bluuebunny/crossref_metadata_2025 huggingface dataset:
A scoping review of ethics considerations in clinical natural language processing
Authors: Bear Don’t Walk Oliver J , Reyes Nieva Harry , Lee Sandra Soo-Jin , Elhadad Noémie
Published: July 2022

Objectives

To review through an ethics lens the state of research in clinical natural language processing (NLP) for the study of bias and fairness, and to identify gaps in research.

Methods

We queried PubMed and Google Scholar for articles published between 2015 and 2021 concerning clinical NLP, bias, and fairness. We analyzed articles using a framework that combines the machine learning (ML) development process (ie, design, data, algorithm, and critique) and bioethical concepts of beneficence, nonmaleficence, autonomy, justice, as well as explicability. Our approach further differentiated between biases of clinical text (eg, systemic or personal biases in clinical documentation towards patients) and biases in NLP applications.

Results

Out of 1162 articles screened, 22 met criteria for full text review. We categorized articles based on the design (N = 2), data (N = 12), algorithm (N = 14), and critique (N = 17) phases of the ML development process.

Discussion

Clinical NLP can be used to study bias in applications reliant on clinical text data as well as explore biases in the healthcare setting. We identify 3 areas of active research that require unique ethical considerations about the potential for clinical NLP to address and/or perpetuate bias: (1) selecting metrics that interrogate bias in models; (2) opportunities and risks of identifying sensitive patient attributes; and (3) best practices in reconciling individual autonomy, leveraging patient data, and inferring and manipulating sensitive information of subgroups. Finally, we address the limitations of current ethical frameworks to fully address concerns of justice. Clinical NLP is a rapidly advancing field, and assessing current approaches against ethical considerations can help the discipline use clinical NLP to explore both healthcare biases and equitable NLP applications.
Amphetamines in Workplace Testing Hair Samples over the Years 2011–2020
Authors: Hill Virginia A , Schaffer Michael I , Paulsen Ryan B , Stowe G Neil
Published: July 2022

Amphetamines (AMPs) in hair were investigated with thousands of workplace testing head and body hair samples collected and analyzed over 10 years and tabulated by year. All samples were washed by a published extensive method prior to confirmation by liquid chromatography–mass spectrometry-mass spectrometry. Presented are concentrations of parent methamphetamine (METH), 3,4-methylenedioxymethamphetamine (MDMA) and methylenedioxyamphetamine as metabolite and AMP as metabolite and without the presence of parent drug. Some differences in METH concentrations from year to year were significant, and some ratios of metabolite to parent drug for both METH and MDMA also varied significantly. While rates of METH use may not have changed significantly, some aspects of the drugs ingested as demonstrated by hair analysis varied over the 10-year period.
Introduction to the Collection: Climate Change, Insect Pests, and Beneficial Arthropods in Production Systems
Authors: Eigenbrode Sanford D , Adhikari Subodh , Kistner-Thomas Erica , Neven Lisa
Published: July 2022

Climate change is expected to alter pressure from insect pests and the abundance and effectiveness of insect pollinators across diverse agriculture and forestry systems. In response to warming, insects are undergoing or are projected to undergo shifts in their geographic ranges, voltinism, abundance, and phenology. Drivers include direct effects on the focal insects and indirect effects mediated by their interactions with species at higher or lower trophic levels. These climate-driven effects are complex and variable, sometimes increasing pest pressure or reducing pollination and sometimes with opposite effects depending on climatic baseline conditions and the interplay of these drivers. This special collection includes several papers illustrative of these biological effects on pests and pollinators. In addition, in response to or anticipating climate change, producers are modifying production systems by introducing more or different crops into rotations or as cover crops or intercrops or changing crop varieties, with potentially substantial effects on associated insect communities, an aspect of climate change that is relatively understudied. This collection includes several papers illustrating these indirect production system-level effects. Together, biological and management-related effects on insects comprise the necessary scope for anticipating and responding to the effects of climate change on insects in agriculture and forest systems.
Preliminary Study on Comparative Efficacy of Four Light Sources for Trapping Culicoides spp. (Diptera: Ceratopogonidae) in Prachuap Khiri Khan Province, Thailand
Authors: Choocherd Suchada , Pattanatanang Khampee , Chimnoi Wissanuwat , Kamyingkird Ketsarin , Tongyoo Pumipat , Phasuk Jumnongjit
Published: July 2022

The light trap is an important tool to determine the presence and abundance of vectors in the field. However, no one has studied the efficiency of light traps for collecting Culicoides in Thailand. In the present study, the efficacy of four light sources was evaluated in Prachuap Khiri Khan province, Thailand. Incandescent (INCND) light, white fluorescent (WHT-FLR) light, ultraviolet fluorescent (UV-FLR) light, and UV light-emitting diode (UV-LED) light were tested using commercial traps. In total, 30,866 individuals of Culicoides species were collected from November 2020 to June 2021, of which 21,016 were trapped on site 1 and 6,731 were trapped on site 2. The two most abundant Culicoides species were C. imicola (54%) and C. oxystoma (31.2%). UV-FLR was highly effective, followed by UV-LED light, WHT-FLR light, and INCND light, respectively, for Culicoides collection. Significantly, more Culicoides species were collected in those traps baited with UV-FLR light, UV-LED light, or WHT-FLR light than for INCND light traps. Traps equipped with UV-FLR lights can be recommended to trap Culcoides biting midges for monitoring purposes.
Refiguring Slavery Through International Law: The 1926 Slavery Convention, the ‘Native Labor Code’ and Racial Capitalism
Authors: Gevers Christopher
Published: July 2022

