bluuebunny/crossref_metadata_2025 huggingface dataset:
Gemini NIFS survey of feeding and feedback in nearby active galaxies – IV. Excitation
Authors: Riffel Rogemar A , Bianchin Marina , Riffel Rogério , Storchi-Bergmann Thaisa , Schönell Astor J , Dahmer-Hahn Luis Gabriel , Dametto Natacha Z , Diniz Marlon R
Published: March 2021

The near-infrared spectra of active galactic nuclei (AGN) present emission lines of different atomic and molecular species. The mechanisms involved in the origin of these emission lines in AGN are still not fully understood. We use J- and K-band integral field spectra of six luminous ($43.1\lt \log L_{\rm bol}/({\rm erg\, s^{-1}})\lt 44.4$) Seyfert galaxies (NGC 788, Mrk 607, NGC 3227, NGC 3516, NGC 5506, and NGC 5899) in the local Universe (0.0039 < z < 0.0136) to investigate the gas excitation within the inner 100–300 pc radius of the galaxies at spatial resolutions of a few tens of parsecs. In all galaxies, the H2 emission originates from thermal processes with excitation temperatures in the range 2400–5200 K. In the high-line ratio (HLR) region of the H2/Brγ versus [Fe ii]/Paβ diagnostic diagram, which includes 29 per cent of the spaxels, shocks are the main excitation mechanism, as indicated by the correlation between the line widths and line ratios. In the AGN region of the diagram (64 per cent of the spaxels) the H2 emission is due to the AGN radiation. The [Fe ii] emission is produced by a combination of photoionization by the AGN radiation and shocks in five galaxies and is dominated by photoionization in NGC 788. The [S ix]1.2523 μm coronal emission line is present in all galaxies, and its flux distributions are extended from 80 to 185 pc from the galaxy nuclei, except for NGC 5899, in which this line is detected only in the integrated spectrum.
IMF-induced intrinsic uncertainties on measuring galaxy distances based on the number of giant stars: the case of the ultradiffuse galaxy NGC 1052-DF2
Authors: Zonoozi Akram Hasani , Haghi Hosein , Kroupa Pavel
Published: March 2021

The surface brightness fluctuation (SBF) technique is one of the distance measurement methods that has been applied on the low surface brightness (LSB) galaxy NGC 1052-DF2 yielding a distance of about 20 Mpc implying it to be a dark matter deficient galaxy. We assume the number of giant stars above a given luminosity threshold to represent the SBF magnitude. The SBF magnitude depends on the distance, but this is degenerate with the star formation history (SFH). Using a stellar population synthesis model, we calculate the number of giant stars for stellar populations with different galaxy-wide stellar initial mass functions (gwIMFs), ages, metallicities, and SFHs. If the gwIMF is the invariant canonical IMF, the 1σ (3σ) uncertainty in colour allows a distance as low as 12 Mpc (8 Mpc). If instead the true underlying gwIMF is the integrated galaxy-wide IMF (IGIMF) then overestimating distances for low-mass galaxies would be a natural result, allowing NGC 1052-DF2 to have a distance of 11 Mpc within the 1σ colour uncertainty. Finally, we show that our main conclusion on the existence of a bias in the SBF distance estimation is not much affected by changing the luminosity lower limit for counting giant stars.
WISDOM project – VIII. Multiscale feedback cycles in the brightest cluster galaxy NGC 0708
Authors: North Eve V , Davis Timothy A , Bureau Martin , Gaspari Massimo , Cappellari Michele , Iguchi Satoru , Liu Lijie , Onishi Kyoko , Sarzi Marc , Smith Mark D , Williams Thomas G
Published: March 2021

We present high-resolution (synthesized beam size 0${_{.}^{\prime\prime}}$088 × 0${_{.}^{\prime\prime}}$083 or 25 × 23 pc2) Atacama Large Millimetre/submillimetre Array 12CO(2–1) line and 236 GHz continuum observations, as well as 5 GHz enhanced Multi-Element Radio Linked Interferometer Network (e-MERLIN) continuum observations, of NGC 0708; the brightest galaxy in the low-mass galaxy cluster Abell 262. The line observations reveal a turbulent, rotating disc of molecular gas in the core of the galaxy, and a high-velocity, blueshifted feature ≈0${_{.}^{\prime\prime}}$4 (≈113 pc) from its centre. The submillimetre continuum emission peaks at the nucleus, but extends towards this anomalous CO emission feature. No corresponding elongation is found on the same spatial scales at 5 GHz with e-MERLIN. We discuss potential causes for the anomalous blueshifted emission detected in this source, and conclude that it is most likely to be a low-mass in-falling filament of material condensing from the hot intracluster medium via chaotic cold accretion, but it is also possible that it is a jet-driven molecular outflow. We estimate the physical properties this structure has in these two scenarios, and show that either explanation is viable. We suggest future observations with integral field spectrographs will be able to determine the true cause of this anomalous emission, and provide further evidence for interaction between quenched cooling flows and mechanical feedback on both small and large scales in this source.
A phage satellite tunes inducing phage gene expression using a domesticated endonuclease to balance inhibition and virion hijacking
Authors: Netter Zoe , Boyd Caroline M , Silvas Tania V , Seed Kimberley D
Published: March 2021

