bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 465: A 3D Bioprinted Human Cardiac Cell Platform to Model the Pathophysiology of Diabetes
Authors: Joddar Binata , AnilKumar Shweta , Alonzo Matthew , Thakur Vikram , CHATTOPADHYAY MUNMUN
Published: October 2020

Type-II diabetes (T2D) patients affected by underlying hyperglycemic (high glucose/blood sugar) conditions often suffer from cardiac atrophy, resulting in tissue mass reduction and debilitating cardiac health. To understand pathophysiological mechanisms during progression of cardiac atrophy, a 3D bioprinted organoid platform was developed from a mixture of hydrogels containing human cardiac cells, including cardiomyocytes (CM), fibroblasts (CF) and endothelial cells (EC), to mimic the functionality of the in-vivo tissue. The organoids were cultured using normoglycemic- or hyperglycemic-conditions. The expression of essential biomarkers in these organoids, for myocardin (Myocd), troponin-I (TRP-I), fibroblast protein-1 (FSP-1) and endothelin-1 (ET-1) was confirmed. To assess the physiological cellular connections during hyperglycemia, the presence of Connexin-43 (CX-43) was assessed in the presence of a CX-43 blocker, gap26. Epigenomic tools were used to simultaneously interrogate histone-modifications by histone 3 lysine 9 mono-methylation (H3K9me1) along with the co-regulation of inflammatory mediators, such as the high mobility group box 1 (HMGB1) and toll like receptor 4 (TLR4) in the cardiac organoids cultured using normal versus hyperglycemic conditions. Organoids exposed to high glucose showed an increased expression of H3K9me1 as well as inflammatory mediators HMGB1 and TLR4. Hyperglycemia also exhibited alterations in expression of Myocd and FSP-1 in the organoids, compared to normoglycemic conditions. Treatment with gap26 affected the CX-43 expression significantly, in organoids cultured under hyperglycemia suggesting that high glucose conditions associated with prolonged diabetes may lead to compromised CM-CF coupling, essential for maintenance of cardiac functionality. Increased levels of H3K9me1 suggest decreased expression of Myocd, which may lead to CM degeneration. Epigenetic modifications including alterations in histone methylation in regulation of the myocardial genes and gap junction proteins under hyperglycemic conditions, may lead to cardiac atrophy. We expect to establish an actual T2D patient iPSC cell derived cardiac platform, to offer new therapeutic opportunities within the field.
Abstract MP113: Protein Hyperacetylation Mediates Bradyarrhythmia in Mice With Mitochondrial Disease
Authors: Dai Dao-Fu , Chu Yi , Yoon Jin-Young
Published: October 2020

Background:
Mice with germline mutation of the mitochondrial respiratory complex I subunit Ndufs4 exhibit progressive neurodegenerative phenotypes resembling Leigh syndrome (LS). Cardiomyocyte-specific Ndufs4
-/-
mice demonstrate protein hyperacetylation and accelerated heart failure in response to pressure overload.

Methods and Results:
LS mice developed bradyarrhythmia with heart rate <400 bpm. EKG showed sick sinus syndrome (SSS) and high degree AV block. Supplementation of Nicotinamide Riboside (NR), which increased cellular NAD
+
, significantly reduced arrhythmia events and restored normal sinus rhythm, as shown by confocal scanning of sinoatrial nodal tissue dissected from LS mouse hearts. Immunoprecipitation and immunohistochemistry using antibody specific for K1479 of Nav
1.5
showed hyperacetylation of LS SA nodal tissue, which was attenuated by NR. HEK293-cells deficient in mitochondrial complex I subunit Ndufs2 had higher DCFDA (ROS) and lower TMRM intensity (mitochondrial membrane potential) compared with Ndufs4 knock-out cells. Ndufs2-knock-out HEK293 cells transfected with wild-type Nav
1.5
showed hyperacetylation of K1479 of Nav
1.5
. Patch clamp showed significantly reduced sodium current (I

Na

) in Ndufs2 deficient HEK293 cells. NR prevented the decrease of I

Na

in Ndufs2 KO cells. HEK293 cells expressing mutant Nav
1.5
constructs mimicking deacetylation (K1479R) had increased I

Na

compared with HEK293 expressing WT Nav
1.5,
suggesting that acetylation status affect Nav1.5 function. Arrythmia was noted in conduction tissue specific HCN4-Ndufs4
-/-
mice, suggested a cell autonomous effect leading to arrhythmia. These findings indicate that mitochondrial complex I deficiency lead to hyperacetylation of Nav
1.5
, reduction of I

Na

, which subsequently cause bradyarrhythmia and this can be reversed by NR. Using echocardiography, we demonstrated significant diastolic dysfunction (decreased E’/A’, prolonged isovolemic relaxation time) in LS mice, which was ameliorated by NR. The calcium transient amplitude and decay rate, an indicator of ryanodine receptor and SERCA2 functions, was significantly decreased by ~15% in LS hearts and this was mitigated by NR, concomitant with reversal of SERCA2 hyperacetylation.