This article charts the refiguration of slavery through international law, the concatenations of slavery, colonialism and their afterlives in the present, and what these might tell us about racial capitalism and international economic law. Drawing on the Black Radical Tradition, it shows how slavery was refigured in two distinct but related respects. First, from the late nineteenth century onwards, international lawyers ‘refigured’ slavery historically, such that ‘antislavery’ became a defining attribute of ‘progressive’, ‘white’, ‘civilization’, and set about building the international legal architecture to confirm this fabrication; culminating in the Slavery Convention (1926) and the League of Nations’ ‘antislavery’ machinery. As a result, as a matter of ‘history’ and international law, the ‘recrudescence’ of slavery could only take place in Africa, and in particular in the two African states not yet under white rule—Liberia and Ethiopia—which laid the basis for the violent interventions in these Black Republics by Italy and the League in the interwar period. Second, the Slavery Convention and the International Labor Organization’s ‘native labor code’—through the figure of the ‘Black Worker’—refigured the afterlives of slavery and colonialism as acceptable, ‘civilizing’ (forced) labor, provided it was under white management. The article ends by showing how white supremacy and Black subordination were refigured, materially and symbolically—at both the international and individual level—through the ‘fabulation of debt’, literal and moral; and, in turn, surfaces slavery and colonialism’s entwined afterlives in the racial capitalist present, including through interntational (economic) law.
Helicobia neuzalmeidae sp. nov., A New Species of Sarcophagidae (Diptera) Reared From a Pig Carcass in the Brazilian Savanna
Authors: Silva José Orlando A , Brasil Leandro S , De-Souza Caroline C , Carvalho-Filho Fernando S
Published: July 2022

A new species of Sarcophagidae (Diptera) in the genus Helicobia Coquillett, Helicobia neuzalmeidae sp. nov., is described based on two male specimens obtained from pig carcasses in savanna-like vegetation in northeastern Brazil (state of Maranhão) during a forensic study. The holotype was obtained from a larva that abandoned the pig carcass to pupate, whereas the paratype was collected with a trap placed above the cage containing the carcass. This is the first record of a Helicobia species reared from a vertebrate carcass.
The Location of Disease-Causing DES Variants Determines the Severity of Phenotype and the Morphology of Sarcoplasmic Aggregates
Authors: Silva André Macedo Serafim , Rodrigo Patricia , Moreno Cristiane Araújo Martins , Mendonça Rodrigo de Holanda , Estephan Eduardo de Paula , Camelo Clara Gontijo , Campos Eliene Dutra , Dias Alexandre Torchio , Nascimento Amom Mendes , Kulikowski Leslie Domenici , Oliveira Acary Souza Bulle , Reed Umbertina Conti , Goldfarb Lev G , Olivé Montse , Zanoteli Edmar
Published: July 2022

Desmin (DES) is the main intermediate muscle filament that connects myofibrils individually and with the nucleus, sarcolemma, and organelles. Pathogenic variants of DES cause desminopathy, a disorder affecting the heart and skeletal muscles. We aimed to analyze the clinical features, morphology, and distribution of desmin aggregates in skeletal muscle biopsies of patients with desminopathy and to correlate these findings with the type and location of disease-causing DES variants. This retrospective study included 30 patients from 20 families with molecularly confirmed desminopathy from 2 neuromuscular referral centers. We identified 2 distinct patterns of desmin aggregates: well-demarcated subsarcolemmal aggregates and diffuse aggregates with poorly delimited borders. Pathogenic variants located in the 1B segment and the tail domain of the desmin molecule are more likely to present with early-onset cardiomyopathy compared to patients with variants in other segments. All patients with mutations in the 1B segment had well-demarcated subsarcolemmal aggregates, but none of the patients with variants in other desmin segments showed such histological features. We suggest that variants located in the 1B segment lead to well-shaped subsarcolemmal desmin aggregation and cause disease with more frequent cardiac manifestations. These findings will facilitate early identification of patients with potentially severe cardiac syndromes.
Impact of national lockdown on the suspected SARS-CoV-2 epidemic in terms of the number of fever cases in North Korea
Authors: Han Changhee , Ryu Sukhyun , Shin Hyewon , Kim Dasom , Modchang Charin
Published: July 2022

After reopening the border, North Korea was experiencing community transmission of SARS-CoV-2 and implemented a nationwide lockdown. We estimated that the mean transmissibility declined to <1 within 5 days after the lockdown and that the lockdown was associated with a moderate decrease in transmissibility by 11% (95% confidence interval, 6–17%).
Abundance stratification in Type Ia supernovae – VI. The peculiar slow decliner SN 1999aa
Authors: Aouad Charles J , Mazzali Paolo A , Hachinger Stephan , Teffs Jacob , Pian Elena , Ashall Chris , Benetti Stefano , Filippenko Alexei V , Tanaka Masaomi
Published: July 2022

