descriptive study, a rat model of autologous tooth transplantation and de novo nerve recruitment was developed by surgically transferring whole developing molars to the autologous tibia. Results Downstream histological analysis performed 6 to 14 weeks after surgery demonstrated integration of molar into tibia in 81% of postoperative rats, with progressive pulpal expression of nerve marker ß-tubulin III suggestive of neuronal recruitment. Conclusions These findings provide a novel model for the study of organ transplantation and support the theory that developing dental tissues may retain nerve-inductive properties postnatally.

Abstract Background The La-related proteins (LARPs) are a superfamily of RNA-binding proteins associated with regulation of gene expression. Evidence points to an important role for post-transcriptional control of gene expression in germinating pollen tubes, which could be aided by RNA-binding proteins. Results In this study, a genome-wide investigation of the LARP proteins in eight plant species was performed. The LARP proteins were classified into three families based on a phylogenetic analysis. The gene structure, conserved motifs, cis-acting elements in the promoter, and gene expression profiles were investigated to provide a comprehensive overview of the evolutionary history and potential functions of ZmLARP genes in maize. Moreover, ZmLARP6c1 was specifically expressed in pollen and ZmLARP6c1 was localized to the nucleus and cytoplasm in maize protoplasts. Overexpression of ZmLARP6c1 enhanced the percentage pollen germination compared with that of wild-type pollen. In addition, transcriptome profiling analysis revealed that differentially expressed genes included PABP homologous genes and genes involved in jasmonic acid and abscisic acid biosynthesis, metabolism, signaling pathways and response in a Zmlarp6c1::Ds mutant and ZmLARP6c1-overexpression line compared with the corresponding wild type. Conclusions The findings provide a basis for further evolutionary and functional analyses, and provide insight into the critical regulatory function of ZmLARP6c1 in maize pollen germination.

Abstract Mammography shifted to digital breast tomosynthesis (DBT) in the US. An automated percentage of breast density (PD) technique designed for two-dimensional (2D) applications was evaluated with DBT using several breast cancer risk prediction measures: normalized-volumetric; dense volume; applied to the volume slices and averaged (slice-mean); and applied to synthetic 2D images. Volumetric measures were derived theoretically. PD was modeled as a function of compressed breast thickness (CBT). The mean and standard deviation of the pixel values were investigated. A matched case–control (CC) study (n = 426 pairs) was evaluated. Odd ratios (ORs) were estimated with 95% confidence intervals. ORs were significant for PD: identical for volumetric and slice-mean measures [OR = 1.43 (1.18, 1.72)] and [OR = 1.44 (1.18, 1.75)] for synthetic images. A 2nd degree polynomial (concave-down) was used to model PD as a function of CBT: location of the maximum PD value was similar across CCs, occurring at 0.41 × CBT, and PD was significant [OR = 1.47 (1.21, 1.78)]. The means from the volume and synthetic images were also significant [ORs ~ 1.31 (1.09, 1.57)]. An alternative standardized 2D synthetic image was constructed, where each pixel value represents the percentage of breast density above its location. Several measures were significant and an alternative method for constructing a standardized 2D synthetic image was produced.

Abstract Background Emotional support (ES) is the most frequently reported support need among older adults with cancer. Yet, the association of ES with cancer outcomes is largely unknown. This study examined the association of ES with health‐related quality of life (HRQoL), mental health, and survival among older adults with gastrointestinal (GI) malignancies. Methods We included newly diagnosed older adults (≥60 years) with GI cancer undergoing self‐reported geriatric assessment at their first clinic visit. ES was measured using an adaptation of the Medical Outcomes Study (dichotomized adequate ES vs. inadequate ES). Outcomes included physical and mental HRQoL, anxiety, depression, and survival. Multivariable linear regression evaluated the association between ES and HRQoL scores. Multivariable logistic regression evaluated the association of ES with anxiety and depression. All models were adjusted for age at geriatric assessments, race, sex, and cancer type/stage. Results 795 participants were included. Median patient age was 68 years (IQR: 64–74), 58% were male, and most cancers were either colorectal (37.9%) or pancreatic (30.8%). Most (77.6%) had adequate ES. Patients with inadequate ES were more likely to be Black (31.5 vs. 20.8%, p = 0.005), disabled (24.1 vs. 10.4%, p

