bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of adverse childhood experiences (ACEs) with obesity and underweight in children
Authors: Hanć Tomasz , Bryl Ewa , Szcześniewska Paula , Dutkiewicz Agata , Borkowska Aneta R. , Paszyńska Elżbieta , Słopień Agnieszka , Dmitrzak-Węglarz Monika
Published: October 2021

Purpose

The aim of the study was to test the hypothesis that adverse childhood experiences (ACEs) are related to both obesity and underweight from childhood, and that the association of ACEs with weight abnormalities is modulated by type of ACEs, sex and socioeconomic status (SES) indices.

Methods

The relations between ACEs (0 vs ≥ 1), ACE accumulation and ACE type with weight status andzscores BMI were assessed in 503 children aged 6–12 years from Poznan, Poland. The effects of interaction of ACEs with sex and SES onzscores BMI were included in the analyses.

Results

ACEs were significantly related to both obesity and underweight, in unadjusted analysis, and when sex and SES indices, such as size of place of residence, people per room in household, and parental education were controlled. The relation of ACEs withzscores BMI was modulated by ACE type, parental subjective assessment of economic situation of a family and parental education. ACE accumulation was not related to an increase of obesity or underweight rate, orzscores BMI.

Conclusion

The study implicates the need for both obesity and underweight prevention in individuals with adverse experiences as early as in childhood.

Level of evidence

III: evidence obtained from well-designed cohort study.
Current Status and Future Perspectives on the Internet of Things in Oncology
Authors: Muhsen Ibrahim N. , Rasheed Omar W. , Habib Eiad A. , Alsaad Rakan K. , Maghrabi Mohannad K. , Rahman Md A. , Sicker Douglas , Wood William A. , Beg Muhammad S. , Sung Anthony D. , Hashmi Shahrukh K.
Published: October 2021

The Internet of Things (IoT) has penetrated many aspects of everyday human life. The use of IoT in healthcare has been expanding over the past few years. In this review, we highlighted the current applications of IoT in the medical literature, along with the challenges and opportunities. IoT use mainly involves sensors and wearables, with potential applications in improving the quality of life, personal health monitoring, and diagnosis of diseases. Our literature review highlights that the current main application studied in the literature is physical activity tracking. In addition, we discuss the current technologies that would help IoT-enabled devices achieve safe, quick, and meaningful data transfer. These technologies include machine learning/artificial intelligence, 5G, and blockchain. Data on current IoT-enabled devices are still limited, and future research should address these devices’ effect on patients’ outcomes and the methods by which their integration in healthcare will avoid increasing costs.
The Clozapine Handbook
Authors: Meyer Jonathan M. , Stahl Stephen M.
Published: October 2021

Real-world and clinical trial data support that clozapine is the only effective antipsychotic for treatment resistant schizophrenia and other severe mental illnesses. Clozapine also reduces rates of suicidality, psychiatric hospitalization and all-cause mortality. However, clozapine is underutilized for two reasons: misunderstandings of its efficacy benefits and misapprehension of, limited knowledge or misinformation about the management of treatment related risks and adverse effects. In response to worldwide efforts to promote clozapine use, this user-friendly Handbook provides clinicians with evidence-based approaches for patient management, as well as logical approaches to the management of clinical situations and adverse effects. It outlines clearly the rationale for specific management decisions and prioritises the options based on this logic. This Handbook is designed for use by clinicians worldwide and is essential reading for all mental health care professionals.
Prescriber's Guide
Authors: Stahl Stephen M.
Published: October 2021

With the range of psychotropic drugs expanding and the usages of existing medications diversifying, we are pleased to present the Seventh Edition of the world's best-selling formulary in psychopharmacology. The new edition features nine new compounds as well as information about several new formulations of existing drugs. Many important new indications are covered for existing drugs, as are updates to the profiles of the entire content and collection, including new injectable and transdermal formulations, as well as updated warnings and indications. The Pearls have all been refreshed and the antipsychotics section has been completely revised. With its easy-to-use, full-colour template-driven navigation system, Prescriber's Guide combines evidence-based data with clinically informed advice to support everyone who is prescribing in the field of mental health.
Moving Pictures and Renaissance Art History
Authors: Emison Patricia
Published: October 2021

Film, like the printed imagery inaugurated during the Renaissance, spread ideas - not least the idea of the power of visual art - across not only geographical and political divides but also strata of class and gender. Moving Pictures and Renaissance Art History examines the early flourishing of film, 1920s-mid-60s, as partly reprising the introduction of mass media in the Renaissance, allowing for innovation that reflected an art free of the control of a patron though required to attract a broad public. Rivalry between word and image, narrative and visual composition shifted in both cases toward acknowledging the compelling nature of the visual. The twentieth century also saw the development of the discipline of art history; transfusions between cinematic practice and art historical postulates and preoccupations are part of the story told here.
COVID-19, the Ubiquitous National Security Threat: Lessons Learned Around the Globe
Authors: Grondel Shannon Havlicak
Published: October 2021