The abundance distribution in the ejecta of the peculiar slowly declining Type Ia supernova (SN Ia) SN 1999aa is obtained by modelling a time series of optical spectra. Similar to SN 1991T, SN 1999aa was characterized by early-time spectra dominated by Fe iii features and a weak Si ii 6355 Å line, but it exhibited a high-velocity Ca ii H&K line and morphed into a spectroscopically normal SN Ia earlier. Three explosion models are investigated, yielding comparable fits. The innermost layers are dominated by ∼0.3 M⊙ of neutron-rich stable iron-group elements, mostly stable iron. Above that central region lies a 56Ni-dominated shell, extending to $v \approx 11\, 000$–$12\, 000$ km s−1, with mass ∼0.65 M⊙. These inner layers are therefore similar to those of normal SNe Ia. However, the outer layers exhibit composition peculiarities similar to those of SN 1991T: The intermediate-mass elements shell is very thin, containing only ∼0.2 M⊙, and is sharply separated from an outer oxygen-dominated shell, which includes ∼0.22 M⊙. These results imply that burning suddenly stopped in SN 1999aa. This is a feature SN 1999aa shares with SN 1991T, and explains the peculiarities of both SNe, which are quite similar in nature apart from the different luminosities. The spectroscopic path from normal to SN 1991T-like SNe Ia cannot be explained solely by a temperature sequence. It also involves composition layering differences, suggesting variations in the progenitor density structure or in the explosion parameters.
An orbital perspective on the starvation, stripping, and quenching of satellite galaxies in the eagle simulations
Authors: Wright Ruby J , Lagos Claudia del P , Power Chris , Stevens Adam R H , Cortese Luca , Poulton Rhys J J
Published: July 2022

Using the eagle (Evolution and Assembly of GaLaxies and their Environments) suite of simulations, we demonstrate that both cold gas stripping and starvation of gas inflow play an important role in quenching satellite galaxies across a range of stellar and halo masses, M⋆ and M200. Quantifying the balance between gas inflows, outflows, and star formation rates, we show that even at z = 2, only $\approx 30{{\ \rm per\ cent}}$ of satellite galaxies are able to maintain equilibrium or grow their reservoir of cool gas – compared to $\approx 50{{\ \rm per\ cent}}$ of central galaxies at this redshift. We find that the number of orbits completed by a satellite on first-infall to a group environment is a very good predictor of its quenching, even more so than the time since infall. On average, we show that intermediate-mass satellites with M⋆ between will be quenched at $10^{9}\, {\rm M}_{\odot }\, {\rm and}\, 10^{10}\, {\rm M}_{\odot }$ first pericenter in massive group environments, $M_{200}\gt 10^{13.5}\, {\rm M}_{\odot }$; and will be quenched at second pericenter in less massive group environments, $M_{200}\lt 10^{13.5}\, {\rm M}_{\odot }$. On average, more massive satellites ($M_{\star }\gt 10^{10}\, {\rm M}_{\odot }$) experience longer depletion time-scales, being quenched between first and second pericenters in massive groups, while in smaller group environments, just $\approx 30{{\ \rm per\ cent}}$ will be quenched even after two orbits. Our results suggest that while starvation alone may be enough to slowly quench satellite galaxies, direct gas stripping, particularly at pericenters, is required to produce the short quenching time-scales exhibited in the simulation.
Extreme blazars: the result of unstable recollimated jets?
Authors: Tavecchio Fabrizio , Costa Agnese , Sciaccaluga Alberto
Published: July 2022

Extreme BL Lacs (EHBL) form a subclass of blazars, which challenge standard emission scenarios. In a recent study it has been argued that their peculiar properties can be explained if emitting electrons are accelerated in a series of oblique shocks induced by the recollimation of the relativistic jet. However, new 3 D simulations of recollimated, weakly magnetized jets reveal that, in correspondence with the first recollimation shock, the flow develops a rapidly growing instability, becomes highly turbulent and decelerates, effectively hampering the formation of the multiple shock structure routinely observed in 2 D simulations. Building on these new findings, we propose here a revised scenario for EHBL, in which the emission is produced by electrons accelerated at the recollimation shock and subsequently further energized through stochastic acceleration in the turbulent downstream flow. We apply a simple version of this scenario to the prototypical EHBL 1ES 0229-200, showing that the spectral energy distribution (SED) can be satisfactorily reproduced with standard values of the main physical parameters.
Whewellite-Bearing Fluid Inclusions in Zircons From a Stromatic Migmatite in the Chinese Sulu Ultrahigh-Pressure Metamorphic Belt
Authors: Fei Chenhui , Liu Jingbo
Published: July 2022

Abundant primary fluid and melt inclusions occur in zircons from a stromatic migmatite sample in the Chinese Sulu ultrahigh-pressure (UHP) metamorphic belt, reflecting an immiscible melt-fluid coexistence during the partial melting process. Raman analysis shows that the fluid inclusions include whewellite, highly disordered carbonaceous matter (CM), diamond, calcite, dawsonite, quartz, cristobalite, H2O-bearing silica glass, muscovite, chalcopyrite, molybdenite, pyrite/pyrrhotite, magnetite, hematite, rutile, CO2 and H2O. The inclusions were entrapped during the exhumation of the rock from UHP to granulite-facies metamorphic conditions. The presence of whewellite suggests that the primary fluids during the entrapment of the inclusions contained some kind of dicarboxylic compound. The highly disordered CM still includes aliphatic hydrocarbon species revealed by the C-H stretching bands at ~2886 and ~2941 cm−1, and a subsidiary band at 1250 cm−1 on the low-frequency side of the D band at 1350 cm−1, indicating that it was derived from incomplete carbonization of an organic compound. The identification of whewellite as well as highly disordered CM in the fluid inclusions provides evidence that abiotic synthesis of organic compounds can happen at elevated pressures and temperatures where both melt and fluids are stable, and in which magnetite and sulphides may play a catalyzing role.
Methylation of a MITE insertion in the MdRFNR1-1 promoter is positively associated with its allelic expression in apple in response to drought stress
Authors: Niu Chundong , Jiang Lijuan , Cao Fuguo , Liu Chen , Guo Junxing , Zhang Zitong , Yue Qianyu , Hou Nan , Liu Zeyuan , Li Xuewei , Tahir Muhammad Mobeen , He Jieqiang , Li Zhongxing , Li Chao , Ma Fengwang , Guan Qingmei
Published: July 2022