Abstract Data modeling requires a sufficient sample size for reproducibility. A small sample size can inhibit model evaluation. A synthetic data generation technique addressing this small sample size problem is evaluated: from the space of arbitrarily distributed samples, a subgroup (class) has a latent multivariate normal characteristic; synthetic data can be generated from this class with univariate kernel density estimation (KDE); and synthetic samples are statistically like their respective samples. Three samples (n = 667) were investigated with 10 input variables (X). KDE was used to augment the sample size in X. Maps produced univariate normal variables in Y. Principal component analysis in Y produced uncorrelated variables in T, where the probability density functions were approximated as normal and characterized; synthetic data was generated with normally distributed univariate random variables in T. Reversing each step produced synthetic data in Y and X. All samples were approximately multivariate normal in Y, permitting the generation of synthetic data. Probability density function and covariance comparisons showed similarity between samples and synthetic samples. A class of samples has a latent normal characteristic. For such samples, this approach offers a solution to the small sample size problem. Further studies are required to understand this latent class.

In a national survey of lead infection preventionists in Thai hospitals, spiritual and religious importance were associated with increased odds of career satisfaction. Cultivating environments for spiritual, religious, and self-care practices within the clinical setting may help facilitate emotional well-being—and prevent burnout—among Thai healthcare workers.

Purpose: Systemic sclerosis, also known as scleroderma, is a rare and chronic autoimmune connective disorder that affects most organs. While clinical findings of scleroderma patients in the context of the eye have been described to include lid fibrosis and glaucoma, almost nothing has been reported regarding ophthalmologic surgical complications in scleroderma patients. Observations: Here, we report bilateral zonular dehiscence and iris prolapse during two independent cataract extractions performed by separate experienced anterior segment surgeons in a patient with known systemic sclerosis. The patient did not have any other known risk factors for these complications to occur. Conclusions: and Importance: In our patient, bilateral zonular dehiscence raised the possibility of poor connective tissue support secondary to scleroderma. We recommend that clinicians are aware of potential complications in performing anterior segment surgery in patients with known or suspected scleroderma.

Objectives There is emerging use of artificial intelligence (AI) models to aid diagnostic imaging. This review examined and critically appraised the application of AI models to identify surgical pathology from radiological images of the abdominopelvic cavity, to identify current limitations and inform future research.Design Systematic review.Data sources Systematic database searches (Medline, EMBASE, Cochrane Central Register of Controlled Trials) were performed. Date limitations (January 2012 to July 2021) were applied.Eligibility criteria Primary research studies were considered for eligibility using the PIRT (participants, index test(s), reference standard and target condition) framework. Only publications in the English language were eligible for inclusion in the review.Data extraction and synthesis Study characteristics, descriptions of AI models and outcomes assessing diagnostic performance were extracted by independent reviewers. A narrative synthesis was performed in accordance with the Synthesis Without Meta-analysis guidelines. Risk of bias was assessed (Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2)).Results Fifteen retrospective studies were included. Studies were diverse in surgical specialty, the intention of the AI applications and the models used. AI training and test sets comprised a median of 130 (range: 5–2440) and 37 (range: 10–1045) patients, respectively. Diagnostic performance of models varied (range: 70%–95% sensitivity, 53%–98% specificity). Only four studies compared the AI model with human performance. Reporting of studies was unstandardised and often lacking in detail. Most studies (n=14) were judged as having overall high risk of bias with concerns regarding applicability.Conclusions AI application in this field is diverse. Adherence to reporting guidelines is warranted. With finite healthcare resources, future endeavours may benefit from targeting areas where radiological expertise is in high demand to provide greater efficiency in clinical care. Translation to clinical practice and adoption of a multidisciplinary approach should be of high priority.PROSPERO registration number CRD42021237249.

Abstract Background Indwelling urinary catheters are commonly used in hospitalized patients, which can lead to the development of urinary catheter complications, including catheter-associated urinary tract infection (CAUTI). Limited reports on the appropriateness of urinary catheter use exist in Japan. This study investigated the prevalence and appropriateness of indwelling urinary catheters, and the incidence of CAUTI in non-intensive care unit (non-ICU) wards in Japanese hospitals. Methods This prospective observational study was conducted in 7 non-ICU wards from 6 hospitals in Japan from October 2017 to June 2018. At each hospital the study teams evaluated urinary catheter prevalence through in-person bedside evaluation for at least 5 days of each week for 3 months. Catheter associated urinary tract infection (CAUTI) incidence and appropriateness of catheter use was collected via chart review. Results We assessed 710 catheter-days over 5528 patient-days. The mean prevalence of indwelling urinary catheter use in participating wards was 13% (range: 5% to 19%), while the mean incidence of CAUTI was 9.86 per 1000 catheter-days (range: 0 to 33.90). Approximately 66% of the urinary catheter days assessed had an appropriate indication for use (range: 17% to 81%). A physician's order for catheter placement was present in only 10% of catheterized patients. Conclusion This multicenter study provides epidemiological information about the appropriate use of urinary catheters in Japanese non-ICU wards. A multimodal intervention may help improve the appropriate use of urinary catheters.

