bluuebunny/crossref_metadata_2025 huggingface dataset:
Obstetric and offspring outcomes in isolated maternal hypothyroxinaemia: a systematic review and meta-analysis
Authors: Zhuo L. , Wang Z. , Yang Y. , Liu Z. , Wang S. , Song Y.
Published: November 2022

Objective

To examine the association between isolated maternal hypothyroxinaemia (IMH) and adverse obstetric outcomes and offspring outcomes and also investigate the effects of levothyroxine therapy on IMH for the above outcomes.

Methods

We systematically searched PubMed, EMBASE, and Cochrane Library, and the reference lists of key reviews were hand searched on June 9, 2021. Two authors independently screened titles/abstracts. Full articles were further assessed if the information suggested that the study met the inclusion/exclusion criteria, and two researchers performed data extraction and risk-of-bias assessment using standardized tables. Summary relative risks or the mean difference between maternal effects and offspring outcomes were calculated by a random-effects model.

Results

We identified 38 eligible articles (35 cohort studies and two randomized controlled trials [RCT]). Meta-analysis showed that maternal IMH was associated with increased gestational diabetes mellitus, preterm premature rupture of membranes, preterm birth, fetal distress, and macrosomia outcomes in IMH compared to euthyroid women, and the relative risks were 1.42 (1.03–1.96), 1.50 (1.05–2.14), 1.33 (1.15–1.55), 1.75 (1.16–2.65) and 1.62 (1.35–1.94), respectively. IMH was not associated with placenta previa, gestational hypertension, pre-eclampsia, intrauterine growth restriction, and offspring outcomes like birth weight, low birth weight infants, fetal macrosomia, neonatal intensive care, neonatal death, or fetal head circumference. In addition, we did not find an association between IMH and adverse offspring cognitive defects. Due to insufficient data for meta-analysis, it failed to pool the evidence of levothyroxine’s therapeutic effect on IMH and their offspring.

Conclusions and relevance

IMH in pregnancy may relate to a few maternal and offspring outcomes. Moreover, there is currently no sufficient evidence that levothyroxine treatment during pregnancy reduces adverse maternal outcomes and disability in offspring. Further investigation to explore the beneficial effects of levothyroxine therapy is warranted.
Understanding the Impact of COVID-19 on People with Severe and Persistent Mental Illness within Rehabilitation Services: A Thematic Analysis
Authors: Pervan Luke , Parker Stephen , Wheeler Maddison , Dark Frances
Published: November 2022

The COVID 19 pandemic has required major changes in healthcare delivery. This study sought to understand the impact of the mental healthcare changes associated with COVID-19 on people living with severe and persisting mental illness (SPMI) and staff working in rehabilitation teams in Queensland in Australia. Telephone interviews were completed with participants diagnosed with SPMI who were supported by the rehabilitation teams of a public mental health service (n = 18). Additionally, an anonymous survey was completed with staff from these teams (n = 20, 17.5% of staff). Both datasets were analysed separately using thematic analysis. Four themes were identified through the analysis of the patient interviews: wishing the whole thing would go away; [COVID-19 has] delayed my recovery; being more socially aware; and (you've) got to be clean (which is a) good thing. Four themes emerged through the analysis of the staff survey data: needing to change the model of care; impact on patients, the impact on staff, positive impact. The perceived impact on participant’s mental health was like that which was reported in the general population. Participants’ emphasised anxiety, loneliness, boredom, and depression rather than a relapse of their primary psychotic illness. Participants noted the pandemic slowed the pace of personal recovery and limited the delivery of specialised rehabilitation programs.
Model Inversion for Precise Path and Trajectory Tracking in an Underactuated, Non-Minimum Phase, Spatial Overhead Crane
Authors: Bettega Jason , Richiedei Dario , Tamellin Iacopo , Trevisani Alberto
Published: November 2022

Purpose

This paper proposes a motion planning technique for precise path and trajectory tracking in an underactuated, non-minimum phase, spatial overhead crane. Besides having a number of independent actuators that is smaller than the number of degrees of freedom, tip control on this system presents unstable internal dynamics that leads to divergent solution of the inverse dynamic problem.

Method

The paper exploits the representation of the controlled output as a separable function of the actuated (i.e., the platform translations) and unactuated (i.e., the swing angles) coordinates to easily formulate the internal dynamics, without any approximation, and to study its stability. Then, output redefinition is adopted within the internal dynamics to stabilize it, leading to stable and causal reference commands for the platform translations.

Results

Besides proposing the theoretical formulation of this novel method, the paper includes the numerical validation and the experimental application on a laboratory setup. Comparison with the state-of-the-art input shaping is also proposed.