Bacteria persist under constant threat of predation by bacterial viruses (phages). Bacteria-phage conflicts result in evolutionary arms races often driven by mobile genetic elements (MGEs). One such MGE, a phage satellite in Vibrio cholerae called PLE, provides specific and robust defense against a pervasive lytic phage, ICP1. The interplay between PLE and ICP1 has revealed strategies for molecular parasitism allowing PLE to hijack ICP1 processes in order to mobilize. Here, we describe the mechanism of PLE-mediated transcriptional manipulation of ICP1 structural gene transcription. PLE encodes a novel DNA binding protein, CapR, that represses ICP1’s capsid morphogenesis operon. Although CapR is sufficient for the degree of capsid repression achieved by PLE, its activity does not hinder the ICP1 lifecycle. We explore the consequences of repression of this operon, demonstrating that more stringent repression achieved through CRISPRi restricts both ICP1 and PLE. We also discover that PLE transduces in modified ICP1-like particles. Examination of CapR homologs led to the identification of a suite of ICP1-encoded homing endonucleases, providing a putative origin for the satellite-encoded repressor. This work unveils a facet of the delicate balance of satellite-mediated inhibition aimed at blocking phage production while successfully mobilizing in a phage-derived particle.
A conserved BAH module within mammalian BAHD1 connects H3K27me3 to Polycomb gene silencing
Authors: Fan Huitao , Guo Yiran , Tsai Yi-Hsuan , Storey Aaron J , Kim Arum , Gong Weida , Edmondson Ricky D , Mackintosh Samuel G , Li Haitao , Byrum Stephanie D , Tackett Alan J , Cai Ling , Wang Gang Greg
Published: March 2021

Trimethylation of histone H3 lysine 27 (H3K27me3) is important for gene silencing and imprinting, (epi)genome organization and organismal development. In a prevalent model, the functional readout of H3K27me3 in mammalian cells is achieved through the H3K27me3-recognizing chromodomain harbored within the chromobox (CBX) component of canonical Polycomb repressive complex 1 (cPRC1), which induces chromatin compaction and gene repression. Here, we report that binding of H3K27me3 by a Bromo Adjacent Homology (BAH) domain harbored within BAH domain-containing protein 1 (BAHD1) is required for overall BAHD1 targeting to chromatin and for optimal repression of the H3K27me3-demarcated genes in mammalian cells. Disruption of direct interaction between BAHD1BAH and H3K27me3 by point mutagenesis leads to chromatin remodeling, notably, increased histone acetylation, at its Polycomb gene targets. Mice carrying an H3K27me3-interaction-defective mutation of Bahd1BAH causes marked embryonic lethality, showing a requirement of this pathway for normal development. Altogether, this work demonstrates an H3K27me3-initiated signaling cascade that operates through a conserved BAH ‘reader’ module within BAHD1 in mammals.
A systematic review and meta-analysis of prospective studies on obesity and risk of inflammatory bowel disease
Authors: Milajerdi Alireza , Abbasi Fatemeh , Esmaillzadeh Ahmad
Published: March 2021

Context

There are only a few systematic reviews on the association of obesity with risk of inflammatory bowel disease (IBD) to date.

Objective

The current study was undertaken to systematically review prospective cohort studies on the association between body mass index (BMI) and risk of IBD. It was carried out according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines.

Data Sources

Relevant prospective cohort studies published from 1969 to July 2020 were searched through PubMed, MEDLINE, SCOPUS, EMBASE, and Google Scholar, using suitable keywords.

Data Extraction

Hazard ratios (HRs) or relative risks (RRs) and 95% confidence intervals (CIs) for IBD or its subtypes across categories of BMI were extracted.

Data Analysis

The log HRs/RRs, including standard errors, were calculated based on reported HRs or RRs and their 95% CIs, and overall effect size was calculated using a fixed-effects model. All statistical analyses were done using STATA version 14.0 (Stata Corp LP, College Station, TX, USA).

Conclusion

Overall, 9 studies were included. Combining findings from 5 studies, a statistically significant 21% lower risk of ulcerative colitis incidence was found in patients with obesity than in those with normal weight (RR, 0.79; 95% CI, 0.68–0.92; I2= 0.0%), but not with risk of ulcerative colitis exacerbation, as found by meta-analysis of 3 studies. Pooling data from 5 studies, no significant differences were seen in the risk of Crohn’s disease incidence between patients in the highest range of BMI and those in the normal range. In addition, no significant nonlinear association was found between BMI and risk of Crohn’s disease (P=0.94). A significant inverse association was found between obesity and total IBD incidence (RR, 0.76; 95% CI, 0.66–0.88; I2=93.2%), but not between increasing BMI and IBD exacerbation, or between increasing BMI and IBD incidence.
Predicting poverty trends by survey-to-survey imputation: the challenge of comparability
Authors: Mathiassen Astrid , Wold Bjørn K. Getz
Published: March 2021

Poverty in low-income countries is usually measured using large and infrequent household consumption surveys. The challenge is to find methods to measure poverty rates more frequently. This study validates a survey-to-survey imputation method, based on a statistical model utilizing consumption surveys and light surveys to measure changes in poverty rates over time. A decade of poverty predictions and regular poverty estimates in Malawi provides a unique case study. The analysis suggests that this modelling approach works within the same context given that households’ demographic composition is included in the model. Predicting poverty using different surveys is challenging because of different aspects of comparability. A new way to account for seasonal coverage strengthens the model when imputing for surveys covering different seasons. It is important for national statistics offices and supporting agencies to prioritize maintaining consistency in the way data are collected in surveys to provide comparable trends over time.
Single-cell metabarcoding reveals biotic interactions of the Arctic calcifier Neogloboquadrina pachyderma with the eukaryotic pelagic community
Authors: Greco Mattia , Morard Raphaël , Kucera Michal
Published: March 2021

