bluuebunny/crossref_metadata_2025 huggingface dataset:
“Race,” Inequality, and Education in the Czech Republic
Authors: Moree Dana , Kosak Felcmanova Alena , Karvayová Magdaléna
Published: April 2023

“Race” and education are profoundly interconnected in the Czech context, and this is especially visible with respect to the issue of the Roma population. The communist regime of the former Czechoslovakia made use of the educational environment to strengthen its ideology through teacher training, discriminative legislation, and changing the content of education. “Race” issues in society were “solved” by segregating most Roma children into what were called “special schools” for the mentally disabled.

The fall of communism introduced freedom and changes to all of society, particularly in the education system, but new education legislation was not passed until 15 years after the fall of communism, and it did not address issues around discrimination sufficiently.

In 2007, the European Court of Human Rights ruled against the Czech Republic for having discriminated against a group of Roma children during the 1990s. This means a discriminatory situation and its consequences were still visible almost 30 years after the fall of communism.

In response to this ruling, inclusion policy began to be promoted in Czech schools as of 2016. The situation from the perspective of legislation has been becoming more equal—the Act on Education has been amended, the financial support for disadvantaged children in education has become more transparent, and so on, but data from research conducted after amendment of the Act on Education show that the situation in or near what are called “socially excluded areas” has become much more difficult. Roma children are segregated not just by the official decisions of school establishers (municipalities) but also through parents, teachers, and head teachers from the majority population who interpret the applicable rules in such a way that Roma children, pupils, and students are concentrated into specific schools and do not attend school together with majority-society (non-Roma) children. “Race” issues, in combination with poverty, are drawing new borders around access to education. Roma children are not always welcome in the schools.

These are reasons why the interconnectedness of the education system with issues related to racism in the context of a transforming society should be carefully analyzed. There are several facets of the topic, which we should take into consideration:

First, terms like race, culture, and ethnicity are very often used without a deeper discussion of their meaning. It is necessary to use them precisely and reflectively. Second, this interconnectedness between race and education works on individual and interpersonal levels, the cultural level, and the structural level. They all should be taken into consideration while planning research, changes, or interventions. Finally, the interplay between these three levels is visible when we analyze real examples from the field (e.g., an intervention initiated by a nongovernmental Roma organization, Awen Amenca, in the city in the Czech Republic with the highest concentration of socially excluded localities).
History of Higher Education in Kenya
Authors: Kithinji Michael Mwenda
Published: April 2023

The history of higher education in Kenya is defined by a struggle for domination by the various forces that have sought to influence the country’s social, economic, and political trajectory in the colonial and postcolonial periods. During the colonial period, the church had a major interest in education, which they viewed as an important tool in their evangelizing mission. However, the colonial government regarded education as an agency for social control as it attempted to mediate the competing interests of the missionaries, white settlers, and African nationalists. Similarly, the postcolonial governments saw education, especially at the higher level as significant due to its role in forming the elite class and as a mechanism for ideological control. Consequently, Kenya’s higher education landscape has witnessed a striking transformation as it served as an arena for powerful competing interests from the colonial period to the present.

The period between the inception of higher education in the late 1940s until the early independence period in the late 1960s was dominated by the colonial inter-territorial policy that severely limited the opportunities to access higher education. While the first postcolonial government of President Kenyatta largely upheld the colonial elitist ideas on higher education, this approach changed when President Moi came into office in 1978. President Moi wanted to leave his mark on education by increasing access to higher education. Many students were thus able to access university education, previously a preserve of the privileged few. University expansion remains an enduring legacy of President Moi’s administration, which the succeeding government of Mwai Kibaki inherited and enhanced.
Planetary Spectroscopy
Authors: Wang Alian
Published: April 2023

Planetary spectroscopy uses physical methods to study the chemical properties of the geological materials on the planetary bodies in our solar system. This article will present twelve types of spectroscopy frequently used in planetary explorations. Their energy (or wavelength) varies from γ-ray (keV) to far-infrared (μm), which involves the transitions of nuclei, atoms, ions, and molecules in planetary materials. The article will cover the basic concept of the transition for each of the twelve types of spectroscopy, along with their legendary science discoveries made during the past planetary exploration missions by the international planetary science and engineering community.

The broad application of spectroscopy in planetary exploration is built upon the fact that only limited extraterrestrial materials were collected (meteorites, cosmic dust, and the returned samples by missions) that enabled the detailed investigations of their properties in laboratories, while spectroscopic measurements can be made on the objects of our solar system remotely and robotically, such as during the flyby, orbiting, lander, and rover missions. In this sense, the knowledge obtained by planetary spectroscopy has contributed to a major portion of planetary sciences.