Summary: Gustatory information is relayed from the anterior tongue by geniculate ganglion neurons and from the posterior tongue by neurons of the petrosal portion of the jugular/nodose/petrosal ganglion complex. Here, we use in vivo calcium imaging in mice to compare the encoding of taste information in the geniculate and petrosal ganglia, at single-neuron resolution. Our data support an anterior/posterior specialization of taste information coding from the tongue to the ganglia, with petrosal neurons more responsive to umami or bitter and less responsive to sweet or salty stimuli than geniculate neurons. We found that umami (50 mM MPG + 1 mM IMP) promotes salivation when applied to the posterior, but not anterior, tongue. This suggests a functional taste map of the mammalian tongue where the anterior and posterior taste pathways are differentially responsive to specific taste qualities, and differentially regulate downstream physiological functions of taste, such as promoting salivation.

Abstract Background The COVID-19 pandemic dramatically influenced the delivery of healthcare. In line with the UK Royal Colleges’ advice the management of acute appendicitis (AA) changed with greater consideration for non-operative management (NOM) or open appendicectomy when operative management (OM) was sought. We describe our experience of the presentation, management and outcomes for these patients to inform care for future viral pandemics. Methods This retrospective, cohort study compared patients diagnosed with AA between March and July 2019 with those during the pandemic period of March to July 2020. Medical records were reviewed to obtain demographics, inflammatory markers, imaging, severity, management, histology, length of stay (LOS) and 90-day outcomes. Results There were 149 and 125 patients in the 2019 and 2020 cohorts respectively. 14 patients (9.4%) had NOM in 2019 versus 31 (24.8%) in 2020 (p = 0.001). In the 2019 operative management (OM) group 125 patients (92.6%) had laparoscopic appendicectomy versus 65 (69.1%) in 2020. 59 patients (39.6%) had a CT in 2019 versus 70 (56%) in 2020. The median LOS was 4 days in 2019 and 3 days in 2020 (p = 0.03). Two patients in each year who received NOM had treatment failure (14.3% in 2019 and 6.5% in 2020). Three patients in 2019 who received OM had treatment failure (2.2%). Of 95 patients tested for COVID-19 all but one tested negative. Conclusion During the COVID-19 pandemic there was no observed increase in severity of AA, patients had a shorter LOS and were more likely to have imaging. NOM proportionally increased with no observed change in outcomes.

Abstract Percent mammographic density (PMD) is a strong breast cancer risk factor, however, other mammographic features, such as V, the standard deviation (SD) of pixel intensity, may be associated with risk. We assessed whether PMD, automated PMD (APD), and V, yielded independent associations with breast cancer risk. We included 1900 breast cancer cases and 3921 matched controls from the Nurses’ Health Study (NHS) and the NHSII. Using digitized film mammograms, we estimated PMD using a computer-assisted thresholding technique. APD and V were determined using an automated computer algorithm. We used logistic regression to generate odds ratios (ORs) and 95% confidence intervals (CIs). Median time from mammogram to diagnosis was 4.1 years (interquartile range: 1.6–6.8 years). PMD (OR per SD:1.52, 95% CI: 1.42, 1.63), APD (OR per SD:1.32, 95% CI: 1.24, 1.41), and V (OR per SD:1.32, 95% CI: 1.24, 1.40) were positively associated with breast cancer risk. Associations for APD were attenuated but remained statistically significant after mutual adjustment for PMD or V. Women in the highest quartile of both APD and V (OR vs Q1/Q1: 2.49, 95% CI: 2.02, 3.06), or PMD and V (OR vs Q1/Q1: 3.57, 95% CI: 2.79, 4.58) had increased breast cancer risk. An automated method of PMD assessment is feasible and yields similar, but somewhat weaker, estimates to a manual measure. PMD, APD and V are each independently, positively associated with breast cancer risk. Women with dense breasts and greater texture variation are at the highest relative risk of breast cancer.