Conclusions:
Despite normal cardiac structure and systolic function, LS mice showed SSS, high degree AV block and diastolic dysfunction, which is mediated by hyperacetylation of Nav
1.5
and SERCA2, respectively. NR significantly reversed both arrhythmia and diastolic dysfunction. Our study demonstrates novel mechanistic link between mitochondrial complex I deficiency and the function of Nav
1.5
and SERCA2.
Abstract MP161: A Calcineurin-hoxb13 Axis Regulates Growth Mode of Mammalian Cardiomyocytes
Authors: Nguyen Ngoc Uyen Nhi , Canseco Diana C , Xiao Feng , Nakada Yuji , Li Shujuan , Lam Nicholas T , Muralidhar Shalini , Savla Jainy J , Hill Joseph A , Wang Zhaoning , Ahmed Mahmoud S , Hubbi Maimon , Menendez-Montes Ivan , Moon Jesung , Ali Shah R , Villalobos Elisa , Elhelaly Waleed M , Thet Suwannee , Tan Wilson Lek Wen , Anene-Nzelu Chukwuemeka George , Foo Roger , Jagoree Roy , Cyert Martha S , Rothermel Beverly A , Sadek Hesham A
Published: October 2020

A major factor in the progression to heart failure in humans is the inability of the adult heart to repair itself after injury. Our group recently demonstrated that the early postnatal mammalian heart is capable of regeneration following injury through proliferation of preexisting cardiomyocytes1,2. We recently also showed that Meis1, a TALE family homeodomain transcription factor, translocates to cardiomyocyte nuclei shortly after birth and mediates postnatal cell cycle arrest3. Here we report that Hoxb13 acts as a Meis1 cofactor in postnatal cardiomyocytes. Cardiomyocyte-specific deletion of Hoxb13 can both extend the postnatal window of cardiomyocyte proliferation and reactivate cardiomyocyte cell cycle in the adult heart. Moreover, adult Meis1/Hoxb13 double knockout hearts display widespread cardiomyocyte mitosis, sarcomere disassembly and an improvement in left ventricular systolic function following myocardial infarction both by echocardiography and MRI. ChIP-seq analysis demonstrates that Meis1 and Hoxb13 act cooperatively to regulate cardiomyocyte maturation and cell cycle. Finally, we show that the calcium-activated protein phosphatase calcineurin dephosphorylates Hoxb13 at serine-204 (S204), resulting in its nuclear localization and cell cycle arrest. Collectively, these results demonstrate that Meis1 and Hoxb13 act cooperatively to regulate cardiomyocyte maturation and proliferation and provide mechanistic insights into the link between hyperplastic and hypertrophic growth of cardiomyocytes.
Julianus of Laodicea and His Astrological Fragments
Authors: László Levente
Published: October 2020

The present paper investigates the texts attributed to the astrological author Julianus of Laodicea. The authenticity of a work ascribed to him is re-examined, the genuine fragments are collected and evaluated, and possible further traces of his work in later literature are explored to correct and update his scholarly image. In an appendix, a critical edition of F18 is offered.
Princesses Born to Concubines: A First Visit to the Women of the Abbasid Household in Late Medieval Cairo
Authors: Banister Mustafa
Published: October 2020

This article presents a study of the women of the Abbasid household in 8th-/14th- and 9th-/15th-century Cairo. Following a discussion of the size and growth of the Abbasid family, the article juxtaposes a late fourteenth-century marriage document, which extolls the virtues of unions made with the caliph’s family, against the historical record of marriages made by Abbasid and non-Abbasid spouses in search of social capital. The study seeks to understand the meaning attached to marriages made with Abbasid family members, and the social advantages the caliphal family hoped to gain in return. By thus reconsidering the role of Abbasid concubines and princesses, we challenge preconceived notions about the agency and mobility of Abbasid family members in late medieval Cairo and demonstrate their freedom of movement in pursuing valuable marriage connections. The article is thus a contribution to broader understandings of notable women in premodern Islamicate societies.
Democratic Autonomy and the Shortcomings of Citizens
Authors: Lovett Adam
Published: October 2020

A widely held picture in political science emphasizes the cognitive shortcomings of us citizens. We’re ignorant. We don’t know much about politics. We’re irrational. We bend the evidence to show our side in the best possible light. And we’re malleable. We let political elites determine our political opinions. This paper is about why these shortcomings matter to democratic values. Some think that democracy’s value consists entirely in its connection to equality. But the import of these shortcomings, I argue, cannot be explained in purely egalitarian terms. To explain it, we must instead think of democracy’s value partly in terms of collective autonomy. Our ignorance and irrationality undermine the epistemic conditions for realizing this kind of autonomy. They stop us knowing the outcomes of our political choices. Our irrationality and malleability undermine the independence conditions for realizing such autonomy. They mean our political choices are subject to problematic kinds of interpersonal influence. Thus, at root, the import of the widely held picture is that, if accurate, it closes off this critical aspect of democracy’s value.
covid-19 Claims and the Law of International Responsibility
Authors: Paparinskis Martins
Published: October 2020

This paper considers the role that the law of international responsibility, both State responsibility and responsibility of international organizations, plays in claims and disputes about covid-19. It proceeds by examining in turn the rubrics of the internationally wrongful act, content of responsibility, and implementation of responsibility. On most points, blackletter law is perfectly capable of answering the questions raised by claims related to covid-19. But evolutionary potential inherent in the normal international legal process should also be recognised, whether it manifests itself by further strengthening current rules, elaborating vague rules by application, filling gaps in current law by generating new practice or even, exceptionally, revisiting rules currently in force.
Mercurius Ubiquitous
Authors: Swank Marisa
Published: October 2020

