bluuebunny/crossref_metadata_2025 huggingface dataset:
3275 Nonclinical factors associated with contralateral prophylactic mastectomy among breast cancer patients in the Surveillance, Epidemiology, and End Results (SEER) database
Authors: Copeland Timothy Paul , Dworsky Jill , Raghavan Kesav , Franc Benjamin
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: The study aims to measure the associations between nonclinical factors and the likelihood of electing contralateral prophylactic mastectomy [(CPM) i.e. bilateral mastectomy for unilateral cancer] among women with breast cancer, with a focus on the roles of race, relationship status, and geographic location. The outcome of interest is a dichotomized surgery type variable (i.e. CPM versus other surgery). METHODS/STUDY POPULATION:. The Surveillance, Epidemiology, and End Results registry was queried to identify female breast cancer patients diagnosed at stage IA through IIIC from 2010 through 2015 and received surgery as part of their primary treatment (n=174,776). A multilevel logistic regression was used to model likelihood of CPM versus less aggressive surgical treatment (i.e. breast conserving surgery or unilateral mastectomy). Fixed-effects included age at diagnosis, race, relationship status, insurance type, county-level median income, county-level population density, stage at diagnosis (low-stage, IA-IIB; advanced-stage, IIIA-IIIC), an interaction term between race and stage at diagnosis, and breast tumor subtype. County of residence was used as a random-effect. RESULTS/ANTICIPATED RESULTS: Among women with low-stage cancer, compared to the reference class of white women, black women had 0.57 times lower odds of CPM (p<0.0001), Hispanic women had 0.69 times lower odds of CPM (p<0.0001), and Asian women had 0.60 times lower odds of CPM (p<0.0001). Among women with advanced-stage cancer, compared to white women, black women had 0.42 times lower odds of CPM (p<0.0001), Hispanic women had 0.51 times lower odds of CPM (p<0.0001), and Asian women had 0.45 times lower odds of CPM (p<0.0001). Compared to the reference class of single, never-married women, divorced/separated women had 1.25 times greater odds of CPM (p<0.0001), widowed women had 1.11 times greater odds of CPM (p=0.009), and married/partnered women had 1.18 times greater odds of CPM (p<0.0001). County-level variation from the random-effect (MOR, 1.49; p<0.001) had a greater influence on CPM election than fixed-effects for insurance class, breast tumor subtype, county median income, county population density, and year of surgery. DISCUSSION/SIGNIFICANCE OF IMPACT: The nonclinical factors associated with variation in breast cancer surgical decision-making suggest patients and providers both may benefit from further education about surgical treatment options. Providers may also benefit from educational materials that highlight treatment selection disparities within specific contexts, such as surgery for primary unilateral breast cancer. To more narrowly tailor future policy interventions, an additional mixed-methods exploration is recommended to clarify how relationship status and location serve as mechanisms for breast cancer decision-making.
3055 Reconstruction of Patient-specific Distal Airway Regeneration Patterns in COPD
Authors: Mahjour Seyed Babak , Gomi Kazunori , Rustam Samir , Dolma Phurbu , Krishnan Jamuna , Elemento Olivier , D’Ovidio Frank , Blackwell Timothy S. , Randell Scott , Shaykhiev Renat
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: The objective of this study was to reconstruct patient-specific distal airway patterns at the tissue- and single-cell resolution and develop personalized distal airway models based on utilization of patient-derived DABCs and autologous region-specific stromal cells. METHODS/STUDY POPULATION: Patient-specific distal airway units, containing parental small bronchiole (<2 mm in diameter, >12th generation) and daughter airway branches, including pre-terminal/terminal bronchioles, leading to alveoli (3-7 units/lung), were dissected. Epithelial and stromal cells were isolated from these units and processed for ddSeq single-cell RNA-sequencing (n=6 samples). Autologous DABCs and stromal cells were isolated, propagated, biobanked, and used for establishment of patient-specific distal airway models (3D-organoids and air-liquid interface-based airway wall model; n=10 samples). Region-specific tissue patterns were evaluated using immunofluorescence and laser-capture microdissection (LCM; n=6 samples). RESULTS/ANTICIPATED RESULTS: Single-cell-based human distal airway transcriptome map (constructed based on the analysis of >6,500 distal airway cells obtained from 6 subjects) identified physiological and COPD-relevant distal airway differentiation patterns, including distal airway-specific secretory phenotype (DASP) characterized with high expression of secretoglobins 3A2 and 3A1, surfactant proteins SFTPB and SFTPA2, and mucin 1, unique signatures of DABCs, and stromal (fibroblasts, smooth muscle, endothelial cell subpopulations) and immune (macrophage, T cells, B cell, mast cells). Immunofluorescence analysis and LCM confirmed distribution of cell type-specific markers with differential expression patterns of DABC and DASP signatures. Patient-derived DABC-stromal co-culture models reproduced 3 regenerative patterns: 1) physiological (high DABC-clonogenic potency, establishment of polarized differentiated organoids and DASP-expressing epithelia); 2) hypo-regenerative (failure of DABCs to form clones, spheres and mechanically stable differentiated epithelial barrier); and 3) hyperplastic (generation of DABC hyperplasia accompanied in some COPD samples by mucous-cell hyperplasia mimicking in vivo remodeling patterns). DISCUSSION/SIGNIFICANCE OF IMPACT: Patient-specific maps and models of distal airway regeneration patterns have been established in this study, which can be used to identify candidate pathways that mediate disease-relevant airway remodeling and potentially utilized as pre-clinical platforms for developing personalized therapeutic approaches to suppress the progression of distal airway remodeling in chronic lung diseases, including COPD.
3352 Surgical Adjuvant of Immunomodulatory Gene Circuits for Treatment of Glioblastoma
Authors: Spatz Jordan Matthew , Wu Ming Ru , Weisinger Karen , Lu Tim , Aghi Manish
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: Glioblastoma (GBM) is a brain cancer with a devastatingly short overall survival of under two years. The poor prognosis of GBM is largely due to cell invasion and maintenance of cancer initiating cells that evade the brain’s innate and adaptive immune responses which enables escape from surgical resection and drives inevitable recurrence. While targeting the brain’s immune microenvironment has long been proposed as a strategy for treating GBM, translational progress has been slow, underscoring the need to investigate the brain’s immune microenvironment for therapeutic avenues. METHODS/STUDY POPULATION: Recent advancements in tunable synthetic immunomodulatory gene circuits targeting metastatic cancers has demonstrated the novel ability to use engineering principles to induce infiltrative cancer cells to express combinatorial immunomodulatory outputs that enable T-cell killing4. Our central hypothesis is: we will be able to significantly improve survival with a lasting immune-mediated control of GBM by using synthetic immunomodulatory gene circuits driving GBM cells to express a local combination of immunomodulatory proteins: human IL15, a surface T-cell engager, PD-L1-CD3 bispecific antibody, and the protein, LIGHT (TNFRSF14). Importantly, the co-expression of LIGHT and anti-PD-L1 therapies was recently shown to rescue PD-L1 checkpoint blockage in the preclinical models of brain tumors and significant enhance survival outcomes highlighting the benefits of novel combinations of immunomodulatory proteins for treatment of GBM. To identify genes whose expression is dramatically upregulated in GBM compared to normal human brain cells, a pooled of six thousand lentiviral oncogene promoters that drive expression of a red-fluorescent protein has been infected into three human GBM cell lines. RESULTS/ANTICIPATED RESULTS: We have successfully infected our GBM cells and are preparing samples for next generation DNA sequencing to determine highly active promoters in GBM that are not expressed in multiple normal brain cells types, astrocytes and neurons. These chosen promoters will then be used to drive an AND gate logic gene circuit immunotherapy outputs which is currently under development for both in-vitro and in-vivo experiments. DISCUSSION/SIGNIFICANCE OF IMPACT: We anticipate that local expression of multiple immune effectors proteins will significantly enhance tumor control and survival in both synergistic murine and human-murine xenograft pre-clinical models of GBM. Ultimately, our goal is to rapidly translate this technology advance into the clinical trial for adult GBM patients.
3107 Understanding barriers to and facilitators of a healthy lifestyle of Hispanic adults with end stage renal disease in hemodialysis: Intensive Development and Experiences in Advancement of Research and Increased Opportunities (IDEARIO)
Authors: Orellano Colon Elsa M , Lugo Luna S. , Rodríguez Ivelisse Rivera , Valentín Carro Natalia , Arbelo Nelson Almodovar