In the coming era of space explorations, more powerful spacecraft will be sent out by mankind, go to deep space, and explore exotic places. Generations of new planetary science payloads, including planetary spectrometers, will be created and will fly. New sciences will be revealed.
World-Systems Analysis
Authors: Denemark Robert A. , Upadhyay Smriti
Published: April 2023

World-systems analysis (WSA) emerged in the 1960s and 1970s in response to methodological nationalism, ahistoricism, and Cold War–era polemics. It is a whole-systems, historically focused, transdisciplinary, and critical approach whose founding scholars include Immanuel Wallerstein, Samir Amin, Giovanni Arrighi, and Andre Gunder Frank. Key early insights regarding development and underdevelopment are reviewed along with the systemic processes that have been identified including core/periphery differentiation and exploitation. Cyclical processes include economic rise/decline, hegemony/rivalry, and labor/capital domination. Secular trends include geographic expansion, mechanization, and commodification. Three revisionist positions are identified: comparative world-systems, world-system history, and world-systems geopolitics. Ongoing world-systems research on inequality, commodity chains, social movements, the environment, world-systems incorporation, trade patterns, gender, family relations, population movements, urbanization, and geographic networks is introduced. World-systems literatures exist in anthropology, archaeology, geography, history, political science, and sociology. Going forward, areas for further development include better integrating agency into WSA, and considerations of world-system conflict.
Archaeological Heritage Management in Tanzania
Authors: Bigambo Richard
Published: April 2023

The idea that various forms of archaeological heritage are important is common among communities in different parts of the world. Similarly, the practices of looking after and ensuring the continued existence of such forms have a long history as well. This is evidenced by the fact that almost every community in the world has their own ways of looking after different aspects that are valued and recognized as archaeological heritage. Such ways usually involve administrative systems and regulations that control the process and guide practitioners that implement different activities related to the management process. Nonetheless, the early 19th century saw the beginning of efforts to standardize the Archaeological Heritage Management (AHM) practices in different parts of the world.

This was done through the introduction of the management systems that formerly existed in Western countries to other parts of the world as an integral part of the colonial infrastructures. The result of this was the exportation of various management values and standards from Western countries to other parts. These newly introduced management systems have always been a source of conflict between the responsible authorities and the local community. Tanzania is among the countries of the world that are endowed with diverse forms of archaeological heritage. As in other former colonies, the current practices of AHM owe their origin to the colonial period and the succession of German and British imperial administrations. The extant system was introduced during the colonial period and has continued to operate, with some modifications introduced during the postcolonial period.
The Emergence of Modern Cosmology
Authors: Kragh Helge
Published: April 2023

The term modern cosmology primarily refers to the developments concerned with the expansion of the universe, its origin billions of years ago, and the concept of dark matter. Similar to the history of any other area of science, the history of cosmology is rich in wrong theories and false trials. According to the simplest version of Brandon Carter’s anthropic principle, carbon-based life could not have originated in a universe evolving just slightly differently from the one observed. The present debate concerning the anthropic principle and its consequences is in some ways strikingly similar to the cosmological controversy of the past between the steady-state theory and relativistic evolution theories.
Baltimore
Authors: Schley David
Published: April 2023

Baltimore, Maryland, rose to prominence in the late 18th century as a hub for the Atlantic wheat trade. A slave city in a slave state, Baltimore was home to the largest free Black community in antebellum America. Nineteenth-century Baltimore saw trend-setting experiments in railroading as well as frequent episodes of collective violence that left the city with the nickname, “mobtown”; one such riot, in 1861, led to the first bloodshed of the Civil War. After the war, Baltimore’s African American community waged organized campaigns to realize civil rights. Residential segregation—both de jure and de facto—posed a particular challenge. Initiatives in Baltimore such as a short-lived segregation ordinance and racial covenants in property deeds helped establish associations between race and property values that shaped federal housing policy during the New Deal. The African American population grew during World War II and strained against the limited housing available to them, prompting protests, often effective, against segregation. Nonetheless, suburbanization, deindustrialization, and redlining have left the city with challenging legacies to confront.
Antisemitism in US History
Authors: Tevis Britt P.
Published: April 2023

Antisemitism in the United States—whether acts of violence, social exclusion, cultural vilification, or political and legal discrimination—has resulted from antidemocratic currents refracted through bigoted beliefs about Jews. Prejudiced conceptualizations of Jews positioned them as outsiders to the nation, emphasizing Jews’ refusal to accept the supremacy of Christ; depicting Jews to be racially distinct (i.e., inferior or dangerous); and imagining Jews as greedy, dirty, untrustworthy, scheming, manipulative, powerful, and dangerous. Antisemitism has consistently been (and continues to be) connected with anti-Black racism, xenophobia, and misogyny. Throughout US history, non-Jews deployed bigoted ideas about Jews for personal, professional, social, and/or political gain. As a result, with degrees of variation, Jews in the United States endured personal hardships, faced collective discrimination, and confronted political intolerance.
Public Health in Uruguay, 1830–1940s
Authors: Birn Anne-Emanuelle , Pollero Raquel
Published: April 2023