The purpose of this work is to construct a strong theoretical base for analytical psychology to engage with psychedelic therapy by drawing out tools already present in Jungian thought. This is done by first offering a brief history of psychedelic therapy and Jungian psychology, focusing on the work of three analysts. Stanislav Grof’s work with LSD therapy is then outlined and explored as a foundation for dialogue with Jungian concepts. Analytical psychology’s use of alchemical concepts and language is applied as a means of understanding psychedelic experience. Concepts of prima materia, Mercurius, the vessel, and subtle body are discussed alongside individuals’ accounts of their LSD sessions. Following these theoretical considerations, the author discusses the implications of a dialogue between analytical psychology and psychedelic therapy and potential future directions.
Reforming International Organizations
Authors: Heldt Eugénia C. , Mahrenbach Laura C.
Published: October 2020

Recent scholarship has highlighted the role of domestic pressures in determining state preferences toward the reform of international organizations (IO s). This article adds a new dimension by examining how partisanship and ministerial control affect state preferences toward IO empowerment. The article derives two expectations from the existing literature. First, partisan position will determine preferences toward IO empowerment. Second, when a government is constituted by multiple parties, the position of the party with the IO’s ministerial portfolio will determine the government’s position toward IO empowerment. The article illustrates this argument by examining the positions of four net donors (Germany, France, the United Kingdom, and the United States) and two net recipients (Brazil and India) during the World Bank’s reforms. By bringing domestic politics back in, this article complements existing studies on the politics of IO reform and weighs in on central debates in comparative politics and international political economy.
Revision of the genus Cyphura Warren, 1902. Part III: The geminia and semiobsoleta species groups from the Indo-Pacific region with five new species (Lepidoptera: Uraniidae: Uraniinae)
Authors: Sinnema Siep , Sinnema-Bloemen Jannie
Published: October 2020

The geminia and semiobsoleta groups of the genus Cyphura
Warren, 1902 (Lepidoptera: Uraniidae) are revised. Five new species are described. There are four new species in the geminia species group: Cyphura pallidata sp. n., C. marcoi sp. n., C. aruensis sp. n., and C. numforensis sp. n. In this group, a lectotype is designated for Strophidia costalis
Butler, 1887, C. subsimilis

Warren, 1902, S. bifasciata
Butler, 1879, C. catenulata
Warren, 1902, Urapteroides approximans
Swinhoe, 1902, U. falka
Swinhoe, 1916, U. swinhoei
Rothschild, 1915 and for U. swinhoei
Joicey & Kaye, 1917. Six new synonyms are proposed: U. gutturalis (Swinhoe, 1916) is a junior synonym of C. geminia (Cramer, 1779), C. subsimilis
Warren, 1902 is a junior synonym of C. costalis (Butler, 1887), C. catenulata
Warren, 1902 and U. approximans (Swinhoe, 1902) are both junior synonyms of C. bifasciata (Butler, 1879), U. falka (Swinhoe, 1916) is a junior synonym of C. pieridaria
Warren, 1902 and U. swinhoei (Joicey & Kaye, 1917) is a junior synonym of C. maxima (Strand, 1912). Urapteroides swinhoei
Rothschild, 1915 is transferred to Cyphura as Cyphura swinhoei (Rothschild, 1915) comb. n.

In the semiobsoleta species group, one new species is described: C. trifasciata sp. n. In this group a lectotype is designated for Urapteroides semiobsoleta
Warren, 1896, U. semiobsoleta reducta
Joicey & Talbot 1916, C. multistrigaria
Warren, 1907 and for C. multistrigaria ab. dealbata
Warren, 1907.
Bangladeshi Poets Writing in English
Authors: Islam Mohammad Shafiqul
Published: October 2020

This article observes that Kaiser Haq has made an immense contribution to Bangladeshi poetry in English, leading the school of English poetry of the country from the front. A relatively new field, Bangladeshi writing in English has started becoming a part of world literature, and its scope, no doubt, is expanding rapidly. The article also focuses on the legacy of Bangladeshi writing in English to demonstrate how Bangladeshi poetry in English has simultaneously progressed. The article argues that Haq’s enormous contributions justify his position as the best English-language poet in Bangladesh. For his poetry, the poet takes material from his motherland and its rich culture, and his style, technique, and diction resonate with those of prominent poetic voices of the world. The article also sheds light on how Haq presents Bangladesh, depicting numerous shades of reality, and how he still dominates in the contemporary scene of Bangladeshi poetry in English.
Australia’s Atomic Past
Authors: Lowe David
Published: October 2020

I ask in this article whether the legacies of Australia’s nuclear past, including the great secrecy surrounding testing of weapons in the 1950s and 1960s, and subsequent clean-ups, have impacted in particular ways that have ongoing ramifications for policy relating to uranium mining and nuclear energy. My starting point is the sustained examination of the pros and cons of developing the nuclear fuel cycle in Australia, a Parliamentary Committee Inquiry from 2006. Contrasting the submissions and discussions of this committee with exhibition and educational materials relating to the legacies of atomic testing, I suggest that one of the biggest opportunities for constructive policy conversation on nuclear energy suffered from the absence of trust among different groups. This derived, in good measure, from distinctive features in popular remembering of Australia’s atomic past. In 2006, it fed the exasperation of nuclear advocates who did not, and perhaps still do not, appreciate that the neat separation of uranium mining and energy generation from Australia’s earlier encounters with the atom is very hard. Relatedly, I argue that the secrecy around governments’ involvement in atomic testing, and its legacies, is likely to be seized on regularly; and likely to sustain what is a reservoir of public mistrust of government policy.
A new species of Polynoncus Burmeister (Coleoptera: Trogidae) from Argentina
Authors: COSTA-SILVA VINÍCIUS , DIÉGUEZ VÍCTOR MANUEL
Published: October 2020