Today is October 1, 2020. In this moment, over 34 million bodies—that we know of—have hosted a deadly virus and more than one million of those bodies have succumbed to the strain of their unwelcome, malignant guest. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—genetically related to, yet different from the coronavirus responsible for the 2003 SARS outbreak—is the virus that causes coronavirus disease 2019 (COVID-19). The virus first materialized in Wuhan, Hubei province, China as early as November 17, 2019, and quickly escalated from a small cluster of cases of what appeared to be pneumonia to a global pandemic by March 11, 2020.
Un trono dividido: El origen y los movimientos de la Banca Jeroglífica 1 de Ixtutz, Guatemala
Authors: Carter Nicholas , Reyes Mara Antonieta , Stuart David , Houston Stephen , Lukach Katharine , O'Neil Megan
Published: October 2021

Aquí presentamos el descubrimiento de una banca jeroglífica esculpida del sitio maya de Ixtutz, Petén, Guatemala. Analizamos la inscripción jeroglífica en la banca y discutimos la historia del objecto en el contexto de su producción, su desmantelamiento y reutilización subsecuente, y la remoción de unas piezas del sitio. Mostramos que dos bloques inscritos de caliza, uno de ellos en una colección privada en Bruselas y el otro en el Los Angeles County Museum of Art, Los Angeles, California, pertenecen al mismo trono, y llamamos para su repatriación voluntaria a Guatemala.
The Match Between Structural Attributes and Content-Based Orientation of Managerial Cognition: An Exploratory fsQCA Study of ‘Hidden Champions’
Authors: Lei Linan , Fu Yanan , Wu Xiaobo , Du Jian
Published: October 2021

Strategic decision makers interpret information and translate it into organizational action through the lens of strategic schemas. How should firms realize high performance with various strategic schemas? Cognitive content and structure have been shown to underlie strategic schemas, but few studies have considered them together. This study employs aggregation analysis to clarify the interaction between cognitive content (technology orientation, market orientation) and structure (complexity, centrality) in affecting the firm performance (FP) of ‘hidden champion’ companies, identified by the Economy and Information Technology Department of Zhejiang Province, China. The empirical method applies fuzzy-set qualitative comparative analysis to generate strategic schema profiles for high FP. This exploratory study fills a gap in the literature on managerial cognition and provides key lessons from ‘hidden champion’ companies in China and their paths for small- and medium-sized enterprises to grow.
An enigmatic lower jaw from the Lower Muschelkalk (Anisian, Middle Triassic) of Winterswijk provides insights into dental configuration, tooth replacement and histology
Authors: Spiekman Stephan N.F. , Klein Nicole
Published: October 2021

In the aftermath of the Permo-Triassic mass extinction event, several reptile lineages radiated to form major components of marine faunas during the entire Mesozoic. The Lower Muschelkalk, which was deposited within a shallow inland sea in the Germanic Basin during the Middle Triassic, is one of the most important regions for understanding the early evolution of Mesozoic marine reptiles. Here, we present a new specimen from the Lower Muschelkalk of Winterswijk in the Netherlands, comprising an isolated left dentary that is morphologically distinct from any well-known Triassic vertebrate. We provide a detailed description of the jaw and the teeth using histological and micro-computed tomographic analyses. The anterior teeth are fang-like and curved, whereas the posterior teeth are wider and triangular-shaped. Tooth implantation is thecodont and teeth are ankylosed to the base of the alveolus. Replacement teeth are developed directly lingual to the functional teeth, starting with the formation of a resorption cavity on the dorsal surface of the alveolar margin. The replacement pattern cannot be observed in detail but is regular in the posterior part of the dentary with each tooth being alternated with an empty alveolus. The specimen can likely be assigned to Eosauropterygia based on its jaw morphology and dental morphology and replacement pattern, and it is remarkably similar to maxillae referred to the enigmatic Lamprosauroides goepperti from the Lower Muschelkalk of Poland. The dentary from Winterswijk lacks enlarged, ‘alveolarised’ crypts and corresponding distinct dental lamina foramina (DLFs) for the replacement teeth, a configuration that is typical of Sauropterygia, but which was likely not omnipresent in this clade. The specimen also exhibits loosely folded plicidentine at the roots of the teeth, likely representing the first identification of this feature in Sauropterygia.
Do parties’ representation failures affect populist attitudes? Evidence from a multinational survey experiment
Authors: Castanho Silva Bruno , Wratil Christopher
Published: October 2021

The rise of populist forces in Western democracies is often linked to representation failures. However, to date we lack causally identified evidence for the effect of parties’ representation on populist attitudes. We address this lacuna through a survey experiment conducted in 12 European Union countries involving 23,257 subjects. Our experiment manipulates citizens’ perceptions of being represented by national parties in the 2019 European elections campaign, and identifies the effect of perceived representation on populist attitudes. The results reveal that poor representation increases populist attitudes in respondents that did not express such attitudes pretreatment, but has no effect among those who were already populist. We demonstrate that this effect is primarily due to parties’ representation failures triggering citizens’ anti-elite sentiment.
The status of sibilant harmony in Diné Bizaad (Navajo)
Authors: Palakurthy Kayla
Published: October 2021

