bluuebunny/crossref_metadata_2025 huggingface dataset:
Inherent Immune Cell Variation Within Colonic Segments Presents Challenges for Clinical Trial Design
Authors: Tyler Christopher J , Guzman Mauricio , Lundborg Luke R , Yeasmin Shaila , Perez-Jeldres Tamara , Yarur Andres , Behm Brian , Dulai Parambir S , Patel Derek , Bamias Giorgos , Rivera-Nieves Jesús
Published: April 2020

Background and Aims

Intestinal biopsy sampling during IBD trials represents a valuable adjunct strategy for understanding drug responses at the tissue level. Given the length and distinctive embryonic origins of the proximal and distal colon, we investigated whether inherent regional differences of immune cell composition could introduce confounders when sampling different disease stages, or pre/post drug administration. Here, we capitalise on novel mass cytometry technology to perform deep immunophenotyping of distinct healthy colonic segments, using the limited numbers of biopsies that can be harvested from patients.

Methods

Biopsies [2.8 mm] were collected from the caecum, transverse colon, descending colon, and rectum of normal volunteers. Intestinal leukocytes were isolated, stained with a panel of 37 antibodies, and mass cytometry data acquired.

Results

Site-specific patterns of leukocyte localisation were observed. The proximal colon featured increased CD8+ T cells [particularly resident memory], monocytes, and CD19+ B cells. Conversely, the distal colon and rectum tissues exhibited enrichment for CD4+ T cells and antibody-secreting cells. The transverse colon displayed increased abundance of both γδ T cells and NK cells. Subsets of leukocyte lineages also displayed gradients of expression along the colon length.

Conclusions

Our results show an inherent regional immune cell variation within colonic segments, indicating that regional mucosal signatures must be considered when assessing disease stages or the prospective effects of trial drugs on leukocyte subsets. Precise protocols for intestinal sampling must be implemented to allow for the proper interpretation of potential differences observed within leukocyte lineages present in the colonic lamina propria.
Integrating evolution into medical education for women’s health care practitioners
Authors: Power Michael L , Snead Carrie , Reed Eda G , Schulkin Jay
Published: April 2020

Evolution is a fundamental principle in biology; however, it has been neglected in medical education. We argue that an evolutionary perspective is especially important for women’s health care providers, as selection will act strongly on reproductive parameters, and the biological costs of female reproduction are generally more resource expensive than for men (e.g. due to gestation and lactation) with greater effects on health and wellbeing. An evolutionary perspective is needed to understand antibiotic resistance, disease and health risks associated with mismatches between our evolved adaptations and current conditions, the importance of the microbiome and the maternal role in how infants acquire and develop their early-life microbiome (vaginal birth, lactation), and the importance of breastmilk as a biochemical signal from mothers to their babies. We present data that obstetrician–gynecologists’ views regarding the inclusion of evolution within their training is generally positive, but many barriers are perceived. Requiring coursework in evolutionary biology with an emphasis on evolutionary medicine prior to enrollment in medical school may be a solution.
Norms in practice: people-centric governance in ASEAN and ECOWAS
Authors: Glas Aarie , Balogun Emmanuel
Published: April 2020

The Association of Southeast Asian Nations (ASEAN) and the Economic Community of West African States (ECOWAS) both recently adopted and institutionalized the norm of people-centric governance. This is potentially transformative for both, signalling a reorientation away from their private and elite-led normative foundations. In practice, however, the norm is understood and enacted in different ways by officials at each organization and with radically different effects. In ASEAN, the norm is understood and enacted in a limited and defensive way. Its institutionalization has led only to selective engagement with civil society and has not altered established modes of regional governance. In ECOWAS, however, the norm is understood as a means to render the organization more inclusive of civil society groups and has transformed the regional project in important ways, shaping the logic and form of regional intervention and conflict prevention. To explore these experiences—convergence in adoption and institutionalization of a norm and variation in its practice and effect—we develop a practice theoretic framework and rely on 76 interviews with regional and state officials. We show that each organizational case is usefully conceptualized as a community of practice wherein external norms are understood and practiced in particular ways and with particular effect.
Terrestrial Locomotion in American Eels (Anguilla rostrata): How Substrate and Incline Affect Movement Patterns
Authors: Redmann Erica , Sheikh Alina , Alqahtani Areej , McCarty-Glenn Mica , Syed Shazrah , Mehta Rita S , Ward Andrea B
Published: April 2020

