bluuebunny/crossref_metadata_2025 huggingface dataset:
Contribution of Kinetic Alfvén Waves to Energetic Electron Precipitation From the Plasma Sheet During a Substorm
Authors: Shen Yangyang , Artemyev Anton V. , Zhang Xiao‐Jia , Zou Ying , Angelopoulos Vassilis , Vasko Ivan , Runov Andrei , Tsai Ethan , Wilkins Colin
Published: April 2023

Energetic (≳50 keV) electron precipitation from the magnetosphere to the ionosphere during substorms can be important for magnetosphere‐ionosphere coupling. Using conjugate observations between the THEMIS, ELFIN, and DMSP spacecraft during a substorm, we have analyzed the energetic electron precipitation, the magnetospheric injection, and the associated plasma waves to examine the role of waves in pitch‐angle scattering plasma sheet electrons into the loss cone. During the substorm expansion phase, ELFIN‐A observed 50–300 keV electron precipitation from the plasma sheet that was likely driven by wave‐particle interactions. The identification of the low‐altitude extent of the plasma sheet from ELFIN is aided by DMSP global auroral images. Combining quasi‐linear theory, numerical test particle simulations, and equatorial THEMIS measurements of particles and fields, we have evaluated the relative importance of kinetic Alfvén waves (KAWs) and whistler‐mode waves in driving the observed precipitation. We find that the KAW‐driven bounce‐averaged pitch‐angle diffusion coefficients near the edge of the loss cone are ∼10−6–10−5 s−1 for these energetic electrons. The due to parallel whistler‐mode waves, observed at THEMIS ∼10‐min after the ELFIN observations, are ∼10−8–10−6 s−1. Thus, at least in this case, the observed KAWs dominate over the observed whistler‐mode waves in the scattering and precipitation of energetic plasma sheet electrons during the substorm injection.
Revised Reconstruction of the Heliospheric Modulation Potential for 1964–2022
Authors: Väisänen Pauli , Usoskin Ilya , Kähkönen Riikka , Koldobskiy Sergey , Mursula Kalevi
Published: April 2023

Galactic cosmic rays (GCRs) impinge on the Earth's atmosphere and generate showers of secondary particles in nuclear collisions with the atmospheric constituents. The flux of GCR near Earth is subjected to heliospheric modulation driven by solar magnetic activity and to geomagnetic shielding. Variability of the GCR flux is continuously monitored by the worldwide network of ground‐based neutron monitors (NMs) since the 1950s. Solar modulation is often quantified via the force‐field approximation parameterized by the modulation potential ϕ, which can be evaluated from the global NM data set. Here we revisit the methodology and provide an updated and extended reconstruction of the heliospheric modulation potential for 1964–2022, using a recent NM yield function and the measurements of the 10 most stable high‐latitude NMs. A key improvement in the reconstructed heliospheric modulation potential is the new daily resolution, which provides new opportunities for further research. Reconstruction uses the root‐mean square error (RMSE) minimization to find the optimum daily and monthly scaling factors for individual NMs. The stability of the reconstruction is analyzed and the errors are estimated. The mean level of uncertainty is low, generally within ±1%, but it is found to depict marginal variability at the 11‐year, annual and 27‐day timescales at the <1% level, indicating that a very small systematic uncertainty is still present.
Associations of perfluoroalkyl substances (PFAS) with lipid and lipoprotein profiles
Authors: Haug Marianne , Dunder Linda , Lind P. Monica , Lind Lars , Salihovic Samira
Published: April 2023

Background

Perfluoroalkyl substances (PFAS) are man-made chemicals with unique properties that are widely distributed in humans and the environment. Recent studies suggest that PFAS are involved in cholesterol metabolism, however, the mechanisms underlying the associations are poorly understood.

Objective

We aimed to evaluate associations of plasma PFAS with detailed lipid and lipoprotein subfractions in an adult population of men and women.

Methods

We measured concentrations of cholesterol and triglycerides in lipoprotein subfractions, apolipoprotein subclasses, as well as fatty acid and different phospholipid measures, using serum proton nuclear magnetic resonance (1H-NMR), and four plasma PFAS using liquid chromatography-mass spectrometry (UHPLC-MS/MS). Measurements were available for 493 participants (all aged 50 years, 50% female). Multivariable linear regression was used to estimate the association of four PFAS with 43 different 1H-NMR measures, with adjustment for body mass index (BMI), smoking, education, and physical activity.

Results

We found that perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorodecanoic acid (PFDA), but not perfluorohexanesulfonate (PFHxS), concentrations were consistently positively associated with concentrations of cholesterol in lipoprotein subfractions, apolipoproteins, as well as composite fatty acid- and phospholipid profiles. The most consistent associations were found for the relationship of PFAS with total cholesterol in intermediate-density lipoprotein (IDL), across all low-density lipoprotein (LDL) subfractions and small high-density lipoprotein (HDL). Moreover, we found weak to null evidence for an association of any of the measured 13 triglyceride lipoprotein subfractions with PFAS.

Conclusions

Our results suggest that plasma PFAS concentrations are associated with cholesterol in small HDL, IDL and all LDL subfractions, as well as apolipoproteins and composite fatty acid and phospholipid profiles but to a lesser extent with triglycerides in lipoproteins. Our findings draw attention to the need for more detailed measurements of lipids across various lipoprotein subfractions and subclasses in assessing the role of PFAS in lipid metabolism.

