bluuebunny/crossref_metadata_2025 huggingface dataset:
Neonatal withdrawal syndrome following in utero exposure to antidepressants: a disproportionality analysis of VigiBase, the WHO spontaneous reporting database
Authors: Gastaldon C. , Arzenton E. , Raschi E. , Spigset O. , Papola D. , Ostuzzi G. , Moretti U. , Trifirò G. , Barbui C. , Schoretsanitis G.
Published: September 2022

Background

Evidence on neonatal withdrawal syndrome following antidepressant intrauterine exposure is limited, particularly for antidepressants other than selective serotonin reuptake inhibitor (SSRIs).

Methods

In our case/non-case pharmacovigilance study, based on VigiBase®, the WHO database of suspected adverse drug reactions, we estimated reporting odds ratio (ROR) and the Bayesian information component (IC) with 95% confidence/credibility intervals (CI) as measures of disproportionate reporting of antidepressant-related neonatal withdrawal syndrome. Antidepressants were first compared to all other medications, then to methadone, and finally within each class of antidepressants: SSRIs, tricyclics (TCA) and other antidepressants. Antidepressants were ranked in terms of clinical priority, based on semiquantitative score ratings. Serious v. non-serious reports were compared.

Results

A total of 406 reports of neonatal withdrawal syndrome in 379 neonates related to 15 antidepressants were included. Disproportionate reporting was detected for antidepressants as a group as compared to all other drugs (ROR: 6.18, 95% CI 5.45–7.01, IC: 2.07, 95% CI 1.92–2.21). Signals were found for TCAs (10.55, 95% CI 8.02–13.88), followed by other antidepressants (ROR: 5.90, 95% CI 4.74–7.36) and SSRIs (ROR: 4.68, 95% CI 4.04–5.42). Significant disproportionality emerged for all individual antidepressants except for bupropion, whereas no disproportionality for any antidepressant was detected v. methadone. Eleven antidepressants had a moderate clinical priority score and four had a weak one. Most frequent symptoms included respiratory symptoms (n = 106), irritability/agitation (n = 75), tremor (n = 52) and feeding problems (n = 40).

Conclusions

Most antidepressants are associated with moderate signals of disproportionate reporting for neonatal withdrawal syndrome, which should be considered when prescribing an antidepressant during pregnancy, irrespective of class.
Wirken Online-Peer-Suizidpräventionsprogramme?
Authors: Hildebrand Anja , Weiss Maren , Braun-Scharm Hellmuth , Stemmler Mark
Published: September 2022

Zusammenfassung. Theoretischer Hintergrund. Suizid ist weltweit die zweithäufigste Todesursache bei jungen Menschen. Es scheint sinnvoll, speziell auf diese Zielgruppe zugeschnittene Angebote anzubieten. Fragestellung. Ziel dieser Untersuchung ist, den von den Nutzenden wahrgenommenen Beratungserfolg eines Online-Peer-Suizidpräventionsprogramms zu ermitteln und zu prüfen, welche Merkmale mit dem Beratungserfolg zusammenhängen. Methode. Daten eines Online-Fragebogens wurden ausgewertet ( N = 318). Ergebnisse. Bei zwei Drittel der Befragten verminderte sich die Suizidalität. Wichtige Variablen zur Vorhersage der Veränderung der Suizidalität waren der Eindruck der Ratsuchenden, dass die Peers die persönlichen Anliegen verstehen und die Anregung zu einer Verhaltensänderung. Das Peerverhalten trug signifikant zur Vorhersage der subjektiven Nützlichkeit und der allgemeinen Situation bei. Schlussfolgerungen. Die Studie liefert positive Ergebnisse hinsichtlich der Evaluierung der Online-Suizidpräventions-Beratung. Da das Verstanden fühlen und das Peerverhalten im Zusammenhang mit dem Beratungserfolg steht, könnte der Peer-Ansatz und die damit einhergehende positive Beziehungserfahrung wichtig sein.
Influence of Snowpack Cold Content on Seasonally Frozen Ground and Its Hydrologic Consequences: A Case Study From Niwot Ridge, CO
Authors: Rush M. J. , Rajaram H.
Published: September 2022

Frozen ground influences subsurface hydrology by reducing soil permeability, impeding infiltration, and inducing surface runoff. As the seasonal snowpack strongly controls the evolution of the ground thermal regime, it is necessary to represent the snowpack in models simulating frozen ground and its hydrologic consequences. Conventional understanding of the relationship between snowcover and frozen ground considers the snowpack as an insulator, shielding the ground from cold winter temperatures and thus inhibiting frozen ground. However, observations and modeling at Niwot Ridge, a seasonally snow‐covered alpine catchment in the headwaters of the Boulder Creek watershed, illustrate that snowpack cold content can promote and preserve frozen ground beneath the snowpack during the snowmelt season, unlike bare ground patches that thaw relatively rapidly due to exposure to solar radiation and warm spring temperatures. We present results from a coupled snowpack and subsurface thermo‐hydrologic model including freeze‐thaw processes that captures these contrasts reasonably well. Our results suggest that the cold snowpack at this site acts as a heat sink and promotes frozen ground, in contrast to the conventional understanding of the snowpack as an insulator. In the subalpine zone, infiltration simulations show that shallow freezing beneath snow‐covered ground has a much stronger effect on infiltration than shallow freezing beneath bare ground because the soil beneath the snow remained frozen during snowmelt, whereas bare patches thawed by the time they received excess snowmelt run‐on.
Magmatic Carbon and Helium in Springs Reveals the Vitality of a Dormant Volcano, Taranaki, New Zealand
Authors: Werner C. , Schipper C. I. , Cronin S. J. , Barry P. H. , Stewart M. K.
Published: September 2022

