bluuebunny/crossref_metadata_2025 huggingface dataset:
What motivates students to decrease or cease substance use?: A scoping review
Authors: Dockray S. , Whelan E. , Dick S. , Davoren M. , Heavin C. , Linehan C. , Byrne M.
Published: February 2022

Objective:

The association between illicit substance use by third-level education students and their mental and physical health is well documented. The aim of this scoping review was to determine factors that contribute to student motivations to reduce or stop their use of illicit substances, and to elaborate on factors that may be pertinent for student-focused behaviour change interventions for substance use.

Method:

We searched eight databases in March 2021 using search terms based on ‘students’, ‘illicit substance use’, and ‘motivations’. We identified 86 research articles that reported on third-level education students’ illicit substance use and included reasons or motives for their use.

Results:

After full-text screening, three studies were eligible for inclusion in the qualitative synthesis. The majority of studies described motives for abstention but did not describe motivation for reducing or stopping current patterns of use of illicit substances.

Conclusion:

Few studies have examined motivations of third-level education students to decrease or cease substance use. Promising avenues for research on motivations to change substance use behaviour include the social contextual factors, perceived effects on social relationships, and actions of friends and family to prompt contemplations of change.
The WASA core catalogue of Late Quaternary depositional sequences in the central Wadden Sea – A manual for the core repository
Authors: Capperucci Ruggero M. , Bartholomä Alexander , Bungenstock Friederike , Enters Dirk , Karle Martina , Wehrmann Achim
Published: February 2022

The reconstruction of submerged palaeolandscapes and detection of settling surfaces along coastal zones became a major research topic within the last two decades. In this context, the WASA project made use of a multidisciplinary approach for defining the extension and describing the characteristics of the Late Pleistocene to Holocene deposits in the central Wadden Sea region. In addition to sub-bottom transects, more than 140 sediment cores were taken in such an area for stratigraphic reconstruction, making use of multi-proxy analysis. To harmonize these data with the existing regional core database (LBEG archive) a new core catalogue was developed, that allows the identification of the local Late Quaternary sedimentary sequences and their characteristic facies. The WASA core catalogue has been successfully applied for reviewing the published data about the stratigraphic sequence of the Wadden Sea, for a better definition in terms of stratigraphic sequences and spatial extent of the Quaternary geological evolution of the region, and for a detailed reconstruction of the coastal palaeoenvironments.
Effects of folic acid and riboflavin on growth performance, nutrient digestion and rumen fermentation in Angus bulls
Authors: Wang Cong , Zhang Jing , Guo Gang , Huo Wenjie , Xia Cheng Qiang , Chen Lei , Zhang Yawei , Pei Caixia , Liu Qiang
Published: February 2022

This study examined the influences of coated folic acid (CFA) and coated riboflavin (CRF) on bull performance, nutrients digestion and ruminal fermentation. Forty-eight Angus bulls based on a randomised block and 2 × 2 factorial design were assigned to four treatments. The CFA of 0 or 6 mg of folic acid/kg DM was supplemented in diets with CRF 0 or 60 mg riboflavin (RF)/kg DM. Supplementation of CRF in diets with CFA had greater increase in daily weight gain and feed efficiency than in diets without CFA. Supplementation with CFA or CRF enhanced digestibility of DM, organic matter, crude protein, neutral-detergent fibre and non-fibre carbohydrate. Ruminal pH and ammonia N content decreased and total volatile fatty acids concentration and acetate to propionate ratio elevated for CFA or CRF addition. Supplement of CFA or CRF increased the activities of fibrolytic enzymes and the numbers of total bacteria, protozoa, fungi, dominant fibrolytic bacteria and Prevotella ruminicola. The activities of α-amylase, protease and pectinase and the numbers of Butyrivibrio fibrisolvens and Ruminobacter amylophilus were increased by CFA but were unaffected by CRF. Blood concentration of folate elevated and homocysteine decreased for CFA addition. The CRF supplementation elevated blood concentrations of folate and RF. These findings suggested that CFA or CRF inclusion had facilitating effects on performance and ruminal fermentation, and combined addition of CFA and CRF had greater increase in performance than CFA or CRF addition alone in bulls.
The Ghent altarpiece after World War II: Restitution, restoration, and redemption
Authors: Graham Jenny
Published: February 2022

Few Old Master paintings possess as turbulent an object history as the Ghent altarpiece, now restored, since World War II, to the city’s cathedral for which it was made. While most accounts focus on the longue durée perspective, especially the work’s looting by Napoleon and Hitler, this article examines the altarpiece’s history following its return to Belgium in 1945. The altarpiece was subject to increased sensitivity at home after its wartime wanderings, and a major controversy ensued when the government backed a radical conservation project, which took place under the direction of Paul Coremans at the Royal Museum in Brussels between 1950 and 1951. The project served to emphasize the rift between north and south in Belgium in the newspaper press and became a focus for the international community as it battled to establish new standards in art restoration in the aftermath of the war.
Back to futures
Authors: PRUIKSMA KLAAS , PFENNING FRANK
Published: February 2022