Conclusion

The results, obtained through different reference trajectories, clearly show that almost exact tracking is obtained also in the experiments, by outperforming the benchmarks.
True uncertainty and ethical AI: regulatory sandboxes as a policy tool for moral imagination
Authors: Undheim Kristin , Erikson Truls , Timmermans Bram
Published: November 2022

We offer a complementary view to the ethical dilemmas discussed in the recent literature by pointing at the epistemological dilemma of true uncertainty, suggesting regulatory sandboxes as an apposite remedy. Using the exemplar case of the regulative sandbox for responsible artificial intelligence established by the Norwegian data protection authorities, we argue that regulative sandboxes have the potential of supporting the development of a more ethical AI through not only reducing uncertainty, but through nurturing moral imaginations.
Corporate Environmental Responsibility in Investor-State Dispute Settlement
Authors: Ishikawa Tomoko
Published: November 2022

This book explores the potential of the current investor-state dispute settlement (ISDS) mechanism to materialise the responsibility of foreign investors through the states' counterclaims and defences at the jurisdictional, merits, and quantum phases. In doing so, it seeks to incorporate the recent developments of ISDS in both international and domestic laws of certain jurisdictions on corporate responsibility, including the parent company's due diligence and legal effects of corporations' voluntary commitments. The book also reflects the interests and perspectives of the victims who suffered loss and injury due to investors' conduct. The author demonstrates that the current system does have the inherent potential to advance responsible investment, even though reforms are needed to overcome its limitations. Fully utilising this potential to reflect investor responsibility in IIA-based dispute settlement mechanisms will help to develop practices based on greater due diligence and responsible business conduct.
Social Inclusion and Mental Health
Authors: Boardman Jed , Killaspy Helen , Mezey Gillian
Published: November 2022

People with mental health conditions are among the most socially excluded groups in society. Mental health conditions are influenced by the social environment, which in turn shapes our social and cultural responses to the people who experience them. Much of what mental health practitioners do is 'essentially social' and the effects of their interventions are hampered by the marginalised status of many of the people that they see. This book documents the ways in which people with mental health conditions are excluded from participating in society and offers some pointers as to how this may be reversed. It highlights the need to reduce mental health inequalities and to consider the importance of material inequalities and social injustices faced by people experiencing mental ill-health. Whilst the challenges are considerable and the solutions wide-ranging, mental health practitioners can play a significant role in facilitating the social inclusion of those with mental health conditions.
On simple models for gravity currents from moving sources
Authors: Ungarish M.
Published: November 2022

The propagation of the gravity current generated from a moving source of buoyancy is of interest in deep-sea mining and related technologies. The study by Ouillon et al. (J. Fluid Mech., vol. 924, 2021, A43) elucidated some salient patterns of the flow concerning a source close to the bottom on the basis of direct numerical simulation on a supercomputer. Here, we present a simple box model that provides further insights and useful analytical approximations for this gravity-current flow system. We show that this flow is very different from that produced by a moving source at the top, studied by Hogg et al. (J. Fluid Mech., vol. 539, 2005, pp. 349–385). The model confirms that the main governing parameter is the ratio

$a$

of speed of source to that of buoyancy propagation. The model points out dependency also on the front-jump Froude number (which implies dependency on the height of the ambient fluid). For a sufficiently large

$a >a_{crit}$

, a supercritical regime appears in which the gravity current forms a wedge behind the moving source; in the subcritical regime, the upstream propagation attains a maximum

$x_m$

at time

$t_m$

. The model predicts the value

$a_{crit}$

, the distance and time

$x_m$

and

$t_m$

in the subcritical case, and the shape of the wedge in the supercritical case, without any adjustable constant. Comparisons with the numerical data show fair agreement.
Accuracy of estimates of serving size using digitally displayed food photographs among Japanese adults
Authors: Shinozaki Nana , Murakami Kentaro
Published: November 2022

We evaluated the accuracy of the estimated serving size using digital photographs in a newly developed food atlas. From 209 food items in the food atlas, we selected 14 items with various appearances for evaluation. At the study site, fifty-four participants aged 18–33 years served fourteen foods in the amount they usually ate. After they left, each food item was weighed by a researcher. The following day, the participants estimated the quantity of each food they served based on food photographs using a web-based questionnaire. We compared the weights of the foods the participants served (true serving sizes) and those determined based on the photographs (estimated serving sizes). For ten of the fourteen food items, significant differences were observed between the estimated and true serving sizes, ranging from a 29⋅8 % underestimation (curry sauce) to a 34⋅0 % overestimation (margarine). On average, the relative difference was 8⋅8 %. Overall, 51⋅6 % of the participants were within ±25 % of the true serving size, 81⋅9 % were within ±50 % and 93⋅4 % were within ±75 %. Bland–Altman plots showed wide limits of agreement and increased variances with larger serving sizes for most food items. Overall, no association was found between estimation errors and participant characteristics. The food atlas has shown potential for assessment of portion size estimation. Further development, refinement and testing are needed to improve the usefulness of the digital food photographic atlas as a portion size estimation aid.
A restrictive, parsimonious theory of footing in directional Harmonic Serialism
Authors: Lamont Andrew
Published: November 2022

This paper develops a theory of footing in Harmonic Serialism (HS; Prince & Smolensky 1993/2004; McCarthy 2000, 2016) where Con contains only directionally evaluated constraints (Eisner 2000, 2002; Lamont 2019, 2022a, 2022b). Directional constraints harmonically order candidates by the location of violations rather than the total number of violations. A central result of adopting directional evaluation is that the constraint Parse($\sigma$) not only motivates iterative footing but also determines where feet surface. This obviates the need for alignment constraints (McCarthy & Prince 1993; McCarthy 2003; Hyde 2012a, 2016), which determine where feet are parsed in HS with constraints that count loci (Pruitt 2010, 2012). The theory uses fewer constraints, is empirically adequate, and makes more restrictive predictions than HS with counting constraints and parallel Optimality Theory (Prince & Smolensky 1993/2004) with directional constraints.
An Interactive Simulation and Visualization Tool for Conventional and Aberration-Corrected Transmission Electron Microscopy
Authors: Li X-Z
Published: November 2022