Little examined, Uruguay’s public health trajectory offers an important window on the country’s larger societal dynamics and the possibilities and limits of public health across Latin America. On one hand, Uruguay lagged behind public health efforts and overall institutionalization compared to other countries in the region, through much of the 19th century. On the other hand, tiny Uruguay became highly engaged with international health, medical, and social policy developments, and it modernized, urbanized, and secularized early, with important implications for health and welfare state-building, epitomized in early 20th-century Batllismo. Still, the country’s economic, epidemic, demographic, social, and political vicissitudes meant that public health efforts, too, oscillated between fulfilling aspirations for an up-to-date and far-reaching hygienic apparatus and seeing these expectations dashed during economic downturns, periods of political repression, and when health successes seemingly turned into failures, as with its prolonged infant mortality stagnation. Uruguay also moved from being an importer of public health models and practices, especially from Europe, to exporting its own innovative approaches, as per its internationally renowned rights-based approach to improving child health, embodied in its 1934 Children’s Code and diffused via the pathbreaking Montevideo-based children’s protection institute. Also sui generis were the multiplicity of roles played by the country’s minuscule pool of public health experts, who served at one and the same time as epidemiological observers, institutional leaders, clinicians, and policy elites, making their impact and interactions both fruitful and fraught. The article traces Uruguay’s public health history across three eras, revealing the untold stories and ups and downs of a small but significant public health actor.
Nominal Inflectional Morphology in Germanic: Adjectives
Authors: Enger Hans-Olav
Published: April 2023

The article surveys the different types of adjective inflection: gradation and agreement. Agreement inflection on adjectives in Germanic can involve gender, number, case, and strong/weak (definiteness). The languages differ in their agreement inflection. The different modes of exponence for the different inflections are shown (e.g., periphrasis, affixation, and vowel change). There are adjectives that are defective and those that are completely indeclinable. The article also surveys deviations such as suppletion and syncretisms. The article shows how the notion of construction may be relevant for Germanic adjective inflection, how there is a difference between attributive and predicative use in that the former typically involves “more inflection,” and this is also shown for cases of semantic agreement. Perhaps some differences between Germanic languages in their adjective inflection relate to sociolinguistic factors.
Unsettling Imperial Science: Centering Convivial Scholarship in Sociolinguistics
Authors: Ndhlovu Finex
Published: April 2023

The universalizing posture of claims made by colonial approaches and their regimes of representation continues to inform most mainstream sociolinguistics research agendas and project designs. Such claims reflect an imperial scientific tradition that overlooks and marginalizes other ways of knowing, particularly those from communities of the global South. Decolonizing sociolinguistics entails doing at least three things. First, we must decolonize ourselves through critical reflection on our own practices and how such practices contribute to the continuation of inequalities in knowledge production and in society. Second is the need to develop new narratives, new words, new grammars, and new vocabularies for eliciting empirical data to support the suppositions and arguments we advance in our anti-conventional and anti-colonial theoretical approaches to language and society research. Such alternative trajectories require a decentering of the dominant (colonial/imperial) voice and an increase in other voices speaking from other equally valid approaches that are currently being overlooked. Third, decolonizing sociolinguistics entails developing new models that draw on a rich collection of thought from a broad spectrum of traditions of knowing. This is about promoting convivial scholarship through mobilizing diverse resources to advance collaborative engagements that link our academic pursuits to public interests, including the interests of marginalized, minority, and global Indigenous communities. Convivial scholarship says the paths we follow in doing sociolinguistics research must be those that are committed to re-membering and rehumanizing Indigenous and other Southern peoples subjected to more than 500 years of coloniality. Decolonizing sociolinguistics must, therefore, mean freeing the field from the colonial tradition of knowing by bringing back to the center historically marginalized Indigenous and Southern knowledge systems. The premise is that a sociolinguistics that works for all must open pathways and avenues for epistemic access and cognitive justice through valuing diverse founts of knowledges as key contours.
Extracorporeal cardiopulmonary resuscitation: A primer for pharmacists
Authors: Brown Caitlin S , Wieruszewski Erin D , Nei Scott D , Vollmer Nicholas J , Mattson Alicia E , Wieruszewski Patrick M
Published: April 2023

Purpose

To describe the use of mechanical circulatory support in the setting of cardiac arrest and summarize pharmacists’ role in extracorporeal cardiopulmonary resuscitation (ECPR).

ECPR is increasingly used to reduce morbidity and improve mortality after cardiac arrest. ECPR employs venoarterial ECMO, which provides full circulatory perfusion and gas exchange in both adult and pediatric patients in cardiac arrest. After the emergency medicine team identifies potential candidates for ECPR, the ECMO team is consulted. If deemed a candidate for ECPR by the ECMO team, the patient is cannulated during ongoing standard cardiopulmonary resuscitation. A multidisciplinary team of physicians, nurses, perfusionists, pharmacists, and support staff is needed for successful ECPR. Pharmacists play a vital role in advanced cardiac life support (ACLS) prior to cannulation. Pharmacists intervene to make pharmacotherapy recommendations during ACLS, prepare medications, and administer medications as allowed by institutional and state regulations. Pharmacists also provide pharmacotherapy support in the selection of anticoagulation agents, ongoing vasopressor administration during ECMO cannulation, and the optimization of medication selection in the peri-ECPR period.

