Retention and the Intersection of Structural Inequities in a Breastfeeding Intervention Study.

Introduction: Women below the poverty threshold have lower representation and retention in breastfeeding studies. Methods: A secondary analysis of a longitudinal randomized controlled self-management for breast and nipple pain during breastfeeding study. Participants completed online surveys at discharge, weeks 1, 2, 3, 6, 9, 12, 18, and 24, with face-to-face interviews at 6 and 24 weeks. Text messages were sent to participants when modules and surveys were due. Retention was assessed in R with descriptive statistics, Mann-Whitney, Pearson's chi-square, and Cox Proportional Hazard Regression. Results: Two hundred and forty-four women (89 ≤$50,000 and 155 >$50,000) were recruited. Retention rates at 1 (93%), 2 (87%), 6 (82%), 9 (77%) and 24 (72%) weeks. For women of low income compared to those of high income there was a hazard ratio (HR) of 2.5 (p=0.0001) for retention. For non-Hispanic Black and Hispanic women compared to the combined non-Hispanic White and Other group, HRs for retention were 3.3 and 2.6 respectively (p=0.0001). Adjustment for age in the final hazard regression model of income, age, race and ethnicity decreased the HR for women of low income to 1.6 and HRs for non-Hispanic Black and Hispanic women to 2.1 and 1.9, respectively (p=.0001). However, none of the individual factors in the model achieved statistical significance. Discussion: Retention in breastfeeding studies impacts breastfeeding duration, a key lifelong preventative health behavior. Despite accessible study design, retention of women desiring to breastfeed was adversely affected by the intersection of income, race and ethnicity, and age.

Appendicitis combined with Meckel's diverticulum obstruction, perforation, and inflammation in children: Three case reports.

BACKGROUND: Meckel's diverticulum is a common congenital malformation of the small intestine, with the three most common complications being obstruction, perforation, and inflammation. To date, only a few cases have been reported worldwide. In children, the clinical symptoms are similar to appendicitis. As most of the imaging features are nonspecific, the preoperative diagnosis is not precise. In addition, the clinical characteristics are highly similar to pediatric acute appendicitis, thus special attention is necessary to distinguish Meckel's diverticulum from pediatric appendicitis. Patients with poor disease control should undergo laparoscopic exploration to avoid serious complications, including intestinal necrosis, intestinal perforation and gastrointestinal bleeding. CASE SUMMARY: This report presents three cases of appendicitis in children combined with intestinal obstruction, which was caused by fibrous bands (ligaments) arising from the top part of Meckel's diverticulum, diverticular perforation, and diverticular inflammation. All three patients, aged 11-12 years, had acute appendicitis as their initial clinical presentation. All were treated by laparoscopic surgery with a favorable outcome. A complete dataset including clinical presentation, diagnostic imaging, surgical information, and histopathologic findings was also provided. CONCLUSION: Preoperative diagnosis of Meckel's diverticulum and its complications is challenging because its clinical signs and complications are similar to those of appendicitis in children. Laparoscopy combined with laparotomy is useful for diagnosis and treatment.

Reassessing endothelial-to-mesenchymal transition in mouse bone marrow: insights from lineage tracing models.

Endothelial cells (ECs) and bone marrow stromal cells (BMSCs) play crucial roles in supporting hematopoiesis and hematopoietic regeneration. However, whether ECs are a source of BMSCs remains unclear. Here, we evaluate the contribution of endothelial-to-mesenchymal transition to BMSC generation in postnatal mice. Single-cell RNA sequencing identifies ECs expressing BMSC markers Prrx1 and Lepr; however, this could not be validated using Prrx1-Cre and Lepr-Cre transgenic mice. Additionally, only a minority of BMSCs are marked by EC lineage tracing models using Cdh5-rtTA-tetO-Cre or Tek-CreERT2. Moreover, Cdh5+ BMSCs and Tek+ BMSCs show distinct spatial distributions and characteristic mesenchymal markers, suggestive of their origination from different progenitors rather than CDH5+ TEK+ ECs. Furthermore, myeloablation induced by 5-fluorouracil treatment does not increase Cdh5+ BMSCs. Our findings indicate that ECs hardly convert to BMSCs during homeostasis and myeloablation-induced hematopoietic regeneration, highlighting the importance of using appropriate genetic models and conducting careful data interpretation in studies concerning endothelial-to-mesenchymal transition.