Contrast transfer function (CTF) is a vital function in transmission electron microscopy (TEM). It expresses to what extent amplitudes converted from the phase changes of the diffracted waves contribute to the TEM image, including the effects of lens aberrations. Simulation is very helpful to understand the application of the function thoroughly. In this work, we develop the CTFscope as a component in the Landyne software suite, to calculate the CTF with temporal and spatial dumping envelopes for conventional TEM and to extend it to various aberrations (up to fifth order) for aberration-corrected (AC)-TEM. It also includes effects on the CTF and imaging due to the objective aperture and image drift for tutorial purposes. The CTFscope has a user-friendly graphical interface for simulation, visualization, saving, and loading of the microscopy conditions and results. It can be used to explore instrumental performance information due to optical aberrations, effects on the resolution of a TEM and AC-TEM, and for teaching electron microscopy courses.
The Effects of Light Intensity and Flow Speed on Biogeochemical Variability Within a Fringing Coral Reef in Onna‐Son, Okinawa, Japan
Authors: Rintoul M. S. , Courtney T. A. , Dohner J. L. , Giddings S. N. , Kekuewa S. A. H. , Mitarai S. , Monismith S. G. , Pezner A. K. , Andersson A. J.
Published: November 2022

Global warming and ocean acidification are driving declines in seawater dissolved oxygen (DO) concentrations and pH. Predicting how these changes will affect shallow, near‐shore environments such as coral reefs is challenging due to their high natural biogeochemical variability present over both spatial (m to km) and temporal (diel to seasonal) scales. To make predictions, we must understand the drivers of this variability. The impact of metabolic processes on coral reef biogeochemical variability has been the subject of significant research effort, however, physical factors, including flow speed and light intensity, have received less attention. Here, we measured seawater flow, photosynthetically active radiation (PAR), pH, and DO at three reef habitats (reef flat, lagoon, and outflow channel) in a fringing coral reef system in Okinawa, Japan for 3 weeks in October 2019. During the study, pH ranged from 7.86 to 8.37 units while DO varied from 127 to 369 μmol/kg. Circulation was primarily wave‐driven with mean flow speeds ranging from 14 to 26 cm/s. Flow direction became increasingly consistent at higher flow speeds and traced benthic striations visible in satellite imagery. Multiple linear regression models of daytime changes in pH and DO versus daily mean flow speed and PAR described 25%–74% of the observed variability across all sites while at night, flow speed alone accounted for 7%–75% of the observed variability. These results demonstrate PAR, water flow speed, and the path water takes play important roles in controlling biogeochemical variability within coral reefs and must be considered when assessing their vulnerability to both local and global environmental change.
Violent Groundwater Eruption Triggered by a Distant Earthquake
Authors: Yan Xin , Shi Zheming , Wang Chi‐Yuen , Ingebritsen Steve E. , Manga Michael
Published: November 2022

It is now well established that earthquakes cause various hydrogeological responses at distances thousands of kilometers from the epicenter. What remains unexplained is the large amplitude and intensity of some responses. Following the 2004 Mw 9.1 Sumatra earthquake, groundwater 3,200 km from the epicenter erupted violently from a well and formed a water fountain reaching a height exceeding 60 m. We model the relevant processes by combining tidal analysis of groundwater level with numerical simulations using a two‐dimensional finite‐element model. We suggest that the eruption resulted from a combination of factors, including a rapid increase of crustal permeability and runaway CO2 exsolution and bubble nucleation induced by the passage of seismic waves. Our results may have implications for some engineering applications such as oil production and CO2 sequestration, and the eruption of hydrothermal features such as geysers.
Wind‐Driven Seasonal Intrusion of Modified Circumpolar Deep Water Onto the Continental Shelf in Prydz Bay, East Antarctica
Authors: Guo Guijun , Gao Libao , Shi Jiuxin , Zu Yongcan
Published: November 2022

Intrusion of warm modified Circumpolar Deep Water (mCDW) is critical to heat transport onto the continental shelf around Antarctica, with substantial impacts on basal melting of ice shelves and sea ice production. We use hydrographic data collected in Prydz Bay, East Antarctica, and atmospheric and ocean reanalyses to investigate the seasonality of mCDW intrusions onto the East Antarctic continental shelf. Mooring measurements confirm that there is significant intrusion of mCDW over the inner continental shelf of Prydz Bay in March–July (austral autumn and early winter). The warming signal of intruded mCDW over the inner shelf is correlated with wind changes north of the shelf break, with a significant lag. This suggests that the autumn‐winter mCDW intrusions over the inner shelf are significantly affected by the wind regime north of the shelf break in January–May, when a southward displacement of the westerly winds occurs. The southward shift of westerly winds drives the shallowest depth of upwelled mCDW to move poleward and contributes more warm water to the shelf break. This results in the shoaling of mCDW near the shelf break in January–May and promotes mCDW intrusions onto the continental shelf. The dynamic barrier imposed on mCDW intrusions by the strong Antarctic Slope Front in January–May is offset by this shoaling of mCDW. This study indicates the strong sensitivity of continental shelves in East Antarctica to atmospheric forcing changes over the Southern Ocean.
SMARCC2 mediates the regulation of DKK1 by the transcription factor EGR1 through chromatin remodeling to reduce the proliferative capacity of glioblastoma
Authors: Li Chiyang , Wang Tong , Gu Junwei , Qi Songtao , Li Junjie , Chen Lei , Wu Hang , Shi Linyong , Song Chong , Li Hong , Zhu Liwen , Lu Yuntao , Zhou Qiang
Published: November 2022