Miniature inverted-repeat transposable elements (MITEs) are widely distributed in the plant genome and can be methylated. However, whether DNA methylation of MITEs is associated with induced allelic expression and drought tolerance is unclear. Here, we identified the drought-inducible MdRFNR1 (root-type ferredoxin-NADP+ oxidoreductase) gene in apple (Malus domestica). MdRFNR1 plays a positive role in drought tolerance by regulating the redox system, including increasing NADP+ accumulation and catalase and peroxidase activities and decreasing NADPH levels. Sequence analysis identified a MITE insertion (MITE-MdRF1) in the promoter of MdRFNR1-1 but not the MdRFNR1-2 allele. MdRFNR1-1 but not MdRFNR1-2 expression was significantly induced by drought stress, which was positively associated with the MITE-MdRF1 insertion and its DNA methylation. The methylated MITE-MdRF1 is recognized by the transcriptional anti-silencing factors MdSUVH1 and MdSUVH3, which recruit the DNAJ domain-containing proteins MdDNAJ1, MdDNAJ2, and MdDNAJ5, thereby activating MdRFNR1-1 expression under drought stress. Finally, we showed that MdSUVH1 and MdDNAJ1 are positive regulators of drought tolerance. These findings illustrate the molecular roles of methylated MITE-MdRF1 (which is recognized by the MdSUVH–MdDNAJ complex) in induced MdRFNR1-1 expression as well as the drought response of apple and shed light on the molecular mechanisms of natural variation in perennial trees.
TaHRC suppresses the calcium-mediated immune response and triggers wheat Fusarium head blight susceptibility
Authors: Chen Hui , Su Zhenqi , Tian Bin , Hao Guixia , Trick Harold N , Bai Guihua
Published: July 2022

A wild-type allele of TaHRC suppresses the calcium-mediated immune response to Fusarium graminearum infection and facilitates the spread of Fusarium head blight disease symptoms within a wheat spike.
Policing and devolution in the UK: The ‘special’ case of Wales
Authors: Jones Robert , Harrison Michael , Jones Trevor
Published: July 2022

Political devolution in the UK has been responsible for major legislative changes to police governance, policy, and practice. Although policing in Wales remains formally part of the unitary ‘England and Wales’ system, the devolution of other key policy areas have contributed to the emergence of a distinctive Welsh policy context. In this paper, we explore the ways in which the devolution settlement in Wales has, albeit inadvertently, resulted in growing divergence from policing in England. We argue that devolution has transformed the operation of policing in Wales and has added a significant degree of complexity for Welsh police forces. The paper raises several important questions for policing in post-devolution Wales and underlines the need for further empirical research that can explore the extent, causes and implications of divergence between the policing systems of the constituent nations of the United Kingdom.
Anomalous enhancement of dilepton production as a precursor of color superconductivity
Authors: Nishimura Toru , Kitazawa Masakiyo , Kunihiro Teiji
Published: July 2022

We compute the modification of the photon self-energy due to dynamical diquark fluctuations developed near the critical temperature of two-flavor superconductivity, which is one of the color superconducting phases, through the Aslamasov–Larkin, Maki–Thompson, and density of states terms, which are responsible for the paraconductivity in metals at vanishing energy and momentum. The analysis is performed through an investigation of the diquark fluctuations within the normal phase determined by the mean-field approximation in the massless two-flavor Nambu–Jona-Lasinio model. It is shown that the rate has a significant enhancement in low-invariant-mass regions over a rather wide range of temperatures in the normal phase. This enhancement is worth exploring in the relativistic heavy-ion collisions, which may thereby reveal the significance of the diquark fluctuations in dense quark matter.
Reliability of Muscle Strength and Muscle Power Assessments Using Isokinetic Dynamometry in Neuromuscular Diseases: A Systematic Review
Authors: van der Woude Danny R , Ruyten Thijs , Bartels Bart
Published: July 2022

Objective

The purpose of this study was to critically appraise and summarize the evidence for reliability of muscle strength and muscle power assessment in patients with neuromuscular diseases (NMDs) using isokinetic dynamometry.

Methods

PubMed, CINAHL, and Embase electronic databases were searched from inception to March 8, 2022. Studies designed to evaluate reliability of muscle strength and power measurements using isokinetic dynamometry were included in this review. First, the methodological quality of the studies was assessed according to the Consensus-Based Standards for the Selection of Health Measurement Instruments guidelines. Next, the quality of measurement properties was determined. Finally, the methodological quality and quality of measurement properties of the studies were combined to obtain a best-evidence synthesis.

Results

A best-evidence synthesis of reliability was performed in 11 studies including postpoliomyelitis syndrome (n = 5), hereditary motor and sensory neuropathy (n = 2), motor neuron diseases (n = 1), myotonic dystrophy (n = 1), and groups of pooled NMDs (n = 2). A best-evidence synthesis on measurement error could not be performed. Quality of evidence on reliability ranged from high in postpoliomyelitis syndrome to very low in hereditary motor and sensory neuropathy, motor neuron diseases, and groups of pooled NMDs. The most frequently used outcome measure was peak torque, which was reliable in all populations (intraclass correlation coefficient >0.7).

Conclusion

The quality of evidence for reliability of isokinetic dynamometry was found to vary substantially among different NMDs. High quality of evidence has been obtained only in patients with postpoliomyelitis syndrome. Further research is needed in the majority of known NMDs to determine reliability and validity of isokinetic dynamometry.