Trogidae (Coleoptera) is a cosmopolitan family with about 350 described species within five extant genera (Zídek 2013, 2017; Strümpher et al. 2014, 2016; Nikolajev 2016). For South American, three genera are recorded: Trox Fabricius, 1775 (Troginae), Omorgus Erichson, 1847 (Omorginae), and Polynoncus Burmeister, 1876 (Omorginae) (Scholtz 1990; Strumpher et al. 2016; Huchet & Costa-Silva 2018).
Energy Storage System Based on Low Power Photovoltaic Power Generation
Authors: Wang Xiran , Gao Yifan , Zhang Minjie , Gu Jiting , Lai Cong
Published: October 2020

The IU and PU characteristic curves of PCs output in photovoltaic generation (PVG) were analyzed according to the working principle of photovoltaic cells (PCs) in the study, so as to provide a theoretical basis for the further improvement of the maximum power point tracking (MPPT) algorithm.
The three-stage charging method was used to charge the battery to improve the energy conversion efficiency in the charging process of the system. The variable step incremental conductance algorithm (ICA) was proposed, which can effectively increase the speed of MPPT in the system and enhance
its stability. By setting up a test platform, verification experiments of the tracking algorithm were performed on sunny (higher light intensity), cloudy (medium light intensity), and rainy (lower light intensity) days. The results showed that the adoption of MPPT algorithm can effectively
increase the output power (OP) of PCs, the OP in sunny days was higher than in cloudy days and OP in cloudy days was higher than in rainy days compared with the system without MPPT algorithm. Compared with the traditional incremental conductance algorithm, the output power of the PCs using
the MPPT algorithm improved by the incremental conductance algorithm had increased by 5.86%. The feasibility and effectiveness of the energy storage system in the study were verified.
Analysis of InGaN Multiple-Quantum-Well Photoelectric Device of Visible Light Communication
Authors: Chi Haitao , Du Yu , Li Gongyu
Published: October 2020

The key to achieving high-speed and high-quality visible light communication is to increase the modulation speed of Light-Emitting Diode (LED). Therefore, in this study, the influence of the Composite Mechanism of Carrier (CMC) on the modulation speed of LED is studied by designing
different structures of the InGaN Multi-quantum-well (MQW) LED active region. Because the carrier subspace waves function of narrow quantum well LED overlaps more frequently and the electron leakage effect is more significant, the compound rate is faster and the modulation bandwidth is higher.
InGaN quantum barrier LED with a content of 1% can increase the weight of radiation recombination, which makes the modulation bandwidth higher than GaN quantum barrier LEDs; when the in content is 5%, electron leakage and Auger recombination have a dominant position. Moreover, because these
two compounding mechanisms have a fast compounding rate, the modulation bandwidth is significantly increased. Then the 405 nm laser-excited photoluminescence (PL) is introduced to analyze the carrier dynamics in the LED and obtain the related processes of carrier distribution and transport.
The proposed carrier microscopic model can well explain change characteristics of the PL luminescence peak, luminous intensity, and half-height width of InGaN/GaN MQW LED with different excitation wavelengths. At low temperature, the PL peak of the InGaN/GaN quantum well LED redshifts with
the increase of temperature, because the weakly bound carrier transfers the obtained energy to the deeply bound energy level of high In content.
Tropical Cyclones Downscaled from Simulations of the Last Glacial Maximum
Authors: Lawton Quinton A. , Korty Robert L. , Zamora Ryan A.
Published: October 2020

The tracks, intensities, and other properties of tropical cyclones downscaled from three models’ simulations of the Last Glacial Maximum (LGM) are analyzed and compared to those of storms downscaled from simulations of the present climate. Globally, the mean maximum intensity of storms generated from each model is lower at LGM, as is the fraction of all storms that reach intensities of category 4 or higher on the Saffir–Simpson hurricane wind scale. The median day of the storm season shifts earlier by an average of one week in all three models in both hemispheres. Two of the three models’ LGM simulations feature a reduction in storm count and global power dissipation index compared to the current climate, but a third shows no significant difference between the two climates. Although each model is forced by the same global changes, differences in the way sea surface temperatures and other large-scale environmental conditions respond in the North Atlantic impart significant differences in the climatology at LGM between models. Our results from the cold LGM provide a novel opportunity to assess how tropical cyclones respond to climate changes.
Surgical Supply Cost Awareness Is Associated With Lower Costs: A Single-Center Experience
Authors: Tseng Joshua , Sax Harry C. , Gewertz Bruce L. , Margulies Daniel R. , Alban Rodrigo F.
Published: October 2020

Surgeons are often unfamiliar with the costs of surgical instrumentation and supplies. We hypothesized that surgeon cost feedback would be associated with a reduction in cost. A multidisciplinary team evaluated surgical supply costs for laparoscopic appendectomies of 7 surgeons (surgeons A-G) at a single-center academic institution. In the intervention, each surgeon was debriefed with their average supply cost per case, their partner’s average supply cost per case, the cost of each surgical instrument/supply, and the cost of alternatives. In addition, the laparoscopic appendectomy tray was standardized to remove extraneous instruments. Pre-intervention (March 2017-February 2018) and post-intervention (March 2018-October 2018) costs were compared. Pre-intervention, the surgeons’ average supply cost per case ranged from $754-$1189; when ranked from most to least expensive, surgeon A > B > C > D > E > F > G. Post-intervention, the surgeons’ average supply cost per case ranged from $676 to $846, and ranked from surgeon G > D > F > C > E > B > A. Overall, the average cost per case was lower in the post-intervention group ($854.35 vs. $731.11, P < .001). This resulted in savings per case of $123.24 (14.4%), to a total annualized savings of $29 151.
Feline musculoskeletal ageing: How are we diagnosing and treating musculoskeletal impairment?
Authors: Dowgray Nathalie , Comerford Eithne
Published: October 2020

Practical relevance:

An understanding of the process of musculoskeletal ageing – which all senior and geriatric cats will experience – is vital to maintaining the health and welfare of our ageing cat population.

