bluuebunny/crossref_metadata_2025 huggingface dataset:
TAAR1 Agonist Ulotaront Improves Glycemic Control and Reduces Body Weight in Rodent Models of Diabetes, Obesity, and Iatrogenic Weight Gain
Authors: Dedic Nina , Jones Philip G. , Hajos-Korcsok Eva , Synan Colleen , Wu Serena , Anacker Christoph , Vickers Steve P. , Hecksher-Sørensen Jacob , Zeni Courtney , Milanovic Snezana , Hopkins Seth C. , Bristow Linda J. , Koblan Kenneth S.
Published: April 2023

Introduction

Preclinical evidence has identified the trace amine-associated receptor 1 (TAAR1) as a novel regulator of metabolic control. Ulotaront is a TAAR1 and 5-HT1A agonist currently in Phase 3 clinical trials for the treatment of schizophrenia. Here we summarize preclinical results assessing the effects of ulotaront on weight and metabolic parameters.

Methods

Effects of ulotaront administration were evaluated on oral glucose tolerance (oGTT), gastric emptying, and in rodent models of weight gain (high-fat diet [HFD]-, corticosterone-, and olanzapine-induced).

Results

Following 15-day oral administration of ulotaront, rats on HFD showed dose-dependent reduction in body weight, food intake, and liver triglyceride content compared to controls. In addition, a more rapid reversal of olanzapine-induced weight gain and food intake was observed in rats switched to ulotaront (vs. vehicle). Consistent with weight-lowering effects in rats, chronic ulotaront treatment normalized corticosterone-induced weight gain in mice. Assessment of oGTT showed a dose-dependent reduction of glucose excursion in response to acute ulotaront administration in naive and diabetic db/db mice. Ulotaront administration also delayed gastric emptying in mice—a likely mechanism driving reductions in glucose excursions during the oGTT. Whole-brain c-fos imaging of ulotaront-treated mice revealed increased neuronal activity in several brain regions associated with regulation of food intake and metabolic signals.

Conclusions

The data indicate that ulotaront not only lacks metabolic liabilities typically associated with antipsychotics but can reduce body weight and improve glucose tolerance in rodent models. The underlying mechanisms may include TAAR1-mediated peripheral effects on glucose homeostasis and/or direct modulation of homeostatic and hedonic neurocircuits regulating energy balance. The beneficial metabolic effects of ulotaront may suggest a substantially improved risk-benefit profile compared to established antipsychotics.

Funding

Sunovion Pharmaceuticals Inc. and Otsuka Pharmaceutical Development & Commercialization, Inc.
Acute Emergence of Suicidal Thoughts Following Lemborexant Initiation: An Adverse Reaction Case Report
Authors: Roberts Thomas , Stryker Homer , Nagalla Madhavi Latha
Published: April 2023

This is a case report highlighting the side effect of suicidal ideation with lemborexant, a novel agent approved for the treatment of insomnia. A 22-year-old man received care at an outpatient psychiatrist for the treatment of major depressive disorder, persistent depressive disorder, generalized anxiety disorder, social phobia, and insomnia. The patient also has a diagnosis of Loeys-Dietz syndrome, a connective tissue disorder. Following numerous medication trials for both depression and insomnia that resulted in partial remission of mood symptoms without improvement in sleep, he was initiated on lemborexant to address insomnia. He was noted to be denying suicidal ideation at the appointment when lemborexant was prescribed. The patient did not take lemborexant until three days after the appointment, at which time he took the recommended dose of 5 mg at bedtime for insomnia. The patient experienced drowsiness immediately following taking this dose; however, he woke up two hours later with new-onset suicidal ideation. The patient was brought to the hospital for this complaint, and the following evening had attempted suicide by hanging in his hospital room. Laboratory investigations showed normal findings in blood chemistries, complete blood count, thyroid stimulating hormone, vitamin B12 level, vitamin D level, and urine illicit drug screening. Differential diagnosis includes acute reaction to insomnia, medication-induced side effect, and major depressive disorder. He had completed trials for insomnia with zolpidem, hydroxyzine, quetiapine, nortriptyline, and trazodone prior to beginning lemborexant. The patient had no history of suicide attempts in the past, but did experience suicidal ideation following a trial of nortriptyline. In the hospital, the lemborexant was discontinued, and clonidine and clonazepam were initiated at bedtime to address insomnia and ruminative thoughts. The patient was discharged with follow-up at his outpatient psychiatrist after his suicidal ideation was in remission, as well as noted improvement in insomnia. This case highlights new-onset suicidal ideation with subsequent suicide attempt after first use of lemborexant in a patient with major depressive disorder. This case is important given lemborexant is a new medication with limited information about its efficacy and safety in major psychiatric disorders.

Funding

No Funding
Assessing the Unmet Clinical Need and Opportunity for Digital Therapeutic Intervention in Schizophrenia: Perspective From People With Schizophrenia
Authors: Campellone Tim , Carretta Carrie , Davidson Charlie , Lakhan Shaheen , Sand Michael
Published: April 2023

Introduction

Recent research has highlighted the increasing ubiquity of smartphone ownership as well as the feasibility of digital interventions within schizophrenia. Digital therapeutics, a subset of digital interventions, have established standards for efficacy and safety and are subject to regulatory oversight as Software as a Medical Device. Here, we present data from a survey that assessed the opportunity and expectations that people with schizophrenia have for a digital therapeutic designed to be delivered on top of antipsychotic pharmacotherapy.