Isotopic and trace-element signals in the calcite shells of the planktonic foraminifera Neogloboquadrina pachyderma represent key proxies to reconstruct past climatic conditions in northern high latitudes. A correct interpretation of these chemical signals requires knowledge of the habitat and trophic interactions of the species. Direct observations on the biological interactions of N. pachyderma in polar environments are lacking and to date no consensus exists on the trophic behavior of this species. Here, we use single-cell metabarcoding to characterize the interactions of 39 specimens of N. pachyderma from two sites in the Baffin Bay with the local eukaryotic pelagic community. Our results show that the eukaryotic interactome of the foraminifera is dominated by diatoms, accounting for >50% of the reads in 17 of the samples, but other groups such as Crustacea and Syndiniales are also present. The high abundance Syndiniales suggests that these parasites could infect N. pachyderma and may play an important role in its population dynamics. Moreover, the strong but taxonomically non-specific association with algae, existing irrespective of depth and occurring in specimens collected far below the photic zone indicates that opportunistically grazed diatom-fueled marine aggregates likely represent the main interaction substrate of N. pachyderma.
Spatiotemporal genetic structure in theDaphnia pulexcomplex from Sierra Nevada lakes (Spain): reproductive mode and first record of North AmericanD.cf.pulexin European alpine lakes
Authors: Conde-Porcuna José M , Veiga Jesús , Moreno Emilio , Jiménez Laura , Ramos-Rodríguez Eloísa , Pérez-Martínez Carmen
Published: March 2021

Daphnia is a good model organism for studying factors affecting dispersal and patterns of genetic diversity. Within this genus, the Daphnia pulex species complex includes lineages from North America and Europe, with some considered invaders in various continents, although their colonization history is poorly known. We used mitochondrial DNA and microsatellite markers to identify the D. pulex complex lineages in Sierra Nevada, determine their reproductive mode and reconstruct their genetic history (over the past ~25 to 65 years). We present the first recording of North American (NA) D. cf. pulex in a European high-mountain lake, showing its arrival ~65 years ago in lake Borreguil without temporal changes in its genetic structure. European (Eu) D. cf. pulicaria is the only lineage present in other Sierra Nevada lakes and also showed no genetic change over time. The results for both species are congruent with obligate parthenogenetic reproduction mode. Moreover, water mineralization may influence the clonal distribution of the D. pulex complex in Sierra Nevada, without ruling out dispersal limitation and/or founder effects. Although NA D. cf. pulex had not spread to other Sierra Nevada lakes, it could threaten Eu D. cf. pulicaria in Sierra Nevada and other European alpine lakes.
Systematic analysis of specific and nonspecific auxin effects on endocytosis and trafficking
Authors: Narasimhan Madhumitha , Gallei Michelle , Tan Shutang , Johnson Alexander , Verstraeten Inge , Li Lanxin , Rodriguez Lesia , Han Huibin , Himschoot Ellie , Wang Ren , Vanneste Steffen , Sánchez-Simarro Judit , Aniento Fernando , Adamowski Maciek , Friml Jiří
Published: March 2021

The phytohormone auxin and its directional transport through tissues are intensively studied. However, a mechanistic understanding of auxin-mediated feedback on endocytosis and polar distribution of PIN auxin transporters remains limited due to contradictory observations and interpretations. Here, we used state-of-the-art methods to reexamine the auxin effects on PIN endocytic trafficking. We used high auxin concentrations or longer treatments versus lower concentrations and shorter treatments of natural indole-3-acetic acid (IAA) and synthetic naphthalene acetic acid (NAA) auxins to distinguish between specific and nonspecific effects. Longer treatments of both auxins interfere with Brefeldin A-mediated intracellular PIN2 accumulation and also with general aggregation of endomembrane compartments. NAA treatment decreased the internalization of the endocytic tracer dye, FM4-64; however, NAA treatment also affected the number, distribution, and compartment identity of the early endosome/trans-Golgi network, rendering the FM4-64 endocytic assays at high NAA concentrations unreliable. To circumvent these nonspecific effects of NAA and IAA affecting the endomembrane system, we opted for alternative approaches visualizing the endocytic events directly at the plasma membrane (PM). Using total internal reflection fluorescence microscopy, we saw no significant effects of IAA or NAA treatments on the incidence and dynamics of clathrin foci, implying that these treatments do not affect the overall endocytosis rate. However, both NAA and IAA at low concentrations rapidly and specifically promoted endocytosis of photo-converted PIN2 from the PM. These analyses identify a specific effect of NAA and IAA on PIN2 endocytosis, thus, contributing to its polarity maintenance and furthermore illustrate that high auxin levels have nonspecific effects on trafficking and endomembrane compartments.
Are There Gender Differences in Neck Pain and Musculoskeletal Disorders of the Cervical Spine Associated with Migraine?
Authors: Xavier Nathan da Silva , Benatto Mariana Tedeschi , Florencio Lidiane Lima , Fernández-de-las-Peñas César , Dach Fabiola , Bevilaqua-Grossi Débora
Published: March 2021

Objective

To evaluate gender differences in clinical characteristics of migraine by examining presence and severity of cutaneous allodynia, migraine-related disability, neck pain and its associated disability, passive mobility of the upper cervical spine, and performance of the deep neck flexor muscles.

Design

Cross-sectional study.

Subjects

30 men and 30 women with migraine.