Synopsis

Fishes overcome a variety of challenges in order to invade the terrestrial environment. Terrestrial invasions by fish occur over a variety of environmental contexts. In order to advance their bodies on land, fishes capable of terrestrial excursions tend to use one of three different types of locomotor modes: axial-based, appendage-based, or axial-appendage-based. Elongate species with reduced appendages, such as the American eel, Anguilla rostrata, rely on axial based locomotion in water and on land. When eels move from water to land as part of their complex life cycle, they inevitably encounter a variety of substrates and must traverse variable degrees of incline. The aim of this study was to determine the effect of substrate and incline on the terrestrial locomotion of the American eel. In order to do this, eels were filmed from a dorsal view on three substrates and four inclines: sand, loose pebbles, and fixed (glued) pebbles at 0°, 5°, 10°, and 15°. We digitized 20 evenly spaced points along the body to examine the following characteristics of locomotion: velocity, distance ratio (DR), and wave parameters such as wave amplitude, frequency, and length and assessed whether substrate, incline, or body position affected these parameters. DR, our metric of movement efficiency, was highest on the flat sand condition and lowest on 15° pebble conditions. Efficiency also varied across the body. Velocity followed a similar pattern being highest on sand at 0° and lowest at the steepest inclines. Wave amplitude generally increased toward the tail but was similar across substrates and inclines. Wave frequency was relatively consistent across the body on both pebble substrates, but on sand, frequency was higher toward the head but decreased toward the tail. Wavelengths on sand were the longest at 0° near the head and shorter wavelengths were observed on steeper inclines. Both pebble substrates elicited lower wavelengths that were more similar across the body. Overall, A. rostrata were more effective in navigating compliant substrates but struggled at steeper inclines. Our findings provide insight into locomotor challenges that American eels may encounter as they move from and between bodies of water.
Zika Virus Circulates at Low Levels in Western and Coastal Kenya
Authors: Gobillot Theodore A , Kikawa Caroline , Lehman Dara A , Kinuthia John , Drake Alison L , Jaoko Walter , Mandaliya Kishorchandra , John-Stewart Grace , McClelland R Scott , Overbaugh Julie
Published: April 2020

Background

Zika virus (ZIKV) was discovered over 70 years ago in East Africa, but little is known about its circulation and pathogenesis there.

Methods

We screened 327 plasma samples collected 2–12 months after febrile illness in Western and coastal Kenya (1993–2016) for binding and neutralizing antibodies to distinguish ZIKV and dengue virus (DENV) responses, which we found were common in coastal Kenya.

Results

Two cases had durable ZIKV-specific antibodies and 2 cases had ZIKV antibodies at similar levels as DENV antibodies.

Conclusions

This suggests low-level ZIKV circulation in Kenya over 2 decades and sets a baseline for future surveillance efforts in East Africa.
Physiological and behavioral sexual maturity of female red deep-sea crabs Chaceon quinquedens (Smith, 1879) (Decapoda: Brachyura: Geryonidae) in the Mid-Atlantic Bight
Authors: Martínez-Rivera Stephanie , Long William Christopher , Stevens Bradley G
Published: April 2020

We describe the physiological and behavioral maturity of the red deep-sea crab, Chaceon quinquedens (Smith, 1879), using ovary and oocyte development and morphological features to estimate the size at 50% sexual maturity (SM50) for females in the Mid-Atlantic Bight. This economically important species inhabits the continental shelf and slope of the western Atlantic from Nova Scotia, Canada to the Gulf of Mexico. Samples were collected by trawling in 2011–2013 and by traps in 2014–2016. We used histological analysis to describe the stages of ovarian development. Five stages of ovarian development were identified: 1, immature; 2, early maturing; 3, late maturing; 4, mature; and 5, redeveloping. A logistic model was used to estimate the SM50 using maximum likelihood methods. Physiological SM50 varied among geographic locations and was estimated at 61.2 mm CL and 70.8 mm CL for females collected near Hudson Canyon and Baltimore and Norfolk canyons, respectively. Behavioral SM50 decreased with latitude and was estimated at 53.9 mm CL, 62.5 mm CL and 65.5 mm CL for Hudson, Baltimore, and Norfolk canyons, respectively. Results implied asynchrony between physiological and behavioral sexual maturity, suggesting that mating occurs prior to completion of ovarian development. This study provides the first evidence of a latitudinal trend in sexual maturity for C. quinquedens. Further investigation is needed to understand the cause of the latitudinal trend as our study presented limitations. Results provide useful information for fisheries management about the reproductive biology of C. quinquedens.
The ECCC’s Contribution to Substantive ICL
Authors: Ambos Kai
Published: April 2020

In this short essay, I will argue that the ‘civilian population’ requirement in crimes against humanity (CAH) provisions (e.g. Article 7(1) ICC Statute) must either be radically restricted by way of a teleological (purpose-based) interpretation or — even better — abolished in future CAH provisions. While the traditional International Humanitarian Law approach certainly needs to be adjusted with regard to CAH, such an adjustment does not resolve the considerable limitation of the protective scope of CAH due to the ‘civilian population’ requirement. The contribution of the Extraordinary Chambers in the Courts of Cambodia to the debate is to be welcomed and serves as a useful starting point for the more radical interpretation and necessary reform of CAH.
South Korea’s nuclear power industry: recovering from scandal
Authors: Andrews-Speed Philip
Published: April 2020

South Korea has one of the world’s more established nuclear power industries with its first commercial reactors being commissioned in 1978. The growth of nuclear power capacity had relied on sustained government support and close coordination with key state-owned enterprises. The tight relationship between politicians, government and companies has resulted in what is colloquially known as the ‘nuclear mafia’. One year after the Fukushima Daiichi nuclear accident in Japan, Korea’s nuclear industry suffered its own crises in 2012. The first was a station blackout at the Kori 1 reactor, the country’s oldest, which was not reported for over a month. The second set of revelations concerned systematic malfeasance along the nuclear supply chain involving the falsification of reports of safety tests on nuclear parts and equipment. Revisions to the Nuclear Safety Act gave greater powers to the newly created Nuclear Safety and Security Commission and placed new reporting obligations on all actors along the nuclear supply chain. These measures were supplemented by more general legislation and regulations on public procurement, the conduct of public officials and corruption. Whilst these steps have the potential to improve governance and integrity in the country’s nuclear power industry, some of the underlying causes of the earlier weaknesses remain. As a consequence, the transformation of Korea’s nuclear industry will be a long process.
Azoospermia Secondary to a Novel X-Autosomal Reciprocal Translocation: 46,Y, t(X:16)(p22.1:p11.2)
Authors: Choi Lindsey , Levy Gary , Donlon Timothy , Sterbis Joseph , Pier Bruce
Published: April 2020

