bluuebunny/crossref_metadata_2025 huggingface dataset:
Operationalizing the Relation Between Affect and Cognition With the Somatic Transform
Authors: MacKinnon Neil J. , Hoey Jesse
Published: June 2021

This article introduces the somatic transform that operationalizes the relation between affect and cognition at the psychological level of analysis by capitalizing on the relation between the cognitive-denotative and affective-connotative meaning of concepts as measured with semantic differential rating scales. Following discussion of levels of analysis, the importance of language at the psychological level, and two principles (inextricability and complementarity) summarizing the relation between affect and cognition that are rendered explicit by the somatic transform, we present affect control theory (ACT) and its Bayesian extension (BayesACT) containing the somatic transform. We conclude by identifying examples of inextricability and complementarity in the social science and neuroscience literatures and discussing how our psychological model might be implemented in a realistic neural model.
Using text analytics to measure an effect of topics and sentiments on social-media engagement: Focusing on Facebook fan page of Toyota
Authors: Chun Heuiju , Leem Byung-Hak , Suh Hyesun
Published: June 2021

In this study we investigate whether Facebook fan-page posting types and topics have a significant effect on engagement. More specifically, the media type and content theme of posting on Facebook are examined to see whether or not there was a difference between content topics. In order to achieve this goal, we set hypotheses as follows: (1) the media types of posting have a significant effect on engagement; (2) the topics and sentiment polarity of posting have a significant effect on engagement. We tested these hypotheses using research procedures as follows: (1) collection and preprocessing of social-media data, including posting types, comments, and reactions on Facebook fan pages, (2) topic modeling of fan-page postings using R and SAS, (3) testing hypotheses using a negative binomial regression model, and (4) implications and insights for social-media marketing. Topic modeling applying to textual data and sentiment analysis were conducted. After that, in order to find the factors to affect the number of Facebook fan-page engagements, the negative binomial regression model including post type, topic, sentiment, reactions of “love,” “haha,” and their interaction as exploratory variables was considered. Finally, the results show that post type is the most influential factor to affect social-media engagement, and content topics, sentiments of posts and comments also have significant effects on it.
Estimating Enhanced Endogenous Glucose Production in Intensive Care Unit Patients with Severe Insulin Resistance
Authors: Yahia Anane , Szlávecz Ákos , Knopp Jennifer L. , Norfiza Abdul Razak Normy , Abu Samah Asma , Shaw Geoff , Chase J. Geoffrey , Benyo Balazs
Published: June 2021

Background:

Critically ill ICU patients frequently experience acute insulin resistance and increased endogenous glucose production, manifesting as stress-induced hyperglycemia and hyperinsulinemia. STAR (Stochastic TARgeted) is a glycemic control protocol, which directly manages inter- and intra- patient variability using model-based insulin sensitivity (SI). The model behind STAR assumes a population constant for endogenous glucose production (EGP), which is not otherwise identifiable.

Objective:

This study analyses the effect of estimating EGP for ICU patients with very low SI (severe insulin resistance) and its impact on identified, model-based insulin sensitivity identification, modeling accuracy, and model-based glycemic clinical control.

Methods:

Using clinical data from 717 STAR patients in 3 independent cohorts (Hungary, New Zealand, and Malaysia), insulin sensitivity, time of insulin resistance, and EGP values are analyzed. A method is presented to estimate EGP in the presence of non-physiologically low SI. Performance is assessed via model accuracy.

Results:

Results show 22%-62% of patients experience 1+ episodes of severe insulin resistance, representing 0.87%-9.00% of hours. Episodes primarily occur in the first 24 h, matching clinical expectations. The Malaysian cohort is most affected. In this subset of hours, constant model-based EGP values can bias identified SI and increase blood glucose (BG) fitting error. Using the EGP estimation method presented in these constrained hours significantly reduced BG fitting errors.

Conclusions:

Patients early in ICU stay may have significantly increased EGP. Increasing modeled EGP in model-based glycemic control can improve control accuracy in these hours. The results provide new insight into the frequency and level of significantly increased EGP in critical illness.
The Challenges of Hosting Televised Deliberations in Ethiopian Media
Authors: Kiflu Gebru K. , Ali Adem C. , Nigussie Hagos
Published: June 2021

This paper explores the factors constraining public service and commercial television channels in constituting the public sphere in Ethiopia. It focuses on three television stations and their respective programs, such as the Ethiopian Broadcasting Corporation's Ethiopian television (ETV)'s Medrek, Fana Broadcasting Corporation's Zuria Meles, and LTV's Sefiw Mehidar. The data was collected starting from 2019 to 2020 in Addis Ababa, the capital city of Ethiopia, where the three TV stations are located. These programs were designed to entertain different views, including ideologies, policies, and strategies to be deliberated and critiqued. They have created opportunities for debate and discussion as the Ethiopian media did not have new program formats for public deliberation-related shows previously. However, results showed that these platforms remained ineffective to entertain a diversity of views. One of the major challenges for this is that the production process encounters multiple obstructions from the media, the guests, and the government authorities. Guests fear to deliberate their views openly and prefer to remain abstinent. Also, the hosts lacked the courage, professionalism, and basic knowledge about the topics for discussion. Government authorities do not want the programs to be critical and deliberative. Equally, failures to achieve an inclusive public sphere are the outcomes of the unstable political landscape in the country. Therefore, due to different factors, including a highly controlled media landscape in Ethiopia, creating platforms for public debate seems unattainable.
Predicting Behavioral Intentions to Prevent or Mitigate COVID-19: A Cross-Cultural Meta-Analysis of Attitudes, Norms, and Perceived Behavioral Control Effects
Authors: Fischer Ronald , Karl Johannes Alfons
Published: June 2021

