Adipose Tissue Distribution and Survival Among Women with Nonmetastatic Breast Cancer.

ObjectivePrevious studies of breast cancer survival have not considered specific depots of adipose tissue such as subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT).MethodsThis study assessed these relationships among 3,235 women with stage II and III breast cancer diagnosed between 2005 and 2013 at Kaiser Permanente Northern California and between 2000 and 2012 at Dana Farber Cancer Institute. SAT and VAT areas (in centimeters squared) were calculated from routine computed tomography scans within 6 (median: 1.2) months of diagnosis, covariates were collected from electronic health records, and vital status was assessed by death records. Hazard ratios (HRs) and 95% CIs were estimated using Cox regression.ResultsSAT and VAT ranged from 19.0 to 891 cm2 and from 0.484 to 454 cm2 , respectively. SAT was related to increased risk of death (127-cm2 increase; HR [95% CI]: 1.13 [1.02-1.26]), but no relationship was found with VAT (78.18-cm2 increase; HR [95% CI]: 1.02 [0.91-1.14]). An association with VAT was noted among women with stage II cancer (stage II: HR: 1.17 [95% CI: 0.99-1.39]; stage III: HR: 0.90 [95% CI: 0.76-1.07]; P interaction < 0.01). Joint increases in SAT and VAT were associated with mortality above either alone (simultaneous 1-SD increase: HR 1.19 [95% CI: 1.05-1.34]).ConclusionsSAT may be an underappreciated risk factor for breast cancer-related death

Stroke impact on mortality and psychologic morbidity within the Childhood Cancer Survivor Study.

BackgroundPoor socioeconomic and health-related quality of life (HRQOL) outcomes in survivors of childhood cancer can lead to distress and overall negatively impact the lives of these individuals. The current report has highlighted the impact of stroke and stroke recurrence on mortality, psychological HRQOL, and socioeconomic outcomes within the Childhood Cancer Survivor Study (CCSS).MethodsThe CCSS is a retrospective cohort study with longitudinal follow-up concerning survivors of pediatric cancer who were diagnosed between 1970 and 1986. Mortality rates per 100 person-years were calculated across 3 periods: 1) prior to stroke; 2) after first stroke and before recurrent stroke; and 3) after recurrent stroke. Socioeconomic outcomes, the standardized Brief Symptoms Inventory-18, the Medical Outcomes Study 36-Item Short Form Health Survey, and the CCSS-Neurocognitive Questionnaire also were assessed.ResultsAmong 14,358 participants (median age, 39.7 years), 224 had a stroke after their cancer diagnosis (single stroke in 161 patients and recurrent stroke in 63 patients). Based on 2636 deaths, all-cause late mortality rates were 0.70 (95% CI, 0.68-0.73) prior to stroke, 1.03 (95% CI, 0.73-1.46) after the first stroke, and 2.42 (95% CI, 1.48-3.94) after the recurrent stroke. Among 7304 survivors, those with stroke were more likely to live with a caregiver (single stroke odds ratio [OR], 2.3 [95% CI, 1.4-3.8]; and recurrent stroke OR, 5.3 [95% CI, 1.7-16.8]) compared with stroke-free survivors. Stroke negatively impacted task efficiency (single stroke OR, 2.4 [95% CI, 1.4-4.1] and recurrent stroke OR, 3.3 [95% CI, 1.1-10.3]) and memory (single stroke OR, 2.1 [95% CI, 1.2-3.7]; and recurrent stroke OR, 3.5 [95% CI, 1.1-10.5]).ConclusionsStroke and stroke recurrence are associated with increased mortality and negatively impact HRQOL measures in survivors of pediatric cancer

Zwitterionic PEG-PC hydrogels modulate the foreign body response in a modulus-dependent manner

Reducing the foreign body response (FBR) to implanted biomaterials will enhance their performance in tissue engineering. Poly(ethylene glycol) (PEG) hydrogels are increasingly popular for this application due to their low cost, ease of use, and the ability to tune their compliance via molecular weight and crosslinking densities. PEG hydrogels can elicit chronic inflammation in vivo, but recent evidence has suggested that extremely hydrophilic, zwitterionic materials and particles can evade the immune system. To combine the advantages of PEG-based hydrogels with the hydrophilicity of zwitterions, we synthesized hydrogels with co-monomers PEG and the zwitterion phosphorylcholine (PC). Recent evidence suggests that stiff hydrogels elicit increased immune cell adhesion to hydrogels, which we attempted to reduce by increasing hydrogel hydrophilicity. Surprisingly, hydrogels with the highest amount of zwitterionic co-monomer elicited the highest FBR we observed. Lowering the hydrogel modulus (165 kPa to 3 kPa), or PC content (20 wt% to 0 wt%), mitigated this effect. A high density of macrophages was found at the surface of implants associated with a high FBR, and mass spectrometry analysis of the proteins adsorbed to these gels implicated extracellular matrix, immune response, and cell adhesion protein categories as drivers of macrophage recruitment to these hydrogels. Overall, we show that modulus regulates macrophage adhesion to zwitterionic-PEG hydrogels, and demonstrate that chemical modifications to hydrogels should be studied in parallel with their physical properties to optimize implant design