Common approaches to concurrent programming begin with languages whose semantics are naturally sequential and add new constructs that provide limited access to concurrency, as exemplified by futures. This approach has been quite successful, but often does not provide a satisfactory theoretical backing for the concurrency constructs, and it can be difficult to give a good semantics that allows a programmer to use more than one of these constructs at a time. We take a different approach, starting with a concurrent language based on a Curry–Howard interpretation of adjoint logic, to which we add three atomic primitives that allow us to encode sequential composition and various forms of synchronization. The resulting language is highly expressive, allowing us to encode futures, fork/join parallelism, and monadic concurrency in the same framework. Notably, since our language is based on adjoint logic, we are able to give a formal account of linear futures, which have been used in complexity analysis by Blelloch and Reid-Miller. The uniformity of this approach means that we can similarly work with many of the other concurrency primitives in a linear fashion, and that we can mix several of these forms of concurrency in the same program to serve different purposes.
Declarative Learning, Priming, and Procedural Learning Performances comparing Individuals with Amnestic Mild Cognitive Impairment, and Cognitively Unimpaired Older Adults
Authors: De Wit Liselotte , Kessels Roy P.C. , Kurasz Andrea M. , Amofa Priscilla , O’Shea Deirdre , Marsiske Michael , Chandler Melanie J. , Piai Vitoria , Lambertus Taylor , Smith Glenn E.
Published: February 2022

Objective:

While declarative learning is dependent on the hippocampus, procedural learning and repetition priming can operate independently from the hippocampus, making them potential targets for behavioral interventions that utilize non-declarative memory systems to compensate for the declarative learning deficits associated with hippocampal insult. Few studies have assessed procedural learning and repetition priming in individuals with amnestic mild cognitive impairment (aMCI).

Method:

This study offers an overview across declarative, conceptual repetition priming, and procedural learning tasks by providing between-group effect sizes and Bayes Factors (BFs) comparing individuals with aMCI and controls. Seventy-six individuals with aMCI and 83 cognitively unimpaired controls were assessed. We hypothesized to see the largest differences between individuals with aMCI and controls on declarative learning, followed by conceptual repetition priming, with the smallest differences on procedural learning.

Results:

Consistent with our hypotheses, we found large differences between groups with supporting BFs on declarative learning. For conceptual repetition priming, we found a small-to-moderate between-group effect size and a non-conclusive BF somewhat in favor of a difference between groups. We found more variable but overall trivial differences on procedural learning tasks, with inconclusive BFs, in line with expectations.

Conclusions:

The current results suggest that conceptual repetition priming does not remain intact in individuals with aMCI while procedural learning may remain intact. While additional studies are needed, our results contribute to the evidence-base that suggests that procedural learning may remain spared in aMCI and helps inform behavioral interventions that aim to utilize procedural learning in this population.
Earth and Space Science Informatics Perspectives on Integrated, Coordinated, Open, Networked (ICON) Science
Authors: Hills D. J. , Damerow J. E. , Ahmmed B. , Catolico N. , Chakraborty S. , Coward C. M. , Crystal‐Ornelas R. , Duncan W. D. , Goparaju L. N. , Lin C. , Liu Z. , Mudunuru M. K. , Rao Y. , Rovetto R. J. , Sun Z. , Whitehead B. P. , Wyborn L. , Yao T.
Published: February 2022

This article is composed of three independent commentaries about the state of Integrated, Coordinated, Open, Networked (ICON) principles (Goldman, et al., 2021b, https://doi.org/10.1029/2021EO153180) in Earth and Space Science Informatics (ESSI) and includes discussion on the opportunities and challenges of adopting them. Each commentary focuses on a different topic: (Section 2) Global collaboration, cyberinfrastructure, and data sharing; (Section 3) Machine learning for multiscale modeling; (Section 4) Aerial and satellite remote sensing for advancing Earth system model development by integrating field and ancillary data. ESSI addresses data management practices, computation and analysis, and hardware and software infrastructure. Our role in ICON science therefore involves collaborative work to assess, design, implement, and promote practices and tools that enable effective data management, discovery, integration, and reuse for interdisciplinary work in Earth and space science disciplines. Networks of diverse people with expertise across Earth, space, and data science disciplines are essential for efficient and ethical exchanges of findable, accessible, interoperable, and reusable (FAIR) research products and practices. Our challenge is then to coordinate the development of standards, curation practices, and tools that enable integrating and reusing multiple data types, software, multi‐scale models, and machine learning approaches across disciplines in a way that is as open and/or FAIR as ethically possible. This is a major endeavor that could greatly increase the pace and potential of interdisciplinary scientific discovery.
Quasi‐Trapped Electron Fluxes Induced by NWC Transmitter and CRAND: Observations and Simulations
Authors: Liu Yangxizi , Xiang Zheng , Ni Binbin , Li Xinlin , Zhang Kun , Fu Song , Gu Xudong , Liu Jiang , Cao Xing
Published: February 2022

Signals from the NWC ground‐based very low frequency (VLF) transmitter can leak into the magnetosphere and scatter trapped energetic electrons into drift loss cones. Recent studies also suggest that cosmic ray albedo neutron decay (CRAND) is probably an important source for quasi‐trapped electrons in the inner belt. To investigate their relative contributions, this study comprehensively analyzes the long‐term variations of quasi‐trapped 206 keV electrons at L = 1.7, which is roughly the L shell where NWC is located. Furthermore, a drift‐diffusion‐source model is used to reproduce longitudinal distributions of quasi‐trapped electrons and investigate sensitivities of simulation results to VLF transmitter intensities. These results suggest that CRAND is the main source of quasi‐trapped hundreds of keV electrons when the NWC station is at dayside. In contrast, pitch angle diffusions become the main source mechanism of these quasi‐trapped electrons when the NWC station operates at nightside with more VLF transmitter energy leaking into the magnetosphere.
Classification of Infrasonic Atmospheric Events Using Electromagnetic Pulse Analysis
Authors: Kahlon Maayan , Lipshtat Azi , Price Colin , Weiss Anthony
Published: February 2022

