Design, Development and Construct Validation of the Children’s

Objective: To design and validate a literature-derived, population-based Children’s Dietary Inflammatory Index (C-DII)TM. Design: The C-DII was developed based on a review of literature through 2010. Dietary data obtained from children in 16 different countries were used to create a reference database for computing C-DII scores based on consumption of macronutrients, vitamins, minerals, and whole foods. Construct validation was performed using quantile regression to assess the association between C-reactive protein (CRP) concentrations and C-DII scores. Data Sources: All data used for construct validation were obtained from children between six and 14 years of age (n = 3300) who participated in the U.S. National Health and Nutrition Examination Survey (NHANES) (2005–2010). Results: The C-DII was successfully validated with blood CRP concentrations in this heterogeneous sample of 3300 children from NHANES (52% male; 29% African American, 25% Mexican American; mean age 11 years). The final model was adjusted for sex, age, race, asthma, body mass index (BMI), and infections. Children in level 3 (i.e., quartiles 3 and 4 combined) of the C-DII (i.e., children with the most pro-inflammatory diets) had a CRP value 0.097 mg/dL higher than that in level 1 (i.e., quartile 1) for CRP values at the 75th percentile of CRP using quantile regression (p \u3c 0.05). Conclusion: The C-DII predicted blood CRP concentrations among children 6–14 years in the NHANES. Further construct validation with CRP and other inflammatory markers is required to deepen understanding of the relationship between the C-DII and markers of inflammation in childre

An RNA interference-based screen of transcription factor genes identifies pathways necessary for sensory regeneration in the avian inner ear

Sensory hair cells of the inner ear are the mechano-electric transducers of sound and head motion. In mammals, damage to sensory hair cells leads to hearing or balance deficits. Non-mammalian vertebrates such as birds can regenerate hair cells after injury. In a previous study, we characterized transcription factor gene expression during chicken hair cell regeneration. In those studies, a laser micro-beam or ototoxic antibiotics were used to damage the sensory epithelia (SE). The current study focused on 27 genes that were up-regulated in regenerating SE compared to untreated SE in the previous study. Those genes were knocked down by siRNA, to determine their requirement for supporting cell proliferation and to measure resulting changes in the larger network of gene expression. We identified 11 genes necessary for proliferation and also identified novel interactive relationships between many of them. Defined components of the WNT, PAX and AP1 pathways were shown to be required for supporting cell proliferation. These pathways intersect on WNT4, which is also necessary for proliferation. Among the required genes, the CCAAT enhancer binding protein, CEBPG, acts downstream of Jun Kinase and JUND in the AP1 pathway. The WNT co-receptor LRP5 acts downstream of CEBPG as does the transcription factor BTAF1. Both of these genes are also necessary for supporting cell proliferation. This is the first large scale screen of its type and suggests an important intersection between the AP1 pathway, the PAX pathway and WNT signaling in the regulation of supporting cell proliferation during inner ear hair cell regeneration

Molecular motors robustly drive active gels to a critically connected state

Living systems often exhibit internal driving: active, molecular processes drive nonequilibrium phenomena such as metabolism or migration. Active gels constitute a fascinating class of internally driven matter, where molecular motors exert localized stresses inside polymer networks. There is evidence that network crosslinking is required to allow motors to induce macroscopic contraction. Yet a quantitative understanding of how network connectivity enables contraction is lacking. Here we show experimentally that myosin motors contract crosslinked actin polymer networks to clusters with a scale-free size distribution. This critical behavior occurs over an unexpectedly broad range of crosslink concentrations. To understand this robustness, we develop a quantitative model of contractile networks that takes into account network restructuring: motors reduce connectivity by forcing crosslinks to unbind. Paradoxically, to coordinate global contractions, motor activity should be low. Otherwise, motors drive initially well-connected networks to a critical state where ruptures form across the entire network.Comment: Main text: 21 pages, 5 figures. Supplementary Information: 13 pages, 8 figure

Local Recurrence Rates are Low in High-Risk Neoadjuvant Breast Cancer in the I-SPY 1 Trial (CALGB 150007/150012; ACRIN 6657)