Impact

By performing an in-depth characterization of circulating cholesterol and triglycerides in lipoprotein subfractions, apolipoprotein, fatty acid, and phospholipid concentrations, this study has expanded upon the limited literature available on the associations of plasma PFAS concentrations beyond clinical routine laboratory testing for lipids.
Feedback activation of EGFR/wild-type RAS signaling axis limits KRASG12D inhibitor efficacy in KRASG12D-mutated colorectal cancer
Authors: Feng Juanjuan , Hu Zhongwei , Xia Xinting , Liu Xiaogu , Lian Zhengke , Wang Hui , Wang Liren , Wang Cun , Zhang Xueli , Pang Xiufeng
Published: April 2023

Colorectal cancer (CRC), which shows a high degree of heterogeneity, is the third most deadly cancer worldwide. Mutational activation of KRASG12D occurs in approximately 10–12% of CRC cases, but the susceptibility of KRASG12D-mutated CRC to the recently discovered KRASG12D inhibitor MRTX1133 has not been fully defined. Here, we report that MRTX1133 treatment caused reversible growth arrest in KRASG12D-mutated CRC cells, accompanied by partial reactivation of RAS effector signaling. Through a drug-anchored synthetic lethality screen, we discovered that epidermal growth factor receptor (EGFR) inhibition was synthetic lethal with MRTX1133. Mechanistically, MRTX1133 treatment downregulated the expression of ERBB receptor feedback inhibitor 1 (ERRFI1), a crucial negative regulator of EGFR, thereby causing EGFR feedback activation. Notably, wild-type isoforms of RAS, including H-RAS and N-RAS, but not oncogenic K-RAS, mediated signaling downstream of activated EGFR, leading to RAS effector signaling rebound and reduced MRTX1133 efficacy. Blockade of activated EGFR with clinically used antibodies or kinase inhibitors suppressed the EGFR/wild-type RAS signaling axis, sensitized MRTX1133 monotherapy, and caused the regression of KRASG12D-mutant CRC organoids and cell line-derived xenografts. Overall, this study uncovers feedback activation of EGFR as a prominent molecular event that restricts KRASG12D inhibitor efficacy and establishes a potential combination therapy consisting of KRASG12D and EGFR inhibitors for patients with KRASG12D-mutated CRC.
Discovery of IHMT-MST1-39 as a novel MST1 kinase inhibitor and AMPK activator for the treatment of diabetes mellitus
Authors: Wang Junjie , Qi Ziping , Wu Yun , Wang Aoli , Liu Qingwang , Zou Fengming , Wang Beilei , Qi Shuang , Cao Jiangyan , Hu Chen , Shi Chenliang , Liang Qianmao , Wang Li , Liu Jing , Wang Wenchao , Liu Qingsong
Published: April 2023

Insulin-producing pancreatic β cell death is the fundamental cause of type 1 diabetes (T1D) and a contributing factor to type 2 diabetes (T2D). Moreover, metabolic disorder is another hallmark of T2D. Mammalian sterile 20-like kinase 1 (MST1) contributes to the progression of diabetes mellitus through apoptosis induction and acceleration of pancreatic β cell dysfunction. AMP-activated protein kinase (AMPK) is an energy sensing kinase and its activation has been suggested as a treatment option for metabolic diseases. Thus, pharmacological inhibition of MST1 and activation of AMPK simultaneously represents a promising approach for diabetes therapy. Here, we discovered a novel selective MST1 kinase inhibitor IHMT-MST1-39, which exhibits anti-apoptosis efficacy and improves the survival of pancreatic β cells under diabetogenic conditions, as well as primary pancreatic islets in an ex vivo disease model. Mechanistically, IHMT-MST1-39 activated AMPK signaling pathway in hepatocytes in vitro, combination of IHMT-MST1-39 and metformin synergistically prevented hyperglycemia and significantly ameliorated glucose tolerance and insulin resistance in diabetic mice. Taken together, IHMT-MST1-39 is a promising anti-diabetic candidate as a single agent or in combination therapy for both T1D and T2D.
The temporal dynamics of transition to psychosis in individuals at clinical high-risk (CHR-P) shows negative prognostic effects of baseline antipsychotic exposure: a meta-analysis
Authors: Raballo Andrea , Poletti Michele , Preti Antonio
Published: April 2023

Meta-analytic evidence indicates that baseline exposure to antipsychotics (AP) in individuals at clinical high-risk for psychosis (CHR-P) is associated with an even higher risk of transition to psychosis. However, the temporal dynamics of such prognostic effect have not been clarified yet. This study was therefore designed to address this knowledge gap. We performed a systematic review and meta-analysis of all longitudinal studies published up to 31 December 2021 on CHR-P individuals identified according to a validated diagnostic procedure and reporting numeric data of transition to psychosis according to baseline antipsychotic exposure. 28 studies covering a total of 2405 CHR-P were included. 554 (23.0%) were exposed to AP at baseline, whereas 1851 (77.0%) were not. At follow-up (12 to 72 months), 182 individuals among AP-exposed (32.9%; 95% CI: 29.4% to 37.8%) and 382 among AP-naive CHR-P (20.6%; 18.8% to 22.8%) developed psychosis. Transition rates increased over time, with the best-fit for an ascending curve peaking at 24 months and reaching then a plateau, with a further increase at 48 months. Baseline AP-exposed CHR-P had higher transition risk at 12 months and then again at 36 and 48 months, with an overall higher risk of transition (fixed-effect model: risk ratio = 1.56 [95% CI: 1.32–1.85]; z = 5.32; p < 0.0001; Random-effect model: risk ratio = 1.56 [95% CI: 1.07–2.26]; z = 2.54; p = 0.0196). In conclusion, the temporal dynamics of transition to psychosis differ in AP-exposed vs. AP-naive CHR-P. Baseline AP exposure in CHR-P is associated with a persistently higher risk of transition at follow up, supporting the rationale for more stringent clinical monitoring in AP-exposed CHR-P. The insufficiency of more granular information in available primary literature (e.g., temporal and quantitative details of AP exposure as well as psychopathological dimensions in CHR-P) did not allow the testing of causal hypotheses on this negative prognostic association.
FHL2 deficiency impairs follicular development and fertility by attenuating EGF/EGFR/YAP signaling in ovarian granulosa cells
Authors: Wang Chen , Sun Hui , Davis John S. , Wang Xiaojie , Huo Lijun , Sun Nan , Huang Qianzhi , Lv Xiangmin , Wang Cheng , He Chunbo , He Changjiu , Zhou Yang , Wu Jiyun , Yang Liguo , Hua Guohua
Published: April 2023