Our previous work shows that dioleoylphosphatidylglycerol (DOPG) accelerates corneal epithelial healing in vitro and in vivo by unknown mechanisms. Prior data demonstrate that DOPG inhibits toll-like receptor (TLR) activation and inflammation induced by microbial components (pathogen-associated molecular patterns, PAMPs) and by endogenous molecules upregulated in psoriatic skin, which act as danger-associated molecular patterns (DAMPs) to activate TLRs and promote inflammation. In the injured cornea, sterile inflammation can result from the release of the DAMP molecule, heat shock protein B4 (HSPB4), to contribute to delayed wound healing. Here, we show in vitro that DOPG inhibits TLR2 activation induced in response to HSPB4, as well as DAMPs that are elevated in diabetes, a disease that also slows corneal wound healing. Further, we show that the co-receptor, cluster of differentiation-14 (CD14), is necessary for PAMP/DAMP-induced activation of TLR2, as well as of TLR4. Finally, we simulated the high-glucose environment of diabetes to show that elevated glucose levels enhance TLR4 activation by a DAMP known to be upregulated in diabetes. Together, our results demonstrate the anti-inflammatory actions of DOPG and support further investigation into its development as a possible therapy for corneal injury, especially in diabetic patients at high risk of vision-threatening complications.

Abstract Parasitism can represent a potent agent of selection, and introduced parasites have the potential to substantially alter their new hosts' ecology and evolution. While significant impacts have been reported for parasites that switch to new host species, the effects of macroparasite introduction into naïve populations of host species with which they have evolved remain poorly understood. Here, we investigate how the estuarine white‐fingered mud crab (Rhithropanopeus harrisii) has adapted to parasitism by an introduced rhizocephalan parasite (Loxothylacus panopaei) that castrates its host. While the host crab is native to much of the East and Gulf Coasts of North America, its parasite is native only to the southern end of this range. Fifty years ago, the parasite invaded the mid‐Atlantic, gradually expanding through previously naïve host populations. Thus, different populations of the same host species have experienced different degrees of historical interaction (and thus potential evolutionary response time) with the parasite: long term, short term, and naïve. In nine estuaries across this range, we examined whether and how parasite prevalence and host susceptibility to parasitism differs depending on the length of the host's history with the parasite. In field surveys, we found that the parasite was significantly more prevalent in its introduced range (i.e., short‐term interaction) than in its native range (long‐term interaction), a result that was also supported by a meta‐analysis of prevalence data covering the 50 years since its introduction. In controlled laboratory experiments, host susceptibility to parasitism was significantly higher in naïve hosts than in hosts from the parasite's native range, suggesting that host resistance to parasitism is under selection. These results suggest that differences in host–parasite historical interaction can alter the consequences of parasite introductions in host populations. As anthropogenically driven range shifts continue, disruptions of host–parasite evolutionary relationships may become an increasingly important driver of ecological and evolutionary change.

Using point-prevalence methodology and the World Health Organization (WHO) Access, Watch, and Reserve Classification, we measured antibiotic use in 5 hospitals in Okinawa, Japan, on October 1, 2020. Overall, 29% of patients were prescribed an antibiotic on the survey date and the 3 most used antibiotics in the “Watch” category were cefazolin, ampicillin-sulbactam, and ampicillin.

Abstract Objective To evaluate the ability of persons with metastatic cancer to self‐assess their medical decision‐making capacity (MDC). To investigate this, we compared an objective measure of MDC with self‐ratings and evaluated predictors of agreement. Methods Data were obtained from a cross‐sectional study of metastatic cancer patients at a large academic medical center. Across all standards of MDC, sensitivity, specificity, and reliability using Gwet's AC1 statistic were calculated using the objective measure as the gold standard. Logistic regression was used to evaluate predictors of agreement between the measures across all MDC standards. Results In those with brain metastases, high sensitivity (greater than 0.7), but low specificity was observed for all standards. Poor reliability was observed across all standards. Higher age resulted in higher odds of disagreement for Standard 3 (appreciation) (OR: 1.07, 95% CI: 1.00, 1.15) and Standard 4 (reasoning) (OR: 1.05, 95% CI: 1.00, 1.10). For Standard 3, chemotherapy use and brain metastases compared to other metastases resulted in higher odds of disagreement (Chemotherapy: OR: 5.62, 95% CI: 1.37, 23.09, Brain Metastases: OR: 5.93, 95% CI: 1.28, 27.55). For Standard 5 (understanding), no predictors were associated with disagreement. Conclusions For less cognitively complex standards (e.g., appreciation), self‐report may be more valid and reliable than more cognitively complex standards (e.g., reasoning or understanding). However, overall, MDC self‐report in the current sample is suboptimal. Thus, the need for detailed assessment of MDC, especially when patients are older or used chemotherapy, is indicated. Other studies should be conducted to assess MDC agreement longitudinally.

