bluuebunny/crossref_metadata_2025 huggingface dataset:
Becoming with Toxicity: Chemical Epigenetics as “Racializing and Sexualizing Assemblage”
Authors: Packer Melina
Published: January 2022

In this article I think through Black feminism and queer theory to critically analyze toxicology. I focus on toxicology's conception of endocrine-disrupting chemicals (EDCs), a class of toxicants that can cause epigenetic changes leading to inheritable health issues. I suggest that Black feminist interventions are particularly necessary for the study of toxicants because multiply marginalized populations are disproportionately more exposed to EDCs. The structural preconditions that generate this uneven, racialized, and sexualized toxic body-burden threaten to turn cultural constructions of race and sex (epistemologies) into biological realities (ontologies). My discursive analysis of key scientific texts on toxicology, EDCs, and epigenetics underscores how Eurocentric biases and eugenic logics permeate and co-constitute biochemical matter. I further argue that these texts’ un/articulated norms regarding the human, sexual behavior, and evolutionary fitness undermine the usefulness of toxicological assessments for environmental justice. I close by urging scientist scholar-activists to reconceive the study of toxicants. A Black feminist approach to toxicity, I suggest, would not only situate chemical exposures in their sociopolitical contexts, but also radically revision what it means to be human.
Medieval Irish medical verse in the nineteenth century: some evidence from material culture
Authors: Hayden Deborah
Published: January 2022

This article presents an edition and translation of an Irish didactic poem found in a large compilation of remedies, charms and prayers that was written in the early sixteenth century by the Roscommon medical scribe Conla Mac an Leagha. The contents of this poem, and of the treatise in which it occurs more generally, are of inherent interest for our understanding of the history of medical learning in medieval Ireland. However, the poem is also of particular significance due to the fact that its penultimate stanza, which invokes the authority of one ‘Colmán mac Oililla’, is attested in two much later sources that provide insight into the transmission and reception of medieval Irish medical texts in the early nineteenth century, as well as into the relationship between manuscript, print and material culture during that period. The two sources in question, one of which is a previously unprovenanced signboard now kept in the Wellcome Collection in London, can both be connected with the work of the Munster ‘herb doctor’ Michael Casey (1752?–1830/31), who in 1825 advertised the publication of a new herbal containing cures derived from much earlier Irish-language medical manuscripts.
Crowds and political violence in early modern Ireland: Galway and the 1641 depositions
Authors: Walter John
Published: January 2022

This article offers a critical analysis of the representation of early modern popular violence provided by the 1641 depositions. Exploring the problems of how reported ‘speech’ was produced and recorded in the 1641 depositions, the article challenges the tendency within the depositions to represent violence as a spontaneous and immediate act, explicable by a racialised reading of Irish ‘barbarity’ and Catholic treachery. Exploiting a large cache of depositions and examinations in the relatively resource-rich urban context of Galway, it offers a micro-historical narrative of two brutal episodes of popular violence there in 1642 to reveal the complex histories and politics that might lie behind acts of violence in the Irish rising. Examining the local impact of the state's policies of anglicisation and Protestantisation, the paper recovers the prolonged, but ultimately unsuccessful, negotiations that preceded popular violence. Contextualizing the episodes, the article locates that violence in the more complex (and divided) politics of the city and in the radical challenges it brought to traditional structures of rule in Galway. Referencing the developing body of work on the politics of early modern crowd actions in Ireland, the article argues that the popular violence was political, both a consequence of and contributor to political change there.
Rediscovering poverty: moneylending in the Republic of Ireland in the 1960s
Authors: Holohan Carole , O'Connell Sean , Savage Robert J.
Published: January 2022

In 1969 R.T.É.'s 7 Days dealt with the issue of illegal moneylending, claiming that Dublin was ‘a city of fear’ where 500 unlicensed moneylenders used violence as a tool to collect debts. The Fianna Fáil government rejected the suggestion that loan sharking was widespread and that Gardaí responses to it were ineffectual; a tribunal of inquiry was established to investigate 7 Days. Previous analyses situated these events within the context of government concerns over the influence of television journalism. This article takes a different approach, analysing moneylending ― rather than 7 Days ― within the context of the rediscovery of poverty during the 1960s. It examines how social and economic changes, including the growth of consumer credit and the re-housing of large numbers of Dubliners, combined to make illegal moneylending more visible. Historical accounts of Ireland in the 1960s have had a top down focus on economic policy and growth. Here, the focus is shifted to personal rather state finances to offer a more nuanced portrayal of a decade often understood as a boom one. Moreover, analysing the nature and conclusions of the tribunal lays bare the contemporary resistance to those attempting to reframe the problem of poverty.
THE PROBABILITY OF ZERO MULTIPLICATION IN FINITE RINGS
Authors: DOLŽAN DAVID
Published: January 2022

LetRbe a finite ring and let${\mathrm {zp}}(R)$denote the nullity degree ofR, that is, the probability that the multiplication of two randomly chosen elements ofRis zero. We establish the nullity degree of a semisimple ring and find upper and lower bounds for the nullity degree in the general case.
God, Tragic Dilemmas, and the Problem of Gratuitous Evil
Authors: Naraghi Arash
Published: January 2022