Chromosomal translocations occur in 10 to 15% of men with azoospermia. Thirty distinct X-autosomal balanced reciprocal translocations have been reported in the literature thus far. We present a novel case of azoospermia with a karyotype of 46,Y,t(X:16)(p22.1:p11.2).

A 26-year-old, healthy, active duty male Solider presented with his dependent female partner for primary infertility. Female anatomical and endocrine evaluations were normal. Initial male evaluation revealed azoospermia on multiple semen analyses. Further evaluation with a detailed physical exam and laboratory tests were normal except for an abnormal karyotype with a reciprocal translocation at chromosomes X and 16. An open testicular biopsy demonstrated 75% late spermatid maturation arrest confirming reproductive potential although significantly reduced.

Men who present with azoospermia should undergo a full endocrine and genetic evaluation with a thorough physical evaluation by an urologist. They can have limited but successful reproductive outcomes if spermatozoa can be isolated during testicular biopsy. Given the high risk of producing genetically unbalanced embryos, genetic counseling and preimplantation genetic testing is essential before pursuing assisted reproductive technology. This case is the first X-autosomal balanced reciprocal translocations involving chromosome 16 and highlights the importance of the X chromosome during spermatogenesis.
Being Prepared for the Next Conflict Part II: Case Analysis of a Military Level 1 Trauma Center
Authors: Wood Thomas T , Roberts Haydn J , Stinner Daniel J
Published: April 2020

Introduction

Combat-related injuries have declined substantially in recent years as we have transitioned to a low-volume combat casualty flow era. Surgeons must remain actively committed to training for the next engagement to maintain life and limb-saving skills. Soft tissue coverage procedures were imperative to the management of complex lower extremity trauma that occurred during recent conflicts. The purpose of this study was to evaluate advanced soft tissue coverage procedures performed on the lower extremity over the previous decade on military and civilian trauma patients at a Department of Defense Level 1 trauma center to provide data that can be used to guide future training efforts.

Materials and Methods

The electronic surgical record system was searched for cases that utilized advanced soft tissue coverage (rotational and free flaps) to the lower extremity. The date of treatment, indication, procedure performed, and military/civilian patient designation were recorded. The data was categorized between military and civilian cases, rotational versus free flap, and indication and then charted over time. It was assessed as moving averages over a 12-month period. Statistically distinct periods were then identified.

Results

From January 2006 to March 2015, 132 advanced soft tissue coverage procedures were performed on the lower extremity (100 military, 32 civilian). Military soft tissue coverage data demonstrated peaks in 2007 and late 2011 to late 2012, averaging 6.5 (3.5–9.6) and 4.5 (3.2–5.8) per quarter, respectively. There were two low periods, from 2008 to mid-2010 and from mid-2012 to the end of the study, averaging 1.1 (0.6–1.6) and 1.8 (1.1–2.6) cases per quarter, respectively. Civilian procedures averaged 0.9 per quarter (0.5–1.2) throughout the study, but notably were equal to the number of military procedures by the last quarter of 2013 at 2.0 (1.2–2.8 civilian, 0.8–3.1 military).

Conclusions

This data supports prior identified trends in military cases correlating increased number of procedures with increased combat activity related to the conflicts in Iraq and Afghanistan in 2007 and 2011, respectively. The data showed relative stability in the numbers of civilian procedures with a slight uptrend beginning in mid-2012. A comparison after mid-2012 shows military procedures declining and civilian procedures increasing to eventually become equivalent at the end of the data collection. These trends follow previously reported data on tibia fracture fixation procedures and lower extremity amputations for the same time periods. These data demonstrate the importance of the civilian trauma mission for maintaining surgical skills relevant to limb salvage, such as rotational and free flaps, during a low-volume combat casualty flow era.
A new spectroscopic analysis of the massive O + O type binary HD 54662 AB
Authors: Barbá R H , Sabín-Sanjulián C , Arias J I , Gamen R C , Morrell N I , Ferrero G , Maíz Apellániz J , Putkuri C , Simón Díaz S , Boyajian T S , Fullerton A W , McSwain M V
Published: April 2020

