bluuebunny/crossref_metadata_2025 huggingface dataset:
Publishing Romance Fiction in the Philippines
Authors: McAlister Jodi , Parnell Claire , Trinidad Andrea Anne
Published: May 2023

The romance publishing landscape in the Philippines is vast and complex, characterised by entangled industrial players, diverse kinds of texts, and siloed audiences. This Element maps the large, multilayered, and highly productive sector of the Filipino publishing industry. It explores the distinct genre histories of romance fiction in this territory and the social, political and technological contexts that have shaped its development. It also examines the close connections between romance publishing and other media sectors alongside unique reception practices. It takes as a central case study the Filipino romance self-publishing collective #RomanceClass, analysing how they navigate this complex local landscape as well as the broader international marketplace. The majority of scholarship on romance fiction exclusively focuses on the Anglo-American industry. By focusing here on the Philippines, the authors hope to disrupt this phenomenon, and to contribute to a more decentred, rhizomatic approach to understanding this genre world.
Vichy's Double Bind
Authors: Varley Karine
Published: May 2023

Vichy's Double Bind advances a significant new interpretation of French collaboration during the Second World War. Arguing that the path to collaboration involved not merely Nazi Germany but Fascist Italy, it suggests that the Vichy French government was caught in a double bind. On the one hand, many of the threats to France's territory, colonial empire and power came from Rome as well as Berlin. On the other, Vichy was caught between the irreconcilable yet inescapable positions of the two Axis governments. Unable to resolve the conflict, Vichy sought to play the two Axis powers against each other. By exploring French dealings with Italy at diplomatic, military and local levels in France and its colonial empire, this book reveals the multi-dimensional and multi-directional nature of Vichy's policy. It therefore challenges many enduring conceptions of collaboration with reference to Franco-German relations and offers a fresh perspective on debates about Vichy France and collaboration with Nazi Germany and Fascist Italy.
The People of Print
Authors: Stenner Rachel , Kramer Kaley , Smith Adam James , Wilson Georgina E. M. , Saunders Joe , Clayton William , Young Jennifer , Farmer Alan B. , Woodring Benjamin , Durrant Michael , Lima Verônica Calsoni , Johnson Rosalind
Published: May 2023

This collection profiles understudied figures in the book and print trades of the seventeenth century. With an equal balance between women and men, it intervenes in the history of the trades, emphasising the broad range of material, cultural, and ideological work these people undertook. It offers a biographical introduction to each figure, placing them in their social, professional, and institutional settings. The collection considers varied print trade roles including that of the printer, publisher, paper-maker, and bookseller, as well as several specific trade networks and numerous textual forms. The biographies draw on extensive new archival research, with details of key sources for further study on each figure. Chronologically organised, this Element offers a primer both on numerous individual figures, and on the tribulations and innovations of the print trade in the century of revolution.
Snow and avalanche climates in the French Alps using avalanche problem frequencies
Authors: Reuter Benjamin , Hagenmuller Pascal , Eckert Nicolas
Published: May 2023

Avalanches result from an interaction of weather and terrain, where past weather and internal snow cover processes play important roles. So far, climatology was mainly based on weather data, as regional snow instability information, such as avalanche activity, is scarce on climatological time scales. We present a new approach to create a snow avalanche climatology from simulations of avalanche problem types based on snow cover simulations of reanalysis data and a cluster analysis. Analyzing the winters between 1958 and 2020 in the French Alps, wet-snow situations dominated natural release. Dry-snow situations with non-persistent and persistent weak layers occurred each on at least one third of the days. Four typical patterns of avalanche problem types were identified. They follow the main orography with more new snow situations in the northern regions and more cases of persistent weak layers in inner-Alpine regions. In the front-ranges and in southern regions wet-snow situations occurred early in winter – typical for coastal snow climates. Agreement with the standard snow climate classification and the geography of the French Alps suggests that mountain regions with similar conditions can now be outlined. This method for snow avalanche climatology will inform avalanche forecasting and facilitate climate change impact studies.
The DESC stellarator code suite. Part 1. Quick and accurate equilibria computations
Authors: Panici D. , Conlin R. , Dudt D.W. , Unalmis K. , Kolemen E.
Published: May 2023

Three-dimensional equilibrium codes are vital for stellarator design and operation, and high-accuracy equilibria are also necessary for stability studies. This paper details comparisons of two three-dimensional equilibrium codes: VMEC, which uses a steepest-descent algorithm to reach a minimum-energy plasma state, and DESC, which minimizes the magnetohydrodynamic (MHD) force error in real space directly. Accuracy as measured by satisfaction of MHD force balance is presented for each code, along with the computation time. It is shown that DESC is able to achieve more accurate solutions, especially near axis. The importance of higher-accuracy equilibria is shown in DESC's better agreement of stability metrics with asymptotic formulae. DESC's global Fourier–Zernike basis also yields solutions with analytic derivatives explicitly everywhere in the plasma volume, provides improved accuracy in the radial direction versus conventional finite differences and allows for exponential convergence. Further, DESC can compute a solution with the same accuracy as VMEC in order-of-magnitude less time.
Garifuna
Authors: Abtahian Maya , Chaturvedi Manasvi , Greenop Cameron
Published: May 2023