This article presents an acoustic phonetic study of contemporary Diné Bizaad (Navajo) sibilant harmony, with a focus on the realization of /s/ and /ʃ/ in two verbal prefixes and one nominal prefix. Data come from wordlists and connected speech recorded in interviews with 50 Diné Bizaad–English bilinguals, aged 18–75 years. The frequency of harmony in each prefix is calculated for speakers of different ages, then acoustic measurements of spectral center of gravity are measured and statistically compared to those in sibilants occurring in harmony-triggering and non-harmony triggering conditions. Results show no significant intergenerational differences in the phonetic or phonological realization of sibilant harmony; speakers consistently and categorically harmonize the two verbal prefixes analyzed here, but rarely harmonize the nominal prefix. This study contributes new phonetic documentation of a typologically rare phonological process and suggests that, in contrast to findings from other studies on endangered languages, sibilant harmony is not undergoing attrition or contact-induced change.
A nonlinear optimal control approach for underactuated power-line inspection robots
Authors: Rigatos Gerasimos , Zervos Nikolaos , Siano Pierluigi , Abbaszadeh Masoud , Pomares Jorge , Wira Patrice
Published: October 2021

The article proposes a nonlinear optimal (H-infinity) control approach for a type of underactuated power-line inspection robots. To implement this control scheme, the state-space model of the power-line inspection robots undergoes first approximate linearization around a temporary operating point, through first-order Taylor series expansion and through the computation of the associated Jacobian matrices. To select the feedback gains of the controller an algebraic Riccati equation is solved at each time step of the control method. The global stability properties of the control loop are proven through Lyapunov analysis. The significance of the article’s results is outlined in the following: (i) the proposed control method is suitable for treating underactuated robotic systems and in general nonlinear dynamical systems with control inputs gain matrices which are in a nonquadratic form, (ii) by achieving stabilization of the power-line inspection robots in underactuation conditions the proposed control method ensures the reliable functioning of these robotic systems in the case of actuators’ failures or enables the complete removal of certain actuators and the reduction of the weight of these robotic systems, (iii) the proposed control method offers a solution to the nonlinear optimal control problem which is of proven global stability while also remaining computationally tractable, (iv) the proposed nonlinear optimal control method retains the advantages of linear optimal control that is fast and accurate tracking of reference setpoints under moderate variations of the control inputs, and (v) by minimizing the amount of energy that is dispersed by the actuators of the power-line inspection robots the proposed control method improves the autonomy and operational capacity of such robotic systems.
Determinants of early lexical acquisition: Effects of word- and child-level factors on Dutch children's acquisition of words
Authors: VERHAGEN Josje , VAN STIPHOUT Mees , BLOM Elma
Published: October 2021

Previous research on the effects of word-level factors on lexical acquisition has shown that frequency and concreteness are most important. Here, we investigate CDI data from 1,030 Dutch children, collected with the short form of the Dutch CDI, to address (i) how word-level factors predict lexical acquisition, once child-level factors are controlled, (ii) whether effects of these word-level factors vary with word class and age, and (iii) whether any interactions with age are due to differences in receptive vocabulary. Mixed-effects regressions yielded effects of frequency and concreteness, but not of word class and phonological factors (e.g., word length, neighborhood density). The effect of frequency was stronger for nouns than predicates. The effects of frequency and concreteness decreased with age, and were not explained by differences in vocabulary knowledge. These findings extend earlier results to Dutch, and indicate that effects of age are not due to increases in vocabulary knowledge.
The role of individual factors in L2 vocabulary learning with cognitive-linguistics-based static and dynamic visual aids
Authors: Sato Takeshi , Lai Yuda , Burden Tyler
Published: October 2021

The present study aims to verify the impact of dynamic aids on learning L2 prepositions in relation to individual learner variables. Situated within the cognitive linguistics (CL) framework and differing from previous research, the present study hypothesizes that dynamic (animated) aids are not equally effective for all learners; rather, their effectiveness differs according to learners’ first languages (L1s) (Chinese or Japanese) and information-processing styles (verbalizers or imagers). To verify this hypothesis, we utilized learning materials comprised of static and dynamic images for three English spatial prepositions (above,on,over). After conducting a Style of Processing questionnaire, we administered three cloze tests (pretest, posttest, and delayed posttest) of target words to Taiwanese and Japanese participants (N= 109), whose L1s differed in terms of their linguistic proximity to English. Although no significant differences were found between the treatment groups in tests for all participants, the results were differentiated by individual factors. In results of a two-way ANOVA, Taiwanese participants showed significantly greater improvement from the pretest to posttest than Japanese participants when the participants used dynamic images, whereas the Japanese group made more learning gains from the posttest to the delayed posttest test. Moreover, imagers obtained more benefits from the visual aids, whether static or dynamic, than verbalizers. Our findings indicate that CL-based visual aids are beneficial and that individual factors, especially learners’ L1, may produce different learning effects, especially in multimedia environments.
Type-based analysis of logarithmic amortised complexity
Authors: Hofmann Martin , Leutgeb Lorenz , Obwaller David , Moser Georg , Zuleger Florian
Published: October 2021

We introduce a novel amortised resource analysis couched in a type-and-effect system. Our analysis is formulated in terms of the physicist’s method of amortised analysis and is potentialbased. The type system makes use of logarithmic potential functions and is the first such system to exhibit logarithmic amortised complexity. With our approach, we target the automated analysis of self-adjusting data structures, like splay trees, which so far have only manually been analysed in the literature. In particular, we have implemented a semi-automated prototype, which successfully analyses the zig-zig case of splaying, once the type annotations are fixed.
Inflammatory cytokines in and cognitive function of adolescents with first-episode schizophrenia, bipolar disorder, or major depressive disorder
Authors: Chen Mu-Hong , Hsu Ju-Wei , Huang Kai-Lin , Tsai Shih-Jen , Tu Pei-Chi , Bai Ya-Mei
Published: October 2021

Background

Few studies have explored the complex relationship of pro- and anti-inflammatory cytokines with cognitive function in adolescents with first-episode schizophrenia, bipolar disorder, or major depressive disorder.