Methods

Participants responded to the questionnaires Migraine Disability Assessment questionnaire, 12-item Allodynia Symptom Checklist, and Neck Disability Index. The mobility of the upper cervical spine was assessed by using the Flexion-Rotation Test. Performance of the deep neck flexor muscles was evaluated by applying the Craniocervical Flexion Test. Comparison of the groups was carried out by using the Student’s t-test or the χ2 test. The prevalence ratio was also calculated.

Results

Women showed a higher prevalence of cutaneous allodynia (P = .001) and a 4 times greater risk of having severe cutaneous allodynia than to men (P = 0.007). No gender differences were observed in migraine-related disability (P = .08). Women showed higher prevalence of self-reported neck pain (P = .03) and increased risk of having this symptom in comparison to men (Prevalence Ratio = 1.69; P = 0.025). However, there were no gender differences in neck pain-related disability (P = .25), mobility of the upper cervical spine (P = .92), or performance of the deep neck flexor muscles (P = .52).

Conclusion

Women with migraine had a higher frequency of self-reported neck pain and higher prevalence and severity of cutaneous allodynia when compared to men. However, the two groups did not differ regarding neck pain-related disability and performance in the physical tests.
Ultrasound, magnetic resonance imaging and radiography of the finger joints in psoriatic arthritis patients
Authors: Polachek Ari , Furer Victoria , Zureik Mirna , Nevo Sharon , Mendel Liran , Levartovsky David , Wollman Jonathan , Aloush Valerie , Tzemah Reut , Elalouf Ofir , Anouk Marina , Berman Mark , Kaufman Ilana , Lahat Yael , Sarbagil-Maman Hagit , Borok Sara , Broyde Adi , Eder Lihi , Paran Daphna , Iluz Moshe , Eshed Iris , Elkayam Ori
Published: March 2021

Objectives

To report the discrepancies and agreements between US, MRI and radiography of the hand in PsA, and to compare the sensitivity and specificity of US and radiography to MRI as the gold standard imaging study in PsA.

Methods

All of the 100 prospectively recruited consecutive PsA patients underwent clinical assessment and concomitant radiographic, US and MRI studies of the MCP, PIP and DIP joints of one hand. Synovitis, flexor tenosynovitis, extensor paratenonitis, erosions and bone proliferations were identified and scored. All readers were blinded to clinical data, and agreement was calculated based on prevalence-adjusted bias-adjusted kappa (PABAK).

Results

The prevalence of synovitis, flexor tenosynovitis, extensor paratenonitis and erosions was similar for US and MRI, while that of bone proliferation was significantly increased in US and radiography compared with MRI (P < 0.001). The absolute agreement between US and MRI was good-to-very good for synovitis (85–96%, PABAK = 0.70–0.92), flexor tenosynovitis (93–98%, PABAK = 0.87–0.96) and extensor paratenonitis (95–98%, PABAK = 0.90–0.97). Agreement between US, MRI and radiography was 96–98% (PABAK = 0.92–0.97) for erosions and 71–93% (PABAK = 0.47–0.87) for bone proliferations. Sensitivity of US with MRI as gold standard was higher for synovitis (0.5–0.86) and extensor paratenonitis (0.63–0.85) than for flexor tenosynovitis (0.1–0.75), while the specificity was high for each pathology (0.89–0.98).

Conclusion

There is very good agreement between US and MRI for the detection of inflammatory changes in finger joints in PsA. US, radiography and MRI have a good-to-very good agreement for destructive changes.
The role of reputation systems in digital discrimination
Authors: Kas Judith , Corten Rense , van de Rijt Arnout
Published: March 2021

Reputation systems are commonplace in online markets, such as on peer-to-peer sharing platforms. These systems have been argued to be a solution to (ethnic) discrimination on such platforms. This argument is based on empirical studies showing that ethnic disadvantages are smaller for users with ratings than for users without ratings. We argue that this conclusion may be premature, because minorities have a harder time accumulating ratings. The greater benefit of ratings to minorities may be offset by their troubles acquiring any, thereby diminishing the potential for reputation systems to reduce discrimination. We tested this counterargument using a unique data set that contains information on all interactions on a peer-to-peer motorcycle rental platform. We find that the reputation system does not reduce initial inequalities between otherwise comparable renters of different ethnicity. Platforms that wish to reduce discrimination should not only make their reputation system more effective, but also help users collect ratings.
An exploratory focus group study on experiences with snakebites: health-seeking behaviour and challenges in rural communities of Kenya
Authors: van Oirschot Janneke , Ooms Gaby I , Okemo Dorothy J , Waldmann Benjamin , Reed Tim
Published: March 2021

Background

Snakebite envenoming is a long-hidden public health threat in the rural communities of Kenya. This study aimed to shed light on the health-seeking behaviour of people bitten by snakes, views on prevention measures and community needs and the consequences for snakebite patients in these areas.

Methods

Six focus group interviews were conducted in communities in the Kajiado (n=3) and Kilifi (n=3) counties.

Results

Traditional first-aid practices such as the use of a tourniquet and/or cutting the wound, use of a black stone and a variety of other traditional remedies were common. Challenges with transportation to health facilities and inadequately resourced facilities complicated accessing medical care. Community members voiced a need to improve access to trained healthcare workers and snakebite treatments at health facilities.

