bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of Micronutrient Deficiency after Bariatric Surgery
Authors: Krzizek Eva-Christina , Brix Johanna Maria , Stöckl Alexander , Parzer Verena , Ludvik Bernhard
Published: April 2021

Introduction: While vitamin deficiency after bariatric surgery has been repeatedly described, few studies have focused on adequate micronutrient status. In this study, we examine the prevalence of vitamin and micronutrient deficiency for the first 3 years after surgery. Methods: Out of 1,216 patients undergoing surgery, 485 who underwent postoperative follow-up in an outpatient clinic between 2010 and 2019 were included in this evaluation (76.9% women, mean age 42 ± 12 years, mean BMI: year 1, 33.9 ± 19.2; year 2, 29.7 ± 8.7; year 3, 26.2 ± 4.0). Weight and cardiovascular risk factors as well as ferritin, vitamin B12, folic acid, 25-OH-vitamin D, vitamin A, vitamin E, zinc, copper, and selenium were evaluated. Deficits were defined as follows: ferritin <15 µg/L, vitamin B12 <197 pg/mL, folic acid <4.4 ng/mL, 25-OH-vitamin D <75 nmol/L, vitamin A <1.05 µmol/L, vitamin E <12 µmol/L, zinc <0.54 mg/L, copper <0.81 mg/L, and selenium <50 µg/L. All patients underwent dietary counselling and substitution of the respective deficits as appropriate. Results: One year after bariatric surgery, 485 patients completed follow-up. This number decreased to 114 patients in year 2, and 80 patients in year 3. Overall, 42.7% (n = 207) underwent sleeve gastrectomy, 43.7% (n = 211) Roux-en-Y-gastric bypass, and 13.9% (n = 67) gastric banding. The following deficits were found (year 1/2/3): ferritin, 21.6/35.0/32.5%; vitamin B12, 14.3/1.8/6.3%; folic acid, 29.7/21.6/15.3%; 25-OH-vitamin D, 70.8/67.0/57.4%; vitamin A, 13.2/8.9/12.8%; vitamin E, 0%; zinc, 1.7/0/1.5%; copper, 10.4/12.2/11.9%; selenium, 11.1/4.3/0%. Conclusion: As seen in other studies, the follow-up frequency decreased over the years. Despite intensive substitution, the extent of some deficiencies increased or did not improve. These results suggest reinforcing measures to motivate patients for regular follow-up visits, considering closer monitoring schedules, and improving supplementation strategies.
A Wrist-Worn Sensor-Derived Frailty Index Based on an Upper-Extremity Functional Test in Predicting Functional Mobility in Older Adults
Authors: Kang Gu Eon , Naik Aanand D. , Ghanta Ravi K. , Rosengart Todd K. , Najafi Bijan
Published: April 2021

Introduction: Preoperative frailty is an independent risk factor for postoperative complications across surgical specialties. Functional mobility such as gait, timed up and go (TUG), and 5 times sit-to-stand (5-STS) are popular preoperative frailty measurements but are not suitable for patients with severe mobility impairment. A wrist-worn sensor-derived frailty index based on an upper-extremity functional test (20-s repetitive elbow flexion-extension task; UEFI) was developed previously; however, its association with functional mobility remained unexplored. We aimed to investigate the predictive power of the UEFI in predicting functional mobility. Methods: We examined correlation between the UEFI and gait speed, TUG duration, and 5-STS duration in 100 older adults (≥ 65 years) using multivariate regression analysis. The UEFI was calculated using slowness, weakness, exhaustion, and flexibility of the sensor-based 20-s repetitive elbow flexion-extension task. Results: The UEFI was a significant predictor for gait speed and TUG duration and 5-STS duration (all R ≥ 0.60; all p < 0.001) with the variance (adjusted R2) of 35–37% for the dependent variables. The multivariate regression analysis revealed significant associations between the UEFI and gait speed (β = −0.84; 95% confidence interval [95% CI] = [−1.19, −0.50]; p < 0.001) and TUG duration (β = 16.2; 95% CI = [9.59, 22.8]; p < 0.001) and 5-STS duration (β = 33.3; 95% CI = [23.6, 43.2]; p < 0.001), found after accounting for confounding variables (e.g., age and fear of falling scale). Conclusions: Our findings suggest that the UEFI can be performed with a wrist-worn sensor and has been validated with other established measures of preoperative frailty. The UEFI can be applied in a wide variety of patients, regardless of mobility limitations, in an outpatient setting.
Lymphatic Malformation Responsive to Sirolimus in Keratinocytic Epidermal Nevus Syndrome with KRAS Mutation: A Case and Brief Literature Discussion
Authors: Sideris Emily , Tng Er Tsing Vivian , Chee Paul
Published: April 2021

We present a rare case of KRAS keratinocytic epidermal nevus syndrome with lymphatic malformation, responsive to treatment with sirolimus, an mTOR inhibitor. A brief review of the current literature regarding sirolimus use in vascular malformations, lymphatic malformations, regional overgrowth syndromes, and RASopathies is discussed.
Low LAL (Lysosomal Acid Lipase) Expression by Smooth Muscle Cells Relative to Macrophages as a Mechanism for Arterial Foam Cell Formation
Authors: Dubland Joshua A. , Allahverdian Sima , Besler Katrina J. , Ortega Carleena , Wang Ying , Pryma Collin S. , Boukais Kamel , Chan Teddy , Seidman Michael A. , Francis Gordon A.
Published: April 2021

Objective:

We previously reported smooth muscle cells (SMCs) represent ≥50% of foam cells in human coronary and ≈70% in apoE (apolipoprotein E)-deficient mouse aortic atheromas and exhibit reduced expression of the cholesterol exporter ABCA1 (ATP-binding cassette transporter A1). A major stimulus for ABCA1 expression is flux of cholesterol out of lysosomes, generated by hydrolysis of lipoprotein cholesteryl esters by LAL (lysosomal acid lipase). In this study, we investigated the potential role lysosomal dysfunction might play in foam cell formation by arterial SMCs.

