bluuebunny/crossref_metadata_2025 huggingface dataset:
Applying the Integrated Sustainability Framework to explore the long-term sustainability of nutrition education programmes in schools: a systematic review
Authors: Fathi Leila Isabella , Walker Jacqueline , Dix Clare Frances , Cartwright Jessica Rose , Joubert Suné , Carmichael Kerri Amelia , Huang Yu-Shan , Littlewood Robyn , Truby Helen
Published: August 2023

Objective:

This review aimed to identify and synthesise the enablers and barriers that influence the long-term (≥ 2 years) sustainment of school-based nutrition programmes.

Design:

Four databases (PubMed, Cochrane Library, Embase and Scopus) were searched to identify studies reporting on the international literature relating to food and nutrition programmes aimed at school-age (5–14 years) children that had been running for ≥ 2 years (combined intervention and follow-up period). Eligible studies were analysed using the Integrated Sustainability Framework (ISF), which involved deductive coding of programme enablers and barriers. A quality assessment was completed, using the Mixed-Methods Appraisal Tool and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Setting:

International school-based nutrition programmes.

Subjects:

Individuals involved with the implementation of school-based nutrition programmes.

Results:

From the 7366 articles identified, thirteen studies (seven qualitative, five mixed methods and one quantitative descriptive) were included, from which the enablers and barriers of eleven different nutrition-related programmes were analysed. Thirty-four factors across the five domains of the ISF were identified that influenced the sustained implementation of programmes. The most common barrier was a lack of organisational readiness and resources, whereas the most common enabler was having adequate external partnerships and a supportive environment.

Conclusions:

These findings have application during the initiation and implementation phases of school-based nutrition programmes. Paying attention to the ‘outer contextual factors’ of the ISF including the establishment and maintenance of robust relationships across whole of government systems, local institutions and funding bodies are crucial for programme sustainment.
The availability and delivery of culturally responsive Australian Aboriginal infant resuscitation education programmes: a structured literature review
Authors: Stephens Nakita , Nilson Caroline , Reibel Tracy , Marriott Rhonda
Published: August 2023

Aim:

To critically appraise the literature to determine availability and identify the cultural responsiveness of infant resuscitation education for Aboriginal and Torres Strait Islander populations.

Background:

Despite overall reductions in infant mortality in the last two decades, Aboriginal people have some of the highest rates of infant mortality of any developed nation. One of the key factors that has attributed to improvements in infant mortality rates is parent and carer education around risk factors and actions of first responders. Identifying gaps in the current basic first-aid initiatives available to Aboriginal communities may contribute to developing resources to contribute to reductions in Aboriginal neonatal mortality rates.

Method:

The review used key terms and Boolean operators across an 11-month time frame searching for research articles utilising the databases of CINAHL, Scopus, Ovid Emcare, Informit, Pubmed and Proquest. After review, 39 articles met the inclusion criteria, 25 articles were discarded due to irrelevant material and 14 articles were included in the structured literature review. The search process was developed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Articles were assessed for validity and inclusion using the Critical Appraisal Skills Program checklist.

Results:

Research literature relating to First Nation community-based CPR and first-aid education programmes in Canada, USA, India, UK and Europe, Asia and Africa were identified; however, none pertaining specifically to CPR and first-aid education in Australian Aboriginal communities were found.

Discussion:

Despite the lack of research evidence relating to infant cardiopulmonary resuscitation (CPR) education for Australian Aboriginal populations, the reviewed studies noted the importance of culturally responsive education designed in collaboration with First Nation peoples, using novel ways of teaching CPR, that align with the language, culture and needs of the communities it is intended for.

Conclusion:

Further research is required to create a framework for the delivery of culturally responsive infant resuscitation education for Australian Aboriginal parents and communities.
A Pioneer in Caribbean History: Franklin Knight Reflects on Cuba
Authors: Knight Franklin W. , Guerra Lillian
Published: August 2023

Lillian: Let's start with you telling a little about yourself.