Female subfertility is an increasing reproductive issue worldwide, which is partially related to abnormal ovarian follicular development. Granulosa cells (GCs), by providing the necessary physical support and microenvironment for follicular development, play critical roles in maintaining female fertility. We previously showed that ectopic expression of four and a half LIM domains 2 (FHL2) promoted ovarian granulosa cell tumor progression. However, its function in follicular development and fertility remains unknown. Here, we confirmed that FHL2 is highly expressed in human and mouse ovaries. FHL2 immunosignals were predominantly expressed in ovarian GCs. A Fhl2 knockout (KO) mouse model was generated to examine its roles in follicular development and fertility. Compared with wildtype, knockout of Fhl2 significantly decreased female litter size and offspring number. Furthermore, Fhl2 deficiency reduced ovarian size and impaired follicular development. RNA-sequencing analysis of GCs isolated from either KO or WT mice revealed that, Fhl2 deletion impaired multiple biological functions and signaling pathways, such as Ovarian Putative Early Atresia Granulosa Cell, ErbB, Hippo/YAP, etc. In vitro studies confirmed that FHL2 silencing suppressed GCs growth and EGF-induced GCs proliferation, while its overexpression promoted GC proliferation and decreased apoptosis. Mechanistic studies indicated that FHL2, via forming complexes with transcriptional factors AP-1 or NF-κB, regulated Egf and Egfr expression, respectively. Besides, FHL2 depletion decreased YAP1 expression, especially the active form of YAP1 (nuclear YAP1) in GCs of growing follicles. EGF, serving as an autocrine/paracrine factor, not only induced FHL2 expression and nuclear accumulation, but also stimulated YAP1 expression and activation. Collectively, our study suggests that FHL2 interacts with EGFR and Hippo/YAP signaling to regulate follicular development and maintain fertility. This study illuminates a novel mechanism for follicular development and a potential therapeutic target to address subfertility.
IL-33 promotes double negative T cell survival via the NF-κB pathway
Authors: Sun Xiaojing , Zhang Chunpan , Sun Fanqi , Li Shuxiang , Wang Yaning , Wang Tingting , Li Li
Published: April 2023

IL-33, which is a crucial modulator of adaptive immune responses far beyond type 2 response, can enhance the function of several T cell subsets and maintain the immune homeostasis. However, the contribution of IL-33 to double negative T (DNT) cell remains unappreciated. Here, we demonstrated that the IL-33 receptor ST2 was expressed on DNT cells, and that IL-33 stimulation increased DNT cells proliferation and survival in vivo and in vitro. Transcriptome sequencing analysis also demonstrated that IL-33 enhanced the biological function of DNT cells, especially effects on proliferation and survival. IL-33 promoted DNT cells survival by regulating Bcl-2, Bcl-xl and Survivin expression. IL-33-TRAF4/6-NF-κB axis activation promoted the transmission of essential division and survival signals in DNT cells. However, IL-33 failed to enhance the expression of immunoregulatory molecules in DNT cells. DNT cells therapy combined with IL-33 inhibited T cells survival and further ameliorated ConA-induced liver injury, which mainly depended on the proliferative effect of IL-33 on DNT cells in vivo. Finally, we stimulated human DNT cells with IL-33, and similar results were observed. In conclusion, we revealed a cell intrinsic role of IL-33 in the regulation of DNT cells, thereby identifying a previously unappreciated pathway supporting the expansion of DNT cells in the immune environment.
Inhibition of the mitochondria-shaping protein Opa1 restores sensitivity to Gefitinib in a lung adenocarcinomaresistant cell line
Authors: Noguchi Masafumi , Kohno Susumu , Pellattiero Anna , Machida Yukino , Shibata Keitaro , Shintani Norihito , Kohno Takashi , Gotoh Noriko , Takahashi Chiaki , Hirao Atsushi , Scorrano Luca , Kasahara Atsuko
Published: April 2023

Drug resistance limits the efficacy of chemotherapy and targeted cancer treatments, calling for the identification of druggable targets to overcome it. Here we show that the mitochondria-shaping protein Opa1 participates in resistance against the tyrosine kinase inhibitor gefitinib in a lung adenocarcinoma cell line. Respiratory profiling revealed that oxidative metabolism was increased in this gefitinib-resistant lung cancer cell line. Accordingly, resistant cells depended on mitochondrial ATP generation, and their mitochondria were elongated with narrower cristae. In the resistant cells, levels of Opa1 were increased and its genetic or pharmacological inhibition reverted the mitochondrial morphology changes and sensitized them to gefitinib-induced cytochrome c release and apoptosis. In vivo, the size of gefitinib-resistant lung orthotopic tumors was reduced when gefitinib was combined with the specific Opa1 inhibitor MYLS22. The combo gefitinib-MYLS22 treatment increased tumor apoptosis and reduced its proliferation. Thus, the mitochondrial protein Opa1 participates in gefitinib resistance and can be targeted to overcome it.
Autophagy in hepatic ischemia–reperfusion injury
Authors: Mao Benliang , Yuan Wei , Wu Fan , Yan Yong , Wang Bailin
Published: April 2023