Methods

Seventy-five people with schizophrenia completed a 10-item survey. Participants were between 22 and 55 years of age, reported no hospitalizations or medication changes within the past 3 months, and were currently seeing a psychiatrist. For each question, participants were asked to rank responses to provide a clear understanding of their preferences.

Results

Patients with schizophrenia reported the survey items that most impacted their daily life were: difficulty meeting new people (17%) and difficulty setting goals/completing activities in daily life and not being productive in their free time (both at 13%). The greatest unmet treatment needs reported by people with schizophrenia were: improving social skills (19%); reducing distress related to disease (19%); and being more productive in their free time (13%). In terms of expectations for what a digital therapeutic would include, the items reported as most important were: sharing progress with providers (13%); teaching ways to deal with symptoms (13%); and helping to set and achieve goals (12%).

Conclusion

Many of the top unmet needs that people with schizophrenia identified can be uniquely targeted by a digital therapeutic that augments their ongoing standard of care.

Funding

Boehringer Ingelheim International GmbH and CLICK Therapeutics, Inc.
Lemborexant and Daridorexant for the Treatment of Insomnia: An Indirect Comparison, Using Number Needed to Treat, Number Needed to Harm, and Likelihood to Be Helped or Harmed
Authors: Citrome Leslie , Juday Timothy , Lundwall Christie
Published: April 2023

Background

To describe lemborexant and daridorexant for insomnia treatment using number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH).

Methods

Dichotomous outcomes were identified from the two registrational daridorexant randomized controlled trials. Analogous data were then extracted for lemborexant from the two lemborexant registration studies.

Results

Using pooled dosage data, lemborexant had a clinically relevant magnitude of therapeutic effect, as evidenced by NNT values versus placebo <10, and NNH values for lemborexant versus placebo were >10, suggesting that lemborexant is relatively tolerable. When comparing response versus discontinuation because of an adverse event (AE) for Month 3, the LHH ranges 5.2 to 10.4 for lemborexant pooled 5 mg and 10 mg doses (a favorable result). For daridorexant, the efficacy outcomes for pooled 25 mg and 50 mg doses generally result in NNT values versus placebo ≥10; in all instances, doses of 50 mg yield more robust NNT estimates than for the 25 mg dose. The rate of discontinuation because of an AE at Month 3 was higher for placebo than for daridorexant, rendering favorable LHH calculations for daridorexant despite the less robust NNT estimates, with an LHH in the range of 90.9 to 125 for Month 3 when comparing response versus discontinuation because of an AE (a favorable result).

Conclusions

Benefit-risk ratio for lemborexant and daridorexant is favorable as measured by NNT, NNH, and LHH. Indirect comparisons suggest an efficacy advantage for lemborexant and a tolerability advantage for daridorexant.

Funding

Eisai Inc.
Imaging and Molecular Annotation of Xenographs and Tumours (IMAXT): High throughput data and analysis infrastructure
Authors: González-Solares Eduardo A. , Dariush Ali , González-Fernández Carlos , Küpcü Yoldaş Aybüke , Molaeinezhad Alireza , Al Sa’d Mohammad , Smith Leigh , Whitmarsh Tristan , Millar Neil , Chornay Nicholas , Falciatori Ilaria , Fatemi Atefeh , Goodwin Daniel , Kuett Laura , Mulvey Claire M. , Páez Ribes Marta , Qosaj Fatime , Roth Andrew , Vázquez-García Ignacio , Watson Spencer S. , Windhager Jonas , Aparicio Samuel , Bodenmiller Bernd , Boyden Ed , Caldas Carlos , Harris Owen , Shah Sohrab P. , Tavaré Simon ,   CRUK IMAXT Grand Challenge Team, Bressan Dario , Hannon Gregory J. , Walton Nicholas A.
Published: April 2023

With the aim of producing a 3D representation of tumors, imaging and molecular annotation of xenografts and tumors (IMAXT) uses a large variety of modalities in order to acquire tumor samples and produce a map of every cell in the tumor and its host environment. With the large volume and variety of data produced in the project, we developed automatic data workflows and analysis pipelines. We introduce a research methodology where scientists connect to a cloud environment to perform analysis close to where data are located, instead of bringing data to their local computers. Here, we present the data and analysis infrastructure, discuss the unique computational challenges and describe the analysis chains developed and deployed to generate molecularly annotated tumor models. Registration is achieved by use of a novel technique involving spherical fiducial marks that are visible in all imaging modalities used within IMAXT. The automatic pipelines are highly optimized and allow to obtain processed datasets several times quicker than current solutions narrowing the gap between data acquisition and scientific exploitation.
The Forest Resistance to Droughts Differentiated by Tree Height in Central Europe
Authors: Li Tiewei , Guo Lanlan , He Bin , Liu Lianyou , Yuan Wenping , Chen Xiuzhi , Hao Xingming , Liu Xuebang , Zheng Hao , Zheng Huan , Wang Rui
Published: April 2023

More frequent droughts are altering the dynamics and function of the European forest ecosystem, which is deeply connected to the global carbon cycle. Tree height is an important structural feature of forests; however, how it regulates the response of forests to droughts remains controversial. By comprehensively examining the variations of satellite‐based vegetation greenness with drought evolution and the legacy effect of drought indicated by radial growth, we observed apparent height‐dependence forests' resistance to drought. Short forests showed lower resistance to drought than taller forests, demonstrating earlier and larger negative vegetation greenness anomalies. Additionally, larger reductions in radial growth after the drought year were also observed for shorter trees, implying an apparent legacy effect of drought on tree growth. The observed resistance differences can be attributed to the differences in the capacity for water absorption and regulation among forests of different heights. Our results provide an integrated explanation of tree‐level function that will be critical in understanding the response of forests and vegetation‐climate feedbacks in more widespread, prolonged, and extreme drought in the future.
Susceptibility of Microseismic Triggering to Small Sinusoidal Stress Perturbations at the Laboratory Scale
Authors: Colledge Martin , Aubry Jérôme , Chanard Kristel , Pétrélis François , Duverger Clara , Bollinger Laurent , Schubnel Alexandre
Published: April 2023