A challenge in monitoring long‐dormant volcanoes is to discover early signs of reawakening. Mineral springs on Taranaki volcano (2,518 m, New Zealand) have elevated carbonate concentrations, δ13CDIC ∼ −5‰ (VPDB) and He isotopes from 5.13 to 5.92 RA, indicating a magmatic volatile source. Stable isotopes demonstrate water recharge occurs near the volcano's summit. Volatile anions and silica are low in a cold (5oC) flank spring at 1,000 m a.s.l., yet elevated in warm springs (25–32oC) associated with travertine deposits at 250–300 m, suggesting a weak hydrothermal component along the flow path. Tritium dating of the cold spring water yields a mean residence time of 7.8 years. This short residence time and magmatic volatile signatures suggest magmatic CO2 persistently flushes Taranaki's upper edifice. Cold spring geochemistry thus reveals volcanic activity at this dormant volcano that otherwise lacks obvious geophysical signs of unrest.
Meridional Propagation of Carbon Dioxide (CO2) Growth Rate and Flux Anomalies From the Tropics Due to ENSO
Authors: Das Chiranjit , Kunchala Ravi Kumar , Chandra Naveen , Chmura Lukasz , Nęcki Jarosław , Patra Prabir K.
Published: September 2022

El Niño Southern Oscillation (ENSO) influence on carbon dioxide (CO2) growth rates are not spatially uniform or simultaneous around the globe. Using atmospheric CO2 observations and atmospheric chemistry‐transport model (ACTM), we show that anomalies in CO2 fluxes and growth rate originate in the tropics, as an effect of ENSO. The CO2 anomalies are then propagated from the equator toward the poles with asymmetric delays. A maximum delay of about 8 and 4 months are found at the northern hemisphere (NH) and southern hemisphere (SH) high latitudes, respectively. This asymmetric time delay is because of the CO2 flux anomaly mainly originate in the tropical SH land and transport of SH air into the NH is slower than that for NH air into the SH. The poleward increase of time delay is more homogeneous in the upper troposphere, as per the ACTM simulations, but observational evidence suffers from gaps in long‐term measurements.
An Improved and Observationally‐Constrained Melt Rate Parameterization for Vertical Ice Fronts of Marine Terminating Glaciers
Authors: Schulz K. , Nguyen A. T. , Pillar H. R.
Published: September 2022

Submarine melting at Greenland's marine terminating glaciers is a crucial, yet poorly constrained process in the coupled ice‐ocean system. Application of Antarctic melt rate representations, derived for floating glacier tongues, to non‐floating marine terminating glaciers commonly found in Greenland, results in a dramatic underestimation of submarine melting. Here, we revisit the physical theory underlying melt rate parameterizations and leverage recently published observational data to derive a novel melt rate parameterization. This is the first parameterization that (a) consistently comprises both convective‐ and shear‐dominated melt regimes, (b) includes coefficients quantitatively constrained using observational data, and (c) is applicable to any vertical glacier front. We show that, compared to the current state‐of‐the‐art approach, the scheme provides an improved fit to observed melt rates on the scale of the terminating front, offering an opportunity to incorporate this critical missing forcing into ocean circulation models.
Pathological oligodendrocyte precursor cells revealed in human schizophrenic brains and trigger schizophrenia-like behaviors and synaptic defects in genetic animal model
Authors: Yu Guangdan , Su Yixun , Guo Chen , Yi Chenju , Yu Bin , Chen Hui , Cui Yihui , Wang Xiaorui , Wang Yuxin , Chen Xiaoying , Wang Shouyu , Wang Qi , Chen Xianjun , Hu Xuelian , Mei Feng , Verkhratsky Alexei , Xiao Lan , Niu Jianqin
Published: September 2022

Although the link of white matter to pathophysiology of schizophrenia is documented, loss of myelin is not detected in patients at the early stages of the disease, suggesting that pathological evolution of schizophrenia may occur before significant myelin loss. Disrupted-in-schizophrenia-1 (DISC1) protein is highly expressed in oligodendrocyte precursor cells (OPCs) and regulates their maturation. Recently, DISC1-Δ3, a major DISC1 variant that lacks exon 3, has been identified in schizophrenia patients, although its pathological significance remains unknown. In this study, we detected in schizophrenia patients a previously unidentified pathological phenotype of OPCs exhibiting excessive branching. We replicated this phenotype by generating a mouse strain expressing DISC1-Δ3 gene in OPCs. We further demonstrated that pathological OPCs, rather than myelin defects, drive the onset of schizophrenic phenotype by hyperactivating OPCs’ Wnt/β-catenin pathway, which consequently upregulates Wnt Inhibitory Factor 1 (Wif1), leading to the aberrant synaptic formation and neuronal activity. Suppressing Wif1 in OPCs rescues synaptic loss and behavioral disorders in DISC1-Δ3 mice. Our findings reveal the pathogenetic role of OPC-specific DISC1-Δ3 variant in the onset of schizophrenia and highlight the therapeutic potential of Wif1 as an alternative target for the treatment of this disease.
Efficacy of psychotropic medications on suicide and self-injury: a meta-analysis of randomized controlled trials
Authors: Huang Xieyining , Harris Lauren M. , Funsch Kensie M. , Fox Kathryn R. , Ribeiro Jessica D.
Published: September 2022