HD 54662 AB is one of the three O + OB binaries known so far with orbital period longer than 1000 d, offering the opportunity to test scenarios of massive star formation and models of single stellar evolution. Here, we present a detailed study of this system based on new high-resolution spectra and data. A disentangling method is used to recover the individual spectra of the primary and secondary components, which are classified as O6.5 V(n)z and O7.5 Vz, respectively. Combining radial velocity measurements and astrometric data, a new absolute orbit with a period of 2113 ± 9 d and an eccentricity of 0.062 ± 0.008 is determined, confirming previous findings. However, absolute masses of 23.8 ± 1.1 M⊙ for the primary and 20.3 ± 1.1 M⊙ for the secondary are obtained, differing from previous determinations but in reasonable agreement with the spectral types of the stars. Primary and secondary components show remarkably different projected rotational velocities (160 and ≲40 $\rm km\, s^{-1}$ , respectively), which is probably related to the formation process of the binary. Contrary to previously interpretations, the star with broader spectral features is the most massive object in the system. Stellar and wind parameters of both stars are derived through quantitative spectroscopic analysis of the disentangled spectra using fastwind models, and they are consistent with the current calibrations for O-type stars. Evolutionary masses and ages are also computed with the bonnsai tool. Ages below 2.5 Ma are obtained, in agreement with the youth expected from their Vz nature.
Pulsing and non-pulsing ULXs: the iceberg emerges
Authors: King Andrew , Lasota Jean-Pierre
Published: April 2020

We show that ultraluminous X-ray sources (ULXs) with coherent X-ray pulsing (PULXs) probably have neutron-star spin axes significantly misaligned from their central accretion discs. Scattering in the funnels collimating their emission and producing their apparent super-Eddington luminosities is the most likely origin of the observed correlation between pulse fraction and X-ray photon energy. Pulsing is suppressed in systems with the neutron-star spin closely aligned to the inner disc, explaining why some ULXs show cyclotron features indicating strong magnetic fields, but do not pulse. We suggest that alignment (or conceivably, field suppression through accretion) generally occurs within a fairly short fraction of the ULX lifetime, so that most neutron-star ULXs become unpulsed. As a result we further suggest that almost all ULXs actually have neutron-star accretors, rather than black holes or white dwarfs, reflecting their progenitor high-mass X-ray binary and supersoft X-ray source populations.
NIHAO – XXIII. Dark matter density shaped by black hole feedback
Authors: Macciò Andrea V , Crespi Samuele , Blank Marvin , Kang Xi
Published: April 2020

We present a systematic analysis of the reaction of dark matter distribution to galaxy formation across more than eight orders of magnitude in stellar mass. We extend the previous work presented in the NIHAO-IV paper by adding 46 new high-resolution simulations of massive galaxies performed with the inclusion of black hole feedback. We show that outflows generated by the active galactic nucleus (AGN) are able to partially counteract the dark matter contraction due to the large central stellar component in massive haloes. The net effect is to relax the central dark matter distribution that moves to a less cuspy density profiles at halo mass larger than ≈3 × 1012 M⊙. The scatter around the mean value of the density profile slope (α) is fairly constant (Δα ≈ 0.3), with the exception of galaxies with halo masses around 1012 M⊙, at the transition from stellar to AGN feedback dominated systems, where the scatter increases by almost a factor of 3. We provide useful fitting formulae for the slope of the dark matter density profiles at few per cent of the virial radius for the whole stellar mass range: 105–1012 M⊙ (2 × 109 to 5 × 1013 M⊙ in halo mass).
Release of promoter–proximal paused Pol II in response to histone deacetylase inhibition
Authors: Vaid Roshan , Wen Jiayu , Mannervik Mattias
Published: April 2020

A correlation between histone acetylation and transcription has been noted for a long time, but little is known about what step(s) in the transcription cycle is influenced by acetylation. We have examined the immediate transcriptional response to histone deacetylase (HDAC) inhibition, and find that release of promoter–proximal paused RNA polymerase II (Pol II) into elongation is stimulated, whereas initiation is not. Although histone acetylation is elevated globally by HDAC inhibition, less than 100 genes respond within 10 min. These genes are highly paused, are strongly associated with the chromatin regulators NURF and Trithorax, display a greater increase in acetylation of the first nucleosomes than other genes, and become transcriptionally activated by HDAC inhibition. Among these rapidly up-regulated genes are HDAC1 (Rpd3) and subunits of HDAC-containing co-repressor complexes, demonstrating feedback regulation upon HDAC inhibition. Our results suggest that histone acetylation stimulates transcription of paused genes by release of Pol II into elongation, and that increased acetylation is not a consequence of their enhanced expression. We propose that HDACs are major regulators of Pol II pausing and that this partly explains the presence of HDACs at active genes.
Enabling large-scale genome editing at repetitive elements by reducing DNA nicking
Authors: Smith Cory J , Castanon Oscar , Said Khaled , Volf Verena , Khoshakhlagh Parastoo , Hornick Amanda , Ferreira Raphael , Wu Chun-Ting , Güell Marc , Garg Shilpa , Ng Alex H M , Myllykallio Hannu , Church George M
Published: April 2020

To extend the frontier of genome editing and enable editing of repetitive elements of mammalian genomes, we made use of a set of dead-Cas9 base editor (dBE) variants that allow editing at tens of thousands of loci per cell by overcoming the cell death associated with DNA double-strand breaks and single-strand breaks. We used a set of gRNAs targeting repetitive elements—ranging in target copy number from about 32 to 161 000 per cell. dBEs enabled survival after large-scale base editing, allowing targeted mutations at up to ∼13 200 and ∼12 200 loci in 293T and human induced pluripotent stem cells (hiPSCs), respectively, three orders of magnitude greater than previously recorded. These dBEs can overcome current on-target mutation and toxicity barriers that prevent cell survival after large-scale genome engineering.
TREND: a platform for exploring protein function in prokaryotes based on phylogenetic, domain architecture and gene neighborhood analyses
Authors: Gumerov Vadim M , Zhulin Igor B
Published: April 2020