Severe immediate hypersensitivity to gadolinium contrast agent after targeted treatment in a patient with alveolar soft part sarcoma: A case report and review of literature.

RATIONALE: Gadolinium-based contrast agents (GBCAs), benefiting from good tolerance and safety, become the priority contrast agents in magnetic resonance imaging. Serious hypersensitivity reactions caused by GBCAs are rare, but occur occasionally. The "immune surveillance" theory proposes that lowered immune function exists in patients with malignance, which decrease the occurrence of atopy. Natural immunosurveillance that enhanced by effective treatment of malignance may increase the risk of hypersensitivity. PATIENT CONCERNS: A 29-year-old female patient suffering from intensive pain with left leg mass was admitted in our hospital. DIAGNOSES: The patient was diagnosed with alveolar soft part sarcoma by histopathology and revealed destruction of the left fibula and lung metastasis by computed tomography scan, and treated with anlotinib hydrochloride, a multi-targeted tyrosine kinase inhibitor. After 4 cycles of effective targeted therapy, the patient developed severe immediate hypersensitivity due to gadopentetate dimeglumine-enhanced magnetic resonance imaging. INTERVENTIONS AND OUTCOMES: The vital signs of the patient returned to normal after rescue. Since then, the patient has not used gadolinium contrast agent again, and currently the condition is stable and still alive. LESSONS: Severe immediate hypersensitivity might be occurred by gadolinium contrast agent in patients with malignance after effective treatment. We explored the potential mechanism of GBCA-inducing hypersensitivity in detail, by especially focusing on the changes of immune environment. Furthermore, we propose new ideas for the safe use of GBCAs in patients with malignancies.

CircECE1 promotes osteosarcoma progression through regulating RAB3D by sponging miR-588.

BACKGROUND: Circular RNAs (circRNAs) have been confirmed to be involved in cancer pathogenesis. However, the underlying mechanism of circRNA endothelin converting enzyme 1 (circECE1) in osteosarcoma (OS) development is still not understood. METHODS: The expression levels of circECE1, microRNA-588 (miR-588) and RAB3D, member RAS oncogene family (RAB3D) were gauged by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. OS cell proliferation was assessed by cell counting kit-8 (CCK-8) assay and 5-ethynyl-2'-deoxyuridine (EdU) assay. OS cell apoptosis rate and metastasis were identified by flow cytometry and transwell assay. Dual-luciferase reporter analysis and RNA immunoprecipitation (RIP) assay were performed to confirm the interactions among circECE1, miR-588 and RAB3D. Xenograft tumor models were established to explore circECE1 function in vivo. Immunohistochemistry (IHC) assay was applied to analyze RAB3D level after circECE1 knockdown. RESULTS: In OS, circECE1 expression was higher than that in normal chondroma tissues. High levels of circECE1 were positively linked to OS cell viability, proliferation, migration and invasion, and negatively linked to OS cell apoptosis rate. It was found that circECE1 was a miR-588 sponge, and miR-588 inhibitor abrogated the influence of si-circECE1 on OS cells. MiR-588 targeted RAB3D to further regulate the pathological process of OS. Moreover, silencing circECE1 blocked OS tumor growth in vivo. CONCLUSION: We elucidated the function of a novel circECE1/miR-588/RAB3D axis in OS progression.

Compact passively Q-switched single-frequency distributed Bragg reflector fiber laser at 2.0 µm.

Based mainly on the distributed Bragg reflector (DBR) short linear cavity with a 1.6-cm-long heavily Tm3+-doped germanate glass fiber and semiconductor saturable absorber mirror (SESAM), a compact passively Q-switched single-frequency fiber laser at around 1950 nm is demonstrated experimentally. By comparing pulse characters of Q-switched operations fulfilled via SESAMs with different parameters, a stable output pulse is optimized to deliver a maximum average power of 22.2 mW, a peak power of 0.67 W, and an optical signal-to-noise ratio over 61 dB. Moreover, the repetition rate of the output pulse can be tuned from 92 to 520 kHz with a narrowest pulse width of 64 ns. To the best of our knowledge, this is the first time a 2.0 µm passively Q-switched single-frequency DBR Tm3+-doped fiber laser has been realized, and it shows great potential application in remote sensing, biomedical science, and nonlinear optics.