Franklin: I was born in 1942 in Jamaica. I went to elementary school, of course, and took the mandatory “Eleven-Plus” general examination in 1953. I then left elementary school and for a year attended a small private high school with my two older brothers. The school system was a little different from the United States. I know that well, because when I came here and told a group of Wisconsin school kids that I had spent six years in high school, they said, “You must have been very dumb.” To which I replied that “that was not the opinion of my teachers.” I didn't realize then that in the United States students spend four years in high school. In Jamaica we spend six, combining middle and high school years. You get in at age 12 or 13 and graduate at 18 or 19.
Toward Robust Parameterizations in Ecosystem‐Level Photosynthesis Models
Authors: Bao Shanning , Alonso Lazaro , Wang Siyuan , Gensheimer Johannes , De Ranit , Carvalhais Nuno
Published: August 2023

In a model simulating dynamics of a system, parameters can represent system sensitivities and unresolved processes, therefore affecting model accuracy and uncertainty. Taking a light use efficiency (LUE) model as an example, which is a typical approach for estimating gross primary productivity (GPP), we propose a Simultaneous Parameter Inversion and Extrapolation approach (SPIE) to overcome issues stemming from plant‐functional‐type (PFT)‐dependent parameterizations. SPIE refers to predicting model parameters using an artificial neural network based on collected variables, including PFT, climate types, bioclimatic variables, vegetation features, atmospheric nitrogen and phosphorus deposition, and soil properties. The neural network was optimized to minimize GPP errors and constrain LUE model sensitivity functions. We compared SPIE with 11 typical parameter extrapolating methods, including PFT‐ and climate‐specific parameterizations, global and PFT‐based parameter optimization, site‐similarity, and regression approaches. All methods were assessed using Nash‐Sutcliffe model efficiency (NSE), determination coefficient and normalized root mean squared error, and contrasted with site‐specific calibrations. Ten‐fold cross‐validated results showed that SPIE had the best performance across sites, various temporal scales and assessing metrics. Taking site‐level calibrations as a benchmark (NSE = 0.95), SPIE performed with an NSE of 0.68, while all the other investigated approaches showed lower NSE. The Shapley value, layer‐wise relevance and partial dependence showed that vegetation features, bioclimatic variables, soil properties and some PFTs determine parameters. SPIE overcomes strong limitations observed in many standard parameterization methods. We argue that expanding SPIE to other models overcomes current limits and serves as an entry point to investigate the robustness and generalization of different models.
A Bootstrap Common Mean Direction Test
Authors: Heslop David , Scealy Janice L. , Wood Andrew T. A. , Tauxe Lisa , Roberts Andrew P.
Published: August 2023

Paleomagnetic statistical inference is underpinned by a family of parametric null hypothesis tests. In many cases, however, paleomagnetic data do not meet the distributional assumptions of these tests, which can lead to spurious inferences. Earlier studies have proposed the bootstrap as a nonparametric alternative for paleomagnetic analysis, which can be applied even when the distributional form of the data is unknown. Key among these approaches is the bootstrap test for a common mean direction, which relies on assessment of the overlap of estimated confidence regions. In its current form, the bootstrap test for a common mean paleomagnetic direction does not consider a null hypothesis and can yield outcomes that cannot be interpreted in terms of a statistical significance level. To resolve these issues, we use recent advances to place such bootstrap tests within a null hypothesis significance testing framework, and unify them with the existing family of paleomagnetic statistical tests. Furthermore, using numerical experiments we demonstrate the applicability of such a nonparametric approach to moderately sized paleomagnetic data sets typical of modern and legacy studies. Finally, we demonstrate how a confidence region can be estimated for the common mean of two sets of directions and how known directions, such as the expected field produced by a geocentric axial dipole, can be compared to that mean.
Evolution of Thrace Macula on Europa: Strike‐Slip Tectonic Control and Identification of the Youngest Terrains
Authors: Matteoni Pietro , Neesemann Alicia , Jaumann Ralf , Hillier Jon , Postberg Frank
Published: August 2023