Impact

The ability of isokinetic dynamometers to capture clinically relevant changes in muscle strength and muscle power in NMDs remains unclear. Isokinetic dynamometry results in NMDs should be interpreted with caution.
Reduced Cathepsin L expression and secretion into the extracellular milieu contribute to lung fibrosis in systemic sclerosis
Authors: Mouawad Joe E , Sharma Shailza , Renaud Ludivine , Pilewski Joseph M , Nadig Satish N , Feghali-Bostwick Carol
Published: July 2022

Objectives

Lung fibrosis is the leading cause of death in SSc, with no cure currently available. Antifibrotic Endostatin (ES) production does not reach therapeutic levels in SSc patients, suggesting a deficit in its release from Collagen XVIII by the main cleavage enzyme, Cathepsin L (CTSL). Thus, elucidating a potential deficit in CTSL expression and activity unravels an underlying molecular cause for SSc-driven lung fibrosis.

Methods

Fibrosis was induced experimentally using TGF-β in vitro, in primary human lung fibroblasts (pLFs), and ex vivo, in human lung tissues. ES and CTSL expression was quantified using ELISA, RT-qPCR, immunoblotting or immunofluorescence. Recombinant NC1-FLAG peptide was used to assess CTSL cleavage activity. CTSL expression was also compared between SSc vs normal (NL)-derived pLFs and lung tissues.

Results

ES levels were significantly reduced in media conditioned by TGF-β-induced pLFs. TGF-β-stimulated pLFs significantly reduced expression and secretion of CTSL into the extracellular matrix (ECM). CTSL was also sequestered in its inactive form into extracellular vesicles, further reducing its availability in the ECM. Media conditioned by TGF-β-induced pLFs showed reduced cleavage of NC1-Flag and reduced release of the antifibrotic ES fragment. SSc-derived pLFs and lung tissues expressed significantly lower levels of CTSL compared with NL.

Conclusions

Our findings identify CTSL as a protein protective against lung fibrosis via its activation of antifibrotic ES, and whose expression in SSc pLFs and lung tissues is suppressed. Identifying strategies to boost CTSL endogenous levels in SSc patients could serve as a viable therapeutic strategy.
Real-Time Symptom Capture of Hallucinations in Schizophrenia with fMRI: Absence of Duration-Dependent Activity
Authors: Gill Karanvir , Percival Chantal , Roes Meighen , Arreaza Leo , Chinchani Abhijit , Sanford Nicole , Sena Walter , Mohammadsadeghi Homa , Menon Mahesh , Hughes Matthew , Carruthers Sean , Sumner Philip , Woods Will , Jardri Renaud , Sommer Iris E , Rossell Susan L , Woodward Todd S
Published: July 2022

Background

While advances in the field of functional magnetic resonance imaging (fMRI) provide new opportunities to study brain networks underlying the experience of hallucinations in psychosis, there are methodological challenges unique to symptom-capture studies.

Study Design

We extracted brain networks activated during hallucination-capture for schizophrenia patients when fMRI data collected from two sites was merged (combined N = 27). A multidimensional analysis technique was applied, which would allow separation of brain networks involved in the hallucinatory experience itself from those involved in the motor response of indicating the beginning and end of the perceived hallucinatory experience. To avoid reverse inference when attributing a function (e.g., a hallucination) to anatomical regions, it was required that longer hallucinatory experiences produce extended brain responses relative to shorter.

Study Results

For radio-speech sound files, an auditory perception brain network emerged, and displayed speech-duration-dependent hemodynamic responses (HDRs). However, in the hallucination-capture blocks, no network showed hallucination-duration-dependent HDRs, but a retrieved network that was anatomically classified as motor response emerged.

Conclusions

During symptom capture of hallucinations during fMRI, no HDR showed duration dependence, but a brain network anatomically matching the motor response network was retrieved. Previous reports on brain networks detected by fMRI during hallucination capture are reviewed in this context; namely, that the brain networks interpreted as involved in hallucinations may in fact be involved only in the motor response indicating the onset of the hallucination.
Single-Cell RNA-Seq Identifies Dynamic Cardiac Transition Program from ADCs Induced by Leukemia Inhibitory Factor
Authors: Yao Jiayi , Ma Feiyang , Zhang Li , Zhu Ching , Jumabay Medet , Yao Zehao , Wang Lumin , Cai Xinjiang , Zhang Daoqin , Qiao Xiaojing , Shivkumar Kalyanam , Pellegrini Matteo , Yao Yucheng , Wu Xiuju , Boström Kristina I
Published: July 2022

Adipose-derived cells (ADCs) from white adipose tissue are promising stem cell candidates because of their large regenerative reserves and the potential for cardiac regeneration. However, given the heterogeneity of ADC and its unsolved mechanisms of cardiac acquisition, ADC-cardiac transition efficiency remains low. In this study, we explored the heterogeneity of ADCs and the cellular kinetics of 39,432 single-cell transcriptomes along the leukemia inhibitory factor (LIF)-induced ADC-cardiac transition. We identified distinct ADC subpopulations that reacted differentially to LIF when entering the cardiomyogenic program, further demonstrating that ADC-myogenesis is time-dependent and initiates from transient changes in nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. At later stages, pseudotime analysis of ADCs navigated a trajectory with 2 branches corresponding to activated myofibroblast or cardiomyocyte-like cells. Our findings offer a high-resolution dissection of ADC heterogeneity and cell fate during ADC-cardiac transition, thus providing new insights into potential cardiac stem cells.
P21-Activated Kinase 4 Pak4 Maintains Embryonic Stem Cell Pluripotency via Akt Activation
Authors: Cheng Fangyuan , Li Mingyue , Thorne Rick Francis , Liu Guangzhi , Zhang Yuwei , Wu Mian , Liu Lianxin
Published: July 2022