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: Physical inactivity and mineral imbalances greatly contribute to morbidity and mortality in patients with end-stage renal disease (ESRD). Barriers for engaging in physical activity and adhering to the hemodialysis diet have been reported predominantly with white participants from countries other than Puerto Rico. Therefore, this study’s aims were to explore the barriers and facilitators that Hispanic adults with end-stage renal disease encountered for engaging in physical activity and adhering to the hemodialysis diet. METHODS/STUDY POPULATION: Three focus groups were conducted among 19 adults living with ESRD who received services from a renal center in Puerto Rico. Sessions were recorded, transcribed, and coded first using inductive methods. RESULTS/ANTICIPATED RESULTS: The presence of fatigue, lack of acceptance of the renal condition, and lack of knowledge of appropriate exercises for patients in hemodialysis were the most frequently reported barriers to engage in physical activities. Cost of the renal diet, limited availability of the renal diet products, the restrictive nature and the lack of Puerto Rican taste of the renal diet, and inadequate educational materials were the most frequent barriers to adhere to the hemodialysis diet reported by the sample. The most commonly reported facilitators to engaging in physical activities were having a positive attitude, opportunities for group exercises, and listening to Hispanic music while exercising. Health benefits, family support, having financial resources, availability of community resources, and having willpower were the most commonly reported facilitators to adhere to the hemodialysis diet. DISCUSSION/SIGNIFICANCE OF IMPACT: We identified a number of culturally relevant individual, interpersonal, institutional, and community-related barriers and facilitators to physical activity and adherence to the hemodialysis diet in patients with ESRD living in Puerto Rico. Evidence-based solutions to overcome these barriers and strategies for enhancing these facilitators should be addressed in future studies aimed at increasing the level of physical activity and increasing adherence to the hemodialysis diet in patients with ESRD living in Puerto Rico.
3486 Sex Differences in the Effects of Severe Food Restriction on Electrolyte Balance
Authors: Queiroz Almeida Jonathas Fernandes , Souza Aline , Ji Hong , Sandberg Kathryn
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: The goal of this study was to determine if there are any sex differences in the pathophysiological effects of sFR. METHODS/STUDY POPULATION: Male Fischer rats (4-month-old) were maintained on a control (CT) (ad libitum regular chow; n=8) or sFR (60% reduction of daily food intake, n=8) diet for 2 weeks. On days 1, 2, 3 and 14, the rats were placed in metabolic cages for food and water intake and 24-hour urine collection. Body weight (BW) is measured daily. After 2 weeks, the animals are given free access to normal chow for 3 months. Short-term and long-term effects of sFR on blood pressure and heart rate will be measured. RESULTS/ANTICIPATED RESULTS: After 2 weeks, the male CT group gained 7% BW (p <0.05), while BW in the sFR males was reduced by 12% (p<0.05 vs. CT). In contrast, female controls did not gain BW while the sFR females lost 18% of their BW. Water intake was reduced by 35%, which was similar to the reduction in females (p=0.18). The hematocrit of sFR male rats was higher (51.1%) than the CT group (45.2%, p<0.05), which was most likely due to the 6% reduction in plasma volume. A similar effect on hematocrit was observed in sRF females. Similarly, also to female rats, sFR had no effect on Na+ and K+ plasma or urine concentrations by day 14 in the male rats. DISCUSSION/SIGNIFICANCE OF IMPACT: sFR has similar effects on electrolyte balance in males and females. Ongoing studies will determine if there is any sex difference in the effects of sFR on blood pressure, heart rate and susceptibility to hypertension and cardiac injury.
3437 Associations of aspirin, non-aspirin NSAIDs, statins, and metformin with risk of biliary cancer: A Swedish population-based cohort study
Authors: Bonilla Lorena Marcano , Schleck Cathy , Harmsen William , Therneau Terry , Sadr-Azodi Omid , Roberts Lewis R , Brusselaers Nele
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: In an effort to elucidate the role of potentially cancer chemopreventive drugs, we leveraged the Mayo Clinic-Karolinska Institute collaboration to create a multidisciplinary team that included an epidemiologist, statisticians, and physicians. We performed a population-based cohort study to examine the association between low dose aspirin, non-aspirin NSAIDs, statins, metformin, other risk factors and the risk of biliary tract cancer (BTC), while assessing confounding by sex. METHODS/STUDY POPULATION: We conducted a nationwide Swedish population-based cohort study using the Swedish Prescribed Drug Registry, which virtually completely enumerates use of prescribed medications nationwide since 2005. BTC diagnosis (intrahepatic cholangiocarcinoma [iCCA], extrahepatic cholangiocarcinoma [eCCA] or gallbladder cancer [GBC]) was ascertained from the Swedish Cancer Registry. Age-scaled Cox models, with exposure as time-varying covariates, were used to calculate hazard ratios (HRs), separately for men and women. RESULTS/ANTICIPATED RESULTS: In the 5.7 million person cohort, the risk of iCCA was significantly lower in men using statins (HR 0.62,95%CI 0.39-1.00, p = 0.05), with a non-significant reduction in women. Statin use was associated with a significantly decreased risk of eCCA in both women (HR 0.60,0.38-0.94, p = 0.03) and men (HR 0.47,0.28-0.80, p = 0.01). Low dose aspirin (HR 0.76,0.60-0.97, p = 0.03) was associated with a lower risk of GBC only in women, while statins (HR 0.72,0.55-0.93, p = 0.01) showed a significantly decreased risk of GBC in women and a non-significant reduction in men. For all BTC subtypes, combined use of low dose aspirin and statins did not confer additional risk reductions beyond those achieved by statins alone. Male and female users of non-aspirin NSAIDs appeared to be at increased risk of BTC and its subtypes. Metformin did not significantly affect risk of BTC. DISCUSSION/SIGNIFICANCE OF IMPACT: Our collaborative efforts allowed us to develop the largest population-based cohort evaluating risk and protective factors for BTC. Our results provide strong evidence in favor of the chemopreventive roles of low dose aspirin and statins in a subtype- and sex-specific manner. Individual risk factors contribute to development of BTC subtypes in different magnitudes. The next steps to translate these findings into clinical practice require randomized clinical trials that validate our results and provide a more complete picture of the risk-benefit ratio.
3517 Cancer-Related Pain is a Predictor of In-hospital Opioid Overdose among Postoperative patients
Authors: Onyeakusi Nnaemeka E , Mukhtar Fahad , Oshunbade Adebamike , Gbadamosi Semiu , Adejumo Adeyinka , Owoh Jude C.
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: Our study’s primary aim is to determine if there is an association between cancer-related pain among patients who underwent major elective procedures and postoperative opioid overdose. In addition, the relationship between cancer-related pain in this population and inpatient mortality, total hospital charge and length of stay was assessed. METHODS/STUDY POPULATION: Our study sample consisted of adults 18 years and older who had at least one of eight elective procedures. Data was obtained from the National Inpatient Sample (NIS). Variables were identified using ICD-9 codes. Our primary predictor was cancer-related pain while our primary outcome was opioid overdose. Secondary outcomes were inpatient mortality, length of stay and total charge. Propensity-matched regression models were employed in assessing the association between cancer-related pain and outcomes of interest. RESULTS/ANTICIPATED RESULTS: Among 4,085,355 selected patients, 0.8% (n = 2,665) had cancer-related pain while 99.92% (n = 4,082,690) had no diagnosis of cancer-related pain. All subjects with cancer-related pain (n = 2,665) were successfully matched to subjects with no diagnosis of cancer-related pain in a 1:5 ratio yielding 13,325 controls. Patients with cancer-related pain had significantly higher odds of opioid overdose (aOR 4.82 [95% CI [2.68-8.67]; p-value <0.0001) and inpatient mortality (aOR 1.39[1.11-1.74]; p-value 0.0043). Patients with cancer-related pain were also likely to stay significantly longer in the hospital (12.76 days vs. 7.88 days) with significantly higher total hospital charges ($140,220 vs. $88,316). DISCUSSION/SIGNIFICANCE OF IMPACT: Pain is a common complication of cancer pathogenesis, diagnosis or treatment. Though a rare outcome, opioid overdose could lead to undesirable outcomes. Cancer patients undergo invasive diagnostic and therapeutic procedures as part of their cancer management or for conditions not related to their primary cancer diagnosis. Safety measures including alternatives to opioids are recommended to prevent the poor clinical outcomes and higher healthcare utilization indices associated with opioid overdose in this population.
English Women Doctors, Contraception and Family Planning in Transnational Perspective (1930s–70s)
Authors: Rusterholz Caroline
Published: March 2019