Conclusion

While communities had high trust in evidence-based medical care, traditional treatment was often sought, causing delays in timely medical attention. Traditional practices were often used in the home environment and these were not usually administered by a traditional healer. The findings illustrate the need to combine improving the availability of effective snakebite treatment and healthcare worker training on snakebite with community education to reduce the impact of snakebite.
What We Learn about Girls’ Education from Interventions That Do Not Focus on Girls
Authors: Evans David K , Yuan Fei
Published: March 2021

What is the best way to improve access and learning outcomes for girls? This review brings together evidence from 267 educational interventions in 54 low- and middle-income countries – regardless of whether the interventions specifically target girls – and identifies their impacts on girls. To improve access and learning, general interventions deliver average gains for girls that are comparable to girl-targeted interventions. General interventions have similar impacts for girls as for boys. Taken together, these findings suggest that many educational gains for girls may be achieved through nontargeted programs. Many of the most effective interventions to improve access for girls relax household-level constraints (such as cash transfer programs), and many of the most effective interventions to improve learning for girls involve improving the pedagogy of teachers. Girl-targeted interventions may make the most sense when addressing constraints that are unique to, or most pronounced for, girls.
Modeling ‘Candidatus Liberibacter asiaticus’ Movement Within Citrus Plants
Authors: Raiol-Junior Laudecir L. , Cifuentes-Arenas Juan C. , Cunniffe Nik J. , Turgeon Robert , Lopes Silvio A.
Published: March 2021

The phloem-limited ‘Candidatus Liberibacter asiaticus’ (Las) causes huanglongbing, a destructive citrus disease. Graft-inoculated potted plants were used to assess Las speed of movement in phloem in the greenhouse, and the impacts of temperature on plant colonization in growth-chamber experiments. For assessment of Las speed, plants were inoculated at the main stem and assessed over time by quantitative PCR (qPCR) or symptoms at various distances from the inoculum. For colonization, the plants were inoculated in one of two opposite top branches, maintained at from 8 to 20°C, from 18 to 30°C, or from 24 to 38°C daily range, and assessed by qPCR of samples taken from noninoculated shoots. For all experiments, frequencies of Las-positive sites were submitted to analysis of variance and binomial generalized linear model and logistic regression analyses. Probabilities of detecting Las in greenhouse plants were functions of time and distance from the inoculation site, which resulted in 2.9 and 3.8 cm day−1 average speed of movement. In growth chambers, the temperature impacted plant colonization by Las, new shoot emission, and symptom expression. After a 7-month exposure time, Las was absent in all new shoots in the cooler environment (average three per plant), and present in 70% at the milder environment (six shoots, severe symptoms) and 25% in the warmer environment (eight shoots, no visible symptoms). Temperature of 25.7°C was the optimum condition for plant colonization. This explains the higher impact and incidence of huanglongbing disease during the winter months or regions of milder climates in Brazil.
Reduction of leukemic burden via bone‐targeted nanoparticle delivery of an inhibitor of C‐chemokine (C‐C motif) ligand 3 (CCL3) signaling
Authors: Ackun‐Farmmer Marian A. , Soto Celia A. , Lesch Maggie L. , Byun Daniel , Yang Lila , Calvi Laura M. , Benoit Danielle S. W. , Frisch Benjamin J.
Published: March 2021

Leukemias are challenging diseases to treat due, in part, to interactions between leukemia cells and the bone marrow microenvironment (BMME) that contribute significantly to disease progression. Studies have shown that leukemic cells secrete C‐chemokine (C‐C motif) ligand 3 (CCL3), to disrupt the BMME resulting in loss of hematopoiesis and support of leukemic cell survival and proliferation. In this study, a murine model of blast crisis chronic myelogenous leukemia (bcCML) that expresses the translocation products BCR/ABL and Nup98/HoxA9 was used to determine the role of CCL3 in BMME regulation. Leukemic cells derived from CCL3−/− mice were shown to minimally engraft in a normal BMME, thereby demonstrating that CCL3 signaling was necessary to recapitulate bcCML disease. Further analysis showed disruption in hematopoiesis within the BMME in the bcCML model. To rescue the altered BMME, therapeutic inhibition of CCL3 signaling was investigated using bone‐targeted nanoparticles (NP) to deliver Maraviroc, an inhibitor of C‐C chemokine receptor type 5 (CCR5), a CCL3 receptor. NP‐mediated Maraviroc delivery partially restored the BMME, significantly reduced leukemic burden, and improved survival. Overall, our results demonstrate that inhibiting CCL3 via CCR5 antagonism is a potential therapeutic approach to restore normal hematopoiesis as well as reduce leukemic burden within the BMME.
Follicle‐stimulating hormone promotes growth of human prostate cancer cell line‐derived tumor xenografts
Authors: Oduwole Olayiwola O. , Poliandri Ariel , Okolo Anthony , Rawson Phil , Doroszko Milena , Chrusciel Marcin , Rahman Nafis A. , Serrano de Almeida Gilberto , Bevan Charlotte L. , Koechling Wolfgang , Huhtaniemi Ilpo T.
Published: March 2021