Chaos terrains are geologically young and extensively disrupted surface features of Europa, thought to be an expression of the subsurface ocean interacting with the surface. The most prominent examples of this terrain on Europa are Conamara Chaos, and Thera and Thrace Maculae, all prime targets for the upcoming JUICE and Europa Clipper missions to assess the astrobiological potential of Europa. Of the three features, Thrace Macula is currently the least studied and understood. It intersects both Agenor Linea to the north and Libya Linea to the south, two important regional‐scale bands whose interaction with Thrace is yet to be fully unraveled, especially in terms of their relative ages of emplacement and activity. Using Galileo Solid State Imager data and Digital Terrain Models, we conducted detailed structural mapping and terrain analysis to develop a novel hypothesis on the mechanisms involved in the study area. We find that Thrace Macula is bordered along most sides by preexisting strike‐slip faults that have constrained its emplacement and areal distribution. We determine a sequence of events in the area involving the formation of Agenor Linea, followed by that of Libya Linea first and Thrace Macula later, and ultimately by strike‐slip tectonic activity likely driven by Libya Linea, that displaced a portion of Thrace Macula. Therefore, Thrace's subsurface material, uprising along faults postdating its formation, represents the freshest possible that could be sampled by future spacecraft in this region, a major consideration for the upcoming Europa Clipper mission.
Particulate Organic Matter in the Atacama Trench: Tracing Sources and Possible Transport Mechanisms to the Hadal Seafloor
Authors: Flores Edgart , Fernández‐Urruzola Igor , Cantarero Sebastian I. , Pizarro‐Koch Matías , Zabel Matthias , Sepúlveda Julio , Ulloa Osvaldo
Published: August 2023

Oceanic trenches are an important sink for organic matter (OM). However, little is known about how much of the OM reaching the hadal region derives from the sunlit surface ocean and other sources. We provide new insight into the OM sources in the Atacama Trench by examining the elemental and stable isotope composition of carbon and nitrogen in bulk OM throughout the entire water column and down to bathyal and hadal sediments. Moreover, we estimated the particulate organic carbon (POC) concentration and downward carbon flux. Our results, based on two‐way variance analysis, showed statistical differences in δ15NPON between the epipelagic zone and the deep zones. However, no statistical differences in δ13CPOC and C:N ratio between hadalpelagic and shallower pelagic zones were found, except for δ13CPOC in the oxygen‐deficient zone. On the contrary, whereas the isotopic signatures of hadal sediments were distinct from those over the entire water column, they were similar to the values in bathyal sediments. Thus, our results suggest that bathyal sediments could contribute more OM to hadal sediments than the different zones of the water column. Indeed, whereas POC flux estimates derived from remote sensing data indicate that ∼16%–27% of POC could evade surface remineralization within the top 200 m and potentially be exported to depths beyond the mesopelagic region, model estimates suggest that ∼3.3% of it could reach hadal depths. Our results provide a quantitative baseline of pelagic‐benthic coupling which can aid in assessment of carbon cycling changes in future climate scenarios.
Climate Induced Thermocline Aging and Ventilation in the Eastern Atlantic Over the Last 32,000 Years
Authors: Beisel Elvira , Frank Norbert , Robinson Laura F. , Lausecker Marleen , Friedrich Ronny , Therre Steffen , Schröder‐Ritzrau Andrea , Butzin Martin
Published: August 2023

The radiocarbon analysis of uranium‐thorium‐dated cold‐water corals (CWCs) provides an excellent opportunity for qualitative reconstruction of past ocean circulation and water mass aging. While mid‐depth water mass aging has been studied in the Atlantic Ocean, the evolution of the thermocline is still largely unknown. Here we present a combined 14C and 230Th/U age record obtained from thermocline dwelling CWCs at various sites in the eastern Atlantic Ocean, with intermittently centennial resolution over the last 32 ka. Shallow dwelling CWCs off Angola, located in the South Atlantic, infer a link between the mid‐depth equatorial Atlantic and Southern Ocean. They confirm a 14C drawdown during the Last Glacial Maximum (LGM) and advocate for a consistent Southern Hemisphere radiocarbon aging of upper thermocline waters, as well as strong depth gradients and high variability. Direct comparison with 14C simulations carried out with an Ocean General Circulation Model yield good agreement for Angola. In contrast, the North Atlantic thermocline shows well‐ventilated water with strong variations near the position of today's Azores Front (AF), neither of which are captured by the model. During the Bølling‐Allerød, we confirm the important role of the AF in separating North and South Atlantic thermocline waters and provide further evidence of a 500 year long deep convection interruption within the Younger Dryas (YD). We conclude that the North and South Atlantic thermocline waters were separately acting carbon reservoirs during the LGM and subsequent deglaciation until the modern circulation was established during the YD.
Multiband Metasurface‐Based Absorber for Applications in X, Ku, and K Bands
Authors: Coelho H. J. S. , Araújo B. , Silva M. W. B. , Ferreira T. N. , Campos A. L. P. S. , Junqueira C. , Kemptner Erich , Osipov Andrey
Published: August 2023