Switch/sucrose-nonfermenting (SWI/SNF) complexes play a key role in chromatin remodeling. Recent studies have found that SMARCC2, as the core subunit of the fundamental module of the complex, plays a key role in its early assembly. In this study, we found a unique function of SMARCC2 in inhibiting the progression of glioblastoma by targeting the DKK1 signaling axis. Low expression of SMARCC2 is found in malignant glioblastoma (GBM) compared with low-grade gliomas. SMARCC2 knockout promoted the proliferation of glioblastoma cells, while its overexpression showed the opposite effect. Mechanistically, SMARCC2 negatively regulates transcription by dynamically regulating the chromatin structure and closing the promoter region of the target gene DKK1, which can be bound by the transcription factor EGR1. DKK1 knockdown significantly reduced the proliferation of glioblastoma cell lines by inhibiting the PI3K–AKT pathway. We also studied the functions of the SWIRM and SANT domains of SMARCC2 and found that the SWIRM domain plays a more important role in the complete chromatin remodeling function of SMARCC2. In addition, in vivo studies confirmed that overexpression of SMARCC2 could significantly inhibit the size of intracranial gliomas in situ in nude mice. Overall, this study shows that SMARCC2, as a tumor suppressor, inhibits the proliferation of glioblastoma by targeting the transcription of the oncogene DKK1 through chromatin remodeling, indicating that SMARCC2 is a potentially attractive therapeutic target in glioblastoma.
Reversion mutations in germline BRCA1/2-mutant tumors reveal a BRCA-mediated phenotype in non-canonical histologies
Authors: Murciano-Goroff Yonina R. , Schram Alison M. , Rosen Ezra Y. , Won Helen , Gong Yixiao , Noronha Anne Marie , Janjigian Yelena Y. , Stadler Zsofia K. , Chang Jason C. , Yang Soo-Ryum , Mandelker Diana , Offit Kenneth , Berger Michael F. , Donoghue Mark T. A. , Bandlamudi Chaitanya , Drilon Alexander
Published: November 2022

The association between loss of BRCA1/2 and a homologous recombination deficiency phenotype is lineage dependent. In BRCA-associated cancers such as breast, ovarian, pancreas and prostate, this phenotype confers sensitivity to PARP inhibitors and platinum-therapies. Somatic reversion mutations restoring BRCA1/2 function mediate resistance, and have exclusively been reported in BRCA-associated tumors. In this study, we analyze matched tumor and normal sequencing from 31,927 patients and identify 846 (2.7%) patients with germline BRCA1/2 variants across 43 different cancer types, including 11 with somatic reversion mutations. While nine are in BRCA-associated tumors, we find two reversion mutations in non-BRCA-associated histologies, namely lung and esophagogastric adenocarcinomas. Both were detected following platinum therapy. Whole exome sequencing confirms the homologous recombination deficiency phenotype of these tumors. While reversion mutations arise in all BRCA-associated cancer types, here we show that reversion mutations arising post-platinum in non-BRCA associated histologies, while rare, may indicate BRCA1/2 mediated tumorigenesis.
RNA-controlled nucleocytoplasmic shuttling of mRNA decay factors regulates mRNA synthesis and a novel mRNA decay pathway
Authors: Chattopadhyay Shiladitya , Garcia-Martinez Jose , Haimovich Gal , Fischer Jonathan , Khwaja Aya , Barkai Oren , Chuartzman Silvia Gabriela , Schuldiner Maya , Elran Ron , Rosenberg Miriam I. , Urim Shira , Deshmukh Shubham , Bohnsack Katherine E. , Bohnsack Markus T. , Perez-Ortin Jose E. , Choder Mordechai
Published: November 2022

mRNA level is controlled by factors that mediate both mRNA synthesis and decay, including the 5’ to 3’ exonuclease Xrn1. Here we show that nucleocytoplasmic shuttling of several yeast mRNA decay factors plays a key role in determining both mRNA synthesis and decay. Shuttling is regulated by RNA-controlled binding of the karyopherin Kap120 to two nuclear localization sequences (NLSs) in Xrn1, location of one of which is conserved from yeast to human. The decaying RNA binds and masks NLS1, establishing a link between mRNA decay and Xrn1 shuttling. Preventing Xrn1 import, either by deleting KAP120 or mutating the two Xrn1 NLSs, compromises transcription and, unexpectedly, also cytoplasmic decay, uncovering a cytoplasmic decay pathway that initiates in the nucleus. Most mRNAs are degraded by both pathways - the ratio between them represents a full spectrum. Importantly, Xrn1 shuttling is required for proper responses to environmental changes, e.g., fluctuating temperatures, involving proper changes in mRNA abundance and in cell proliferation rate.
Optically trapped room temperature polariton condensate in an organic semiconductor
Authors: Wei Mengjie , Verstraelen Wouter , Orfanakis Konstantinos , Ruseckas Arvydas , Liew Timothy C. H. , Samuel Ifor D. W. , Turnbull Graham A. , Ohadi Hamid
Published: November 2022