Chemical castration in prostate cancer can be achieved with gonadotropin‐releasing hormone (GnRH) agonists or antagonists. Their effects differ by the initial flare of gonadotropin and testosterone secretion with agonists and the immediate pituitary‐testicular suppression by antagonists. While both suppress luteinizing hormone (LH) and follicle‐stimulating hormone (FSH) initially, a rebound in FSH levels occurs during agonist treatment. This rebound is potentially harmful, taken the expression of FSH receptors (R) in prostate cancer tissue. We herein assessed the role of FSH in promoting the growth of androgen‐independent (PC‐3, DU145) and androgen‐dependent (VCaP) human prostate cancer cell line xenografts in nude mice. Gonadotropins were suppressed with the GnRH antagonist degarelix, and effects of add‐back human recombinant FSH were assessed on tumor growth. All tumors expressed GnRHR and FSHR, and degarelix treatment suppressed their growth. FSH supplementation reversed the degarelix‐evoked suppression of PC‐3 tumors, both in preventive (degarelix and FSH treatment started upon cell inoculation) and therapeutic (treatments initiated 3 weeks after cell inoculation) setting. A less marked, though significant FSH effect occurred in DU145, but not in VCaP xenografts. FSHR expression in the xenografts supports direct FSH stimulation of tumor growth. Testosterone supplementation, to maintain the VCaP xenografts, apparently masked the FSH effect on their growth. Treatment with the LH analogue hCG did not affect PC‐3 tumor growth despite their expression of luteinizing hormone/choriongonadotropin receptor. In conclusion, FSH, but not LH, may directly stimulate the growth of androgen‐independent prostate cancer, suggesting that persistent FSH suppression upon GnRH antagonist treatment offers a therapeutic advantage over agonist.
Proteomic and phospholipidomic characterization of extracellular vesicles inducing tumor microenvironment in Epstein‐Barr virus‐associated lymphomas
Authors: Ito Masatoshi , Kudo Kai , Higuchi Hiroshi , Otsuka Hiroko , Tanaka Masayuki , Fukunishi Nahoko , Araki Takuma , Takamatsu Masako , Ino Yoko , Kimura Yayoi , Kotani Ai
Published: March 2021

Epstein‐Barr virus (EBV) causes malignant carcinomas including B cell lymphomas accompanied by the systemic inflammation. Previously, we observed that phosphatidylserine (PS)‐exposing subset of extracellular vesicles (EVs) secreted from an EBV strain Akata‐transformed lymphoma (Akata EVs) convert surrounding phagocytes into tumor‐associated macrophages (TAMs) via induction of inflammatory response, which is in part mediated by EBV‐derived micro RNAs. However, it is still unclear about EV‐carried other potential inflammatory factors associated with TAM formation in EBV lymphomas. To this end, we sought to explore proteomic and phospholipidomic profiles of PS‐exposing EVs derived from EBV‐transformed lymphomas. Mass spectrometric analysis revealed that several immunomodulatory proteins including integrin αLβ2 and fibroblast growth factor 2 (FGF2) were highly expressed in PS‐exposing Akata EVs compared with another EBV strain B95‐8‐transformed lymphoma‐derived counterparts which significantly lack TAM‐inducing ability. Pharmacological inhibition of either integrin αLβ2 or FGF2 hampered cytokine induction in monocytic cultured cells elicited by PS‐exposing Akata EVs, suggesting the involvement of these proteins in EV‐mediated TAM induction in EBV lymphomas. In addition, phospholipids containing precursors of immunomodulatory lipid mediators were also enriched in PS‐exposing Akata EVs compared with B95‐8 counterparts. Phospholipidomic analysis of fractionated Akata EVs by density gradient centrifugation further demonstrated that PS‐exposing Akata EVs might be identical to certain Akata EVs in low density fractions containing exosomes. Therefore, we concluded that a variety of immunomodulatory cargo molecules in a certain EV subtype are presumably conducive to the development of EBV lymphomas.
Prevalence and Clinical Characteristics of Patients With Sepsis Discharge Diagnosis Codes and Short Lengths of Stay in U.S. Hospitals
Authors: Kuye Ifedayo , Anand Vijay , Klompas Michael , Chan Christina , Kadri Sameer S. , Rhee Chanu
Published: March 2021

Objectives:

Some patients diagnosed with sepsis have very brief hospitalizations. Understanding the prevalence and clinical characteristics of these patients may provide insight into how sepsis diagnoses are being applied as well as the breadth of illnesses encompassed by current sepsis definitions.

Design:

Retrospective observational study.

Setting:

One-hundred ten U.S. hospitals in the Cerner HealthFacts dataset (primary cohort) and four hospitals in Eastern Massachusetts (secondary cohort used for detailed medical record reviews).

Patients:

Adults hospitalized from April 2016 to December 2017.

Interventions:

None.

Measurements and Main Results:

We identified hospitalizations with International Classification of Diseases, 10th Edition codes for sepsis (including sepsis, septicemia, severe sepsis, and septic shock) and compared “short stay sepsis” patients (defined as discharge alive within 3 d) versus nonshort stay sepsis patients using detailed electronic health record data. In the Cerner cohort, 67,733 patients had sepsis discharge diagnosis codes, including 6,918 (10.2%) with short stays. Compared with nonshort stay sepsis patients, short stay patients were younger (median age 60 vs 67 yr) and had fewer comorbidities (median Elixhauser score 5 vs 13), lower rates of positive blood cultures (8.2% vs 24.1%), lower rates of ICU admission (6.2% vs 31.6%), and less frequently had severe sepsis/septic shock codes (13.5% vs 36.6%). Almost all short stay and nonshort stay sepsis patients met systemic inflammatory response syndrome criteria at admission (84.5% and 87.5%, respectively); 47.2% of those with short stays had Sequential Organ Failure Assessment scores of 2 or greater at admission versus 73.2% of those with longer stays. Findings were similar in the secondary four-hospital cohort. Medical record reviews demonstrated that physicians commonly diagnosed sepsis based on the presence of systemic inflammatory response syndrome criteria, elevated lactates, or positive blood cultures without concurrent organ dysfunction.