Garifuna (cab, ISO 639-3) is spoken by the Garifuna people (previously known as Black Caribs and currently also by the plural Garinagu – Cayetano 1993), who reside along the Caribbean coast of Central America in communities in Belize, Honduras, Guatemala and Nicaragua, as well as in a large immigrant population in the United States. Population estimates in the literature for Garifuna speakers worldwide vary widely, but Aikhenvald (1999: 72) estimated between 30 and 100,000 speakers of the language. The latest census in Belize reports a population of 19,639 people who report at least one of their ethnicities as Garifuna and 8,442 people who report speaking Garifuna well enough to hold a conversation (Statistical Institute of Belize 2010 census).
A HTA of what? Reframing through including patient perspectives in health technology assessment processes
Authors: Gunn Callum J. , Regeer Barbara J. , Zuiderent-Jerak Teun
Published: May 2023

Objectives

Despite increasing emphasis on the inclusion of patient input in health technology assessment (HTA) in Europe in particular, questions remain as to the integration of patient insight alongside other HTA inputs. This paper aims to explore how HTA processes, while ensuring the scientific quality of assessments, “make do” with patient knowledge elicited through patients’ involvement mechanisms.

Methods

The qualitative study analyzed institutional HTA and patient involvement in four European country contexts. We combined documentary analysis with interviews with HTA professionals, patient organizations, and health technology industry representatives, complemented with observational findings made during a research stay at an HTA agency.

Results

We present three vignettes which showcase how different parameters of assessment become reframed upon the positioning of patient knowledge alongside other forms of evidence and expertise. Each vignette explores patients’ involvement during an assessment of a different type of technology and at a different stage of the HTA process. First, cost-effectiveness considerations were reframed during an appraisal of a rare disease medicine based on patient and clinician input regarding its treatment pathway; in the second vignette reframing amounted to what counts as a meaningful outcome measure for a glucose monitoring device; in the third, evaluating pediatric transplantation services involved reframing an option’s appropriateness from a question of moral to one of legal acceptability.

Conclusions

Making do with patient knowledge in HTA involves reframing of what is being assessed. Conceptualizing patients’ involvement in this way helps us to consider the inclusion of patient knowledge not as complementary to, but as something that can transform the assessment process.
Quantitative phase analysis of commercial ammonium phosphates by PXRD for application in biological systems
Authors: Ferreira Fabio F. , Pereira Aline P. C. , Reis Ianny B. , Sasaki Bianca R. S. , Fávaro Wagner J. , Durán Nelson
Published: May 2023

Although being an old concern, phosphate analysis is still a tremendous challenge. While many different experimental techniques are found in the literature, very few use powder X-ray diffraction (PXRD) patterns for quantitative phase analysis of different phosphate types. Our measurements performed in four commercial samples of diammonium hydrogen phosphate ((NH4)2HPO4) (DAP) show the existence of phosphate contamination mixtures, such as ammonium dihydrogen phosphate (NH4H2PO4) (ADP). The larger the amount of ADP, the larger the microstrain induced in the DAP phase, which impacts both the aggregation of the nanoparticles in solution and the final anticancer activity of the nanostructure. This study shows that PXRD is an excellent technique for quantitative phase analysis to determine the presence and amount of phosphate contamination in diammonium hydrogen phosphate samples.
Genetic and epidemiological analyses of infection load and its relationship with psychiatric disorders
Authors: Nudel Ron , Hougaard David M. , Werge Thomas , Benros Michael E.
Published: May 2023

Severe infections and psychiatric disorders have a large impact on both society and the individual. Studies investigating these conditions and the links between them are therefore important. Most past studies have focused on binary phenotypes of particular infections or overall infection, thereby losing some information regarding susceptibility to infection as reflected in the number of specific infection types, or sites, which we term infection load. In this study we found that infection load was associated with increased risk for attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, depression, schizophrenia and overall psychiatric diagnosis. We obtained a modest but significant heritability for infection load (h2 = 0.0221), and a high degree of genetic correlation between it and overall psychiatric diagnosis (rg = 0.4298). We also found evidence supporting a genetic causality for overall infection on overall psychiatric diagnosis. Our genome-wide association study for infection load identified 138 suggestive associations. Our study provides further evidence for genetic links between susceptibility to infection and psychiatric disorders, and suggests that a higher infection load may have a cumulative association with psychiatric disorders, beyond what has been described for individual infections.
Caregiver and provider attitudes toward family-centred rounding in paediatric acute care cardiology
Authors: Gal Dana B. , Rodts Megan , Hills Brittney K. , Kipps Alaina K. , Char Danton S. , Pater Colleen , Madsen Nicolas L.
Published: May 2023

Family-centered rounding has emerged as the gold standard for inpatient paediatrics rounds due to its association with improved family and staff satisfaction and reduction of harmful errors. Little is known about family-centered rounding in subspecialty paediatric settings, including paediatric acute care cardiology.

In this qualitative, single centre study, we conducted semi-structured interviews with providers and caregivers eliciting their attitudes toward family-centered rounding. An a priori recruitment approach was used to optimise diversity in reflected opinions. A brief demographic survey was completed by participants. We completed thematic analysis of transcribed interviews using grounded theory.