Many philosophers have argued that the existence of gratuitous evil is the most serious objection against the existence of an all-perfect God. I argue that the idea of a moral dilemma (or, more accurately, atragicdilemma) may either (1) provide a moral justification for God to permit the existence of gratuitous evil, or (2) offer a theodicy of divine tragedy to explain why evils in the world are not necessarily gratuitous, or if they are, why they cannot provide a piece of decisive evidence to reject the existence of an all-perfect God.
Self-control in first grade predicts success in the transition to adulthood
Authors: Johnson Sara B. , Voegtline Kristin M. , Ialongo Nicholas , Hill Karl G. , Musci Rashelle J.
Published: January 2022

Childhood self-control has been linked with better health, criminal justice, and economic outcomes in adulthood in predominately white cohorts outside of the United States. We investigated whether self-control in first grade predicted success in the transition to adulthood in a longitudinal cohort of first graders who participated in a universal intervention trial to prevent poor achievement and reduce aggression in Baltimore schools. We also explored whether the intervention moderated the relationship between self-control and young adult outcomes. Teachers rated self-control using the Teacher Observation of Classroom Adaptation-Revised. Study outcomes were on-time high school graduation, college participation, teen pregnancy, substance use disorder, criminal justice system involvement, and incarceration (ages 19–26). Latent profile analysis was used to identify classes of childhood self-control. A high self-control class (n= 279, 48.1%), inattentive class (n= 201, 35.3%), and inattentive/hyperactive class (n= 90, 16.6%) were identified. Children with better self-control were more likely to graduate on time and attend college; no significant class differences were found for teen pregnancy, substance use disorder, criminal justice system involvement, or incarceration. A classroom-based intervention reduced criminal justice system involvement and substance use disorder among children with high self-control. Early interventions to promote child self-control may have long-term individual and social benefits.
Can we predict risk for cardiac involvement in paediatric inflammatory multi-system syndrome?
Authors: Yakut Nurhayat , Tanidir Ibrahim Cansaran , Yakut Kahraman , Sahin Sezgin , Kilinc Arda , Kabasakal Irem , Cetinkaya Merih , Onal Hasan , Ozturk Erkut
Published: January 2022

Introduction:

Increasing recognition of paediatric inflammatory multi-system syndrome is a cause of concern. This study aimed to evaluate children with paediatric inflammatory multi-system syndrome and compare the clinical and laboratory features of children with and without cardiac involvement.

Material and methods:

We conducted a prospective single-centre study including 57 (male 37, 65%) patients with paediatric inflammatory multi-system syndrome at a tertiary care hospital between November, 2020 and March, 2021. The mean age was 8.8 ± 4.5 years (range, 10 months–16.7 years).

Results:

The most frequent symptoms were fever (100%), abdominal pain (65%) and diarrhoea (42%). SARS-CoV-2 PCR and serology tests were positive in 3 (5%) and 52 (91%) patients, respectively. Eight patients required intensive care support. Nineteen patients (33%) had cardiac involvement (valvular regurgitation in 15, left ventricular systolic dysfunction in 11 and coronary artery dilation in 1). The presence and duration of cough and intensive care admissions were significantly higher in children with cardiac involvement than those without it. The cut-off values of troponin T, pro-brain natriuretic peptide and interleukin 6 for predicting cardiac involvement were 11.65 ng/L (95% confidence interval, 0.63–0.90; sensitivity, 0.63; specificity, 0.84; area under the curve: 0.775, p = 0.009), 849.5 pg/mL (95% CI, 0.54–0.86; sensitivity, 0.63; specificity, 0.63; area under the curve: 0.706, p = 0.009) and 39.8 pg/mL (95% CI, 0.54–0.85; sensitivity, 0.63; specificity, 0.60; area under the curve: 0.698, p = 0.023), respectively.

Conclusions:

Cardiac involvement in children with paediatric inflammatory multi-system syndrome is common. The risk of cardiac involvement can be predicted by troponin T, pro-brain natriuretic peptide and interleukin 6 levels.
Cardiovascular magnetic resonance in children with suspected myocarditis: current practice and applicability of adult protocols
Authors: Pitak Barbara , Opgen-Rhein Bernd , Schubert Stephan , Reineker Katja , Wiegand Gesa , Boecker Dorothée , Rentzsch Axel , Ruf Bettina , Özcan Sevinc , Wannenmacher Bardo , Pickardt Thomas , Seidel Franziska , Messroghli Daniel
Published: January 2022

Background:

Cardiovascular magnetic resonance serves as a useful tool in diagnosing myocarditis. Current adult protocols are yet to be validated for children; thus, it remains unclear if the methods used can be applied with sufficient image quality in children. This study assesses the use of cardiovascular magnetic resonance in children with suspected myocarditis.

Methods:

Image data from clinical cardiovascular magnetic resonance studies performed in children enrolled in Mykke between June 2014 and April 2019 were collected and analysed. The quality of the data sets was evaluated using a four-point quality scale (4: excellent, 3: good, 2: moderate, 1: non-diagnostic).

Results:

A total of 102 patients from 9 centres were included with a median age (interquartile range) of 15.4(10.7-16.6) years, 137 cardiovascular magnetic resonance studies were analysed. Diagnostic image quality was found in 95%. Examination protocols were consistent with the original Lake Louise criteria in 58% and with the revised criteria in 35%. Older patients presented with better image quality, with the best picture quality in the oldest age group (13-18 years). Sedation showed a negative impact on image quality in late gadolinium enhancement and oedema sequences. No such correlation was seen in cardiac function assessment sequences. In contrast to initial scans, in follow-up examinations, the use of parametric mapping increased while late gadolinium enhancement and oedema sequences decreased.