We examined the effectiveness of attitudes, subjective norms, and perceived behavioral control (PBC) of the theory of planned behavior on COVID-19 relevant behavioral intentions and behaviors. We conducted a meta-analysis of 335 effect sizes from 83 samples across 31 countries ( N = 68,592). We found strongest effects for PBC, but contrary to previous research also moderately strong effects of subjective norms. Focusing on systematic context effects: (a) norm–behavior associations at individual level were strengthened if population norms were stronger; (b) collectivism strengthened norm effects in line with cultural theories, but also attitude and PBC associations, suggesting that COVID-relevant behaviors show collective action properties; (c) in line with cultural theory, tightness–looseness strengthened normative effects on behaviors; and (d) contrary to post-modernization theory, national wealth weakened attitude and PBC associations. These analyses provide new theoretical and practical insights into behavioral dynamics during an acute public health crisis.
Cephalic/cardiac neural crest cell and moyamoya disease
Authors: Ota Takahiro , Komiyama Masaki
Published: June 2021

Background

The neural crest is a transient structure present in early embryogenesis. Cephalic neural crest cells migrate into the pharyngeal arches and the frontonasal process that becomes the forehead and midfacial structures. They also contribute to forming the media of the arteries of the circle of Willis and their branches. The cardiac neural crest produces vascular smooth muscle cells in the ascending aorta, cardiac septum and coronary arteries.

Methods

In this review, we evaluate the role of the neural crest in moyamoya disease and the pathological implications from the concurrence of moyamoya disease and cardiovascular diseases from the point of view of neural crest cell distributions.

Results

Midline craniofacial and central nervous system anomalies with eye anomalies, morning glory disc anomaly in patients with moyamoya disease can both be explained as a subtype of cephalic neurocristopathy. Further, the association between moyamoya disease and cardiac manifestations (congenital cardiac defects and coronary artery disease) have also been reported. Both the cephalic neural crest and cardiac neural crest contribute to these concurrent arterial diseases, as cardio-cephalic neurocristopathy.

Conclusion

The concept of cephalic/cardio-cephalic neurocristopathy provides a new perspective to understanding the underlying aetiological associations and to developing future therapeutic approaches for concomitant moyamoya disease and cardiovascular diseases.
Detection of severe acute respiratory syndrome corona virus 2 in cervico-vaginal secretion of COVID-19-affected female: A prospective observational study from India
Authors: Agarwal Mukta , Basumatary Swmkwr , Bhusan Divendu , Pati Binod Kumar
Published: June 2021

Background:

The novel severe acute respiratory syndrome corona virus 2 (also known as 2019-nCoV) is a highly infectious agent and is declared as a global public health emergency by the World Health Organisation. The main known transmission route of severe acute respiratory syndrome corona virus 2 is through respiratory air droplets. Although recent studies have revealed that the virus is detectable in the throat, blood, urine, anal swabs, tears and even faeces; however, modes of transmission other than respiratory droplets has not been studied much. Knowledge on the presence of the virus in the female genital tract may help determine the risk of sexual transmission as well as the risk of mother-to-child transmission. However, not much data are available yet regarding the presence of the virus in the female genital system. Hence, to explore the presence of the virus in the female genital system and possibility of sexual transmission, a study was conducted where in we tried to detect severe acute respiratory syndrome corona virus 2 in cervico-vaginal secretions.

Methods:

From July 2020 to September 2020, 35 COVID-19-positive female patients admitted to tertiary care teaching institute of Eastern India, which is now declared dedicated Corona Hospital and Centre of Excellence for COVID-19 care, who consented for the research were enrolled in this prospective observational study. Proper gynaecological history, clinical records along with laboratory findings of the patient was recorded. The possibility of the sexual transmission of the virus from female to her male partner was to be ascertained by testing the presence of severe acute respiratory syndrome corona virus 2 in the vaginal, cervical secretions by reverse transcriptase polymerase chain reaction.

Results:

All 35 COVID-19-positive female patients were tested for severe acute respiratory syndrome corona virus 2 in their vaginal and cervical secretions by reverse transcriptase polymerase chain reaction. All the samples were tested negative for the virus.