Small transient stress perturbations are prone to trigger (micro)seismicity. In the Earth's crust, these stress perturbations can be caused by various sources such as the passage of seismic waves, forcing by tides, or hydrological seasonal loads. A better understanding of the dynamic of earthquake triggering by stress perturbations is essential to improve our understanding of earthquake physics and our consideration of seismic hazard. Here, we study an experimental sandstone‐gouge‐filled fault system undergoing combined far field loading and periodic stress perturbations (of variable amplitude and frequency) at crustal pressure conditions. Microseismicity—in the form of acoustic emissions (AEs)—strains, and stresses, are continuously recorded in order to study the response of microseismicity as a function of loading rate, amplitude, and frequency of a periodic stress perturbation. The observed AE distributions do not follow the predictions of either a Coulomb failure model, taking into account both constant loading and oscillation‐induced strain rates, or a rate and state model. A susceptibility of the system's AE response to the amplitude of the confinement pressure perturbation is estimated, which highlights a linear relation between confinement pressure amplitude and the AE response amplitude, observations which agree with recent higher frequency experimental results on dynamic triggering. The magnitude‐frequency distribution of AEs is also computed. The Gutenberg‐Richter b‐value oscillates with stress oscillations. Our experiments may help complement our understanding of the influence of low inertia stress phenomena on the distribution of seismicity, such as observations of dynamic triggering and seismicity modulation by tides or hydrological loading.
Tracing Sediment Melt Activity in the Sub‐Continental Lithosphere: Insights From Zn‐Fe Stable Isotopes
Authors: Zhang Ganglan , Liu Yongsheng , Xu Rong , Moynier Frédéric , Zhu Yangtao , Ren Huange , Jiang Xin , Li Ming
Published: April 2023

Recycling of upper crustal sediments through slab subduction contributes to sub‐continental lithospheric refertilization and heterogeneity. However, the nature of recycled upper crustal components is unclear and direct evidence for sediment melt activity in the sub‐continental lithosphere is lacking. Here, we integrate major and trace elements, zircon U‐Pb dating, Sr‐Nd‐Zn‐Fe isotopic compositions of clinopyroxenites (crust‐mantle boundary) and a “glassy” xenolith from the North China Craton to relate their petrogenesis to the potential recycling of upper continental crust and provide direct insight into the sediment melt‐rock interaction. The clinopyroxenites have relatively uniform δ56Fe values (the permil deviation of the 56Fe/54Fe ratio from the IRMM014; −0.05‰–0.07‰, except for one outlier) and are not affected by melt metasomatism. The clinopyroxenites have highly variable whole‐rock δ66Zn values (the permil deviation of the 66Zn/64Zn ratio from the JMC‐Lyon standard) between 0.04‰ and 0.46‰, that closely correlate with Rb/La, K/U, Ba/Th, and Th/Nb ratios, and generate arrays that trend toward a composition similar to the “glassy” xenolith. The “glassy” xenolith has a high δ66Zn value (0.43‰ ± 0.05‰, 2SD) and a significantly low 143Nd/144Nd ratio (0.510991). This evidence implies that the “glassy” xenolith may represent a quenched sediment melt formed by the melting of carbonate‐bearing terrigenous sediments that may also be responsible for the metasomatism of clinopyroxenite xenoliths. The geochemical evidence from the “glassy” and clinopyroxenite xenoliths provides a direct evidence for the activity of sediment melt with upper continental crust components in the sub‐continental lithosphere.
Vertical Coupling of Gusts in the Lower Boundary Layer During Super Typhoons and Squall Lines
Authors: Zhou Qian‐Jin , Li Lei , Chan Pak Wai , Cheng Xue‐Ling , Yang Hong‐Long , Lan Chang‐Xing , Su Jia‐Chen
Published: April 2023

Identifying the coupling relationships between gusts at different altitudes of weather systems over land is essential to recognize the inherent energy transfer patterns of different types of windy weather systems and design civil structures and infrastructures. Using the time‐lagged convergent cross‐mapping (LCCM) and data obtained from the 356‐m‐high Shenzhen Meteorological Gradient Tower, we present an observational study of the gusts and momentum flux of two super typhoons (STs) and two squall lines (SLs). Compared to STs, the gusts in SLs are characterized by high amplitude bursts and first occur near the surface. Bivariate toy models and observational data showed that LCCM reliably identifies coupling relationships in the nonlinear system. Subsequently, we systematically demonstrated that LCCM can identify long‐distance interactions of multilevel gusts in different types of gale weather systems. Finally, the downward transportation of energy in ST was verified from the perspective of wind structure and turbulent vertical flux. The upper‐level STs gusts varied ahead of the lower‐level gusts, whereas the SLs showed the opposite result, which is consistent with the coupling relationship obtained by the LCCM method. The results of the study are expected to enhance the understanding of the characteristics of multilevel energy transfer of TC and SL boundary layers over land, provide useful information for validating numerical weather prediction models of damaging weather systems, and facilitate gale hazard prevention in coastal regions.
Impact Generation of Holes in the Early Lunar Crust: Scaling Relations
Authors: Jackson Alan P. , Perera Viranga , Gabriel Travis S. J.
Published: April 2023