Conclusion:

Cardiovascular magnetic resonance protocols for the assessment of adult myocarditis can be applied to children without significant constraints in image quality. Given the lack of specific recommendations for children, cardiovascular magnetic resonance protocols should follow recent recommendations for adult cardiovascular magnetic resonance.
Concomitant pulmonary and neurological embolisation in a Down patient after SARS-CoV-2 vaccine: what is missing?
Authors: Di Molfetta Arianna , Volpe Sonia , Cesario Marco , Mollo Pasquale , Boncompagni Duino , Di Ruzza Giancarlo , Menichelli Maurizio
Published: January 2022

A 40-year-old Down patient without previous cardiological history was admitted to our institution for dyspnoea after COVID-19 vaccine. CT scan revealed a pulmonary thromboembolism. One week later, he developed neurological impairment and CT scan evidenced a left parietal ischaemic lesion. Concomitantly, he underwent echocardiography showing an atrioventricular septal defect typically associated to Down syndrome and never diagnosed earlier. The diagnosis of paradoxical embolisation was then supposed. Echocardiography also revealed a severe right heart section dilatation, with bidirectional shunt on the septal defects and systemic right heart pressure. Down patients affected by CHD are more prone to develop pulmonary vasculopathy than non-syndromic patients. In this case, the pulmonary vasculopathy was further exacerbated by the pulmonary embolism and by the late diagnosis of CHD. Finally, an appropriate timely diagnosis of atrioventricular septal defect could potentially avoid the neurological complication in this patient.
Hemispheric Differences in Self-evaluation Errors of Upper Extremity Movement in Patients with Chronic Stroke
Authors: Choi Sola , Won Jongim , Park Kyuenam , Kim Sujin
Published: January 2022

Objective:

There is growing evidence that the side of brain lesions results in distinct upper extremity deficits in motor control, movement behavior, and emotional and cognitive function poststroke. We investigated self-evaluation errors, which are the differences in scores between patient self-evaluation and clinician evaluations, and compared patients with left hemisphere damage (LHD) and right hemisphere damage (RHD) poststroke.

Method:

Twenty-eight patients with chronic stroke (LHD = 16) performed the actual amount of the test twice with a one-week interval. We videotaped the participants' movements, and participants with stroke and evaluators graded the quality of movement scores by watching video recordings.

Results:

Self-evaluation errors were significantly lower in patients with LHD than in those with RHD (t= 2.350,p= .019). Interestingly, this error did not change after the clinician provided the correct score as feedback. Chi-squared analysis revealed that more patients with LHD underestimated their movements (χ2= 9.049,p= .002), while more patients with RHD overestimated (χ2= 7.429,p= .006) in the send evaluation. Furthermore, there were no correlations between self-evaluation error and age, cognitive function, physical impairment, ability to control emotions, or onset months poststroke.

Conclusions:

Patients with stroke and therapists evaluated the same movements differently, and this can be dependent on hemispheric damage. Therapists might need to encourage patients with LHD who underestimate their movement to ensure continuous use of their more-affected arm. Patients with RHD who overestimate their movement might need treatment to overcome impaired self-awareness, such as video recordings, to protect from unexpected dangerous situations.
A multi-factor study of the development of English receptive skills by young Danish children
Authors: Cadierno Teresa , Hansen Mikkel B. , Lauridsen Jørgen T. , Eskildsen Søren W. , Fenyvesi Katalin , Hannibal Jensen Signe
Published: January 2022

This longitudinal study examined the influence of child-specific and environmental factors on the development of English receptive vocabulary and grammar by two groups of Danish children: Early Starters (ES) and Late Starters (LS). Age of onset, gender, language aptitude and SES significantly predicted both outcome measures. English competence beliefs (ECB) were positively related to L2 proficiency but only for children with low foreign language classroom anxiety (FLCA), suggesting a dynamic relationship between ECB and FLCA. Extramural audiovisual viewing and reading played a differential role for ES vs. LS whereas extramural English speaking significantly interacted with gender. Finally, child-specific factors explained more of the variance in English proficiency than environmental factors. This finding, which contradicts results obtained in instructed settings (e.g., Sun, Steinkrauss, Tendeiro & de Bot, 2016) but parallels those in naturalistic settings (e.g., Paradis, 2011), supports the special status of English in countries with a high degree of informal contact with English.
My Training Incumbent Is Doing a Good Job: An Empirical Investigation of Personal, Religious and Psychological Factors Shaping Curates’ Evaluation of their Training Incumbent within the Anglican Church in England and Wales
Authors: Smith Greg , Francis Leslie J.
Published: January 2022