Clinical challenges:

Assessment of the feline musculoskeletal system is not always straightforward. Diagnosis of impairment relies on input from owners and veterinarians in terms of visual observation, and clinical and orthopaedic examination, in addition to diagnostic imaging

Audience:

This review is written for the primary care veterinary team.

Aims:

The goals are to raise awareness and improve clinical diagnosis of musculoskeletal impairment as a result of ageing. The article also reviews therapeutic options and considers the evidence available for the prevention/deceleration of musculoskeletal ageing and impairment.

Evidence base:

There is good evidence of a high prevalence of osteoarthritis (OA) and degenerative joint disease (DJD) in older cats. There is also good evidence to indicate that functional impairment and chronic pain are sequelae of musculoskeletal disease. However, there is a paucity of information for what is best practice for the management and treatment of musculoskeletal impairment in a clinical situation. There is also a lack of evidence on how prevention of central stimulation of the nervous system caused by musculoskeletal impairment and, in turn the development of chronic pain, can be avoided.
Resistance to histone deacetylase inhibitors confers hypersensitivity to oncolytic reovirus therapy
Authors: Islam Shariful , Espitia Claudia M. , Persky Daniel O. , Carew Jennifer S. , Nawrocki Steffan T.
Published: October 2020

Despite the promising antilymphoma activity of histone deacetylase (HDAC) inhibitors as a drug class, resistance is a significant clinical issue. Elucidating the molecular mechanisms driving HDAC inhibitor resistance and/or the specific targets that are altered in drug-resistant cells may facilitate the development of strategies that overcome drug resistance and are more effective for refractory patients. We generated novel T-cell lymphoma (TCL) cell line models of acquired resistance to the HDAC inhibitor belinostat to identify potential effective therapies. Belinostat-resistant cells displayed significant cross-resistance to other HDAC inhibitors including romidepsin, panobinostat, and vorinostat. Consistent with a lack of sensitivity to HDAC inhibitors, the resistant cells failed to induce increased acetylated histones. Drug-resistant cells featured significantly decreased expression of the key antiviral mediators IRF1 and STAT1. On the basis of these findings, we investigated the efficacy of the clinical formulation of reovirus (Reolysin) in parental and drug-resistant models. Our investigation revealed that HDAC inhibitor–resistant cells displayed enhanced vulnerability to reovirus replication and cell death in both in vitro and in vivo models compared with their parental counterparts. Importantly, Reolysin also significantly increased the antilymphoma activity of belinostat in HDAC inhibitor–resistant cells. Our data demonstrate that Reolysin alone or in combination with belinostat is a novel therapeutic strategy to treat TCL patients who develop resistance to HDAC inhibitors.
Analysing the meta-interaction between pathways by gene set topological impact analysis
Authors: Yan Shen , Chi Xu , Chang Xiao , Tian Mengliang
Published: October 2020

Background

Pathway analysis is widely applied in transcriptome analysis. Given certain transcriptomic changes, current pathway analysis tools tend to search for the most impacted pathways, which provides insight into underlying biological mechanisms. Further refining of the enriched pathways and extracting functional modules by “crosstalk” analysis have been proposed. However, the upstream/downstream relationships between the modules, which may provide extra biological insights such as the coordination of different functional modules and the signal transduction flow have been ignored.

Results

To quantitatively analyse the upstream/downstream relationships between functional modules, we developed a novel GEne Set Topological Impact Analysis (GESTIA), which could be used to assemble the enriched pathways and functional modules into a super-module with a topological structure. We showed the advantages of this analysis in the exploration of extra biological insight in addition to the individual enriched pathways and functional modules.

Conclusions

GESTIA can be applied to a broad range of pathway/module analysis result. We hope that GESTIA may help researchers to get one additional step closer to understanding the molecular mechanism from the pathway/module analysis results.
Veno-venous extracorporeal membrane oxygenation successfully treated a case of severe pulmonary hemorrhage caused by leptospirosis
Authors: Wang H. J. , Chen G. Z. , Zhou C. J. , FU Y. , YAO L. N.
Published: October 2020

Background

Pulmonary hemorrhage is an important complication of leptospirosis. Once acute respiratory distress syndrome (ARDS) occurs as a secondary condition, treatment is extremely difficult and the mortality rate is very high.

Case presentation

The patient was a 49-year-old. He was admitted to the hospital because he had experienced a fever and cough for 4 days. Hemorrhage, respiratory failure, ARDS and other symptoms appeared soon after admission. Due to severe pulmonary hemorrhage secondary to ARDS, mechanical ventilation was performed through tracheal intubation. During intubation, the patient suffered cardiac arrest, and the patient’s condition worsened. He was confirmed to have leptospirosis through second-generation sequencing of the alveolar lavage fluid. Finally, we successfully treated the patient with penicillin as an anti-infective medication and venous-venous extracorporeal membrane oxygenation (v-vECMO). To the best of our knowledge, this report is the first to describe the successful application of ECMO in mainland China.