Increasingly, women with stage 2 and 3 breast cancers receive neoadjuvant therapy, after which many are eligible for breast-conserving surgery (BCS). The question often arises as to whether BCS, if achievable, provides adequate local control. We report the results of local recurrence (LR) from the I-SPY 1 Trial in the setting of maximal multidisciplinary treatment where approximately 50 % of patients were treated with BCS

The solsticial pause on Mars: 1. A planetary wave reanalysis

Large-scale planetary waves are diagnosed from an analysis of profiles retrieved from the Thermal Emission Spectrometer aboard the Mars Global Surveyor spacecraft during its scientific mapping phase. The analysis is conducted by assimilating thermal profiles and total dust opacity retrievals into a Mars global circulation model. Transient waves are largest throughout the northern hemisphere autumn, winter and spring period and almost absent during the summer. The southern hemisphere exhibits generally weaker transient wave behaviour. A striking feature of the low-altitude transient waves in the analysis is that they show a broad subsidiary minimum in amplitude centred on the winter solstice, a period when the thermal contrast between the summer hemisphere and the winter pole is strongest and baroclinic wave activity might be expected to be strong. This behaviour, here called the ‘solsticial pause,’ is present in every year of the analysis. This strong pause is under-represented in many independent model experiments, which tend to produce relatively uniform baroclinic wave activity throughout the winter. This paper documents and diagnoses the transient wave solsticial pause found in the analysis; a companion paper investigates the origin of the phenomenon in a series of model experiments

A core outcome set for studies of gestational diabetes mellitus prevention and treatment

AIMS/HYPOTHESIS: The aim of this systematic review was to develop core outcome sets (COSs) for trials evaluating interventions for the prevention or treatment of gestational diabetes mellitus (GDM). METHODS: We identified previously reported outcomes through a systematic review of the literature. These outcomes were presented to key stakeholders (including patient representatives, researchers and clinicians) for prioritisation using a three-round, e-Delphi study. A priori consensus criteria informed which outcomes were brought forward for discussion at a face-to-face consensus meeting where the COS was finalised. RESULTS: Our review identified 74 GDM prevention and 116 GDM treatment outcomes, which were presented to stakeholders in round 1 of the e-Delphi study. Round 1 was completed by 173 stakeholders, 70% (121/173) of whom went on to complete round 2; 84% (102/121) of round 2 responders completed round 3. Twenty-two GDM prevention outcomes and 30 GDM treatment outcomes were discussed at the consensus meeting. Owing to significant overlap between included prevention and treatment outcomes, consensus meeting stakeholders agreed to develop a single prevention/treatment COS. Fourteen outcomes were included in the final COS. These consisted of six maternal outcomes (GDM diagnosis, adherence to the intervention, hypertensive disorders of pregnancy, requirement and type of pharmacological therapy for hyperglycaemia, gestational weight gain and mode of birth) and eight neonatal outcomes (birthweight, large for gestational age, small for gestational age, gestational age at birth, preterm birth, neonatal hypoglycaemia, neonatal death and stillbirth). CONCLUSIONS/INTERPRETATION: This COS will enable future GDM prevention and treatment trials to measure similar outcomes that matter to stakeholders and facilitate comparison and combination of these studies. TRIAL REGISTRATION: This study was registered prospectively with the Core Outcome Measures in Effectiveness Trials (COMET) database: http://www.comet-initiative.org/studies/details/686/

The unusual M-dwarf Warm Jupiter TOI-1899~b: Refinement of orbital and planetary parameters

TOI-1899~b is a rare exoplanet, a temperate Warm Jupiter orbiting an M-dwarf, first discovered by \citet{Canas2020_toi1899} from a TESS single-transit event. Using new radial velocities (RVs) from the precision RV spectrographs HPF and NEID, along with additional TESS photometry and ground-based transit follow-up, we are able to derive a much more precise orbital period of $P = 29.090312_{-0.000035}^{+0.000036}$~d, along with a radius of $R_p = 0.99\pm0.03$~\unit{R_{J}}. We have also improved the constraints on planet mass, $M_p = 0.67\pm{0.04}$~\unit{M_{J}}, and eccentricity, which is consistent with a circular orbit at 2$\sigma$ ($e = 0.044_{-0.027}^{+0.029}$). TOI-1899~b occupies a unique region of parameter space as the coolest known ($T_{eq} \approx$ 380~K) Jovian-sized transiting planet around an M-dwarf; we show that it has great potential to provide clues regarding the formation and migration mechanisms of these rare gas giants through transmission spectroscopy with JWST as well as studies of tidal evolution.Comment: 19 pages, 7 figures, 3 tables, submitted to AJ (comments welcome