Methods

In total, 26, 35, and 29 adolescents with first-episode schizophrenia, bipolar disorder, and major depressive disorder, respectively, and 22 age- and sex-matched controls were included in the current study. Cytokines, namely interleukin (IL)-2, IL-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP), were assessed. The Wisconsin Card Sorting Test (WCST) and the working memory task were administered to assess cognitive function.

Results

Using generalized linear models with adjustment for demographic data and clinical symptoms, patients with bipolar disorder were found to exhibit the highest levels of CRP (P = .023), IL-6 (P = .022), and TNF-α (P = .011), and had the lowest IL-2 levels (P = .034) among the four groups. According to the results of the WCST and working memory task, adolescents with schizophrenia exhibited the lowest performance in cognitive function. In addition, among the assessed cytokines, only CRP levels (P = .027) were negatively associated with WCST scores.

Discussion

Dysregulated pro- and anti-inflammatory cytokines and impaired cognitive functioning were observed in first-episode adolescent-onset schizophrenia, bipolar disorder, and major depressive disorder. The altered cytokine profiles may play important roles in the pathophysiology of schizophrenia, bipolar disorder, and major depressive disorder.
A Liquid Metal Encapsulation for Analyzing Porous Nanomaterials by Atom Probe Tomography
Authors: Kim Se-Ho , El-Zoka Ayman A , Gault Baptiste
Published: October 2021

Analyzing porous (nano)materials via atom probe tomography has been notoriously difficult. Voids and pores act as concentrators of the electrostatic pressure, which results in premature specimen failure, and the electrostatic field distribution near voids leads to aberrations that are difficult to predict. In this study, we propose a new encapsulating method for porous samples using a low melting point Bi–In–Sn alloy, known as Field's metal. As a model material, we used porous iron made by direct-hydrogen reduction of single-crystalline wüstite. The complete encapsulation was performed using in situ heating on the stage of a scanning electron microscope. No visible corrosion nor dissolution of the sample occurred. Subsequently, specimens were shaped by focused ion-beam milling under cryogenic conditions at −190°C. The proposed approach is versatile and can be applied to provide good quality atom probe datasets from micro/nanoporous materials.
Sources of psychological distress among primary care physicians during the COVID-19 pandemic’s first wave in Spain: a cross-sectional study
Authors: Cebrián-Cuenca Ana , Mira José Joaquín , Caride-Miana Elena , Fernández-Jiménez Antonio , Orozco-Beltrán Domingo
Published: October 2021

Background:

The COVID-19 pandemic is affecting people worldwide. In Spain, the first wave was especially severe.

Objectives:

This study aimed to identify sources and levels of distress among Spanish primary care physicians (PCPs) during the first wave of the pandemic (April 2020).

Methods:

A cross-sectional study was conducted using a survey that included sociodemographic data, a description of working conditions related to distress [such as gaps in training in protective measures, cleaning, and hygiene procedures in work setting, unavailability of personal protective equipments (PPEs) and COVID-19 RT-PCR test, and lack of staff due to be infected] and a validated scale, the ‘Self-applied Acute Stress Scale’ (EASE). The survey was answered by a non-probability sampling of PCPs working in family healthcare centres from different regions of Spain. Analysis of variance and multivariate linear regression analysis were performed.

Results:

In all, out of 518 PCP participants, 123 (23.7%) obtained high psychological distress scores. Only half of them had received information about the appropriate use of PPE. PCP characteristics associated with higher levels of distress include female gender [1.69; 95% confidence interval (CI) 0.54, 2.84]; lack of training in protective measures (1.96; 95% CI 0.94, 2.99); unavailable COVID-19 RT-PCR for health care workers after quarantine or COVID-19 treatment (−0.77 (−1.52, −0.02). Reinforcing disinfection of the work environment (P < 0.05), availability of PPEs (P < 0.05), and no healthcare professional was infected (P < 0.05) were related to the lowest distress score.

Conclusions:

A better understanding of the sources of distress among PCPs could prevent its effect on future outbreaks.
China's Participation in the Second Hague Conference and the Concept of Equal Sovereignty in International Law
Authors: MITCHELL Ryan Martínez
Published: October 2021

Despite the Qing Empire's formal inclusion as a member of the Eurocentric community of states by the turn of the 20th century, its lack of full sovereign status was frequently reasserted in practice. This included proceedings where legal norms were unilaterally applied to it as an object of regulation, provoking a pursuit of agency. In particular, the unprecedented foreign occupation and administration of China after the Boxer crisis of 1899–1901 spurred efforts in pedagogy, legal reform, and diplomacy. Several such efforts subsequently overlapped at the Second Hague Conference in 1907. There, Qing diplomats for the first time influenced multilateral negotiations, and discovered a nascent solidarity with other “weak” states in Latin America and Asia. Joint struggle against great power initiatives sparked new conversations about the equality of states, however, major questions about the implications of sovereign status for genuine agency, and the contingent forms of international legal “progress,” remained unresolved.
Tailoring the properties of quantum dot-micropillars by ultrafast optical injection of free charge carriers
Authors: Peinke Emanuel , Sattler Tobias , Torelly Guilherme M. , Souza Patricia L. , Perret Sylvain , Bleuse Joël , Claudon Julien , Vos Willem L. , Gérard Jean-Michel
Published: October 2021