Approach and Results:

Human monocyte-derived macrophages (macrophages) and arterial SMCs were treated with aggregated LDL (low-density lipoprotein) to increase intracellular cholesterol and investigated for lysosomal and postlysosomal cholesterol metabolism defects. Human and mouse atheromas were analyzed for LAL expression. Unlike macrophages, aggregated LDL uptake failed to upregulate ABCA1 expression, downregulate new cholesterol synthesis, or to significantly increase 27-hydroxycholesterol levels in SMCs. Confocal microscopy revealed retention of neutral lipids within lysosomal compartments in SMCs, while macrophages showed most lipids as cytosolic droplets.
LIPA
(lipase A) mRNA levels and LAL protein were markedly reduced in SMCs. Treatment of SMCs with medium containing LAL resulted in significantly reduced lysosomal lipid accumulation and increased cholesterol efflux to apoA-I (apolipoprotein AI). Human and mouse atheromas exhibited low LAL/
Lipa
expression in intimal SMCs when compared with intimal macrophages.

Conclusions:

These findings indicate the inherently low level of LAL in SMCs compared with macrophages is associated with reduced capacity to catabolize atherogenic lipoproteins and is a mechanism for SMC foam cell formation in atherosclerosis.
Hypertension and Prohypertensive Antineoplastic Therapies in Cancer Patients
Authors: van Dorst Daan C.H. , Dobbin Stephen J.H. , Neves Karla B. , Herrmann Joerg , Herrmann Sandra M. , Versmissen Jorie , Mathijssen Ron H.J. , Danser A.H. Jan , Lang Ninian N.
Published: April 2021

The development of a wide range of novel antineoplastic therapies has improved the prognosis for patients with a wide range of malignancies, which has increased the number of cancer survivors substantially. Despite the oncological benefit, cancer survivors are exposed to short- and long-term adverse cardiovascular toxicities associated with anticancer therapies. Systemic hypertension, the most common comorbidity among cancer patients, is a major contributor to the increased risk for developing these adverse cardiovascular events. Cancer and hypertension have common risk factors, have overlapping pathophysiological mechanisms and hypertension may also be a risk factor for some tumor types. Many cancer therapies have prohypertensive effects. Although some of the mechanisms by which these antineoplastic agents lead to hypertension have been characterized, further preclinical and clinical studies are required to investigate the exact pathophysiology and the optimal management of hypertension associated with anticancer therapy. In this way, monitoring and management of hypertension before, during, and after cancer treatment can be improved to minimize cardiovascular risks. This is vital to optimize cardiovascular health in patients with cancer and survivors, and to ensure that advances in terms of cancer survivorship do not come at the expense of increased cardiovascular toxicities.
Hypertension
Authors: Madhur Meena S. , Elijovich Fernando , Alexander Matthew R. , Pitzer Ashley , Ishimwe Jeanne , Van Beusecum Justin P. , Patrick David M. , Smart Charles D. , Kleyman Thomas R. , Kingery Justin , Peck Robert N. , Laffer Cheryl L. , Kirabo Annet
Published: April 2021

Elevated cardiovascular risk including stroke, heart failure, and heart attack is present even after normalization of blood pressure in patients with hypertension. Underlying immune cell activation is a likely culprit. Although immune cells are important for protection against invading pathogens, their chronic overactivation may lead to tissue damage and high blood pressure. Triggers that may initiate immune activation include viral infections, autoimmunity, and lifestyle factors such as excess dietary salt. These conditions activate the immune system either directly or through their impact on the gut microbiome, which ultimately produces chronic inflammation and hypertension. T cells are central to the immune responses contributing to hypertension. They are activated in part by binding specific antigens that are presented in major histocompatibility complex molecules on professional antigen-presenting cells, and they generate repertoires of rearranged T-cell receptors. Activated T cells infiltrate tissues and produce cytokines including interleukin 17A, which promote renal and vascular dysfunction and end-organ damage leading to hypertension. In this comprehensive review, we highlight environmental, genetic, and microbial associated mechanisms contributing to both innate and adaptive immune cell activation leading to hypertension. Targeting the underlying chronic immune cell activation in hypertension has the potential to mitigate the excess cardiovascular risk associated with this common and deadly disease.
Is God Redeemable?
Authors: Askani Hans-Christoph
Published: April 2021

We might suggest two possible ways of understanding our question: Can God be redeemed? and: Must God be redeemed? In both cases the question sounds blasphemous. But following the movement that Franz Rosenzweig develops in The Star of Redemption, I suggest that the living relation initiated by God, as God created the world and as God revealed himself to the human being, would be an abstract construction if, on the one hand, the human being and the world did not need each other in order to become what they are and what they could be, and if, on the other hand, God was not implicated in this mutual relationship.
Moving to the Music
Authors: Laferrière Carolyn M.
Published: April 2021