A common type system for clinical natural language processing

Background: One challenge in reusing clinical data stored in electronic medical records is that these data are heterogenous. Clinical Natural Language Processing (NLP) plays an important role in transforming information in clinical text to a standard representation that is comparable and interoperable. Information may be processed and shared when a type system specifies the allowable data structures. Therefore, we aim to define a common type system for clinical NLP that enables interoperability between structured and unstructured data generated in different clinical settings. Results: We describe a common type system for clinical NLP that has an end target of deep semantics based on Clinical Element Models (CEMs), thus interoperating with structured data and accommodating diverse NLP approaches. The type system has been implemented in UIMA (Unstructured Information Management Architecture) and is fully functional in a popular open-source clinical NLP system, cTAKES (clinical Text Analysis and Knowledge Extraction System) versions 2.0 and later. Conclusions: We have created a type system that targets deep semantics, thereby allowing for NLP systems to encapsulate knowledge from text and share it alongside heterogenous clinical data sources. Rather than surface semantics that are typically the end product of NLP algorithms, CEM-based semantics explicitly build in deep clinical semantics as the point of interoperability with more structured data types

Formation of CO2 on a carbonaceous surface: a quantum chemical study

The formation of CO2 in the gas phase and on a polyaromatic hydrocarbon surface (coronene) via three possible pathways is investigated with density functional theory. Calculations show that the coronene surface catalyses the formation of CO2 on model grain surfaces. The addition of O-3 to CO is activated by 2530 K in the gas phase. This barrier is lowered by 253 K for the Eley-Rideal mechanism and 952 K for the hot-atom mechanism on the surface of coronene. Alternative pathways for the formation of CO2 are the addition of O-3 to the HCO radical, followed by dissociation of the HCO2 intermediate. The O + HCO addition is barrierless in the gas phase and on the surface and is more than sufficiently exothermic to subsequently cleave the H-C bond. The third mechanism, OH + CO addition followed by H removal from the energized HOCO intermediate, has a gas-phase exit barrier that is 1160 K lower than the entrance barrier. On the coronene surface, however, both barriers are almost equal. Because the HOCO intermediate can also be stabilized by energy dissipation to the surface, it is anticipated that for the surface reaction the adsorbed HOCO could be a long-lived intermediate. In this case, the stabilized HOCO intermediate could react, in a barrierless manner, with a hydrogen atom to form H-2 + CO2, HCO2H, or H2O + CO

Chemical and Biological Assessment of Angelica Roots from Different Cultivated Regions in a Chinese Herbal Decoction Danggui Buxue Tang

Roots of Angelica sinensis (Danggui) have been used in promoting blood circulation as herbal medicine for over 2000 years in China. Another species of Angelica roots called A. gigas is being used in Korea. To reveal the efficiency of different Angelica roots, the chemical and biological properties of Angelica roots from different cultivated regions were compared. Roots of A. sinensis contained higher levels of ferulic acid, Z-ligustilide, and senkyunolide A, while high amounts of butylphthalide and Z-butylenephthalide were found in A. gigas roots. The extracts deriving from A. gigas roots showed better effects in osteogenic and estrogenic properties than that of A. sinensis from China. However, this difference was markedly reduced when the Angelica roots were being prepared in a Chinese herbal decoction together with Astragali Radix as Danggui Buxue Tang. In contrast, the herbal decoction prepared from A. sinensis roots showed better responses in cell cultures. In addition, the extracts of A. gigas roots showed strong cell toxicity both as single herb and as Danggui Buxue Tang. This result revealed the distinct properties of Angelica roots from China and Korea suggesting the specific usage of herb in preparing a unique herbal decoction