Hepatic ischemia–reperfusion injury (HIRI) is a major complication of liver resection or liver transplantation that can seriously affect patient’s prognosis. There is currently no definitive and effective treatment strategy for HIRI. Autophagy is an intracellular self-digestion pathway initiated to remove damaged organelles and proteins, which maintains cell survival, differentiation, and homeostasis. Recent studies have shown that autophagy is involved in the regulation of HIRI. Numerous drugs and treatments can change the outcome of HIRI by controlling the pathways of autophagy. This review mainly discusses the occurrence and development of autophagy, the selection of experimental models for HIRI, and the specific regulatory pathways of autophagy in HIRI. Autophagy has considerable potential in the treatment of HIRI.
Counteracting gemcitabine+nab-paclitaxel induced dysbiosis in KRAS wild type and KRASG12D mutated pancreatic cancer in vivo model
Authors: Panebianco Concetta , Pisati Federica , Villani Annacandida , Andolfo Annapaola , Ulaszewska Marynka , Bellini Edoardo , Ferro Carmelapia , Lombardi Renato , Orsenigo Fabrizio , Latiano Tiziana Pia , Belmonte Beatrice , Tripodo Claudio , Perri Francesco , Pazienza Valerio
Published: April 2023

Pancreatic cancer (PC) has a very low survival rate mainly due to late diagnosis and refractoriness to therapies. The latter also cause adverse effects negatively affecting the patients’ quality of life, often requiring dose reduction or discontinuation of scheduled treatments, compromising the chances of cure. We explored the effects of a specific probiotic blend on PC mice xenografted with KRAS wild-type or KRASG12D mutated cell lines alone or together with gemcitabine+nab-paclitaxel treatment to then assess tumor volume and clinical pathological variables. Beside a semi-quantitative histopathological evaluation of murine tumor and large intestine samples, histochemical and immunohistochemical analyses were carried out to evaluate collagen deposition, proliferation index Ki67, immunological microenvironment tumor-associated, DNA damage markers and also mucin production. Blood cellular and biochemical parameters and serum metabolomics were further analyzed. 16S sequencing was performed to analyze the composition of fecal microbiota. Gemcitabine+nab-paclitaxel treatment impaired gut microbial profile in KRAS wild-type and KRASG12D mice. Counteracting gemcitabine+nab-paclitaxel- induced dysbiosis through the administration of probiotics ameliorated chemotherapy side effects and decreased cancer-associated stromatogenesis. Milder intestinal damage and improved blood count were also observed upon probiotics treatment as well as a positive effect on fecal microbiota, yielding an increase in species richness and in short chain fatty acids producing- bacteria. Mice’ serum metabolomic profiles revealed significant drops in many amino acids upon probiotics administration in KRAS wild-type mice while in animals transplanted with PANC-1 KRASG12D mutated all treated groups showed a sharp decline in serum levels of bile acids with respect to control mice. These results suggest that counteracting gemcitabine+nab-paclitaxel-induced dysbiosis ameliorates chemotherapy side effects by restoring a favorable microbiota composition. Relieving adverse effects of the chemotherapy through microbiota manipulation could be a desirable strategy in order to improve pancreatic cancer patients’ quality of life and to increase the chance of cure.
Using conservation genetics to prioritise management options for an endangered songbird
Authors: Alves Fernanda , Banks Sam C. , Edworthy Max , Stojanovic Dejan , Langmore Naomi E. , Heinsohn Robert
Published: April 2023

Genetic data can be highly informative for answering questions relevant to practical conservation efforts, but remain one of the most neglected aspects of species recovery plans. Framing genetic questions with reference to practical and tractable conservation objectives can help bypass this limitation of the application of genetics in conservation. Using a single-nucleotide polymorphism dataset from reduced-representation sequencing (DArTSeq), we conducted a genetic assessment of remnant populations of the endangered forty-spotted pardalote (Pardalotus quadragintus), a songbird endemic to Tasmania, Australia. Our objectives were to inform strategies for the conservation of genetic diversity in the species and estimate effective population sizes and patterns of inter-population movement to identify management units relevant to population conservation and habitat restoration. We show population genetic structure and identify two small populations on mainland Tasmania as ‘satellites’ of larger Bruny Island populations connected by migration. Our data identify management units for conservation objectives relating to genetic diversity and habitat restoration. Although our results do not indicate the immediate need to genetically manage populations, the small effective population sizes we estimated for some populations indicate that they are vulnerable to genetic drift, highlighting the urgent need to implement habitat restoration to increase population size and to conduct genetic monitoring. We discuss how our genetic assessment can be used to inform management interventions for the forty-spotted pardalote and show that by assessing contemporary genetic aspects, valuable information for conservation planning and decision-making can be produced to guide actions that account for genetic diversity and increase chances of recovery in species of conservation concern.
Variability conceals emerging trend in 100yr projections of UK local hourly rainfall extremes
Authors: Kendon Elizabeth J. , Fischer Erich M. , Short Chris J.
Published: April 2023