Conclusion:

Findings from this study reveals that severe acute respiratory syndrome corona virus 2 is not present in the cervical and vaginal secretions, and the possibility of transmission from female to her male partner by vaginal sexual intercourse is unlikely.
Dual drug-induced aseptic meningoencephalitis: More than a suggestion
Authors: Coletti Moja Mario , Riva Giovanna , Catalfamo Edoardo
Published: June 2021

We present the case of a patient with a first single episode of a dual drug-induced aseptic mening (DIAM) due to amoxicillin and ibuprofen and a short review of updated literature. A 76-year-old man was admitted to our hospital with slowness and confusion following a dental and gingival inflammation treated with oral amoxicillin 500 mg bid and ibuprofen 600 mg tid for 1 week. His mental state and higher functions abruptly worsened after therapy increase leading to hospitalization. Both the drugs were stopped and the patient improved rapidly within 2–3 days and was released asymptomatic after a week. On the basis of this temporal relationship with a comprehensive negative neuroimaging and laboratory testing for viral, bacterial, and mycobacterial micro-organisms, a DIAM by amoxicillin and ibuprofen was diagnosed. We support the hypothesis that this dual therapy was causative because of the progressive onset of central nervous system symptoms starting at a low amoxicillin dose with a high ibuprofen intake and that this sort of chemical meningoencephalitis was mostly due to the pharmacokinetic of amoxicillin after its dose increase. To our knowledge, this is the first documented publication of a severe first episode of DIAM with predominant higher function involvement caused by these two drugs commonly used together, amoxicillin and ibuprofen.
Dislocation of the metacarpophalangeal joint of the index finger requiring open reduction due to the presence of an intra-articular sesamoid bone
Authors: O’Neill Elizabeth S , Qin Mia M , Chen Kevin J , Hansdorfer Marek A , Doscher Matthew E
Published: June 2021

Complex dislocation of the metacarpophalangeal joint of the index finger is rare and often requires surgical intervention. Here, we present a case of an index finger metacarpophalangeal joint dislocation requiring open reduction due to obstruction by a displaced volar plate and the intra-articular entrapment of a sesamoid bone. Surgical approach was performed dorsally, allowing easy visualization of the volar plate and sesamoid bone as well as minimizing risk to the radial digital nerve to the index finger. Postoperatively, the patient reported good functional return despite the delay in definitive management.
Successfully superior mesenteric artery stenting in operated type A aortic dissection complicated with delayed mesenteric malperfusion
Authors: Geana Roxana Carmen , Pavel Platon , Nayyerani Reza , Kulcsar Iulia , Tulin Adrian , Honciuc Oana , Balescu Irina , Bacalbasa Nicolae , Stiru Ovidiu , Iliescu Vlad Anton , Parasca Catalina Andreea
Published: June 2021

Here, we describe a case of a 61-year-old male patient with acute type A aortic dissection involving the ascending aorta, aortic arch, descending aorta, and the abdominal aorta down to the iliac bifurcation with evidence of left common iliac artery occlusion. Computed tomography angiography revealed progressive dissection into the superior mesenteric artery and left renal artery with no clinical signs of mesenteric ischemia. Emergent ascending aortic reconstruction of the dissected aorta relieves the leg ischemia. On a postoperative day 9, the evolution was complicated by massive right hemothorax. Although the patient was hemodynamically stable after obtaining hemostasis, the patient developed paralytic ileus with a high elevated lactate level. Visceral malperfusion was not detected by exploratory laparotomy. Emergency abdominal aortic angiography revealed superior mesenteric artery intermittent occlusion, successfully treated by stenting implantation.
The Role of Systemic and Leadership Factors in Influencing Malaysia’s Joint Military Involvementin the Saudi-led Coalition in Yemen,2015–2018
Authors: Idris Asmady , Salleh Asri
Published: June 2021

Malaysia’s military involvement in the Saudi-led coalition in Yemen Ops Yemen II (2015–2018) had been a subject of rigorous debate in the country. Those who opposed it saw the operation as a breach of Malaysia’s Non-Alignment Policy, especially when it involves military operation in a foreign country’s civil war. The main objective of this study is to critically analyze why and how the Barisan Nasional (BN)-led Malaysian government decided to send armed forces to participate in the Saudi-led military operations stationed in Riyadh. In examining this, an analysis on the role of systemic and leadership factors within the conceptual framework of the foreign policy of developing countries is used to explain the character of Malaysia’s joint military operation with Saudi Arabia in the Yemen Crisis. The method and data analysis of this article were mostly derived from written documentary analysis and discussion with related individuals. The findings indicated that both systemic political pressure and the role of leadership were constantly and constructively influenced intersubjective interactions with other domestic factors, which played a vital role in Malaysia’s decision to join the Saudi-led military operations.
Book review: Yogesh Snehi. Spatialising Popular Sufi Shrines in Punjab: Dreams, Memories, Territoriality
Authors: Rezavi Syed Ali Nadeem
Published: June 2021

Yogesh Snehi. Spatialising Popular Sufi Shrines in Punjab: Dreams, Memories, Territoriality (Routledge, South Asian Edition), Shimla 2019, xx + 256 pp., ₹995 (hb).
Colonialism and knowledge transformation: A study of Victorian India
Authors: Kumar Deepak
Published: June 2021

When a civilisation with its own traditional systems of science and philosophy encounters modern knowledge emanating from Europe, a complex change in the former must result. In India, the situation was complicated by the fact that the flagbearers of modern science had also become the masters of the country, and their interests as rulers did not necessarily accord with the pursuit of a full-scale modernising project. The article traces the development of Indian response to the European impact, and how Indian intellectuals began to imbibe modern values, adjusting (not abandoning) their own cultural heritage.
Book review: Margaret jones, Striving for Equity: Health Care in Sri Lanka from Independence to the Millennium, 1948–2000
Authors: Kumar Deepak
Published: June 2021