After its formation, the Moon is widely believed to have possessed a deep, global magma ocean. As it cooled, an anorthositic crust formed, floating atop this magma ocean and acting as an insulating blanket. As well as forming the Moon, the Moon‐forming giant impact also released more than a lunar mass of debris into heliocentric orbit. Reimpacting debris subjected the newly formed Moon to an extremely intense bombardment. We have conducted a suite of impact simulations for a range of conditions representative of this early period. We find that impact outcomes can be divided into four regimes and construct scaling relations for the transitions between these regimes and size of impact features. Exposure of liquid magma to the surface is generally more efficient than previously assumed, implying significant shortening of the solidification time of the Lunar Magma Ocean. Comparison with work on icy satellites also suggests that penetration of a solid crust overlying liquid is a relatively universal process with weak dependence on target material properties.
Cold Collar Reproduced by a Venus GCM With the Akatsuki Horizontal Wind Assimilation
Authors: Ando Hiroki , Fujisawa Yukiko , Sugimoto Norihiko , Takagi Masahiro , Matsuda Yoshihisa
Published: April 2023

The thermal structure of the upper atmosphere in the Venus polar region is reproduced by the assimilation of horizontal winds in low‐ and mid‐latitudes derived from the Akatsuki ultra‐violet images. The obtained structure is well consistent with infrared and radio occultation measurements. In particular, the unique thermal features in the Venus polar vortex such as the cold collar and the warm polar region in our model are realistic: the level where the cold collar is located and the temperature difference between the cold collar and the warm polar region are consistent with data. The reasons why the thermal structure of the upper atmosphere in the Venus polar region is realistic are that the zonal wind distribution around the cloud top level and the structure of the residual mean meridional circulation induced by the thermal tides are improved with respect to the model without data assimilation. Our results also suggest that the thermal structure in the Venus upper polar region is closely related to the atmospheric dynamics.
L1 and Off Sun‐Earth Line Visible‐Light Imaging of Earth‐Directed CMEs: An Analysis of Inconsistent Observations
Authors: Harrison Richard A. , Davies Jackie A. , Barnes David , Möstl Christian
Published: April 2023

The efficacy of coronal mass ejection (CME) observations as a key input to space weather forecasting is explored by comparing on and off Sun‐Earth line observations from the ESA/NASA SOHO and NASA STEREO spacecraft. A comparison is made of CME catalogs based on L1 coronagraph imagery and off Sun‐Earth line coronagraph and heliospheric imager observations, for the year 2011. Analysis reveals inconsistencies in the identification of a number of potentially Earth‐directed CMEs. The catalogs reflect our ability to identify and characterize CMEs, so any discrepancies can impact our prediction of Earth‐directed CMEs. We show that 15 CMEs, which were observed by STEREO, that had estimated directions compatible with Earth‐directed events, had no identified halo/partial halo counterpart listed in the L1 coronagraph CME catalog. In situ data confirms that for 9 of these there was a consistent L1 Interplanetary CME (ICME). The number of such “discrepant” events is significant compared to the number of ICMEs recorded at L1 in 2011, stressing the need to address space weather monitoring capabilities, particularly with the inclusion of off Sun‐Earth line observation. While the study provides evidence that some halo CMEs are simply not visible in near‐Earth coronagraph imagery, there is evidence that some halo CMEs viewed from L1 are compromised by preceding CME remnants or the presence of multiple‐CMEs. This underlines (a) the value of multiple vantage point CME observation, and (b) the benefit of off Sun‐Earth line platform heliospheric imaging, and coronagraph imaging, for the efficient identification and tracking of Earth‐directed events.
Downcoast Redistribution of Changjiang Diluted Water Due To Typhoon Chan‐Hom (2015)
Authors: Lin Yunpeng , Li Yunhai , Cong Shuai , Liu Meng , Wang Liang , Zheng Binxin , Xu Jingping
Published: April 2023

Typhoons are known to substantially influence the coastal circulation and the associated biogeochemical processes. The transport of Changjiang diluted water (CDW), an important source to the coastal current in the East China Sea (ECS), varies markedly under the influence of typhoons. This study quantitively details the downcoast transport of CDW driven by Typhoon Chan‐Hom in the summer of 2015. Salinity measurements 3 days after the typhoon's passage showed the presence of a large volume of low‐salinity water, up to 70‐km wide and 20‐m thick along the Zhejiang‐Fujian coastal area with an estimated freshwater volume of 3.7 × 1010 m3. A three‐endmember mixing model shows that the CDW's contribution to the study area's surface waters (<10 m) immediately after the typhoon was as high as 40% (average 32%), much greater than the contribution under normal summer conditions of 8% (average 3%). The vast spreading of CDW along the Zhejiang‐Fujian coast created a strong stratification in the upper water column that limited the diffusion of CDW in the study area. The calculated and observed results suggest that these abnormal low‐salinity water could stay in the study area for 13–21 days. Additional nutrients in the CDW elevated the Chlorophyll‐a concentration in the upper water column (mean 3.74 mg m−3) and produced large amount of particulate organic carbon.
A tabletop X-ray tomography instrument for nanometer-scale imaging: reconstructions
Authors: Levine Zachary H. , Alpert Bradley K. , Dagel Amber L. , Fowler Joseph W. , Jimenez Edward S. , Nakamura Nathan , Swetz Daniel S. , Szypryt Paul , Thompson Kyle R. , Ullom Joel N.
Published: April 2023