Drawing on detailed questionnaire data (including personal, religious and psychological factors) provided by 416 pairs of curates and training incumbents, the present study addresses two core research questions. The first research question develops and tests a new measure: the Smith Attitude toward Training Incumbents Scale (SATIS). The second research question explores the influence of personal, religious and psychological characteristics of both the curate and the training incumbent in predicting curates’ positive attitude toward the training incumbent. The data demonstrated that religious factors (Catholic or Evangelical, Liberal or Conservative, Charismatic or not Charismatic) were not significant. However, both personal and psychological factors of the curates themselves were significant. The curates who rated their training incumbent more highly were older and more emotionally stable. Personal factors were also significant for the training incumbents, but not psychological factors. The curates rated more highly the experience of working with younger training incumbents. The most satisfactory experience of curacy was associated with older and emotionally stable curates working with younger training incumbents.
South Pole Station Ground‐Based and Cluster Satellite Measurements of Leaked and Escaping Auroral Kilometric Radiation
Authors: LaBelle James , Yearby Keith , Pickett Jolene S.
Published: January 2022

Previous work suggests that Auroral Kilometric Radiation (AKR) leaks to low altitudes. To investigate this phenomenon, wideband wave measurements have been conducted simultaneously at South Pole, Antarctica, and at the Cluster satellites, during 35 intervals in 2018–2020. Leaked AKR is observed ∼5% of the time at South Pole and escaping AKR ∼31% of the time at Cluster satellites. Both types of AKR are composed of fine structure, and similar fine structure is often observed simultaneously in the AKR at the different locations. Around 0317 UT on 29 June 2020, identical features were observed simultaneously. Cluster interferometry shows that the footprint of the source field line during this event lies within a few hundred kilometers of South Pole. The estimated emitted power of the escaping AKR observed at Cluster in this event exceeds that of the leaked AKR observed at South Pole by many orders of magnitude, suggesting that mode conversion involved in generating leaked AKR is relatively inefficient. AKR fine structure which is identical at the two locations comprises ∼0.1%–0.3% of AKR observed at Cluster when the South Pole receiver operates, and ∼2% of AKR observed at South Pole when at least one Cluster satellite is tuned to the appropriate frequency range. The relatively low occurrence rates of coincident fine structure may be attributed partly to geometric and beaming considerations but also suggest that processes involved in generating leaked AKR at levels detectable at ground level have lower probability than those generating escaping AKR at levels detectable by distant spacecraft.
Ionospheric Disturbances in Low‐ and Midlatitudes During the Geomagnetic Storm on 26 August 2018
Authors: Chang Hyeyeon , Kil Hyosub , Sun Andrew K. , Zhang Shun‐Rong , Lee Jiyun
Published: January 2022

Plasma density depletions at midlatitudes during geomagnetic storms are often understood in terms of equatorial plasma bubbles (EPBs) due to their morphological similarity. However, our study reports the observations that reveal the generation of plasma depletions at midlatitudes by local sources. During the geomagnetic storm on 26 August 2018, the Defense Meteorological Satellite Program and Swarm satellites detected plasma depletions at midlatitudes in the Asian sector in the absence of EPBs in the equatorial region. This observation and the total electron content (TEC) maps over Japan demonstrate that traveling ionospheric disturbances (TIDs) are the sources of midlatitude plasma depletions in the Asian sector. Near the west coast of the United States, the development of a narrow TEC depletion band was identified from TEC maps. The TEC depletion band, which is elongated in the northwest–southeast direction, moves toward the west with a velocity of approximately 240 m/s. The TEC at the TEC depletion band is about 5 TEC units (1016 m−2) smaller than the ambient TEC. As this band is confined to the midlatitudes, this phenomenon is not associated with an EPB. The characteristics of the TEC depletion band are consistent with those of medium‐scale TIDs. Observations in the Asian sector and the TEC depletion band over the United States demonstrate that plasma depletions can develop at midlatitudes by local sources. Therefore, the morphological similarity between midlatitude irregularities and EPBs or their coincident occurrence does not provide corroborating evidence of their connection.
Marine Boundary Layer Decoupling and the Stable Isotopic Composition of Water Vapor
Authors: Galewsky Joseph , Jensen Michael P. , Delp Jacqueline
Published: January 2022

Decoupling of the subcloud layer in stratocumulus‐topped marine boundary layers (STMBL) influences low‐cloud cover by limiting the supply of water vapor from the surface. However, the relative importance of mixing between surface fluxes and other reservoirs of water vapor as a function of the degree of decoupling is poorly understood. Water vapor transport within the STMBL and its response to decoupling is explored using surface measurements of water vapor isotopic composition that were obtained from Graciosa Island, Azores, during the summer and fall of 2018. The data show an inverse relationship between the decoupling metric, Δq, and the degree of drying from an isotopically depleted water vapor source. The isotopic data require some degree of drying with an isotopically depleted source for coupled conditions, and likely require a small amount of mixing even for strongly decoupled conditions. The data are consistent with mixing between purely local reservoirs of water vapor, subjected to a small amount of condensation and fractionation, and do not require the invocation of large‐scale transport of water vapor aloft or additional cloud‐formation effects aloft.
Influence of Suspended Aquaculture on Hydrodynamics and Nutrient Supply in the Coastal Yellow Sea
Authors: He Yuqing , Xuan Jiliang , Ding Ruibin , Shen Hui , Zhou Feng
Published: January 2022