This paper explores the influence of English female doctors on the creation of the International Planned Parenthood Federation (IPPF) and the production and circulation of contraceptive knowledge in England and, to a lesser extent in France, between 1930 and 1970. By drawing on the writings of female doctors and proceedings of international conferences as well as the archives of the British Medical Women’s Federation (MWF) and Family Planning Association (FPA), on the one hand, andMouvement Français pour le Planning Familial(MFPF), on the other, this paper explores the agency of English female doctors at the national and transnational level. I recover their pioneering work and argue that they were pivotal in legitimising family planning within medical circles. I then turn to their influence on French doctors after World War II. Not only were English medical women active and experienced agents in the family planning movement in England; they also represented a conduit of information and training crucial for French doctors. Transfer of knowledge across the channel was thus a decisive tool for implementing family planning services in France.
Securing Trade: The Military Labor of the British Occupation of Manila, 1762–1764
Authors: Thomas Megan C.
Published: March 2019

Military labor played a key role in conquering and preserving ports as nodes in trading networks. This article treats the military labor of the British occupation of Manila from 1762 to 1764, during the Seven Years War. It examines the motley crew that formed the British forces, exploring British categories of military laborers sent from Madras. The particular combination of forces composed for this expedition had more to do with the East India Company's concerns in Madras than with what was thought to be needed to take and hold Manila. These military laborers were sometimes unruly, insisting on better pay, and deserting when it was not forthcoming. The story of the British occupation of Manila highlights how ideas about desertion traveled along with military laborers from one port city to another in the Indian Ocean world, and what happened when they did.
Holding doctrinal belief as an artefact
Authors: KALMYKOVA ELENA
Published: March 2019