Conclusions:

In this large U.S. cohort, one in 10 patients coded for sepsis were discharged alive within 3 days. Although most short stay patients met systemic inflammatory response syndrome criteria, they met Sepsis-3 criteria less than half the time. Our findings underscore the incomplete uptake of Sepsis-3 definitions, the breadth of illness severities encompassed by both traditional and new sepsis definitions, and the possibility that some patients with sepsis recover very rapidly.
Identifying sensitive windows of airborne lead exposure associated with behavioral outcomes at age 12
Authors: Rasnick Erika , Ryan Patrick H. , Bailer A. John , Fisher Thomas , Parsons Patrick J. , Yolton Kimberly , Newman Nicholas C. , Lanphear Bruce P. , Brokamp Cole
Published: March 2021

Background:

Despite the precipitous decline of airborne lead concentrations following the removal of lead in gasoline, lead is still detectable in ambient air in most urban areas. Few studies, however, have examined the health effects of contemporary airborne lead concentrations in children.

Methods:

We estimated monthly air lead exposure among 263 children (Cincinnati Childhood Allergy and Air Pollution Study; Cincinnati, OH; 2001–2005) using temporally scaled predictions from a validated land use model and assessed neurobehavioral outcomes at age 12 years using the parent-completed Behavioral Assessment System for Children, 2nd edition. We used distributed lag models to estimate the effect of airborne lead exposure on behavioral outcomes while adjusting for potential confounding by maternal education, community-level deprivation, blood lead concentrations, greenspace, and traffic related air pollution.

Results:

We identified sensitive windows during mid- and late childhood for increased anxiety and atypicality scores, whereas sensitive windows for increased aggression and attention problems were identified immediately following birth. The strongest effect was at age 12, where a 1 ng/m3 increase in airborne lead exposure was associated with a 3.1-point (95% confidence interval: 0.4, 5.7) increase in anxiety scores. No sensitive windows were identified for depression, somatization, conduct problems, hyperactivity, or withdrawal behaviors.

Conclusions:

We observed associations between exposure to airborne lead concentrations and poor behavioral outcomes at concentrations 10 times lower than the National Ambient Air Quality Standards set by the US Environmental Protection Agency.
Reconstruction of the Midfoot Area with Vascularized Chimeric Osteocutaneous Scapula Flap: A Case Report
Authors: Arata Jun , Tsuge Itaru , Kumakiri Masanori , Yamashita Teruyo , Kaito Shuko , Yong Yoon , Yamada Shigeru
Published: March 2021

We report a case of reconstruction of a left midfoot defect with a chimeric partial scapula and skin flap in a 20-year-old man. After radical debridement, bone and soft tissue defects were reconstructed with a chimeric scapula and skin flap. The postoperative course was uneventful. The patient could walk well without support, and bone union was achieved 6 months after surgery. In 14 months of follow-up, no clinical complications (including new ulcer or stress fracture) were noted and full ambulation was achieved, with the patient returning to his previous work. We suggest that the chimeric scapula and skin flap may be a useful alternative option for midfoot reconstruction.
The prognostic value of IL-8 for the death of severe or critical patients with COVID-19
Authors: Li Hui , Zhang Jun , Fang Chen , Zhao Xuming , Qian Bin , Sun Yihui , Zhou Yan , Hu Ji , Huang Yun , Ma Qi , Hui Jie
Published: March 2021

Inflammation has been believed to contribute to coronavirus disease 2019 (COVID-19). Risk factors for death of COVID-19 pneumonia have not yet been well established.

In this retrospective cohort study, we included the deceased patients in COVID-19 specialized ICU with laboratory-confirmed COVID-19 from Guanggu hospital area of Tongji Hospital from February 8th to March 30th. Demographic, clinical, laboratory, and outcome data were extracted from electronic medical records using a standard data collection form. We used Spearman rank correlation and Cox regression analysis to explore the risk factors associated with in-hospital death, especially the association between inflammatory cytokines and death.

A total of 205 severe/critical COVID-19 pneumonia patients were admitted in the COVID-19 specialized ICU and 75 deceased patients were included in the final analysis. The median age of the deceasing patients was 70 years (IQR 65–79). The common symptoms were fever (78.9%), cough (70.4%), and expectoration (39.4%). The BNP and CRP levels were far beyond the normal reference range. In the Spearman rank correlation analysis, IL-8 was found to be significantly associated with the time from onset to death (rs= −0.30, P = .034) and that from admission to death (rs= −0.32, P = .019). Cox regression showed after adjusting age and sex, IL-8 levels were still significantly associated with the time from onset to death (P = .003) and that from admission to death (P 
= .01).

IL-8 levels were associated with in-hospital death in severe/critical COVID-19 patients, which could help clinicians to identify patients with high risk of death at an early stage.
Zina percutaneous screw fixation combined with endoscopic lumbar intervertebral fusion under intraoperative neuromonitoring
Authors: Yu Tong , Wu Jiu-Ping , Zhang Jun , Yu Hai-Chi , Yuan Tian-Yang , Xu De-Rui , Yun Zhi-He , He Tao , Liu Rui , Liu Qin-Yi
Published: March 2021

Introduction:

Traditional open discectomy and intervertebral fusion surgery is the common strategy for lumbar disc herniation (LDH). However, it has the disadvantages of long recovery time and severe paravertebral soft tissue injury. Zina percutaneous screw fixation combined with endoscopic lumbar intervertebral fusion (ZELIF), as a novel minimally invasive surgical technique for LDH, has the advantages in quicker recovery, less soft tissue destruction, shorter hospital stays and less pain. We report a novel technique of ZELIF under intraoperative neuromonitoring (INM) for the treatment of LDH.

Patient concerns:

A 51-year-old male presented to our hospital with left lower extremity pain and numbness for 1 year.