The Comprehensive Nuclear‐Test‐Ban Treaty Organization (CTBTO) operates the international monitoring system (IMS), consisting of four complementary technologies: Seismic, hydroacoustic, infrasound, and radionuclide, to detect events that might indicate a treaty violation. Infrasound is the main technology aimed at detecting atmospheric nuclear explosions. However, there are many other sources of infrasound signals, which are low frequency inaudible sound‐waves in the atmosphere, that are detected. To deny that the source is of a nuclear nature, requires a lot of resources. As opposed to most other sources of infrasound, nuclear explosions also emit an electromagnetic pulse (EMP). Thus, if an infrasonically detected event is not accompanied by an EMP, it is certain that it has not originated from a nuclear explosion. In this research we use electromagnetic data recorded by a single antenna to examine coincidence of infrasonically detected events with detected EMPs. We show that a large fraction of infrasonically detected events are not accompanied by any EMP and thus the need to analyze them in the context of the IMS is eliminated. For those infrasonically detected events that do coincide with EMPs, we use machine learning techniques to classify the EMPs as either lightning or a potential explosion. We show that one can identify the lightning out of the EMPs. By filtering out all lightning signals one can almost always verify that there is no EMP other than lightning, which coincided with the infrasonically detected event. This way we can dramatically reduce the number of infrasound signals which require manual analysis.
Physical Interpretation of Time‐Varying StorAge Selection Functions in a Bench‐Scale Hillslope Experiment via Geophysical Imaging of Ages of Water
Authors: Meira Neto Antônio Alves , Kim Minseok , Troch Peter A.
Published: February 2022

Understanding transit times (TT) and residence times (RT) distributions of water in catchments has recently received a great deal of attention in hydrologic research since it can inform about important processes relevant to the quality of water delivered by streams and landscape resilience to anthropogenic inputs. The theory of transit time distributions (TTD) is a practical framework for understanding TT of water in natural landscapes but, due to its lumped nature, it can only hint at the possible internal processes taking place in the subsurface. While allowing for the direct observation of water movement, Electrical Resistivity Imaging (ERI) can be leveraged to better understand the internal variability of water ages within the subsurface, thus enabling the investigation of the physical processes controlling the time‐variability of TTD. In this study, we estimated time‐variable TTD of a bench‐scale bare‐soil sloping soil lysimeter through the StorAge Selection (SAS) framework, a traditional lumped‐systems method, based on sampling of output tracer concentrations, as well as through an ERI SAS one, based on spatially distributed images of water ages. We compared the ERI‐based SAS results with the output‐based estimates to discuss the viability of ERI at laboratory experiments for understanding TTD. The ERI‐derived images of the internal evolution of water ages were able to elucidate the internal mechanisms driving the time‐variability of ages of water being discharged by the system, which was characterized by a delayed discharge of younger water starting at the highest storage level and continuing throughout the water table recession.
Seeing is believing
Authors: Krasikov Sergey , Kivshar Yuri
Published: February 2022

Bound states in the continuum are realized in many optical systems as “dark states”, and their presence can be detected in the regime of leaky modes via resonances in far-fields. Here the authors reveal previously unseen structure of bound states in the continuum by exploring strong near-field localization in dielectric metasurfaces.
Multi-omic characterization of genome-wide abnormal DNA methylation reveals diagnostic and prognostic markers for esophageal squamous-cell carcinoma
Authors: Xi Yiyi , Lin Yuan , Guo Wenjia , Wang Xinyu , Zhao Hengqiang , Miao Chuanwang , Liu Weiling , Liu Yachen , Liu Tianyuan , Luo Yingying , Fan Wenyi , Lin Ai , Chen Yamei , Sun Yanxia , Ma Yulin , Niu Xiangjie , Zhong Ce , Tan Wen , Zhou Meng , Su Jianzhong , Wu Chen , Lin Dongxin
Published: February 2022

This study investigates aberrant DNA methylations as potential diagnosis and prognosis markers for esophageal squamous-cell carcinoma (ESCC), which if diagnosed at advanced stages has <30% five-year survival rate. Comparing genome-wide methylation sites of 91 ESCC and matched adjacent normal tissues, we identified 35,577 differentially methylated CpG sites (DMCs) and characterized their distribution patterns. Integrating whole-genome DNA and RNA-sequencing data of the same samples, we found multiple dysregulated transcription factors and ESCC-specific genomic correlates of identified DMCs. Using featured DMCs, we developed a 12-marker diagnostic panel with high accuracy in our dataset and the TCGA ESCC dataset, and a 4-marker prognostic panel distinguishing high-risk patients. In-vitro experiments validated the functions of 4 marker host genes. Together these results provide additional evidence for the important roles of aberrant DNA methylations in ESCC development and progression. Our DMC-based diagnostic and prognostic panels have potential values for clinical care of ESCC, laying foundations for developing targeted methylation assays for future non-invasive cancer detection methods.
Metabolomic signature and mitochondrial dynamics outline the difference between vulnerability and resilience to chronic stress
Authors: Brivio Paola , Audano Matteo , Gallo Maria Teresa , Gruca Piotr , Lason Magdalena , Litwa Ewa , Fumagalli Fabio , Papp Mariusz , Mitro Nico , Calabrese Francesca
Published: February 2022