The strong nonlinearities of exciton-polariton condensates in lattices make them suitable candidates for neuromorphic computing and physical simulations of complex problems. So far, all room temperature polariton condensate lattices have been achieved by nanoimprinting microcavities, which by nature lacks the crucial tunability required for realistic reconfigurable simulators. Here, we report the observation of a quantised oscillating nonlinear quantum fluid in 1D and 2D potentials in an organic microcavity at room temperature, achieved by an on-the-fly fully tuneable optical approach. Remarkably, the condensate is delocalised from the excitation region by macroscopic distances, leading both to longer coherence and a threshold one order of magnitude lower than that with a conventional Gaussian excitation profile. We observe different mode selection behaviour compared to inorganic materials, which highlights the anomalous scaling of blueshift with pump intensity and the presence of sizeable energy-relaxation mechanisms. Our work is a major step towards a fully tuneable polariton simulator at room temperature.
A charged diatomic triple-bonded U≡N species trapped in C82 fullerene cages
Authors: Meng Qingyu , Abella Laura , Yao Yang-Rong , Sergentu Dumitru-Claudiu , Yang Wei , Liu Xinye , Zhuang Jiaxin , Echegoyen Luis , Autschbach Jochen , Chen Ning
Published: November 2022

Actinide diatomic molecules are ideal models to study elusive actinide multiple bonds, but most of these diatomic molecules have so far only been studied in solid inert gas matrices. Herein, we report a charged U≡N diatomic species captured in fullerene cages and stabilized by the U-fullerene coordination interaction. Two diatomic clusterfullerenes, viz. UN@Cs(6)-C82 and UN@C2(5)-C82, were successfully synthesized and characterized. Crystallographic analysis reveals U-N bond lengths of 1.760(7) and 1.760(20) Å in UN@Cs(6)-C82 and UN@C2(5)-C82. Moreover, U≡N was found to be immobilized and coordinated to the fullerene cages at 100 K but it rotates inside the cage at 273 K. Quantum-chemical calculations show a (UN)2+@(C82)2− electronic structure with formal +5 oxidation state (f1) of U and unambiguously demonstrate the presence of a U≡N bond in the clusterfullerenes. This study constitutes an approach to stabilize fundamentally important actinide multiply bonded species.
Enhanced activity of Alzheimer disease-associated variant of protein kinase Cα drives cognitive decline in a mouse model
Authors: Lordén Gema , Wozniak Jacob M. , Doré Kim , Dozier Lara E. , Cates-Gatto Chelsea , Patrick Gentry N. , Gonzalez David J. , Roberts Amanda J. , Tanzi Rudolph E. , Newton Alexandra C.
Published: November 2022

Exquisitely tuned activity of protein kinase C (PKC) isozymes is essential to maintaining cellular homeostasis. Whereas loss-of-function mutations are generally associated with cancer, gain-of-function variants in one isozyme, PKCα, are associated with Alzheimer’s disease (AD). Here we show that the enhanced activity of one variant, PKCα M489V, is sufficient to rewire the brain phosphoproteome, drive synaptic degeneration, and impair cognition in a mouse model. This variant causes a modest 30% increase in catalytic activity without altering on/off activation dynamics or stability, underscoring that enhanced catalytic activity is sufficient to drive the biochemical, cellular, and ultimately cognitive effects observed. Analysis of hippocampal neurons from PKCα M489V mice reveals enhanced amyloid-β-induced synaptic depression and reduced spine density compared to wild-type mice. Behavioral studies reveal that this mutation alone is sufficient to impair cognition, and, when coupled to a mouse model of AD, further accelerates cognitive decline. The druggability of protein kinases positions PKCα as a promising therapeutic target in AD.
Multi-omics analysis identifies osteosarcoma subtypes with distinct prognosis indicating stratified treatment
Authors: Jiang Yafei , Wang Jinzeng , Sun Mengxiong , Zuo Dongqing , Wang Hongsheng , Shen Jiakang , Jiang Wenyan , Mu Haoran , Ma Xiaojun , Yin Fei , Lin Jun , Wang Chongren , Yu Shuting , Jiang Lu , Lv Gang , Liu Feng , Xue Linghang , Tian Kai , Wang Gangyang , Zhou Zifei , Lv Yu , Wang Zhuoying , Zhang Tao , Xu Jing , Yang Liu , Zhao Kewen , Sun Wei , Tang Yujie , Cai Zhengdong , Wang Shengyue , Hua Yingqi
Published: November 2022

Osteosarcoma (OS) is a primary malignant bone tumor that most commonly affects children, adolescents, and young adults. Here, we comprehensively analyze genomic, epigenomic and transcriptomic data from 121 OS patients. Somatic mutations are diverse within the cohort, and only TP53 is significantly mutated. Through unsupervised integrative clustering of the multi-omics data, we classify OS into four subtypes with distinct molecular features and clinical prognosis: (1) Immune activated (S-IA), (2) Immune suppressed (S-IS), (3) Homologous recombination deficiency dominant (S-HRD), and (4) MYC driven (S-MD). MYC amplification with HR proficiency tumors is identified with a high oxidative phosphorylation signature resulting in resistance to neoadjuvant chemotherapy. Potential therapeutic targets are identified for each subtype, including platinum-based chemotherapy, immune checkpoint inhibitors, anti-VEGFR, anti-MYC and PARPi-based synthetic lethal strategies. Our comprehensive integrated characterization provides a valuable resource that deepens our understanding of the disease, and may guide future clinical strategies for the precision treatment of OS.
Differential compartmentalization of myeloid cell phenotypes and responses towards the CNS in Alzheimer’s disease
Authors: Fernández Zapata Camila , Giacomello Ginevra , Spruth Eike J. , Middeldorp Jinte , Gallaccio Gerardina , Dehlinger Adeline , Dames Claudia , Leman Julia K. H. , van Dijk Roland E. , Meisel Andreas , Schlickeiser Stephan , Kunkel Desiree , Hol Elly M. , Paul Friedemann , Parr Maria Kristina , Priller Josef , Böttcher Chotima
Published: November 2022