ALS-linked mutations induce aberrant conformations within the SOD1 protein that are thought to underlie the pathogenic mechanism of SOD1-mediated ALS. Although clinical trials are underway for gene silencing of SOD1, these approaches reduce both wild-type and mutated forms of SOD1. Here, we sought to develop anti-SOD1 nanobodies with selectivity for mutant and misfolded forms of human SOD1 over wild-type SOD1. Characterization of two anti-SOD1 nanobodies revealed that these biologics stabilize mutant SOD1 in vitro. Further, SOD1 expression levels were enhanced and the physiological subcellular localization of mutant SOD1 was restored upon co-expression of anti-SOD1 nanobodies in immortalized cells. In human motor neurons harboring the SOD1 A4V mutation, anti-SOD1 nanobody expression promoted neurite outgrowth, demonstrating a protective effect of anti-SOD1 nanobodies in otherwise unhealthy cells. In vitro assays revealed that an anti-SOD1 nanobody exhibited selectivity for human mutant SOD1 over endogenous murine SOD1, thus supporting the preclinical utility of anti-SOD1 nanobodies for testing in animal models of ALS. In sum, the anti-SOD1 nanobodies developed and presented herein represent viable biologics for further preclinical testing in human and mouse models of ALS.

Colorectal cancer (CRC) and cardiovascular diseases (CVD) share several risk factors. We examined the relationships between CRC screening and CVD history by race/ethnicity and sex. Data from 15 states across the United States with high age-adjusted CVD rates from the 2012–2016 Behavioral Risk Factor Surveillance System were used to examine prevalence of self-reported screening for CRC among 179,276 adults ages 50–75 years with and without history of CVD. Multivariable logistic regression was used to evaluate the association between socio-demographics and CRC screening in the expansion and stable phases of the Affordable Care Act (ACA) era. Prevalence of CRC screening was high among those with history of CVD. After multivariable adjustment, Whites and Hispanics with CVD had 19% (95%[CI]: 1.13–1.26) and 50% (95%[CI]: 1.10–2.06) higher odds for CRC screening, respectively, versus those without CVD. Individuals in both sexes with CVD had higher odds for CRC screening compared those without CVD. Strikingly, the odds for CRC screening in Hispanics with history of CVD were 72% higher in the stable phase of the ACA era for the fully adjusted model. Whites and Hispanics with history of CVD are more likely to undergo CRC screening, perhaps due to greater exposure to the healthcare system due to CVD. This association was not observed in Blacks. Interventions are needed to improve CRC screening rates among Blacks, especially due to their well-documented higher risk of CVD.

Members of the La-related protein family (LARPs) contain a conserved La module, which has been associated with RNA-binding activity. Expression of the maize gene GRMZM2G323499/Zm00001d018613, a member of the LARP family, is highly specific to pollen, based on both transcriptomic and proteomic assays. This suggests a pollen-specific RNA regulatory function for the protein, designated ZmLARP6c1 based on sequence similarity to the LARP6 subfamily in Arabidopsis. To test this hypothesis, a Ds-GFP transposable element insertion in the ZmLarp6c1 gene (tdsgR82C05) was obtained from the Dooner/Du mutant collection. Sequencing confirmed that the Ds-GFP insertion is in an exon, and thus likely interferes with ZmLARP6c1 function. Tracking inheritance of the insertion via its endosperm-expressed GFP indicated that the mutation was associated with reduced transmission from a heterozygous plant when crossed as a male (ranging from 0.5 to 26.5% transmission), but not as a female. Furthermore, this transmission defect was significantly alleviated when less pollen was applied to the silk, reducing competition between mutant and wild-type pollen. Pollen grain diameter measurements and nuclei counts showed no significant differences between wild-type and mutant pollen. However, in vitro, mutant pollen tubes were significantly shorter than those from sibling wild-type plants, and also displayed altered germination dynamics. These results are consistent with the idea that ZmLARP6c1 provides an important regulatory function during the highly competitive progamic phase of male gametophyte development following arrival of the pollen grain on the silk. The conditional, competitive nature of the Zmlarp6c1::Ds male sterility phenotype (i.e., reduced ability to produce progeny seed) points toward new possibilities for genetic control of parentage in crop production.