We review recent studies of cavity switching induced by the optical injection of free carriers in micropillar cavities containing quantum dots. Using the quantum dots as a broadband internal light source and a streak camera as detector, we track the resonance frequencies for a large set of modes with picosecond time resolution. We report a record-fast switch-on time constant (1.5 ps) and observe major transient modifications of the modal structure of the micropillar on the 10 ps time scale: mode crossings are induced by a focused symmetric injection of free carriers, while a lifting of several mode degeneracies is observed when off-axis injection breaks the rotational symmetry of the micropillar. We show theoretically and experimentally that cavity switching can be used to tailor the dynamic properties of the coupled QD–cavity system. We report the generation of ultrashort spontaneous emission pulses (as short as 6 ps duration) by a collection of frequency-selected QDs in a switched pillar microcavity. These pulses display a very small coherence length, attractive for ultrafast speckle-free imaging. Moreover, the control of QD-mode coupling on the 10 ps time scale establishes cavity switching as an appealing resource for quantum photonics.
Downregulation of kainate receptors regulating GABAergic transmission in amygdala after early life stress is associated with anxiety-like behavior in rodents
Authors: Englund Jonas , Haikonen Joni , Shteinikov Vasilii , Amarilla Shyrley Paola , Atanasova Tsvetomira , Shintyapina Alexandra , Ryazantseva Maria , Partanen Juha , Voikar Vootele , Lauri Sari E.
Published: October 2021

Early life stress (ELS) is a well-characterized risk factor for mood and anxiety disorders. GABAergic microcircuits in the amygdala are critically implicated in anxiety; however, whether their function is altered after ELS is not known. Here we identify a novel mechanism by which kainate receptors (KARs) modulate feedforward inhibition in the lateral amygdala (LA) and show that this mechanism is downregulated after ELS induced by maternal separation (MS). Specifically, we show that in control rats but not after MS, endogenous activity of GluK1 subunit containing KARs disinhibit LA principal neurons during activation of cortical afferents. GluK1 antagonism attenuated excitability of parvalbumin (PV)-expressing interneurons, resulting in loss of PV-dependent inhibitory control and an increase in firing of somatostatin-expressing interneurons. Inactivation of Grik1 expression locally in the adult amygdala reduced ongoing GABAergic transmission and was sufficient to produce a mild anxiety-like behavioral phenotype. Interestingly, MS and GluK1-dependent phenotypes showed similar gender specificity, being detectable in male but not female rodents. Our data identify a novel KAR-dependent mechanism for cell-type and projection-specific functional modulation of the LA GABAergic microcircuit and suggest that the loss of GluK1 KAR function contributes to anxiogenesis after ELS.
The proteomic architecture of schizophrenia iPSC-derived cerebral organoids reveals alterations in GWAS and neuronal development factors
Authors: Notaras Michael , Lodhi Aiman , Fang Haoyun , Greening David , Colak Dilek
Published: October 2021

Schizophrenia (Scz) is a brain disorder that has a typical onset in early adulthood but otherwise maintains unknown disease origins. Unfortunately, little progress has been made in understanding the molecular mechanisms underlying neurodevelopment of Scz due to ethical and technical limitations in accessing developing human brain tissue. To overcome this challenge, we have previously utilized patient-derived Induced Pluripotent Stem Cells (iPSCs) to generate self-developing, self-maturating, and self-organizing 3D brain-like tissue known as cerebral organoids. As a continuation of this prior work, here we provide an architectural map of the developing Scz organoid proteome. Utilizing iPSCs from n = 25 human donors (n = 8 healthy Ctrl donors, and n = 17 Scz patients), we generated 3D cerebral organoids, employed 16-plex isobaric sample-barcoding chemistry, and simultaneously subjected samples to comprehensive high-throughput liquid-chromatography/mass-spectrometry (LC/MS) quantitative proteomics. Of 3,705 proteins identified by high-throughput proteomic profiling, we identified that just ~2.62% of the organoid global proteomic landscape was differentially regulated in Scz organoids. In sum, just 43 proteins were up-regulated and 54 were down-regulated in Scz patient-derived organoids. Notably, a range of neuronal factors were depleted in Scz organoids (e.g., MAP2, TUBB3, SV2A, GAP43, CRABP1, NCAM1 etc.). Based on global enrichment analysis, alterations in key pathways that regulate nervous system development (e.g., axonogenesis, axon development, axon guidance, morphogenesis pathways regulating neuronal differentiation, as well as substantia nigra development) were perturbed in Scz patient-derived organoids. We also identified prominent alterations in two novel GWAS factors, Pleiotrophin (PTN) and Podocalyxin (PODXL), in Scz organoids. In sum, this work serves as both a report and a resource that researchers can leverage to compare, contrast, or orthogonally validate Scz factors and pathways identified in observational clinical studies and other model systems.
MS4A15 drives ferroptosis resistance through calcium-restricted lipid remodeling
Authors: Xin Shan , Mueller Constanze , Pfeiffer Susanne , Kraft Vanessa A. N. , Merl-Pham Juliane , Bao Xuanwen , Feederle Regina , Jin Xiang , Hauck Stefanie M. , Schmitt-Kopplin Philippe , Schick Joel A.
Published: October 2021