In this article, I consider how empirical research on religious belief poses a puzzle for the relationship between religious doctrines and lived religion, and develop one solution to that puzzle. The empirical evidence shows that believers are commonly incorrect about the content of doctrinal statements, and apparently not much interested in that content. I argue that this finding calls for a new understanding of the role of doctrinal commitments in religious life. I propose that in many cases believers relate to doctrinal statements in rather the way that they relate to sacred artefacts, that is, by way of an attitude of reverence and strong adherence, and independently of any attempt to discern the content of doctrinal claims. I note how this account avoids some of the difficulties of alternative solutions, which may undermine the claim of religious beliefs to count as genuine beliefs.
Occupational therapy and primary care
Authors: Bolt Marije , Ikking Tiska , Baaijen Rosa , Saenger Stephanie
Published: March 2019

This article is the first in a series of two articles about Occupational Therapy and Primary Care. This first article describes the health policy context in which primary health care should be strengthened. A definition of occupational therapy is given and the scope of the profession is explained. Based on a survey amongst the (experts of) member associations of COTEC, an overview is given of the main target groups and how occupational therapy is embedded and organized in different countries. In a position statement it is argued why occupational therapy can and should contribute to a comprehensive integrated primary care and challenges to strengthen the position of the profession are described.
Encountering sexual and gender minority youth in healthcare: an integrative review
Authors: Laiti Minna , Pakarinen Anni , Parisod Heidi , Salanterä Sanna , Sariola Salla
Published: March 2019

Aim

To describe the encounters with sexual and gender minority (SGM) youth in healthcare based on the existing research.

Background

The development of sexual orientation and gender identity can create challenges in an SGM youth’s life, and they may need support from health professionals. Heteronormativity has been recognised as a barrier to the identification of diversity in sexuality and gender, and no previous literature review has studied heteronormativity thoroughly.

Methods

An integrative review following Whittemore and Knafl was conducted. A literature search was systematically undertaken in six databases (PubMed/MEDLINE, CINAHL, Cochrane Library, PsycINFO, Eric, and Academic Search Premier). Finally, 18 research articles were included. Data were analysed deductively with the theoretical framework from Stevi Jackson’s (2006) article to understand the role of heteronormativity in the healthcare of SGM youth.

Findings

The encounters with SGM youth consisted of two simultaneous themes.Heteronormative careincluded three elements: (1) the effect of heteronormativity on health professionals’ competence to work with SGM youth, (2) false assumptions about SGM youth, and (3) the influence of heteronormativity on encounters with SGM youth.Diversity-affirming careincluded two elements: (4) the considerateness of health professionals towards SGM youth and (5) inclusive care of SGM youth.