Stress is the foremost environmental factor involved in the pathophysiology of major depressive disorder (MDD). However, individual differences among people are critical as some people exhibit vulnerability while other are resilient to repeated exposure to stress. Among the others, a recent theory postulates that alterations of energy metabolism might contribute to the development of psychopathologies. Here we show that the bioenergetic status in the ventral hippocampus (vHip), a brain subregion tightly involved in the regulation of MDD, defined the development of vulnerability or resilience following two weeks of chronic mild stress. Among the different metabolomic signatures observed, the glycolysis and tricarboxylic acid cycle may be specifically involved in defining vulnerability, revealing a previously unappreciated mechanism of sensitivity to stress. These findings point to mitochondrial morphology and recycling as critical in the ability to cope with stress. We show that vulnerable rats favor mitochondrial fusion to counteract the overproduction of reactive oxidative species whereas resilient rats activate fission to guarantee metabolic efficiency. Our results indicate that the modulation of the energetic metabolite profile in vHip under chronic stress exposure may represent a mechanism to explain the difference between vulnerable and resilient rats, unraveling novel and promising targets for specific therapeutic interventions.
High-mobility hydrogenated polycrystalline In2O3 (In2O3:H) thin-film transistors
Authors: Magari Yusaku , Kataoka Taiki , Yeh Wenchang , Furuta Mamoru
Published: February 2022

Oxide semiconductors have been extensively studied as active channel layers of thin-film transistors (TFTs) for electronic applications. However, the field-effect mobility (μFE) of oxide TFTs is not sufficiently high to compete with that of low-temperature-processed polycrystalline-Si TFTs (50–100 cm2V−1s−1). Here, we propose a simple process to obtain high-performance TFTs, namely hydrogenated polycrystalline In2O3 (In2O3:H) TFTs grown via the low-temperature solid-phase crystallization (SPC) process. In2O3:H TFTs fabricated at 300 °C exhibit superior switching properties with µFE = 139.2 cm2V−1s−1, a subthreshold swing of 0.19 Vdec−1, and a threshold voltage of 0.2 V. The hydrogen introduced during sputter deposition plays an important role in enlarging the grain size and decreasing the subgap defects in SPC-prepared In2O3:H. The proposed method does not require any additional expensive equipment and/or change in the conventional oxide TFT fabrication process. We believe these SPC-grown In2O3:H TFTs have a great potential for use in future transparent or flexible electronics applications.
Controlling process instability for defect lean metal additive manufacturing
Authors: Qu Minglei , Guo Qilin , Escano Luis I. , Nabaa Ali , Hojjatzadeh S. Mohammad H. , Young Zachary A. , Chen Lianyi
Published: February 2022

The process instabilities intrinsic to the localized laser-powder bed interaction cause the formation of various defects in laser powder bed fusion (LPBF) additive manufacturing process. Particularly, the stochastic formation of large spatters leads to unpredictable defects in the as-printed parts. Here we report the elimination of large spatters through controlling laser-powder bed interaction instabilities by using nanoparticles. The elimination of large spatters results in 3D printing of defect lean sample with good consistency and enhanced properties. We reveal that two mechanisms work synergistically to eliminate all types of large spatters: (1) nanoparticle-enabled control of molten pool fluctuation eliminates the liquid breakup induced large spatters; (2) nanoparticle-enabled control of the liquid droplet coalescence eliminates liquid droplet colliding induced large spatters. The nanoparticle-enabled simultaneous stabilization of molten pool fluctuation and prevention of liquid droplet coalescence discovered here provide a potential way to achieve defect lean metal additive manufacturing.
Single-cell gene fusion detection by scFusion
Authors: Jin Zijie , Huang Wenjian , Shen Ning , Li Juan , Wang Xiaochen , Dong Jiqiao , Park Peter J. , Xi Ruibin
Published: February 2022

Gene fusions can play important roles in tumor initiation and progression. While fusion detection so far has been from bulk samples, full-length single-cell RNA sequencing (scRNA-seq) offers the possibility of detecting gene fusions at the single-cell level. However, scRNA-seq data have a high noise level and contain various technical artifacts that can lead to spurious fusion discoveries. Here, we present a computational tool, scFusion, for gene fusion detection based on scRNA-seq. We evaluate the performance of scFusion using simulated and five real scRNA-seq datasets and find that scFusion can efficiently and sensitively detect fusions with a low false discovery rate. In a T cell dataset, scFusion detects the invariant TCR gene recombinations in mucosal-associated invariant T cells that many methods developed for bulk data fail to detect; in a multiple myeloma dataset, scFusion detects the known recurrent fusionIgH-WHSC1, which is associated with overexpression of theWHSC1oncogene. Our results demonstrate that scFusion can be used to investigate cellular heterogeneity of gene fusions and their transcriptional impact at the single-cell level.
Kastor and Polluks polypeptides encoded by a single gene locus cooperatively regulate VDAC and spermatogenesis
Authors: Mise Shintaro , Matsumoto Akinobu , Shimada Keisuke , Hosaka Toshiaki , Takahashi Masatomo , Ichihara Kazuya , Shimizu Hideyuki , Shiraishi Chisa , Saito Daisuke , Suyama Mikita , Yasuda Tomoharu , Ide Toru , Izumi Yoshihiro , Bamba Takeshi , Kimura-Someya Tomomi , Shirouzu Mikako , Miyata Haruhiko , Ikawa Masahito , Nakayama Keiichi I.
Published: February 2022