We show three-dimensional reconstructions of a region of an integrated circuit from a 130 nm copper process. The reconstructions employ x-ray computed tomography, measured with a new and innovative high-magnification x-ray microscope. The instrument uses a focused electron beam to generate x-rays in a 100 nm spot and energy-resolving x-ray detectors that minimize backgrounds and hold promise for the identification of materials within the sample. The x-ray generation target, a layer of platinum, is fabricated on the circuit wafer itself. A region of interest is imaged from a limited range of angles and without physically removing the region from the larger circuit. The reconstruction is consistent with the circuit’s design file.
Nucleotide binding halts diffusion of the eukaryotic replicative helicase during activation
Authors: Ramírez Montero Daniel , Sánchez Humberto , van Veen Edo , van Laar Theo , Solano Belén , Diffley John F. X. , Dekker Nynke H.
Published: April 2023

The eukaryotic replicative helicase CMG centrally orchestrates the replisome and leads the way at the front of replication forks. Understanding the motion of CMG on the DNA is therefore key to our understanding of DNA replication. In vivo, CMG is assembled and activated through a cell-cycle-regulated mechanism involving 36 polypeptides that has been reconstituted from purified proteins in ensemble biochemical studies. Conversely, single-molecule studies of CMG motion have thus far relied on pre-formed CMG assembled through an unknown mechanism upon overexpression of individual constituents. Here, we report the activation of CMG fully reconstituted from purified yeast proteins and the quantification of its motion at the single-molecule level. We observe that CMG can move on DNA in two ways: by unidirectional translocation and by diffusion. We demonstrate that CMG preferentially exhibits unidirectional translocation in the presence of ATP, whereas it preferentially exhibits diffusive motion in the absence of ATP. We also demonstrate that nucleotide binding halts diffusive CMG independently of DNA melting. Taken together, our findings support a mechanism by which nucleotide binding allows newly assembled CMG to engage with the DNA within its central channel, halting its diffusion and facilitating the initial DNA melting required to initiate DNA replication.
Global navigation of Lithium in water bodies and emerging human health crisis
Authors: Adeel Muhammad , Zain Muhammad , Shakoor Noman , Ahmad Muhammad Arslan , Azeem Imran , Aziz Muhammad Abdullah , Tulcan Robert Xavier Supe , Rathore Akshit , Tahir Muhammad , Horton Robert , Xu Ming , Yukui Rui
Published: April 2023

The production of lithium (Li) increased by 256% in recent years due to unprecedented demands from technological industries. Intensive harvesting poses serious impacts on the sustainability of Li production. Herein, we address the global Li cycle and predict the peak production to reach 740000 million tons in 2041. Global Li accumulation in water bodies is mapped, and the consequences on human health of a wide range (<0.06–>20 mg L−1) of Li concentrations in drinking water are explored. The implications to human health of Li exposure remains unresolved and needs further investigation. There are still no recommendations on safe limits of Li in drinking water for humankind. In conclusion, there is an emergency call to health governing bodies, environmental protection agencies and scientific communities for urgent efforts on sustainable production of Li and identify their thresholds levels in drinking water to minimize the emerging consequences of Li on humans.
A new kinematic dataset of lower limbs action for balance testing
Authors: Dong Anqi , Wang Fei , Shuai ZhenYu , Zhang Kaiyu , Qian Dexing , Tian Yinsheng
Published: April 2023

Balance is a common performance but nevertheless an essential part of performance analysis investigations in ski. Many skier pay attention to the training of balance ability in training. Inertial Measurement Unit, as a kind of Multiplex-type human motion capture system, is widely used because of its humanized human-computer interaction design, low energy consumption and more freedom provided by the environment. The purpose of this research is to use sensor to establish a kinematics dataset of balance test tasks extracted from skis to help quantify skier’ balance ability. Perception Neuron Studio motion capture device is used in present. The dataset contains a total of 20 participants’ data (half male) of the motion and sensor data, which is collected at a 100 Hz sampling frequency. To our knowledge, this dataset is the only one that uses a BOSU ball in the balance test. We hope that this dataset will contribute to multiple fields of cross-technology integration in physical training and functional testing, including big-data analysis, sports equipment design and sports biomechanical analysis.
A distributable German clinical corpus containing cardiovascular clinical routine doctor’s letters
Authors: Richter-Pechanski Phillip , Wiesenbach Philipp , Schwab Dominic M. , Kiriakou Christina , He Mingyang , Allers Michael M. , Tiefenbacher Anna S. , Kunz Nicola , Martynova Anna , Spiller Noemie , Mierisch Julian , Borchert Florian , Schwind Charlotte , Frey Norbert , Dieterich Christoph , Geis Nicolas A.
Published: April 2023

We present CARDIO:DE, the first freely available and distributable large German clinical corpus from the cardiovascular domain. CARDIO:DE encompasses 500 clinical routine German doctor’s letters from Heidelberg University Hospital, which were manually annotated. Our prospective study design complies well with current data protection regulations and allows us to keep the original structure of clinical documents consistent. In order to ease access to our corpus, we manually de-identified all letters. To enable various information extraction tasks the temporal information in the documents was preserved. We added two high-quality manual annotation layers to CARDIO:DE, (1) medication information and (2) CDA-compliant section classes. To the best of our knowledge, CARDIO:DE is the first freely available and distributable German clinical corpus in the cardiovascular domain. In summary, our corpus offers unique opportunities for collaborative and reproducible research on natural language processing models for German clinical texts.
Mass spectrometry-based proteomic strategy for ecchymotic skin examination in forensic pathology
Authors: Toma Lorenzo , Vignali Giulia , Maffioli Elisa , Tambuzzi Stefano , Giaccari Roberta , Mattarozzi Monica , Nonnis Simona , Milioli Marco , Franceschetti Lorenzo , Paredi Gianluca , Negri Armando , Riccardi Benedetta , Cattaneo Cristina , Careri Maria , Tedeschi Gabriella , Bruno Stefano
Published: April 2023