Effects of aquaculture on hydrodynamics and associated nutrient supply in a typical aquaculture area of the coastal Yellow Sea are investigated with high‐resolution model experiments and in situ data. The results show a significant reduction in nutrient supply, which is associated with alternations of three hydrodynamic conditions: the onshore current across the outer‐boundary of aquaculture area, upwelling within the offshore (depth >10 m) aquaculture area, and water exchange in the near‐coastal (depth <10 m) aquaculture area. First, the onshore current in the bottom layer of the aquaculture boundary, which transports high‐concentration nutrients from the major nutrient source of offshore bottom water, is significantly weakened by suspended aquaculture. As a result, nutrient supply from offshore sources is reduced by 50%−60%. Second, the upwelling velocities in the offshore aquaculture area are reduced by 2–6 × 10−3 cm/s, which leads to an approximately 25% reduction in nutrient supply to the euphotic layer. Third, the water exchange in the near‐coastal aquaculture area remains approximately unchanged because the weakened onshore currents within the aquaculture layers (0–4 m) are compensated by the enhanced onshore currents in the lower layers. As a result, the nutrient supply in the near‐coastal aquaculture area does not significantly change, whereas the nutrient supply in the offshore aquaculture area has been reduced by approximately 60%.
Incorporating Microtopography in a Land Surface Model and Quantifying the Effect on the Carbon Cycle
Authors: Graham J. D. , Ricciuto D. M. , Glenn N. F. , Hanson P. J.
Published: January 2022

Northern peatlands are a terrestrial carbon store, with an annual sink of 0.1 Pg C yr−1 and a total storage estimate of 547 Pg C. Northern peatlands are also major contributors of atmospheric methane. Most land surface models do not accurately represent peatland carbon emissions, partly because they do not represent the hydrologic cycle and/or microtopography adequately. Interactions between water table depth and microtopography in peatlands influence decomposition and modulate CO2 and CH4 fluxes. A modified version of the land surface component of the Energy Exascale Earth System Model, was recently created to represent the microtopography and hydrology of a raised dome bog in northern Minnesota, USA. In this study, three microtopographic parameters are analyzed in the modified version: hummock height, hummock‐hollow spacing, and percent hollow. Terrestrial laser scanning observations are used to set uncertainty bounds for these parameters. Our model experiment results suggest that carbon‐related quantities of interest (QOI) were typically the most sensitive to hummock height, and those QOI (especially net ecosystem exchange, NEE) were sensitive to interactions between parameters. Furthermore, NEE was most relatively influenced by microtopographic parameters in the model, varying by 35%. We found that increasing hummock height resulted in more C being stored in plant tissue and less in soil organic matter. This coincided with decreases in Sphagnum and increases in Picea and shrub net primary production. These results suggest that future studies may consider extending prognostic capabilities of carbon cycling by incorporating hummock hollow microtopography into earth system models.
Nonvolatile electrical switching of optical and valleytronic properties of interlayer excitons
Authors: Ye Tong , Li Yongzhuo , Li Junze , Shen Hongzhi , Ren Junwen , Ning Cun-Zheng , Li Dehui
Published: January 2022

Long-lived interlayer excitons (IXs) in van der Waals heterostructures (HSs) stacked by monolayer transition metal dichalcogenides (TMDs) carry valley-polarized information and thus could find promising applications in valleytronic devices. Current manipulation approaches for valley polarization of IXs are mainly limited in electrical field/doping, magnetic field or twist-angle engineering. Here, we demonstrate an electrochemical-doping method, which is efficient, in-situ and nonvolatile. We find the emission characteristics of IXs in WS2/WSe2 HSs exhibit a large excitonic/valley-polarized hysteresis upon cyclic-voltage sweeping, which is ascribed to the chemical-doping of O2/H2O redox couple trapped between WSe2 and substrate. Taking advantage of the large hysteresis, a nonvolatile valley-addressable memory is successfully demonstrated. The valley-polarized information can be non-volatilely switched by electrical gating with retention time exceeding 60 min. These findings open up an avenue for nonvolatile valley-addressable memory and could stimulate more investigations on valleytronic devices.
Functional neuroanatomy of mania
Authors: Cotovio Gonçalo , Oliveira-Maia Albino J.
Published: January 2022

Mania, the diagnostic hallmark of bipolar disorder, is an episodic disturbance of mood, sleep, behavior, and perception. Improved understanding of the neurobiology of mania is expected to allow for novel avenues to address current challenges in its diagnosis and treatment. Previous research focusing on the impairment of functional neuronal circuits and brain networks has resulted in heterogenous findings, possibly due to a focus on bipolar disorder and its several phases, rather than on the unique context of mania. Here we present a comprehensive overview of the evidence regarding the functional neuroanatomy of mania. Our interpretation of the best available evidence is consistent with a convergent model of lateralized circuit dysfunction in mania, with hypoactivity of the ventral prefrontal cortex in the right hemisphere, and hyperactivity of the amygdala, basal ganglia, and anterior cingulate cortex in the left hemisphere of the brain. Clarification of dysfunctional neuroanatomic substrates of mania may contribute not only to improve understanding of the neurobiology of bipolar disorder overall, but also highlights potential avenues for new circuit-based therapeutic approaches in the treatment of mania.
EEG as a translational biomarker and outcome measure in fragile X syndrome
Authors: Kenny Aisling , Wright Damien , Stanfield Andrew C.
Published: January 2022