Extreme precipitation is projected to intensify with warming, but how this will manifest locally through time is uncertain. Here, we exploit an ensemble of convection-permitting transient simulations to examine the emerging signal in local hourly rainfall extremes over 100-years. We show rainfall events in the UK exceeding 20 mm/h that can cause flash floods are 4-times as frequent by 2070s under high emissions; in contrast, a coarser resolution regional model shows only a 2.6x increase. With every degree of regional warming, the intensity of extreme downpours increases by 5-15%. Regional records of local hourly rainfall occur 40% more often than in the absence of warming. However, these changes are not realised as a smooth trend. Instead, as a result of internal variability, extreme years with record-breaking events may be followed by multiple decades with no new local rainfall records. The tendency for extreme years to cluster poses key challenges for communities trying to adapt.
Hematopoietic stem-cell gene therapy is associated with restored white matter microvascular function in cerebral adrenoleukodystrophy
Authors: Lauer Arne , Speroni Samantha L. , Choi Myoung , Da Xiao , Duncan Christine , McCarthy Siobhan , Krishnan Vijai , Lusk Cole A. , Rohde David , Hansen Mikkel Bo , Kalpathy-Cramer Jayashree , Loes Daniel J. , Caruso Paul A. , Williams David A. , Mouridsen Kim , Emblem Kyrre E. , Eichler Florian S. , Musolino Patricia L.
Published: April 2023

Blood-brain barrier disruption marks the onset of cerebral adrenoleukodystrophy (CALD), a devastating cerebral demyelinating disease caused by loss of ABCD1 gene function. The underlying mechanism are not well understood, but evidence suggests that microvascular dysfunction is involved. We analyzed cerebral perfusion imaging in boys with CALD treated with autologous hematopoietic stem-cells transduced with the Lenti-D lentiviral vector that contains ABCD1 cDNA as part of a single group, open-label phase 2-3 safety and efficacy study (NCT01896102) and patients treated with allogeneic hematopoietic stem cell transplantation. We found widespread and sustained normalization of white matter permeability and microvascular flow. We demonstrate that ABCD1 functional bone marrow-derived cells can engraft in the cerebral vascular and perivascular space. Inverse correlation between gene dosage and lesion growth suggests that corrected cells contribute long-term to remodeling of brain microvascular function. Further studies are needed to explore the longevity of these effects.
Long distance multiplexed quantum teleportation from a telecom photon to a solid-state qubit
Authors: Lago-Rivera Dario , Rakonjac Jelena V. , Grandi Samuele , Riedmatten Hugues de
Published: April 2023

Quantum teleportation is an essential capability for quantum networks, allowing the transmission of quantum bits (qubits) without a direct exchange of quantum information. Its implementation between distant parties requires teleportation of the quantum information to matter qubits that store it for long enough to allow users to perform further processing. Here we demonstrate long distance quantum teleportation from a photonic qubit at telecom wavelength to a matter qubit, stored as a collective excitation in a solid-state quantum memory. Our system encompasses an active feed-forward scheme, implementing a conditional phase shift on the qubit retrieved from the memory, as required by the protocol. Moreover, our approach is time-multiplexed, allowing for an increase in the teleportation rate, and is directly compatible with the deployed telecommunication networks, two key features for its scalability and practical implementation, that will play a pivotal role in the development of long-distance quantum communication.
Ring-closing C–O/C–O metathesis of ethers with primary aliphatic alcohols
Authors: Liu Hongmei , Huang Qing , Liao Rong-zhen , Li Man , Xie Youwei
Published: April 2023

In canonical organic chemistry textbooks, the widely adopted mechanism for the classic transetherifications between ethers and alcohols starts with the activation of the ether in order to weaken the C–O bond, followed by the nucleophilic attack by the alcohol hydroxy group, resulting in a net C–O/O–H σ-bond metathesis. In this manuscript, our experimental and computational investigation of a Re2O7mediated ring-closing transetherification challenges the fundamental tenets of the traditional transetherification mechanism. Instead of ether activation, the alternative activation of the hydroxy group followed by nucleophilic attack of ether is realized by commercially available Re2O7through the formation of perrhenate ester intermediate in hexafluoroisopropanol (HFIP), which results in an unusual C–O/C–O σ-bond metathesis. Due to the preference for the activation of alcohol rather than ether, this intramolecular transetherification reaction is therefore suitable for substrates bearing multiple ether moieties, unparalleled by any previous methods.
Mining of lattice distortion, strength, and intrinsic ductility of refractory high entropy alloys
Authors: Tandoc Christopher , Hu Yong-Jie , Qi Liang , Liaw Peter K.
Published: April 2023

Severe lattice distortion is a prominent feature of high-entropy alloys (HEAs) considered a reason for many of those alloys’ properties. Nevertheless, accurate characterizations of lattice distortion are still scarce to only cover a tiny fraction of HEA’s giant composition space due to the expensive experimental or computational costs. Here we present a physics-informed statistical model to efficiently produce high-throughput lattice distortion predictions for refractory non-dilute/high-entropy alloys (RHEAs) in a 10-element composition space. The model offers improved accuracy over conventional methods for fast estimates of lattice distortion by making predictions based on physical properties of interatomic bonding rather than atomic size mismatch of pure elements. The modeling of lattice distortion also implements a predictive model for yield strengths of RHEAs validated by various sets of experimental data. Combining our previous model on intrinsic ductility, a data mining design framework is demonstrated for efficient exploration of strong and ductile single-phase RHEAs.
A general-purpose material property data extraction pipeline from large polymer corpora using natural language processing
Authors: Shetty Pranav , Rajan Arunkumar Chitteth , Kuenneth Chris , Gupta Sonakshi , Panchumarti Lakshmi Prerana , Holm Lauren , Zhang Chao , Ramprasad Rampi
Published: April 2023