In total, 38 interviews representing the views of 48 individuals (11 providers, 37 caregivers) were completed. Three themes emerged: rounds as a moment of mutual accountability, caregivers’ empathy for providers, and providers’ objections to family-centered rounding. Providers’ objections were further categorised into themes of assumptions about caregivers, caregiver choices during rounds, and risk for exacerbation of bias and inequity.

Caregivers and providers in the paediatric acute care cardiology setting echoed some previously described attitudes toward family-centered rounding. Many of the challenges surrounding family-centered rounding might be addressed through access to training for caregivers and providers alike. Hospitals should invest in systems to facilitate family-centered rounding if they choose to implement this model of care as the current state risks erosion of provider–caregiver relationship.
How Philosophy Can Support Community-Led Change: Reflections from Bristol Campaigns for Racial Justice
Authors: Burch-Brown Joanna
Published: May 2023

How can philosophy expand to be a discipline via which young people from diverse backgrounds feel they can make a direct and positive contribution to their communities? In this chapter I suggest some creative methods by which philosophers can support community-led change. Collaborators and I have been developing the approaches described here through work on issues of racial justice, but they can be applied to campaigns or public debate on any topic. Developing more community-led, socially engaged methods has the potential to make philosophy a more attractive discipline for young people from diverse backgrounds who are keen to use their skills to make a positive difference to their communities.
Saving Chinese laborers from Sinophobia: Sino-Korean, born-translated literature
Authors: Han Inhye
Published: May 2023

This article examines the work of Korean writer Chu Yosŏp, originally written in Korean taking the guise of a Korean translation of a Chinese-language story (born-translated literature). Chu's audience was steeped in Sinophobia orchestrated by the colonizing Japanese empire. His unprecedented genre recounts the lesser-known, lived experiences of the Chinese lower class that Korean-language news media failed to report. My analysis of Chu's work demonstrates, first, that the feigned Chinese voices of this genre illuminate transnational Sino-Korean affinities that were forcibly suppressed by colonial policies and discourses. Second, born-translated literature upends and reconfigures the colonial structure of surrogate feeling, in which the colonized emote in the service of the colonizer. Third, Chu's aesthetic strategy of deconstructing colonial affect attends to and redirects evershifting cultural processes, rather than tackling discrete entities, to surmount the active–passive divide. In so doing, his literature seeks to refashion a politico-aesthetic ecosystem encompassing the Sino-Korean clash, rather than confounding specific ideologies. Finally, the aesthetic for the lower-class Chinese people in Chu's born-translated stories is predicated on metaphysical ethics in which antithetical others mutate into inviolable others, and in which the practice of saving others dovetails with transforming ourselves.
The co-occurrence and cumulative prevalence of hypertension, rheumatoid arthritis, and hypothyroidism in preterm-born women in the Women’s Health Initiative
Authors: Brewer Pamela L. , D’Agata Amy L. , Roberts Mary B. , Saquib Nazmus , Schnatz Peter F. , Manson JoAnn , Eaton Charles B. , Sullivan Mary C.
Published: May 2023

Emerging evidence suggests that preterm-born individuals (<37 weeks gestation) are at increased risk of developing chronic health conditions in adulthood. This study compared the prevalence, co-occurrence, and cumulative prevalence of three female predominant chronic health conditions – hypertension, rheumatoid arthritis [RA], and hypothyroidism – alone and concurrently. Of 82,514 U.S. women aged 50–79 years enrolled in the Women’s Health Initiative, 2,303 self-reported being born preterm. Logistic regression was used to analyze the prevalence of each condition at enrollment with birth status (preterm, full term). Multinomial logistic regression models analyzed the association between birth status and each condition alone and concurrently. Outcome variables using the 3 conditions were created to give 8 categories ranging from no disease, each condition alone, two-way combinations, to having all three conditions. The models adjusted for age, race/ethnicity, and sociodemographic, lifestyle, and other health-related risk factors. Women born preterm were significantly more likely to have any one or a combination of the selected conditions. In fully adjusted models for individual conditions, the adjusted odds ratios (aORs) were 1.14 (95% CI, 1.04, 1.26) for hypertension, 1.28 (1.12, 1.47) for RA, and 1.12 (1.01, 1.24) for hypothyroidism. Hypothyroidism and RA were the strongest coexisting conditions [aOR 1.69, 95% CI (1.14, 2.51)], followed by hypertension and RA [aOR 1.48, 95% CI (1.20, 1.82)]. The aOR for all three conditions was 1.69 (1.22, 2.35). Perinatal history is pertinent across the life course. Preventive measures and early identification of risk factors and disease in preterm-born individuals are essential to mitigating adverse health outcomes in adulthood.
Tracking the Transition From a Gondwana LIP to the South Atlantic Ocean With Geochronological and Geochemical Indicators
Authors: Carvas K. Z. , Marques L. S. , Vasconcelos P. M. , Ubide T.
Published: May 2023