Using psychotropic medications to treat and prevent self-injurious thoughts and behaviors (SITBs) has become increasingly popular, but conclusive evidence supporting the efficacy this approach remains elusive. To empirically examine whether psychotropic medications are efficacious treatments for SITBs, the present meta-analysis comprehensively summarizes all published randomized controlled trials (RCTs) that have reported the causal effects of psychotropic medications on suicide and self-injury. A total of 251 papers from 718 unique RCTs were included. A frequentist pairwise approach was adopted for meta-analyses. Potential effect modifiers were examined via met regressions and potential biases were evaluated through sensitivity analyses. On average, medications yielded an 8% reduction in SITB frequency and a reduction of 0.2 standard deviations in symptoms and severity. Findings were largely consistent across potential effect modifiers, and significant evidence of publication bias was not detected. Only one medication class (i.e., antipsychotics) and two specific medications (i.e., citalopram, ketamine) produced larger-than-average treatment effects. Psychostimulants and typical antipsychotics may produce iatrogenic effects. Less than 4% of included studies required individuals to exhibit SITBs, and nearly half of analyzed effects were drawn from studies that excluded individuals on the basis of SITB risk. Taken together, findings suggest that psychotropic medications produce small treatment effects on SITBs; however, these findings should be considered in light of the methodological constraints of the existing literature, including the lack of studies intentionally including individuals with SITBs. It is critical for future RCTs to prioritize including individuals with existing SITBs to further clarify treatment effects in self-injurious and suicidal populations. Additional research is needed to better understand the treatment mechanisms of psychotropic medications and identify the causal processes underlying SITBs.
MIIP functions as a novel ligand for ITGB3 to inhibit angiogenesis and tumorigenesis of triple-negative breast cancer
Authors: Gao Yujing , Fang Yujie , Huang Yongli , Ma Rui , Chen Xixi , Wang Fang , Pei Xiuying , Gao Yuanqi , Chen Xuehua , Liu Xinrui , Shan Jingxuan , Li Pu
Published: September 2022

Migration and invasion inhibitory protein (MIIP) has been identified as a tumor suppressor in various cancer types. Although MIIP is reported to exert tumor suppressive functions by repressing proliferation and metastasis of cancer cells, the detailed mechanism is poorly understood. In the present study, we found MIIP is a favorable indicator of prognosis in triple-negative breast cancer. MIIP could inhibit tumor angiogenesis, proliferation, and metastasis of triple-negative breast cancer cells in vivo and in vitro. Mechanistically, MIIP directly interacted with ITGB3 and suppressed its downstream signaling. As a result, β-catenin was reduced due to elevated ubiquitin-mediated degradation, leading to downregulated VEGFA production and epithelial mesenchymal transition. More importantly, we found RGD motif is essential for MIIP binding with ITGB3 and executing efficient tumor-suppressing effect. Our findings unravel a novel mechanism by which MIIP suppresses tumorigenesis in triple-negative breast cancer, and MIIP is thus a promising molecular biomarker or therapeutic target for the disease.
LncRNA SNHG1 regulates neuroblastoma cell fate via interactions with HDAC1/2
Authors: Hsu Chia-Lang , Yin Chieh-Fan , Chang Yi-Wen , Fan Ya-Chih , Lin Shih-Han , Wu Yu-Ching , Huang Hsuan-Cheng , Juan Hsueh-Fen
Published: September 2022

The small nucleolar RNA host gene 1 (SNHG1) is a novel oncogenic long non-coding RNA (lncRNA) aberrantly expressed in different tumor types. We previously found highly expressed SNHG1 was associated with poor prognosis and MYCN status in neuroblastoma (NB). However, the molecular mechanisms of SNHG1 in NB are still unclear. Here, we disrupted endogenous SNHG1 in the MYCN-amplified NB cell line SK-N-BE(2)C using the CRISPR/Cas9 system and demonstrated the proliferation and colony formation ability of SNHG1-knowndown cells were suppressed. The transcriptome analysis and functional assays of SNHG1-knockdown cells revealed SNHG1 was involved in various biological processes including cell growth, migration, apoptosis, cell cycle, and reactive oxygen species (ROS). Interestingly, the expression of core regulatory circuitry (CRC) transcription factors in MYCN-amplified NB, including PHOX2B, HAND2, GATA3, ISL1, TBX1, and MYCN, were decreased in SNHG1-knockdown cells. The chromatin-immunoprecipitation sequencing (ChIP-seq) and transposase-accessible chromatin using sequencing (ATAC-seq) analyses showed that chromatin status of these CRC members was altered, which might stem from interactions between SNHG1 and HDAC1/2. These findings demonstrate that SNHG1 plays a crucial role in maintaining NB identity via chromatin regulation and reveal the function of the lncRNA SNHG1 in NB.
Evolutionary origin of vertebrate OCT4/POU5 functions in supporting pluripotency
Authors: Sukparangsi Woranop , Morganti Elena , Lowndes Molly , Mayeur Hélène , Weisser Melanie , Hammachi Fella , Peradziryi Hanna , Roske Fabian , Hölzenspies Jurriaan , Livigni Alessandra , Godard Benoit Gilbert , Sugahara Fumiaki , Kuratani Shigeru , Montoya Guillermo , Frankenberg Stephen R. , Mazan Sylvie , Brickman Joshua M.
Published: September 2022