Mass spectrometry (MS)-based proteomics has recently attracted the attention from forensic pathologists. This work is the first report of the development of a shotgun bottom-up proteomic approach based on rapid protein extraction and nano-liquid chromatography/high-resolution mass spectrometry applied to full-thickness human skin for the differential analysis of normal and ecchymotic tissues to identify new biomarkers for bruise characterization and dating. We identified around 2000 proteins from each pooled extract. The method showed excellent precision on independent replicates, with Pearson correlation coefficients always higher than 95%. Glycophorin A, a known biomarker of vital wounds from immunochemical studies, was identified only in ecchymotic tissues, as confirmed by Western blotting analysis. This finding suggests that this protein can be used as a MS-detectable biomarker of wound vitality. By focusing on skin samples from individuals with known wound dating, besides Glycophorin A, other proteins differentially expressed in ecchymotic samples and dependant on wound age were identified, although further analysis on larger datasets are needed to validate these findings. This study paves the way for an in-depth investigation of the potential of MS-based techniques for wound examination in forensic pathology, overcoming the limitations of immunochemical assays.
Non-invasive mass and temperature quantifications with spectral CT
Authors: Liu Leening P. , Hwang Matthew , Hung Matthew , Soulen Michael C. , Schaer Thomas P. , Shapira Nadav , Noël Peter B.
Published: April 2023

Spectral CT has been increasingly implemented clinically for its better characterization and quantification of materials through its multi-energy results. It also facilitates calculation of physical density, allowing for non-invasive mass measurements and temperature evaluations by manipulating the definition of physical density and thermal volumetric expansion, respectively. To develop spectral physical density quantifications, original and parametrized Alvarez–Macovski model and electron density-physical density model were validated with a phantom. The best physical density model was then implemented on clinical spectral CT scans of ex vivo bovine muscle to determine the accuracy and effect of acquisition parameters on mass measurements. In addition, the relationship between physical density and changes in temperature was evaluated by scanning and subjecting the tissue to a range of temperatures. The parametrized Alvarez–Macovski model performed best in both model development and validation with errors within ± 0.02 g/mL. No effect from acquisition parameters was observed in mass measurements, which demonstrated accuracy with a maximum percent error of 0.34%. Furthermore, physical density was strongly correlated (R of 0.9781) to temperature changes through thermal volumetric expansion. Accurate and precise spectral physical density quantifications enable non-invasive mass measurements for pathological detection and temperature evaluation for thermal therapy monitoring in interventional oncology.
A multi-omics integrative analysis based on CRISPR screens re-defines the pluripotency regulatory network in ESCs
Authors: Ruan Yan , Wang Jiaqi , Yu Meng , Wang Fengsheng , Wang Jiangjun , Xu Yixiao , Liu Lianlian , Cheng Yuda , Yang Ran , Zhang Chen , Yang Yi , Wang JiaLi , Wu Wei , Huang Yi , Tian Yanping , Chen Guangxing , Zhang Junlei , Jian Rui
Published: April 2023

A comprehensive and precise definition of the pluripotency gene regulatory network (PGRN) is crucial for clarifying the regulatory mechanisms in embryonic stem cells (ESCs). Here, after a CRISPR/Cas9-based functional genomics screen and integrative analysis with other functional genomes, transcriptomes, proteomes and epigenome data, an expanded pluripotency-associated gene set is obtained, and a new PGRN with nine sub-classes is constructed. By integrating the DNA binding, epigenetic modification, chromatin conformation, and RNA expression profiles, the PGRN is resolved to six functionally independent transcriptional modules (CORE, MYC, PAF, PRC, PCGF and TBX). Spatiotemporal transcriptomics reveal activated CORE/MYC/PAF module activity and repressed PRC/PCGF/TBX module activity in both mouse ESCs (mESCs) and pluripotent cells of early embryos. Moreover, this module activity pattern is found to be shared by human ESCs (hESCs) and cancers. Thus, our results provide novel insights into elucidating the molecular basis of ESC pluripotency.
Synthesis of vancomycin fluorescent probes that retain antimicrobial activity, identify Gram-positive bacteria, and detect Gram-negative outer membrane damage
Authors: Zhang Bing , Phetsang Wanida , Stone M. Rhia L. , Kc Sanjaya , Butler Mark S. , Cooper Matthew A. , Elliott Alysha G. , Łapińska Urszula , Voliotis Margaritis , Tsaneva-Atanasova Krasimira , Pagliara Stefano , Blaskovich Mark A. T.
Published: April 2023

Antimicrobial resistance is an urgent threat to human health, and new antibacterial drugs are desperately needed, as are research tools to aid in their discovery and development. Vancomycin is a glycopeptide antibiotic that is widely used for the treatment of Gram-positive infections, such as life-threatening systemic diseases caused by methicillin-resistantStaphylococcus aureus(MRSA). Here we demonstrate that modification of vancomycin by introduction of an azide substituent provides a versatile intermediate that can undergo copper-catalysed azide−alkyne cycloaddition (CuAAC) reaction with various alkynes to readily prepare vancomycin fluorescent probes. We describe the facile synthesis of three probes that retain similar antibacterial profiles to the parent vancomycin antibiotic. We demonstrate the versatility of these probes for the detection and visualisation of Gram-positive bacteria by a range of methods, including plate reader quantification, flow cytometry analysis, high-resolution microscopy imaging, and single cell microfluidics analysis. In parallel, we demonstrate their utility in measuring outer-membrane permeabilisation of Gram-negative bacteria. The probes are useful tools that may facilitate detection of infections and development of new antibiotics.
Supramolecular Chemistry, Fluorescence, and Sensing
Authors: Czarnik Anthony W.
Published: April 2023