Evidence of early oceanization during transition from large igneous provinces (LIPs) to new ocean crust is mostly missing in the geological record. Mafic dykes geochemically akin to mid‐ocean ridge basalts (MORBs) occur in late stages of LIPs, but their tectonic role during margin evolution remains poorly constrained. Here we use whole‐rock and high‐resolution clinopyroxene chemistry of two distinct types of mafic dykes from the southeastern Brazilian margin to show that a MORB‐like plumbing system became magmatically active in the central South Atlantic ∼2 Ma after the volcanic peak of the Paraná‐Etendeka Magmatic Province. The LIP basaltic dyke compositions resulted from the mixing between a highly metasomatized lithospheric mantle comprising enriched DMM and Archean contributions. The lack of elemental oscillatory zoning in clinopyroxene crystals suggests that they were produced by a single magma pulse, consistent with the strong magma fluxes in LIPs. In contrast, the MORB‐like dykes, which exhibit strong similarities with South Atlantic MORBs, are interpreted to represent early stages of oceanization deriving from the mixing of enriched asthenospheric melts either with ancient SCLM contributions or small crustal assimilation. The MORB‐like intrusions ascended and cooled rapidly along faults and were fed by numerous magma injections that suggest episodic decompression of the asthenospheric source ∼20 Ma before the birth of central South Atlantic. The combination of subduction‐influenced and MORB‐like dykes is recurrent in ancient and modern rifts globally, suggesting that thinned lithospheric blocks affected by ancient subduction events may become more susceptible to early oceanization in rifted margins.
Uncertainty and Emergent Constraints on Enhanced Ecosystem Carbon Stock by Land Greening
Authors: Bian Chenyu , Xia Jianyang , Zhang Xuanze , Huang Kun , Cui Erqian , Zhou Jian , Wei Ning , Wang Ying‐Ping , Lombardozzi Danica , Goll Daniel S. , Knauer Jürgen , Arora Vivek , Yuan Wenping , Sitch Stephen , Friedlingstein Pierre , Luo Yiqi
Published: May 2023

Significant land greening since the 1980s has been detected through satellite observation, forest inventory, and Earth system modeling. However, whether and to what extent global land greening enhances ecosystem carbon stock remains uncertain. Here, using 40 global models, we first detected a positive correlation between the terrestrial ecosystem carbon stock and leaf area index (LAI) over time. Then, we diagnose the source of uncertainty of simulated the sensitivities of ecosystem carbon stock to LAI based on a traceability analysis. We found that the sensitivity of gross primary productivity (GPP) to LAI is the largest contributor to the model uncertainty in more than 60% of the vegetated grids. Using the ensemble of four long‐term global data sets of GPP and three satellite LAI products from 1982 to 2014, we provided an emergent constraint on the ecosystem carbon stock increase as 0.75 ± 0.46 kg C m−2 per unit LAI over global land areas. Furthermore, the biome‐based results reveal that the tropical forest regions have the highest inter‐model variation and model bias. Overall, this study identifies the uncertainty source and provides constrained estimates of the greening effect on ecosystem carbon stock at the global scale.
Transient Shoaling, Over‐Deepening and Settling of the Calcite Compensation Depth at the Eocene‐Oligocene Transition
Authors: Taylor V. E. , Westerhold T. , Bohaty S. M. , Backman J. , Dunkley Jones T. , Edgar K. M. , Egan K. E. , Lyle M. , Pälike H. , Röhl U. , Zachos J. , Wilson P. A.
Published: May 2023

The major Cenozoic shift from a shallow (∼3–4 km) to deep (∼4.5 km) calcite compensation depth (CCD) occurred at the Eocene‐Oligocene Transition (∼34 Ma), suggesting a strong relationship between calcium carbonate (CaCO3) cycling and Antarctic glaciation. However, the linkages between these two events are debated. Here we present new records of bulk sediment stable isotope and carbonate composition from a depth transect of sites in the low‐latitude Pacific Ocean and one site from the South Atlantic Ocean, together with a new benthic foraminiferal stable isotope record (δ13Cb and δ18Ob) from the Pacific where the sedimentary sequence is most expanded. Our records reveal a short‐lived (∼300 Kyr) CCD shoaling event closely associated with a negative carbon isotope excursion in the latest Eocene. This event is immediately followed by CCD deepening which occurs in two rapid (∼40 Kyr‐long) steps. Our data show that the first of these deepening steps represents recovery from the latest Eocene shoaling event while the second was closely associated with a rapid increase in δ18Ob and shows a distinctive over‐deepening and settling pattern to >5 and 4.4 km, respectively. These results, together with good agreement between Pacific and South Atlantic records, strongly suggest that the carbon cycle was perturbed globally shortly before the inception of Antarctic glaciation. Once large‐scale Antarctic glaciation was initiated, rapid further change in global seawater chemistry triggered transitory deep ocean carbonate burial fluxes far exceeding their early Oligocene steady state values.
Multi-ancestry meta-analysis and fine-mapping in Alzheimer’s disease
Authors: Lake Julie , Warly Solsberg Caroline , Kim Jonggeol Jeffrey , Acosta-Uribe Juliana , Makarious Mary B. , Li Zizheng , Levine Kristin , Heutink Peter , Alvarado Chelsea X. , Vitale Dan , Kang Sarang , Gim Jungsoo , Lee Kun Ho , Pina-Escudero Stefanie D. , Ferrucci Luigi , Singleton Andrew B. , Blauwendraat Cornelis , Nalls Mike A. , Yokoyama Jennifer S. , Leonard Hampton L.
Published: May 2023