Conclusions

Leptospirosis can induce serious but transient ARDS with a better prognosis than other causes of ARDS. Our patient was successfully treated with V-vECMO.
Who fails to return within 30 days after being tested positive for HIV/STI in a free testing centre?
Authors: Rolland Camille , de La Rochebrochard Elise , Piron Prescillia , Shelly Marc , Segouin Christophe , Troude Pénélope
Published: October 2020

Background

Some patients who test positive for sexually transmitted infections (STIs) fail to return for results and treatment. To target improvement actions, we need to find out who these patients are. This study aimed to explore factors associated with failure to return within 30 days (FTR30) after testing among patients with positive results in a free STI testing centre in Paris.

Methods

All patients with at least one positive result between October 2016 and May 2017 and who completed a self-administered questionnaire were included in this cross-sectional study (n = 214). The questionnaire included sociodemographic factors, sexual behaviour and history of testing. Factors associated with FTR30 were assessed using logistic regression models.

Results

More than two-thirds of patients were men (72%), and the median age of patients was 27 years. Most patients were born in metropolitan France (56%) or in sub-Saharan Africa (22%). Men who had sex with men represented 36% of the study population. The FTR30 rate was 14% (95% CI [10–19%]). In multivariate analysis, previous HIV testing in younger persons (aOR: 3.36, 95% CI [1.27–8.84]), being accompanied by another person at the pretest consultation (aOR: 3.45, 95% CI [1.36–8.91]), and lower self-perceived risk of HIV infection (aOR: 2.79, 95% CI [1.07–7.30]) were associated with a higher FTR30. Testing for chlamydia/gonorrhoea without presumptive treatment was associated with a lower FTR30 (aOR: 0.21, 95% CI [0.07–0.59]).

Conclusions

These factors that affect failure to return are related to the patient’s representations and involvement in the STI screening process. Increasing health literacy and patient empowerment could help to decrease failure to return after being tested positive for HIV/STI.

Trial registration

Not applicable.
Evaluating sensitivity and specificity of handheld point-of-care ultrasound testing for gynecologic pathology: a pilot study for use in low resource settings
Authors: Toscano Marika , Szlachetka Kam , Whaley Natalie , Thornburg Loralei L.
Published: October 2020

Background

Point-of-care ultrasound (POC-US) is a diagnostic test conducted at the site of patient care with direct interpretation by the clinician, providing immediate results. POC-US for gynecologic application is not well characterized by current literature yet has the potential to increase access in limited resource settings. We compared the diagnostics of three POC-US devices for gynecologic (GYN) pathology and then performed evaluation of sensitivity and specificity of a single best POC-US device for intended use in a low resource setting.

Methods

This is prospective, pilot descriptive study of 60 subjects. In part 1, comparison of three POC-US devices was performed. Twenty subjects underwent POC-US with three test units [GE Vscan (Vscan), Sonosite Iviz (Iviz), Philips Lumify (Lumify)] followed by diagnostic ultrasound (Dx-US) for reference imaging. Image quality and correlation for devices was scored by blinded reviewers and quantitative measurements of GYN pathology were compared. In part 2, forty subjects underwent POC-US validation with the highest scoring device (Lumify) and Dx-US for reference imaging. Concordance of POC-US operator-interpreted diagnosis with reference imaging interpretation were assessed by Cohen’s unweighted kappa coefficient. Accuracy and agreement of POC-US were assessed by linear regression and Bland–Altman plot analysis. Sensitivity and specificity of POC-US for gynecologic pathologies were calculated.

Results

In aggregate qualitative measurements, Lumify and Iviz units performed superiorly to Vscan. There was no statistically significant difference in quantitative measurements between devices, but a trend towards lower mean error was seen for Lumify and Iviz as compared to Vscan. Lumify device had highest overall scoring and was selected for further testing. In validation comparison of Lumify to Dx-US, no statistically significant differences were found for measurements of endometrium, uterus, ovaries, adnexal pathology, or leiomyomata, (P < 0.02) with excellent agreement in operator-interpreted diagnosis (Kappa > 0.7). Sensitivity and specificity of detecting pathology was 80–100% with PPV and NPV 76–100%.

Conclusion

Among three POC-US devices, Lumify and Iviz devices show highest potential for successful application to clinical gynecologic ultrasound. Clinician-performed POC-US has high diagnostic accuracy, sensitivity, and specificity for basic GYN anatomy and pathology. POC-US is an acceptable and feasible diagnostic tool with potential for future application in a low resource setting to increase access to ultrasound.
The COVID-19 nephrology compendium: AKI, CKD, ESKD and transplantation
Authors: Kant Sam , Menez Steven P. , Hanouneh Mohamed , Fine Derek M. , Crews Deidra C. , Brennan Daniel C. , Sperati C. John , Jaar Bernard G.
Published: October 2020