The support of pluripotent cells over time is an essential feature of development. In eutherian embryos, pluripotency is maintained from naïve states in peri-implantation to primed pluripotency at gastrulation. To understand how these states emerged, we reconstruct the evolutionary trajectory of the Pou5 gene family, which contains the central pluripotency factor OCT4. By coupling evolutionary sequence analysis with functional studies in mouse embryonic stem cells, we find that the ability of POU5 proteins to support pluripotency originated in the gnathostome lineage, prior to the generation of two paralogues, Pou5f1 and Pou5f3 via gene duplication. In osteichthyans, retaining both genes, the paralogues differ in their support of naïve and primed pluripotency. The specialization of these duplicates enables the diversification of function in self-renewal and differentiation. By integrating sequence evolution, cell phenotypes, developmental contexts and structural modelling, we pinpoint OCT4 regions sufficient for naïve pluripotency and describe their adaptation over evolutionary time.
Preclinical and randomized clinical evaluation of the p38α kinase inhibitor neflamapimod for basal forebrain cholinergic degeneration
Authors: Jiang Ying , Alam John J. , Gomperts Stephen N. , Maruff Paul , Lemstra Afina W. , Germann Ursula A. , Stavrides Philip H. , Darji Sandipkumar , Malampati Sandeep , Peddy James , Bleiwas Cynthia , Pawlik Monika , Pensalfini Anna , Yang Dun-Sheng , Subbanna Shivakumar , Basavarajappa Balapal S. , Smiley John F. , Gardner Amanda , Blackburn Kelly , Chu Hui-May , Prins Niels D. , Teunissen Charlotte E. , Harrison John E. , Scheltens Philip , Nixon Ralph A.
Published: September 2022

The endosome-associated GTPase Rab5 is a central player in the molecular mechanisms leading to degeneration of basal forebrain cholinergic neurons (BFCN), a long-standing target for drug development. As p38α is a Rab5 activator, we hypothesized that inhibition of this kinase holds potential as an approach to treat diseases associated with BFCN loss. Herein, we report that neflamapimod (oral small molecule p38α inhibitor) reduces Rab5 activity, reverses endosomal pathology, and restores the numbers and morphology of BFCNs in a mouse model that develops BFCN degeneration. We also report on the results of an exploratory (hypothesis-generating) phase 2a randomized double-blind 16-week placebo-controlled clinical trial (Clinical trial registration: NCT04001517/EudraCT #2019-001566-15) of neflamapimod in mild-to-moderate dementia with Lewy bodies (DLB), a disease in which BFCN degeneration is an important driver of disease expression. A total of 91 participants, all receiving background cholinesterase inhibitor therapy, were randomized 1:1 between neflamapimod 40 mg or matching placebo capsules (taken orally twice-daily if weight <80 kg or thrice-daily if weight >80 kg). Neflamapimod does not show an effect in the clinical study on the primary endpoint, a cognitive-test battery. On two secondary endpoints, a measure of functional mobility and a dementia rating-scale, improvements were seen that are consistent with an effect on BFCN function. Neflamapimod treatment is well-tolerated with no study drug associated treatment discontinuations. The combined preclinical and clinical observations inform on the validity of the Rab5-based pathogenic model of cholinergic degeneration and provide a foundation for confirmatory (hypothesis-testing) clinical evaluation of neflamapimod in DLB.
The role of renewables for rapid transitioning of the power sector across states in India
Authors: Gulagi Ashish , Ram Manish , Bogdanov Dmitrii , Sarin Sandeep , Mensah Theophilus Nii Odai , Breyer Christian
Published: September 2022

Recent events like heatwaves and abnormal rainfall are a glimpse of the devastating effects of human induced climate change. No country is immune to its effects, but a developing country like India is particularly vulnerable. This research, for the individual states of India, explores the technical feasibility and economic viability of a renewable transition pathway for the power sector. Based on the assumptions of this study, we show that a renewables-based power system by 2050 is lower in cost than the current  coal dominated system, has zero greenhouse gas emissions and provides reliable electricity to around 1.7 billion people. Electricity generation will be based on solar PV, wind energy, and hydropower, while batteries and multi-fuel reciprocating internal combustion engines based on synthetic fuels provide the required flexibility to the power system. This transition would address  multiple imperatives: affordability, accessibility, and sustainability without compromising economic growth.
Reaction-based fluorogenic probes for detecting protein cysteine oxidation in living cells
Authors: Ferreira Renan B. , Fu Ling , Jung Youngeun , Yang Jing , Carroll Kate S.
Published: September 2022

‘Turn-on’ fluorescence probes for detecting H2O2 in cells are established, but equivalent tools to monitor the products of its reaction with protein cysteines have not been reported. Here we describe fluorogenic probes for detecting sulfenic acid, a redox modification inextricably linked to H2O2 signaling and oxidative stress. The reagents exhibit excellent cell permeability, rapid reactivity, and high selectivity with minimal cytotoxicity. We develop a high-throughput assay for measuring S-sulfenation in cells and use it to screen a curated kinase inhibitor library. We reveal a positive association between S-sulfenation and inhibition of TK, AGC, and CMGC kinase group members including GSK3, a promising target for neurological disorders. Proteomic mapping of GSK3 inhibitor-treated cells shows that S-sulfenation sites localize to the regulatory cysteines of antioxidant enzymes. Our studies highlight the ability of kinase inhibitors to modulate the cysteine sulfenome and should find broad application in the rapidly growing field of redox medicine.
Resolving molecular diffusion and aggregation of antibody proteins with megahertz X-ray free-electron laser pulses
Authors: Reiser Mario , Girelli Anita , Ragulskaya Anastasia , Das Sudipta , Berkowicz Sharon , Bin Maddalena , Ladd-Parada Marjorie , Filianina Mariia , Poggemann Hanna-Friederike , Begam Nafisa , Akhundzadeh Mohammad Sayed , Timmermann Sonja , Randolph Lisa , Chushkin Yuriy , Seydel Tilo , Boesenberg Ulrike , Hallmann Jörg , Möller Johannes , Rodriguez-Fernandez Angel , Rosca Robert , Schaffer Robert , Scholz Markus , Shayduk Roman , Zozulya Alexey , Madsen Anders , Schreiber Frank , Zhang Fajun , Perakis Fivos , Gutt Christian
Published: September 2022