This paper serves as a brief introduction to a recent MOISA-sponsored panel at the Annual Meeting of the Society of Classical Studies, held in Washington, D.C. from January 2–5, 2020. Three of these papers will appear in the current and subsequent issues as articles that, together with two additional contributions, are broadly dedicated to the theme of music and dance in Greek and Roman antiquity.
A new water mite genus from Kazakhstan (Acari, Hydrachnidia, Hydryphantidae)
Authors: TUZOVSKIJ PETR V. , STOLBOV VITALY A.
Published: April 2021

This paper describes a new genus of the water mite family Hydryphantidae. The material was collected by V. Stolbov in 2019 in running waters in Kazakhstan. The material was sampled with a common hand net with 250 µm mesh size. The water mites were fixed in 75% ethanol.
Checklist of Staphylinidae (Coleoptera) of El Salvador
Authors: PABLO-CEA JOSÉ D. , ASENJO ANGÉLICO , NAVARRETE-HEREDIA JOSÉ L. , NEWTON ALFRED F.
Published: April 2021

This paper is primarily a compilation of published data on the staphylinid beetle species reported for El Salvador. It is based on taxonomic and ecological literature, with inclusion of some new records from different entomological collections. Thirty eight genera and 96 species are reported in the list, including a first country record: Eulissus chalybaeus. Country-level distribution outside of El Salvador, locality references and topographic zones are included for each species. In the list, three endemic species are recorded: Seeversiella badia, S. minima and Stenus salvadorensis. It is remarkable that 14 genera (37%) and 52 species (54%) have only been reported at a country level in the literature, without a specific locality of collection, indicating the need for local inventories of this coleopteran family in the salvadoran territory.
New Caledonian species misplaced in Horaeomorphus Schaufuss belong in Heterotetramelus Franz (Coleoptera, Staphylinidae, Scydmaeninae)
Authors: JAŁOSZYŃSKI PAWEŁ
Published: April 2021

Horaeomorphus Schaufuss is an easily identifiable genus of Stenichnini, predominantly distributed in the Australasian realm. Many scydmaenines occurring in other regions, however, have been misplaced in Horaeomorphus, and therefore the true distribution of this genus remains unclear. In previous studies several new genera were established for Australian species misplaced in Horaeomorphus, and a few species misplaced in Euconnus Thomson, Stenichnus Thomson, and Syndicus Motschulsky were transferred to Horaeomorphus. Three species that inhabit New Caledonia were placed in this genus: Horaeomorphus australis Franz, H. baloghi Franz, and H. novaecaledoniae Franz. Examination of these taxa revealed that none of them was conspecific with the SE Asian type species of Horaeomorphus. Three new combinations are proposed: Heterotetramelus (s. str.) australis (Franz) comb. n., Heterotetramelus (s. str.) baloghi (Franz) comb. n., and Heterotetramelus (s. str.) novaecaledoniae (Franz) comb. n.; each species is redescribed.
Tubuliferous Thysanoptera in Australia with an enlarged tenth abdominal segment (Phlaeothripidae, Idolothripinae), including six new species
Authors: MOUND LAURENCE A. , TREE DESLEY J.
Published: April 2021

Remarkable structural variation in the tenth abdominal segment of some Phlaeothripidae species is discussed, together with its behavioural significance. Two tropical genera are newly recorded from Australia: in Acallurothrips Bagnall four species are recorded, A. darumbali sp.n., A. erubi sp.n., A. yagara sp.n. and A. nogutii Kurosawa, and in Neosmerinthothrips Schmutz two species are recorded, N. barrowi sp.n. and N. turrbali sp.n. The genus Ozothrips was previously based on five species from New Zealand, but O. meanjini sp.n. is here described from Queensland. Four species of Pygothrips are recorded from Australia, a genus that is widespread in tropical countries.
Lake-effect rains over Lake Victoria and their association with Mesoscale Convective Systems
Authors: Nicholson Sharon E. , Klotter Douglas , Hartman Adam T.
Published: April 2021

This article examined rainfall enhancement over Lake Victoria. Estimates of over-lake rainfall were compared with rainfall in the surrounding lake catchment. Four satellite products were initially tested against estimates based on gauges or water balance models. These included TRMM 3B43, IMERG V06 Final Run (IMERG-F), CHIRPS2, and PERSIANN-CDR. There was agreement among the satellite products for catchment rainfall but a large disparity among them for over-lake rainfall. IMERG-F was clearly an outlier, exceeding the estimate from TRMM 3B43 by 36%. The overestimation by IMERG-F was likely related to passive microwave assessments of strong convection, such as prevails over Lake Victoria. Overall, TRMM 3B43 showed the best agreement with the "ground truth" and was used in further analyses. Over-lake rainfall was found to be enhanced compared to catchment rainfall in all months. During the March-to-May long rains the enhancement varied between 40% and 50%. During the October-to-December short rains the enhancement varied between 33% and 44%. Even during the two dry seasons the enhancement was at least 20% and over 50% in some months. While the magnitude of enhancement varied from month to month, the seasonal cycle was essentially the same for over-lake and catchment rainfall, suggesting that the dominant influence on over-lake rainfall is the large-scale environment. The association with Mesoscale Convective Systems (MCSs) was also evaluated. The similarity of the spatial patterns of rainfall and MCS count each month suggested that these produced a major share of rainfall over the lake. Similarity in interannual variability further supported this conclusion.
Utilizing Incident-Based Crime Data to Inform Strategic Interventions
Authors: Rydberg Jason , Stone Rebecca , McGarrell Edmund F.
Published: April 2021