Although several long noncoding RNAs (lncRNAs) have recently been shown to encode small polypeptides, those in testis remain largely uncharacterized. Here we identify two sperm-specific polypeptides, Kastor and Polluks, encoded by a single mouse locus (Gm9999) previously annotated as encoding a lncRNA. Both Kastor and Polluks are inserted in the outer mitochondrial membrane and directly interact with voltage-dependent anion channel (VDAC), despite their different amino acid sequences. Male VDAC3-deficient mice are infertile as a result of reduced sperm motility due to an abnormal mitochondrial sheath in spermatozoa, and deficiency of both Kastor and Polluks also severely impaired male fertility in association with formation of a similarly abnormal mitochondrial sheath. Spermatozoa lacking either Kastor or Polluks partially recapitulate the phenotype of those lacking both. Cooperative function of Kastor and Polluks in regulation of VDAC3 may thus be essential for mitochondrial sheath formation in spermatozoa and for male fertility.
Ultra-sensitive measurement of transverse displacements with linear photonic gears
Authors: Barboza Raouf , Babazadeh Amin , Marrucci Lorenzo , Cardano Filippo , de Lisio Corrado , D’Ambrosio Vincenzo
Published: February 2022

Accurately measuring mechanical displacements is essential for a vast portion of current technologies. Several optical techniques accomplish this task, allowing for non-contact sensing even below the diffraction limit. Here we introduce an optical encoding technique, dubbed “linear photonic gears”, that enables ultra-sensitive measurements of a transverse displacement by mapping it into the polarization rotation of a laser beam. In ordinary ambient conditions, we measure the relative shift between two objects with a resolution of 400 pm. We argue that a resolution of 50 pm should be achievable with existing state-of-the-art technologies. Our single-optical-path scheme is intrinsically stable and it could be implemented as a compact sensor, using cost effective integrated optics. We anticipate it may have a strong impact on both research and industry.
Wide-field mid-infrared single-photon upconversion imaging
Authors: Huang Kun , Fang Jianan , Yan Ming , Wu E , Zeng Heping
Published: February 2022

Frequency upconversion technique, where the infrared signal is nonlinearly translated into the visible band to leverage the silicon sensors, offers a promising alternation for the mid-infrared (MIR) imaging. However, the intrinsic field of view (FOV) is typically limited by the phase-matching condition, thus imposing a remaining challenge to promote subsequent applications. Here, we demonstrate a wide-field upconversion imaging based on the aperiodic quasi-phase-matching configuration. The acceptance angle is significantly expanded to about 30°, over tenfold larger than that with the periodical poling crystal. The extended FOV is realized in one shot without the need of parameter scanning or post-processing. Consequently, a fast snapshot allows to facilitate high-speed imaging at a frame rate up to 216 kHz. Alternatively, single-photon imaging at room temperature is permitted due to the substantially suppressed background noise by the spectro-temporal filtering. Furthermore, we have implemented high-resolution time-of-flight 3D imaging based on the picosecond optical gating. These presented MIR imaging features with wide field, fast speed, and high sensitivity might stimulate immediate applications, such as non-destructive defect inspection, in-vivo biomedical examination, and high-speed volumetric tomography.
SIRT1 selectively exerts the metabolic protective effects of hepatocyte nicotinamide phosphoribosyltransferase
Authors: Higgins Cassandra B. , Mayer Allyson L. , Zhang Yiming , Franczyk Michael , Ballentine Samuel , Yoshino Jun , DeBosch Brian J.
Published: February 2022

Calorie restriction abates aging and cardiometabolic disease by activating metabolic signaling pathways, including nicotinamide adenine dinucleotide (NAD+) biosynthesis and salvage. Nicotinamide phosphoribosyltransferase (NAMPT) is rate-limiting in NAD+ salvage, yet hepatocyte NAMPT actions during fasting and metabolic duress remain unclear. We demonstrate that hepatocyte NAMPT is upregulated in fasting mice, and in isolated hepatocytes subjected to nutrient withdrawal. Mice lacking hepatocyte NAMPT exhibit defective FGF21 activation and thermal regulation during fasting, and are sensitized to diet-induced glucose intolerance. Hepatocyte NAMPT overexpression induced FGF21 and adipose browning, improved glucose homeostasis, and attenuated dyslipidemia in obese mice. Hepatocyte SIRT1 deletion reversed hepatocyte NAMPT effects on dark-cycle thermogenesis, and hepatic FGF21 expression, but SIRT1 was dispensable for NAMPT insulin-sensitizing, anti-dyslipidemic, and light-cycle thermogenic effects. Hepatocyte NAMPT thus conveys key aspects of the fasting response, which selectively dissociate through hepatocyte SIRT1. Modulating hepatocyte NAD+ is thus a potential mechanism through which to attenuate fasting-responsive disease.
Association between olanzapine concentration and metabolic dysfunction in drug-naive and chronic patients: similarities and differences
Authors: Kang Dongyu , Lu Jinjun , Liu Wenqing , Shao Ping , Wu Renrong
Published: February 2022