The ever-increasing number of materials science articles makes it hard to infer chemistry-structure-property relations from literature. We used natural language processing methods to automatically extract material property data from the abstracts of polymer literature. As a component of our pipeline, we trained MaterialsBERT, a language model, using 2.4 million materials science abstracts, which outperforms other baseline models in three out of five named entity recognition datasets. Using this pipeline, we obtained ~300,000 material property records from ~130,000 abstracts in 60 hours. The extracted data was analyzed for a diverse range of applications such as fuel cells, supercapacitors, and polymer solar cells to recover non-trivial insights. The data extracted through our pipeline is made available at polymerscholar.org which can be used to locate material property data recorded in abstracts. This work demonstrates the feasibility of an automatic pipeline that starts from published literature and ends with extracted material property information.
Challenges in, and recommendations for, hyperspectral imaging in ex vivo malignant glioma biopsy measurements
Authors: Walke Anna , Black David , Valdes Pablo A. , Stummer Walter , König Simone , Suero-Molina Eric
Published: April 2023

The visualization of protoporphyrin IX (PPIX) fluorescence with the help of surgical microscopes during 5-aminolevulinic acid-mediated fluorescence-guided resection (FGR) of gliomas is still limited at the tumor margins. Hyperspectral imaging (HI) detects PPIX more sensitively but is not yet ready for intraoperative use. We illustrate the current status with three experiments and summarize our own experience using HI: (1) assessment of HI analysis algorithm using pig brain tissue, (2) a partially retrospective evaluation of our experience from HI projects, and (3) device comparison of surgical microscopy and HI. In (1), we address the problem that current algorithms for evaluating HI data are based on calibration with liquid phantoms, which have limitations. Their pH is low compared to glioma tissue; they provide only one PPIX photo state and only PPIX as fluorophore. Testing the HI algorithm with brain homogenates, we found proper correction for optical properties but not pH. Considerably more PPIX was measured at pH 9 than at pH 5. In (2), we indicate pitfalls and guide HI application. In (3), we found HI superior to the microscope for biopsy diagnosis (AUC = 0.845 ± 0.024 (cut-off 0.75 µg PPIX/ml) vs. 0.710 ± 0.035). HI thus offers potential for improved FGR.
Parasitic infection in the scyphozoan Rhizostoma pulmo (Macri, 1778)
Authors: Motta Gregorio , Caffara Monica , Fioravanti Maria Letizia , Bottaro Massimiliano , Avian Massimo , Terlizzi Antonio , Tedesco Perla
Published: April 2023

Very little information is reported for parasites of cnidarians, therefore, the present work aimed to investigate parasitic infections in one of the most widespread jellyfish in the Mediterranean Sea, Rhizostoma pulmo. The goals were to determine prevalence and intensity of parasites in R. pulmo, identify the species involved through morphological and molecular analysis, test whether infection parameters differ in different body parts and in relation to jellyfish size. 58 individuals were collected, 100% of them infected with digenean metacercariae. Intensity varied between 18.7 ± 6.7 per individual in 0–2 cm diameter jellyfish up to 505 ± 50.6 in 14 cm ones. Morphological and molecular analyses suggest that the metacercariae belonged to the family Lepocreadiidae and could be possibly assigned to the genus Clavogalea. Prevalence values of 100% suggest that R. pulmo is an important intermediate host in the life cycle of lepocreadiids in the region. Our findings also support the hypothesis that R. pulmo is an important part in the diet of teleost fish, which are reported as definitive hosts of lepocreadiids, since trophic transmission is necessary for these parasites to complete their life cycles. Parasitological data may therefore be useful to investigate fish-jellyfish predation, integrating traditional methods such as gut contents analysis.
Treatment with fibroblast growth factor 19 increases skeletal muscle fiber size, ameliorates metabolic perturbations and hepatic inflammation in 5/6 nephrectomized mice
Authors: Benoit Berengère , Beau Alice , Bres Émilie , Chanon Stéphanie , Pinteur Claudie , Vieille-Marchiset Aurélie , Jalabert Audrey , Zhang Hao , Garg Priyanka , Strigini Maura , Vico Laurence , Ruzzin Jérôme , Vidal Hubert , Koppe Laetitia
Published: April 2023

Chronic kidney disease (CKD) is associated with osteosarcopenia, and because a physical decline in patients correlates with an increased risk of morbidity, an improvement of the musculoskeletal system is expected to improve morbi-mortality. We recently uncovered that the intestinal hormone Fibroblast Growth Factor 19 (FGF19) is able to promote skeletal muscle mass and strength in rodent models, in addition to its capacity to improve glucose homeostasis. Here, we tested the effects of a treatment with recombinant human FGF19 in a CKD mouse model, which associates sarcopenia and metabolic disorders. In 5/6 nephrectomized (5/6Nx) mice, subcutaneous FGF19 injection (0.1 mg/kg) during 18 days increased skeletal muscle fiber size independently of food intake and weight gain, associated with decreased gene expression of myostatin. Furthermore, FGF19 treatment attenuated glucose intolerance and reduced hepatic expression of gluconeogenic genes in uremic mice. Importantly, the treatment also decreased gene expression of liver inflammatory markers in CKD mice. Therefore, our results suggest that FGF19 may represent a novel interesting therapeutic strategy for a global improvement of sarcopenia and metabolic complications in CKD.
Flood sensitivity assessment of super cities
Authors: Wang Zijun , Chen Xiangyu , Qi Zhanshuo , Cui Chenfeng
Published: April 2023