Myeloid cells are suggested as an important player in Alzheimer´s disease (AD). However, its continuum of phenotypic and functional changes across different body compartments and their use as a biomarker in AD remains elusive. Here, we perform multiple state-of-the-art analyses to phenotypically and metabolically characterize immune cells between peripheral blood (n = 117), cerebrospinal fluid (CSF, n = 117), choroid plexus (CP, n = 13) and brain parenchyma (n = 13). We find that CSF cells increase expression of markers involved in inflammation, phagocytosis, and metabolism. Changes in phenotype of myeloid cells from AD patients are more pronounced in CP and brain parenchyma and upon in vitro stimulation, suggesting that AD-myeloid cells are more vulnerable to environmental changes. Our findings underscore the importance of myeloid cells in AD and the detailed characterization across body compartments may serve as a resource for future studies focusing on the assessment of these cells as biomarkers in AD.
Engineering superconducting qubits to reduce quasiparticles and charge noise
Authors: Pan Xianchuang , Zhou Yuxuan , Yuan Haolan , Nie Lifu , Wei Weiwei , Zhang Libo , Li Jian , Liu Song , Jiang Zhi Hao , Catelani Gianluigi , Hu Ling , Yan Fei , Yu Dapeng
Published: November 2022

Identifying, quantifying, and suppressing decoherence mechanisms in qubits are important steps towards the goal of engineering a quantum computer or simulator. Superconducting circuits offer flexibility in qubit design; however, their performance is adversely affected by quasiparticles (broken Cooper pairs). Developing a quasiparticle mitigation strategy compatible with scalable, high-coherence devices is therefore highly desirable. Here we experimentally demonstrate how to control quasiparticle generation by downsizing the qubit, capping it with a metallic cover, and equipping it with suitable quasiparticle traps. Using a flip-chip design, we shape the electromagnetic environment of the qubit above the superconducting gap, inhibiting quasiparticle poisoning. Our findings support the hypothesis that quasiparticle generation is dominated by the breaking of Cooper pairs at the junction, as a result of photon absorption by the antenna-like qubit structure. We achieve record low charge-parity switching rate (<1 Hz). Our aluminium devices also display improved stability with respect to discrete charging events.
A class-mismatched TCR bypasses MHC restriction via an unorthodox but fully functional binding geometry
Authors: Singh Nishant K. , Alonso Jesus A. , Devlin Jason R. , Keller Grant L. J. , Gray George I. , Chiranjivi Adarsh K. , Foote Sara G. , Landau Lauren M. , Arbuiso Alyssa G. , Weiss Laura I. , Rosenberg Aaron M. , Hellman Lance M. , Nishimura Michael I. , Baker Brian M.
Published: November 2022

MHC restriction, which describes the binding of TCRs from CD4+T cells to class II MHC proteins and TCRs from CD8+T cells to class I MHC proteins, is a hallmark of immunology. Seemingly rare TCRs that break this paradigm exist, but mechanistic insight into their behavior is lacking. TIL1383I is a prototypical class-mismatched TCR, cloned from a CD4+T cell but recognizing the tyrosinase tumor antigen presented by the class I MHC HLA-A2 in a fully functional manner. Here we find that TIL1383I binds this class I target with a highly atypical geometry. Despite unorthodox binding, TCR signaling, antigen specificity, and the ability to use CD8 are maintained. Structurally, a key feature of TIL1383I is an exceptionally long CDR3β loop that mediates functions that are traditionally performed separately by hypervariable and germline loops in canonical TCR structures. Our findings thus expand the range of known TCR binding geometries compatible with normal function and specificity, provide insight into the determinants of MHC restriction, and may help guide TCR selection and engineering for immunotherapy.
Fundamentals and future applications of electrochemical energy conversion in space
Authors: Brinkert Katharina , Mandin Philippe
Published: November 2022

Long-term space missions require power sources and energy storage possibilities, capable at storing and releasing energy efficiently and continuously or upon demand at a wide operating temperature range, an ultra-high vacuum environment and a significantly reduced buoyant force. Electrochemical energy conversion systems play already a major role e.g., during launch and on the International Space Station, and it is evident from these applications that future human space missions - particularly to Moon and Mars - will not be possible without them. Here, we will provide an overview of currently existing electrochemical conversion technologies for space applications such as battery systems and fuel cells and outline their role in materials design and fabrication as well as fuel production. The focus lies on the current operation of these energy conversion systems in space as well as the challenges posed on them by this special environment. Future experiment designs which could help elucidating and optimizing their key operating parameters for an efficient and long-term operation are discussed.
Dose-response meta-analysis on urate, gout, and the risk for Parkinson’s disease
Authors: Chang Hongtao , Wang Benqiao , Shi Yue , Zhu Ruixia
Published: November 2022