A public health approach to violence prevention involves the empirical identification of groups and communities at the highest risk for violence to inform targeted interventions. We demonstrate the utility of complete incident-level crime data toward this end. Data for 32,056 unique incidents involving homicide, aggravated assault, and robbery were extracted from the 2013 Michigan Incident Crime Reporting system, a statewide National Incident-Based Reporting System (NIBRS) data system. Differential victimization rates were calculated across demographic subgroups and jurisdictions to identify patterns in risk. Two-stage least squares regression models were estimated to examine correlates of variation in excess risk. Analyses identified young Black males and females at relatively high risk for violent victimization, and that this risk was amplified within cities with disproportionately high crime rates. Multivariate models suggested concentrated disadvantage as the most stable correlate of variation in excess risk across Michigan cities and towns. The results highlight the importance of expanding NIBRS adoption and the deployment of focused interventions involving both short-term enforcement and long-term social reinvestment.
Large-Capacity Magazines and the Casualty Counts in Mass Shootings
Authors: Kleck Gary
Published: April 2021

Do bans on large-capacity magazines (LCMs) for semiautomatic firearms have significant potential for reducing the number of deaths and injuries in mass shootings? The most common rationale for an effect of LCM use is that they allow mass killers to fire many rounds without reloading. LCMs are known to have been used in less than one third of 1% of mass shootings. News accounts of 23 shootings in which more than six people were killed or wounded and LCMs were known to have been used, occurring in the United States in 1994–2013, were examined. There was only one incident in which the shooter may have been stopped by bystander intervention when he tried to reload. In all of these 23 incidents, the shooter possessed either multiple guns or multiple magazines, meaning that the shooter, even if denied LCMs, could have continued firing without significant interruption by either switching loaded guns or changing smaller loaded magazines with only a 2- to 4-seconds delay for each magazine change. Finally, the data indicate that mass shooters maintain such slow rates of fire that the time needed to reload would not increase the time between shots and thus the time available for prospective victims to escape.
Classifying Prisoner Returns
Authors: Gaes Gerald G. , Luallen Jeremy , Rhodes William , Edgerton Jared
Published: April 2021

Scholars often use administrative corrections data to identify the reasons that offenders return to prison, though such data usually obscure more complex processes underlying the cause of a return. This article describes the procedural nuances that make it difficult to record prison return paths and discusses these limitations. We focus on data elements and recording practices commonly found in administrative databases and discuss whether and how researchers may use these data to reliably identify/classify returns. We provide empirical demonstrations of these arguments using publicly available data and conclude that more extensive data are often needed to accomplish this objective.
Proceedings of the Sleep and Epilepsy Workshop: Section 3 Mortality: Sleep, Night, and SUDEP
Authors: Buchanan Gordon F. , Gluckman Bruce J. , Kalume Franck K. , Lhatoo Samden , Maganti Rama K. , Noebels Jeffrey L. , Simeone Kristina A. , Quigg Mark S. , Pavlova Milena K.
Published: April 2021

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy. Likely pathophysiological mechanisms include seizure-induced cardiac and respiratory dysregulation. A frequently identified feature in SUDEP cases is that they occur at night. This raises the question of a role for sleep state in regulating of SUDEP. An association with sleep has been identified in a number of studies with patients and in animal models. The focus of this section of the Sleep and Epilepsy Workshop was on identifying and understanding the role for sleep and time of day in the pathophysiology of SUDEP.
Conspiracy-Beliefs and Receptivity to Disconfirmatory Information: A Study Using the BADE Task
Authors: Georgiou Neophytos , Delfabbro Paul , Balzan Ryan
Published: April 2021

Conspiracy theory (CT) beliefs are thought to be related to a number of individual differences that make certain individuals more prone to this style of reasoning. In this study, we investigate (a) the relationship between CT beliefs and a standardized measure of judgment (the Bias Against Disconfirmatory Evidence task or BADE) and (b) the extent to which BADE scores are related to specific measures of psychopathology, including schizotypy and delusion-proneness, as measured by the Peters et al.’s Delusions Inventory. The BADE is an evidence integration bias and captures the extent to which individuals display a reduced willingness to integrate disconfirmatory evidence. A total of 358 individuals recruited from an online panel completed standardized measures of CT beliefs, measures of psychopathology, and a standardized BADE task. The results showed that CT-prone individuals showed a stronger BADE effect (i.e., biases against confirmatory and disconfirmatory evidence and a stronger liberal acceptance of absurd statements) and overall poorer evidence integration. Our results suggest that a reduced tendency to revise beliefs in the face of disconfirmatory evidence may contribute to the maintenance of CT beliefs, despite the availability of extensive counter-evidence.
An Exploration of School Organization Metaphors and Their Contribution to School Change
Authors: Whang Nai-Ying
Published: April 2021

This study explores the development of organizational theory through understanding comprehensive resources of metaphors and the synergy of these metaphors’ changes in momentum. The comprehensive resources of organizational metaphors emphasize that exploration and detection of the complementary relationship between multiple metaphors can promote the development of organizational theory and the acquisition of generic competence requirements to stimulate the synergistic momentum for school reform and to respond to student needs. In this study, questionnaires were used to analyze the opinions of 409 school members across 28 middle schools. The questionnaire explored 17 metaphors and their qualitative meanings. Subsequently, according to the meanings of the metaphor momentum, 41 principals, administrative staff, teachers, and parents were interviewed. The results demonstrate that with bureaucracy as the core of the thought, machine metaphor, community metaphor, politics metaphor, organism metaphor, and brain metaphor interact to promote the development of school organization theory to stimulate school change.
Examining the Antecedents of User Donation Intentions Toward Social Media Articles: Moderation Effects of Social Contagion
Authors: Asante Isaac Owusu , Fang Jiaming , Darko Dennis Fiifi , Altab Hossin M. D.
Published: April 2021

