bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-Polarization in Storage Rings
Authors: Gianfelice-Wendt Eliana
Published: April 2023

This is an advance summary of a forthcoming article in the Oxford Research Encyclopedia of Physics. Please check back later for the full article.

The conditions for the Sokolov-Ternov effect to occur are approximately satisfied by electrons (or positrons) circulating on the design orbit of a planar storage ring. Indeed, self-polarization was first observed in the electron/positron colliders Anneau de Collisions d’Orsay (ACO) and VEPP-2. Beam polarization offers an additional tool for understanding the physics events. The possibility of having polarized electron/positron beams for free is therefore appealing. However, the Sokolov-Ternov polarization time constant, proportional to 1/γ5 and to the third power of the bending radius, restricts the region of interest for self-polarization. For the about 100 km Future Circular Collider (FCC) under study at CERN, the polarization constant is about 10 days at 45 GeV beam energy. At high energy the randomization of the particle trajectory due to photon emission in a storage ring with finite alignment precision of the magnets introduces spin diffusion and limits the attainable polarization.

In addition, in a collider the force exerted by the counter-rotating particles impact the beam polarization. This force increases with beam intensity and experiments are reluctant to pass up luminosity for polarization. To this day the electron(positron)/proton collider HERA has been the only high energy collider where electron (and positron) self-polarization was an integral part of the physics program.
The Violence at Jonestown
Authors: Moore Rebecca
Published: April 2023

The eruption of violence carried out by members of Peoples Temple, in which more than nine hundred men, women, and children died by ingesting cyanide-laced fruit punch in 1978, seemed incomprehensible. Scholars, journalists, pundits, and government officials presented a variety of explanations to account for the mass murder–suicides of US citizens that occurred in Jonestown, Guyana. The range of analyses in the weeks, months, and years that followed sought to understand why group members assassinated a US congressman and fatally shot four other people, why parents murdered their children, and why they then took their own lives.

Shocked by news reports and goaded by professional cult-watchers, popular opinion focused on so-called brainwashed followers who did as they were told under the authority of a charismatic—some said deranged—leader. Psychiatrists and psychologists tended to blame maladjusted individuals seeking refuge from autonomy and independence. Scholars who specialize in new religions studies noted historical precedents, religious beliefs (especially apocalyptic theology), and the influence of cultural opponents—relatives, the news media, and government actors—placing pressure on the group. Political analysts found religion in general, cult leaders, and vulnerable followers responsible. Contesting official and consensus understanding, conspiracy theorists viewed the deaths as mass murder rather than mass suicide. Some former members of Peoples Temple adopted this perspective, although many came to believe that residents had been conditioned by coercive practices to follow the leader.

In the late 20th and early 21st centuries, documents and audiotapes generated in Jonestown have illuminated the community’s internal practices and rhetoric and have served to complicate traditional views. This evidence has made it clear that Jonestown leaders conspired to develop a mass suicide plan to be enacted when the community faced imminent destruction. Although the logistics were carefully crafted, the various justifications for this irrevocable step remain obscure and ambiguous.
Cattle in Latin American History
Authors: Sluyter Andrew
Published: April 2023

People on other continents had been raising domesticated cattle for millennia, mainly breeds of humped zebu (Bos indicus) in the tropics and of humpless taurine (Bos taurus) in temperate latitudes by the time the first cattle reached the Americas in 1493. From an initial beachhead on the Caribbean island of Hispaniola, by the close of the 16th century, cattle had reached ranching frontiers throughout the region, from New Spain to the Pampas of the Río de la Plata. While regional varieties of cattle—such as the Corriente of Mexico, the Longhorn of the borderlands, and the Criollo of the Pampas—developed on each of the frontiers, they shared many characteristics: an emphasis on raising large herds of feral cattle on an open range to the virtual exclusion of crops in order to produce hides, tallow, and beef. Over the colonial period, herders pushed into new frontiers, and their social, cultural, and environmental characteristics became differentiated through the hybridization of antecedent African, European, and Indigenous practices. In addition to ranching, cattle became central to many other aspects of colonial societies, incorporated into farming to provide meat and dairy products as well as used as draft animals to pull carts and plows and power sugar and grain mills. Cattle had a major impact on Indigenous peoples, who not only adopted them into their agricultural systems but also suffered crop damage from free-ranging herds. In terms of environmental impacts, cattle herding had a broad impact on the vegetation of grasslands through grazing, rangeland burning, and the introduction of African grasses. Throughout much of Latin America, the end of the colonial period in the 19th century resulted in not only an expansion of cattle ranching but also the closing of the open range. The opening of export markets, urbanization, growing domestic markets, technological changes such as wire fences and refrigerated shipping, genocidal wars against Indigenous peoples to open new ranching frontiers, and the abolition of slavery all irrevocably altered the patterns and processes established during colonial times. Enclosing pastures with wire fences, for example, permitted ranchers to control breeding and thereby maintain European breeds such as Aberdeen Angus and Hereford that largely replaced Longhorns and other colonial breeds. In the 20th century, ranchers with herds of zebu breeds, such as Indubrasil, began to expand into new frontiers in tropical forests, particularly the Amazon, with immense impacts on Indigenous peoples and the environment.
Design and Rationale of the Home Blood Pressure Telemonitoring Linked with Community Health Workers to Improve Blood Pressure (LINKED-BP) Program
Authors: Commodore-Mensah Yvonne , Liu Xiaoyue , Ogungbe Oluwabunmi , Ibe Chidinma , Amihere Johnitta , Mensa Margaret , Martin Seth S , Crews Deidra , Carson Kathryn A , Cooper Lisa A , Himmelfarb Cheryl R
Published: April 2023

BACKGROUND

Disparities in hypertension outcomes persist among Black and Hispanic adults and persons living in poverty in the United States. The “LINKED-BP Program” is a multi-level intervention linking home blood pressure (BP) monitoring with a mobile health application, support from community health workers (CHWs), and BP measurement training at primary care practices to improve BP. This study is part of the American Heart Association RESTORE (AddREssing Social Determinants TO pRevent hypErtension) Network. This study aims to examine the effect of the LINKED-BP Program on BP reduction and to evaluate the reach, adoption, sustainability, and cost-effectiveness of the intervention.