The pandemic of coronavirus disease 2019 (CoVID-19) has been an unprecedented period. The disease afflicts multiple organ systems, with acute kidney injury (AKI) a major complication in seriously ill patients. The incidence of AKI in patients with CoVID-19 is variable across numerous international studies, but the high incidence of AKI and its associated worse outcomes in the critical care setting are a consistent finding. A multitude of patterns and mechanisms of AKI have been elucidated, and novel strategies to address shortage of renal replacement therapy equipment have been implemented. The disease also has had consequences on longitudinal management of patients with chronic kidney disease and end stage kidney disease. Kidney transplant recipients may be especially susceptible to CoVID-19 as a result of immunosuppression, with preliminary studies demonstrating high mortality rates. Increased surveillance of disease with low threshold for testing and adjustment of immunosuppression regimen during acute periods of illness have been recommended.
Influence of dialysate temperature on creatinine peritoneal clearance in peritoneal dialysis patients: a randomized trial
Authors: Fontana Francesco , Torelli Chiara , Giovanella Silvia , Ligabue Giulia , Alfano Gaetano , Gerritsen Karin , Selgas Rafael , Cappelli Gianni
Published: October 2020

Background

Patients on continuous ambulatory peritoneal dialysis (PD) are encouraged to warm dialysate to 37 °C before peritoneal infusion; main international PD guidelines do not provide specific recommendation, and patients generally warm dialysate batches partially or do not warm them at all. Warming of dialysate is a time-consuming procedure, not free from potential risks (i.e. degradation of glucose), and should be justified by a clear clinical benefit.

Methods

We designed a single blind randomized controlled trial where 18 stable PD patients were randomized to receive a peritoneal equilibration test either with dialysate at a controlled temperature of 37 °C (intervention group) or with dialysate warmed with conventional methods (control group). Primary end-point was a higher peritoneal creatinine clearance in patients in the intervention group.

Results

Patients in the intervention group did not show a significantly higher peritoneal creatinine clearance when compared to the control group (6.38 ± 0.52 ml/min vs 5.65 ± 0.37 ml/min, p = 0.2682). Similar results were obtained for urea peritoneal clearance, mass transfer area coefficient of creatinine and urea. There were no significant differences in total abdominal discomfort questionnaire score, blood pressure and body temperature between the two groups.

Conclusions

Using peritoneal dialysate at different temperatures without causing significant side effects to patients appears feasible. We report a lack of benefit of warming peritoneal dialysate to 37 °C on peritoneal clearances; future PD guidelines should not reinforce this recommendation.

Trial registration

NCT04302649, ClinicalTrials.gov; date of registration 10/3/2020 (retrospectively registered).
An integrated autophagy-related gene signature predicts prognosis in human endometrial Cancer
Authors: Zhang Jun , Wang Ziwei , Zhao Rong , An Lanfen , Zhou Xing , Zhao Yingchao , Wang Hongbo
Published: October 2020

Background

Globally, endometrial cancer is the fourth most common malignant tumor in women and the number of women being diagnosed is increasing. Tumor progression is strongly related to the cell survival-promoting functions of autophagy. We explored the relationship between endometrial cancer prognoses and the expression of autophagy genes using human autophagy databases.

Methods

The Cancer Genome Atlas was used to identify autophagy related genes (ARGs) that were differentially expressed in endometrial cancer tissue compared to healthy endometrial tissue. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were referenced to identify important biological functions and signaling pathways related to these differentially expressed ARGs. A prognostic model for endometrial cancer was constructed using univariate and multivariate Cox, and Least Absolute Shrinkage and Selection Operator regression analysis. Endometrial cancer patients were divided into high- and low-risk groups according to risk scores. Survival and receiver operating characteristic (ROC) curves were plotted for these patients to assess the accuracy of the prognostic model. Using immunohistochemistry the protein levels of the genes associated with risk were assessed.

Results

We determined 37 ARGs were differentially expressed between endometrial cancer and healthy tissues. These genes were enriched in the biological processes and signaling pathways related to autophagy. Four ARGs (CDKN2A, PTK6, ERBB2 and BIRC5) were selected to establish a prognostic model of endometrial cancer. Kaplan–Meier survival analysis suggested that high-risk groups have significantly shorter survival times than low-risk groups. The area under the ROC curve indicated that the prognostic model for survival prediction was relatively accurate. Immunohistochemistry suggested that among the four ARGs the protein levels of CDKN2A, PTK6, ERBB2, and BIRC5 were higher in endometrial cancer than healthy endometrial tissue.

Conclusions

Our prognostic model assessing four ARGs (CDKN2A, PTK6, ERBB2, and BIRC5) suggested their potential as independent predictive biomarkers and therapeutic targets for endometrial cancer.
Interventions on cognitions and perceptions that influence work participation of employees with chronic health problems: a scoping review
Authors: De Wit Mariska , Horreh Bedra , Daams Joost G. , Hulshof Carel T. J. , Wind Haije , de Boer Angela G. E. M.
Published: October 2020

Background

Cognitions and perceptions, such as motivation and return to work (RTW) expectations, can influence work participation of employees with chronic health problems. This makes these cognitions and perceptions important factors for occupational health professionals to intervene upon in order to increase work participation. There is, however, no overview of interventions that influence these factors and are aimed at increasing work participation. Therefore, the purpose of this scoping review is to explore available interventions that are focused on cognitions and perceptions of employees with chronic health problems and aimed at increasing work participation.

Methods

A scoping review was carried out following the framework of Arksey and O’Malley. Ovid MEDLINE and PsycINFO were searched for original papers published between January 2013 and June 2020. We included studies that describe interventions that focus on at least one of ten cognitions and perceptions and on work participation. The risk of bias of the studies included was assessed using quality assessment tools from the Joanna Briggs Institute.