Discovery of Novel Dual Extracellular Regulated Protein Kinases (ERK) and Phosphoinositide 3-Kinase (PI3K) Inhibitors as a Promising Strategy for Cancer Therapy.

Concomitant inhibition of MAPK and PI3K signaling pathways has been recognized as a promising strategy for cancer therapy, which effectively overcomes the drug resistance of MAPK signaling pathway-related inhibitors. Herein, we report the scaffold-hopping generation of a series of 1H-pyrazolo[3,4-d]pyrimidine dual ERK/PI3K inhibitors. Compound 32d was the most promising candidate, with potent inhibitory activities against both ERK2 and PI3Kα which displays superior anti-proliferative profiles against HCT116 and HEC1B cancer cells. Meanwhile, compound 32d possessed acceptable pharmacokinetic profiles and showed more efficacious anti-tumor activity than GDDC-0980 and the corresponding drug combination (BVD-523 + GDDC-0980) in HCT-116 xenograft model, with a tumor growth inhibitory rate of 51% without causing observable toxic effects. All the results indicated that 32d was a highly effective anticancer compound and provided a promising basis for further optimization towards dual ERK/PI3K inhibitors.

A Genome-Wide View of Transcriptional Responses during Aphis glycines Infestation in Soybean.

Soybean aphid (Aphis glycines Matsumura) is one of the major limiting factors in soybean production. The mechanism of aphid resistance in soybean remains enigmatic as little information is available about the different mechanisms of antibiosis and antixenosis. Here, we used genome-wide gene expression profiling of aphid susceptible, antibiotic, and antixenotic genotypes to investigate the underlying aphid-plant interaction mechanisms. The high expression correlation between infested and non-infested genotypes indicated that the response to aphid was controlled by a small subset of genes. Plant response to aphid infestation was faster in antibiotic genotype and the interaction in antixenotic genotype was moderation. The expression patterns of transcription factor genes in susceptible and antixenotic genotypes clustered together and were distant from those of antibiotic genotypes. Among them APETALA 2/ethylene response factors (AP2/ERF), v-myb avian myeloblastosis viral oncogene homolog (MYB), and the transcription factor contained conserved WRKYGQK domain (WRKY) were proposed to play dominant roles. The jasmonic acid-responsive pathway was dominant in aphid-soybean interaction, and salicylic acid pathway played an important role in antibiotic genotype. Callose deposition was more rapid and efficient in antibiotic genotype, while reactive oxygen species were not involved in the response to aphid attack in resistant genotypes. Our study helps to uncover important genes associated with aphid-attack response in soybean genotypes expressing antibiosis and antixenosis.

Constructing chiral bicyclo[3.2.1]octanes via palladium-catalyzed asymmetric tandem Heck/carbonylation desymmetrization of cyclopentenes.

Transition-metal-catalyzed tandem Heck/carbonylation reaction has emerged as a powerful tool for the synthesis of structurally diverse carbonyl molecules, as well as natural products and pharmaceuticals. However, the asymmetric version was rarely reported, and remains a challenging topic. Herein, we describe a palladium-catalyzed asymmetric tandem Heck/carbonylation desymmetrization of cyclopentenes. Alcohols, phenols and amines are employed as versatile coupling reagents for the construction of multifunctional chiral bicyclo[3.2.1]octanes with one all-carbon quaternary and two tertiary carbon stereogenic centers in high diastereo- and enantioselectivities. This study represents an important progress in both the asymmetric tandem Heck/carbonylation reactions and enantioselective difunctionalization of internal alkenes.

Synthesis of Indole-Fused Polycyclics via Rhodium-Catalyzed Undirected C-H Activation/Alkene Insertion.

A Rh(III)-catalyzed undirected C-H activation/alkene insertion to synthesize diversified indole-fused polycyclics has been developed. Intramolecular electrophilic cyclization generated a 3-indolyl rhodium species that went through an aryl-to-aryl 1,4-rhodium migration to realize the C-H activation. The subsequent [4 + 2] carboannulation or hydroarylation of alkenes could be achieved, respectively, by simply adjusting the additives of the reaction.