METHODS

Using a hybrid type I effectiveness-implementation design, 600 adults who have elevated BP or untreated stage 1 hypertension without diabetes, chronic kidney disease, history of cardiovascular disease (stroke or coronary heart disease) and age < 65 years will be recruited from 20 primary care practices including community health centers in the Maryland area. The practices are randomly assigned to the intervention or the enhanced usual care arms. Patients in the LINKED-BP Program receive training on home BP monitoring, BP telemonitoring through the Sphygmo app, and CHW telehealth visits for education and counseling on lifestyle modification over 12 months. The primary clinical outcome is change from baseline in systolic BP at 6 and 12 months.

DISCUSSIONS

The LINKED-BP Program tests a sustainable, scalable approach to prevent hypertension and advance health equity. The findings will inform implementation strategies that address social determinants of health and barriers to hypertension prevention in underserved populations.

ClinicalTrials.gov IDENTIFIER

NCT05180045.
How molting locusts avoid cannibalism
Authors: Maeno Koutaro Ould , Piou Cyril , Whitman Douglas W , Ould Ely Sidi , Ould Mohamed Sid’Ahmed , Jaavar Mohamed El Hacen , Ould Babah Ebbe Mohamed Abdallahi
Published: April 2023

Group living has various benefits, but it also carries costs, such as risk of cannibalism. Molting is a vulnerable period of being cannibalized in juvenile arthropods, but how gregarious arthropods avoid this threat is poorly understood. Here, we examined how actively migrating gregarious nymphs of desert locust, Schistocerca gregaria, avoid cannibalism during molting, in the Sahara Desert of Mauritania. In the field, gregarious nymphs cyclically march and feed on grass during the day. Our field observations found that marching behavior helped separating pre-molting and cannibalistic non-molting nymphs. Cannibalistic non-molting nymphs marched away from roost plants, leaving sedentary pre-molting nymphs behind, creating cannibal-free spaces. Some non-molting nymphs reached a pre-molting state after daytime marching, thus both pre- and non-molting nymphs roosted on same plants at night. However, pre-molting nymphs moved away from conspecifics prior to molting. Starvation experiments confirmed that food-satiation decreased cannibalistic necrophagy. Physiological surveys of diel feeding and molting patterns revealed that nymphs molted at times when conspecifics were food-satiated rather than hungry. Hence, our results indicate that behavioral and physiological traits of gregarious locusts could function to spatiotemporally separate molting locusts from cannibalistic conspecifics, thus reducing molting-associated cannibalism. This is the first report of migration-dependent molting synchrony as a mechanism reducing costs of aggregation in gregarious arthropods.
Mito-nuclear discordance in the phenotypically variable Andean hummingbirdsCoeligena bonaparteiandCoeligena helianthea(Trochilidae)
Authors: Palacios Catalina , Campagna Leonardo , Parra Juan Luis , Cadena Carlos Daniel
Published: April 2023

The interplay among evolutionary mechanisms like gene flow and selection may result in discordant signals between mitochondrial DNA, nuclear markers and phenotypes. The Andean hummingbirds Coeligena bonapartei and Coeligena helianthea showed differentiation in the gene ND2 which is discordant with plumage coloration but consistent with geography. We analysed complete mitochondrial genomes of individuals from Coeligena bonapartei bonapartei, Coeligena bonapartei consita, Coeligena helianthea helianthea, and Coeligena helianthea tamai to inform their evolutionary history. We found genetic structure despite low genetic differentiation among these populations. Phylogenetic and network analyses based on mitogenomes showed a northern vs. southern differentiation pattern which is discordant with the relationships based on nuclear markers and the coloration phenotypes (serving as a basis for taxonomy). Mitogenomes of the two nominate subspecies are indistinguishable, suggesting incomplete lineage sorting or introgression, while those of C. b. consita and C. h. tamai are more similar to each other than they are to their respective nominate subspecies. Our results indicate that various evolutionary mechanisms drove the divergence in phenotypes, and nuclear and mitochondrial genomes of Coeligena hummingbirds, playing out over a complex biogeographic scenario likely involving periods of isolation and secondary contact. We outline hypotheses to be tested with future analyses of genome-wide variation.
Buruli ulcer: application of thermography for remote diagnosis of a neglected tropical disease
Authors: Yotsu Rie R , Vagamon Bamba , Almamy Diabate  , Aka N’guessan , Yeboue Luc Kowaci Gontran , Yao Aubin , Blanton Ronald E
Published: April 2023