Ferroptosis is an iron-dependent form of cell death driven by biochemical processes that promote oxidation within the lipid compartment. Calcium (Ca2+) is a signaling molecule in diverse cellular processes such as migration, neurotransmission, and cell death. Here, we uncover a crucial link between ferroptosis and Ca2+through the identification of the novel tetraspanin MS4A15. MS4A15 localizes to the endoplasmic reticulum, where it blocks ferroptosis by depleting luminal Ca2+stores and reprogramming membrane phospholipids to ferroptosis-resistant species. Specifically, prolonged Ca2+depletion inhibits lipid elongation and desaturation, driving lipid droplet dispersion and formation of shorter, more saturated ether lipids that protect phospholipids from ferroptotic reactive species. We further demonstrate that increasing luminal Ca2+levels can preferentially sensitize refractory cancer cell lines. In summary, MS4A15 regulation of anti-ferroptotic lipid reservoirs provides a key resistance mechanism that is distinct from antioxidant and lipid detoxification pathways. Manipulating Ca2+homeostasis offers a compelling strategy to balance cellular lipids and cell survival in ferroptosis-associated diseases.
Loss of Numb promotes hepatic progenitor expansion and intrahepatic cholangiocarcinoma by enhancing Notch signaling
Authors: Shu Yuke , Xu Qing , Xu Yahong , Tao Qing , Shao Mingyang , Cao Xiaoyue , Chen Yuwei , Wu Zhenru , Chen Menglin , Zhou Yongjie , Zhou Ping , Shi Yujun , Bu Hong
Published: October 2021

Numb, a stem cell fate determinant, acts as a tumor suppressor and is closely related to a wide variety of malignancies. Intrahepatic cholangiocarcinoma (iCCA) originates from hepatic progenitors (HPCs); however, the role of Numb in HPC malignant transformation and iCCA development is still unclear. A retrospective cohort study indicated that Numb was frequently decreased in tumor tissues and suggests poor prognosis in iCCA patients. Consistently, in a chemically induced iCCA mouse model, Numb was downregulated in tumor cells compared to normal cholangiocytes. In diet-induced chronic liver injury mouse models, Numb ablation significantly promoted histological impairment, HPC expansion, and tumorigenesis. Similarly, Numb silencing in cultured iCCA cells enhanced cell spheroid growth, invasion, metastasis, and the expression of stem cell markers. Mechanistically, Numb was found to bind to the Notch intracellular domain (NICD), and Numb ablation promoted Notch signaling; this effect was reversed when Notch signaling was blocked by γ-secretase inhibitor treatment. Our results suggested that loss of Numb plays an important role in promoting HPC expansion, HPC malignant transformation, and, ultimately, iCCA development in chronically injured livers. Therapies targeting suppressed Numb are promising for the treatment of iCCA.
High-coverage metabolomics uncovers microbiota-driven biochemical landscape of interorgan transport and gut-brain communication in mice
Authors: Lai Yunjia , Liu Chih-Wei , Yang Yifei , Hsiao Yun-Chung , Ru Hongyu , Lu Kun
Published: October 2021

The mammalian gut harbors a complex and dynamic microbial ecosystem: the microbiota. While emerging studies support that microbiota regulates brain function with a few molecular cues suggested, the overall biochemical landscape of the “microbiota-gut-brain axis” remains largely unclear. Here we use high-coverage metabolomics to comparatively profile feces, blood sera, and cerebral cortical brain tissues of germ-free C57BL/6 mice and their age-matched conventionally raised counterparts. Results revealed for all three matrices metabolomic signatures owing to microbiota, yielding hundreds of identified metabolites including 533 altered for feces, 231 for sera, and 58 for brain with numerous significantly enriched pathways involving aromatic amino acids and neurotransmitters. Multicompartmental comparative analyses single out microbiota-derived metabolites potentially implicated in interorgan transport and the gut-brain axis, as exemplified by indoxyl sulfate and trimethylamine-N-oxide. Gender-specific characteristics of these landscapes are discussed. Our findings may be valuable for future research probing microbial influences on host metabolism and gut-brain communication.
Divergent abiotic spectral pathways unravel pathogen stress signals across species
Authors: Zarco-Tejada P. J. , Poblete T. , Camino C. , Gonzalez-Dugo V. , Calderon R. , Hornero A. , Hernandez-Clemente R. , Román-Écija M. , Velasco-Amo M. P. , Landa B. B. , Beck P. S. A. , Saponari M. , Boscia D. , Navas-Cortes J. A.
Published: October 2021