Targeted treatments for fragile X syndrome (FXS) have frequently failed to show efficacy in clinical testing, despite success at the preclinical stages. This has highlighted the need for more effective translational outcome measures. EEG differences observed in FXS, including exaggerated N1 ERP amplitudes, increased resting gamma power and reduced gamma phase-locking in the sensory cortices, have been suggested as potential biomarkers of the syndrome. These abnormalities are thought to reflect cortical hyper excitability resulting from an excitatory (glutamate) and inhibitory (GABAergic) imbalance in FXS, which has been the target of several pharmaceutical remediation studies. EEG differences observed in humans also show similarities to those seen in laboratory models of FXS, which may allow for greater translational equivalence and better predict clinical success of putative therapeutics. There is some evidence from clinical trials showing that treatment related changes in EEG may be associated with clinical improvements, but these require replication and extension to other medications. Although the use of EEG characteristics as biomarkers is still in the early phases, and further research is needed to establish its utility in clinical trials, the current research is promising and signals the emergence of an effective translational biomarker.
Oral ixazomib-dexamethasone vs oral pomalidomide-dexamethasone for lenalidomide-refractory, proteasome inhibitor-exposed multiple myeloma: a randomized Phase﻿ 2 trial
Authors: Dimopoulos Meletios A. , Schjesvold Fredrik , Doronin Vadim , Vinogradova Olga , Quach Hang , Leleu Xavier , Montes Yolanda Gonzalez , Ramasamy Karthik , Pompa Alessandra , Levin Mark-David , Lee Cindy , Mellqvist Ulf Henrik , Fenk Roland , Demarquette Hélène , Sati Hamdi , Vorog Alexander , Labotka Richard , Du Jichang , Darif Mohamed , Kumar Shaji
Published: January 2022

Multiple myeloma (MM) patients typically receive several lines of combination therapy and first-line treatment commonly includes lenalidomide. As patients age, they become less tolerant to treatment, requiring convenient/tolerable/lenalidomide-free options. Carfilzomib and/or bortezomib-exposed/intolerant, lenalidomide-refractory MM patients with ≥2 prior lines of therapy were randomized 3:2 to ixazomib-dexamethasone (ixa-dex) (n = 73) or pomalidomide-dexamethasone (pom-dex) (n = 49) until progression/toxicity. Median progression-free survival (mPFS) was 7.1 vs 4.8 months with ixa-dex vs pom-dex (HR 0.847, 95% CI 0.535–1.341, P = 0.477; median follow-up: 15.3 vs 17.3 months); there was no statistically significant difference between arms. In patients with 2 and ≥3 prior lines of therapy, respectively, mPFS was 11.0 vs 5.7 months (HR 1.083, 95% CI 0.547–2.144) and 5.7 vs 3.7 months (HR 0.686, 95% CI 0.368–1.279). Among ixa-dex vs pom-dex patients, 69% vs 81% had Grade ≥3 treatment-emergent adverse events (TEAEs), 51% vs 53% had serious TEAEs, 39% vs 36% had TEAEs leading to drug discontinuation, 44% vs 32% had TEAEs leading to dose reduction, and 13% vs 13% died on study. Quality of life was similar between arms and maintained during treatment. Ixa-dex represents an important lenalidomide-free, oral option for this heavily pretreated, lenalidomide-refractory, proteasome inhibitor-exposed population.

Trial registration: ClinicalTrials.gov number, NCT03170882.
The multifaceted role of ferroptosis in liver disease
Authors: Chen Junyi , Li Xiaopeng , Ge Chaodong , Min Junxia , Wang Fudi
Published: January 2022

Ferroptosis is an iron-dependent form of non-apoptotic cell death characterized by excessive lipid peroxidation and associated with a plethora of pathological conditions in the liver. Emerging evidence supports the notion that dysregulated metabolic pathways and impaired iron homeostasis play a role in the progression of liver disease via ferroptosis. Although the molecular mechanisms by which ferroptosis causes disease are poorly understood, several ferroptosis-associated genes and pathways have been implicated in liver disease. Here, we review the physiological role of the liver in processing nutrients, our current understanding of iron metabolism, the characteristics of ferroptosis, and the mechanisms that regulate ferroptosis. In addition, we summarize the role of ferroptosis in the pathogenesis of liver disease, including liver injury, non-alcoholic steatohepatitis, liver fibrosis, liver cirrhosis, and hepatocellular carcinoma. Finally, we discuss the therapeutic potential of targeting ferroptosis for managing liver disease.
Antisense oligonucleotide silencing of FUS expression as a therapeutic approach in amyotrophic lateral sclerosis
Authors: Korobeynikov Vladislav A. , Lyashchenko Alexander K. , Blanco-Redondo Beatriz , Jafar-Nejad Paymaan , Shneider Neil A.
Published: January 2022