We here report a proof of concept of using thermography for teledermatology practice for skin of colour using an example of an early case of Buruli ulcer – a neglected tropical disease that mainly affects people living in remote communities of Africa. In the presented case, the full extent of the lesion and lymphangitis were further and more precisely detected by thermography than even with the naked eye. Redness, an important sign of inflammation, can be masked in individuals with skin of colour. If thermal images can be transmitted to remote dermatologists in addition to regular photographs in the practice of teledermatology, this may improve diagnostic and prognostic accuracy, especially for this neglected population.
Diagnostic implications of MOG-IgG detection in sera and cerebrospinal fluids
Authors: Matsumoto Yuki , Kaneko Kimihiko , Takahashi Toshiyuki , Takai Yoshiki , Namatame Chihiro , Kuroda Hiroshi , Misu Tatsuro , Fujihara Kazuo , Aoki Masashi
Published: April 2023

The spectrum of MOG-IgG-associated disease (MOGAD) includes optic neuritis (ON), myelitis (MY), acute disseminated encephalomyelitis (ADEM), brainstem encephalitis, cerebral cortical encephalitis (CE) and AQP4-IgG-negative neuromyelitis optica spectrum disorder (NMOSD). In MOGAD, MOG-IgG are usually detected in sera (MOG-IgGSERUM), but there have been some seronegative MOGAD cases with MOG-IgG in CSF (MOG-IgGCSF), and its diagnostic implications remains unclear.

In this cross-sectional study, we identified patients with paired serum and CSF sent from all over Japan for testing MOG-IgG. Two investigators blinded to MOG-IgG status classified them into suspected MOGAD (ADEM, CE, NMOSD, ON, MY and Others) or not based on the current recommendations. The MOG-IgGSERUM and MOG-IgGCSF titres were assessed with serial 2-fold dilutions to determine end point titres [≥1:128 in serum and ≥1:1 (no dilution) in CSF were considered positive]. We analysed the relationship between MOG-IgGSERUM, MOG-IgGCSF and the phenotypes with multivariable regression.

A total of 671 patients were tested [405 with suspected MOGAD, 99 with multiple sclerosis, 48 with AQP4-IgG-positive NMOSD and 119 with other neurological diseases (OND)] before treatment. In suspected MOGAD, 133 patients (33%) tested MOG-IgG-positive in serum and/or CSF; 94 (23%) double-positive (ADEM 36, CE 15, MY 8, NMOSD 9, ON 15 and Others 11); 17 (4.2%) serum-restricted-positive (ADEM 2, CE 0, MY 3, NMOSD 3, ON 5 and Others 4); and 22 (5.4%) CSF-restricted-positive (ADEM 3, CE 4, MY 6, NMOSD 2, ON 0 and Others 7). None of AQP4-IgG-positive NMOSD, multiple sclerosis or OND cases tested positive for MOG-IgGSERUM, but two with multiple sclerosis cases were MOG-IgGCSF-positive; the specificities of MOG-IgGSERUM and MOG-IgGCSF in suspected MOGAD were 100% [95% confidence interval (CI) 99–100%] and 99% (95% CI 97–100%), respectively. Unlike AQP4-IgG-positive NMOSD, the correlation between MOG-IgGSERUM and MOG-IgGCSF titres in MOGAD was weak. Multivariable regression analyses revealed MOG-IgGSERUM was associated with ON and ADEM, whereas MOG-IgGCSF was associated with ADEM and CE. The number needed to test for MOG-IgGCSF to diagnose one additional MOGAD case was 13.3 (14.3 for ADEM, 2 for CE, 19.5 for NMOSD, infinite for ON, 18.5 for MY and 6.1 for Others).

In terms of MOG-IgGSERUM/CSF status, most cases were double-positive while including either serum-restricted (13%) or CSF-restricted (17%) cases. These statuses were independently associated with clinical phenotypes, especially in those with ON in serum and CE in CSF, suggesting pathophysiologic implications and the utility of preferential diagnostic testing. Further studies are warranted to deduce the clinical and pathological significance of compartmentalized MOG-IgG.
Glucocorticoid-driven mitochondrial damage stimulates Tau pathology
Authors: Du Fang , Yu Qing , Swerdlow Russell H , Waites Clarissa L
Published: April 2023

Prolonged exposure to glucocorticoids, the main stress hormones, damages the brain and is a risk factor for depression and Alzheimer's disease. Two major drivers of glucocorticoid-related neurotoxicity are mitochondrial dysfunction and Tau pathology; however, the molecular/cellular mechanisms precipitating these events, and their causal relationship, remain unclear.

Using cultured murine hippocampal neurons and 4–5-month-old mice treated with the synthetic glucocorticoid dexamethasone, we investigate the mechanisms underlying glucocorticoid-induced mitochondrial damage and Tau pathology.

We find that glucocorticoids stimulate opening of the mitochondrial permeability transition pore via transcriptional upregulation of its activating component, cyclophilin D. Inhibition of cyclophilin D is protective against glucocorticoid-induced mitochondrial damage as well as Tau phosphorylation and oligomerization in cultured neurons. We further identify the mitochondrially-targeted compound mito-apocynin as an inhibitor of glucocorticoid-induced permeability transition pore opening, and show that this compound protects against mitochondrial dysfunction, Tau pathology, synaptic loss, and behavioural deficits induced by glucocorticoids in vivo. Finally, we demonstrate that mito-apocynin and the glucocorticoid receptor antagonist mifepristone rescue Tau pathology in cytoplasmic hybrid cells, an ex vivo Alzheimer's disease model wherein endogenous mitochondria are replaced with mitochondria from Alzheimer's subjects.