Second-generation antipsychotics are widely used to treat schizophrenia but their use could induce metabolic dysfunction. To balance efficacy and side effects, various guidelines recommend the use of therapeutic drug monitoring. Given the controversial relationship between olanzapine serum concentration and metabolic dysfunction, its use in clinical practice is still debated. To address this issue, we conducted a prospective cohort study to explore the associations in patients with schizophrenia. Specifically, first-episode drug-naive patients and patients with chronic schizophrenia were recruited. All participants received olanzapine monotherapy for 8 weeks. Anthropometric parameters and metabolic indices were tested at baseline and at week 8, and olanzapine serum concentration was tested at week 4. After 8 weeks of observation, body weight and BMI increased significantly in drug-naive patients. Moreover, triglycerides and LDL increased significantly in both drug-naive and chronic patients. Among chronic patients, those who have never used olanzapine/clozapine before had a significantly higher increase in weight and BMI than those who have previously used olanzapine/clozapine. Furthermore, olanzapine concentration was associated with changes in weight, BMI, and LDL levels in the drug-naive group and glucose, triglyceride and LDL levels in chronic patients who have not used olanzapine/clozapine previously. In conclusion, the metabolic dysfunction induced by olanzapine is more severe and dose-dependent in drug-naive patients but independent in patients with chronic schizophrenia. Future studies with a longer period of observation and a larger sample are warranted.
Inhibition of spleen tyrosine kinase decreases donor specific antibody levels in a rat model of sensitization
Authors: Tempest-Roe Shenzhen , Prendecki Maria , McAdoo Stephen P. , Clarke Candice , Tanna Anisha , Turner-Stokes Tabitha , Masuda Esteban S. , Willicombe Michelle , Cook H. Terence , Roufosse Candice , Taube David , Pusey Charles D. , Tam Frederick W. K.
Published: February 2022

Antibody mediated rejection is a major cause of renal allograft loss. Circulating preformed donor specific antibodies (DSA) can result as a consequence of blood transfusion, pregnancy or prior transplantation. Current treatment strategies are limited due to partial or transient efficacy, adverse side-effects or patient unsuitability. Previous in vivo studies exploring autoimmune diseases have shown that spleen tyrosine kinase (SYK) signalling is involved in the development of pathogenic autoantibody. The role of SYK in allogenic antibody production is unknown, and we investigated this in a rodent model of sensitization, established by the transfusion of F344 whole blood into LEW rats. Two-week treatment of sensitized rats with selective SYK inhibitor fostamatinib strongly blocked circulating DSA production without affecting overall total immunoglobulin levels, and inhibition was sustained up to 5 weeks post-completion of the treatment regimen. Fostamatinib treatment did not affect mature B cell subset or plasma cell levels, which remained similar between non-treated controls, vehicle treated and fostamatinib treated animals. Our data indicate fostamatinib may provide an alternative therapeutic option for patients who are at risk of sensitization following blood transfusion while awaiting renal transplant.
Prevalence of Trypanosoma and Sodalis in wild populations of tsetse flies and their impact on sterile insect technique programmes for tsetse eradication
Authors: Dieng Mouhamadou M. , Dera Kiswend-sida M. , Moyaba Percy , Ouedraogo Gisele M. S. , Demirbas-Uzel Guler , Gstöttenmayer Fabian , Mulandane Fernando C. , Neves Luis , Mdluli Sihle , Rayaisse Jean-Baptiste , Belem Adrien M. G. , Pagabeleguem Soumaïla , de Beer Chantel J. , Parker Andrew G. , Van Den Abbeele Jan , Mach Robert L. , Vreysen Marc J. B. , Abd-Alla Adly M. M.
Published: February 2022

The sterile insect technique (SIT) is an environment friendly and sustainable method to manage insect pests of economic importance through successive releases of sterile irradiated males of the targeted species to a defined area. A mating of a sterile male with a virgin wild female will result in no offspring, and ultimately lead to the suppression or eradication of the targeted population. Tsetse flies, vectors of African Trypanosoma, have a highly regulated and defined microbial fauna composed of three bacterial symbionts that may have a role to play in the establishment of Trypanosoma infections in the flies and hence, may influence the vectorial competence of the released sterile males. Sodalis bacteria seem to interact with Trypanosoma infection in tsetse flies. Field-caught tsetse flies of ten different taxa and from 15 countries were screened using PCR to detect the presence of Sodalis and Trypanosoma species and analyse their interaction. The results indicate that the prevalence of Sodalis and Trypanosoma varied with country and tsetse species. Trypanosome prevalence was higher in east, central and southern African countries than in west African countries. Tsetse fly infection rates with Trypanosoma vivax and T. brucei sspp were higher in west African countries, whereas tsetse infection with T. congolense and T. simiae, T. simiae (tsavo) and T. godfreyi were higher in east, central and south African countries. Sodalis prevalence was high in Glossina morsitans morsitans and G. pallidipes but absent in G. tachinoides. Double and triple infections with Trypanosoma taxa and coinfection of Sodalis and Trypanosoma were rarely observed but it occurs in some taxa and locations. A significant Chi square value (< 0.05) seems to suggest that Sodalis and Trypanosoma infection correlate in G. palpalis gambiensis, G. pallidipes and G. medicorum. Trypanosoma infection seemed significantly associated with an increased density of Sodalis in wild G. m. morsitans and G. pallidipes flies, however, there was no significant impact of Sodalis infection on trypanosome density.
A retrospective cohort study on association of age and physician decision making for or against rapid sequence intubation in unconscious patients
Authors: Eichlseder Michael , Eichinger Michael , Hallmann Barbara , Honnef Gabriel , Metnitz Philipp , Prause Gerhard , Zoidl Philipp , Zajic Paul
Published: February 2022