In the context of global urbanization, more and more people are attracted to these cities with superior geographical conditions and strategic positions, resulting in the emergence of world super cities. However, with the increasing of urban development, the underlying surface of the city has changed, the soil originally covered with vegetation has been substituted by hardened pavement such as asphalt and cement roads. Therefore, the infiltration capacity of urban rainwater is greatly limited, and waterlogging is becoming more and more serious. In addition, the suburbs of the main urban areas of super cities are usually villages and mountains, and frequent flash floods seriously threaten the life and property safety of people in there. Flood sensitivity assessment is an effective method to predict and mitigate flood disasters. Accordingly, this study aimed at identifying the areas vulnerable to flood by using Geographic Information System (GIS) and Remote Sensing (RS) and apply Logistic Regression (LR) model to create a flood sensitivity map of Beijing. 260 flood points in history and 12 predictors [elevation, slope, aspect, distance to rivers, Topographic Wetness Index (TWI), Stream Power Index (SPI), Sediment Transport Index (STI), curvature, plan curvature, Land Use/Land Cover (LULC), soil, and rainfall] were used in this study. Even more noteworthy is that most of the previous studies discussed flash flood and waterlogging separately. However, flash flood points and waterlogging points were included together in this study. We evaluated the sensitivity of flash flood and waterlogging as a whole and obtained different results from previous studies. In addition, most of the previous studies focused on a certain river basin or small towns as the study area. Beijing is the world's ninth largest super cities, which was unusual in previous studies and has important reference significance for the flood sensitivity analysis of other super cities. The flood inventory data were randomly subdivided into training (70%) and test (30%) sets for model construction and testing using the Area Under Curve (AUC), respectively. The results turn out that: (1) elevation, slope, rainfall, LULC, soil and TWI were highly important among these elements, and were the most influential variables in the assessment of flood sensitivity. (2) The AUC of the test dataset revealed a prediction rate of 81.0%. The AUC was greater than 0.8, indicating that the model assessment accuracy was high. (3) The proportion of high risk and extremely high risk areas was 27.44%, including 69.26% of the flood events in this study, indicating that the flood distribution in these areas was relatively dense and the susceptibility was high. Super cities have a high population density, and once flood disasters occur, the losses brought by them are immeasurable. Thus, flood sensitivity map can provide meaningful information for policy makers to enact appropriate policies to reduce future damage.
Stroke Care Pathway ensures high-quality stroke management in the COVID-19 pandemic
Authors: Mayer-Suess Lukas , ter Telgte Annemieke , Praxmarer Silvia , Willeit Johann , Wöll Ewald , Geley Theresa , Rinner Heinrich , Knoflach Michael , Kiechl Stefan ,   The Tyrolean Stroke Pathway Group, Maurer Andreas , Schinnerl Adolf , Rauter-Rzehak Alexandra , Tür Andreas , Oberwinkler Bernhard , Dengg Christian , Loidl Patrick , Schoenherr Gudrun , Seiwald Gudrun , Kreuzer Hans , Schoenherr Hans-Robert , Matzak Heinrich , Spiss Heinrich , Kathrein Hermann , Gänzer Hannes , Schöch Johannes , Grossmann Josef , Runge Julia , Willeit Karin , Boehme Christian , Klingenschmid Gerhard , Toell Thomas , Pechlaner Raimund , Hametner Eva , Schmidauer Christoph , Sojer Martin , Berek Klaus , Engelhardt Klaus , Mayr Markus , Baubin Michael , Kaiser Norbert , Perfler Robert , Erlacher Thomas , Fluckinger Thomas , Grander Wilhelm
Published: April 2023

The aim of our study was to assess whether a well-established federal state-wide Stroke Care Pathway delivering high quality stroke care can cope with the COVID-19 pandemic and associated measures to contain the virus spread. The retrospective analysis is based on a prospective, quality-controlled, population-based registry of all stroke patients in the Tyrol, a federal state of Austria and one of the early hot-spots of COVID-19 in Europe. Patient characteristics, pre-hospital management, intra-hospital management and post-hospital were analysed. All residents of the Tyrol suffering ischemic stroke in 2020 (n = 1160) and four pre-COVID-19 years (n = 4321) were evaluated. In 2020, the annual number of stroke patients was the highest in this population-based registry. When local hospitals were overwhelmed with SARS-CoV-2-patients, stroke subjects were temporarily allocated to the comprehensive stroke centre. Stroke severity, quality metrics of stroke management, serious complications, and post-stroke mortality did not differ between 2020 and the four comparator years. Notably, iv. thrombolysis-rate was similar (19.9% versus 17.4%, P = 0.25) and endovascular stroke treatment even better (5.9% versus 3.9%, P = 0.003) but resources for in-patient rehabilitation were limited (25.8% versus 29.8%, P = 0.009). Concluding, a well-established Stroke Care Pathway was able to maintain high-quality acute stroke care even when challenged by a global pandemic.
Predicting wellbeing over one year using sociodemographic factors, personality, health behaviours, cognition, and life events
Authors: Chilver Miranda R. , Champaigne-Klassen Elyse , Schofield Peter R. , Williams Leanne M. , Gatt Justine M.
Published: April 2023