These findings show that mitochondrial permeability transition pore opening is a precipitating factor in glucocorticoid-induced mitochondrial dysfunction, and that this event stimulates Tau pathogenesis. Our data also link glucocorticoids to mitochondrial dysfunction and Tau pathology in the context of Alzheimer's disease and suggest that mitochondria are promising therapeutic targets for mitigating stress- and Tau-related brain damage.
Recent-onset erythematous tender plaques and nodules in a child with nephrotic syndrome
Authors: Benny Benetta , Kaur Maninder , Thirunavukkarasu Balamurugan , Singh Saurabh , Patra Suman
Published: April 2023

A 10-year-old girl with nephrotic syndrome who was on systemic corticosteroids presented with multiple erythematous tender nodules over her trunk and extremities. Histopathology showed mild lobular panniculitis with needle-shaped crystals. The lesions subsided spontaneously without any sequelae within 3 weeks.
Cutaneous and ocular persistent yellowish plaques: a clinicopathological challenge
Authors: Jones Meriem , Ghannem Azza , Gara Soumaya , Boukari Mejdi , Bel Hadj Kacem Linda , Rammeh Soumaya , Zeglaoui Faten
Published: April 2023

A 65-year-old woman presented with a 2-year history of an erythematous plaque on the right cheek, the patient was also found to have hyperaemia of the nasal bulbar conjunctiva of the right eye. The usefulness of cutaneous and eye dermoscopy in diagnosis when clinical presentation is challenging is discussed.
Secretory-IgA binding to intestinal microbiota attenuates inflammatory reactions as the intestinal barrier of preterm infants matures
Authors: Mahdally Sarah M , Izquierdo Mariana , Viscardi Rose M , Magder Laurence S , Crowley Helena M , Bafford Andrea C , Drachenberg Cinthia B , Farfan Mauricio J , Fasano Alessio , Sztein Marcelo B , Salerno-Goncalves Rosangela
Published: April 2023

Previous work has shown that Secretory-IgA (SIgA) binding to the intestinal microbiota is variable and may regulate host inflammatory bowel responses. Nevertheless, the impact of the SIgA functional binding to the microbiota remains largely unknown in preterm infants whose immature epithelial barriers make them particularly susceptible to inflammation. Here, we investigated SIgA binding to intestinal microbiota isolated from stools of preterm infants <33 weeks gestation with various levels of intestinal permeability. We found that SIgA binding to intestinal microbiota attenuates inflammatory reactions in preterm infants. We also observed a significant correlation between SIgA affinity to the microbiota and the infant’s intestinal barrier maturation. Still, SIgA affinity was not associated with developing host defenses, such as the production of mucus and inflammatory calprotectin protein, but it depended on the microbiota shifts as the intestinal barrier matures. In conclusion, we reported an association between the SIgA functional binding to the microbiota and the maturity of the preterm infant’s intestinal barrier, indicating that the pattern of SIgA coating is altered as the intestinal barrier matures.
Plasmablasts in previously immunologically naïve COVID-19 patients express markers indicating mucosal homing and secrete antibodies cross-reacting with SARS-CoV-2 variants and other beta-coronaviruses
Authors: Lundgren Anna , Leach Susannah , Axelsson Hannes , Isakson Pauline , Nyström Kristina , Scharf Lydia , Andersson Bengt A , Miron Nicolae , Marklund Emelie , Andersson Lars-Magnus , Gisslén Magnus , Angeletti Davide , Bemark Mats
Published: April 2023

Antigen-specific class-switched antibodies are detected at the same time or even before IgM in serum of non-vaccinated individuals infected with SARS-CoV-2. These derive from the first wave of plasmablasts formed. Hence, the phenotype and specificity of plasmablasts can reveal information about early B-cell activation. Here we have analyzed B cells and plasmablasts circulating in blood of COVID-19 patients not previously exposed to SARS-CoV-2 during and after disease. We find that during infection with the original Wuhan strain, plasmablasts in blood produce IgA1, IgG1, and IgM, and that most express CCR10 and integrin β1, only some integrin β7, while the majority lack CCR9. Plasmablast-secreted antibodies are reactive to the spike (S) and nucleocapsid (N) proteins of the Wuhan strain as well as later variants of concern, but also bind S proteins from endemic and non-circulating betacoronaviruses. In contrast, after recovery, antibodies produced from memory B cells target variants of SARS-CoV-2 and SARS-CoV-1 but compared to previously non-infected individuals do not show increased binding to endemic coronaviruses. This suggests that the early antibody response to a large extent stems from pre-existing cross-reactive class-switched memory B cells, and that although newly formed memory cells target the novel SARS-CoV-2 virus the numbers of broadly cross-reactive memory B cells do not increase extensively. The observations give insight into the role of pre-existing memory B cells in early antibody responses to novel pathogens and may explain why class-switched antibodies are detected early in the serum of COVID-19 patients.
Automating the Deployment of Cyber Range with OpenStack
Authors: Zhou Shaohong , He Junjiang , Li Tao , Lan Xiaolong , Wang Yunpeng , Zhao Hui , Li Yihong
Published: April 2023