Rhodium(III)-Catalyzed Intramolecular Olefin Hydroarylation of Aromatic Aldehydes Using a Transient Directing Group.

A Rh(III)-catalyzed intramolecular olefin hydroarylation of aromatic aldehydes with a transient directing group has been described. The bidentate directing groups in situ generated from aromatic aldehydes and ß-alanine could enable the subsequent C-H activation and hydroarylation with excellent site selectivities and high functional group compatibility. The further conversion of the aldehyde group showcased the broad application prospects of this methodology.

Pd-Catalyzed Alkyne Insertion/C-H Activation/[4 + 2] Carboannulation of Alkenes to the Synthesis of Polycyclics.

An unprecedented Pd-catalyzed alkyne insertion/C-H activation/intramolecular [4 + 2] carboannulation of alkenes has been reported. In this transformation, the C-H activation was triggered by an in situ generated alkenylpalladium species via the Pd-catalyzed cross-coupling reaction of aryl iodides and alkynes. Subsequently, the resulting five-membered C, C-palladacycle intermediates were added across the alkenes, providing a unique approach to access diversified polycyclics in good efficiency. Two new rings and three C-C bonds were formed in one pot.

Comparative Proteomic Analysis of Coregulation of CIPK14 and WHIRLY1/3 Mediated Pale Yellowing of Leaves in Arabidopsis.

Pale yellowing of leaf variegation is observed in the mutant Arabidopsis lines Calcineurin B-Like-Interacting Protein Kinase14 (CIPK14) overexpression (oeCIPK14) and double-knockout WHIRLY1/WHIRLY3 (why1/3). Further, the relative distribution of WHIRLY1 (WHY1) protein between plastids and the nucleus is affected by the phosphorylation of WHY1 by CIPK14. To elucidate the coregulation of CIPK14 and WHIRLY1/WHIRLY3-mediated pale yellowing of leaves, a differential proteomic analysis was conducted between the oeCIPK14 variegated (oeCIPK14-var) line, why1/3 variegated (why1/3-var) line, and wild type (WT). More than 800 protein spots were resolved on each gel, and 67 differentially abundant proteins (DAPs) were identified by matrix-assisted laser desorption ionization-time of flight/time of flight mass spectrometry (MALDI-TOF/TOF-MS). Of these 67 proteins, 34 DAPs were in the oeCIPK14-var line and 33 DAPs were in the why1/3-var line compared to the WT. Five overlapping proteins were differentially expressed in both the oeCIPK14-var and why1/3-var lines: ATP-dependent Clp protease proteolytic subunit-related protein 3 (ClpR3), Ribulose bisphosphate carboxylase large chain (RBCL), Beta-amylase 3 (BAM3), Ribosome-recycling factor (RRF), and Ribulose bisphosphate carboxylase small chain (RBCS). Bioinformatics analysis showed that most of the DAPs are involved in photosynthesis, defense and antioxidation pathways, protein metabolism, amino acid metabolism, energy metabolism, malate biosynthesis, lipid metabolism, and transcription. Thus, in the why1/3-var and oeCIPK14-var lines, there was a decrease in the photosystem parameters, including the content of chlorophyll, the photochemical efficiency of photosystem (PS II) (Fv/Fm), and electron transport rates (ETRs), but there was an increase in non-photochemical quenching (NPQ). Both mutants showed high sensitivity to intense light. Based on the annotation of the DAPs from both why1/3-var and oeCIPK14-var lines, we conclude that the CIPK14 phosphorylation-mediated WHY1 deficiency in plastids is related to the impairment of protein metabolism, leading to chloroplast dysfunction.

PET/CT in the diagnosis and prognosis of osteosarcoma.

Osteosarcoma is an aggressive malignancy that usually occurs in children and young adults, and long-term survival is only about 20% in patients with metastasis or recurrent disease. Traditional non-invasive techniques, such as positron-emission tomography (PET) scanning, magnetic resonance imaging (MRI) or computed tomography (CT) scanning, may not identify single lesions in the early stage or accurately detect small lesions. A novel technique, positron emission tomography/computed tomography (PET/CT), which is widely used in clinical practice, shows more accuracy, sensitivity, and specificity in the diagnosis of osteosarcoma. PET/CT provides information not only for diagnosis of primary lesion and metastases, but also for histological response to neoadjuvant chemotherapy and prognosis. Here, we review the role of PET/CT in the diagnosis and prognosis of osteosarcoma.