Margaret jones, Striving for Equity: Health Care in Sri Lanka from Independence to the Millennium, 1948–2000 (Hyderabad: Orient BlackSwan), 2020, pp. xiv + 259, Hardcover, ₹790.
Hindus and Muslims in Medieval North India: Stages of Reciprocal Perception
Authors: Vanina Eugenia
Published: June 2021

Migrating to India and becoming a part of its population, the Muslims passed through different stages in their perception by Hindus. The article discusses these stages of this process–from alienation to familiarity, from generalisation to individualisation–as reflected in some literary texts of medieval epoch. A significant contributor to this development was the growth of Muslim population due not to migration only, but, more significantly, to the conversion of local people who, accepting the new religion, remained familiar with many aspects of regional culture and lifestyle. The other side of the process, the Muslim view of Hindus, is also studied, to demonstrate that, despite observable differences, the followers of both religions took the same direction that led to the recognition of the ‘other’ as a natural part of a socially and culturally heterogeneous entity
Female Workers and Heads of Households in Buenos Aires Countryside During the Nineteenth Century (San Vicente, Buenos Aires, Argentina, 1815–1895)
Authors: Contente Claudia
Published: June 2021

Rural Buenos Aires, as many other regions of what constitutes Argentina today, underwent some radical transformations during the course of the nineteenth century. We here study San Vicente, a rural area where micro-family households were predominant, in order to explore two complementary aspects of the changing social environment. First, the possibilities women had of being the heads of households as well as the resources available to them to earn their living by different means. Secondly, how their position in society evolved during this period. Our main sources are data gathered from the register of inhabitants of 1815 and the National Population Censuses of 1869 and 1895, which we will complement with data from the economic census carried out in 1895. We will see that when competition intensified, there came to be fewer opportunities for women to head households or businesses.
The Development of White Democracy in an Australian Aboriginal Locality
Authors: Byrne Paula Jane
Published: June 2021

Early expressions of democracy in one Australian locality emerged from punitive raids by Whites on Aboriginal camps. Such actions occurred side by side with active and imaginative participation in the institutions of the democratic state, which challenged the reach of government. This polity was brought into being amidst confusion, which also created, by its gaps, opportunities for the unenfranchised, such being women and the Aboriginal people. Yet it was also blind to the Aboriginals’ interests and sought to exclude them altogether from the new order being fashioned.
Life During COVID-19: The Student Experience
Authors: LaRosa Julianne , Doran Cierrah , Guth Amanda , Varshney Karan , Anaele Beverly , Davis Kaitlyn , DiDonato Stephen , Romney Martha , Keddem Shimrit , Frasso Rosemary
Published: June 2021

This study’s objectives were to provide university faculty and administration examples of the challenges students face during COVID-19 and give students a chance to process their experiences with one another. A team of student researchers and interdisciplinary faculty members conducted a photo-elicitation study. Participants were instructed to take photographs for up to 10 days that helped them describe life during the pandemic. The students were subsequently interviewed about their photos over a video conferencing platform. We conducted semistructured photo-elicitation interviews with 43 university students from April 20, 2020, to May 26, 2020. Qualitative analysis of interview transcripts revealed that students were affected by the pandemic at three levels: individual, interpersonal, and organizational. Participant responses are a call to action for educators to prioritize safety, connection, and wellness in their pedagogical practices. The students who participated in this project made a clear statement to faculty about their learning and well-being needs. Learning cannot be prioritized over loss of safety amid the pandemic, health concerns, or social injustices.
Community narratives and local impacts of invasion in the Eastern Cape: A critical invasion ethnography of black wattle
Authors: Reynolds Jules M
Published: June 2021

Since 1995, the South African government has spearheaded a national invasive species campaign known as the Working for Water Program with the dual objectives of invasive species eradication and rural development. This national narrative on invasive species reflects a politicized research agenda and a wealth of material resources directed toward eradication, yet does not accurately portray the reality of invasion at the village level. In particular, Acacia mearnsii de Wild, or the black wattle tree, is classified as one of the worst invasive species in South Africa and a primary target for Working for Water, yet represents an important livelihood resource for rural communities and impacts community members differentially. To better understand these local rural realties, I use a critical invasion science approach to interrogate the local experiences and narratives of black wattle invasion in a rural pastoral community in the Eastern Cape. Within this community, local understandings and impacts of black wattle are nuanced, spatially variable, and reflect complex knowledge politics and political economies. As invasion research moves to incorporate the human and local dimension of invasion for improved policy, it is imperative to fully consider this differentiation of perspectives and impacts within the local community.
What Theory Is and Can Be: Forms of Theorizing in Organizational Scholarship
Authors: Cornelissen Joep , Höllerer Markus A. , Seidl David
Published: June 2021

Theory is at the very heart of organizational scholarship and a key criterion for evaluating the quality and contribution of our research. Focusing on conceptual rather than empirical work, this editorial essay highlights the wide range of forms that theorizing might take – and how it, in consequence, materializes in different types of theory papers. Next to the propositional form of theory building, which has so far dominated reflections in the literature, we discuss the particularities of process, configurational, perspectival, and meta-theorizing, as well as various forms of critique. We demonstrate how these forms of theorizing differ in terms of their aims, style of reasoning, their contributions, and the way in which they are written up as papers. In view of the rather different roles that each of these forms of theorizing serve, we propagate, in line with the ethos of Organization Theory, a pluralistic stance when it comes to advancing theory in organization studies.
Characteristics of seismic motions at a concrete gravity dam site and suggestions for setting the engineering bedrock
Authors: Yasuda Nario , Cao Zengyan
Published: June 2021