Cyber Range is an experimental platform based on virtualization technology to construct a controlled simulation environment, providing a real-world simulation environment for cybersecurity personnel to conduct various practical exercises. The problem is that generating a virtual environment satisfying the requirements is labor-intensive and time-consuming. To resolve the above problem, this paper proposes a system to automate the deployment of a cyber range. In our method, the first step is to collect virtual machines (VMs) related to cybersecurity and extract relevant features. Then, machine learning is used to classify VMs to reduce the cost of manual VMs selection. Lastly, leveraging the popular OpenStack cloud platform as the deployment platform enhances the applicability of the cyber range. When it comes time to deploy a virtual environment, the instructor only needs to provide some brief description information of a virtual environment. Then, the system will automatically parse the description file to complete the automated deployment of the virtual environment. This system has been successfully applied to the cyber range of Sichuan University for daily teaching tasks.
Results of the Eighth Scientific Workshop of ECCO: Pathophysiology and Risk Factors of Postoperative Crohn’s Disease Recurrence after an Ileocolonic Resection
Authors: Rivière Pauline , Bislenghi Gabriele , Hammoudi Nassim , Verstockt Bram , Brown Steven , Oliveira-Cunha Melissa , Bemelman Willem , Pellino Gianluca , Kotze Paulo Gustavo ,   the 8th Scientific Workshop of the European Crohn’s and Colitis Organisation, Dragoni Gabriele , Allocca Mariangela , Noor Nurulamin M , Pouillon Lieven , Mañosa Míriam , Savarino Edoardo , Allez Matthieu , Kapizioni Christina , Arebi Naila , Carvello Michele , De Vries Annemarie C , Domènech Eugeni , Myrelid Pär , Ferrante Marc , Panis Yves
Published: April 2023

Postoperative recurrence [POR] after an ileocolonic resection with ileocolonic anastomosis is frequently encountered in patients with Crohn’s disease. The 8th Scientific Workshop of ECCO reviewed the available evidence on the pathophysiology and risk factors for POR. In this paper, we discuss published data on the role of the microbiome, the mesentery, the immune system and the genetic background. In addition to investigating the causative mechanisms of POR, identification of risk factors is essential to tailor preventive strategies. Potential clinical, surgical and histological risk factors are presented along with their limitations. Emphasis is placed on unanswered research questions, guiding prevention of POR based on individual patient profiles.
A cost analysis of orthodontic space closure and implant treatment in patients missing maxillary lateral incisors with a long-term perspective
Authors: Hedmo Cecilia , Lindsten Rune , Josefsson Eva , Davidson Thomas
Published: April 2023

Objective

Few studies within orthodontics present both economic and clinical findings. Missing maxillary lateral incisors is a frequently occurring anomaly. The treatment alternatives most used are orthodontic space closure and prosthetic replacement of the missing tooth. Our aim is to compare the total societal costs of orthodontic space closure (SC) and implant therapy (IT) in patients missing maxillary lateral incisors.

Methods

Records of 32 patients treated with SC (n = 18) or IT (n = 14) due to missing maxillary lateral incisors were retrieved from the archives. Direct costs and indirect costs in the short- and long-term were analysed using a cost analysis with a societal perspective up of to 12 years post-treatment.

Results

Comparing cases treated with SC and IT, the difference in direct short-term costs for treatment is €735.54, whereas SC is the least costly. There is no difference between SC and IT in short-term parent loss of productivity, long-term loss of productivity, costs for transportation, or direct long-term costs. A difference was found between SC and IT—in favour of SC—when comparing patients’ loss of productivity (P = 0.007), short-term societal costs (P < 0.001), long-term societal costs (P = 0.037), and total societal costs (P < 0.001).

Limitations

There is a limited number of patient records. Local factors such as subsidies, urban versus rural areas, taxes, etc. can influence monetary variables, so the transferability to other settings may be limited.

Conclusion

Patients treated with SC have a lower total societal cost compared to patients treated with IT. There was a difference in productivity loss for patients between SC and IT; however, concerning other indirect parameters and direct long-term costs, there was no difference between the two treatments.
Is ‘immigrant optimism’ in educational choice a problem? Ethnic gaps in Swedish upper secondary school completion
Authors: Dollmann Jörg , Jonsson Jan O , Mood Carina , Rudolphi Frida
Published: April 2023

In many Western countries, researchers have documented ambitious educational choices among students of immigrant origin, for example, the tendency to choose academically more demanding routes than others at given levels of school achievement (e.g. grades, GPA). While this may indicate integration, some warn against an ‘immigrant optimism trap’, because choosing more demanding tracks at lower levels of GPA may increase risks of non-completion. Using longitudinal Swedish population data (n ≈ 90,000), we estimate an upper secondary ‘ethnic completion gap’ of 12 per cent to the detriment of students of immigrant background. We then address the ‘trap hypothesis’ via two analyses. The first shows that if students of immigration background would make similar educational choices as other students at the same GPA, the completion gap would shrink by 3.4 percentage points. The second analysis, based on simulations, suggests that restricting admission to academic programmes based on prior GPA, would lead to a massive relocation of low- and mid-GPA students to—usually less demanding—vocational programmes, but would only reduce the completion gap by 2.2 percentage points. These changes must be considered marginal in view of the substantial restrictions of choice that either of these measures would entail. We conclude that completion gaps are not primarily a result of unfounded immigrant optimism, and that optimistic choices are likely to be a net positive for integration by improving the chances of immigrant youth to reach tertiary-level qualifications and professional occupations.
EHRA expert consensus document on the management of arrhythmias in frailty syndrome, endorsed by the Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), Latin America Heart Rhythm Society (LAHRS), and Cardiac Arrhythmia Society of Southern Africa (CASSA)
Authors: Savelieva Irina , Fumagalli Stefano , Kenny Rose Anne , Anker Stefan , Benetos Athanase , Boriani Giuseppe , Bunch Jared , Dagres Nikolaos , Dubner Sergio , Fauchier Laurent , Ferrucci Luigi , Israel Carsten , Kamel Hooman , Lane Deirdre A , Lip Gregory Y H , Marchionni Niccolò , Obel Israel , Okumura Ken , Olshansky Brian , Potpara Tatjana , Stiles Martin K , Tamargo Juan , Ungar Andrea , Kosiuk Jedrzej , Larsen Torben Bjerregaard , Dinov Borislav , Estner Heidi , Garcia Rodrigue , Moscoso Costa Francisco Manuel , Lampert Rachel , Lin Yenn-Jiang , Chin Ashley , Rodriguez Heliodoro Antonio , Strandberg Timo , Grodzicki Tomasz
Published: April 2023