Key steps in a computational study of protein function involve analysis of (i) relationships between homologous proteins, (ii) protein domain architecture and (iii) gene neighborhoods the corresponding proteins are encoded in. Each of these steps requires a separate computational task and sets of tools. Currently in order to relate protein features and gene neighborhoods information to phylogeny, researchers need to prepare all the necessary data and combine them by hand, which is time-consuming and error-prone. Here, we present a new platform, TREND (tree-based exploration of neighborhoods and domains), which can perform all the necessary steps in automated fashion and put the derived information into phylogenomic context, thus making evolutionary based protein function analysis more efficient. A rich set of adjustable components allows a user to run the computational steps specific to his task. TREND is freely available at http://trend.zhulinlab.org.
A proteinase-free DNA replication machinery for in vitro and in vivo amplified MicroRNA imaging
Authors: Wei Jie , Wang Huimin , Gong Xue , Wang Qing , Wang Hong , Zhou Yangjie , Wang Fuan
Published: April 2020

The construction of robust, modular and compact DNA machinery facilitates us to build more intelligent and ingenious sensing strategies in complex biological systems. However, the performance of conventional DNA amplifiers is always impeded by their limited in-depth amplifications and miscellaneously enzymatic requirements. Here, a proteinase-free reciprocal DNA replication machinery is developed by exploiting the synergistic cross-activation between hybridization chain reaction (HCR) and DNAzyme. The DNAzyme provides an efficient way to simplify the sophisticated design of HCR machinery and simultaneously to promote the amplification capacity. And the HCR-assembled tandem DNAzyme nanowires produce numerous new triggers for reversely stimulating HCR amplifier as systematically explored by experiments and computer-aided simulations. The reciprocal amplifier can be executed as a versatile and powerful sensing platform for analyzing miRNA in living cells and even in mice, originating from the inherent reaction accelerations and multiple-guaranteed recognitions. The reciprocal catalytic DNA machine holds great potential in clinical diagnosis and assessment.
Long-term clinically relevant rodent model of methotrexate-induced cognitive impairment
Authors: Berlin Connor , Lange Katharine , Lekaye H Carl , Hopland Kelsey , Phillips Samantha , Piao Jinghua , Tabar Viviane
Published: April 2020

Background

With the enhanced use of chemotherapy and the advent of increased patient survival rates, there are an increasing number of cancer survivors living with chemotherapy-induced cognitive impairment. A growing number of clinical studies have brought to light the association of agents like methotrexate in generating these neurological sequelae, although mechanisms remain unclear.

Methods

Here, we use a clinically relevant regimen of several cycles of methotrexate and leucovorin rescue to develop a model of chemotherapy-induced cognitive impairment, and investigate the in vivo long-term (16 mo) impact of high-dose systemic methotrexate on white matter cellular dynamics as assessed by stereology, animal behavior, and diffusion tensor imaging.

Results

Our results indicate that at 6 and 16 months post-chemotherapy, methotrexate-treated rats exhibit a significant and permanent decrease in the number of oligodendrocytes and their progenitors in the white matter, in corpus callosum volumes, and myelin basic protein. These findings are associated with mostly delayed deficits in performance on Morris Water Maze and Novel Object Recognition tasks. Diffusion tensor imaging demonstrates significantly decreased fractional anisotropy values in the callosum genu, body, and splenium, as well as previously unassessed areas like the fimbria. Interestingly, these white matter changes are preceded by an earlier, transient decrement in white matter microglia at 3 months, and hippocampal neural progenitors at 3 and 6 months.

Conclusion

These results demonstrate a significant negative impact of methotrexate on the oligodendrocyte compartment and white matter, associated with cognitive impairment. The data also support the use of diffusion tensor imaging in monitoring white matter integrity in this context.
Large-scale mortality gap between SLE and control population is associated with increased infection-related mortality in lupus
Authors: Kedves Melinda , Kósa Fruzsina , Kunovszki Péter , Takács Péter , Szabó Melinda Zsuzsanna , Karyekar Chetan , Lofland Jennifer H , Nagy György
Published: April 2020

Objective

The aim of the present study was to analyse the incidence, prevalence, mortality and cause of death data of adult SLE patients and matched controls in a full-populational, nationwide, retrospective study.

Methods

This non-interventional study was based on database research of the National Health Insurance Fund of Hungary. A total of 7888 patients were included in the analyses, within which two subgroups of incident patients were created: the ‘All incident SLE patients’ group consisted of all incident SLE patients (4503 patients), while the ‘Treated SLE patients’ group contained those who received relevant therapy in the first 6 months after diagnosis (2582 patients).

Results

The median age of the SLE population was found to be 46.5 years (women 85%). The incidence rate was 4.86 and 2.78 per 100 000 inhabitants in the ‘All incident SLE patients’ and ‘Treated SLE patients’ groups, respectively. The standardized mortality ratio was 1.63 and 2.09 in the ‘All incident SLE patients’ and ‘Treated SLE patients’ groups, respectively. Overall survival was significantly lower (P < 0.001) in both groups than in the general population, with hazard ratio = 2.17 in the ‘All incident SLE patients’ group and hazard ratio = 2.75 in the ‘Treated SLE patients’ group. There was no significant difference between SLE and control deaths regarding cerebrovascular conditions as the cause of death. Generally, cancer-related deaths were less common, while haematological cancer and infection-related deaths were more common in SLE patients.