Plant pathogens pose increasing threats to global food security, causing yield losses that exceed 30% in food-deficit regions. Xylella fastidiosa (Xf) represents the major transboundary plant pest and one of the world’s most damaging pathogens in terms of socioeconomic impact. Spectral screening methods are critical to detect non-visual symptoms of early infection and prevent spread. However, the subtle pathogen-induced physiological alterations that are spectrally detectable are entangled with the dynamics of abiotic stresses. Here, using airborne spectroscopy and thermal scanning of areas covering more than one million trees of different species, infections and water stress levels, we reveal the existence of divergent pathogen- and host-specific spectral pathways that can disentangle biotic-induced symptoms. We demonstrate that uncoupling this biotic–abiotic spectral dynamics diminishes the uncertainty in the Xf detection to below 6% across different hosts. Assessing these deviating pathways against another harmful vascular pathogen that produces analogous symptoms, Verticillium dahliae, the divergent routes remained pathogen- and host-specific, revealing detection accuracies exceeding 92% across pathosystems. These urgently needed hyperspectral methods advance early detection of devastating pathogens to reduce the billions in crop losses worldwide.
A dry lunar mantle reservoir for young mare basalts of Chang’e-5
Authors: Hu Sen , He Huicun , Ji Jianglong , Lin Yangting , Hui Hejiu , Anand Mahesh , Tartèse Romain , Yan Yihong , Hao Jialong , Li Ruiying , Gu Lixin , Guo Qian , He Huaiyu , Ouyang Ziyuan
Published: October 2021

The distribution of water in the Moon’s interior carries implications for the origin of the Moon1, the crystallization of the lunar magma ocean2 and the duration of lunar volcanism2. The Chang’e-5 mission returned some of the youngest mare basalt samples reported so far, dated at 2.0 billion years ago (Ga)3, from the northwestern Procellarum KREEP Terrane, providing a probe into the spatiotemporal evolution of lunar water. Here we report the water abundances and hydrogen isotope compositions of apatite and ilmenite-hosted melt inclusions from the Chang’e-5 basalts. We derive a maximum water abundance of 283 ± 22 μg g−1 and a deuterium/hydrogen ratio of (1.06 ± 0.25) × 10–4 for the parent magma. Accounting for low-degree partial melting of the depleted mantle followed by extensive magma fractional crystallization4, we estimate a maximum mantle water abundance of 1–5 μg g−1, suggesting that the Moon’s youngest volcanism was not driven by abundant water in its mantle source. Such a modest water content for the Chang’e-5 basalt mantle source region is at the low end of the range estimated from mare basalts that erupted from around 4.0 Ga to 2.8 Ga (refs. 5,6), suggesting that the mantle source of the Chang’e-5 basalts had become dehydrated by 2.0 Ga through previous melt extraction from the Procellarum KREEP Terrane mantle during prolonged volcanic activity.
Circadian clocks guide dendritic cells into skin lymphatics
Authors: Holtkamp Stephan J. , Ince Louise M. , Barnoud Coline , Schmitt Madeleine T. , Sinturel Flore , Pilorz Violetta , Pick Robert , Jemelin Stéphane , Mühlstädt Michael , Boehncke Wolf-Henning , Weber Jasmin , Laubender David , Philippou-Massier Julia , Chen Chien-Sin , Holtermann Leonie , Vestweber Dietmar , Sperandio Markus , Schraml Barbara U. , Halin Cornelia , Dibner Charna , Oster Henrik , Renkawitz Jörg , Scheiermann Christoph
Published: October 2021

Migration of leukocytes from the skin to lymph nodes (LNs) via afferent lymphatic vessels (LVs) is pivotal for adaptive immune responses1,2. Circadian rhythms have emerged as important regulators of leukocyte trafficking to LNs via the blood3,4. Here, we demonstrate that dendritic cells (DCs) have a circadian migration pattern into LVs, which peaks during the rest phase in mice. This migration pattern is determined by rhythmic gradients in the expression of the chemokine CCL21 and of adhesion molecules in both mice and humans. Chronopharmacological targeting of the involved factors abrogates circadian migration of DCs. We identify cell-intrinsic circadian oscillations in skin lymphatic endothelial cells (LECs) and DCs that cogovern these rhythms, as their genetic disruption in either cell type ablates circadian trafficking. These observations indicate that circadian clocks control the infiltration of DCs into skin lymphatics, a process that is essential for many adaptive immune responses and relevant for vaccination and immunotherapies.
Curvature flows, scaling laws and the geometry of attrition under impacts
Authors: Pál Gergő , Domokos Gábor , Kun Ferenc
Published: October 2021

Impact induced attrition processes are, beyond being essential models of industrial ore processing, broadly regarded as the key to decipher the provenance of sedimentary particles. Here we establish the first link between microscopic, particle-based models and the mean field theory for these processes. Based on realistic computer simulations of particle-wall collision sequences we first identify the well-known damage and fragmentation energy phases, then we show that the former is split into the abrasion phase with infinite sample lifetime (analogous to Sternberg’s Law) at finite asymptotic mass and the cleavage phase with finite sample lifetime, decreasing as a power law of the impact velocity (analogous to Basquin’s Law). This splitting establishes the link between mean field models (curvature-driven partial differential equations) and particle-based models: only in the abrasion phase does shape evolution emerging in the latter reproduce with startling accuracy the spatio-temporal patterns (two geometric phases) predicted by the former.
Individualized stress detection using an unmodified car steering wheel
Authors: Balters Stephanie , Gowda Nikhil , Ordonez Francisco , Paredes Pablo E.
Published: October 2021