Conclusion

With the growing use of ECPR, pharmacists should be aware of their role in medication optimization during ECPR.
Tirzepatide: Clinical review of the “twincretin” injectable
Authors: Krauss Zach , Hintz Alexandra , Fisk Rebecca
Published: April 2023

Purpose

To provide an overview of the safety and efficacy, pharmacology, dosing, place in therapy, and clinical trials for tirzepatide, a novel glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) agonist for treatment of type 2 diabetes.

Diabetes is a chronic disease state with a high burden on healthcare spending and patient quality of life. Incretin-influencing agents such as GLP-1 receptor agonists have gained favor as diabetes therapeutic options due to their impact on multiple glycemic factors as well as resulting weight loss and cardiovascular benefits. Tirzepatide was approved in 2022 for the management of type 2 diabetes and utilizes GLP-1 receptor agonism along with GIP agonism to simultaneously address 2 incretin pathways. Thus far, the SURPASS and SURMOUNT trials, for which findings have been published, have shown great efficacy of tirzepatide in glycosylated hemoglobin and weight reduction in multiple subgroup populations with and without diabetes. Tirzepatide has similar gastrointestinal adverse reactions and contraindications as traditional GLP-1 receptor agonists.

Conclusion

Tirzepatide is a novel agent on the market for type 2 diabetes management that offers targeting of a familiar pathway along with the new GIP pathway to address glycemic control in patients with diabetes. Tirzepatide is approved for use in patients with diabetes and may serve as a strong option for patients requiring improved glycemic and weight control.
3D-MSNet: a point cloud-based deep learning model for untargeted feature detection and quantification in profile LC-HRMS data
Authors: Wang Ruimin , Lu Miaoshan , An Shaowei , Wang Jinyin , Yu Changbin
Published: April 2023

Motivation

Liquid chromatography coupled with high-resolution mass spectrometry is widely used in composition profiling in untargeted metabolomics research. While retaining complete sample information, mass spectrometry (MS) data naturally have the characteristics of high dimensionality, high complexity, and huge data volume. In mainstream quantification methods, none of the existing methods can perform direct 3D analysis on lossless profile MS signals. All software simplify calculations by dimensionality reduction or lossy grid transformation, ignoring the full 3D signal distribution of MS data and resulting in inaccurate feature detection and quantification.

Results

On the basis that the neural network is effective for high-dimensional data analysis and can discover implicit features from large amounts of complex data, in this work, we propose 3D-MSNet, a novel deep learning-based model for untargeted feature extraction. 3D-MSNet performs direct feature detection on 3D MS point clouds as an instance segmentation task. After training on a self-annotated 3D feature dataset, we compared our model with nine popular software (MS-DIAL, MZmine 2, XCMS Online, MarkerView, Compound Discoverer, MaxQuant, Dinosaur, DeepIso, PointIso) on two metabolomics and one proteomics public benchmark datasets. Our 3D-MSNet model outperformed other software with significant improvement in feature detection and quantification accuracy on all evaluation datasets. Furthermore, 3D-MSNet has high feature extraction robustness and can be widely applied to profile MS data acquired with various high-resolution mass spectrometers with various resolutions.

Availability and implementation

3D-MSNet is an open-source model and is freely available at https://github.com/CSi-Studio/3D-MSNet under a permissive license. Benchmark datasets, training dataset, evaluation methods, and results are available at https://doi.org/10.5281/zenodo.6582912.
Standardized perioperative management in acute abdominal surgery: Swedish SMASH controlled study
Authors: Timan Terje J , Karlsson Ove , Sernert Ninni , Prytz Mattias
Published: April 2023

Background

Acute high-risk abdominal surgery is common, as are the attendant risks of organ failure, need for intensive care, mortality, or long hospital stay. This study assessed the implementation of standardized management.

Methods

A prospective study of all adults undergoing emergency laparotomy over an interval of 42 months (2018–2021) was undertaken; outcomes were compared with those of a retrospective control group. A new standardized clinical protocol was activated for all patients including: prompt bedside physical assessment by the surgeon and anaesthetist, interprofessional communication regarding location of resuscitation, elimination of unnecessary factors that might delay surgery, improved operating theatre competence, regular epidural, enhanced recovery care, and frequent early warning scores. The primary endpoint was 30-day mortality. Secondary endpoints were duration of hospital stay, need for intensive care, and surgical complications.

Results

A total of 1344 patients were included, 663 in the control group and 681 in the intervention group. The use of antibiotics increased (81.4 versus 94.7 per cent), and the time from the decision to operate to the start of surgery was reduced (3.80 versus 3.22 h) with use of the new protocol. Fewer anastomoses were performed (22.5 versus 16.8 per cent). The 30-day mortality rate was 14.5 per cent in the historical control group and 10.7 per cent in the intervention group (P = 0.045). The mean duration of hospital (11.9 versus 10.2 days; P = 0.007) and ICU (5.40 versus 3.12 days; P = 0.007) stays was also reduced. The rate of serious surgical complications (grade IIIb–V) was lower (37.6 versus 27.3 per cent; P = <0.001).