In this paper, a slotted‐circle patch metasurface that can efficiently absorb electromagnetic (EM) waves in three different bands is proposed. Based on the fundamental resonance of a single circular patch, EM resonances are generated making slits in the circular patch leading to multi‐band operation. Simulation results show that the proposed structure can absorb signals in three different bands, namely at 8.10, 15.39, and 19.7 GHz with absorption peaks of 99.8%, 99.7%, and 99.8%, and absorption bandwidths of 132, 181, and 90 MHz, respectively. The absorption mechanism is discussed on the basis of the single‐layer effective medium model and the analysis of surface current and electric field distributions. Furthermore, the experimental results show good agreement with the numerical simulations, with an average absorption greater than 99%. The 2‐mm thick absorber is electrically thin, corresponding to ∼λ/18 at its lowest operating frequency. Compared to other published designs, the proposed absorber has a single resonator with simple geometry, but operates in multiband. Therefore, it can be used in many applications such as anechoic chambers, scattering control, photodetectors, microbolometers, and solar cells. The proposed metasurface absorber can be used for microwave energy harvesting as well as sensor and radar cross‐section reduction applications.
Real-time programmable metasurface for terahertz multifunctional wave front engineering
Authors: Lan Feng , Wang Luyang , Zeng Hongxin , Liang Shixiong , Song Tianyang , Liu Wenxin , Mazumder Pinaki , Yang Ziqiang , Zhang Yaxin , Mittleman Daniel M.
Published: August 2023

Terahertz (THz) technologies have become a focus of research in recent years due to their prominent role in envisioned future communication and sensing systems. One of the key challenges facing the field is the need for tools to enable agile engineering of THz wave fronts. Here, we describe a reconfigurable metasurface based on GaN technology with an array-of-subarrays architecture. This subwavelength-spaced array, under the control of a 1-bit digital coding sequence, can switch between an enormous range of possible configurations, providing facile access to nearly arbitrary wave front control for signals near 0.34 THz. We demonstrate wide-angle beam scanning with 1° of angular precision over 70 GHz of bandwidth, as well as the generation of multi-beam and diffuse wave fronts, with a switching speed up to 100 MHz. This device, offering the ability to rapidly reconfigure a propagating wave front for beam-forming or diffusively scattered wide-angle coverage of a scene, will open new realms of possibilities in sensing, imaging, and networking.
Extracellular RNAs-TLR3 signaling contributes to cognitive impairment after chronic neuropathic pain in mice
Authors: Zhang Xueying , Gao Rui , Zhang Changteng , Teng Yi , Chen Hai , Li Qi , Liu Changliang , Wu Jiahui , Wei Liuxing , Deng Liyun , Wu Lining , Ye-Lehmann Shixin , Mao Xiaobo , Liu Jin , Zhu Tao , Chen Chan
Published: August 2023

Chronic pain is often associated with cognitive decline, which could influence the quality of the patient’s life. Recent studies have suggested that Toll-like receptor 3 (TLR3) is crucial for memory and learning. Nonetheless, the contribution of TLR3 to the pathogenesis of cognitive decline after chronic pain remains unclear. The level of TLR3 in hippocampal neurons increased in the chronic constriction injury (CCI) group than in the sham group in this study. Importantly, compared to the wild-type (WT) mice, TLR3 knockout (KO) mice and TLR3-specific neuronal knockdown mice both displayed improved cognitive function, reduced levels of inflammatory cytokines and neuronal apoptosis and attenuated injury to hippocampal neuroplasticity. Notably, extracellular RNAs (exRNAs), specifically double-stranded RNAs (dsRNAs), were increased in the sciatic nerve, serum, and hippocampus after CCI. The co-localization of dsRNA with TLR3 was also increased in hippocampal neurons. And the administration of poly (I:C), a dsRNA analog, elevated the levels of dsRNAs and TLR3 in the hippocampus, exacerbating hippocampus-dependent memory. In additon, the dsRNA/TLR3 inhibitor improved cognitive function after CCI. Together, our findings suggested that exRNAs, particularly dsRNAs, that were present in the condition of chronic neuropathic pain, activated TLR3, initiated downstream inflammatory and apoptotic signaling, caused damage to synaptic plasticity, and contributed to the etiology of cognitive impairment after chronic neuropathic pain.
PRC1 suppresses a female gene regulatory network to ensure testicular differentiation
Authors: Maezawa So , Yukawa Masashi , Hasegawa Kazuteru , Sugiyama Ryo , Iizuka Mizuho , Hu Mengwen , Sakashita Akihiko , Vidal Miguel , Koseki Haruhiko , Barski Artem , DeFalco Tony , Namekawa Satoshi H.
Published: August 2023