Fenobody: A Ferritin-Displayed Nanobody with High Apparent Affinity and Half-Life Extension.

Nanobodies consist of a single domain variable fragment of a camelid heavy-chain antibody. Nanobodies have potential applications in biomedical fields because of their simple production procedures and low cost. Occasionally, nanobody clones of interest exhibit low affinities for their target antigens, which, together with their short half-life limit bioanalytical or therapeutic applications. Here, we developed a novel platform we named fenobody, in which a nanobody developed against H5N1 virus is displayed on the surface of ferritin in the form of a 24mer. We constructed a fenobody by substituting the fifth helix of ferritin with the nanobody. TEM analysis showed that nanobodies were displayed on the surface of ferritin in the form of 6 × 4 bundles, and that these clustered nanobodies are flexible for antigen binding in spatial structure. Comparing fenobodies with conventional nanobodies currently used revealed that the antigen binding apparent affinity of anti-H5N1 fenobody was dramatically increased (∼360-fold). Crucially, their half-life extension in a murine model was 10-fold longer than anti-H5N1 nanobody. In addition, we found that our fenobodies are highly expressed in Escherichia coli, and are both soluble and thermo-stable nanocages that self-assemble as 24-polymers. In conclusion, our results demonstrate that fenobodies have unique advantages over currently available systems for apparent affinity enhancement and half-life extension of nanobodies. Our fenobody system presents a suitable platform for various large-scale biotechnological processes and should greatly facilitate the application of nanobody technology in these areas.

Origin of the Reflectin Gene and Hierarchical Assembly of Its Protein.

Cephalopods, the group of animals including octopus, squid, and cuttlefish, have remarkable ability to instantly modulate body coloration and patterns so as to blend into surrounding environments [1, 2] or send warning signals to other animals [3]. Reflectin is expressed exclusively in cephalopods, filling the lamellae of intracellular Bragg reflectors that exhibit dynamic iridescence and structural color change [4]. Here, we trace the possible origin of the reflectin gene back to a transposon from the symbiotic bioluminescent bacterium Vibrio fischeri and report the hierarchical structural architecture of reflectin protein. Intrinsic self-assembly, and higher-order assembly tightly modulated by aromatic compounds, provide insights into the formation of multilayer reflectors in iridophores and spherical microparticles in leucophores and may form the basis of structural color change in cephalopods. Self-assembly and higher-order assembly in reflectin originated from a core repeating octapeptide (here named protopeptide), which may be from the same symbiotic bacteria. The origin of the reflectin gene and assembly features of reflectin protein are of considerable biological interest. The hierarchical structural architecture of reflectin and its domain and protopeptide not only provide insights for bioinspired photonic materials but also serve as unique "assembly tags" and feasible molecular platforms in biotechnology.

Defect Facilitated Phonon Transport through Kinks in Boron Carbide Nanowires.

Nanowires of complex morphologies, such as kinked wires, have been recently synthesized and demonstrated for novel devices and applications. However, the effects of these morphologies on thermal transport have not been well studied. Through systematic experimental measurements, we show that single-crystalline, defect-free kinks in boron carbide nanowires can pose a thermal resistance up to ∼30 times larger than that of a straight wire segment of equivalent length. Analysis suggests that this pronounced resistance can be attributed to the combined effects of backscattering of highly focused phonons and required mode conversion at the kink. Interestingly, it is also found that instead of posing resistance, structural defects in the kink can actually assist phonon transport through the kink and reduce its resistance. Given the common kink-like wire morphology in nanoelectronic devices and required low thermal conductivity for thermoelectric devices, these findings have important implications in precise thermal management of electronic devices and thermoelectrics.

Influence of Intracranial Air on Electrode Position and Clinical Outcomes following Deep Brain Stimulation for Parkinson's Disease.