X-ray free-electron lasers (XFELs) with megahertz repetition rate can provide novel insights into structural dynamics of biological macromolecule solutions. However, very high dose rates can lead to beam-induced dynamics and structural changes due to radiation damage. Here, we probe the dynamics of dense antibody protein (Ig-PEG) solutions using megahertz X-ray photon correlation spectroscopy (MHz-XPCS) at the European XFEL. By varying the total dose and dose rate, we identify a regime for measuring the motion of proteins in their first coordination shell, quantify XFEL-induced effects such as driven motion, and map out the extent of agglomeration dynamics. The results indicate that for average dose rates below 1.06 kGy μs−1 in a time window up to 10 μs, it is possible to capture the protein dynamics before the onset of beam induced aggregation. We refer to this approach as correlation before aggregation and demonstrate that MHz-XPCS bridges an important spatio-temporal gap in measurement techniques for biological samples.
Insular cortical circuits as an executive gateway to decipher threat or extinction memory via distinct subcortical pathways
Authors: Wang Qi , Zhu Jia-Jie , Wang Lizhao , Kan Yan-Peng , Liu Yan-Mei , Wu Yan-Jiao , Gu Xue , Yi Xin , Lin Ze-Jie , Wang Qin , Lu Jian-Fei , Jiang Qin , Li Ying , Liu Ming-Gang , Xu Nan-Jie , Zhu Michael X. , Wang Lu-Yang , Zhang Siyu , Li Wei-Guang , Xu Tian-Le
Published: September 2022

Threat and extinction memories are crucial for organisms’ survival in changing environments. These memories are believed to be encoded by separate ensembles of neurons in the brain, but their whereabouts remain elusive. Using an auditory fear-conditioning and extinction paradigm in male mice, here we discovered that two distinct projection neuron subpopulations in physical proximity within the insular cortex (IC), targeting the central amygdala (CeA) and nucleus accumbens (NAc), respectively, to encode fear and extinction memories. Reciprocal intracortical inhibition of these two IC subpopulations gates the emergence of either fear or extinction memory. Using rabies-virus-assisted tracing, we found IC-NAc projection neurons to be preferentially innervated by intercortical inputs from the orbitofrontal cortex (OFC), specifically enhancing extinction to override fear memory. These results demonstrate that IC serves as an operation node harboring distinct projection neurons that decipher fear or extinction memory under the top-down executive control from OFC.
Characterizing DNA methylation signatures of retinoblastoma using aqueous humor liquid biopsy
Authors: Li Hong-Tao , Xu Liya , Weisenberger Daniel J. , Li Meng , Zhou Wanding , Peng Chen-Ching , Stachelek Kevin , Cobrinik David , Liang Gangning , Berry Jesse L.
Published: September 2022

Retinoblastoma (RB) is a cancer that forms in the developing retina of babies and toddlers. The goal of therapy is to cure the tumor, save the eye and maximize vision. However, it is difficult to predict which eyes are likely to respond to therapy. Predictive molecular biomarkers are needed to guide prognosis and optimize treatment decisions. Direct tumor biopsy is not an option for this cancer; however, the aqueous humor (AH) is an alternate source of tumor-derived cell-free DNA (cfDNA). Here we show that DNA methylation profiling of the AH is a valid method to identify the methylation status of RB tumors. We identify 294 genes directly regulated by methylation that are implicated in p53 tumor suppressor (RB1, p53, p21, and p16) and oncogenic (E2F) pathways. Finally, we use AH to characterize molecular subtypes that can potentially be used to predict the likelihood of treatment success for retinoblastoma patients.
Mechanism driven design of trimer Ni1Sb2 site delivering superior hydrogenation selectivity to ethylene
Authors: Ge Xiaohu , Dou Mingying , Cao Yueqiang , Liu Xi , Yuwen Qiang , Zhang Jing , Qian Gang , Gong Xueqing , Zhou Xinggui , Chen Liwei , Yuan Weikang , Duan Xuezhi
Published: September 2022

Mechanism driven catalyst design with atomically uniform ensemble sites is an important yet challenging issue in heterogeneous catalysis associated with breaking the activity-selectivity trade-off. Herein, a trimer Ni1Sb2 site in NiSb intermetallic featuring superior selectivity is elaborated for acetylene semi-hydrogenation via a theoretical guidance with a precise synthesis strategy. The trimer Ni1Sb2 site in NiSb intermetallic is predicted to endow acetylene reactant with an adequately but not excessively strong σ-adsorption mode while ethylene product with a weak π-adsorption one, where such compromise delivers higher ethylene formation rate. An in-situ trapping of molten Sb by Ni strategy is developed to realize the construction of Ni1Sb2 site in the intermetallic P63/mmc NiSb catalysts. Such catalyst exhibits ethylene selectivity up to 93.2% at 100% of acetylene conversion, significantly prevailing over the referred Ni catalyst. These insights shed new lights on rational catalyst design by taming active sites to energetically match targeted reaction pathway.
Neural probe system for behavioral neuropharmacology by bi-directional wireless drug delivery and electrophysiology in socially interacting mice
Authors: Yoon Yousang , Shin Hyogeun , Byun Donghak , Woo Jiwan , Cho Yakdol , Choi Nakwon , Cho Il-Joo
Published: September 2022