The earthquake records of a concrete gravity dam with eight seismographs were spectrally analyzed to clarify the characteristics of the seismic motions at each monitoring station. Based on the analysis results, whether it is appropriate to use such earthquake records to generate the input ground motion in assessments of the seismic performance of dams was discussed. It was found that the earthquake records at the dam base show reduced amplitudes at frequencies corresponding to the natural vibration modes of the dam. When these earthquake records are used to generate the input ground motion in an assessment of the seismic performance of a dam, sufficient consideration should be given to this feature. Suggestions on where to install seismographs at dam sites are presented. Based on the numerical simulation of the seismic response of the dam, it is suggested that the engineering bedrock should be considered to be located at a depth of at least 1.5 times the dam height, and the shear wave velocity of the rock at that depth should preferably be 2000 m/s or more. Since this study uses seismic motions recorded across the entire dam site, including the deep rock, which is globally rare, it is considered that the basic conclusions obtained in the article can provide a reference for other concrete dams.
A factor VIIIa–mimetic bispecific antibody, Mim8, ameliorates bleeding upon severe vascular challenge in hemophilia A mice
Authors: Østergaard Henrik , Lund Jacob , Greisen Per J. , Kjellev Stine , Henriksen Anette , Lorenzen Nikolai , Johansson Eva , Røder Gustav , Rasch Morten G. , Johnsen Laust B. , Egebjerg Thomas , Lund Søren , Rahbek-Nielsen Henrik , Gandhi Prafull S. , Lamberth Kasper , Loftager Mette , Andersen Lisbeth M. , Bonde Amalie C. , Stavenuiter Fabian , Madsen Daniel E. , Li Xun , Holm Thomas L. , Ley Carsten D. , Thygesen Peter , Zhu Haisun , Zhou Rong , Thorn Karina , Yang Zhiru , Hermit Mette B. , Bjelke Jais R. , Hansen Bjarne G. , Hilden Ida
Published: June 2021

Hemophilia A is a bleeding disorder resulting from deficient factor VIII (FVIII), which normally functions as a cofactor to activated factor IX (FIXa) that facilitates activation of factor X (FX). To mimic this property in a bispecific antibody format, a screening was conducted to identify functional pairs of anti-FIXa and anti-FX antibodies, followed by optimization of functional and biophysical properties. The resulting bispecific antibody (Mim8) assembled efficiently with FIXa and FX on membranes, and supported activation with an apparent equilibrium dissociation constant of 16 nM. Binding affinity with FIXa and FX in solution was much lower, with equilibrium dissociation constant values for FIXa and FX of 2.3 and 1.5 µM, respectively. In addition, the activity of Mim8 was dependent on stimulatory activity contributed by the anti-FIXa arm, which enhanced the proteolytic activity of FIXa by 4 orders of magnitude. In hemophilia A plasma and whole blood, Mim8 normalized thrombin generation and clot formation, with potencies 13 and 18 times higher than a sequence-identical analogue of emicizumab. A similar potency difference was observed in a tail vein transection model in hemophilia A mice, whereas reduction of bleeding in a severe tail-clip model was observed only for Mim8. Furthermore, the pharmacokinetic parameters of Mim8 were investigated and a half-life of 14 days shown in cynomolgus monkeys. In conclusion, Mim8 is an activated FVIII mimetic with a potent and efficacious hemostatic effect based on preclinical data.
Specific targeting of the KRAS mutational landscape in myeloma as a tool to unveil the elicited antitumor activity
Authors: Sacco Antonio , Federico Cinzia , Todoerti Katia , Ziccheddu Bachisio , Palermo Valentina , Giacomini Arianna , Ravelli Cosetta , Maccarinelli Federica , Bianchi Giada , Belotti Angelo , Ribolla Rossella , Favasuli Vanessa , Revenko Alexey S. , Macleod A. Robert , Willis Brandon , Cai Hongbo , Hauser Joana , Rooney Claire , Willis Sophie E. , Martin Philip Lloyd , Staniszewska Anna , Ambrose Helen , Hanson Lyndsey , Cattaneo Chiara , Tucci Alessandra , Rossi Giuseppe , Ronca Roberto , Neri Antonino , Mitola Stefania , Bolli Niccolò , Presta Marco , Moschetta Michele , Ross Sarah , Roccaro Aldo M.
Published: June 2021

Alterations in KRAS have been identified as the most recurring somatic variants in the multiple myeloma (MM) mutational landscape. Combining DNA and RNA sequencing, we studied 756 patients and observed KRAS as the most frequently mutated gene in patients at diagnosis; in addition, we demonstrated the persistence or de novo occurrence of the KRAS aberration at disease relapse. Small-molecule inhibitors targeting KRAS have been developed; however, they are selective for tumors carrying the KRASG12C mutation. Therefore, there is still a need to develop novel therapeutic approaches to target the KRAS mutational events found in other tumor types, including MM. We used AZD4785, a potent and selective antisense oligonucleotide that selectively targets and downregulates all KRAS isoforms, as a tool to dissect the functional sequelae secondary to KRAS silencing in MM within the context of the bone marrow niche and demonstrated its ability to significantly silence KRAS, leading to inhibition of MM tumor growth, both in vitro and in vivo, and confirming KRAS as a driver and therapeutic target in MM.
The hidden history of hypersensitivity pneumonitis
Authors: Barnes Hayley , Jones Kirk , Blanc Paul
Published: June 2021