Various sociodemographic, psychosocial, cognitive, and life event factors are associated with mental wellbeing; however, it remains unclear which measures best explain variance in wellbeing in the context of related variables. This study uses data from 1017 healthy adults from the TWIN-E study of wellbeing to evaluate the sociodemographic, psychosocial, cognitive, and life event predictors of wellbeing using cross-sectional and repeated measures multiple regression models over one year. Sociodemographic (age, sex, education), psychosocial (personality, health behaviours, and lifestyle), emotion and cognitive processing, and life event (recent positive and negative life events) variables were considered. The results showed that while neuroticism, extraversion, conscientiousness, and cognitive reappraisal were the strongest predictors of wellbeing in the cross-sectional model, while extraversion, conscientiousness, exercise, and specific life events (work related and traumatic life events) were the strongest predictors of wellbeing in the repeated measures model. These results were confirmed using tenfold cross-validation procedures. Together, the results indicate that the variables that best explain differences in wellbeing between individuals at baseline can vary from the variables that predict change in wellbeing over time. This suggests that different variables may need to be targeted to improve population-level compared to individual-level wellbeing.
Connectome and regulatory hubs of CAGE highly active enhancers
Authors: Briend Mewen , Rufiange Anne , Moncla Louis-Hippolyte Minvielle , Mathieu Samuel , Bossé Yohan , Mathieu Patrick
Published: April 2023

Evidence indicates that enhancers are transcriptionally active. Herein, we investigated transcriptionally active enhancers by using cap analysis of gene expression (CAGE) combined with epigenetic marks and chromatin interactions. We identified CAGE-tag highly active (CHA) enhancers as distant regulatory elements with CAGE-tag ≥ 90th percentile and overlapping with H3K27ac peaks (4.5% of enhancers). CHA enhancers were conserved between mouse and man and were independent from super-enhancers in predicting cell identity with lower P-values. CHA enhancers had increased open chromatin and a higher recruitment of cell-specific transcription factors as well as molecules involved in 3D genome interactions. HiChIP analysis of enhancer-promoter looping indicated that CHA enhancers had a higher density of anchor loops when compared to regular enhancers. A subset of CHA enhancers and promoters characterized by a high density of chromatin loops and forming hub regulatory units were connected to the promoter of immediate early response genes, genes involved in cancer and encoding for transcription factors. Promoter of genes within hub CHA regulatory units were less likely to be paused. CHA enhancers were enriched in gene variants associated with autoimmune disorders and had looping with causal candidate genes as revealed by Mendelian randomization. Hence, CHA enhancers form a dense hierarchical network of chromatin interactions between regulatory elements and genes involved in cell identity and disorders.
Accuracy of pilot balloon palpation for cuff pressure assessment in small versus large sized tubes: a prospective non-randomized observational study
Authors: Ban Min Gi , Kim So Yeon , Kim Min Soo , Park Wyun Kon , Kwon Young In , Kim Hyun Joo
Published: April 2023

Pilot balloon palpation is still a commonly used method to evaluate cuff pressure of the endotracheal tube after intubation. This study determined whether the size of the tracheal tube influenced the accuracy of pilot balloon palpation. A prospective observational analysis of 208 patients intubated with an endotracheal tube of internal diameter (ID) 6.0 or 8.0 was conducted. An anesthesiologist judged the cuff pressure by manual pilot balloon palpation, and then measured the cuff pressure with a pressure gauge. Cuff pressure exceeding 20–30 cmH2O was defined as false recognition. The intracuff pressure was significantly higher in ID 6.0 tube than in the ID 8.0 tube (41.9 ± 18.8 cmH2O vs. 30.3 ± 11.9 cmH2O, p < 0.001). The number of patients that were mistakenly perceived to have appropriate cuff pressure by pilot balloon palpation was significantly higher in the ID 6.0 group compared to the ID 8.0 group (85 (81.7%) vs. 64 (61.5%), p = 0.001). Therefore, a smaller tube size may further increase risk of inaccurate measurement by pilot balloon palpation and although pressure gauge is recommended for all sizes to maximize accuracy, groups with increased risk factors should be targeted for standardized use of the pressure gauge.
Serum proteins for monitoring and predicting visual function in patients with recent optic neuritis
Authors: Kim Hyo Jae , Lee Eun-Jae , Kim Sang-Yeob , Kim Hyunjin , Kim Keon-Woo , Kim Seungmi , Kim Hyunji , Seo Dayoung , Lee Byung Joo , Lim Hyun Taek , Kim Kwang-Kuk , Lim Young-Min
Published: April 2023

It is unclear whether serum proteins can serve as biomarkers to reflect pathological changes and predict recovery in inflammation of optic nerve. We evaluated whether serum proteins could monitor and prognosticate optic neuritis (ON). We prospectively recruited consecutive patients with recent ON, classified as ON with anti-aquaporin-4 antibody (AQP4-ON), ON with anti-myelin oligodendrocyte glycoprotein antibody (MOG-ON), and double-seronegative ON (DSN-ON). Using ultrasensitive single-molecule array assays, we measured serum neurofilament light chain and glial fibrillary acidic protein (GFAP), and brain-derived neurotrophic factor (BDNF). We analyzed the markers according to disease group, state, severity, and prognosis. We enrolled 60 patients with recent ON (15 AQP4-ON; 14 MOG-ON; 31 DSN-ON). At baseline, AQP4-ON group had significantly higher serum GFAP levels than did other groups. In AQP4-ON group, serum GFAP levels were significantly higher in the attack state than in the remission state and correlated with poor visual acuity. As a prognostic indicator, serum BDNF levels were positively correlated with follow-up visual function in the AQP4-ON group (r = 0.726,p = 0.027). Serum GFAP reflected disease status and severity, while serum BDNF was identified as a prognostic biomarker in AQP4-ON. Serum biomarkers are potentially helpful for patients with ON, particularly those with AQP4-ON.