Genome-wide association studies (GWAS) of Alzheimer’s disease are predominantly carried out in European ancestry individuals despite the known variation in genetic architecture and disease prevalence across global populations. We leveraged published GWAS summary statistics from European, East Asian, and African American populations, and an additional GWAS from a Caribbean Hispanic population using previously reported genotype data to perform the largest multi-ancestry GWAS meta-analysis of Alzheimer’s disease and related dementias to date. This method allowed us to identify two independent novel disease-associated loci on chromosome 3. We also leveraged diverse haplotype structures to fine-map nine loci with a posterior probability >0.8 and globally assessed the heterogeneity of known risk factors across populations. Additionally, we compared the generalizability of multi-ancestry- and single-ancestry-derived polygenic risk scores in a three-way admixed Colombian population. Our findings highlight the importance of multi-ancestry representation in uncovering and understanding putative factors that contribute to risk of Alzheimer’s disease and related dementias.
Lipid profile after omega-3 supplementation in neonates with intrauterine growth retardation: a randomized controlled trial
Authors: Elsheikh Mai , El Amrousy Doaa , El-Mahdy Heba , Dawoud Heba , Harkan Ahmed , El-Barky Amany
Published: May 2023

Background

Neonates with intrauterine growth restriction (IUGR) have a high lipid profile that predisposes them to cardiovascular disease later in life. We aimed to evaluate the effect of omega 3 supplementation on serum leptin level, lipid profile, and growth in neonates with IUGR.

Methods

This clinical trial was conducted on 70 full-term neonates with IUGR. Neonates were randomly divided into two equal groups; the treatment group: received omega 3 supplement (40 mg/kg/day) for 2 weeks after the establishment of full feeding, and the control group, who were followed up to full feeding without any supplementation. Serum leptin level, total cholesterol (TC), high-density lipoprotein (HDL), triglycerides (TG), low-density lipoprotein (LDL), and anthropometric measurement were evaluated at admission and after 2 weeks of omega 3 supplementation in both groups.

Results

After treatment, HDL significantly increased, unlike TC, TG, LDL, LDL, and serum leptin levels, which significantly decreased in the treatment group compared to the control group after treatment. Interestingly, weight, length, and ponderal index greatly increased in omega 3-treated neonates compared to the control group.

Conclusion

Omega 3 supplementations lowered serum leptin level, TG, TC, LDL, and VLDL but increased HDL and growth in neonates with IUGR.

Clinical trial registration

The study was registered at clinicaltrials.gov (NCT05242107).

Impact

Neonates with intrauterine growth retardation (IUGR) were reported to have a high lipid profile that predisposes them to cardiovascular disease later in life. Leptin is a hormone that adjusts dietary intake and body mass and has a significant role in fetal development. Omega 3 is known to be essential for neonatal growth and brain development.

We aimed to evaluate the effect of omega 3 supplementation on serum leptin level, lipid profile, and growth in neonates with IUGR.

We found that omega 3 supplementations lowered serum leptin level and serum lipid profile but increased high density lipoprotein and growth in neonates with IUGR.
Initial evidence regarding the neurobiological basis of psychological symptoms in dementia caregivers
Authors: Smagula Stephen F. , Aizenstein Howard J.
Published: May 2023

Mood symptoms and disorders are common in dementia caregivers, who can be exposed to a myriad of potential stressors including their care recipient’s neuropsychiatric symptoms. Existing evidence indicates that the effects of potentially stressful exposures on mental health depend on the caregiver’s individual characteristics and responses. Specifically, prior studies indicate that risk factors measured on psychological (e.g., emotion-focused/behaviorally disengaged coping responses) and behavioral (e.g., sleep and activity restriction) levels of analysis may confer the effects of caregiving exposures on mental health. Theoretically, this process from caregiving stressors and other risk factors to mood symptoms is neurobiologically mediated. This article reviews recent studies that used brain imaging to identify neurobiological factors that are related to psychological outcomes in caregivers. Available observational data indicate that psychological outcomes in caregivers are related to differences in the structure/function of regions involved in socio-affective information processing (prefrontal), autobiographical memory (the posterior cingulate), and stress (amygdala). In addition, two small randomized controlled trials using repeated brain imaging showed that Mentalizing Imagery Therapy (a mindfulness program) increased prefrontal network connectivity and reduced mood symptoms. These studies raise the possibility that, in the future, brain imaging may be useful to detect the neurobiological basis of a given caregiver’s mood vulnerability and guide the selection of interventions that are known to modify it. However, there remains a need for evidence on whether brain imaging improves on simpler/inexpensive measurement modalities like self-report for identifying vulnerable caregivers and matching them with efficacious interventions. In addition, to target interventions, more evidence is needed regarding the effects that both risk factors and interventions have on mood neurobiology (e.g., how persistent emotion-focused coping, sleep disruption, and mindfulness affect brain function).
Tunnelling nanotubes between neuronal and microglial cells allow bi-directional transfer of α-Synuclein and mitochondria
Authors: Chakraborty Ranabir , Nonaka Takashi , Hasegawa Masato , Zurzolo Chiara
Published: May 2023