Hypersensitivity pneumonitis (HP) is a relatively new construct, first reported in the early 20th century, despite major aetiological factors (farming, bird husbandry) having been part of human activities for millennia. Initial confirmed HP reports included exposure to farming and forestry (1932) and bird exposure (1965), much more recently than is often assumed. Later changes in occupational and living practices have led to HP associated with isocyanates, machine coolants, indoor mould, hot tubs and other exposures. Evolution of our pathological understanding of interstitial lung disease in general, wider computed tomography utilisation and advances in immunology and genomics have shaped our modern conceptualisation of HP. Examining historical accounts of HP and its causative factors not only considers when the first cases were recognised, but also explores why the disease emerged at specific times and places, and may provide further insights relevant to the mechanisms underlying HP and disease prevention.
Transcriptomics of bronchoalveolar lavage cells identifies new molecular endotypes of sarcoidosis
Authors: Vukmirovic Milica , Yan Xiting , Gibson Kevin F. , Gulati Mridu , Schupp Jonas C. , DeIuliis Giuseppe , Adams Taylor S. , Hu Buqu , Mihaljinec Antun , Woolard Tony N. , Lynn Heather , Emeagwali Nkiruka , Herzog Erica L. , Chen Edward S. , Morris Alison , Leader Joseph K. , Zhang Yingze , Garcia Joe G.N. , Maier Lisa A. , Collman Ronald G. , Drake Wonder P. , Becich Michael J. , Hochheiser Harry , Wisniewski Steven R. , Benos Panayiotis V. , Moller David R. , Prasse Antje , Koth Laura L. , Kaminski Naftali
Published: June 2021

Background

Sarcoidosis is a multisystem granulomatous disease of unknown origin with a variable and often unpredictable course and pattern of organ involvement. In this study we sought to identify specific bronchoalveolar lavage (BAL) cell gene expression patterns indicative of distinct disease phenotypic traits.

Methods

RNA sequencing by Ion Torrent Proton was performed on BAL cells obtained from 215 well-characterised patients with pulmonary sarcoidosis enrolled in the multicentre Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study. Weighted gene co-expression network analysis and nonparametric statistics were used to analyse genome-wide BAL transcriptome. Validation of results was performed using a microarray expression dataset of an independent sarcoidosis cohort (Freiburg, Germany; n=50).

Results

Our supervised analysis found associations between distinct transcriptional programmes and major pulmonary phenotypic manifestations of sarcoidosis including T-helper type 1 (Th1) and Th17 pathways associated with hilar lymphadenopathy, transforming growth factor-β1 (TGFB1) and mechanistic target of rapamycin (MTOR) signalling with parenchymal involvement, and interleukin (IL)-7 and IL-2 with airway involvement. Our unsupervised analysis revealed gene modules that uncovered four potential sarcoidosis endotypes including hilar lymphadenopathy with increased acute T-cell immune response; extraocular organ involvement with PI3K activation pathways; chronic and multiorgan disease with increased immune response pathways; and multiorgan involvement, with increased IL-1 and IL-18 immune and inflammatory responses. We validated the occurrence of these endotypes using gene expression, pulmonary function tests and cell differentials from Freiburg.

Conclusion

Taken together, our results identify BAL gene expression programmes that characterise major pulmonary sarcoidosis phenotypes and suggest the presence of distinct disease molecular endotypes.
MULTI-PHACET: multidimensional clinical phenotyping of hospitalised acute COPD exacerbations
Authors: MacDonald Martin I. , Osadnik Christian R. , Bulfin Lauren , Leahy Elizabeth , Leong Paul , Shafuddin Eskandarain , Hamza Kais , King Paul T. , Bardin Philip G.
Published: June 2021

Background

The generic term “exacerbation” does not reflect the heterogeneity of acute exacerbations of COPD (AECOPD). We utilised a novel algorithmic strategy to profile exacerbation phenotypes based on underlying aetiologies.

Methods

Patients hospitalised for AECOPD (n=146) were investigated for aetiological contributors summarised in a mnemonic acronym ABCDEFGX (A: airway virus; B: bacterial; C: co-infection; D: depression/anxiety; E: eosinophils; F: failure (cardiac); G: general environment; X: unknown). Results from clinical investigations were combined to construct AECOPD phenotypes. Relationships to clinical outcomes were examined for both composite phenotypes and their specific aetiological components. Aetiologies identified at exacerbation were reassessed at outpatient follow-up.