Exploiting the pluripotent properties of embryonic stem cells (ESCs) holds great promise for regenerative medicine. Nevertheless, directing ESC differentiation into specialized cell lineages requires intricate control governed by both intrinsic and extrinsic factors along with the actions of specific signaling networks. Here, we reveal the involvement of the p21-activated kinase 4 (Pak4), a serine/threonine kinase, in sustaining murine ESC (mESC) pluripotency. Pak4 is highly expressed in R1 ESC cells compared with embryonic fibroblast cells and its expression is progressively decreased during differentiation. Manipulations using knockdown and overexpression demonstrated a positive relationship between Pak4 expression and the clonogenic potential of mESCs. Moreover, ectopic Pak4 expression increases reprogramming efficiency of Oct4-Klf4-Sox2-Myc-induced pluripotent stem cells (iPSCs) whereas Pak4-knockdown iPSCs were largely incapable of generating teratomas containing mesodermal, ectodermal and endodermal tissues, indicative of a failure in differentiation. We further establish that Pak4 expression in mESCs is transcriptionally driven by the core pluripotency factor Nanog which recognizes specific binding motifs in the Pak4 proximal promoter region. In turn, the increased levels of Pak4 in mESCs fundamentally act as an upstream activator of the Akt pathway. Pak4 directly binds to and phosphorylates Akt at Ser473 with the resulting Akt activation shown to attenuate downstream GSK3β signaling. Thus, our findings indicate that the Nanog-Pak4-Akt signaling axis is essential for maintaining mESC self-renewal potential with further importance shown during somatic cell reprogramming where Pak4 appears indispensable for multi-lineage specification.
An Interferon-γ/FLT3 Axis Positively Regulates Hematopoietic Progenitor Cell Expansion from Human Pluripotent Stem Cells
Authors: Kitajima Kenji , Shingai Minako , Ando Hikaru , Hamasaki Mako , Hara Takahiko
Published: July 2022

Since it became possible to differentiate human pluripotent stem cells (hPSCs) into hematopoietic cells in vitro, great efforts have been made to obtain highly potent hematopoietic stem/progenitor cells (HSPCs) from hPSCs. Immunophenotypical HSPCs can be obtained from hPSCs, but their repopulating potential in vivo is low. Here, we developed a novel hematopoietic differentiation method for human-induced pluripotent stem cells (hiPSCs) to determine why the existing hPSC differentiation systems are inadequate. hiPSC-derived CD45+CD34+ cells in our system were mostly CD38− immunophenotypical HSPCs. The vast majority of human CD45+CD34+ cells in umbilical cord blood, fetal liver, and bone marrow are CD38+ hematopoietic progenitor cells (HPCs); therefore, the poor production of CD38+ HPCs was indicative of a systematic problem. hiPSC-derived CD45+CD34+ cells did not express FLT3, a receptor tyrosine kinase. Exogenous FLT3 activity significantly enhanced the production of CD38+ HPCs from hiPSCs. Thus, poor production of CD38+ HPCs was due to a lack of FLT3 expression. Interferon-γ upregulated expression of FLT3 and increased the number of CD38+ HPCs among hiPSC-derived CD45+CD34+ cells. These results suggest that the poor production of CD38+ HPCs with hPSC differentiation systems is due to a lack of FLT3 expression, and that the addition of interferon-γ can solve this problem.
Phylogenomics Supports the Monophyly of Aphelids and Fungi and Identifies New Molecular Synapomorphies
Authors: Galindo Luis Javier , Torruella Guifré , López-García Purificación , Ciobanu Maria , Gutiérrez-Preciado Ana , Karpov Sergey A , Moreira David
Published: July 2022

The supergroup Holomycota, composed of Fungi and several related lineages of unicellular organisms (Nucleariida, Rozellida, Microsporidia, and Aphelida), represents one of the major branches in the phylogeny of eukaryotes. Nevertheless, except for the well-established position of Nucleariida as the first holomycotan branch to diverge, the relationships among the other lineages have so far remained unresolved largely owing to the lack of molecular data for some groups. This was notably the case aphelids, a poorly known group of endobiotic phagotrophic protists that feed on algae with cellulose walls. The first molecular phylogenies including aphelids supported their sister relationship with Rozellida and Microsporidia which, collectively, formed a new group called Opisthosporidia (the “Opisthosporidia hypothesis”). However, recent phylogenomic analyses including massive sequence data from two aphelid genera, Paraphelidium and Amoeboaphelidium, suggested that the aphelids are sister to fungi (the “Aphelida $+$ Fungi hypothesis”). Should this position be confirmed, aphelids would be key to understanding the early evolution of Holomycota and the origin of Fungi. Here, we carry out phylogenomic analyses with an expanded taxonomic sampling for aphelids after sequencing the transcriptomes of two species of the genus Aphelidium (Aphelidium insulamus and Aphelidium tribonematis) in order to test these competing hypotheses. Our new phylogenomic analyses including species from the three known aphelid genera strongly rejected the Opisthosporidia hypothesis. Furthermore, comparative genomic analyses further supported the Aphelida $+$ Fungi hypothesis via the identification of 19 orthologous genes exclusively shared by these two lineages. Seven of them originated from ancient horizontal gene transfer events predating the aphelid–fungal split and the remaining 12 likely evolved de novo, constituting additional molecular synapomorphies for this clade. Ancestral trait reconstruction based on our well-resolved phylogeny of Holomycota suggests that the progenitor of both fungi and rozellids, was aphelid-like, having an amoeboflagellate state and likely preying endobiotically on cellulose-containing, cell-walled organisms. Two lineages, which we propose to call Phytophagea and Opisthophagea, evolved from this ancestor. Phytophagea, grouping aphelids and classical fungi, mainly specialized in endobiotic predation of algal cells. Fungi emerged from this lineage after losing phagotrophy in favor of osmotrophy. Opisthophagea, grouping rozellids and Microsporidia, became parasites, mostly of chitin-containing hosts. This lineage entered a progressive reductive process that resulted in a unique lifestyle, especially in the highly derived Microsporidia. [Aphelida, fungi, Holomycota, horizontal gene transfer, phylogenomics, synapomorphy.]
IDphy: An International Online Resource for Molecular and Morphological Identification of Phytophthora
Authors: Abad Z. Gloria , Burgess Treena I. , Redford Amanda J. , Bienapfl John C. , Srivastava Subodh , Mathew Reny , Jennings Krysta
Published: July 2022