Conclusion

Infections, especially sepsis, had the largest positive effect on top of the extra mortality of SLE. This highlights that SLE patients are at increased risk of infection-related death.
Inflammation, reward circuitry and symptoms of anhedonia and PTSD in trauma-exposed women
Authors: Mehta Neeti D , Stevens Jennifer S , Li Zhihao , Gillespie Charles F , Fani Negar , Michopoulos Vasiliki , Felger Jennifer C
Published: April 2020

Trauma exposure is associated with increased inflammatory biomarkers (e.g. C-reactive protein [CRP] and cytokines), and inflammation has been shown to impact corticostriatal reward circuitry and increase anhedonia-related symptoms. We examined resting-state functional MRI in a high-trauma inner-city population of African-American women (n = 56), who reported on average five different types of trauma exposures, to investigate whether inflammation correlated with functional connectivity (FC) in corticostriatal reward circuitry in association with symptoms of anhedonia and PTSD. Plasma CRP negatively correlated with bilateral ventral striatum (VS) to ventromedial prefrontal cortex (vmPFC) FC (P < 0.01). In participants where plasma was available to also measure cytokines and their soluble receptors, left (L)VS-vmPFC FC negatively correlated with an inflammatory composite score (previously shown to be increased in plasma and cerebrospinal fluid of depressed patients with high CRP) only in women with significant PTSD symptoms (n = 14; r = −0.582, P = 0.029) and those who experienced moderate–severe childhood trauma (r = −0.595, P = 0.009). Exploratory analyses indicated that LVS-vmPFC FC correlated with anhedonia-related subscales from the Beck Depression Inventory (r = −0.691, P = 0.004) and PTSD Symptom Scale (avoidance/numbness; r = −0.514, P = 0.042) in participants with an inflammatory score over the median (n = 16). Results suggest that inflammation contributes to compromised reward circuitry and symptoms of anhedonia and PTSD in trauma-exposed women.
Exercising before a nap benefits memory better than napping or exercising alone
Authors: Mograss Melodee , Crosetta Monica , Abi-Jaoude Joanne , Frolova Elizaveta , Robertson Edwin M , Pepin Veronique , Dang-Vu Thien Thanh
Published: April 2020

Sleep leads to the enhancement of memory, and physical exercise also improves memory along with beneficial effects on sleep quality. Potentially, sleep and exercise may operate independently upon memory; alternatively, they may operate synergistically to boost memory above and beyond exercise or sleep alone. We tested this hypothesis in 115 young healthy adults (23 ± 3.9 years) randomly allocated to one of the four conditions in a 2 (exercise vs. no exercise) × 2 (nap vs. no nap) design. The exercise intervention consisted of a 40-minute, moderate intensity cycling, while the no exercise condition was an equivalent period of rest. This was followed by a learning session in which participants memorized a set of 45 neutral pictures for a later test. Subsequently, participants were exposed to either a 60-minute sleep period (nap) or an equivalent time of resting wakefulness, followed by a visual recognition test. We found a significant interaction between the effects of exercise and nap (p = 0.014, η p2 = 0.053), without significant main effects of exercise or nap conditions. Participants who experienced both exercise plus nap were significantly more accurate (83.8 ± 2.9) than those who only napped (81.1 ± 5.4, p = 0.027) and those who only exercised (78.6 ± 10.3, p = 0.012). Within the combined nap plus exercise group, higher recognition accuracies were associated with higher sleep spindle densities (r = 0.46, p = 0.015). Our results demonstrate that short-term exercise and a nap improve recognition memory over a nap or exercise alone. Exercise and sleep are not independent factors operating separately upon memory but work together to enhance long-term memory.
Sharing Psychotherapy Notes with Patients: Therapists’ Attitudes and Experiences
Authors: Chimowitz Hannah , O’Neill Stephen , Leveille Suzanne , Welch Katrina , Walker Jan
Published: April 2020

Evidence suggests that the practice of sharing clinicians’ notes with patients via online patient portals may increase patient engagement and improve patient–clinician relationships while requiring little change in providers’ workflow. Authors examined clinical social workers’ experiences and attitudes related to open psychotherapy notes using focus groups and telephone interviews. Twenty-four of 29 eligible therapists agreed to open their notes to patients, and nine participated in this study. Participants were generally positive about their experiences and reported few disruptions to their workload or practice. However, they were hesitant to bring up notes to patients during sessions, and they discussed the benefits of open therapy notes mostly hypothetically. The five therapists who did not share notes worried that open notes would be detrimental to therapeutic relationships, patient well-being, and workflow. However, the concern they discussed most often related to the electronic health record rather than to open notes, because therapy notes are visible to all authorized clinicians as part of the general medical record. Future research is needed to deepen our understanding of the risks and benefits of open psychotherapy notes and to inform development of training programs to support therapists in opening notes.
Comparative Phylogenetics of Papilio Butterfly Wing Shape and Size Demonstrates Independent Hindwing and Forewing Evolution
Authors: Owens H L , Lewis D S , Condamine F L , Kawahara A Y , Guralnick R P
Published: April 2020