Each new ability to visualize analyte concentrations in real-time portends the fabrication of new sensors. Potential applications include fiber optic-based remoting sensing of solution species and the monitoring of concentrations within living cells. A fluorescent chemosensor is a compound of abiotic origin that complexes to an analyte reversibly with concomitant fluorescence signal transduction transduction. Such chemosensors have been used for fluorimetric metal ion determination for over 100 years. The advent of ligand engineering has introduced a more systematic approach to the design of chemosensors with new selectivities and signal transduction schemes. The technological driving force to achieve useful chemosensors will stimulate investigation of new topics in molecule recognition, fluorescent signal transduction, and their intersection.
Fluorescent Sensors for Reactive Oxygen Species
Authors: Li Ping , Tang Bo
Published: April 2023

As the chemical by-products of cell metabolism, reactive oxygen species (ROS) are widely involved in signal transduction of physiological processes. However, when redox homeostasis is out of balance, excessive production of ROS may lead to or promote multiple pathologies. Currently, the diverse chemical properties of ROS and their biological mechanism are still poorly understood. Therefore, powerful tools need to be exploited to elucidate the chemical biology of ROS. Non-invasive fluorescence imaging techniques have gradually matured for tracking of active molecules. This chapter summarizes the fluorescent sensors for ROS in living cells and in vivo.
Molecular Fluorescent Probes for the Detection and Imaging of Sulfane Sulfur and Reactive Selenium Species
Authors: Wang Zhenkai , Yu Feifei , Xing Yanlong , Wang Rui , Liu Heng , Cheng Ziyi , Jin Jianfeng , Zhao Linlu , Yu Fabiao
Published: April 2023

Oxidative stress occurs when the intracellular redox homeostasis is disrupted, which is considered to be one of the important factors leading to aging and disease. Antioxidants of non-enzymatic reactive chalcogenide species play an important role in redox homeostasis, among which sulfane sulfur species and reactive selenium species are particularly indispensable. As a class of antioxidants with potential clinical biomarker value, the intracellular levels and distribution of sulfane sulfur and reactive selenium species can directly prove the dynamic state of oxidative stress, which may reveal the difference between physiological and pathological processes. Fluorescence bioimaging technology has the advantages of high temporal and spatial resolution, low invasiveness and fast response, and has become a powerful tool for intracellular detection. Herein, we have summarized the design strategy and development of fluorescent probes for the detection of sulfane sulfur and reactive selenium species. We have also highlighted the important physiological and pathological roles and mechanisms of these reactive species. We expect to point out a path centred on fluorescence imaging for the detection of representative biological reactive species in living systems.
Efficient biosynthesis of 5-aminolevulinic acid from glutamate via whole-cell biocatalyst in immobilized engineered Escherichia coli
Authors: Luo Ying , Liu Liang , Yang Jinshui , Su Anping , Yu Qijun , Wang Entao , Yuan Hongli
Published: April 2023

Development of a whole-cell catalysis system for an efficient conversion of glutamate to 5-aminolevulinic acid.
Sustainable valorisation of renewables through dialkyl carbonates and isopropenyl esters
Authors: Fiorani Giulia , Perosa Alvise , Selva Maurizio
Published: April 2023

This review showcases the most recent application of commercially relevant linear and alkylene organic carbonates and a representative enol ester, isopropenyl acetate (iPAc), for the chemical upgrading of renewable-based compounds and biopolymers.
Eco-friendly Egyptian blue (CaCuSi4O10) dye for luminescent solar concentrator applications
Authors: Rajaramanan Tharmakularasa , Keykhaei Mansoureh , Gourji Fatemeh Heidari , Ravirajan Punniamoorthy , Senthilnanthanan Meena , Frette Øyvind , Velauthapillai Dhayalan
Published: April 2023

An Egyptian blue integrated luminescent solar concentrator (LSC) is reported.
Can magnetotransport properties provide insight into the functional groups in semiconducting MXenes?
Authors: Koshi Namitha Anna , Mandia Anup Kumar , Muralidharan Bhaskaran , Lee Seung-Cheol , Bhattacharjee Satadeep
Published: April 2023

Hall scattering factors of Sc2CF2, Sc2CO2 and Sc2C(OH)2 are calculated using Rode's iterative approach by solving the Boltzmann transport equation.
High-efficiency reactor and its tandem module with Au–Co–CoOx-coated glass beads for continuous-flow reduction of dyeing wastewater
Authors: Sun Li , Sun Mengying , Zhi Yuan , Zhang Hua , Shan Yuejin , Dou Binlin , Chen Jian , Zhang Lixin
Published: April 2023

Au–Co–CoOx-coated glass beads were chosen as packing materials to construct a reactor for continuous-flow reduction of dyeing wastewater. The reactor and its tandem module show superior catalytic capacity, operating stability and reusability.
Synchronous amelioration of SnO2surface aggregation and buried layer defects by sodium salts for high-efficiency and stable perovskite solar cells
Authors: Zha Leying , Ning Lei , Zhang Pengyun , Du Pingfan , Xiong Jie , Song Lixin
Published: April 2023