Conclusion

This review summarised how SGM youth were encountered in healthcare and how heteronormativity was affecting their healthcare. Furthermore, this review identified elements that supported diversity-affirming care. With diversity-affirming care, SGM youth may access the information and support they need from healthcare. Further research is needed about how diversity-affirming care can be applied to the healthcare of SGM youth and how elements of heteronormative care are occurring globally in the healthcare of SGM youth. The perceptions of transgender and other gender minority youth were under-represented in the studies and research needs to focus more on how they are encountered in healthcare.
Ancient River Discovery Confirms Mediterranean Nearly Dried Up in the Miocene
Authors: Johnson-Groh Mara
Published: March 2019

Sedimentary deposits reveal a Nile-sized river system flowing from what are today Turkey and Syria.
Metal-free dehydropolymerisation of phosphine-boranes using cyclic (alkyl)(amino)carbenes as hydrogen acceptors
Authors: Oldroyd Nicola L. , Chitnis Saurabh S. , Annibale Vincent T. , Arz Marius I. , Sparkes Hazel A. , Manners Ian
Published: March 2019

The divalent carbene carbon centre in cyclic (alkyl)(amino)carbenes (CAACs) is known to exhibit transition-metal-like insertion into E–H σ-bonds (E = H, N, Si, B, P, C, O) with formation of new, strong C–E and C–H bonds. Although subsequent transformations of the products represent an attractive strategy for metal-free synthesis, few examples have been reported. Herein we describe the dehydrogenation of phosphine-boranes, RR’PH·BH3, using a CAAC, which behaves as a stoichiometric hydrogen acceptor to release monomeric phosphinoboranes, [RR’PBH2], under mild conditions. The latter species are transient intermediates that either polymerise to the corresponding polyphosphinoboranes, [RR’PBH2]n (R = Ph; R’ = H, Ph or Et), or are trapped in the form of CAAC-phosphinoborane adducts, CAAC·H2BPRR’ (R = R’ = tBu; R = R’ = Mes). In contrast to previously established methods such as transition metal-catalysed dehydrocoupling, which only yield P-monosubstituted polymers, [RHPBH2]n, the CAAC-mediated route also provides access to P-disubstituted polymers, [RR’PBH2]n (R = Ph; R’ = Ph or Et).
ATAD3A oligomerization causes neurodegeneration by coupling mitochondrial fragmentation and bioenergetics defects
Authors: Zhao Yuanyuan , Sun Xiaoyan , Hu Di , Prosdocimo Domenick A. , Hoppel Charles , Jain Mukesh K. , Ramachandran Rajesh , Qi Xin
Published: March 2019

Mitochondrial fragmentation and bioenergetic failure manifest in Huntington’s disease (HD), a fatal neurodegenerative disease. The factors that couple mitochondrial fusion/fission with bioenergetics and their impacts on neurodegeneration however remain poorly understood. Our proteomic analysis identifies mitochondrial protein ATAD3A as an interactor of mitochondrial fission GTPase, Drp1, in HD. Here we show that, in HD, ATAD3A dimerization due to deacetylation at K135 residue is required for Drp1-mediated mitochondrial fragmentation. Disturbance of ATAD3A steady state impairs mtDNA maintenance by disrupting TFAM/mtDNA binding. Blocking Drp1/ATAD3A interaction with a peptide, DA1, abolishes ATAD3A oligomerization, suppresses mitochondrial fragmentation and mtDNA lesion, and reduces bioenergetic deficits and cell death in HD mouse- and patient-derived cells. DA1 treatment reduces behavioral and neuropathological phenotypes in HD transgenic mice. Our findings demonstrate that ATAD3A plays a key role in neurodegeneration by linking Drp1-induced mitochondrial fragmentation to defective mtDNA maintenance, suggesting that DA1 might be useful for developing HD therapeutics.
A polymer-direct-intercalation strategy for MoS2/carbon-derived heteroaerogels with ultrahigh pseudocapacitance
Authors: Feng Nan , Meng Ruijin , Zu Lianhai , Feng Yutong , Peng Chengxin , Huang Jimei , Liu Guanglei , Chen Bingjie , Yang Jinhu
Published: March 2019

The intercalation strategy has become crucial for 2D layered materials to achieve desirable properties, however, the intercalated guests are often limited to metal ions or small molecules. Here, we develop a simple, mild and efficient polymer-direct-intercalation strategy that different polymers (polyethyleneimine and polyethylene glycol) can directly intercalate into the MoS2 interlayers, forming MoS2-polymer composites and interlayer-expanded MoS2/carbon heteroaerogels after carbonization. The polymer-direct-intercalation behavior has been investigated by substantial characterizations and molecular dynamic calculations. The resulting composite heteroaerogels possess 3D conductive MoS2/C frameworks, expanded MoS2 interlayers (0.98 nm), high MoS2 contents (up to 74%) and high Mo valence (+6), beneficial to fast and stable charge transport and enhanced pseudocapacitive energy storage. Consequently, the typical MoS2/N-doped carbon heteroaerogels exhibit outstanding supercapacitor performance, such as ultrahigh capacitance, remarkable rate capability and excellent cycling stability. This study offers a new intercalation strategy which may be generally applicable to 2D materials for promising energy applications.
Identifying Pb-free perovskites for solar cells by machine learning
Authors: Im Jino , Lee Seongwon , Ko Tae-Wook , Kim Hyun Woo , Hyon YunKyong , Chang Hyunju
Published: March 2019