In-car passive stress sensing could enable the monitoring of stress biomarkers while driving and reach millions of commuters daily (i.e., 123 million daily commuters in the US alone). Here, we present a nonintrusive method to detect stress solely from steering angle data of a regular car. The method uses inverse filtering to convert angular movement data into a biomechanical Mass Spring Damper model of the arm and extracts its damped natural frequency as an approximation of muscle stiffness, which in turn reflects stress. We ran a within-subject study (N = 22), in which commuters drove a vehicle around a closed circuit in both stress and calm conditions. As hypothesized, cohort analysis revealed a significantly higher damped natural frequency for the stress condition (P = .023, d = 0.723). Subsequent automation of the method achieved rapid (i.e., within 8 turns) stress detection in the individual with a detection accuracy of 77%.
Passing rail traffic reduces bat activity
Authors: Jerem Paul , Mathews Fiona
Published: October 2021

Rail transport is expanding, with a global increase in infrastructure of up to one-third predicted by 2050. Greater reliance on rail is expected to benefit the environment at a planetary level, by mitigating transport-related carbon emissions. However, smaller-scale, more direct consequences for wildlife are unclear, as unlike roads, railway impacts on animal ecology are rarely studied. As a group, bats frequently interact with transport networks due to their broad distribution and landscape-scale movements. Additionally, their nocturnality, and use of echolocation mean bats are likely to be affected by light and noise emitted by trains. To investigate whether passing trains affect bat activity levels, we monitored the two most abundant UK species using ultrasonic detectors at 12 wooded rail-side sites in southern England. Activity fell by ≥ 30–50% each time a train passed, for at least two minutes. Consequently, activity was reduced for no less than one-fifth of the time at sites with median rail traffic, and two-thirds or more of the time at the busiest site. Such activity changes imply repeated evasive action and/or exclusion from otherwise favourable environments, with potential for corresponding opportunity or energetic costs. Hence, disturbance by passing trains may disadvantage bats in most rail-side habitats.
Increasing urinary podocyte mRNA excretion and progressive podocyte loss in kidney contribute to the high risk of long-term renal disease caused by preterm birth
Authors: Ding Fangrui , Gao Qi , Tian Xiuying , Mo Jiali , Zheng Jun
Published: October 2021

Podocyte abnormalities are common mechanism driving the progression of glomerular diseases, which account for most chronic kidney diseases (CKDs). However, the role of podocyte in the mechanism of high-risk long-term CKD caused by prematurity has not been well clarified. In present study, urine samples of 86 preterm infants and 32 full-term infants were collected, and podocyte-specific podocin mRNA levels in urine pellet were applied to indicate urinary podocyte mRNA excretion. In addition, in a preterm animal rat model, preterm rats were identified by delivery 2 days early. From the age of 3 weeks–12 months, urine samples were collected to examine podocyte mRNA excretion by measuring podocyte-specific podocin mRNA levels. Kidney samples at the age of 3 weeks, 2 months, and 12 months were collected from 8, 5 and 6 preterm rats and 9, 6 and 8 full-term rats, respectively, to examine podocyte density and podocyte area by measuring the podocyte specific nuclear marker WT-1 and the podocyte specific marker synaptopodin. As results, a more than threefold increase of urinary podocyte-specific podocin mRNA excretion rate was found in preterm infants compared with full-term infants. In addition, there was negative correlation between gestational age at birth and urinary podocin mRNA excretion. In preterm rats, a reduction in the total number of differentiated podocytes in glomeruli and an increased podocyte podocin mRNA excretion rate in urine were detected at the end of kidney differentiation. Moreover, long-term follow-up data in preterm rats showed there was an increased the risk of renal disease indicated by persistent podocyte mRNA loss, proteinuria, and enlarged glomeruli. In conclusion, increasing podocyte mRNA excretion in urine and podocyte loss in kidney led by prematurity drive the progression of long-term abnormal kidney function and could potentially explain the high risk of long-term CKD in preterm infants.
Implications for conservation and game management of the roadkill levels of the endemic Iberian hare (Lepus granatensis)
Authors: Duarte Jesús , Romero David , Rubio Pablo J. , Farfán Miguel A. , Fa Julia E.
Published: October 2021

The Iberian hare (Lepus granatensis) is an important small game species endemic to the Iberian Peninsula for which the incidence of roadkill is unknown. We surveyed Iberian hare–vehicle accidents on road networks in southern Spain, focusing on roads that mainly run through favorable habitats for this species: Mediterranean landscapes with plots of arable crops, olive groves, and vineyards. We recorded roadkills over a 5-month period, estimated hare accident densities on roads, and compared these numbers to hare hunting yields in adjoining hunting estates. We also analyzed the spatial patterns of and potential factors influencing hare roadkills. We detected the existence of black spots for hare roadkills in areas with high landscape heterogeneity that also included embankments and nearby crossroads and had high traffic intensity. Hare roadkill levels ranged from 5 to 25% of the annual harvest of hares killed on neighboring hunting estates. We suggest that road collisions should be considered in Iberian hare conservation in addition to hunting, since they may represent an additive source of mortality. Game managers should address the issue of hare roadkill in harvest planning to compensate for hare accidents, adjusting hunting quotas to account for this unnatural source of mortality. Our results suggest future directions for applied research in road ecology, including further work on demographic compensation and roadkill mitigation.