The inclusion of BCA molecules in SnO2improves film coverage of ETL, regulates energy level, increases electron transport and migration ability, and enhances crystallization of perovskite. Overall, PSCs fabricated in open-air achieve a champion efficiency of 20.24%.
Two Fe(iii)/Eu(iii) Salophen complex-based optical sensors for determination of organophosphorus pesticide monocrotophos
Authors: Li Qian , Yang Jing , Yu Wenzhan , He Liqiong , Zhou Renlong , Nie Changming , Liao Lifu , Xiao Xilin
Published: April 2023

Two Fe(iii)/Eu(iii) Salophen complex-based optical sensors for determination of organophosphorus pesticide monocrotophos in camellia oil and tap water.
Observation of proton-transfer-coupled spin transition by single-crystal neutron-diffraction measurement
Authors: Nakanishi Takumi , Hori Yuta , Shigeta Yasuteru , Sato Hiroyasu , Wu Shu-Qi , Kiyanagi Ryoji , Munakata Koji , Ohhara Takashi , Sato Osamu
Published: April 2023

New iron(ii) complex exhibiting the proton transfer coupled spin transition and easy single crystal formation was developed. The change of nuclear position with the spin transition was successfully detected by the neutron diffraction measurement.
Highly efficient CsPbBr3@glass@polyurethane composite film as flexible liquid crystal display backlight
Authors: Zhang Guoxing , Jiang Dongliang , Zhu Xinghua , Lan Yuemei , Wang Dong , Zhang Xuejie , Wang Bo , Gao Yan , Zeng Qingguang , Chen Yan
Published: April 2023

The lumen efficiency of the device is 54.27 lm W−1. The generating a triangle area was calculated as 135% of the NTSC space and 190% of the Rec. 709 space. The display with this WLED as backlight will have a wider color gamut and more vivid picture.
Identifying and aggregating high-quality pathogen data: a new approach for potable reuse regulatory development
Authors: Darby Emily , Olivieri Adam , Haas Charles , Di Giovanni George , Jakubowski Walter , Leddy Menu , Nelson Kara L. , Rock Channah , Slifko Theresa , Pecson Brian M.
Published: April 2023

Studies measuring pathogens in wastewater were screened based on data relevance and quality criteria. Distributions of aggregated datasets can be used to support development of pathogen treatment requirements for direct potable reuse.
Improving endothelial health with food-derived H2S donors: an in vitro study with S-allyl cysteine and with a black-garlic extract enriched in sulfur-containing compounds
Authors: Geddo Federica , Querio Giulia , Asteggiano Alberto , Antoniotti Susanna , Porcu Alessandra , Occhipinti Andrea , Medana Claudio , Gallo Maria Pia
Published: April 2023

S-allyl cysteine and a black-garlic extract improve endothelial health.
Catalytic fate of structurally characterized manganese(iii)–salen complexes towards efficient transformation of primary amides to amines or nitriles using hydrosilane
Authors: Bandopadhyay Nilaj , Paramanik Krishnendu , Sarkar Gayetri , Chatterjee Souvik , Roy Suvojit , Panda Subhra Jyoti , Purohit Chandra Shekhar , Biswas Bhaskar , Das Hari Sankar
Published: April 2023

Simple salen-based manganese(iii) complexes show excellent catalytic activity towards the hydrosilylative transformation of primary amides to their corresponding primary amines under mild reaction conditions.
One-dimensional TeSe nano-heterojunction: formation, calculations, carrier dynamics, and application in broad-spectrum photodetectors
Authors: Xing Chenyang , Li Zihao , Bang Jian , Wei Songrui , Peng Zhengchun
Published: April 2023

Seawater contains many electrolytes, is abundant in nature, environmentally friendly, and chemically stable, and exhibits substantial potential for replacement of traditional inorganic electrolytes in photoelectrochemical-type photodetectors (PDs).
Acid and alkali-resistant fabric-based triboelectric nanogenerator for self-powered intelligent monitoring of protective clothing in highly corrosive environments
Authors: Chen Ting , Song Wei-Zhi , Zhang Meng , Sun De-Jun , Zhang Duo-Shi , Li Chang-Long , Cui Wen-Ying , Fan Ting-Ting , Ramakrishna Seeram , Long Yun-Ze
Published: April 2023

The corrosion of materials severely limits the application scenarios of triboelectric nanogenerators (TENGs), especially in laboratories, chemical plants and other fields where leakage of chemically corrosive solutions is common.
Synthetic strategies of heterocycle-integrated pyridopyrimidine scaffolds supported by nano-catalysts
Authors: Hammouda Mohamed M. , Rashed Marwa M. , Elattar Khaled M. , Osman Amany M. A.
Published: April 2023

The current review explores the scope of the synthetic strategies supported by nano-catalysts and biological aspects of heterocycles-integrated pyridopyrimidine scaffolds.
Enantioselective catalytic remote perfluoroalkylation of α-branched enals driven by light
Authors: Balletti Matteo , Wachsmuth Tommy , Di Sabato Antonio , Hartley Will C. , Melchiorre Paolo
Published: April 2023

A photochemical organocatalytic method for the enantioselective incorporation of perfluoroalkyl and trifluoromethyl fragments at the remote γ position of α-branched enals is reported.
Continuous transition of colloidal crystals through stable random orders
Authors: Ahn Juhong , Chen Liwen , Underhill Patrick T. , Freychet Guillaume , Zhernenkov Mikhail , Lee Sangwoo
Published: April 2023

The stacking probability diagram of block copolymer micellar colloids documenting a continuous transition from FCC to HCP through RHCP structures.