Donations to articles on social media, as a new behavior, have been trending in recent years. Unlike donations to a charitable and nonprofit organization or victims, donations to social media articles have been accorded minimal attention from academic researchers. From the stimuli–organism–response framework, this study proposed a model to investigate the factors that influence the donation intentions of users on social media toward articles. Our results demonstrate that the credibility of the article determines users’ donation intentions. The results also indicate that the perceived value (usefulness and enjoyment) of the article mediates the effects of article credibility on users’ donation intentions. The social contagion nature of the article is also proven to moderate the magnitude of impacts on donation intention by users’ perceived usefulness, perceived enjoyment, and perception of article credibility.
Can “Live Streaming” Really Drive Visitors to the Destination? From the Aspect of “Social Presence”
Authors: Zhang Wenkun , Wang Yanan , Zhang Tao
Published: April 2021

The combination of live-streaming technology and tourism is an important development in the evolution of tourism experiences. Research on live-streaming tourism is becoming popular, but empirical studies on the relationship between live streaming and travel intention remain underexplored. The aim of this article is to determine whether live streaming has an impact on travel intention. This article collects 614 questionnaires and uses structural equation models (SEMs) to test the relevant hypotheses. This study makes some contributions to the literature on live-streaming tourism. First, it explains the relationship between live streaming and travel intention from the perspective of social presence: The presence of a destination image, the presence of an interaction, and the presence of production can effectively improve people’s trust and, in return, influence their travel intention. Second, this article verifies the role of trust in tourism management. This article is one of the earliest studies on the relationship between live streaming and travel intention, which has significance for the development of tourism management–related theories and practical management.
Licorice: A Potential Herb in Overcoming SARS-CoV-2 Infections
Authors: Ng Swee Li , Khaw Kooi-Yeong , Ong Yong Sze , Goh Hui Poh , Kifli Nurolaini , Teh Siew Phooi , Ming Long Chiau , Kotra Vijay , Goh Bey Hing
Published: April 2021

The management of the global pandemic outbreak due to the coronavirus disease (COVID-19) has been challenging with no exact dedicated treatment nor established vaccines at the beginning of the pandemic. Nonetheless, the situation seems to be better controlled with the recent COVID-19 vaccines roll-out globally as active immunisation to prevent COVID-19. The extensive usage and trials done in recent outbreak in China has shown the effectiveness of traditional Chinese Medicines (TCM) in improving the wellbeing of COVID-19 patients. Therefore, COVID-19 Prevention and Treatment guidelines has listed a number of recommended concoctions meant for COVID-19 patients. Licorice, more commonly known as Gancao in Chinese Pinyin, is known as one of the most frequently used ingredients in TCM prescriptions for treatment of epidemic diseases. Interestingly, it is deemed as food ingredient as well, where it is normally used in Western cuisines’ desserts and sweets. The surprising fact that licorice appeared in the top 10 main ingredients used in TCM prescriptions in COVID-19 has drawn great attention from researchers in revealing its biological potential in overcoming this disease. To date, there are no comprehensive review on licorice and its benefits when used in COVID-19. Thus, in this current review, the possible benefits, mechanism of actions, safety and limitations of licorice were explored in hope to provide a quick reference guide for its preclinical and clinical experimental set-up in this very critical moment of pandemic.
Tetherin/BST2, a physiologically and therapeutically relevant regulator of platelet receptor signalling
Authors: Zhao Xiaojuan , Alibhai Dominic , Sun Ting , Khalil Jawad , Hutchinson James L. , Olzak Kaya , Williams Christopher M. , Li Yong , Sessions Richard , Cross Stephen , Seager Richard , Aungraheeta Riyaad , Leard Alan , McKinnon Caroline M. , Phillips David , Zhang Lei , Poole Alastair W. , Banting George , Mundell Stuart J.
Published: April 2021

The reactivity of platelets, which play a key role in the pathogenesis of atherothrombosis, is tightly regulated. The integral membrane protein tetherin/bone marrow stromal antigen-2 (BST-2) regulates membrane organization, altering both lipid and protein distribution within the plasma membrane. Because membrane microdomains have an established role in platelet receptor biology, we sought to characterize the physiological relevance of tetherin/BST-2 in those cells. To characterize the potential importance of tetherin/BST-2 to platelet function, we used tetherin/BST-2−/− murine platelets. In the mice, we found enhanced function and signaling downstream of a subset of membrane microdomain–expressing receptors, including the P2Y12, TP thromboxane, thrombin, and GPVI receptors. Preliminary studies in humans have revealed that treatment with interferon-α (IFN-α), which upregulates platelet tetherin/BST-2 expression, also reduces adenosine diphosphate–stimulated platelet receptor function and reactivity. A more comprehensive understanding of how tetherin/BST-2 negatively regulates receptor function was provided in cell line experiments, where we focused on the therapeutically relevant P2Y12 receptor (P2Y12R). Tetherin/BST-2 expression reduced both P2Y12R activation and trafficking, which was accompanied by reduced receptor lateral mobility specifically within membrane microdomains. In fluorescence lifetime imaging-Förster resonance energy transfer (FLIM-FRET)–based experiments, agonist stimulation reduced basal association between P2Y12R and tetherin/BST-2. Notably, the glycosylphosphatidylinositol (GPI) anchor of tetherin/BST-2 was required for both receptor interaction and observed functional effects. In summary, we established, for the first time, a fundamental role of the ubiquitously expressed protein tetherin/BST-2 in negatively regulating membrane microdomain–expressed platelet receptor function.
Selective drug combination vulnerabilities in STAT3- and TP53-mutant malignant NK cells
Authors: Parri Elina , Kuusanmäki Heikki , Bulanova Daria , Mustjoki Satu , Wennerberg Krister
Published: April 2021