Tunnelling Nanotubes (TNTs) facilitate contact-mediated intercellular communication over long distances. Material transfer via TNTs can range from ions and intracellular organelles to protein aggregates and pathogens. Prion-like toxic protein aggregates accumulating in several neurodegenerative pathologies, such as Alzheimer’s, Parkinson’s, and Huntington’s diseases, have been shown to spread via TNTs not only between neurons, but also between neurons-astrocytes, and neurons-pericytes, indicating the importance of TNTs in mediating neuron–glia interactions. TNT-like structures were also reported between microglia, however, their roles in neuron-microglia interaction remain elusive. In this work, we quantitatively characterise microglial TNTs and their cytoskeletal composition, and demonstrate that TNTs form between human neuronal and microglial cells. We show thatα-Synuclein (α-Syn) aggregates increase the global TNT-mediated connectivity between cells, along with the number of TNT connections per cell pair. Homotypic TNTs formed between microglial cells, and heterotypic TNTs between neuronal and microglial cells are furthermore shown to be functional, allowing movement of bothα-Syn and mitochondria. Quantitative analysis shows thatα-Syn aggregates are transferred predominantly from neuronal to microglial cells, possibly as a mechanism to relieve the burden of accumulated aggregates. By contrast, microglia transfer mitochondria preferably toα-Syn burdened neuronal cells over the healthy ones, likely as a potential rescue mechanism. Besides describing novel TNT-mediated communication between neuronal and microglial cells, this work allows us to better understand the cellular mechanisms of spreading neurodegenerative diseases, shedding light on the role of microglia.
TIM-3 increases the abundance of type-2 dendritic cells during Leishmania donovani infection by enhancing IL-10 production via STAT3
Authors: Mishra Manish , Yadav Manisha , Kumar Sandeep , Kumar Raj , Sen Pradip
Published: May 2023

The outcome of the disease visceral leishmaniasis (VL), caused by Leishmania donovani (LD), largely relies on the relative dominance of host-protective type-1 T helper (Th1) cell response versus disease-promoting type-2 T helper (Th2) cell response. The Th1 and Th2 responses, in turn, are believed to be elicited by type-1 conventional dendritic cells (cDC1) and type-2 conventional DCs (cDC2), respectively. However, it is still unknown which DC subtype (cDC1 or cDC2) predominates during chronic LD infection and the molecular mechanism governing such occurrence. Here we report that in chronically infected mice, the splenic cDC1-cDC2 balance shifted toward the cDC2 subtype and that the receptor T cell immunoglobulin and mucin protein-3 (TIM-3) expressed by DCs played a key role in mediating this effect. Transfer of TIM-3-silenced DCs in fact prevented the predominance of the cDC2 subtype in mice with chronic LD infection. We also found that LD actually upregulated TIM-3 expression on DCs by triggering a TIM-3-mediated signaling pathway STAT3 (signal transducer and activator of transcription 3)→interleukin (IL)-10→c-Src→transcription factors Ets1, Ets2, USF1, and USF2. Notably, TIM-3 promoted STAT3 activation via a non-receptor tyrosine kinase Btk. Adoptive transfer experiments further demonstrated a critical role for STAT3-driven TIM-3 upregulation on DCs in increasing cDC2 abundance in chronically infected mice, which ultimately aided disease pathogenesis by augmenting Th2 responses. These findings document a new immunoregulatory mechanism contributing to disease pathology during LD infection and define TIM-3 as a key mediator of this process.
Butyrate limits inflammatory macrophage niche in NASH
Authors: Sarkar Ankita , Mitra Priya , Lahiri Abhishake , Das Tanusree , Sarkar Jit , Paul Sandip , Chakrabarti Partha
Published: May 2023

Immune cell infiltrations with lobular inflammation in the background of steatosis and deregulated gut-liver axis are the cardinal features of non-alcoholic steatohepatitis (NASH). An array of gut microbiota-derived metabolites including short-chain fatty acids (SCFA) multifariously modulates NASH pathogenesis. However, the molecular basis for the favorable impact of sodium butyrate (NaBu), a gut microbiota-derived SCFA, on the immunometabolic homeostasis in NASH remains elusive. We show that NaBu imparts a robust anti-inflammatory effect in lipopolysaccharide (LPS) stimulated or classically activated M1 polarized macrophages and in the diet-induced murine NASH model. Moreover, it impedes monocyte-derived inflammatory macrophage recruitment in liver parenchyma and induces apoptosis of proinflammatory liver macrophages (LM) in NASH livers. Mechanistically, by histone deactylase (HDAC) inhibition NaBu enhanced acetylation of canonical NF-κB subunit p65 along with its differential recruitment to the proinflammatory gene promoters independent of its nuclear translocation. NaBu-treated macrophages thus exhibit transcriptomic signatures that corroborate with a M2-like prohealing phenotype. NaBu quelled LPS-mediated catabolism and phagocytosis of macrophages, exhibited a differential secretome which consequently resulted in skewing toward prohealing phenotype and induced death of proinflammatory macrophages to abrogate metaflammation in vitro and in vivo. Thus NaBu could be a potential therapeutic as well as preventive agent in mitigating NASH.
Single cell transcriptomics clarifies the basophil differentiation trajectory and identifies pre-basophils upstream of mature basophils
Authors: Miyake Kensuke , Ito Junya , Nakabayashi Jun , Shichino Shigeyuki , Ishiwata Kenji , Karasuyama Hajime
Published: May 2023