Conclusion

Standardized management protocols improved outcomes after emergency laparotomy.
Blood transcriptome sequencing identifies biomarkers able to track disease stages in spinocerebellar ataxia type 3
Authors: Raposo Mafalda , Hübener-Schmid Jeannette , Ferreira Ana F , Vieira Melo Ana Rosa , Vasconcelos João , Pires Paula , Kay Teresa , Garcia-Moreno Hector , Giunti Paola , Santana Magda M , Pereira de Almeida Luis , Infante Jon , van de Warrenburg Bart P , de Vries Jeroen J , Faber Jennifer , Klockgether Thomas , Casadei Nicolas , Admard Jakob , Schöls Ludger ,   European Spinocerebellar ataxia type 3/Machado-Joseph disease Initiative (ESMI) study group, Krahe Janna , Reetz Kathrin , González José , Gonzalez Carlos , Baptista Carlos , Lemos João , Giordano Ilaria , Grobe-Einsler Marcus , Önder Demet , Silva Patrick , Januário Cristina , Ribeiro Joana , Cunha Inês , Lemos João , Pinto Maria M , Timmann Dagmar , Steiner Katharina M , Thieme Andreas , Ernst Thomas M , Jacobi Heike , Solanky Nita , Gonzalez-Robles Cristina , Van Gaalen Judith , Pelayo-Negro Ana Lara , Manrique Leire , Hengel Holger , Synofzik Matthis , Ilg Winfried , Riess Olaf , Lima Manuela
Published: April 2023

Transcriptional dysregulation has been described in spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD), an autosomal dominant ataxia caused by a polyglutamine expansion in the ataxin-3 protein. As ataxin-3 is ubiquitously expressed, transcriptional alterations in blood may reflect early changes that start before clinical onset and might serve as peripheral biomarkers in clinical and research settings. Our goal was to describe enriched pathways and report dysregulated genes, which can track disease onset, severity or progression in carriers of the ATXN3 mutation (pre-ataxic subjects and patients).

Global dysregulation patterns were identified by RNA sequencing of blood samples from 40 carriers of ATXN3 mutation and 20 controls and further compared with transcriptomic data from post-mortem cerebellum samples of MJD patients and controls. Ten genes—ABCA1, CEP72, PTGDS, SAFB2, SFSWAP, CCDC88C, SH2B1, LTBP4, MEG3 and TSPOAP1—whose expression in blood was altered in the pre-ataxic stage and simultaneously, correlated with ataxia severity in the overt disease stage, were analysed by quantitative real-time PCR in blood samples from an independent set of 170 SCA3/MJD subjects and 57 controls.

Pathway enrichment analysis indicated the Gαi signalling and the oestrogen receptor signalling to be similarly affected in blood and cerebellum. SAFB2, SFSWAP and LTBP4 were consistently dysregulated in pre-ataxic subjects compared to controls, displaying a combined discriminatory ability of 79%. In patients, ataxia severity was associated with higher levels of MEG3 and TSPOAP1.

We propose expression levels of SAFB2, SFSWAP and LTBP4 as well as MEG3 and TSPOAP1 as stratification markers of SCA3/MJD progression, deserving further validation in longitudinal studies and in independent cohorts.
Spike-microstates correlate with interictal epileptogenic discharges: a marker for hidden epileptic activity
Authors: Rochas Vincent , Gschwind Markus , Nedeltchev Krassen , Seeck Margitta
Published: April 2023

Objectively estimating disease severity and treatment success is a main problem in outpatient managing of epilepsy. Self-reported seizures diaries are well-known to underestimate the actual seizure count, and repeated EEGs might not show interictal epileptiform discharges (IEDs), although patients suffer from seizures. In this prospective study, we investigate the potential of microstate analysis to monitor epilepsy patients independently of their IED count.

From our databank of candidates for epilepsy surgery, we included 18 patients who underwent controlled resting EEG sessions (with eyes closed, 30 min), at around the same time of the day, during at least four days (range: 4–8 days; mean: 5). Nine patients with temporal foci, six with extratemporal foci, and three with generalized epilepsy were included. Each patient’s IEDs were marked and the topographic voltage maps of the IED peaks were averaged, and an individual average spike topography (AST) was created. The AST was then backfitted to each timepoint of the whole EEG resulting in the Spike-Microstate (SMS). The presence of the SMS in the residual EEG outside of the short IEDs epochs was determined for each recording session in each patient and correlated with the occurrence of the IEDs across all recording session, as well as with the drug charge of each day.

Overall, SMS was much more represented in the routine EEG than the IEDs: they were identified 262 times more often than IEDs. The SMS time coverage correlated significantly with the IED occurrence rate (rho = 0.56; P < 0.001). If only patients with focal epilepsy were considered, this correlation was even higher rho = 0.69 (P < 0.001). Drug charge per day did not correlate with SMS.