The complex forces that shape butterfly wings have long been a subject of experimental and comparative research. Butterflies use their wings for flight, camouflage, mate recognition, warning, and mimicry. However, general patterns and correlations among wing shape and size evolution are still poorly understood. We collected geometric morphometric measurements from over 1400 digitized museum specimens of Papilio swallowtails and combined them with phylogenetic data to test two hypotheses: 1) forewing shape and size evolve independently of hindwing shape and size and 2) wing size evolves more quickly than wing shape. We also determined the major axes of wing shape variation and discovered that most shape variability occurs in hindwing tails and adjacent areas. We conclude that forewing shape and size are functionally and biomechanically constrained, whereas hindwings are more labile, perhaps in response to disruptive selective pressure for Batesian mimicry or against predation. The development of a significant, re-usable, digitized data resource will enable further investigation on tradeoffs between flight performance and ecological selective pressures, along with the degree to which intraspecific, local-scale selection may explain macroevolutionary patterns. [Batesian mimicry; Lepidoptera; geometric morphometrics; museum specimens.]
Investigation of hypoglycemic effects, oxidative stress potential and xanthine-oxidase activity of polyphenols (gallic acid, catechin) derived from faba bean on 3T3-L1 cell line: insights into molecular docking and simulation study
Authors: Choudhary Dhiraj Kumar , Chaturvedi Navaneet , Singh Amit , Mishra Abha
Published: April 2020

Hypoglycemic potential and xanthine-oxidase (XO) activity of polyphenols from faba bean were evaluated in the 3T3-L1 cell line, and an interaction study in silico with XO was performed with considerable bioactive components of acetone extract of faba beans. The protonated and fragmented behavior of acetone seed extract revealed the presence of gallic acid (MS/MS, m/z 169) and catechin (MSn, m/z 288.3). Flow cytometry study explained the effect of hydrogen peroxide (H2O2) on cell line as cell death was increased from 9.72 to 41.66% as compared to the control (without H2O2). The atomic force microscopy (AFM), scanning electron microscopy and reactive oxygen species measurement also confirmed the protective effect of polyphenols in the 3T3-L1 cell lines. Oxidative stress through propidium iodide and 4′,6-diamidino-2-phenylindole staining demonstrated that the apoptotic ratio was 0.35 ± 2.62 (P < 0.05) and 30 ± 2.54% in H2O2-treated cells, respectively, as compared to control. The observations of flow cytometry and confocal microscopy marked the effect of seed extract (0.86 ± 0.031, 3.52 ± 0.52, P < 0.05), on glucose uptake in cells through the better relative fluorescence intensity than that of the control. Moreover, molecular docking and molecular dynamics simulation studies gave an insight into the predicted residues that hold favorable polyphenolic-specific interactions. The probable binding modes of the gallic acid and catechin from this study may extend the knowledge of the XO-polyphenol interactions and offered the way to design the analogs of acetone seed extract with reduced toxicity.
Taxonomic revision of the pampas catLeopardus colocolacomplex (Carnivora: Felidae): an integrative approach
Authors: Nascimento Fabio Oliveira Do , Cheng Jilong , Feijó Anderson
Published: April 2020

The pampas cat Leopardus colocola has been subject to conflicting classifications over the years. Currently, one polytypic species with seven subspecies is recognized, but integrative taxonomic study for this debated group has never been done. Here, we combine the broadest morphological coverage of the pampas cat to date with molecular data and ecological niche models to clarify its species composition and test the validity of recently proposed subspecies. The multiple lines of evidence derived from morphology, molecular, biogeography and climatic niche datasets converged on the recognition of five monotypic species: L. braccatus, L. colocola, L. garleppi (including thomasi, budini, steinbachi, crespoi and wolffsohni as synonyms), L. munoai and L. pajeros (including crucina as synonym). These five species are morphologically diagnosable based on skin and skull traits, have evolved in distinct climatic niche spaces and were recovered in molecular species delimitation. Contrary to previous taxonomic arrangements, we do not recognize subspecies in pampas cats. To objectively define the two most controversial species, we designate neotypes for L. colocola and L. pajeros. The diversification of pampas cats is associated with Middle Pleistocene glaciations, but additional genetic samples from the central Andean region are still needed to conclusively reconstruct its evolutionary history.
Draft Genome Sequence Resource for Phyllachora maydis—An Obligate Pathogen That Causes Tar Spot of Corn with Recent Economic Impacts in the United States
Authors: Telenko Darcy E. P. , Ross Tiffanna J. , Shim Sujoung , Wang Qinhu , Singh Raksha
Published: April 2020

Phyllachora maydis is an important fungal pathogen that causes tar spot of corn and has led to significant yield loss in the United States and other countries. P. maydis is an obligate biotroph belonging to the Sordariomycetes class of Ascomycota. Due to the challenges posed by their obligate nature, there is no genome sequence available in the Phyllachora genus. P. maydis isolate PM01 was collected from a corn field in Indiana and the genome was determined by next-generation sequencing. The assembly size is 45.7 Mb, with 56.46% repetitive sequences. There are 5,992 protein-coding genes and 59 are predicted as effector proteins. This genome resource will increase our understanding of genomic features of P. maydis and will assist in studying the corn–P. maydis interaction and identifying potential resistant candidates for corn breeding programs.
Patterns of Care for Stage II-III Rectosigmoid Cancers in the United States, 2004-2015
Authors: Sanford Nina N. , Aguilera Todd A. , Beg Muhammad S. , Sanjeevaiah Aravind , Hong Theodore S. , Wo Jennifer Y. , Folkert Michael R.
Published: April 2020

Objectives:

Although current guidelines continue to recommend trimodality therapy for stage II to III rectal cancers, a lower incidence of local recurrence has been observed in patients with upper rectal tumors, including those in the rectosigmoid. In practice, patients with upper rectal tumors may not be receiving all 3 modalities of therapy. Patterns of care for patients with rectosigmoid cancers have not previously been described.