Outcomes after Total Skin-sparing Mastectomy and Immediate Reconstruction in 657 Breasts

ABSTRACT Background. Total skin-sparing mastectomy (TSSM), a technique comprising removal of all breast and nipple tissue while preserving the entire skin envelope, is increasingly offered to women for therapeutic and prophylactic indications. However, standard use of the procedure remains controversial as a result oft concerns regarding oncologic safety and risk of complications. Methods. Outcomes from a prospectively maintained database of patients undergoing TSSM and immediate breast reconstruction from 2001 to 2010 were reviewed. Outcome measures included postoperative complications, tumor involvement of the nipple-areolar complex (NAC) on pathologic analysis, and cancer recurrence. Results. TSSM was performed on 657 breasts in 428 patients. Indications included in situ cancer [111 breasts (16.9 %)], invasive cancer [301 breasts (45.8 %)], and prophylactic risk-reduction [245 breasts (37.3 %)]. A total of 210 patients (49 %) had neoadjuvant chemotherapy, 78 (18.2 %) had adjuvant chemotherapy, and 114 (26.7 %) had postmastectomy radiotherapy. Nipple tissue contained in situ cancer in 11 breasts (1.7 %) and invasive cancer in 9 breasts (1.4 %); management included repeat excision (7 cases), NAC removal (9 cases), or radiotherapy without further excision (4 cases). Ischemic complications included 13 cases (2 %) of partial nipple loss, 10 cases (1.5 %) of complete nipple loss, and 78 cases (11.9 %) of skin flap necrosis. Overall locoregional recurrence rate was 2 % (median follow-up 28 months), with a 2.4 % rate observed in the subset of patients with at least 3 years' follow-up (median 45 months). No NAC skin recurrences were observed. Conclusions. In this large, high-risk cohort, TSSM was associated with low rates of NAC complications, nipple involvement, and locoregional recurrence. Mastectomy with complete preservation of the skin envelope has been developed as an extension of skin-sparing mastectomy to improve aesthetic and psychological outcomes for patients. Nipple-sparing, or total skin-sparing, mastectomy techniques entail complete removal of all breast tissue with excision of the nipple tissue while preserving the entire skin envelope. The technique of total skin-sparing mastectomy (TSSM) is differentiated from subcutaneous mastectomy in that minimal, if any, nipple tissue is left behind. However, as with the initial reaction to skin-sparing mastectomy, there is still significant concern that preservation of the nipple-areolar complex (NAC) skin may increase locoregional recurrence rates. Although this concern has limited the widespread adoption of the technique, the recent publication of several studies with longer follow-up describing recurrence rates similar to those after skin-sparing mastectomy demonstrate that the technique does not appear to jeopardize oncologic safety

Transcriptome Analysis Reveals Strain-Specific and Conserved Stemness Genes in Schmidtea mediterranea

The planarian Schmidtea mediterranea is a powerful model organism for studying stem cell biology due to its extraordinary regenerative ability mediated by neoblasts, a population of adult somatic stem cells. Elucidation of the S. mediterranea transcriptome and the dynamics of transcript expression will increase our understanding of the gene regulatory programs that regulate stem cell function and differentiation. Here, we have used RNA-Seq to characterize the S. mediterranea transcriptome in sexual and asexual animals and in purified neoblast and differentiated cell populations. Our analysis identified many uncharacterized genes, transcripts, and alternatively spliced isoforms that are differentially expressed in a strain or cell type-specific manner. Transcriptome profiling of purified neoblasts and differentiated cells identified neoblast-enriched transcripts, many of which likely play important roles in regeneration and stem cell function. Strikingly, many of the neoblast-enriched genes are orthologs of genes whose expression is enriched in human embryonic stem cells, suggesting that a core set of genes that regulate stem cell function are conserved across metazoan species