Gonadal sex determination and differentiation are controlled by somatic support cells of testes (Sertoli cells) and ovaries (granulosa cells). In testes, the epigenetic mechanism that maintains chromatin states responsible for suppressing female sexual differentiation remains unclear. Here, we show that Polycomb repressive complex 1 (PRC1) suppresses a female gene regulatory network in postnatal Sertoli cells. We genetically disrupted PRC1 function in embryonic Sertoli cells after sex determination, and we found that PRC1-depleted postnatal Sertoli cells exhibited defective proliferation and cell death, leading to the degeneration of adult testes. In adult Sertoli cells, PRC1 suppressed specific genes required for granulosa cells, thereby inactivating the female gene regulatory network. Chromatin regions associated with female-specific genes were marked by Polycomb-mediated repressive modifications: PRC1-mediated H2AK119ub and PRC2-mediated H3K27me3. Taken together, this study identifies a critical Polycomb-based mechanism that suppresses ovarian differentiation and maintains Sertoli cell fate in adult testes.
The role of epithelial-mesenchymal transition and autophagy in pancreatic ductal adenocarcinoma invasion
Authors: Yang Jian , Liu Ying , Liu Shi
Published: August 2023

Of all pancreatic cancer (PC) cases, approximately 90% are pancreatic ductal adenocarcinoma (PDAC), which progress rapidly due to its high degree of invasiveness and high metastatic potential. Epithelial-mesenchymal transition (EMT) is a prerequisite for cancer cell invasion and spread, and it is mediated by the specific cellular behaviors and the tumor microenvironment. Autophagy has long been a target of cancer therapy, and it has been considered to play a dual and contradictory role, particularly regarding EMT-mediated PDAC invasion. This review discusses the characteristics and the biological role of EMT and autophagy from a cellular perspective, explaining invasion as a survival behavior of PDAC, with the aim of providing novel insights into targeting EMT and autophagy to overcome PDAC invasion.
A single-cell transcriptional landscape of immune cells shows disease-specific changes of T cell and macrophage populations in human achalasia
Authors: Liu Zu-Qiang , Dai Hao , Yao Lu , Chen Wei-Feng , Wang Yun , Ma Li-Yun , Li Xiao-Qing , Lin Sheng-Li , He Meng-Jiang , Gao Ping-Ting , Liu Xin-Yang , Xu Jia-Xin , Xu Xiao-Yue , Wang Ke-Hao , Wang Li , Chen Luonan , Zhou Ping-Hong , Li Quan-Lin
Published: August 2023

Achalasia is a rare motility disorder of the esophagus caused by the gradual degeneration of myenteric neurons. Immune-mediated ganglionitis has been proposed to underlie the loss of myenteric neurons. Here, we measure the immune cell transcriptional profile of paired lower esophageal sphincter (LES) tissue and blood samples in achalasia and controls using single-cell RNA sequencing (scRNA-seq). In achalasia, we identify a pattern of expanded immune cells and a specific transcriptional phenotype, especially in LES tissue. We show C1QC+ macrophages and tissue-resident memory T cells (TRM), especially ZNF683+ CD8+ TRM and XCL1+ CD4+ TRM, are significantly expanded and localized surrounding the myenteric plexus in the LES tissue of achalasia. C1QC+ macrophages are transcriptionally similar to microglia of the central nervous system and have a neurodegenerative dysfunctional phenotype in achalasia. TRM also expresses transcripts of dysregulated immune responses in achalasia. Moreover, inflammation increases with disease progression since immune cells are more activated in type I compared with type II achalasia. Thus, we profile the immune cell transcriptional landscape and identify C1QC+ macrophages and TRM as disease-associated immune cell subsets in achalasia.
Antigen-dependent IL-12 signaling in CAR T cells promotes regional to systemic disease targeting
Authors: Lee Eric Hee Jun , Murad John P. , Christian Lea , Gibson Jackson , Yamaguchi Yukiko , Cullen Cody , Gumber Diana , Park Anthony K. , Young Cari , Monroy Isabel , Yang Jason , Stern Lawrence A. , Adkins Lauren N. , Dhapola Gaurav , Gittins Brenna , Chang Wen-Chung , Martinez Catalina , Woo Yanghee , Cristea Mihaela , Rodriguez-Rodriguez Lorna , Ishihara Jun , Lee John K. , Forman Stephen J. , Wang Leo D. , Priceman Saul J.
Published: August 2023