A candidate relativistic tidal disruption event at 340 Mpc

We present observations of an extreme radio flare, VT J024345.70-284040.08, hereafter VT J0243, from the nucleus of a galaxy with evidence for historic Seyfert activity at redshift $z=0.074$. Between NRAO VLA Sky Survey observations in 1993 to VLA Sky Survey observations in 2018, VT J0243 rose from a ${\sim}$GHz radio luminosity of $\nu L_\nu \lesssim 10^{38}$ erg s$^{-1}$ to $\nu L_\nu{\sim}10^{40}$ erg s$^{-1}$, and still continues to brighten. The radio spectral energy distribution (SED) evolution is consistent with a nascent jet that has slowed over ${\sim}3000$ days with an average $0.1 < \langle \beta \rangle < 0.6$. The jet is energetic (${\sim}10^{51-52}$ erg), and had a radius ${\sim}0.7$ pc in Dec. 2021. X-ray observations suggest a persistent or evolving corona, possibly associated with an accretion disk, and IR and optical observations constrain any high-energy counterpart to be sub-Eddington. VT J0243 may be an example of a young, off-axis radio jet from a slowly evolving tidal disruption event. Other more mysterious triggers for the accretion enhancement and jet launching are possible. In either case, VT J0243 is a unique example of a nascent jet, highlighting the unknown connection between supermassive black holes, the properties of their accretion flows, and jet launching.Comment: 20 pages, 5 figures, 3 tables. Submitted to Ap

Impact of detergent on biophysical properties and immune response of the IpaDB fusion protein, a candidate subunit vaccine against Shigella species.

Shigella spp. are causative agents of bacillary dysentery, a human illness with high global morbidity levels, particularly among elderly and infant populations. Shigella infects via the fecal-oral route, and its virulence is dependent upon a type III secretion system (T3SS). Two components of the exposed needle tip complex of the Shigella T3SS, invasion plasmid antigen D (IpaD) and IpaB, have been identified as broadly protective antigens in the mouse lethal pneumonia model. A recombinant fusion protein (DB fusion) was created by joining the coding sequences of IpaD and IpaB. The DB fusion is coexpressed with IpaB's cognate chaperone, IpgC, for proper recombinant expression. The chaperone can then be removed by using the mild detergents octyl oligooxyethelene (OPOE) or N,N-dimethyldodecylamine N-oxide (LDAO). The DB fusion in OPOE or LDAO was used for biophysical characterization and subsequent construction of an empirical phase diagram (EPD). The EPD showed that the DB fusion in OPOE is most stable at neutral pH below 55°C. In contrast, the DB fusion in LDAO exhibited remarkable thermal plasticity, since this detergent prevents the loss of secondary and tertiary structures after thermal unfolding at 90°C, as well as preventing thermally induced aggregation. Moreover, the DB fusion in LDAO induced higher interleukin-17 secretion and provided a higher protective efficacy in a mouse challenge model than did the DB fusion in OPOE. These data indicate that LDAO might introduce plasticity to the protein, promoting thermal resilience and enhanced protective efficacy, which may be important in its use as a subunit vaccine

Higher carbohydrate intake is associated with increased risk of allâ cause and diseaseâ specific mortality in head and neck cancer patients: results from a prospective cohort study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145268/1/ijc31413.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145268/2/ijc31413-sup-0001-suppinfo01.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145268/3/ijc31413_am.pd

The effect of compressive strain on the Raman modes of the dry and hydrated BaCe0.8Y0.2O3 proton conductor

The BaCe0.8Y0.2O3-{\delta} proton conductor under hydration and under compressive strain has been analyzed with high pressure Raman spectroscopy and high pressure x-ray diffraction. The pressure dependent variation of the Ag and B2g bending modes from the O-Ce-O unit is suppressed when the proton conductor is hydrated, affecting directly the proton transfer by locally changing the electron density of the oxygen ions. Compressive strain causes a hardening of the Ce-O stretching bond. The activation barrier for proton conductivity is raised, in line with recent findings using high pressure and high temperature impedance spectroscopy. The increasing Raman frequency of the B1g and B3g modes thus implies that the phonons become hardened and increase the vibration energy in the a-c crystal plane upon compressive strain, whereas phonons are relaxed in the b-axis, and thus reveal softening of the Ag and B2g modes. Lattice toughening in the a-c crystal plane raises therefore a higher activation barrier for proton transfer and thus anisotropic conductivity. The experimental findings of the interaction of protons with the ceramic host lattice under external strain may provide a general guideline for yet to develop epitaxial strained proton conducting thin film systems with high proton mobility and low activation energy