Assessing the neurological and behavioral effects of drugs is important in developing pharmacological treatments, as well as understanding the mechanisms associated with neurological disorders. Herein, we present a miniaturized, wireless neural probe system with the capability of delivering drugs for the real-time investigation of the effects of the drugs on both behavioral and neural activities in socially interacting mice. We demonstrate wireless drug delivery and simultaneous monitoring of the resulting neural, behavioral changes, as well as the dose-dependent and repeatable responses to drugs. Furthermore, in pairs of mice, we use a food competition assay in which social interaction was modulated by the delivery of the drug, and the resulting changes in their neural activities are analyzed. During modulated food competition by drug injection, we observe changes in neural activity in mPFC region of a participating mouse over time. Our system may provide new opportunities for the development of studying the effects of drugs on behaviour and neural activity.
60 million years of glaciation in the Transantarctic Mountains
Authors: Barr Iestyn D. , Spagnolo Matteo , Rea Brice R. , Bingham Robert G. , Oien Rachel P. , Adamson Kathryn , Ely Jeremy C. , Mullan Donal J. , Pellitero Ramón , Tomkins Matt D.
Published: September 2022

The Antarctic continent reached its current polar location ~83 Ma and became shrouded by ice sheets ~34 Ma, coincident with dramatic global cooling at the Eocene-Oligocene boundary. However, it is not known whether the first Antarctic glaciers formed immediately prior to this or were present significantly earlier. Here we show that mountain glaciers were likely present in the Transantarctic Mountains during the Late Palaeocene (~60–56 Ma) and middle Eocene (~48–40 Ma). Temperate (warm-based) glaciers were prevalent during the Late Eocene (~40–34 Ma) and, in reduced numbers, during the Oligocene (~34–23 Ma), before larger, likely cold-based, ice masses (including ice sheets) dominated. Some temperate mountain glaciers were present during the Miocene Climatic Optimum (~15 Ma), before a widespread switch to cold-based glaciation. Our findings highlight the longevity of glaciation in Antarctica and suggest that glaciers were present even during the Early-Cenozoic greenhouse world.
The natural history and genetic diversity of Haemophilus influenzae infecting the airways of adults with cystic fibrosis
Authors: Izydorczyk Conrad , Waddell Barbara J. , Weyant Robert B. , Surette Michael G. , Somayaji Ranjani , Rabin Harvey R. , Conly John M. , Church Deirdre L. , Parkins Michael D.
Published: September 2022

Haemophilus influenzae is a Gram-negative pathobiont, frequently recovered from the airways of persons with cystic fibrosis (pwCF). Previous studies of H. influenzae infection dynamics and transmission in CF predominantly used molecular methods, lacking resolution. In this retrospective cohort study, representative yearly H. influenzae isolates from all pwCF attending the Calgary Adult CF Clinic with H. influenzae positive sputum cultures between 2002 and 2016 were typed by pulsed-field gel electrophoresis. Isolates with shared pulsotypes common to ≥ 2 pwCF were sequenced by Illumina MiSeq. Phylogenetic and pangenomic analyses were used to assess genetic relatedness within shared pulsotypes, and epidemiological investigations were performed to assess potential for healthcare associated transmission. H. influenzae infection was observed to be common (33% of patients followed) and dynamic in pwCF. Most infected pwCF exhibited serial infections with new pulsotypes (75% of pwCF with ≥ 2 positive cultures), with up to four distinct pulsotypes identified from individual patients. Prolonged infection by a single pulsotype was only rarely observed. Intra-patient genetic diversity was observed at the single-nucleotide polymorphism and gene content levels. Seven shared pulsotypes encompassing 39% of pwCF with H. influenzae infection were identified, but there was no evidence, within our sampling scheme, of direct patient-to-patient infection transmission.
The role of mindful acceptance and lucid dreaming in nightmare frequency and distress
Authors: Tzioridou Sofia , Dresler Martin , Sandberg Kristian , Mueller Erik M.
Published: September 2022

A theoretical and empirical association between lucid dreaming and mindfulness, as well as lucid dreaming and nightmares has previously been observed; however, the relationship between nightmares and mindfulness has received surprisingly little attention. Here, we present the findings of two studies exploring the relation of nightmare frequency and distress with two components of mindfulness, termed presence and acceptance, as well as lucid dreaming. Study 1 (N = 338) consisted of a low percentage of frequent lucid dreamers whereas Study 2 (N = 187) consisted primarily of frequent lucid dreamers that used lucid dream induction training techniques and meditation. Across studies, nightmare-related variables showed a more robust association with mindful acceptance as opposed to mindful presence. Moreover, individuals with high levels of meditation expertise and practice of lucid dreaming induction techniques reported lower nightmare frequency. Finally, in Study 2, which consisted of frequent lucid dreamers, a positive correlation between lucid dreaming frequency and mindfulness was apparent. The present findings support the notion that wakeful mindfulness is associated with the quality of dreams and extend previous research by suggesting a disentangled role of the two facets of mindfulness in dream variation. This association remains open for experimental manipulation, the result of which could have clinical implications.
Development and application of an environment monitoring system based on IPv6
Authors: Li Xiuhong , Hao Xuejie , Yin Lizeyan , Ma Yushuang , Sun Meiying , Yang Rongjin
Published: September 2022

The widespread use of the Internet of Things (Iot) makes it possible to connect everything but having enough IP addresses is a fundamental requirement of this paradigm. All previous environmental monitoring systems in China are based on IPv4. In combination with the characteristics and requirements of China's atmospheric environment monitoring system, this paper develops a monitoring system based on IPv6 technology. Users can directly access the monitoring equipment through the IPv6 website to view data and configure operations. This paper first introduces the design and implementation of the software and hardware of the system, then introduces the simplification of IPv6 protocol, the transplantation of IPv6 protocol on ARM and the design and implementation of embedded Web server system. The experimental results show that the developed atmospheric environment monitoring system can realize continuous data acquisition based on IPv6 and provide data-driven support for environmental protection management and decision-making.
Developing a hybrid time-series artificial intelligence model to forecast energy use in buildings
Authors: Ngo Ngoc-Tri , Pham Anh-Duc , Truong Thi Thu Ha , Truong Ngoc-Son , Huynh Nhat-To
Published: September 2022