There is an increasing proportion of the general population surviving to old age with significant chronic disease, multi-morbidity, and disability. The prevalence of pre-frail state and frailty syndrome increases exponentially with advancing age and is associated with greater morbidity, disability, hospitalization, institutionalization, mortality, and health care resource use. Frailty represents a global problem, making early identification, evaluation, and treatment to prevent the cascade of events leading from functional decline to disability and death, one of the challenges of geriatric and general medicine. Cardiac arrhythmias are common in advancing age, chronic illness, and frailty and include a broad spectrum of rhythm and conduction abnormalities. However, no systematic studies or recommendations on the management of arrhythmias are available specifically for the elderly and frail population, and the uptake of many effective antiarrhythmic therapies in these patients remains the slowest. This European Heart Rhythm Association (EHRA) consensus document focuses on the biology of frailty, common comorbidities, and methods of assessing frailty, in respect to a specific issue of arrhythmias and conduction disease, provide evidence base advice on the management of arrhythmias in patients with frailty syndrome, and identifies knowledge gaps and directions for future research.
Computer-aided design of a cyclic di-AMP synthesizing enzyme CdaA inhibitor
Authors: Neumann Piotr , Kloskowski Patrick , Ficner Ralf
Published: April 2023

Cyclic di-AMP (c-di-AMP) is an essential secondary messenger regulating cell wall homeostasis and myriads of physiological processes in several Gram-positive and mycobacteria, including human pathogens. Hence, c-di-AMP synthesizing enzymes (DACs) have become a promising antibacterial drug target. To overcome a scarcity of small molecule inhibitors of c-di-AMP synthesizing enzyme CdaA, a computer-aided design of a new compound that should block the enzyme has been performed. This has led to the identification of a molecule comprising two thiazole rings and showing inhibitory potential based on ITC measurements. Thiazole scaffold is a good pharmacophore nucleus known due to its various pharmaceutical applications. It is contained in more than 18 FDA-approved drugs as well as in dozens of experimental drugs. Hence, the designed inhibitor can serve as a potent lead compound for further development of inhibitor against CdaA.
Differentially Expressed Genes Associated with Body Size Changes and Transposable Element Insertions between Caenorhabditis elegans and Its Sister Species, Caenorhabditis inopinata
Authors: Kawahara Kazuma , Inada Taruho , Tanaka Ryusei , Dayi Mehmet , Makino Takashi , Maruyama Shinichiro , Kikuchi Taisei , Sugimoto Asako , Kawata Masakado
Published: April 2023

Why the recently discovered nematode Caenorhabditis inopinata differs so greatly from its sibling species Caenorhabditis elegans remains unknown. A previous study showed that C. inopinata has more transposable elements (TEs), sequences that replicate and move autonomously throughout the genome, potentially altering the expression of neighboring genes. In this study, we focused on how the body size of this species has evolved and whether TEs could affect the expression of genes related to species-specific traits such as body size. First, we compared gene expression levels between C. inopinata and C. elegans in the L4 larval and young adult stages—when growth rates differ most prominently between these species—to identify candidate genes contributing to their differences. The results showed that the expression levels of collagen genes were consistently higher in C. inopinata than in C. elegans and that some genes related to cell size were differentially expressed between the species. Then, we examined whether genes with TE insertions are differentially expressed between species. Indeed, the genes featuring C. inopinata-specific TE insertions had higher expression levels in C. inopinata than in C. elegans. These upregulated genes included those related to body size, suggesting that these genes could be candidates for artificial TE insertion to examine the role of TEs in the body size evolution of C. inopinata.
Genomic determination of breeding systems and trans-specific evolution of HD MAT genes in suilloid fungi
Authors: Ke Yi-Hong , Branco Sara , Bazzicalupo Anna L , Nguyen Nhu H , Liao Hui-Ling , Kennedy Peter , Bruns Thomas D , Kuo Alan , LaButti Kurt , Barry Kerrie , Grigoriev Igor , Vilgalys Rytas
Published: April 2023

Studying the signatures of evolution can help to understand genetic processes. Here, we demonstrate how the existence of balancing selection can be used to identify the breeding systems of fungi from genomic data. The breeding systems of fungi are controlled by self-incompatibility loci that determine mating types between potential mating partners, resulting in strong balancing selection at the loci. Within the fungal phylum Basidiomycota, two such self-incompatibility loci, namely HD MAT locus and P/R MAT locus, control mating types of gametes. Loss of function at one or both MAT loci results in different breeding systems and relaxes the MAT locus from balancing selection. By investigating the signatures of balancing selection at MAT loci, one can infer a species’ breeding system without culture-based studies. Nevertheless, the extreme sequence divergence among MAT alleles imposes challenges for retrieving full variants from both alleles when using the conventional read-mapping method. Therefore, we employed a combination of read-mapping and local de novo assembly to construct haplotypes of HD MAT alleles from genomes in suilloid fungi (genera Suillus and Rhizopogon). Genealogy and pairwise divergence of HD MAT alleles showed that the origins of mating types predate the split between these two closely related genera. High sequence divergence, trans-specific polymorphism, and the deeply diverging genealogy confirm the long-term functionality and multiallelic status of HD MAT locus in suilloid fungi. This work highlights a genomics approach to studying breeding systems regardless of the culturability of organisms based on the interplay between evolution and genetics.
Three-Way Cell-Based Screening of Antistress Compounds: Identification, Validation, and Relevance to Old-Age-Related Pathologies
Authors: Zhang Huayue , Wang Jia , Prakash Jay , Zhang Zhenya , Kaul Sunil C , Wadhwa Renu
Published: April 2023