Results

Hospitalised AECOPDs were remarkably diverse, with 26 distinct phenotypes identified. Multiple aetiologies were common (70%) and unidentifiable aetiology rare (4.1%). If viruses were detected (29.5%), patients had longer hospitalisation (7.7±5.6versus6.0±3.9 days, p=0.03) despite fewer “frequent exacerbators” (9.3%versus37%, p=0.001) and lower mortality at 1 year (p=0.03). If bacterial infection was found (40.4%), patients were commonly “frequent exacerbators” (44%versus18.4%, p=0.001). Eosinophilic exacerbations (28%) were associated with lower pH (7.32±0.06versus7.36±0.09, p=0.04), higher venous carbon dioxide tension (PvCO2) (53.7±10.5versus48.8±12.8, p=0.04), greater noninvasive ventilation (NIV) usage (34.1%versus18.1%) but shorter hospitalisation (4 (3–5)versus6 (4–9) days, p<0.001) and lower infection rates (41.4%versus80.9%, p<0.0001). Cardiac dysfunction and severe anxiety/depression were common in both infective and non-infective exacerbations. Characteristics identified at exacerbation often persisted after recovery.

Conclusions

Hospitalised AECOPDs have numerous causes, often in combination, that converge in complex, multi-faceted phenotypes. Clinically important differences in outcomes suggest that a phenotyping strategy based on aetiologies can enhance AECOPD management.
Targeting dynamic hyperinflation in moderate-to-severe asthma: a randomised controlled trial
Authors: van der Meer Akke-Nynke , de Jong Kim , Hoekstra-Kuik Aranka , Bel Elisabeth H. , ten Brinke Anneke
Published: June 2021

Background

Dynamic hyperinflation is highly prevalent in moderate-to-severe asthma, which may significantly impede activities of daily life. We hypothesised that dynamic hyperinflation in asthma is due to inflammation of large and small airways and can be reduced by systemic anti-inflammatory treatment. Therefore, we investigated the effect of systemic glucocorticoids on dynamic hyperinflation in moderate-to-severe asthma patients and explored the relationships between inflammatory markers and changes in dynamic hyperinflation.

Methods

In this randomised placebo-controlled trial we included 32 asthma patients on inhaled glucocorticoid therapy showing dynamic hyperinflation, defined by a ≥10% reduction in inspiratory capacity measured by standardised metronome-paced tachypnea test. Patients received either triamcinolone (80 mg) or placebo intramuscularly. Before and 2 weeks after treatment, patients completed respiratory health questionnaires, had blood eosinophils and exhaled nitric oxide levels measured, and underwent lung function and dynamic hyperinflation testing.

Results

After adjustment for potential confounders, dynamic hyperinflation was significantly reduced by 28.1% in the triamcinolone group and increased by 9.4% in the placebo group (p=0.027). In the triamcinolone-treated patients, the reduction in dynamic hyperinflation was greater in patients with higher blood eosinophils at baseline (r=−0.592, p=0.020) and tended to be associated with a reduction in blood eosinophils (r=0.412, p=0.127) and exhaled nitric oxide (r=0.442, p=0.099).

Conclusions

This exploratory study suggests that dynamic hyperinflation in asthma can be reduced by systemic anti-inflammatory treatment, particularly in patients with elevated blood eosinophils. This supports the hypothesis that dynamic hyperinflation in asthma is due to airway inflammation and should be considered an important target for treatment.
Prospective association between use of electronic cigarettes and use of conventional cigarettes: a systematic review and meta-analysis
Authors: Adermark Louise , Galanti Maria Rosaria , Ryk Charlotta , Gilljam Hans , Hedman Linnea
Published: June 2021

Objective

The aim of this systematic review and meta-analysis was to assess the association between e-cigarette use and subsequent initiation or recurrence of cigarette smoking.

Data sources

A systematic literature search was finalised on 11 November 2019 using PubMed (including MEDLINE), EMBASE, Cochrane Library, Scopus, PubMed Health, NICE Evidence Search, PROSPERO, CRD and PsycInfo.

Study selection

Studies were included if meeting the following criteria: reporting empirical results; longitudinal observational design with a minimum of 3 months of follow-up; including general population samples; allowing for the comparison between users and nonusers of e-cigarettes. Studies rated as having high risk of bias were excluded. Studies were independently assessed by at least two authors. The procedures described by PRISMA were followed, and the quality of evidence was rated using GRADE.

Data synthesis

30 longitudinal studies from 22 different cohorts assessing e-cigarette use among nonsmokers or never-smokers at baseline, and subsequent use of cigarette smoking at follow-up, were included in this review. A random-effects meta-analysis based on 89 076 participants showed a pooled unadjusted odds ratio (OR) of cigarette smoking among baseline nonsmoker e-cigarette users compared with nonusers of 4.68 (CI 3.64–6.02), while the adjusted OR was 3.37 (CI 2.68–4.24). These results were consistent irrespective of whether the outcome was measured as ever-smoking or as past 30-day smoking. The evidence was graded as moderate.

Conclusions

Use of e-cigarettes may predict the initiation or recurrence of cigarette smoking.
Designs of InGaN Micro-LED Structure for Improving Quantum Efficiency at Low Current Density
Authors: Lu Shiqiang , Li Jinchai , Huang Kai , Liu Guozhen , Zhou Yinghui , Cai Duanjun , Zhang Rong , Kang Junyong
Published: June 2021

Here we report a comprehensive numerical study for the operating behavior and physical mechanism of nitride micro-light-emitting-diode (micro-LED) at low current density. Analysis for the polarization effect shows that micro-LED suffers a severer quantum-confined Stark effect at low current density, which poses challenges for improving efficiency and realizing stable full-color emission. Carrier transport and matching are analyzed to determine the best operating conditions and optimize the structure design of micro-LED at low current density. It is shown that less quantum well number in the active region enhances carrier matching and radiative recombination rate, leading to higher quantum efficiency and output power. Effectiveness of the electron blocking layer (EBL) for micro-LED is discussed. By removing the EBL, the electron confinement and hole injection are found to be improved simultaneously, hence the emission of micro-LED is enhanced significantly at low current density. The recombination processes regarding Auger and Shockley–Read–Hall are investigated, and the sensitivity to defect is highlighted for micro-LED at low current density.