Mature natural killer (NK) cell neoplasms are rare but very aggressive types of cancers. With currently available treatments, they have a very poor prognosis and, as such, are an example of group of cancers in which the development of effective precision therapies is needed. Using both short- and long-term drug sensitivity testing, we explored novel ways to target NK-cell neoplasms by combining the clinically approved JAK inhibitor ruxolitinib with other targeted agents. We profiled 7 malignant NK-cell lines in drug sensitivity screens and identified that these exhibit differential drug sensitivities based on their genetic background. In short-term assays, various classes of drugs combined with ruxolitinib seemed highly potent. Strikingly, resistance to most of these combinations emerged rapidly when explored in long-term assays. However, 4 combinations were identified that selectively eradicated the cancer cells and did not allow for development of resistance: ruxolitinib combined with the mouse double-minute 2 homolog (MDM2) inhibitor idasanutlin in STAT3-mutant, TP53 wild-type cell lines; ruxolitinib combined with the farnesyltransferase inhibitor tipifarnib in TP53-mutant cell lines; and ruxolitinib combined with either the glucocorticoid dexamethasone or the myeloid cell leukemia-1 (MCL-1) inhibitor S63845 but both without a clear link to underlying genetic features. In conclusion, using a new drug sensitivity screening approach, we identified drug combinations that selectively target mature NK-cell neoplasms and do not allow for development of resistance, some of which can be applied in a genetically stratified manner.
Continuous positive airway pressure improves blood pressure and serum cardiovascular biomarkers in obstructive sleep apnoea and hypertension
Authors: Lui Macy Mei-Sze , Tse Hung-Fat , Lam David Chi-Leung , Lau Kui-Kai , Chan Carmen Wing-Sze , Ip Mary Sau-Man
Published: April 2021

Background

The impact of treatment for obstructive sleep apnoea (OSA) on reduction of cardiovascular risk is unclear. This study aimed to examine the effect of continuous positive airway pressure (CPAP) on ambulatory blood pressure (BP) and subclinical myocardial injury in subjects with OSA and hypertension.

Methods

This was a parallel-group randomised controlled trial. Subjects with hypertension requiring at least three antihypertensive medications and moderate-to-severe OSA were enrolled. Eligible subjects were randomised (1:1) to receive either CPAP treatment or control (no CPAP) for 8 weeks. Changes in ambulatory BP and serum biomarkers were compared. Stratified analysis according to circadian BP pattern was performed.

Results

92 subjects (75% male; mean±sdage 51±8 years and apnoea–hypopnoea index 40±8 events·h−1, taking an average of 3.4 (range 3–6) antihypertensive drugs) were randomised. The group on CPAP treatment, compared with the control group, demonstrated a significant reduction in 24-h systolic BP (−4.4 (95% CI −8.7– −0.1) mmHg; p=0.046), 24-h diastolic BP (−2.9 (95% CI −5.5– −0.2) mmHg; p=0.032), daytime systolic BP (−5.4 (95% CI −9.7– −1.0) mmHg; p=0.016) and daytime diastolic BP (−3.4 (95% CI −6.1– −0.8) mmHg; p=0.012). CPAP treatment was associated with significant BP lowering only in nondippers, but not in dippers. Serum troponin I (mean difference −1.74 (95% CI −2.97– −0.50) pg·mL−1; p=0.006) and brain natriuretic peptide (−9.1 (95% CI −17.6– −0.6) pg·mL−1; p=0.036) were significantly reduced in CPAP compared with the control group.

Conclusions

In a cohort with OSA and multiple cardiovascular risk factors including difficult-to-control hypertension, short-term CPAP treatment improved ambulatory BP, and alleviated subclinical myocardial injury and strain.
Prevalence, incidence and characteristics of chronic cough among adults from the Canadian Longitudinal Study on Aging
Authors: Satia Imran , Mayhew Alexandra J. , Sohel Nazmul , Kurmi Om , Killian Kieran J. , O'Byrne Paul M. , Raina Parminder
Published: April 2021

The global prevalence of chronic cough is highly variable, ranging from 2% to 18%. There is a lack of data on the prevalence and incidence of chronic cough in the general population.The objective of this study was to investigate the prevalence and incidence of chronic cough in a sample of Canadian adults, and how these are influenced by age, sex, smoking, respiratory symptoms, medical comorbidities and lung function.

Participants with chronic cough were identified from the Canadian Longitudinal Study on Aging (CLSA) based on self-reported daily cough in the past 12 months. This is a prospective, nationally generalisable, stratified random sample of adults aged 45–85 years at baseline recruited between 2011 and 2015, and followed-up 3 years later. The prevalence and incidence per 100 person-years are described, with adjustments for age, sex and smoking.

Of the 30 097 participants, 29 972 completed the chronic cough question at baseline and 26 701 did so at follow-up. The prevalence of chronic cough was 15.8% at baseline and 17.6% at follow-up with 10.4–17.1% variation across seven provinces included in the CLSA comprehensive sample. Prevalence increased with age and current smoking, and was higher in males (15.2%), Caucasians (14%) and those born in North America, Europe or Oceania (14%). The incidence of chronic cough adjusted for age, sex and smoking was higher in males and in underweight and obese subjects. Subjects with respiratory symptoms, airway diseases, lower forced expiratory volume in 1 s (% predicted), cardiovascular diseases, psychological disorders, diabetes and chronic pain had a higher incidence of chronic cough.