A variety of environmental stress stimuli have been linked to poor quality of life, tissue dysfunctions, and ailments including metabolic disorders, cognitive impairment, and accelerated aging. Oxidative, metal, and hypoxia stresses are largely associated with these phenotypes. Whereas drug development and disease therapeutics have advanced remarkably in last 3 decades, there are still limited options for stress management. Because the latter can effectively decrease the disease burden, we performed cell-based screening of antistress compounds by recruiting 3 chemical models of oxidative (paraquat), metal (cadmium nitrate), or hypoxia (cobalt chloride) stresses. The screening of 70 compounds for their ability to offer protection against oxidative, metal, and hypoxia stresses resulted in the selection of 5 compounds: Withaferin-A (Wi-A), methoxy Withaferin-A (mWi-A), Withanone (Wi-N), triethylene glycol (TEG), and Ashwagandha (Withania somnifera) leaf M2-DMSO extract (M2DM). Molecular assays revealed that whereas stress caused increase in (a) apoptosis, (b) reactive oxygen species accumulation coupled with mitochondrial depolarization, (c) DNA double-strand breaks, and (d) protein aggregation, low nontoxic doses of the selected compounds caused considerable protection. Furthermore, Wi-N, TEG, and their mixture-treated normal human fibroblasts (at young, mature, and senescent stages representing progressively increasing accumulation of stress) showed increase in proliferation. Taken together, these results suggested 3-way (oxidative, metal, and hypoxia) antistress potential of Wi-N and TEG that may be useful for management of environmental and old-age–related pathologies.
Dynapenic Abdominal Obesity Increases Risk for Falls Among Adults Aged ≥50 Years: A Prospective Analysis of the Irish Longitudinal Study on Ageing
Authors: Smith Lee , López Sánchez Guillermo F , Veronese Nicola , Soysal Pinar , Rahmati Masoud , Jacob Louis , Kostev Karel , Haro Josep Maria , Alghamdi Abdullah Ahmed , Butler Laurie , Barnett Yvonne , Keyes Helen , Tully Mark A , Shin Jae Il , Koyanagi Ai
Published: April 2023

Background

There is a scarcity of studies examining the longitudinal relationship between dynapenic abdominal obesity (DAO; ie, impairment in muscle strength and high waist circumference) and future fall risk. Therefore, we aimed to investigate the prospective association between DAO at baseline and falls occurring during 2 years of follow-up in a nationally representative sample of middle-aged and older individuals from Ireland.

Methods

Data from 2 consecutive waves of the Irish Longitudinal Study on Ageing survey were analyzed. Dynapenia was defined as handgrip strength of <26 kg for men and <16 kg for women. Abdominal obesity was defined as a waist circumference of >88 cm for women and >102 cm for men. DAO was assessed at Wave 1 (2009–2011) and was defined as having both dynapenia and abdominal obesity. Falls occurring between Wave 1 and Wave 2 (2012–2013) were self-reported. Multivariable logistic regression analysis was conducted.

Results

Data on 5 275 individuals aged ≥50 years were analyzed (mean [standard deviation {SD}] age 63.2 [8.9] years; 48.8% males). After adjustment for potential confounders, compared to no dynapenia and no abdominal obesity at baseline, DAO was significantly associated with 1.47 (95% confidence interval [CI]: 1.14–1.89) times higher odds for falls at 2-year follow-up. Dynapenia alone (odds ratio [OR] = 1.08; 95% CI: 0.84–1.40) and abdominal obesity alone (OR = 1.09; 95% CI: 0.91–1.29) were not significantly associated with falls at follow-up.

Conclusions

DAO increased the risk for falls among middle-aged and older adults in Ireland. Interventions to prevent or reverse DAO may be beneficial for fall reduction.
Licensing libel in seventeenth-century England: John White’s First Century of Scandalous, Malignant Priests in context/s
Authors: Fullerton Samuel
Published: April 2023

This article explores the polemical history of John White’s First Century of Scandalous, Malignant Priests (1643) to argue that the revolutionary public culture of England’s mid-century civil wars transformed seventeenth-century libellous politics by rendering ad hominem defamation into a routine element of formal partisan print culture for the first time in English history. The article concludes by demonstrating that when the Century reappeared in print eighty years later to excoriate a new generation of clergymen, public defamation had become a mundane, although still controversial, element of English political culture.
Chromosomal microdeletion leading to pituitary gigantism through hormone-gene overexpression
Authors: Katoh-Fukui Yuko , Hattori Atsushi , Zhang Ruogu , Terao Miho , Takada Shuji , Nakabayashi Kazuhiko , Hata Kenichiro , Yamada Yutaka , Matsuura Nobuo , Fukami Maki
Published: April 2023