Synopsis: The polarization-induced QCSE, the carrier transport and matching, and recombination processes of InGaN micro-LEDs operating at low current density are numerically investigated. Based on the understanding of these device behaviors and mechanisms, specifically designed epitaxial structures including two QWs, highly doped or without EBL and p-GaN with high hole concentration for the efficient micro-LED emissive display are proposed. The sensitivity to defect density is also highlighted for micro-LED.
RNAdetector: a free user-friendly stand-alone and cloud-based system for RNA-Seq data analysis
Authors: La Ferlita Alessandro , Alaimo Salvatore , Di Bella Sebastiano , Martorana Emanuele , Laliotis Georgios I. , Bertoni Francesco , Cascione Luciano , Tsichlis Philip N. , Ferro Alfredo , Bosotti Roberta , Pulvirenti Alfredo
Published: June 2021

Background

RNA-Seq is a well-established technology extensively used for transcriptome profiling, allowing the analysis of coding and non-coding RNA molecules. However, this technology produces a vast amount of data requiring sophisticated computational approaches for their analysis than other traditional technologies such as Real-Time PCR or microarrays, strongly discouraging non-expert users. For this reason, dozens of pipelines have been deployed for the analysis of RNA-Seq data. Although interesting, these present several limitations and their usage require a technical background, which may be uncommon in small research laboratories. Therefore, the application of these technologies in such contexts is still limited and causes a clear bottleneck in knowledge advancement.

Results

Motivated by these considerations, we have developed RNAdetector, a new free cross-platform and user-friendly RNA-Seq data analysis software that can be used locally or in cloud environments through an easy-to-use Graphical User Interface allowing the analysis of coding and non-coding RNAs from RNA-Seq datasets of any sequenced biological species.

Conclusions

RNAdetector is a new software that fills an essential gap between the needs of biomedical and research labs to process RNA-Seq data and their common lack of technical background in performing such analysis, which usually relies on outsourcing such steps to third party bioinformatics facilities or using expensive commercial software.
Lactobacillus rhamnosus GG modifies the metabolome of pathobionts in gnotobiotic mice
Authors: Kim Jinhee , Balasubramanian Iyshwarya , Bandyopadhyay Sheila , Nadler Ian , Singh Rajbir , Harlan Danielle , Bumber Amanda , He Yuling , Kerkhof Lee J. , Gao Nan , Su Xiaoyang , Ferraris Ronaldo P.
Published: June 2021

Background

Lactobacillus rhamnosus GG (LGG) is the most widely used probiotic, but the mechanisms underlying its beneficial effects remain unresolved. Previous studies typically inoculated LGG in hosts with established gut microbiota, limiting the understanding of specific impacts of LGG on host due to numerous interactions among LGG, commensal microbes, and the host. There has been a scarcity of studies that used gnotobiotic animals to elucidate LGG-host interaction, in particular for gaining specific insights about how it modifies the metabolome. To evaluate whether LGG affects the metabolite output of pathobionts, we inoculated with LGG gnotobiotic mice containing Propionibacterium acnes, Turicibacter sanguinis, and Staphylococcus aureus (PTS).

Results

16S rRNA sequencing of fecal samples by Ion Torrent and MinION platforms showed colonization of germ-free mice by PTS or by PTS plus LGG (LTS). Although the body weights and feeding rates of mice remained similar between PTS and LTS groups, co-associating LGG with PTS led to a pronounced reduction in abundance of P. acnes in the gut. Addition of LGG or its secretome inhibited P. acnes growth in culture. After optimizing procedures for fecal metabolite extraction and metabolomic liquid chromatography-mass spectrometry analysis, unsupervised and supervised multivariate analyses revealed a distinct separation among fecal metabolites of PTS, LTS, and germ-free groups. Variables-important-in-projection scores showed that LGG colonization robustly diminished guanine, ornitihine, and sorbitol while significantly elevating acetylated amino acids, ribitol, indolelactic acid, and histamine. In addition, carnitine, betaine, and glutamate increased while thymidine, quinic acid and biotin were reduced in both PTS and LTS groups. Furthermore, LGG association reduced intestinal mucosal expression levels of inflammatory cytokines, such as IL-1α, IL-1β and TNF-α.

Conclusions

LGG co-association had a negative impact on colonization of P. acnes, and markedly altered the metabolic output and inflammatory response elicited by pathobionts.
Retraction Note to: Differential regulation of wild-type and mutant alpha-synuclein binding to synaptic membranes by cytosolic factors
Authors: Wislet-Gendebien Sabine , Visanji Naomi P. , Whitehead Shawn N. , Marsilio Diana , Hou Weimin , Figeys Daniel , Fraser Paul E. , Bennett Steffany A. L. , Tandon Anurag
Published: June 2021

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12868-021-00644-1