In this proof-of-concept study, the time coverage of SMS correlated strongly with the occurrence rate of the IEDs, they can be retrieved in the scalp EEG at a much higher occurrence rate. We conclude that SMS, once obtained for a given patient, are a more abundant marker of hidden epileptic activity than IEDs, in particular in focal epilepsy, and can be used also in absence of IEDs. Future larger studies are needed to verify its potential as monitoring tool and to determine cut-off values when drug protection becomes imperfect.
Parasagittal dural space hypertrophy and amyloid-β deposition in Alzheimer’s disease
Authors: Song Alexander K , Hett Kilian , Eisma Jarrod J , McKnight Colin D , Elenberger Jason , Stark Adam J , Kang Hakmook , Yan Yan , Considine Ciaran M , Donahue Manus J , Claassen Daniel O
Published: April 2023

One of the pathological hallmarks of Alzheimer’s and related diseases is the increased accumulation of protein amyloid-β in the brain parenchyma. As such, recent studies have focused on characterizing protein and related clearance pathways involving perivascular flow of neurofluids, but human studies of these pathways are limited owing to limited methods for evaluating neurofluid circulation non-invasively in vivo. Here, we utilize non-invasive MRI methods to explore surrogate measures of CSF production, bulk flow and egress in the context of independent PET measures of amyloid-β accumulation in older adults. Participants (N = 23) were scanned at 3.0 T with 3D T2-weighted turbo spin echo, 2D perfusion-weighted pseudo-continuous arterial spin labelling and phase-contrast angiography to quantify parasagittal dural space volume, choroid plexus perfusion and net CSF flow through the aqueduct of Sylvius, respectively. All participants also underwent dynamic PET imaging with amyloid-β tracer 11C-Pittsburgh Compound B to quantify global cerebral amyloid-β accumulation. Spearman’s correlation analyses revealed a significant relationship between global amyloid-β accumulation and parasagittal dural space volume (rho = 0.529, P = 0.010), specifically in the frontal (rho = 0.527, P = 0.010) and parietal (rho = 0.616, P = 0.002) subsegments. No relationships were observed between amyloid-β and choroid plexus perfusion nor net CSF flow. Findings suggest that parasagittal dural space hypertrophy, and its possible role in CSF-mediated clearance, may be closely related to global amyloid-β accumulation. These findings are discussed in the context of our growing understanding of the physiological mechanisms of amyloid-β aggregation and clearance via neurofluids.
The wild mouse bone marrow has a unique myeloid and lymphoid composition and phenotype
Authors: Muir Andrew , Bennett Alex , Smith Hannah , Logunova Larisa , Wolfenden Andrew , Fenn Jonathan , Lowe Ann E , Brass Andy , Grainger John R , Konkel Joanne E , Bradley Janette E , Mair Iris , Else Kathryn J
Published: April 2023

The murine bone marrow has a central role in immune function and health as the primary source of leukocytes in adult mice. Laboratory mice provide a human-homologous, genetically manipulable and reproducible model that has enabled an immeasurable volume of high-quality immunological research. However, recent research has questioned the translatability of laboratory mouse research into humans and proposed that the exposure of mice to their wild and natural environment may hold the key to further immunological breakthroughs. To date, there have been no studies providing an in-depth cellular analysis of the wild mouse bone marrow. This study utilized wild mice from an isolated island population (Isle of May, Scotland, UK) and performed flow cytometric and histological analysis to characterize the myeloid, lymphoid, hematopoietic progenitor, and adipocyte compartments within the wild mouse bone marrow. We find that, compared to laboratory mouse bone marrow, the wild mouse bone marrow differs in every cell type assessed. Some of the major distinctions include; a smaller B cell compartment with an enriched presence of plasma cells, increased proportions of KLRG1+ CD8+ T cells, diminished CD11b expression in the myeloid lineage and a five-fold enlargement of the eosinophil compartment. We conclude that the wild mouse bone marrow is dramatically distinct from its laboratory counterparts, with multiple phenotypes that to our knowledge have never been observed in laboratory models. Further research into these unique features may uncover novel immunological mechanisms and grant a greater understanding of the role of the immune system in a natural setting.
Myocardial tissue characterization by segmental T2 mapping in thalassaemia major: detecting inflammation beyond iron
Authors: Meloni Antonella , Pistoia Laura , Positano Vincenzo , Martini Nicola , Borrello Rita Laura , Sbragi Sara , Spasiano Anna , Casini Tommaso , Bitti Pier Paolo , Putti Maria Caterina , Cuccia Liana , Allò Massimo , Massei Francesco , Sanna Paola Maria Grazia , De Caterina Raffaele , Quaia Emilio , Cademartiri Filippo , Pepe Alessia
Published: April 2023

Aims

We measured myocardial T2 values by a segmental approach in thalassaemia major (TM) patients, comparing such values against T2* values for the detection of myocardial iron overload (MIO), evaluating their potential in detecting subclinical inflammation, and correlating with clinical status.