The development of a reliable energy use prediction model is still difficult due to the inherent complex pattern of energy use data. There are few studies developing a prediction model for the one-day-ahead energy use prediction in buildings and optimizing the hyperparameters of a prediction model is necessary. This study aimed to propose a hybrid artificial intelligence model for forecasting one-day ahead time-series energy consumption in buildings. The proposed model was developed based on the integration of the Seasonal Autoregressive integrated Moving average, the Firefly-inspired Optimization algorithm, and the support vector Regression (SAMFOR). A large dataset of energy consumption in 30-min intervals, temporal data, and weather data from six real-world buildings in Vietnam was used to train and test the model. Sensitivity analyses were performed to identify appropriate model inputs. Comparison results show that the SAMFOR model was more effective than the others such as the seasonal autoregressive integrated moving average (SARIMA) and support vector regression (SVR), SARIMA-SVR, and random forests (RF) models. Evaluation results on real-world building depicted that the proposed SAMFOR model achieved the highest accuracy with the root-mean-square error (RMSE) of 1.77 kWh in, mean absolute percentage error (MAPE) of 9.56%, and correlation coefficient (R) of 0.914. The comparison results confirmed that the SAMFOR model was effective for forecasting one-day-ahead energy consumption. The study contributes to (1) the knowledge domain by proposing the hybrid SAMFOR model for forecasting energy consumption in buildings; and (2) the state of practice by providing building managers or users with a powerful tool for analyzing and improving building energy performance.
MISPR: an open-source package for high-throughput multiscale molecular simulations
Authors: Atwi Rasha , Bliss Matthew , Makeev Maxim , Rajput Nav Nidhi
Published: September 2022

Computational tools provide a unique opportunity to study and design optimal materials by enhancing our ability to comprehend the connections between their atomistic structure and functional properties. However, designing materials with tailored functionalities is complicated due to the necessity to integrate various computational-chemistry software (not necessarily compatible with one another), the heterogeneous nature of the generated data, and the need to explore vast chemical and parameter spaces. The latter is especially important to avoid bias in scattered data points-based models and derive statistical trends only accessible by systematic datasets. Here, we introduce a robust high-throughput multi-scale computational infrastructure coined MISPR (Materials Informatics for Structure–Property Relationships) that seamlessly integrates classical molecular dynamics (MD) simulations with density functional theory (DFT). By enabling high-performance data analytics and coupling between different methods and scales, MISPR addresses critical challenges arising from the needs of automated workflow management and data provenance recording. The major features of MISPR include automated DFT and MD simulations, error handling, derivation of molecular and ensemble properties, and creation of output databases that organize results from individual calculations to enable reproducibility and transparency. In this work, we describe fully automated DFT workflows implemented in MISPR to compute various properties such as nuclear magnetic resonance chemical shift, binding energy, bond dissociation energy, and redox potential with support for multiple methods such as electron transfer and proton-coupled electron transfer reactions. The infrastructure also enables the characterization of large-scale ensemble properties by providing MD workflows that calculate a wide range of structural and dynamical properties in liquid solutions. MISPR employs the methodologies of materials informatics to facilitate understanding and prediction of phenomenological structure–property relationships, which are crucial to designing novel optimal materials for numerous scientific applications and engineering technologies.
Assessment of video see-through smart glasses for augmented reality to support technicians during milking machine maintenance
Authors: Sara Gabriele , Todde Giuseppe , Caria Maria
Published: September 2022

Smart glasses for augmented reality are digital technology under investigation in the agricultural sector. The potential of augmented reality was underlined, in some scientific contributions, as a support tool for farmers' activities and for the decision-making process. One of the most practical applications studied for augmented reality was in maintenance operations, where the use of smart glasses showed high capability. This work focuses on the evaluation of the performance and applicability of smart glasses with a video see-through display system and testing the device's available functions in agricultural frameworks. In addition, an augmented assistance scenario describing the main steps involved in the functioning of the maintenance operation was developed for milking machine inspection. The audio–video quality, battery life, detection capabilities of markers, and voice control interaction system were evaluated. The results showed the capabilities of smart glasses to reach augmented information from a long distance in a short time interval and to transmit audio and video with a high level of detail, allowing discrimination of small objects during remote assistance with reduced delay. The built maintenance scenario represents an example of augmented reality digital assistance application in the inspection and maintenance of the milking machine. The device performance and the proposed maintenance scenario underline the potential that augmented reality could have in the agricultural sector to assist and guide both farmers and technicians to timely problem solving. This solution fits into the agriculture 4.0 perspective, which is increasingly focused on digital transformation to improve farms’ efficiency and sustainability.
3D optical illusion as visualisation tools in spatial planning and development
Authors: Kaźmierczak Rafał , Szczepańska Agnieszka
Published: September 2022