Results

In total, 29 studies were identified that studied interventions aimed at changing at least one of ten cognitions and perceptions in order to change work participation. The interventions that were included mainly focused on changing recovery and RTW expectations, self-efficacy, feelings of control, perceived health, fear-avoidance beliefs, perceived work-relatedness of the health problem, coping strategies and catastrophizing. No interventions were found that focused on changing motivation or on optimism/pessimism. Four interventions were judged as effective in changing coping, self-efficacy, fear-avoidance beliefs, or perceived work-relatedness and work participation according to results of randomized controlled trials.

Conclusions

This review provides an overview of interventions that focus on changing cognitions and perceptions and work participation. Evidence was found for four effective interventions focused on changing these factors and increasing work participation. Occupational health professionals may use the overview of interventions to help employees with chronic health problems to increase their work participation.
Risk factors for incident delirium among urological patients: a systematic review and meta-analysis with GRADE summary of findings
Authors: Sanyaolu L. , Scholz A. F. M. , Mayo I. , Coode-Bate J. , Oldroyd C. , Carter B. , Quinn T. , Hewitt J.
Published: October 2020

Background

Post-operative delirium is an important, yet under-researched complication of surgery. Patients undergoing urological surgery may be at especially high risk of POD, as they are often older, and interventions can be associated with conditions that trigger delirium. The main aim of this systematic review was to evaluate the available evidence for risk factors in this patient group.

Methods

Five databases were searched (MEDLINE, Web of Science, EMBASE, CINAHL and PsychInfo) between January 1987 and June 2019. The Newcastle–Ottawa Scale was used to assess for risk of bias. Pooled odds ratio or mean difference (MD) for individual risk factors were estimated using the Mantel–Haenzel and inverse variance methods.

Results

Seven articles met the inclusion criteria, giving a total population of 1937. The incidence of POD ranged from 5 to 29%. Three studies were deemed low risk of bias and four at a high risk of bias. Nine risk factors were suitable for meta-analysis, with age (MD 4.314 95% CI 1.597, 7.032 p = 0.002) and the clock drawing test (MD − 2.443 95% CI − 3.029, − 1.857 p < 0.001) having a statistically significant association with POD in pooled analyses.

Conclusion

Delirium is common in urological patients. This review has identified a lack of studies in this surgical population, with wide heterogeneity and high risk of bias. It also highlights a number of potential risk factors for post-operative delirium, of which some are modifiable. However, the strength of evidence is weak at present and so future research should focus on assessing comparable risk factors in this patient group in order to inform future clinical practice.

Review registrationThe review protocol was prospectively registered with the PROSPERO database (reference CRD42017054613)
Isoniazid-induced gynaecomastia: report of a paediatric case and review of literature
Authors: Poon Sarah Wing Yiu , Siu Ka Ka , Tsang Anita Man Ching
Published: October 2020

Background

Gynaecomastia is a fairly common condition in puberty but is rare in prepubertal boys. While it is necessary to exclude possible endocrinopathay in prepubertal gynaecomastia, medication is an important and potentially reversible cause to consider in new onset gynaecomastia. Isoniazid-induced gynaecomastia has been reported in adult males, but none was reported in the paediatric population and general paediatricians may not be aware of this uncommon side effect.

Case presentation

We hereby report a 11-year-old prepubertal boy who developed gynaecomastia while taking anti-tuberculosis drugs. Investigations excluded endocrinopathies. Gynaecomastia subsided 8 weeks after stopping isoniazid.

Conclusion

This case is the first paediatric case report describing the association of gynaecomastia with isoniazid use. It is important for general paediatricians to recognize this entity, as prompt diagnosis and cessation of the offending drug can lead to resolution of the problem.
Xanthine oxidase inhibitory activity of a new isocoumarin obtained from Marantodes pumilum var. pumila leaves
Authors: Aladdin Nor-Ashila , Husain Khairana , Jalil Juriyati , Sabandar Carla Wulandari , Jamal Jamia Azdina
Published: October 2020

Background

In traditional Malay medicine,Marantodes pumilum(Blume) Kuntze (family Primulaceae) is commonly used by women to treat parturition, flatulence, dysentery, dysmenorrhea, gonorrhea, and bone diseases. Preliminary screening of some Primulaceae species showed that they possess xanthine oxidase inhibitory activity. Thus, this study aimed to investigate the xanthine oxidase inhibitory activity of three varieties ofM. pumilumand their phytochemical compounds.

Method

Dichloromethane, methanol, and water extracts of the leaves and roots ofM. pumilumvar.alata,M. pumilumvar.pumila,andM. pumilumvar.lanceolatawere tested using an in vitro xanthine oxidase inhibitory assay. Bioassay-guided fractionation and isolation were carried out on the most active extract using chromatographic techniques. The structures of the isolated compounds were determined using spectroscopic techniques.

Results

The most active dichloromethane extract ofM. pumilumvar.pumilaleaves (IC50 = 161.6 μg/mL) yielded one new compound, 3,7-dihydroxy-5-methoxy-4,8-dimethyl-isocoumarin (1), and five known compounds, viz. ardisiaquinone A (2), maesanin (3), stigmasterol (4), tetracosane (5), and margaric acid (6). The new compound was found to be the most active xanthine oxidase inhibitor with an IC50value of 0.66 ± 0.01 μg/mL, which was not significantly different (p > 0.05) from that of the positive control, allopurinol (IC50 = 0.24 ± 0.00 μg/mL).

Conclusion

This study suggests that the new compound 3,7-dihydroxy-5-methoxy-4,8-dimethyl-isocoumarin (1), which was isolated from the dichloromethane extract ofM. pumilumvar.pumilaleaves, could be a potential xanthine oxidase inhibitor.