In unconscious individuals, rapid sequence intubation (RSI) may be necessary for cardiopulmonary stabilisation and avoidance of secondary damage. Opinions on such invasive procedures in people of older age vary. We thus sought to evaluate a possible association between the probability of receiving prehospital RSI in unconsciousness and increasing age. We conducted a retrospective study in all missions (traumatic and non-traumatic) of the prehospital emergency physician response unit in Graz between January 1st, 2010 and December 31st, 2019, which we searched for Glasgow Coma Scale (GCS) below 9. Cardiac arrests were excluded. We performed multivariable regression analysis for RSI with age, GCS, independent living, and suspected cause as independent variables. Of the 769 finally included patients, 256 (33%) received RSI, whereas 513 (67%) did not. Unadjusted rates of RSI were significantly lower in older patients (aged 85 years and older) compared to the reference group aged 50–64 years (13% vs. 51%, p < 0.001). In multivariable regression analysis, patients aged 85 years and older were also significantly less likely to receive RSI [OR (95% CI) 0.76 (0.69–0.84)]. We conclude that advanced age, especially 85 years or older, is associated with significantly lower odds of receiving prehospital RSI in cases of unconsciousness.
A sex- and gender-based analysis of factors associated with linear growth in infants in Ecuadorian Andes
Authors: Evers Emily C. , Waters William F. , Gallegos-Riofrío Carlos Andres , Lutter Chessa K. , Stewart Christine P. , Iannotti Lora L.
Published: February 2022

Although female infants may have an early life biological advantage over males, gendered treatment can alter health outcomes. Ecuador has an unusually high ratio of male to female infant mortality, but gender norms have been reported to favor boys. This analysis of baseline data from the Lulun Project, a randomized controlled trial conducted in rural Andean communities of Ecuador, investigates the roles of sex and gender in undernutrition among infants 6 to 9 months of age. Twenty-four-hour recall frequencies were used to assess dietary intake. Food outcome models were analyzed as prevalence ratios calculated using a binomial distribution with a log link or robust Poisson regression. Linear regression was used to analyze the continuous growth outcome length-for-age z score. Socioeconomic and health history variables were comparable between male and female infants. Boys were more often fed liquids other than breastmilk within their first 3 days of life (17.1% vs. 5.2%, P = 0.026). Compared with girls, boys were less likely to be fed eggs by 33% (95% CI 0.46, 0.96), cheese, yogurt, or other milk products by 40% (95% CI 0.39, 0.92), yellow fruit by 44% (95% CI 0.33, 0.97), water by 37% (95% CI 0.45, 0.88), thin porridge by 29% (95% CI 0.56, 0.92), and tea without milk by 67% (95% CI 0.11, 0.99). Prevalence of boys with an adequate dietary diversity score (≥ 4) was reduced by 27% relative to girls (95% CI 0.54, 0.99). Males fared worse in length-for-age z scores (− 2.16 vs. − 1.56, P = 0.000), weight-for-age z scores (− 0.86 vs. − 0.33, P = 0.002), prevalence of stunting (50.6% vs. 23.4%, P = 0.000), and plasma concentrations of dimethylglycine (1.25 vs. 1.65 µg/mL, P = 0.021). After adjusting for demographic, caregiver perceptions of appetite, and biological factors, length-for-age z score for a male child was 0.62 units lower than for a female (95% CI − 0.98, − 0.26). Male infants were shown to receive lower quality complementary foods and have worse anthropometric measures than female infants.

Trial registration clinicaltrials.gov, NCT02446873. Registered February 28, 2015, https://clinicaltrials.gov/ct2/show/NCT02446873.
Short-term physiologic response of the green microalga Picochlorum sp. (BPE23) to supra-optimal temperature
Authors: Barten Robin , Kleisman Michelle , D’Ermo Giulia , Nijveen Harm , Wijffels Rene H. , Barbosa Maria J.
Published: February 2022

Photobioreactors heat up significantly during the day due to irradiation by sunlight. High temperatures affect cell physiology negatively, causing reduced growth and productivity. To elucidate the microalgal response to stressful supra-optimal temperature, we studied the physiology of Picochlorum sp. (BPE23) after increasing the growth temperature from 30 °C to 42 °C, whereas 38 °C is its optimal growth temperature. Cell growth, cell composition and mRNA expression patterns were regularly analyzed for 120 h after increasing the temperature. The supra-optimal temperature caused cell cycle arrest for 8 h, with concomitant changes in metabolic activity. Accumulation of fatty acids was observed during this period to store unspent energy which was otherwise used for growth. In addition, the microalgae changed their pigment and fatty acid composition. For example, palmitic acid (C16:0) content in the polar fatty acid fraction increased by 30%, hypothetically to reduce membrane fluidity to counteract the effect of increased temperature. After the relief of cell cycle arrest, the metabolic activity of Picochlorum sp. (BPE23) reduced significantly over time. A strong response in gene expression was observed directly after the increase in temperature, which was dampened in the remainder of the experiment. mRNA expression levels associated with pathways associated with genes acting in photosynthesis, carbon fixation, ribosome, citrate cycle, and biosynthesis of metabolites and amino acids were downregulated, whereas the proteasome, autophagy and endocytosis were upregulated.
Human psychophysical discrimination of spatially dependant Pancharatnam–Berry phases in optical spin-orbit states
Authors: Sarenac D. , Silva A. E. , Kapahi C. , Cory D. G. , Thompson B. , Pushin D. A.
Published: February 2022