Spatial planning and development use various visualisation methods. Technological advancements in visualisation techniques have allowed imaging to shift from 2 to 3D dimensions. 3D optical illusion, which converts information recorded in the digital form into a three-dimensional presentation, can be a new tool for presenting spatial development solutions. Since a optical illusion is a direct spatial presentation, it requires neither specialist preparation nor spatial imagination. For this reason, it can become an effective means of visual communication with the public in the area of spatial planning and development. This article shows an example of the imaging of a model element of spatial development (a building) using the 3D illusion technique. Collected opinions of the test group of viewers confirm the usefulness of this tool. The presented 3D visualisation effect evoked positive reactions among the viewers. The use of the hologram technique in spatial planning and development appears to be justified and is an interesting research trend.
A hybrid data-driven solution to facilitate safe mud window prediction
Authors: Gowida Ahmed , Ibrahim Ahmed Farid , Elkatatny Salaheldin
Published: September 2022

Safe mud window (SMW) defines the allowable limits of the mud weights that can be used while drilling O&G wells. Controlling the mud weight within the SMW limits would help avoid many serious problems such as wellbore instability issues, loss of circulation, etc. SMW can be defined by the minimum mud weight below which shear failure (breakout) may occur (MWBO) and the maximum mud weight above which tensile failure (breakdown) may occur (MWBD). These limits can be determined from the geomechanical analysis of downhole formations. However, such analysis is not always accessible for most drilled wells. Therefore, in this study, a new approach is introduced to develop a new data-driven model to estimate the safe mud weight range in no time and without additional cost. New models were developed using an artificial neural network (ANN) to estimate both MWBO and MWBD directly from the logging data that are usually available for most wells. The ANN-based models were trained using actual data from a Middle Eastern field before being tested by an unseen dataset. The models achieved high accuracy exceeding 92% upon comparing the predicted and observed output values. Additionally, new equations were established based on the optimized ANN models’ weights and biases whereby both MWBO and MWBD can be calculated without the need for any complicated codes. Finally, another dataset from the same field was then used to validate the new equations and the results demonstrated the high robustness of the new equations to estimate MWBO and MWBD with a low mean absolute percentage error of 0.60% at maximum. So, unlike the costly conventional approaches, the newly developed equations would facilitate determining the SMW limits in a timely and economically effective way, with high accuracy whenever the logging data are available.
Semi-quantification of the binding constant based on bond breaking in a combined acoustic–gravitational field
Authors: Miyagawa Akihisa , Oshiyama Kengo , Nagatomo Shigenori , Nakatani Kiyoharu
Published: September 2022

The present study demonstrated the semi-quantification of the binding constant for small interactions based on bond breaking in a coupled acoustic-gravitational field.
Micro-physical parameter dynamic evolution behaviour of a natural ester molecular chain under a changing electric field and its correlation mechanism with lightning impulse discharge: theoretical analysis
Authors: Ye Wenyu , Hao Jian , Gao Chenyu , Zhang Jingwen , Zhang Junyi , Liao Ruijin
Published: September 2022

The influence mechanism of the molecular spatial configuration on its microscopic parameters under different electric field strengths was studied to help understand the differences in the lightning impulse discharge behavior of different natural esters.
Monitoring MgCl2 hydrate formation from aqueous solutions using terahertz time-domain spectroscopy
Authors: Yan Yuyue , Zhang Jiaqi , Ren Guanhua , Zhou Lu , Liu Liyuan , Zhang Xueqian , Chen Ligang , Ouyang Chunmei , Han Jiaguang
Published: September 2022

Freezing-induced hydrate formation from MgCl2 aqueous solution was monitored using terahertz time-domain spectroscopy.
Modulation of gut microbiota and hypoglycemic/hypolipidemic activity of flavonoids from the fruits ofLycium barbarumon high-fat diet/streptozotocin-induced type 2 diabetic mice
Authors: Yang Tingting , Zhou Wangting , Xu Weiqi , Ran Linwu , Yan Yamei , Lu Lu , Mi Jia , Zeng Xiaoxiong , Cao Youlong
Published: September 2022

This study is aimed to determine the effects of flavonoids fromLycium barbarum(LBFs) on the high-fat diet (HFD)/streptozotocin (STZ)-induced type 2 diabetes in mice.
Ecofriendly urea-free pretreatment to enhance the inkjet printing performance of reactive dye inks on cotton fabrics
Authors: Wang Lei , Xie Guangyuan , Hu Hanchang , Zhu Qiuyu , Zhou Jing , Yu Zhicheng
Published: September 2022

In our work, a urea-free dye fixation process was developed to eliminate the use of urea and improve the dye fixation of reactive dyes to decrease the environmental influence of the inkjet printing industry.
Evaluation of the antimicrobial potential of cerium-based perovskite (CeCuO3) synthesized by a hydrothermal method
Authors: Soren Siba , Chakroborty Subhendu , Mahalik Rakesh Ranjan , Parhi Purnendu , Pal Kaushik , Behera Debendra , Sahoo Chita Ranjan , Padhy Rabindra N. , Aulakh Manpreet Kaur , Sareen Shweta , Krishna Suresh Babu Naidu
Published: September 2022

A hydrothermally synthesized CeCuO3 perovskite nanomaterial has been used as a disinfectant against microorganisms causing urinary tract infections (UTIs).
All-natural hydrogel electrolytes prepared by a universal strategy for supercapacitors
Authors: Liu Rui , Zhang Qianqian , Ran Fen
Published: September 2022

A traditional method for preparing a gel electrode membrane is generally free radical polymerization or chemical cross-linking, which inevitably introduces toxic substances.
Vitrimers trigger covalent bonded bio-silica fused composite materials for recycling, reshaping, and self-healing applications
Authors: Sriharshitha Salendra , Krishnadevi Krishnamoorthy , Prasanna Dakshinamoorthy
Published: September 2022

Bio-based benzoxazines used eugenol and incorporated bio-silica (BS) and trimethylolpropane-tris(3-mercaptopropionate) (SH) for self-healing, recycling, and reshaping applications.