Chimeric antigen receptor (CAR) T cell therapeutic responses are hampered by limited T cell trafficking, persistence, and durable anti-tumor activity in solid tumors. However, these challenges can be largely overcome by relatively unconstrained synthetic engineering strategies. Here, we describe CAR T cells targeting tumor-associated glycoprotein-72 (TAG72), utilizing the CD28 transmembrane domain upstream of the 4-1BB co-stimulatory domain as a driver of potent anti-tumor activity and IFNγ secretion. CAR T cell-mediated IFNγ production facilitated by IL-12 signaling is required for tumor cell killing, which is recapitulated by engineering an optimized membrane-bound IL-12 (mbIL12) molecule in CAR T cells. These T cells show improved antigen-dependent T cell proliferation and recursive tumor cell killing in vitro, with robust in vivo efficacy in human ovarian cancer xenograft models. Locoregional administration of mbIL12-engineered CAR T cells promotes durable anti-tumor responses against both regional and systemic disease in mice. Safety and efficacy of mbIL12-engineered CAR T cells is demonstrated using an immunocompetent mouse model, with beneficial effects on the immunosuppressive tumor microenvironment. Collectively, our study features a clinically-applicable strategy to improve the efficacy of locoregionally-delivered CAR T cells engineered with antigen-dependent immune-modulating cytokines in targeting regional and systemic disease.
Experimental validation of the free-energy principle with in vitro neural networks
Authors: Isomura Takuya , Kotani Kiyoshi , Jimbo Yasuhiko , Friston Karl J.
Published: August 2023

Empirical applications of the free-energy principle are not straightforward because they entail a commitment to a particular process theory, especially at the cellular and synaptic levels. Using a recently established reverse engineering technique, we confirm the quantitative predictions of the free-energy principle using in vitro networks of rat cortical neurons that perform causal inference. Upon receiving electrical stimuli—generated by mixing two hidden sources—neurons self-organised to selectively encode the two sources. Pharmacological up- and downregulation of network excitability disrupted the ensuing inference, consistent with changes in prior beliefs about hidden sources. As predicted, changes in effective synaptic connectivity reduced variational free energy, where the connection strengths encoded parameters of the generative model. In short, we show that variational free energy minimisation can quantitatively predict the self-organisation of neuronal networks, in terms of their responses and plasticity. These results demonstrate the applicability of the free-energy principle to in vitro neural networks and establish its predictive validity in this setting.
Metagenomic surveillance uncovers diverse and novel viral taxa in febrile patients from Nigeria
Authors: Oguzie Judith U. , Petros Brittany A. , Oluniyi Paul E. , Mehta Samar B. , Eromon Philomena E. , Nair Parvathy , Adewale-Fasoro Opeoluwa , Ifoga Peace Damilola , Odia Ikponmwosa , Pastusiak Andrzej , Gbemisola Otitoola Shobi , Aiyepada John Oke , Uyigue Eghosasere Anthonia , Edamhande Akhilomen Patience , Blessing Osiemi , Airende Michael , Tomkins-Tinch Christopher , Qu James , Stenson Liam , Schaffner Stephen F. , Oyejide Nicholas , Ajayi Nnenna A. , Ojide Kingsley , Ogah Onwe , Abejegah Chukwuyem , Adedosu Nelson , Ayodeji Oluwafemi , Liasu Ahmed A. , Okogbenin Sylvanus , Okokhere Peter O. , Park Daniel J. , Folarin Onikepe A. , Komolafe Isaac , Ihekweazu Chikwe , Frost Simon D. W. , Jackson Ethan K. , Siddle Katherine J. , Sabeti Pardis C. , Happi Christian T.
Published: August 2023