Methods and results

One-hundred and sixty-six patients (102 females, 38.29 ± 11.49years) enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network underwent magnetic resonance imaging for the assessment of hepatic, pancreatic, and cardiac iron overload (T2* technique), of biventricular function (cine images), and of replacement myocardial fibrosis [late gadolinium enhancement (LGE)]. T2 and T2* values were quantified in all 16 myocardial segments, and the global value was the mean of all segments. Global heart T2 values were significantly higher in TM than in a cohort of 80 healthy subjects. T2 and T2* values were significantly correlated. Out of the 25 patients with a decreased global heart T2* value, 11 (44.0%) had reduced T2 values. No patient with a normal T2* value had a decreased T2 value.

Eleven (6.6%) patients had a decreased global heart T2 value, 74 (44.6%) a normal global heart T2 value, and 81 (48.8%) an increased global heart T2 value. Biventricular function was comparable amongst the three groups, whilst LGE was significantly more frequent in patients with reduced vs. increased global heart T2 value. Compared with the other two groups, patients with reduced T2 values had significantly higher hepatic and pancreatic iron deposition.

Conclusion

In TM, T2 mapping does not offer any advantage in terms of sensitivity for MIO assessment but detects subclinical myocardial inflammation.
Utility of cardiac magnetic resonance imaging for pre-operatively evaluating the degree of caseous calcification of the mitral annulus infiltration within the left ventricular myocardium: a case report
Authors: Hishikawa Takanori , Ohashi Takeki , Kageyama Soichiro , Kojima Akinori
Published: April 2023

Background

Depending on the degree of infiltration of dry mitral annulus calcification (MAC) into the left ventricular myocardium, calcification removal may cause thinning of the left ventricular wall and increase the risk of post-operative left ventricular rupture. Therefore, the degree of pre-operative infiltration into the left ventricular myocardium should be assessed as accurately as possible. We report a case of caseous calcification of the mitral annulus (CCMA), a subtype of MAC, in an 84-year-old woman; cardiac magnetic resonance imaging (MRI) was useful in assessing the degree of left ventricular infiltration of calcification.

Case summary

The patient was referred to our hospital for surgery due to respiratory distress and severe mitral insufficiency. Echocardiography revealed a mass under the posterior mitral annulus adjacent to the mitral valve ring, suspected to be a CCMA. Cardiac MRI was performed to assess the risk of left ventricular rupture. Pre-operatively, no valve ring or left ventricular myocardium infiltration was confirmed. Surgical caseous calcification removal and artificial valve implantation within the preserved valve annulus were then performed. The patient had an uneventful post-operative course and was discharged without complications on the 21st post-operative day.

Discussion

In this CCMA case, a pre-operative cardiac MRI was useful for evaluating the degree of the valve annulus and left ventricular myocardial involvement and estimating the risk of left ventricular rupture.
Unraveling Firms: Demand, Productivity and Markups Heterogeneity
Authors: Forlani Emanuele , Martin Ralf , Mion Giordano , Muûls Mirabelle
Published: April 2023

We develop a novel framework that simultaneously allows recovering heterogeneity in demand, quantity total factor productivity and markups across firms while leaving the correlation between the three dimensions unrestricted. We accomplish this by explicitly introducing demand heterogeneity and systematically exploiting assumptions used in previous productivity estimation approaches. In doing so, we provide an exact decomposition of revenue productivity in terms of the underlying heterogeneities, thus bridging the gap between quantity and revenue productivity estimations. We use Belgian firms’ production data to quantify total factor productivity, demand and markups, and show how they are correlated with each other across time and with measures obtained from other approaches. In doing so, we find quantity total factor productivity and demand to be strongly negatively correlated with each other, so suggesting a trade-off between the quality of a firm’s products and their production cost. We also show how our framework provides deeper and sharper insights on the response of firms to increasing import competition from China. In particular, we find that changes in revenue productivity materialise as the outcome of complex and sometimes offsetting changes in quantity total factor productivity, demand, markups and production scale.
Electrocardiographic markers of subclinical atrial fibrillation detected by implantable loop recorder: insights from the LOOP Study
Authors: Xing Lucas Yixi , Diederichsen Søren Zöga , Højberg Søren , Krieger Derk W , Graff Claus , Olesen Morten S , Nielsen Jonas Bille , Brandes Axel , Køber Lars , Haugan Ketil Jørgen , Svendsen Jesper Hastrup
Published: April 2023

Aims

Insights into subclinical atrial fibrillation (AF) development are warranted to inform the strategies of screening and subsequent clinical management upon AF detection. Hence, this study sought to characterize the onset and progression of subclinical AF with respect to 12-lead electrocardiogram (ECG) parameters.