Pituitary gigantism is a rare endocrinopathy characterized by tall stature due to growth hormone (GH) hypersecretion. This condition is generally linked to a genetic predisposition to tumors that produce GH or GH-releasing hormone (GHRH). Here, we report a Japanese woman who exhibited prominent body growth from infancy to reach an adult height of 197.4 cm (+7.4 standard deviation). Her blood GH levels were markedly elevated. She carried no pathogenic variants in known growth-controlling genes but had a hitherto unreported 752 kb heterozygous deletion at 20q11.23. The microdeletion was located 8.9 kb upstream of GHRH and encompassed exons 2–9 of a ubiquitously expressed gene TTI1 together with 12 other genes, pseudogenes and non-coding RNAs. Transcript analyses of the patient’s leukocytes showed that the microdeletion produced chimeric mRNAs consisting of exon 1 of TTI1 and all coding exons of GHRH. In silico analysis detected promoter-associated genomic features around TTI1 exon 1. Genome-edited mice carrying the same microdeletion recapitulated accelerated body growth from a few weeks after birth. The mutant mice developed pituitary hyperplasia and exhibited ectopic Ghrh expression in all tissues examined. Thus, the extreme phenotype of pituitary gigantism in the patient likely reflects GHRH overexpression driven by an acquired promoter. The results of this study indicate that germline submicroscopic deletions have the potential to cause conspicuous developmental abnormalities due to gene overexpression. Furthermore, this study provides evidence that constitutive expression of a hormone-encoding gene can result in congenital disease.
Modelled dispersal of snow crab (Chionoecetes opilio) larvae and potential settlement areas in the western Barents Sea
Authors: Huserbråten M , Hjelset A M , Danielsen H E H , Hvingel C , Agnalt A-L
Published: April 2023

Since the mid-1990s, a snow crab (Chionoecetes opilio) population has established in the eastern Barents Sea. Spawning females and newly hatched larvae are now also found in the central Barents Sea, warranting speculations on a further westward colonization by pelagic larvae. Here, we model the potential for larval dispersal and settlement into uncolonized areas in the western Barents Sea. We used a biophysical model of ocean currents and hydrography, coupled with a Lagrangian dispersal algorithm and larval survival functions as response to temperature. The model predicts limited dispersal from the central Barents Sea to western areas, primarily due to a mismatch between prevailing temperature regimes and temperature tolerances for the different larval stages. In addition, there was limited westward transport of water masses with temperatures that would allow completion of the pelagic larval development. We speculate that for larvae to successfully supply benthic recruits to the remaining uncolonized areas in the western Barents Sea, adult crabs would first need to establish new spawning aggregations, for example along the western slopes of the Barents Sea shelf. Immediate implications are limited potential for expanding the fishery to the western areas of the Barents Sea.
Development of an in vitro pharmacokinetic/pharmacodynamic model in the presence of serum for studying micafungin activity against Candida albicans: a need for revision of CLSI susceptibility breakpoints
Authors: Beredaki Maria-Ioanna , Arendrup Maiken C , Andes David , Meletiadis Joseph
Published: April 2023

Background

The CLSI breakpoint for micafungin and Candida albicans is 0.25 mg/L, higher than the CLSI epidemiological cut-off value (0.03 mg/L) whereas the EUCAST values are identical (0.016 mg/L). We developed a novel in vitro dialysis-diffusion pharmacokinetic/pharmacodynamic (PK/PD) model, confirmed correlation to in vivo outcome and studied micafungin pharmacodynamics against Canida albicans.

Methods

Four C. albicans isolates, including a weak (F641L) and a strong (R647G) fks1 mutants, were studied using a 104 cfu/mL inoculum and RPMI medium with and without 10% pooled human serum. The exposure-effect relationship fAUC0–24/MIC was described for CLSI and EUCAST methodology. Monte Carlo simulation analysis included standard (100 mg i.v.) and higher (150–300 mg) doses q24h to determine the corresponding probability of target attainment (PTA).

Results

The in vitro PK/PD targets for stasis/1-log kill were 36/57 fAUC0–24/MIC in absence and 2.8/9.2 fAUC0–24/MIC in the presence of serum, and similar for wild-type and fks mutant isolates. The PTAs for both PK/PD targets were high (>95%) for EUCAST susceptible isolates but not for CLSI susceptible non-wild-type isolates (CLSI MICs 0.06–0.25 mg/L). 300 mg q24h was needed to attain PK/PD targets for non-wild-type isolates with CLSI MICs 0.06–0.125 mg/L and EUCAST MICs 0.03–0.06 mg/L.

Conclusion

The in vitro 1-log kill effect corresponded to stasis in animal model and mycological response in patients with invasive candidiasis, thereby validating the model for studying pharmacodynamics of echinocandins in vitro. EUCAST breakpoints were well supported by our findings but our data questions whether the current CLSI breakpoint, which is higher than the epidemiological cut-off values, is appropriate.
Animal pharmacokinetics/pharmacodynamics (PK/PD) infection models for clinical development of antibacterial drugs: lessons from selected cases
Authors: Moore Jason N , Poon Lucas , Pahwa Sonia , Bensman Timothy , Wei Xiaohui (Tracey) , Danielsen Zhixia Yan , Jang Seong
Published: April 2023

In the wake of emerging antimicrobial resistance, antibacterial drug development has become more critical. At the same time, development of antibacterial drugs targeting specific pathogens or resistance phenotypes that may have low prevalence presents challenges because it is difficult to conduct large, randomized controlled trials for such drugs. Animal models have increasingly supported clinical development of antibacterials; however, more work is needed to optimize the design and application of these animal models to ensure clear and actionable translation to further human investigation. This review discusses recent case studies of animal infection models used to support antibacterial drug development in order to illuminate considerations for future development of novel antibacterial drugs.