The relationship between Parkinson’s disease (PD) and urate or gout has attracted significant interest in recent years, but the results were conflicting. This dose-response meta-analysis aimed to estimate the correlation between urate levels or gout and the risk for PD. The Embase, PubMed, and Medline databases were searched for studies that investigated the relationship between the risk for PD and urate levels or gout. Random-effects or fixed-effects models were used to obtain pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs). Fifteen studies, involving 449,816 participants and 14,687 cases in total, were included in the meta-analysis. High serum urate levels were associated with decreased risk for PD (RR 0.44 [95% CI 0.32–0.55]). Subgroup analysis according to sex revealed a neuroprotective effect of high urate levels against PD among females (0.68 [95% CI 0.43–0.93]) and males (0.49 [95% CI 0.34–0.64]). The risk for PD was lowered by 6% (0.94 [95% CI 0.90–0.98]) for each 1 mg/dl increase in serum urate level and reduced by 13% (0.87 [95% CI 0.80–0.95]) with each 2 mg/dl increase in serum urate level. However, gout was not closely correlated with the risk for PD (0.97 [95% CI 0.85–1.09]). Higher serum urate levels reduced the risk for PD, which was decreased by 6% (relative risk reduction) for each 1 mg/dl increase in serum urate levels. And the results indicated that urate may exert protective effects against the development of PD.
Antiphase response of the Indonesian–Australian monsoon to millennial-scale events of the last glacial period
Authors: Scroxton Nick , Gagan Michael K. , Ayliffe Linda K. , Hantoro Wahyoe S. , Hellstrom John C. , Cheng Hai , Edwards R. Lawrence , Zhao Jian-xin , Suwargadi Bambang W. , Rifai Hamdi
Published: November 2022

Antiphase behaviour of monsoon systems in alternate hemispheres is well established at yearly and orbital scales in response to alternating sensible heating of continental landmasses. At intermediate timescales without a sensible heating mechanism both in-phase and antiphase behaviours of northern and southern hemisphere monsoon systems are recorded at different places and timescales. At present, there is no continuous, high resolution, precisely dated record of millennial-scale variability of the Indonesian–Australian monsoon during the last glacial period with which to test theories of paleomonsoon behaviour. Here, we present an extension of the Liang Luar, Flores, speleothem δ18O record of past changes in southern hemisphere summer monsoon intensity back to 55.7 kyr BP. Negative δ18O excursions (stronger monsoon) occur during Heinrich events whereas positive excursions (weaker monsoon) occur during Dansgaard-Oeschger interstadials—a first order antiphase relationship with northern hemisphere summer monsoon records. An association of negative δ18O excursions with speleothem growth phases in Liang Luar suggests that these stronger monsoons are related to higher rainfall amounts. However, the response to millennial-scale variability is inconsistent, including a particularly weak response to Heinrich event 3. We suggest that additional drivers such as underlying orbital-scale variability and drip hydrology influence the δ18O response.
Predicting the risk of osteoporosis in older Vietnamese women using machine learning approaches
Authors: Bui Hanh My , Ha Minh Hoang , Pham Hoang Giang , Dao Thang Phuoc , Nguyen Thuy-Trang Thi , Nguyen Minh Loi , Vuong Ngan Thi , Hoang Xuyen Hong Thi , Do Loc Tien , Dao Thanh Xuan , Le Cuong Quang
Published: November 2022

Osteoporosis contributes significantly to health and economic burdens worldwide. However, the development of osteoporosis-related prediction tools has been limited for lower-middle-income countries, especially Vietnam. This study aims to develop prediction models for the Vietnamese population as well as evaluate the existing tools to forecast the risk of osteoporosis and evaluate the contribution of covariates that previous studies have determined to be risk factors for osteoporosis. The prediction models were developed to predict the risk of osteoporosis using machine learning algorithms. The performance of the included prediction models was evaluated based on two scenarios; in the first one, the original test parameters were directly modeled, and in the second the original test parameters were transformed into binary covariates. The area under the receiver operating characteristic curve, the Brier score, precision, recall and F1-score were calculated to evaluate the models’ performance in both scenarios. The contribution of the covariates was estimated using the Permutation Feature Importance estimation. Four models, namely, Logistic Regression, Support Vector Machine, Random Forest and Neural Network, were developed through two scenarios. During the validation phase, these four models performed competitively against the reference models, with the areas under the curve above 0.81. Age, height and weight contributed the most to the risk of osteoporosis, while the correlation of the other covariates with the outcome was minor. Machine learning algorithms have a proven advantage in predicting the risk of osteoporosis among Vietnamese women over 50 years old. Additional research is required to more deeply evaluate the performance of the models on other high-risk populations.
Confocal laser endomicroscope with distal MEMS scanner for real-time histopathology
Authors: Lee Miki , Li Gaoming , Li Haijun , Duan Xiyu , Birla Mayur B. , Chang Tse-Shao , Turgeon Danielle K. , Oldham Kenn R. , Wang Thomas D.
Published: November 2022