Recent advances in computing power have enabled the generation of large datasets for materials, enabling data-driven approaches to problem-solving in materials science, including materials discovery. Machine learning is a primary tool for manipulating such large datasets, predicting unknown material properties and uncovering relationships between structure and property. Among state-of-the-art machine learning algorithms, gradient-boosted regression trees (GBRT) are known to provide highly accurate predictions, as well as interpretable analysis based on the importance of features. Here, in a search for lead-free perovskites for use in solar cells, we applied the GBRT algorithm to a dataset of electronic structures for candidate halide double perovskites to predict heat of formation and bandgap. Statistical analysis of the selected features identifies design guidelines for the discovery of new lead-free perovskites.
Field-recorded data on habitat, density, growth and movement of Nephrops norvegicus
Authors: Power Anne Marie , Merder Julian , Browne Patricia , Freund Jan A. , Fullbrook Liam , Graham Conor , Kennedy Robert J. , O’Carroll Jack P. J. , Wieczorek Alina M. , Johnson Mark P.
Published: March 2019

The availability of growth data in N. norvegicus is important for management purposes due to a lack of aging criteria and the commercial importance of fisheries in this species. Growth varies as a function of stock density, hence comparisons of growth rates between stocks at known density is particularly valuable. Growth is also related to starting size in males, making raw data on size-specific growth rates more valuable. Internally injected passive tags allowed us to track the growth of male and female individuals over one or two years. The spatial position of tagged recaptures was recorded to measure site fidelity of tagged releases. A total of 3300 pots were fished and their spatial positions were recorded to enable Catch Per Unit Effort calculations. Similarly, spatially geo-referenced v-notching and notched recovery enables spatially gridded densities to be calculated. Finally, acoustic mapping was carried out both on and off the fishing ground and was ground-truthed with sedimentology from grabs at 22 stations. These data are useful for fisheries and macroecological studies.
Mutant p53 regulates LPA signaling through lysophosphatidic acid phosphatase type 6
Authors: Chryplewicz Agnieszka , Tienda Samantha M. , Nahotko Dominik A. , Peters Pamela N. , Lengyel Ernst , Eckert Mark A.
Published: March 2019

Emerging evidence has indicated that high-grade serous ovarian cancer (HGSOC) originates in the fallopian tube, where the earliest known genetic lesion is the mutation of TP53. In addition to such genetic changes, HGSOC is characterized by altered metabolism, including the production of oncogenic lipids such as lysophosphatidic acid (LPA). To understand the crosstalk between TP53 mutations and LPA signaling, we utilized primary fallopian tube epithelial cells (FTEC) engineered to overexpress mutant p53. We found that gain-of-function (GOF) p53 mutations downregulated the LPA-degrading enzyme lysophosphatidic acid phosphatase type 6 (ACP6), leading to upregulation of focal adhesion signaling in an LPA-dependent manner. Although highly expressed in normal fallopian tube epithelium, ACP6 expression was significantly reduced in ovarian cancer tumors and early in situ lesions. Downregulation of ACP6 in ovarian cancer cells was necessary and sufficient to support HGSOC proliferation, adhesion, migration, and invasion. Using mouse models of metastasis, we established that attenuation of ACP6 expression was associated with increased tumor burden. Conversely, overexpression of ACP6 suppressed invasive behavior. These data identify an involvement of oncogenic p53 mutations in LPA signaling and HGSOC progression through regulation of ACP6 expression.
Low survival rate and muscle fiber-dependent aging effects in the McArdle disease mouse model
Authors: Real-Martinez Alberto , Brull Astrid , Huerta Jordi , Tarrasó Guillermo , Lucia Alejandro , Martin Miguel Angel , Arenas Joaquin , Andreu Antoni L. , Nogales-Gadea Gisela , Vissing John , Krag Thomas O. , de Luna Noemi , Pinós Tomàs
Published: March 2019

McArdle disease is an autosomal recessive disorder caused by the absence of the muscle glycogen phosphorylase, which leads to impairment of glycogen breakdown. The McArdle mouse, a model heavily affected by glycogen accumulation and exercise intolerance, was used to characterize disease progression at three different ages. The molecular and histopathological consequences of the disease were analyzed in five different hind-limb muscles (soleus, extensor digitorum longus, tibialis anterior, gastrocnemius and quadriceps) of young (8-week-old), adult (35-week-old) and old (70-week-old) mice. We found that McArdle mice have a high perinatal and post-weaning mortality. We also observed a progressive muscle degeneration, fibrosis and inflammation process that was not associated with an increase in muscle glycogen content during aging. Additionally, this progressive degeneration varied among muscle and fiber types. Finally, the lack of glycogen content increase was associated with the inactivation of glycogen synthase and not with compensatory expression of the Pygl and/or Pygb genes in mature muscle.
Comparative study on the effects of Cr, V, and Mo carbides for hydrogen-embrittlement resistance of tempered martensitic steel
Authors: Lee Junmo , Lee Taekyung , Mun Dong-Jun , Bae Chul Min , Lee Chong Soo
Published: March 2019

In this study, the ideal alloying element (among Cr, V, and Mo carbides) to enhance the resistance to hydrogen embrittlement (HE) in a tempered martensitic steel was investigated. Four types of steels were designed to contain cementites, Cr-rich M7C3 carbides, V carbides, and Mo carbides, respectively. These steels were tailored to possess a comparable tensile strength (~1.6 GPa). The HE resistances of these steels were evaluated through the slow strain rate test and cyclic corrosion test. The results showed an enhanced HE resistance, characterized by a high notch fracture strength after hydrogen charging, in the samples containing V carbides and Mo carbides. In particular, Mo carbide was regarded as the most ideal alloying element for HE resistance because of the high resistivity parameter, inhibited hydrogen penetration, and suppressed strength loss by internal hydrogen.
The dual roles of RPE65 S-palmitoylation in membrane association and visual cycle function
Authors: Uppal Sheetal , Liu Tingting , Poliakov Eugenia , Gentleman Susan , Redmond T. Michael
Published: March 2019