BACKGROUND: The introduction of intracranial air during deep brain stimulation (DBS) surgery is believed to negatively impact targeting accuracy and clinical outcomes. OBJECTIVE: To quantify the relationship between intracranial air (ICA) volumes, targeting accuracy, and clinical outcomes in patients undergoing subthalamic nucleus (STN) DBS for Parkinson's disease. METHODS: ICA in 73 consecutive STN DBS cases (146 leads) was measured by high-resolution CT and correlated with proximal lead bowing, electrode displacement, targeting accuracy, and clinical outcomes at 6 and 12 months. RESULTS: There was a statistically significant correlation of ICA volume (mean ± SEM: 21.3 ± 13.7 cm3) and proximal lead bowing (2.8 ± 1.4 mm, r = 0.34, p = 0.01). There was no significant correlation of ICA with targeting error (2.0 ± 1.2 mm), distal contact deviation (1.2 ± 0.7 mm), motor Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III improvement at 6 months (42.3 ± 4.5%) or 12 months (30.3 ± 7.7%), or dopaminergic medication reduction at 6 months (44.7± 4.2%) or 12 months (32.9 ± 5.9%). Comparison of top and bottom ICA quintile extremes also revealed no differences in these measures. CONCLUSIONS: Though the proximal DBS lead bends in association with ICA, movement of the distal contact, targeting error, and clinical outcomes are not affected by ICA. This unexpected finding is maintained at ICA quintile extremes.

Stent-assisted coiling of cerebrovascular aneurysms: experience at a large tertiary care center with a focus on predictors of recurrence.

BACKGROUND: Stent-assisted coiling is commonly used to treat wide-necked and fusiform cerebral aneurysms. We evaluated our institutional experience with stent-assisted coiling of cerebral aneurysms to elucidate potential risk factors for recurrence. METHODS: A retrospective analysis of patients undergoing stent-assisted coiling of cerebral aneurysms from 2005 to 2012 resulted in 122 patients with 122 aneurysms. Demographic, peri-procedural, medical comorbidity, and follow-up data were collected. Primary outcomes of interest were procedural safety, efficacy, and aneurysm recurrence. Univariate and multivariate logistic regression and χ2 tests determined the statistical significance of the risk factors. RESULTS: All 122 stent-assisted coiling procedures led to satisfactory obliteration of the aneurysm (3.3% complication rate). Twenty-one (17.2%) patients experienced recurrence at average follow-up of 297 days. Fifteen (71.4%) clinically significant recurrences required retreatment. Eleven of 30 (36.7%) procedures using Enterprise stents had recurrence compared with only 10 of 92 (10.9%) procedures using Neuroform stents (p=0.001). Average coiling packing density (PD) was 20.3% with Enterprise stents and 22.5% with Neuroform stents (p=0.8). In multivariate logistic regression, recurrences requiring recoiling were significantly associated with Enterprise stents (OR 8.57, 95% CI 1.97 to 37.19; p=0.004), females (OR 0.19, 95% CI 0.04 to 1.00; p=0.05), and postoperative dextran use (OR 8.42, 95% CI 1.40 to 50.58; p=0.02). Aneurysms with <20% PD were more likely to have a clinically significant recurrence than aneurysms with >20% PD (19% vs 5.1%; p=0.02). CONCLUSIONS: Stent-assisted coiling for wide-necked cerebral aneurysms has a high therapeutic success rate with low procedure-related morbidity and mortality. Clinically significant recurrences may occur more frequently with Enterprise stents, in aneurysms with low PD, and with post-procedural dextran use.

Thermal conductivity of individual silicon nanoribbons.

The thermal conductivities of two groups of silicon nanoribbons of ∼20 and ∼30 nm thickness and various widths have been measured and analyzed through combining the Callaway model and the Fuchs-Sondheimer (FS) reduction function. The results show that while the data for the ∼30 nm thick ribbons can be well-explained by the classical size effect, the measured thermal conductivities for the ∼20 nm thick ribbons deviate from the prediction remarkably, and size effects beyond phonon-boundary scattering must be considered. The measurements of the Young's modulus of the thin nanoribbons yield significantly lower values than the corresponding bulk value, which could lead to a reduced phonon group velocity and subsequently thermal conductivity. This study helps to build a regime map for thermal conductivity versus nanostructures' surface-area-to-volume ratio that clearly delineates two regions where size effects beyond the Casimir limit are important or not important.