Basophils are the rarest granulocytes and are recognized as critical cells for type 2 immune responses. However, their differentiation pathway remains to be fully elucidated. Here, we assess the ontogenetic trajectory of basophils by single-cell RNA sequence analysis. Combined with flow cytometric and functional analyses, we identify c-Kit-CLEC12Ahi pre-basophils located downstream of pre-basophil and mast cell progenitors (pre-BMPs) and upstream of CLEC12Alo mature basophils. The transcriptomic analysis predicts that the pre-basophil population includes previously-defined basophil progenitor (BaP)-like cells in terms of gene expression profile. Pre-basophils are highly proliferative and respond better to non-IgE stimuli but less to antigen plus IgE stimulation than do mature basophils. Although pre-basophils usually remain in the bone marrow, they emerge in helminth-infected tissues, probably through IL-3-mediated inhibition of their retention in the bone marrow. Thus, the present study identifies pre-basophils that bridge the gap between pre-BMPs and mature basophils during basophil ontogeny.
Acidic CO2-to-HCOOH electrolysis with industrial-level current on phase engineered tin sulfide
Authors: Shen Haifeng , Jin Huanyu , Li Haobo , Wang Herui , Duan Jingjing , Jiao Yan , Qiao Shi-Zhang
Published: May 2023

Acidic CO2-to-HCOOH electrolysis represents a sustainable route for value-added CO2 transformations. However, competing hydrogen evolution reaction (HER) in acid remains a great challenge for selective CO2-to-HCOOH production, especially in industrial-level current densities. Main group metal sulfides derived S-doped metals have demonstrated enhanced CO2-to-HCOOH selectivity in alkaline and neutral media by suppressing HER and tuning CO2 reduction intermediates. Yet stabilizing these derived sulfur dopants on metal surfaces at large reductive potentials for industrial-level HCOOH production is still challenging in acidic medium. Herein, we report a phase-engineered tin sulfide pre-catalyst (π-SnS) with uniform rhombic dodecahedron structure that can derive metallic Sn catalyst with stabilized sulfur dopants for selective acidic CO2-to-HCOOH electrolysis at industrial-level current densities. In situ characterizations and theoretical calculations reveal the π-SnS has stronger intrinsic Sn-S binding strength than the conventional phase, facilitating the stabilization of residual sulfur species in the Sn subsurface. These dopants effectively modulate the CO2RR intermediates coverage in acidic medium by enhancing *OCHO intermediate adsorption and weakening *H binding. As a result, the derived catalyst (Sn(S)-H) demonstrates significantly high Faradaic efficiency (92.15 %) and carbon efficiency (36.43 %) to HCOOH at industrial current densities (up to −1 A cm−2) in acidic medium.
PI16+ reticular cells in human palatine tonsils govern T cell activity in distinct subepithelial niches
Authors: De Martin Angelina , Stanossek Yves , Lütge Mechthild , Cadosch Nadine , Onder Lucas , Cheng Hung-Wei , Brandstadter Joshua D. , Maillard Ivan , Stoeckli Sandro J. , Pikor Natalia B. , Ludewig Burkhard
Published: May 2023

Fibroblastic reticular cells (FRCs) direct the interaction and activation of immune cells in discrete microenvironments of lymphoid organs. Despite their important role in steering innate and adaptive immunity, the age- and inflammation-associated changes in the molecular identity and functional properties of human FRCs have remained largely unknown. Here, we show that human tonsillar FRCs undergo dynamic reprogramming during life and respond vigorously to inflammatory perturbation in comparison to other stromal cell types. The peptidase inhibitor 16 (PI16)-expressing reticular cell (PI16+ RC) subset of adult tonsils exhibited the strongest inflammation-associated structural remodeling. Interactome analysis combined with ex vivo and in vitro validation revealed that T cell activity within subepithelial niches is controlled by distinct molecular pathways during PI16+ RC–lymphocyte interaction. In sum, the topological and molecular definition of the human tonsillar stromal cell landscape reveals PI16+ RCs as a specialized FRC niche at the core of mucosal immune responses in the oropharynx.
A motor association area in the depths of the central sulcus
Authors: Jensen Michael A. , Huang Harvey , Valencia Gabriela Ojeda , Klassen Bryan T. , van den Boom Max A. , Kaufmann Timothy J. , Schalk Gerwin , Brunner Peter , Worrell Gregory A. , Hermes Dora , Miller Kai J.
Published: May 2023

Cells in the precentral gyrus directly send signals to the periphery to generate movement and are principally organized as a topological map of the body. We find that movement-induced electrophysiological responses from depth electrodes extend this map three-dimensionally throughout the gyrus. Unexpectedly, this organization is interrupted by a previously undescribed motor association area in the depths of the midlateral aspect of the central sulcus. This ‘Rolandic motor association’ (RMA) area is active during movements of different body parts from both sides of the body and may be important for coordinating complex behaviors.
Organic geochemical evidence of human-controlled fires at Acheulean site of Valdocarros II (Spain, 245 kya)
Authors: Stancampiano Lavinia M. , Rubio-Jara Susana , Panera Joaquín , Uribelarrea David , Pérez-González Alfredo , Magill Clayton R.
Published: May 2023