Methods and results

We included AF-naïve individuals aged 70–90 years with additional stroke risk factors who underwent implantable loop recorder (ILR) monitoring in the LOOP Study. Using data from daily ILR recordings and the computerized analysis of baseline ECG, we studied empirically selected ECG parameters for AF detection (≥6 min), cumulative AF burden, long-lasting AF (≥24 h), and AF progression. Of 1370 individuals included, 419 (30.6%) developed AF during follow-up, with a mean cumulative AF burden of 1.5% [95% CI: 1.2–1.8]. Several P-wave-related and ventricular ECG parameters were associated with new-onset AF and with cumulative AF burden in AF patients. P-wave duration (PWD), P-wave terminal force in Lead V1, and interatrial block (IAB) further demonstrated significant associations with long-lasting AF. Among AF patients, we observed an overall reduction in cumulative AF burden over time (IRR 0.70 [95% CI: 0.51–0.96]), whereas IAB was related to an increased risk of progression to AF ≥24 h (HR 1.86 [95% CI: 1.02–3.39]). Further spline analysis also revealed longer PWD to be associated with this progression in AF duration.

Conclusion

We identified several ECG parameters associated with new-onset subclinical AF detected by ILR. Especially PWD and IAB were robustly related to the onset and the burden of AF as well as progression over time.
Bayesian optimization for demographic inference
Authors: Noskova Ekaterina , Borovitskiy Viacheslav
Published: April 2023

Inference of demographic histories of species and populations is one of the central problems in population genetics. It is usually stated as an optimization problem: find a model’s parameters that maximize a certain log-likelihood. This log-likelihood is often expensive to evaluate in terms of time and hardware resources, critically more so for larger population counts. Although genetic algorithm-based solution has proven efficient for demographic inference in the past, it struggles to deal with log-likelihoods in the setting of more than three populations. Different tools are therefore needed to handle such scenarios. We introduce a new optimization pipeline for demographic inference with time consuming log-likelihood evaluations. It is based on Bayesian optimization, a prominent technique for optimizing expensive black box functions. Comparing to the existing widely used genetic algorithm solution, we demonstrate new pipeline’s superiority in the limited time budget setting with four and five populations, when using the log-likelihoods provided by the moments tool.
Developing an Appropriate Evolutionary Baseline Model for the Study of Human Cytomegalovirus
Authors: Howell Abigail A , Terbot John W , Soni Vivak , Johri Parul , Jensen Jeffrey D , Pfeifer Susanne P
Published: April 2023

Human cytomegalovirus (HCMV) represents a major threat to human health, contributing to both birth defects in neonates as well as organ transplant failure and opportunistic infections in immunocompromised individuals. HCMV exhibits considerable interhost and intrahost diversity, which likely influences the pathogenicity of the virus. Therefore, understanding the relative contributions of various evolutionary forces in shaping patterns of variation is of critical importance both mechanistically and clinically. Herein, we present the individual components of an evolutionary baseline model for HCMV, with a particular focus on congenital infections for the sake of illustration—including mutation and recombination rates, the distribution of fitness effects, infection dynamics, and compartmentalization—and describe the current state of knowledge of each. By building this baseline model, researchers will be able to better describe the range of possible evolutionary scenarios contributing to observed variation as well as improve power and reduce false-positive rates when scanning for adaptive mutations in the HCMV genome.
Four Past Path-Builders Incorporated the Humanities and Arts Into Gerontology’s Scientific Frontiers
Authors: Achenbaum W Andrew
Published: April 2023

Scholars and practitioners in the humanities and arts are collaborating with bio-medico-psycho-social scientists and clinicians in projects that illuminate current understandings of how “aging” processes unfold and what they may mean in creating the future of the Gerontological Society of America. Moving ahead by connecting backwards, we should emulate past path-builders who imagined an interdisciplinary agenda that incorporated humanistic perspectives as they imparted scientific age-based insights to experts and lay audiences. Elie Metchnikoff, G. Stanley Hall, Robert N. Butler, and Gene D. Cohen demonstrated critical humanist thinking about aging and dying in advancing gerontology’s scientific frontiers.
Dynamic rupture simulations based on interseismic locking models—taking the Suoerkuli section of the Altyn Tagh fault as an example
Authors: Gu Yuhao , Zhang Zhenguo , Wang Wenqiang , Wang Zijia
Published: April 2023

For simulating the dynamic rupture process in earthquake scenarios, the stress distribution along the fault remains unclear owing to a lack of direct measurements. Regional stress fields are often resolved onto the fault plane to determine the stress distribution along it. To overcome this limitation, we considered different interseismic locking models to better constrain the actual stress distribution. Specifically, we took the Suoerkuli section in the middle of the Altyn Tagh fault, China, and conducted dynamic rupture simulations to obtain possible earthquake scenarios. The surface rupture length and moment magnitude obtained from the simulations were consistent with those of historical earthquakes. Compared with the traditional stress field resolution method, our approach led to better constrained fault rupture extent and distribution characteristics of regional intensity, thereby avoiding overestimations of earthquake damage. We conclude that examining regional seismic hazards and risks based on seismic dynamic rupture simulations that account for the locking ratio of the fault plane is advantageous, and should be encouraged.