We tested the ability of human observers to discriminate distinct profiles of spatially dependant geometric phases when directly viewing stationary structured light beams. Participants viewed polarization coupled orbital angular momentum (OAM) states, or “spin-orbit” states, in which the OAM was induced through Pancharatnam–Berry phases. The coupling between polarization and OAM in these beams manifests as spatially dependant polarization. Regions of uniform polarization are perceived as specifically oriented Haidinger’s brushes, and study participants discriminated between two spin-orbit states based on the rotational symmetry in the spatial orientations of these brushes. Participants used self-generated eye movements to prevent adaptation to the visual stimuli. After initial training, the participants were able to correctly discriminate between two spin-orbit states, differentiated by OAM $$=\pm 1$$

=
±
1

, with an average success probability of $$69\%$$

69
%

($$S.D. = 22\%$$

S
.
D
.
=
22
%

, $$p = 0.01$$

p
=
0.01

). These results support our previous observation that human observers can directly perceive spin-orbit states, and extend this finding to non-rotating beams, OAM modes induced via Pancharatnam–Berry phases, and the discrimination of states that are differentiated by OAM.
Different syngeneic tumors show distinctive intrinsic tumor-immunity and mechanisms of actions (MOA) of anti-PD-1 treatment
Authors: Jin Ying , An Xiaoyu , Mao Binchen , Sun Ruilin , Kumari Rajendra , Chen Xiaobo , Shan Yongli , Zang Mingfa , Xu Ling , Muntel Jan , Beeler Kristina , Bruderer Roland , Reiter Lukas , Guo Sheng , Zhou Demin , Li Qi-Xiang , Ouyang Xuesong
Published: February 2022

Cancers are immunologically heterogeneous. A range of immunotherapies target abnormal tumor immunity via different mechanisms of actions (MOAs), particularly various tumor-infiltrate leukocytes (TILs). We modeled loss of function (LOF) in four common anti-PD-1 antibody-responsive syngeneic tumors, MC38, Hepa1-6, CT-26 and EMT-6, by systematical depleting a series of TIL lineages to explore the mechanisms of tumor immunity and treatment. CD8+-T-cells, CD4+-T-cells, Treg, NK cells and macrophages were individually depleted through either direct administration of anti-marker antibodies/reagents or using DTR (diphtheria toxin receptor) knock-in mice, for some syngeneic tumors, where specific subsets were depleted following diphtheria toxin (DT) administration. These LOF experiments revealed distinctive intrinsic tumor immunity and thus different MOAs in their responses to anti-PD-1 antibody among different syngeneic tumors. Specifically, the intrinsic tumor immunity and the associated anti-PD-1 MOA were predominately driven by CD8+ cytotoxic TILs (CTL) in all syngeneic tumors, excluding Hepa1-6 where CD4+ Teff TILs played a key role. TIL-Treg also played a critical role in supporting tumor growth in all four syngeneic models as well as M2-macrophages. Pathway analysis using pharmacodynamic readouts of immuno-genomics and proteomics on MC38 and Hepa1-6 also revealed defined, but distinctive, immune pathways of activation and suppression between the two, closely associated with the efficacy and consistent with TIL-pharmacodynamic readouts. Understanding tumor immune-pathogenesis and treatment MOAs in the different syngeneic animal models, not only assists the selection of the right model for evaluating new immunotherapy of a given MOA, but also can potentially help to understand the potential disease mechanisms and strategize optimal immune-therapies in patients.
In vitro and in vivo functions of T cells produced in complemented thymi of chimeric mice generated by blastocyst complementation
Authors: Yamazaki Kazuto , Kubara Kenji , Ishii Satoko , Li Peng , Dairiki Ryo , Hihara Taro , Ishizuka Yuta , Izumi Yukina , Kumai Minoru , Kamisako Tsutomu , Ishizaki Hiroyoshi , Sato Hideyuki , Masaki Hideki , Mizuno Naoaki , Mitsuhashi Kaoru , Ito Masashi , Hamanaka Sanae , Yamaguchi Tomoyuki , Watanabe Motoo , Sugiyama Fumihiro , Nakauchi Hiromitsu
Published: February 2022

Blastocyst complementation is an intriguing way of generating humanized animals for organ preparation in regenerative medicine and establishing novel models for drug development. Confirming that complemented organs and cells work normally in chimeric animals is critical to demonstrating the feasibility of blastocyst complementation. Here, we generated thymus-complemented chimeric mice, assessed the efficacy of anti-PD-L1 antibody in tumor-bearing chimeric mice, and then investigated T-cell function. Thymus-complemented chimeric mice were generated by injecting C57BL/6 (B6) embryonic stem cells into Foxn1nu/nu morulae or blastocysts. Flow cytometry data showed that the chimeric mouse thymic epithelial cells (TECs) were derived from the B6 cells. T cells appeared outside the thymi. Single-cell RNA-sequencing analysis revealed that the TEC gene-expression profile was comparable to that in B6 mice. Splenic T cells of chimeric mice responded very well to anti-CD3 stimulation in vitro; CD4+ and CD8+ T cells proliferated and produced IFNγ, IL-2, and granzyme B, as in B6 mice. Anti-PD-L1 antibody treatment inhibited MC38 tumor growth in chimeric mice. Moreover, in the chimeras, anti-PD-L1 antibody restored T-cell activation by significantly decreasing PD-1 expression on T cells and increasing IFNγ-producing T cells in the draining lymph nodes and tumors. T cells produced by complemented thymi thus functioned normally in vitro and in vivo. To successfully generate humanized animals by blastocyst complementation, both verification of the function and gene expression profiling of complemented organs/cells in interspecific chimeras will be important in the near future.