The prevalence and incidence of chronic cough is high in the CLSA sample with geographic, ethnic and gender differences, influenced by a number of medical comorbidities.
The lower respiratory airway wall in children in health and disease
Authors: Fayon Michael , Beaufils Fabien
Published: April 2021

Alone or in association with other lung or thorax component disorders, the airway wall (AWW) remains one of the most frequently involved elements in paediatric lung diseases. A myriad of AWW disorders will present with similar symptomatology. It is thus important for the clinician to reappraise the normal development and structure of the AWW to better understand the underlying disease patterns. We herein provide an overview of the structure of the AWW and a description of its development from the fetal period to adulthood. We also detail the most common AWW changes observed in several acute and chronic respiratory disorders as well as after cigarette smoke or chronic pollution exposure. We then describe the relationship between the AWW structure and lung function. In addition, we present the different ways of investigating the AWW structure, from biopsies and histological analyses to the most recent noninvasive airway (AW) imaging techniques. Understanding the pathophysiological processes involved in an individual patient will lead to the judicious choice of nonspecific or specific personalised treatments, in order to prevent irreversible AW damage.
Lung volume reduction in emphysema: a pragmatic prospective cohort study
Authors: Dooms Christophe , Blondeel Astrid , Ceulemans Laurens J. , Coolen Johan , Everaerts Stephanie , Demeyer Heleen , Troosters Thierry , Verleden Geert , Van Raemdonck Dirk , Janssens Wim
Published: April 2021

Limited guidance exists for the implementation of lung volume reduction interventions in routine clinical care. We designed a pragmatic study to evaluate a strategy including endoscopic lung volume reduction (ELVR) and lung volume reduction surgery (LVRS) in heterogeneous emphysema.

This prospective monocentre cohort study evaluated ELVRversusno-ELVR, followed by a cohort study evaluating LVRS. Primary outcome was the proportion of subjects with a forced expiratory volume in 1 s (FEV1) improvement of ⩾100 mL at 3-month follow-up. Changes in FEV1, residual volume (RV), 6-min walk distance (6MWD) and quality of life (St George's Respiratory Questionnaire (SGRQ)) were evaluated at 6-month follow-up. Hospital stay and treatment-related serious adverse events were monitored.

From 106 subjects screened, 38 subjects were enrolled comparing ELVR (n=20) with no-ELVR (n=18). After 6 months’ follow-up, eligible patients were referred for LVRS (n=16) with another 6-month follow-up. At 3-month follow-up, 70% of ELVR compared to 11% of no-ELVR (p<0.001) and 69% of LVRS had an FEV1improvement of ⩾100 mL. Between-group differences (mean±sem) for ELVRversusno-ELVR at 6-month follow-up were FEV1+0.21±0.05 L; RV −0.95±0.21 L; 6MWD 58±17 m and SGRQ −18±5 points. At 6-month follow-up, within-group differences (mean±sem) for LVRS showed FEV1+0.27±0.06 L; RV −1.49±0.22 L and 6MWD +75±18 m. Serious adverse events in 81%versus45% of subjects (p=0.04) and a median hospital stay of 15versus5 days (p<0.001) were observed for LVRSversusELVR, respectively.

This pragmatic prospective cohort study supports a clinical approach with ELVR as a less invasive first option and LVRS as powerful alternative in severe heterogeneous emphysema.
Circulating Tfh cell and subsets distribution are associated with low‐responsiveness to hepatitis B vaccination
Authors: Yin Mingjuan , Xiong Yongzhen , Liang Dongmei , Tang Hao , Hong Qian , Liu Gang , Zeng Jinmei , Lian Tingyu , Huang Jingxiao , Ni Jindong
Published: April 2021

Background

An estimated 5–10 % of healthy vaccinees lack adequate antibody response following receipt of a standard three-dose hepatitis B vaccination regimen. The cellular mechanisms responsible for poor immunological responses to hepatitis B vaccine have not been fully elucidated to date.

Methods

There were 61 low responders and 56 hyper responders involved in our study. Peripheral blood samples were mainly collected at D7, D14 and D28 after revaccinated with a further dose of 20 µg of recombinant hepatitis B vaccine.

Results

We found low responders to the hepatitis B vaccine presented lower frequencies of circulating follicular helper T (cTfh) cells, plasmablasts and a profound skewing away from cTfh2 and cTfh17 cells both toward cTfh1 cells. Importantly, the skewing of Tfh cell subsets correlated with IL-21 and protective antibody titers. Based on the key role of microRNAs involved in Tfh cell differentiation, we revealed miR-19b-1 and miR-92a-1 correlated with the cTfh cell subsets distribution and antibody production.