Among the outstanding questions about the emergence of human-controlled fire is the systematic recurrence between the geochemical remains of fire and its preservation in the archaeological record, as the use of fire is considered a technological landmark, especially for its importance in food cooking, defensive strategies, and heating. Here we report fossil lipid biomarkers associated with incomplete combustion of organic matter at the Valdocarros II site, one of the largest European Acheulean sites in Spain dated to marine isotopic stage (MIS) 8/7 (~ 245 kya) allowing a multiproxy analysis of human-controlled fire use. Our results reveal isolated cases of highly concentrated and diverse polycyclic aromatic hydrocarbons (PAHs) and alkylated PAHs (APAHs), along with diagnostic conifer-derived triterpenoids in two hearth-like archaeological structures. The presence of combustion byproducts suggests the presence of anthropogenic (controlled) fires at Valdocarros—one of the oldest evidence of fire use in Europe-in association with Acheulean tools and bones. Hominins possibly used fire for two main activities, as a means of defense against predators and cooking. Our results help to better delineate major gaps in our current knowledge of human-controlled fire in the context of the Middle-Pleistocene in Europe and suggest that human ancestors were able to control fire before at least 250 kya.
Applying appropriate frequency criteria to advance acoustic behavioural guidance systems for fish
Authors: Holgate A. , White P. R. , Leighton T. G. , Kemp P. S.
Published: May 2023

Deterrents that use acoustics to guide fish away from dangerous areas depend on the elicitation of avoidance in the target species. Acoustic deterrents select the optimum frequency based on an assumption that highest avoidance is likely to occur at the greatest sensitivity. However, such an assumption may be unfounded. Using goldfish (Carassius auratus) as a suitable experimental model, this study tested this as a null hypothesis. Under laboratory conditions, the deterrence thresholds of individual goldfish exposed to 120 ms tones at six frequencies (250–2000 Hz) and four Sound Pressure Levels (SPL 115–145 dB) were quantified. The deterrence threshold defined as the SPL at which 25% of the tested population startled was calculated and compared to the hearing threshold obtained using Auditory Evoked Potential and particle acceleration threshold data. The optimum frequency to elicit a startle response was 250 Hz; different from the published hearing and particle acceleration sensitivities based on audiograms. The difference between the deterrence threshold and published hearing threshold data varied from 47.1 dB at 250 Hz to 76 dB at 600 Hz. This study demonstrates that information obtained from audiograms may poorly predict the most suitable frequencies at which avoidance behaviours are elicited in fish.
Geomorphological assessment of the preservation of archaeological tell sites
Authors: Forti Luca , Brandolini Filippo , Oselini Valentina , Peyronel Luca , Pezzotta Andrea , Vacca Agnese , Zerboni Andrea
Published: May 2023

Tells are multi-layered, archaeological mounds representing anthropogenic landforms common in arid regions. In such contexts, the preservation of the archaeological record is mined by ongoing climate changes, shift in land use, and intense human overgrazing. Such natural and human-driven factors tune the response of archaeological soils and sediments to erosion. Geomorphology offers a plethora of tools for mapping natural and anthropogenic landforms and evaluating their response to unremitting weathering, erosional and depositional processes. Here, we present a geomorphological investigation on two anthropogenic mounds in the Kurdistan Region of Iraq, with a special focus on the ongoing erosional processes mining their slope stability and threatening the preservation of the local archaeological landscape. Applying the revised universal soil loss equation model for soil loess derived from UAV imagery and implemented with geoarchaeological investigation, we assess the erosion rate along anthropogenic mounds and estimate the risk of losing archaeological deposits. We argue that a large-scale application of our approach in arid and semi-arid regions may improve our ability to (i) estimate the rate of soil and/or archaeological sediments loss, (ii) propose mitigation strategies to prevent the dismantling of the archaeological record, and (iii) schedule archaeological operations in areas of moderate to extreme erosion risk.
An organ-on-chip device with integrated charge sensors and recording microelectrodes
Authors: Aydogmus Hande , Hu Michel , Ivancevic Lovro , Frimat Jean-Philippe , van den Maagdenberg Arn M. J. M. , Sarro Pasqualina M. , Mastrangeli Massimo
Published: May 2023

Continuous monitoring of tissue microphysiology is a key enabling feature of the organ-on-chip (OoC) approach for in vitro drug screening and disease modeling. Integrated sensing units are particularly convenient for microenvironmental monitoring. However, sensitive in vitro and real-time measurements are challenging due to the inherently small size of OoC devices, the characteristics of commonly used materials, and external hardware setups required to support the sensing units. Here we propose a silicon-polymer hybrid OoC device that encompasses transparency and biocompatibility of polymers at the sensing area, and has the inherently superior electrical characteristics and ability to house active electronics of silicon. This multi-modal device includes two sensing units. The first unit consists of a floating-gate field-effect transistor (FG-FET), which is used to monitor changes in pH in the sensing area. The threshold voltage of the FG-FET is regulated by a capacitively-coupled gate and by the changes in charge concentration in close proximity to the extension of the floating gate, which functions as the sensing electrode. The second unit uses the extension of the FG as microelectrode, in order to monitor the action potential of electrically active cells. The layout of the chip and its packaging are compatible with multi-electrode array measurement setups, which are commonly used in electrophysiology labs. The multi-functional sensing is demonstrated by monitoring the growth of induced pluripotent stem cell-derived cortical neurons. Our multi-modal sensor is a milestone in combined monitoring of different, physiologically-relevant parameters on the same device for future OoC platforms.