Phytophthora, with 203 species, is a genus of high importance in agriculture worldwide. Here, we present the online resource “IDphy”, developed to facilitate the correct identification of species of Phytophthora using the type specimens from the original descriptions wherever possible. IDphy emphasizes species of high economic impact and regulatory concern for the United States. IDphy presents an interactive Lucid key and a tabular key for 161 culturable species described as of May 2018, including 141 ex-types and 20 well-authenticated specimens. IDphy contains standard operating procedures for morphological and molecular characterization, as well as a glossary, image gallery, and numerous links. Each of the 161 factsheets includes access to nomenclature and morphological and molecular features, including sequences of the internal transcribed spacer ribosomal DNA, cytochrome C oxidase subunit I (barcoding genes), YPT1, β-tubulin, elongation factor 1a, L10, heat shock protein 90, and other genes. IDphy contains an innovative in silico BLAST and phylogenetic sequence analysis using NCBI. The IDphy mobile app, released in August 2021 (free for Android or iOS), allows users to take the Lucid key into the laboratory. IDphy is the first online identification tool based on the ex-types implemented for plant pathogens. In this article, we also include information for 21 new species and one hybrid described after the publication of IDphy, the status of the specimens of the types and ex-types at international herbaria and culture collections, and the status of genomes at the GenBank (currently 153 genome assemblies which correspond to 42 described species, including 16 ex-types). The effectiveness of the IDphy online resource and the content of this article could inspire other researchers to develop additional identification tools for other important groups of plant pathogens.
Novel Detection and Quantification Approach of Erwinia amylovora In Vitro and In Planta Using SYBR Green-Based Real-Time PCR Assay
Authors: Jin Yong Ju , Lee Seung Yeup , Kong Hyun Gi , Yang Su In , Ham Hyeonheui , Lee Mi-Hyun , Park Dong Suk
Published: July 2022

Fire blight, caused by the bacterial pathogen Erwinia amylovora, is a highly destructive disease of apple and pear. Because the apple tree gets systemically infected with E. amylovora and eventually dies, E. amylovora is a considerably important pathogen in the orchard that requires long-term management. In addition, it is crucial to prevent the spread of the pathogen by expeditious diagnosis. In this study, via comparative approaches to the genome sequences of the strains of various Erwinia spp., we designed specific primers targeting a hypothetical gene that is single copy and located in the chromosomal DNA of E. amylovora. This primer set specifically amplified the DNA of E. amylovora but no other bacteria, including E. pyrifoliae, Pectobacterium spp., Pantoea spp., and Dickeya chrysanthemi. Furthermore, the SYBR Green-based real-time PCR using the primer set allowed accurate estimation of the population of E. amylovora. Developing a rapid and accurate diagnostic method using the novel primer set enables effective defense against pathogen spread through continuous monitoring and quick response.
Characterization of Legal Claims Involving Patients with Pyoderma Gangrenosum
Authors: Pfeifer Hailey J. , Orfaly Victoria E. , Rick Jonathan W. , Damitio Christopher , Ortega Loayza Alex G.
Published: July 2022

OBJECTIVE

To review the litigation literature related to patients with pyoderma gangrenosum (PG) to characterize the legal issues they face.

DATA SOURCES

Data sources include law databases Casetext and Lexis Nexis.

STUDY SELECTION

All disability and medical liability claims directly involving patients with PG were included.

DATA EXTRACTION

Data extraction came directly from Casetext and Lexis Nexis. All cases extracted came from September 1965 to December 2020. This resulted in 32 cases, 18 of which were excluded because they did not mention the plaintiff having a diagnosis of PG (n = 14).

DATA SYNTHESIS

The review found a total of six medical liability cases in which adverse health outcomes were reported, including prolonged suffering (2/6 cases), unnecessary treatments or procedures (2/6), exacerbation of disease (1/6 cases), and permanent scarring (1/6 cases). Despite this, two plaintiffs won their case and only one of them received any monetary award. Similarly, of the eight disability claims in the review, four were ruled in the favor of the plaintiffs and only two resulted in immediate awarding of benefits. Half of medical liability cases occurred in correctional facilities after the denial of appropriate care.

CONCLUSIONS

The findings demonstrate a need for access to specialty care in incarcerated populations. Cases that occurred in a hospital setting also stress the importance of initiatives such as telemedicine to efficiently increase access to care in a cost-effective manner. Further, PG has been recognized as a severe impairment in disability claims despite patients being denied because they were deemed able to perform other work.
ALDH2 mutation results in excessive basal nitric oxide production and a delayed response to nitroglycerin
Authors: Zhu Hongming , Hu Jingjing , Dong Zhen , Liu Yang , Sun Xiaolei , Sun Aijun
Published: July 2022

Background and purpose:

Nitroglycerin tolerance is a common phenomenon in patients with coronary artery disease (CAD). Aldehyde dehydrogenase 2 (ALDH2) is the enzyme that metabolizes nitroglycerin to its active form nitric oxide (NO). Previous studies showed altered nitroglycerin in subjects with ALDH2 mutation, but the functional impact on endothelial cells is not fully understood.