Conclusions

Our findings highlighted a decrease in cTfh cells and specific subset skewing contribute to reduced antibody responses in low responders.
The emerging role of exosomal miRNAs as a diagnostic and therapeutic biomarker in Mycobacterium tuberculosis infection
Authors: Mirzaei Rasoul , Babakhani Sajad , Ajorloo Parisa , Ahmadi Razieh Heidari , Hosseini-Fard Seyed Reza , Keyvani Hossein , Ahmadyousefi Yaghoub , Teimoori Ali , Zamani Farhad , Karampoor Sajad , Yousefimashouf Rasoul
Published: April 2021

Tuberculosis (TB), caused byMycobacterium tuberculosis(Mtb), has been the world’s driving fatal bacterial contagious disease globally. It continues a public health emergency, and around one-third of the global community has been affected by latent TB infection (LTBI). This is mostly due to the difficulty in diagnosing and treating patients with TB and LTBI. Exosomes are nanovesicles (40–100 nm) released from different cell types, containing proteins, lipids, mRNA, and miRNA, and they allow the transfer of one’s cargo to other cells. The functional and diagnostic potential of exosomal miRNAs has been demonstrated in bacterial infections, including TB. Besides, it has been recognized that cells infected by intracellular pathogens such as Mtb can be secreting an exosome, which is implicated in the infection’s fate. Exosomes, therefore, open a unique viewpoint on the investigative process of TB pathogenicity. This study explores the possible function of exosomal miRNAs as a diagnostic biomarker. Moreover, we include the latest data on the pathogenic and therapeutic role of exosomal miRNAs in TB.
Effects of microwave irradiation on the moisture content of various wood chip fractions obtained from different tree species
Authors: Aniszewska Monika , Słowiński Krzysztof , Tulska Ewa , Zychowicz Witold
Published: April 2021

The paper proposes the use of microwave irradiation to lower the initial moisture content of wood chips. The study involved willow and fir chips fractionated by means of a sieve separator and unfractionated ash chips. The wood chips were exposed to a constant microwave power of 800 W for 30 s, 60 s, 120 s and 180 s. The chips were weighed before and after irradiation to measure loss of moisture. It was found that the decline in moisture content increased with wood chip size for a given irradiation time and microwave power. The initial moisture content of wood chips was not found to significantly affect loss of moisture as the drying rates of wood chips with higher and lower moisture content exposed to microwaves were not statistically different. The results showed that irradiation intensity increased with the time of exposure to microwaves and unit radiant energy per unit of evaporated moisture decreased with increasing wood chip size in the 3.15–31.50 mm range.
Harvestman: a framework for hierarchical feature learning and selection from whole genome sequencing data
Authors: Frisby Trevor S. , Baker Shawn J. , Marçais Guillaume , Hoang Quang Minh , Kingsford Carl , Langmead Christopher J.
Published: April 2021

Background

Supervised learning from high-throughput sequencing data presents many challenges. For one, the curse of dimensionality often leads to overfitting as well as issues with scalability. This can bring about inaccurate models or those that require extensive compute time and resources. Additionally, variant calls may not be the optimal encoding for a given learning task, which also contributes to poor predictive capabilities. To address these issues, we presentHarvestman, a method that takes advantage of hierarchical relationships among the possible biological interpretations and representations of genomic variants to perform automatic feature learning, feature selection, and model building.

Results

We demonstrate thatHarvestmanscales to thousands of genomes comprising more than 84 million variants by processing phase 3 data from the 1000 Genomes Project, one of the largest publicly available collection of whole genome sequences. Using breast cancer data from The Cancer Genome Atlas, we show thatHarvestmanselects a rich combination of representations that are adapted to the learning task, and performs better than a binary representation of SNPs alone. We compareHarvestmanto existing feature selection methods and demonstrate that our method is moreparsimonious—it selects smaller and less redundant feature subsets while maintaining accuracy of the resulting classifier.

Conclusion

Harvestmanis a hierarchical feature selection approach for supervised model building from variant call data. By building a knowledge graph over genomic variants and solving an integer linear program ,Harvestmanautomatically and optimally finds the right encoding for genomic variants. Compared to other hierarchical feature selection methods,Harvestmanis faster and selects features more parsimoniously.
A tail of two pandas— whole genome k-mer signature analysis of the red panda (Ailurus fulgens) and the Giant panda (Ailuropoda melanoleuca)
Authors: Cserhati Matyas
Published: April 2021

Background

The red panda (Ailurus fulgens) is a riddle of morphology, making it hard to tell whether it is an ursid, a procyonid, a mustelid, or a member of its own family. Previous genetic studies have given quite contradictory results as to its phylogenetic placement.

Results

A recently developed whole genome-based algorithm, the Whole Genome K-mer Signature algorithm was used to analyze the genomes of 28 species of Carnivora, including A. fulgens and several felid, ursid, mustelid, one mephitid species. This algorithm has the advantage of holistically using all the information in the genomes of these species. Being a genomics-based algorithm, it also reduces stochastic error to a minimum. Besides the whole genome, the mitochondrial DNA from 52 mustelids, mephitids, ursids, procyonids and A. fulgens were aligned to draw further phylogenetic inferences.

The results from the whole genome study suggested that A. fulgens is a member of the mustelid clade (p = 9·10− 97). A. fulgens also separates from the mephitid Spilogala gracilis. The giant panda, Ailuropoda melanoleuca also clusters away from A. fulgens, together with other ursids (p = 1.2·10− 62). This could be due to the geographic isolation of A. fulgens from other mustelid species. However, results from the mitochondrial study as well as neighbor-joining methods based on the sequence identity matrix suggests that A. fulgens forms a monophyletic group. A Maximum Likelihood tree suggests that A. fulgens and Ursidae form a monophyletic group, although the bootstrap value is weak.

Conclusions

The main conclusion that we can draw from this study is that on a whole genome level A. fulgens possibly belongs to the mustelid clade, and not an ursid or a mephitid. This despite the fact that previously some researchers classified A. fulgens and A. melanoleuca as relatives. Since the genotype determines the phenotype, molecular-based classification takes precedence over morphological classifications. This affirms the results of some previous studies, which studied smaller portions of the genome. However, mitochondrial analyses based on neighbor-joining and maximum likelihood methods suggest otherwise.