Association with the endoplasmic reticulum (ER) membrane is a critical requirement for the catalytic function of RPE65. Several studies have investigated the nature of the RPE65-membrane interaction; however, complete understanding of its mode of membrane binding is still lacking. Previous biochemical studies suggest the membrane interaction can be partly attributed to S-palmitoylation, but the existence of RPE65 palmitoylation remains a matter of debate. Here, we re-examined RPE65 palmitoylation, and its functional consequence in the visual cycle. We clearly demonstrate that RPE65 is post-translationally modified by a palmitoyl moiety, but this is not universal (about 25% of RPE65). By extensive mutational studies we mapped the S-palmitoylation sites to residues C112 and C146. Inhibition of palmitoylation using 2-bromopalmitate and 2-fluoropalmitate completely abolish its membrane association. Furthermore, palmitoylation-deficient C112 mutants are significantly impeded in membrane association. Finally, we show that RPE65 palmitoylation level is highly regulated by lecithin:retinol acyltransferase (LRAT) enzyme. In the presence of all-trans retinol, LRAT substrate, there is a significant decrease in the level of palmitoylation of RPE65. In conclusion, our findings suggest that RPE65 is indeed a dynamically-regulated palmitoylated protein and that palmitoylation is necessary for regulating its membrane binding, and to perform its normal visual cycle function.
A High Energy Density Azobenzene/Graphene Oxide Hybrid with Weak Nonbonding Interactions for Solar Thermal Storage
Authors: Pang Wenhui , Xue Jijun , Pang Hua
Published: March 2019

Incorporating photochromic chromophores into polymer composites provides the possibility of a reversible photoswitch of the intrinsic properties of these materials. In this paper we report a route to attach azobenzene (AZO) moiety covalently to graphene oxide (GO) to create chromophore/graphene oxide (AZO-GO) hybrid, in which GO is both part of the chromophore and the template. Due to the high grafting density of AZO moiety and the low mass of the novel structure, the hybrid is a potential solar thermal storage material with high energy density of about 240 Wh·kg−1. It is found that C-H···π interaction between the cis-AZO chromophores and the aromatic rings of the substrate induces collective electronic modifications of GO at critical percentage of cis-isomers and reduce the thermal barrier of π-π* transition of the chromophores directly, which results in two sections of first-order reactions during the photoisomerization of trans- to cis-hybrid and also thermally stabilizes the cis-hybrid. Our findings demonstrate that high-performance AZO–GO hybrid can be manipulated by optimizing intermolecular nonbonding interactions.
Bi0.9Ho0.1FeO3/TiO2 Composite Thin Films: Synthesis and Study of Optical, Electrical and Magnetic Properties
Authors: Islam Md. Rafiqul , Zubair M. A. , Bashar M. S. , Rashid A. K. M. B.
Published: March 2019

A visible light active Bi0.9Ho0.1FeO3 nanoparticles/TiO2 composite thin films with different mol.% of Bi0.9Ho0.1FeO3 were successfully prepared via non-aqueous sol-gel method. The incorporation of 5, 10 and 20 mol.% Bi0.9Ho0.1FeO3 nanoparticles in the precursor solution of TiO2 brings modifications in the functional properties of the composite thin films. XPS analysis indicates that interdiffusion of Fe3+, Ho3+, Bi3+/Ti4+ ions through the interfaces between Bi0.9Ho0.1FeO3 nanoparticles and TiO2 matrix reduces the concentration of Ti3+ ions. X-ray diffraction analysis affirms that TiO2 and Bi0.9Ho0.1FeO3 retain anatase and orthorhombic phase respectively in composite films. The composite thin film containing 20 mol.% Bi0.9Ho0.1FeO3 nanoparticles exhibits the most prominent absorption phenomenon in visible region and has significantly reduced indirect band gap of 2.46 eV compared to that of pure TiO2 (3.4 eV). Hall effect measurements confirm that the resistivity of composite film increases by ∼2.33 orders of magnitude and its carrier concentration decreases by 1.8 orders of magnitude at 5 mol.% Bi0.9Ho0.1FeO3 nanoparticles addition compared to those of pure TiO2 film. Moreover, the pure film exhibits diamagnetism, whereas the composite films have both large ferromagnetic and small diamagnetic components. The findings in this research justify that the composite film can be a potential candidate for making improved photocatalyst, resistors and spintronic devices.
Glucocorticoids do not influence a secondary sexual trait or its behavioral expression in eastern fence lizards
Authors: MacLeod K. J. , McCormick G. L. , Langkilde T.
Published: March 2019