Diagnosis:

Lumbar disc herniation (LDH).

Interventions:

This patient was treated with Zina percutaneous screw fixation combined with endoscopic neural decompression, endplate preparation, and intervertebral fusion through Kambin's triangle. Each step of the operation was performed under INM.

Outcomes:

The follow-up period lasted 12 months; the hospitalization lasted 4 nights; the blood loss volume was 65 ml, and the time of operation was 266 min. INM showed no neurological damage during the surgery. No surgical complications, including neurological deterioration, cage migration, non-union, instrumentation failure or revision operation, were observed during the follow-up period. Visual Analogue Scale (VAS) score reduced from 7 to 1; the Oswestry Disability Index (ODI) decreased from 43 to 14; the EQ-5D score was 10 preoperatively and 15 at the final follow-up visit; the Physical Component Summary of the 36-Item Short Form Health Survey (SF-36) was 48 preoperatively and 49 at the last follow up visit; the SF-36 Mental Component Summary was 47 before surgery and decreased to 41 postoperatively.

Conclusion:

ZELIF under INM may represent a feasible, safe and effective alternative to endoscopic intervertebral fusion and percutaneous screw fixation, for decompressing the lumbar's exiting nerve root directly with minimal invasion in selected patients.
Evaluating the role of GSTP1 genetic polymorphism (rs1695, 313A>G) as a predictor in cyclophosphamide-induced toxicities
Authors: Gong Jin-Yu , Peng Si-Yin , Xing Kai , Fan Li , Tan Sheng-Lan , Luo Zhi-Ying , Yuan Hai-Yan , Xu Ping , Luo Jian-Quan
Published: March 2021

The association between Glutathione S-transferase Pi 1(GSTP1) genetic polymorphism (rs1695, 313A>G) and cyclophosphamide-induced toxicities has been widely investigated in previous studies, however, the results were inconsistent. This study was performed to further elucidate the association.

A comprehensive search was conducted in PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and Wan Fang database up to January 5, 2020. Risk ratios (RRs) and 95% confidence intervals (95% CIs) were used to estimate the association between GSTP1 rs1695 polymorphism and cyclophosphamide-induced hemotoxicity, gastrointestinal toxicity, infection, and neurotoxicity.

A total of 13 studies were eventually included. Compared with the GSTP1 rs1695 AA genotype carriers, patients with AG and GG genotypes had an increased risk of cyclophosphamide-induced gastrointestinal toxicity (RR, 1.61; 95% CI, 1.18–2.19; P = .003) and infection (RR, 1.57; 95% CI, 1.00–2.48; P = .05) in the overall population. In the subgroup analyses, there were significant associations between GSTP1 rs1695 polymorphism and the risk of cyclophosphamide-induced myelosuppression (RR, 2.10; 95% CI, 1.60–2.76; P < .00001), gastrointestinal toxicity (RR, 1.77; 95%CI, 1.25–2.53; P = .001), and infection (RR, 2.01; 95% CI, 1.14–3.54; P = .02) in systemic lupus erythematosus (SLE) or lupus nephritis syndrome patients, but not in cancer patients.

Our results confirmed an essential role for the GSTP1 rs1695 polymorphism in the prediction of cyclophosphamide-induced myelosuppression, gastrointestinal toxicity, and infection in SLE or lupus nephritis syndrome patients. More studies are necessary to validate our findings in the future.
Prognostic significance of postoperative change of PALBI grade for patients with hepatocellular carcinoma after hepatectomy
Authors: Wang Zheng-Xia , Peng Wei , Zhang Xiao-Yun , Wen Tian-Fu , Li Chuan
Published: March 2021

The platelet-albumin-bilirubin (PALBI) grade plays critical role in evaluating liver function. However, the change of PALBI grade from the preoperative to postoperative period in predicting patient outcomes after hepatectomy remains unclear.

A total of 489 HCC patients who underwent hepatectomy in West China Hospital between January, 2010 and June, 2016 were analyzed retrospectively.ΔPALBI grade was calculated by PALBI grade at the first postoperative month - preoperative PALBI grade.ΔPALBI >0 was considered as stable; otherwise, worse PALBI grade was considered. Kaplan– Meier method and Cox proportional hazard regression analyses were performed for survival analysis. Prognostic model was constructed by nomogram method.

Three hundred forty two patients and 147 patients were classified into training group and validation group, respectively. In the training group, results from Cox model suggested that worse PALBI grade (HR 1.328, 95% CI 1.010–1.746, P = .042), tumor size (HR 1.460, 95% CI 1.058–2.015, P = .021), microvascular invasion (MVI, HR 1.802, 95% CI 1.205–2.695, P < .001), and high alpha-fetoprotein level (AFP, HR 1.364, 95% CI 1.044–1.781, P = .023) negatively influenced postoperative recurrence. Similarly, worse PALBI grade (HR 1.403, 95% CI 1.020–1.930, P = .038), tumor size (HR 1.708, 95% CI 1.157–2.520, P = .007), MVI (HR 1.914, 95% CI 1.375–2.663, P < .001), and presence of cirrhosis (HR 1.773, 95% CI 1.226–2.564, P = .002) had negatively impacts on overall survival. Patients with worse PALBI grade had worse recurrence free (RFS) and overall survival (OS). The prognostic model incorporating the change of PALBI grade constructed in training group and tested in the validation group could perform well in predicting the outcomes.

Postoperative change of PALBI grade was independently risk factor related with prognosis. Prognostic model incorporating the change of PALBI grade might be a useful index to predict the prognosis of HCC patients following hepatectomy.