In flowering plants, gene expression in the haploid male gametophyte (pollen) is essential for sperm delivery and double fertilization. Pollen also undergoes dynamic epigenetic regulation of expression from transposable elements (TEs), but how this process interacts with gene expression is not clearly understood. To explore relationships among these processes, we quantified transcript levels in four male reproductive stages of maize (tassel primordia, microspores, mature pollen, and sperm cells) via RNA-seq. We found that, in contrast with vegetative cell-limited TE expression in Arabidopsis pollen, TE transcripts in maize accumulate as early as the microspore stage and are also present in sperm cells. Intriguingly, coordinate expression was observed between highly expressed protein-coding genes and their neighboring TEs, specifically in mature pollen and sperm cells. To investigate a potential relationship between elevated gene transcript level and pollen function, we measured the fitness cost (male-specific transmission defect) of GFP-tagged coding sequence insertion mutations in over 50 genes identified as highly expressed in the pollen vegetative cell, sperm cell, or seedling (as a sporophytic control). Insertions in seedling genes or sperm cell genes (with one exception) exhibited no difference from the expected 1:1 transmission ratio. In contrast, insertions in over 20% of vegetative cell genes were associated with significant reductions in fitness, showing a positive correlation of transcript level with non-Mendelian segregation when mutant. Insertions in maize gamete expressed2 (Zm gex2), the sole sperm cell gene with measured contributions to fitness, also triggered seed defects when crossed as a male, indicating a conserved role in double fertilization, given the similar phenotype previously demonstrated for the Arabidopsis ortholog GEX2. Overall, our study demonstrates a developmentally programmed and coordinated transcriptional activation of TEs and genes in pollen, and further identifies maize pollen as a model in which transcriptomic data have predictive value for quantitative phenotypes.

OBJECTIVE:To describe the presence of practice effects in persons with Alzheimer disease (AD) or mild cognitive impairment (MCI) and to evaluate how practice effects affect cognitive progression and the outcome of clinical trials. METHODS:Using data from a meta-database consisting of 18 studies including participants from the Alzheimer disease Cooperative Study (ADCS) and the Alzheimer Disease Neuroimaging Initiative (ADNI) with ADAS-Cog11 as the primary outcome, we defined practice effects based on the improvement in the first two ADAS-Cog11 scores and then estimated the presence of practice effects and compared the cognitive progression between participants with and without practice effects. The robustness of practice effects was investigated using CDR SB, an outcome independent the definition itself. Furthermore, we evaluated how practice effects can affect sample size estimation. RESULTS:The overall percent of practice effects for AD participants was 39.0% and 53.3% for MCI participants. For AD studies, the mean change from baseline to 2 years was 12.8 points for the non-practice effects group vs 7.4 for the practice effects group; whereas for MCI studies, it was 4.1 for non-practice effects group vs 0.2 for the practice effects group. AD participants without practice effects progressed 0.9 points faster than those with practice effects over a period of 2 years in CDR-SB; whereas for MCI participants, the difference is 0.7 points. The sample sizes can be different by over 35% when estimated based on participants with/without practice effects. CONCLUSION:Practice effects were prevalent and robust in persons with AD or MCI and affected the cognitive progression and sample size estimation. Planning of future AD or MCI clinical trials should account for practice effects to avoid underpower or considers target trials or stratification analysis based on practice effects.

Estrogen receptor alpha (ERα) plays critical roles in the etiology and treatment of breast cancer. Here the authors synthesize benzopyrans with variable side chains to identify antiestrogenic compounds and characterize OP-1074, a compound that exhibits pure antiestrogenic activity by inducing the degradation of ERα and possesses greater potency than tamoxifen or fulvestrant in a xenograft model.

Mouse incisors constantly renew from a slow cycling population of mesenchymal stem cells. Here, the authors show that upon cutting of adult incisors, a sub-population of dental mesenchymal stem cells reactivates, allowing an increased growth rate and rapid regeneration.

Abstract The PREDICTS project—Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (https://www.nhm.ac.uk/our-science/our-work/biodiversity/predicts.html)—has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.