Methods:

In the first step of in vitro experiments, we examined functional properties of induced pluripotent stem cell-derived CD144+ endothelial cells (iPSC-ECs) that expressed wildtype (WT) vs ALDH2+/− variant. In the second step of human studies, diameter of the left anterior descending (LAD) coronary artery was determined using angiography in 151 adult volunteers (111 with WT ALDH2, 32 with ALDH2+/− and 8 with ALDH2−/− genotype) prior to as well as after intracoronary injection of 200-μg nitroglycerin.

Results:

Briefly, the ALDH2+/− iPSC-ECs demonstrated impaired low-density lipoprotein (LDL) uptake, proliferation, migration, tube formation, oxidative stress resistance, and viability. In comparison to the WT control, the ALDH2+/− iPSC-ECs had elevated NO production under baseline conditions, but exhibited a delayed NO release after nitroglycerin treatment. Exposure to 10-μg/mL nitroglycerin for 2 h increased NO production in WT iPSC-ECs but 4-h exposure was required to stimulate NO production in the ALDH2+/− iPSC-ECs. In comparison to the WT control, the subjects carrying the ALDH2+/− variants had seemingly larger LAD coronary artery diameter (3.5 and 3.8 mm vs 3.4 mm in the WT control), but attenuated vasodilatory response to nitroglycerin (ALDH2MUT group vs the WT control, 7.1 ± 0.6% vs 10.1 ± 0.8%, P = 0.024).

Conclusion:

These findings indicated elevated NO production by endothelia cells under basal conditions but attenuated response to nitroglycerin upon ALDH2 mutation.
Elevated plasma homocysteine level is associated with poor ST-segment resolution in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention at high altitude
Authors: Liu Bei , Yang Shujuan , Yang Lixia , Zhang Bin , Guo Ruiwei
Published: July 2022

Background and purpose:

Poor ST-segment resolution (STR) is strongly associated with poor prognosis in patients with ST segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). previous studies suggested higher HCY level in the people who live in high altitudes, so a retrospective analysis is conducted to examine the potential relationship between elevated serum HCY and poor STR after PPCI at high altitudes.

Methods:

This retrospective analysis included 308 high-altitude dwelling patients (1800-2200 meters elevation from the sea level) undergoing PPCI for STEMI during a period from September 2021 to March 2022. Clinical data were collected and statistically analyzed.

Results:

In comparison to the patients with normal plasma homocysteine (≤15 mmol/L; n = 155), patients with elevated homocysteine (>15 mmol/L) had higher percentage of men (92.81% vs. 80.00%; p = 0.001) and smoker (79.08% vs. 63.87%; p = 0.003), but no difference in other key baseline characteristics. The rate of complete ST-segment resolution after PPCI (≥ 70%) was 83.23% in the control group and 49.67% in the elevated HCY group (p ≤ 0.001). In multivariable regression analysis, poor ST-segment resolution (<70%) was independently associated with longer pain-to-balloon time (OR 0.832; 95%CI: 0.775–0.894), lower uric acid (OR 1.003; 95%CI: 1.000-1.005), and elevated HCY (OR 0.957 vs. normal HCY; 95%CI: 0.937–0.977).

Conclusion:

Elevated plasma HCY level was associated with poor ST segment resolution in patients undergoing PPCI STEMI at high altitude.
Low-dose aspirin for the prevention of atherothrombosis across the cardiovascular risk continuum
Authors: Walker Jaqui
Published: July 2022

At the 2021 International Aspirin Foundation Symposium of Oriental Congress of Cardiology, a panel of distinguished cardiologists from around the world gathered to present their recent research findings and discuss viewpoints of aspirin use along the entire continuum of cardiovascular disease (CVD) prevention in the general population as well as in specific patient groups.

Aspirin produces long-lasting effects on platelet function and cumulative inhibition of platelet thromboxane production by irreversibly inactivating the prostaglandin H-synthase (PGHS). Consistent with saturability of platelet cyclooxygenase 1 (COX-1) inactivation and thromboxane A2 (TXA2) suppression at low doses, a body of convincing evidence showed no additional benefit from high versus low-dose aspirin.

Trials of aspirin as primary prevention trials are challenging due to the low event rate and reduced patient compliance over time. Nevertheless, evidence from the ASCEND and TIPS3 trials supported the benefit of aspirin in primary cardiovascular prevention.

The Chinese population has among the highest CVD risk in the world. Significant achievement has been made in this respect. For example, the benefit of aspirin use as primary prevention is now recognized in the Chinese guidelines similar to the US, European guidelines, with some unique features that are helpful for the Chinese population (eg, greater emphasis on dynamical reassessment of risk versus benefit).

As secondary prevention in patients with transient ischaemic attack (TIA) and minor stroke, low-dose aspirin reduces the risk of major recurrent stroke as well as stroke severity.

Peripheral arterial disease (PAD) management and screening is of growing importance. The COMPASS and VOYAGER studies provide new evidence for dual-pathway inhibition (DPI) antithrombotic therapy with low-dose aspirin and reduced-dose rivaroxaban.

A major concern with the use of aspirin is the risk of gastrointestinal (GI) bleeding. Strategies to protect patients include eradication of Helicobacter pylori infection and co-prescription of proton pump inhibitors. Different P2Y12 inhibitors and low-dose aspirin have similar levels of bleeding risk, but the risk is magnified when these agents are taken together.