Effective infectious disease surveillance in high-risk regions is critical for clinical care and pandemic preemption; however, few clinical diagnostics are available for the wide range of potential human pathogens. Here, we conduct unbiased metagenomic sequencing of 593 samples from febrile Nigerian patients collected in three settings: i) population-level surveillance of individuals presenting with symptoms consistent with Lassa Fever (LF); ii) real-time investigations of outbreaks with suspected infectious etiologies; and iii) undiagnosed clinically challenging cases. We identify 13 distinct viruses, including the second and third documented cases of human blood-associated dicistrovirus, and a highly divergent, unclassified dicistrovirus that we name human blood-associated dicistrovirus 2. We show that pegivirus C is a common co-infection in individuals with LF and is associated with lower Lassa viral loads and favorable outcomes. We help uncover the causes of three outbreaks as yellow fever virus, monkeypox virus, and a noninfectious cause, the latter ultimately determined to be pesticide poisoning. We demonstrate that a local, Nigerian-driven metagenomics response to complex public health scenarios generates accurate, real-time differential diagnoses, yielding insights that inform policy.
Myonectin protects against skeletal muscle dysfunction in male mice through activation of AMPK/PGC1α pathway
Authors: Ozaki Yuta , Ohashi Koji , Otaka Naoya , Kawanishi Hiroshi , Takikawa Tomonobu , Fang Lixin , Takahara Kunihiko , Tatsumi Minako , Ishihama Sohta , Takefuji Mikito , Kato Katsuhiro , Shimizu Yuuki , Bando Yasuko K. , Inoue Aiko , Kuzuya Masafumi , Miura Shinji , Murohara Toyoaki , Ouchi Noriyuki
Published: August 2023

To maintain and restore skeletal muscle mass and function is essential for healthy aging. We have found that myonectin acts as a cardioprotective myokine. Here, we investigate the effect of myonectin on skeletal muscle atrophy in various male mouse models of muscle dysfunction. Disruption of myonectin exacerbates skeletal muscle atrophy in age-associated, sciatic denervation-induced or dexamethasone (DEX)-induced muscle atrophy models. Myonectin deficiency also contributes to exacerbated mitochondrial dysfunction and reduces expression of mitochondrial biogenesis-associated genes including PGC1α in denervated muscle. Myonectin supplementation attenuates denervation-induced muscle atrophy via activation of AMPK. Myonectin also reverses DEX-induced atrophy of cultured myotubes through the AMPK/PGC1α signaling. Furthermore, myonectin treatment suppresses muscle atrophy in senescence-accelerated mouse prone (SAMP) 8 mouse model of accelerated aging or mdx mouse model of Duchenne muscular dystrophy. These data indicate that myonectin can ameliorate skeletal muscle dysfunction through AMPK/PGC1α-dependent mechanisms, suggesting that myonectin could represent a therapeutic target of muscle atrophy.
Combining gut microbiota modulation and chemotherapy by capecitabine-loaded prebiotic nanoparticle improves colorectal cancer therapy
Authors: Lang Tianqun , Zhu Runqi , Zhu Xiao , Yan Wenlu , Li Yu , Zhai Yihui , Wu Ting , Huang Xin , Yin Qi , Li Yaping
Published: August 2023

Colorectal cancer (CRC) therapy efficiency can be influenced by the microbiota in the gastrointestinal tract. Compared with traditional intervention, prebiotics delivery into the gut is a more controllable method for gut microbiota modulatory therapy. Capecitabine (Cap), the first-line chemotherapeutic agent for CRC, lacks a carrier that can prolong its half-life. Here, we construct a Cap-loaded nanoparticle using the prebiotic xylan-stearic acid conjugate (SCXN). The oral administration of SCXN delays the drug clearance in the blood and increases the intra-tumoral Cap concentration in the CRC mouse model. SCXN also facilitates the probiotic proliferation and short chain fatty acid production. Compared with free Cap, SCXN enhances the anti-tumor immunity and increases the tumor inhibition rate from 5.29 to 71.78%. SCXN exhibits good biocompatibility and prolongs the median survival time of CRC mice from 14 to 33.5 d. This prebiotics-based nanoparticle provides a promising CRC treatment by combining gut microbiota modulation and chemotherapy.
Backbone spiking sequence as a basis for preplay, replay, and default states in human cortex
Authors: Vaz Alex P. , Wittig John H. , Inati Sara K. , Zaghloul Kareem A.
Published: August 2023