Methods:

The National Cancer Database (NCDB) was used to identify patients diagnosed with stage II to III rectosigmoid cancer who underwent definitive surgery between 2004 and 2015. Multivariable logistic regression defined adjusted odds ratio and associated 95% confidence intervals of receipt of any pelvic radiotherapy and preoperative and postoperative pelvic radiotherapy. Multivariable logistic regression also assessed odds of treatment with any chemotherapy and multiagent chemotherapy.

Results:

Among 8410 patients, 3566 (42.4%) received any pelvic radiotherapy, of which 2516 (70.6%) were treated with preoperative radiotherapy. Factors associated with receipt of radiotherapy included male sex, white race, younger age, positive clinical nodes and positive margins (P<0.001). Among patients with clinically positive nodes, 1980 (48.6%) received any radiotherapy and among those with pathologically positive nodes, 1532 (37.9%) received radiotherapy. A total of 5708 patients (67.9%) received any chemotherapy including 3020 (52.9%) with multiagent chemotherapy. A total of 2579 (30.7%) of the cohort was treated with surgery alone and among patients who were T3N0, this proportion rose to 42.5%.

Conclusions:

Less than half of patients with stage II to III rectosigmoid cancers are treated with radiation therapy and approximately one third do not receive chemotherapy. Ongoing and future studies may help to better tailor treatment for rectosigmoid tumors to optimize the therapeutic ratio. Our work may serve as a benchmark on which to compare future practice patterns.
Brain Metastases From Gynecologic Malignancies
Authors: Nasioudis Dimitrios , Persaud Anitra , Taunk Neil K. , Latif Nawar A.
Published: April 2020

Objective:

The objective of this study was to investigate the prevalence, clinicopathologic characteristics, management, and outcomes of patients with brain metastasis (BM) from gynecologic malignancies in a large hospital-based database.

Materials and Methods:

The National Cancer Database (NCDB) was accessed and patients with ovarian, uterine, or cervical cancer and BM were identified. We identified those who received radiation therapy (RT) as whole-brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS). Kaplan-Meier curves were generated to determine median overall survival (OS) and compared with the log-rank test.

Results:

A total of 853 patients with BM were identified. The rate of BMs upon diagnosis was 0.4% (211/57,160) for patients with cervical cancer, 0.2% (498/243,785) for patients with uterine, and 0.2% (144/92,301) for ovarian malignancies. Only 30.4% had isolated BM, while 52.2% had lung metastasis. Approximately half of the patients (50.1%) received chemotherapy, while brain RT was administered to 324 (38%) patients. Among patients who received brain RT, only 60 (18.5%) had SRS, while 264 (81.5%) had WBRT. Patients who underwent SRS had a better survival (n=47, median OS=9 mo) than those who received WBRT (n=201, median OS=4.73 mo, P=0.018), or those who did not receive any brain RT (n=370, median OS=4.01 mo, P=0.007).

Conclusions:

The incidence of BM among patients with gynecologic malignancies is rare and associated with poor survival. For select patients, SRS may be associated with prolonged survival.
Use of the CUSUM and Shewhart control chart methods to identify changes of public health significance using childhood blood lead surveillance data
Authors: Dignam Timothy , Hodge James , Chuke Stella , Mercado Carlos , Ettinger Adrienne S. , Flanders W. Dana
Published: April 2020

Background:

Local, state, and national childhood blood lead surveillance is based on healthcare providers and clinical laboratories reporting test results to public health departments. Increased interest in detecting blood lead level (BLL) patterns and changes of potential public health significance in a timely manner has highlighted the need for surveillance systems to rapidly detect and investigate these events.

Objective:

Decrease the time to detect changes in surveillance patterns by using an alerting algorithm developed and assessed through historical child blood lead surveillance data analysis.

Methods:

We applied geographic and temporal data-aggregation strategies on childhood blood lead surveillance data and developed a novel alerting algorithm. The alerting algorithm employed a modified cumulative summary/Shewhart algorithm, initially applied on 113 months of data from two jurisdictions with a known increase in the proportion of children <6 years of age with BLLs ≥5 µg/dl.

Results:

Alert signals retrospectively identified time periods in two jurisdictions where a known change in the proportion of children <6 years of age with BLLs ≥5 µg/dl occurred. Additionally, we identified alert signals among six of the 18 (33%) randomly selected counties assessed where no previously known or suspected pattern changes existed.

Conclusion:

The modified cumulative summary/Shewhart algorithm provides a framework for enhanced blood lead surveillance by identifying changes in the proportion of children with BLLs ≥5 µg/dl. The algorithm has the potential to alert public health officials to changes requiring further important public health investigation.