Secondary sexual traits and associated behaviors can be influenced by environmental factors such as exposure to stressors. Such effects may be mediated by the physiological stress response, which is typified by the release of glucocorticoid hormones. The effects of glucocorticoids on sexual traits such as plumage and display coloration have most commonly been studied in isolation rather than in conjunction with other pertinent aspects of signalling, such as behavior and habitat use, though these have substantial potential to alter signal perception. Here we test the effects of corticosterone (CORT), a common glucocorticoid, on a secondary sexual trait (badge coloration) in male eastern fence lizards (Sceloporus undulatus), and behaviors associated with its expression. We show that neither baseline nor experimentally manipulated CORT levels were associated with badge coloration. Further, elevation of CORT levels in the field did not alter signalling or associated territorial behaviors. There was a trend for CORT-treatment to influence perch height selection, which may influence signal perception. We suggest that future studies investigating the effects of environmental stressors and associated physiological changes on secondary sexual traits should consider behaviors and ecology relevant to signal perception in order to best understand the influence of stressors in nature.
Mitochondrial function in immature bovine oocytes is improved by an increase of cellular cyclic AMP
Authors: Hashimoto Shu , Yamanaka Masaya , Yamochi Takayuki , Iwata Hisataka , Kawahara-Miki Ryouka , Inoue Masayasu , Morimoto Yoshiharu
Published: March 2019

Although in vitro maturation (IVM) of oocytes is important for assisted reproduction, the rate of development of embryos from IVM oocytes is lower than from their in vivo counterparts. It has been shown that an artificial increase of intracellular cAMP before culture significantly improves oocyte developmental competence in cattle and mice. Here, we revealed that forskolin and 3-isobutyl-1-methylxanthine treatment of prophase-stage oocytes induced the expression of genes required for glycolysis, fatty acid degradation, and the mitochondrial electron transport system and improved mitochondrial functions and ATP levels in oocytes without involving nuclear maturation. We propose the existence of a comprehensive energy-supply system in oocytes under follicle-stimulating hormone stimulation as a potential explanation of how oocytes acquire developmental competence.
Geochemical study of carbonate concretions from the aqueduct of Nîmes (southern France): a climatic record for the first centuries AD?
Authors: Benjelloun Yacine , Carlut Julie , Hélie Jean-François , Chazot Gilles , Le Callonnec Laurence
Published: March 2019

The first centuries AD in the Mediterranean region have generally been associated with a warm, stable climate. High-resolution sedimentary archives sensitive to local environmental change are needed to switch from this general frame to the regional scale. Similarly to cave speleothems, laminated carbonate deposits can grow in the channels of aqueducts which transported water from karstic springs during the Roman period. The deposits of the aqueduct of Nîmes (SE France) are exceptional since they may represent several centuries of paleoenvironmental record with a seasonal resolution. δ18O, δ13C and trace elements were measured in three samples from this aqueduct. The comparison of the geochemical signals with the fine texture of the deposits evidenced the seasonal nature of the lamination observed. This allowed us to document the evolution of environment as recorded through the deposit for the period 50–275 AD. The concretions of the aqueduct of Nîmes document rather stable climatic conditions for the first three centuries AD, as well as a local vegetation change possibly linked to an increased in land use.
Improved survival prognostication of node-positive malignant melanoma patients utilizing shotgun proteomics guided by histopathological characterization and genomic data
Authors: Betancourt Lazaro Hiram , Pawłowski Krzysztof , Eriksson Jonatan , Szasz A. Marcell , Mitra Shamik , Pla Indira , Welinder Charlotte , Ekedahl Henrik , Broberg Per , Appelqvist Roger , Yakovleva Maria , Sugihara Yutaka , Miharada Kenichi , Ingvar Christian , Lundgren Lotta , Baldetorp Bo , Olsson Håkan , Rezeli Melinda , Wieslander Elisabet , Horvatovich Peter , Malm Johan , Jönsson Göran , Marko-Varga György
Published: March 2019

Metastatic melanoma is one of the most common deadly cancers, and robust biomarkers are still needed, e.g. to predict survival and treatment efficiency. Here, protein expression analysis of one hundred eleven melanoma lymph node metastases using high resolution mass spectrometry is coupled with in-depth histopathology analysis, clinical data and genomics profiles. This broad view of protein expression allowed to identify novel candidate protein markers that improved prediction of survival in melanoma patients. Some of the prognostic proteins have not been reported in the context of melanoma before, and few of them exhibit unexpected relationship to survival, which likely reflects the limitations of current knowledge on melanoma and shows the potential of proteomics in clinical cancer research.
Seismic detection of strong ground motions by MW5.6 North Korean nuclear explosion
Authors: Hong Tae-Kyung , Lee Junhyung , Park Seongjun , Yoon Hyun Ho , Kim Woohan , Shin Jin Soo
Published: March 2019

The North Korean nuclear explosion test site in Punggye-ri is located in a seismically quiescent region on a stable Precambrian basement. The 3 September 2017 MW5.6 North Korean underground nuclear explosion (UNE) test produced unprecedented strong ground motions. The peak ground accelerations might reach tens to hundreds m/s2 on the surface of the UNE test site, decaying exponentially with distance. Ten shallow events with magnitudes greater than or equal to ML2.5 and source depths less than 3 km followed the 2017 UNE for 5 months in an area with a radius of 15 km from the UNE where strong ground shaking was experienced. The largest event with MW3.7 occurred 20 days after the 2017 UNE test at shallow depths less than 3 km. Its moment tensor solution indicates a combined source behavior with comparable strengths of double-couple and compensated linear vector dipole (CLVD) components, suggesting an unusual event different from typical natural earthquakes in the Korean Peninsula. The clustered shallow seismic events appeared to have occurred in damaged media that were effectively perturbed by the strong ground motions of the UNE.