Fused in sarcoma (FUS) is an RNA-binding protein that is genetically and pathologically associated with rare and aggressive forms of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). To explore the mechanisms by which mutant FUS causes neurodegeneration in ALS-FTD, we generated a series of FUS knock-in mouse lines that express the equivalent of ALS-associated mutant FUSP525L and FUSΔEX14 protein. In FUS mutant mice, we show progressive, age-dependent motor neuron loss as a consequence of a dose-dependent gain of toxic function, associated with the insolubility of FUS and related RNA-binding proteins. In this disease-relevant mouse model of ALS-FUS, we show that ION363, a non-allele-specific FUS antisense oligonucleotide, efficiently silences Fus and reduces postnatal levels of FUS protein in the brain and spinal cord, delaying motor neuron degeneration. In a patient with ALS with a FUSP525L mutation, we provide preliminary evidence that repeated intrathecal infusions of ION363 lower wild-type and mutant FUS levels in the central nervous system, resulting in a marked reduction in the burden of FUS aggregates that are a pathological hallmark of disease. In mouse genetic and human clinical studies, we provide evidence in support of FUS silencing as a therapeutic strategy in FUS-dependent ALS and FTD.
Long-term safety and efficacy of lentiviral hematopoietic stem/progenitor cell gene therapy for Wiskott–Aldrich syndrome
Authors: Magnani A. , Semeraro M. , Adam F. , Booth C. , Dupré L. , Morris E. C. , Gabrion A. , Roudaut C. , Borgel D. , Toubert A. , Clave E. , Abdo C. , Gorochov G. , Petermann R. , Guiot M. , Miyara M. , Moshous D. , Magrin E. , Denis A. , Suarez F. , Lagresle C. , Roche A. M. , Everett J. , Trinquand A. , Guisset M. , Bayford J. Xu , Hacein-Bey-Abina S. , Kauskot A. , Elfeky R. , Rivat C. , Abbas S. , Gaspar H. B. , Macintyre E. , Picard C. , Bushman F. D. , Galy A. , Fischer A. , Six E. , Thrasher A. J. , Cavazzana M.
Published: January 2022

Patients with Wiskott–Aldrich syndrome (WAS) lacking a human leukocyte antigen-matched donor may benefit from gene therapy through the provision of gene-corrected, autologous hematopoietic stem/progenitor cells. Here, we present comprehensive, long-term follow-up results (median follow-up, 7.6 years) (phase I/II trial no. NCT02333760) for eight patients with WAS having undergone phase I/II lentiviral vector-based gene therapy trials (nos. NCT01347346 and NCT01347242), with a focus on thrombocytopenia and autoimmunity. Primary outcomes of the long-term study were to establish clinical and biological safety, efficacy and tolerability by evaluating the incidence and type of serious adverse events and clinical status and biological parameters including lentiviral genomic integration sites in different cell subpopulations from 3 years to 15 years after gene therapy. Secondary outcomes included monitoring the need for additional treatment and T cell repertoire diversity. An interim analysis shows that the study meets the primary outcome criteria tested given that the gene-corrected cells engrafted stably, and no serious treatment-associated adverse events occurred. Overall, severe infections and eczema resolved. Autoimmune disorders and bleeding episodes were significantly less frequent, despite only partial correction of the platelet compartment. The results suggest that lentiviral gene therapy provides sustained clinical benefits for patients with WAS.
High-throughput segmentation of unmyelinated axons by deep learning
Authors: Plebani Emanuele , Biscola Natalia P. , Havton Leif A. , Rajwa Bartek , Shemonti Abida Sanjana , Jaffey Deborah , Powley Terry , Keast Janet R. , Lu Kun-Han , Dundar M. Murat
Published: January 2022

Axonal characterizations of connectomes in healthy and disease phenotypes are surprisingly incomplete and biased because unmyelinated axons, the most prevalent type of fibers in the nervous system, have largely been ignored as their quantitative assessment quickly becomes unmanageable as the number of axons increases. Herein, we introduce the first prototype of a high-throughput processing pipeline for automated segmentation of unmyelinated fibers. Our team has used transmission electron microscopy images of vagus and pelvic nerves in rats. All unmyelinated axons in these images are individually annotated and used as labeled data to train and validate a deep instance segmentation network. We investigate the effect of different training strategies on the overall segmentation accuracy of the network. We extensively validate the segmentation algorithm as a stand-alone segmentation tool as well as in an expert-in-the-loop hybrid segmentation setting with preliminary, albeit remarkably encouraging results. Our algorithm achieves an instance-level $$F_1$$

F
1

score of between 0.7 and 0.9 on various test images in the stand-alone mode and reduces expert annotation labor by 80% in the hybrid setting. We hope that this new high-throughput segmentation pipeline will enable quick and accurate characterization of unmyelinated fibers at scale and become instrumental in significantly advancing our understanding of connectomes in both the peripheral and the central nervous systems.
Extracting microplastic decay rates from field data
Authors: Metz T. , Koch M. , Lenz P.
Published: January 2022

Being able to estimate and predict future microplastic distributions in the environment is one of the major challenges of the rapidly developing field of microplastic research. However, this task can only be achieved if our understanding of the decay of individual microplastic particles is significantly enhanced. Here, we show by using a rate equation model that currently available data of size distributions measured at single times cannot provide useful insights into this process. To analyze what data contains more information we generated more complex artificial data mimicking subsequent measurements using a stochastic simulation algorithm. Applying our model to this data revealed the following minimal requirements for future experimental data: (1) data should be collected as time series at identical spots and (2) size measurements should be combined with mass measurements. In contrast to currently available data, flux rates and decay parameters of individual particles can be extracted from such data.
Revealing the effect of seed phosphorus concentration on seedling vigour and growth of rice using mutagenesis approach
Authors: Yugandhar Poli , Veronica Nallamothu , Subrahmanyam D. , Brajendra P. , Nagalakshmi S. , Srivastava Akanksha , Voleti S. R. , Sarla N. , Sundaram R. M. , Sevanthi Amitha Mithra , Singh A. K. , Mangrauthia Satendra K.
Published: January 2022