Confocal laser endomicroscopy is an emerging methodology to perform real time optical biopsy. Fluorescence images with histology-like quality can be collected instantaneously from the epithelium of hollow organs. Currently, scanning is performed at the proximal end of probe-based instruments used routinely in the clinic, and flexibility to control the focus is limited. We demonstrate use of a parametric resonance scanner packaged in the distal end of the endomicroscope to perform high speed lateral deflections. An aperture was etched in the center of the reflector to fold the optical path. This design reduced the dimensions of the instrument to 2.4 mm diameter and 10 mm length, allowing for forward passage through the working channel of a standard medical endoscope. A compact lens assembly provides lateral and axial resolution of 1.1 and 13.6 μm, respectively. A working distance of 0 μm and field-of-view of 250 μm × 250 μm was achieved at frame rates up to 20 Hz. Excitation at 488 nm was delivered to excite fluorescein, an FDA-approved dye, to generate high tissue contrast. The endomicroscope was reprocessed using a clinically-approved sterilization method for 18 cycles without failure. Fluorescence images were collected during routine colonoscopy from normal colonic mucosa, tubular adenomas, hyperplastic polyps, ulcerative colitis, and Crohn’s colitis. Individual cells, including colonocytes, goblet cells, and inflammatory cells, could be identified. Mucosal features, such as crypt structures, crypt lumens, and lamina propria, could be distinguished. This instrument has potential to be used as an accessory during routine medical endoscopy.
High intra-task and low inter-task correlations of motor skills in humans creates an individualized behavioural pattern
Authors: Kasuga Shoko , Heming Ethan , Lowrey Catherine , Scott Stephen H.
Published: November 2022

Our motor system allows us to generate an enormous breadth of voluntary actions, but it remains unclear whether and how much motor skill translates across tasks. For example, if an individual is good at gross motor control, are they also good at fine motor control? Previous research about the generalization across motor skills has been equivocal. Here, we compare human performance across five different motor skills. High correlation between task measures would suggest a certain level of underlying sensorimotor ability that dictates performance across all task types. Low correlation would suggest specificity in abilities across tasks. Performance on a reaching task, an object-hitting task, a bimanual coordination task, a rapid motion task and a target tracking task, was examined twice in a cohort of 25 healthy individuals. Across the cohort, we found relatively high correlations for different spatial and temporal parameters within a given task (16–53% of possible parameter pairs were significantly correlated, with significant r values ranging from 0.53 to 0.97) but relatively low correlations across different tasks (2.7–4.4% of possible parameter pairs were significantly correlated, with significant r values ranging from 0.53–0.71). We performed a cluster analysis across all individuals using 76 performance measures across all tasks for the two repeat testing sessions and demonstrated that repeat tests were commonly grouped together (16 of 25 pairs were grouped next to each other). These results highlight that individuals have different abilities across motor tasks, and that these patterns are consistent across time points.
Designing metal chelates of halogenated sulfonamide Schiff bases as potent nonplatinum anticancer drugs using spectroscopic, molecular docking and biological studies
Authors: Elsamra Rehab M. I. , Masoud Mamdouh S. , Ramadan Ahmed M.
Published: November 2022

In this contribution, five Ni(II) complexes have been synthesized from sulfonamide-based Schiff bases (SB1–SB5) that comprise bromo or iodo substituents in the salicylidene moiety. The chemical structures of these compounds were extensively elucidated by different analytical and physicochemical studies. All ligands act as bidentate chelators with ON binding mode yielding octahedral, square planar, or tetrahedral geometries. The phenolic OH at δ 12.80 ppm in the free Schiff base SB2 vanishes in the 1H NMRspectrum of diamagnetic complex [Ni(SB2–H)2] favoring the OH deprotonation prior to the chelation with Ni(II) ion. The appearance of twin molecular ion peaks ([M − 1]+ and [M + 1]+) is due to the presence of bromine isotopes (79Br and 81Br) in the mass spectra of most cases. Also, the thermal decomposition stages of all complexes confirmed their high thermal stability and ended with the formation of NiO residue of mass 6.42% to 14.18%. Besides, antimicrobial activity and cytotoxicity of the ligands and some selected complexes were evaluated. Among the ligands, SB4 showed superior antimicrobial efficacy with MIC values of 0.46, 7.54, and 0.95 µM against B. subtilis, E. coli, and A. fumigatus strains, respectively. The consortium of different substituents as two bromine atoms either at positions 3 and/or 5 on the phenyl ring and a thiazole ring is one of the reasons behind the recorded optimal activity. Moreover, there is a good correlation between the cytotoxicity screening (IC50) and molecular docking simulation outcomes that predicted a strong binding of SB2 (16.0 μM), SB4 (18.8 μM), and SB5 (6.32 μM) to the breast cancer protein (3s7s). Additionally, [Ni(SB4–H)2] (4.33 µM) has nearly fourfold potency in comparison with cisplatin (19.0 μM) against breast carcinoma cells (MCF-7) and is highly recommended as a promising, potent, as well as low-cost non-platinum antiproliferative agent after further drug authorization processes.
Noninvasive stimulation of the ventromedial prefrontal cortex modulates rationality of human decision-making
Authors: Kroker Thomas , Wyczesany Miroslaw , Rehbein Maimu Alissa , Roesmann Kati , Wessing Ida , Junghöfer Markus
Published: November 2022

The framing-effect is a bias that affects decision-making depending on whether the available options are presented with positive or negative connotations. Even when the outcome of two choices is equivalent, people have a strong tendency to avoid the negatively framed option. The ventromedial prefrontal cortex (vmPFC) is crucial for rational decision-making, and dysfunctions in this region have been linked to cognitive biases, impulsive behavior and gambling addiction. Using a financial decision-making task in combination with magnetoencephalographic neuroimaging, we show that excitatory compared to inhibitory non-invasive transcranial direct current stimulation (tDCS) of the vmPFC reduces framing-effects while improving the assessment of loss-probabilities, ultimately leading to increased overall gains. Behavioral and neural data consistently suggest that this improvement in rational decision-making is predominately due to an attenuation of biases towards negative affect (loss-aversion and risk-aversion). These findings recommend further research towards clinical applications of vmPFC-tDCS as in addictive disorders.