The harvested plant products, specifically, the grains of cereals are major drivers of soil phosphorus (P) depletion. However, the breeding or biotechnology efforts to develop low P seeds have not been attempted because of possible adverse effects on seedling vigour and crop establishment. Several studies have contradictory observations on influence of seed P on seedling vigour. Lack of appropriate genetic material has been the major bottleneck in reaching the consensus. In this study, we used 30 EMS induced mutants of rice cultivar Nagina22 to understand the role of seed P on seedling vigour and associated physiological processes. Seedling vigour, morpho-physiological characteristics, acid phosphatases, alpha-amylase, and expression of P transporter genes were analyzed in seedlings obtained from seeds of high and low grain P mutants. The study suggests that seed P has a significant role on seedling vigour, chlorophyll content and photosynthesis process of young seedlings, and P transport from roots. Notably, we identified few mutants such as NH4791, NH4785, NH4714, NH4663, NH4614, and NH4618 which showed least influence of low seed P on seedling vigour and other metabolic processes. Therefore, these mutants can be used in breeding programs aiming for development of low P grains. Also, these and other identified mutants can be used to decipher the genetic and molecular mechanisms regulating the differential response of seed P on germination, seedling vigour and several other physiological processes influencing the crop growth and establishment.
The application of a deep learning system developed to reduce the time for RT-PCR in COVID-19 detection
Authors: Lee Yoonje , Kim Yu-Seop , Lee Da-in , Jeong Seri , Kang Gu-Hyun , Jang Yong Soo , Kim Wonhee , Choi Hyun Young , Kim Jae Guk , Choi Sang-hoon
Published: January 2022

Reducing the time to diagnose COVID-19 helps to manage insufficient isolation-bed resources and adequately accommodate critically ill patients. There is currently no alternative method to real-time reverse transcriptase polymerase chain reaction (RT-PCR), which requires 40 cycles to diagnose COVID-19. We propose a deep learning (DL) model to improve the speed of COVID-19 RT-PCR diagnosis. We developed and tested a DL model using the long short-term memory method with a dataset of fluorescence values measured in each cycle of 5810 RT-PCR tests. Among the DL models developed here, the diagnostic performance of the 21st model showed an area under the receiver operating characteristic (AUROC), sensitivity, and specificity of 84.55%, 93.33%, and 75.72%, respectively. The diagnostic performance of the 24th model showed an AUROC, sensitivity, and specificity of 91.27%, 90.00%, and 92.54%, respectively.
Near-infrared photoluminescence of Portland cement
Authors: Meng Wei , Bachilo Sergei M. , Parol Jafarali , Nagarajaiah Satish , Weisman R. Bruce
Published: January 2022

Portland cement emits bright near-infrared photoluminescence that can be excited by light wavelengths ranging from at least 500–1000 nm. The emission has a peak wavelength near 1140 nm and a width of approximately 30 nm. Its source is suggested to be small particles of silicon associated with calcium silicate phases. The luminescence peak wavelength appears independent of the cement hydration state, aggregates, and mechanical strain but increases weakly with increasing temperature. It varies slightly with the type of cement, suggesting a new non-contact method for identifying cement formulations. After a thin opaque coating is applied to a cement or concrete surface, subsequent formation of microcracks exposes the substrate’s near-infrared emission, revealing the fracture locations, pattern, and progression. This damage would escape detection in normal imaging inspections. Near-infrared luminescence imaging may therefore provide a new tool for non-destructive testing of cement-based structures.
Impact of hemolysis on multi-OMIC pancreatic biomarker discovery to derisk biomarker development in precision medicine studies
Authors: Searfoss Richard , Shah Punit , Ofori-Mensa Kennedy , Bussberg Valerie , Tolstikov Vladimir , Greenwood Bennett , Li Hongyan , Richardson Kris , Miller Gregory M. , DeCicco Corinne , Granger Elder , Rodrigues Leonardo O. , Grund Eric M. , Moser A. James , Sarangarajan Rangaprasad , Narain Niven R. , Kiebish Michael A.
Published: January 2022

Cancer biomarker discovery is critically dependent on the integrity of biofluid and tissue samples acquired from study participants. Multi-omic profiling of candidate protein, lipid, and metabolite biomarkers is confounded by timing and fasting status of sample collection, participant demographics and treatment exposures of the study population. Contamination by hemoglobin, whether caused by hemolysis during sample preparation or underlying red cell fragility, contributes 0–10 g/L of extraneous protein to plasma, serum, and Buffy coat samples and may interfere with biomarker detection and validation. We analyzed 617 plasma, 701 serum, and 657 buffy coat samples from a 7-year longitudinal multi-omic biomarker discovery program evaluating 400+ participants with or at risk for pancreatic cancer, known as Project Survival. Hemolysis was undetectable in 93.1% of plasma and 95.0% of serum samples, whereas only 37.1% of buffy coat samples were free of contamination by hemoglobin. Regression analysis of multi-omic data demonstrated a statistically significant correlation between hemoglobin concentration and the resulting pattern of analyte detection and concentration. Although hemolysis had the greatest impact on identification and quantitation of the proteome, distinct differentials in metabolomics and lipidomics were also observed and correlated with severity. We conclude that quality control is vital to accurate detection of informative molecular differentials using OMIC technologies and that caution must be exercised to minimize the impact of hemolysis as a factor driving false discovery in large cancer biomarker studies.