Sequences of spiking activity have been heavily implicated as potential substrates of memory formation and retrieval across many species. A parallel line of recent evidence also asserts that sequential activity may arise from and be constrained by pre-existing network structure. Here we reconcile these two lines of research in the human brain by measuring single unit spiking sequences in the temporal lobe cortex as participants perform an episodic memory task. We find the presence of an average backbone spiking sequence identified during pre-task rest that is stable over time and different cognitive states. We further demonstrate that these backbone sequences are composed of both rigid and flexible sequence elements, and that flexible elements within these sequences serve to promote memory specificity when forming and retrieving new memories. These results support the hypothesis that pre-existing network dynamics serve as a scaffold for ongoing neural activity in the human cortex.
Saddles as rotational locks within shape-assisted self-assembled nanosheets
Authors: Woods Joseph F. , Gallego Lucía , Maisch Amira , Renggli Dominik , Cuocci Corrado , Blacque Olivier , Steinfeld Gunther , Kaech Andres , Spingler Bernhard , Vargas Jentzsch Andreas , Rickhaus Michel
Published: August 2023

Two-dimensional (2D) materials are a key target for many applications in the modern day. Self-assembly is one approach that can bring us closer to this goal, which usually relies upon strong, directional interactions instead of covalent bonds. Control over less directional forces is more challenging and usually does not result in as well-defined materials. Explicitly incorporating topography into the design as a guiding effect to enhance the interacting forces can help to form highly ordered structures. Herein, we show the process of shape-assisted self-assembly to be consistent across a range of derivatives that highlights the restriction of rotational motion and is verified using a diverse combination of solid state analyses. A molecular curvature governed angle distribution nurtures monomers into loose columns that then arrange to form 2D structures with long-range order observed in both crystalline and soft materials. These features strengthen the idea that shape becomes an important design principle leading towards precise molecular self-assembly and the inception of new materials.
Using orbital sensitivity analysis to pinpoint the role of orbital interactions in thermoelectric power factor
Authors: Zhang Wenhao , Halet Jean-François , Mori Takao
Published: August 2023

The modification of the electronic band structure is of critical importance for thermoelectric materials whose heat to electricity power generation is related to carrier effective mass and alignment of semiconductor band edges. One approach to optimize the electronic band structure is by modification of orbital interactions through doping or alloying. While the current ab-initio quantum chemical calculations can help us to investigate orbital components of electronic bands, they reveal little information on the relative tunability of electronic states and transport properties with respect to orbital interactions. In this work, we present a method, based on a symmetry-adapted tight-binding model and sensitivity analysis, that can pinpoint the role of orbital interactions in determining electronic band structure and transport properties. As an application, a systematic theoretical analysis is used to show how the power factor of PbTe can/cannot be improved by playing with interatomic orbital interactions. The orbital interaction sensitivity analysis introduced in this work can easily be applied to other compounds or properties.
Dynamic matrices with DNA-encoded viscoelasticity for cell and organoid culture
Authors: Peng Yu-Hsuan , Hsiao Syuan-Ku , Gupta Krishna , Ruland André , Auernhammer Günter K. , Maitz Manfred F. , Boye Susanne , Lattner Johanna , Gerri Claudia , Honigmann Alf , Werner Carsten , Krieg Elisha
Published: August 2023

Three-dimensional cell and organoid cultures rely on the mechanical support of viscoelastic matrices. However, commonly used matrix materials lack control over key cell-instructive properties. Here we report on fully synthetic hydrogels based on DNA libraries that self-assemble with ultrahigh-molecular-weight polymers, forming a dynamic DNA-crosslinked matrix (DyNAtrix). DyNAtrix enables computationally predictable and systematic control over its viscoelasticity, thermodynamic and kinetic parameters by changing DNA sequence information. Adjustable heat activation allows homogeneous embedding of mammalian cells. Intriguingly, stress-relaxation times can be tuned over four orders of magnitude, recapitulating mechanical characteristics of living tissues. DyNAtrix is self-healing, printable, exhibits high stability, cyto- and haemocompatibility, and controllable degradation. DyNAtrix-based cultures of human mesenchymal stromal cells, pluripotent stem cells, canine kidney cysts and human trophoblast organoids show high viability, proliferation and morphogenesis. DyNAtrix thus represents a programmable and versatile precision matrix for advanced approaches to biomechanics, biophysics and tissue engineering.
Towards a circular economy: valorization of banana peels by developing bio-composites thermal insulators
Authors: Mohamed Gehad R. , Mahmoud Rehab K. , Shaban Mohamed , Fahim Irene S. , Abd El‑Salam H. M. , Mahmoud Hamada M.
Published: August 2023

The building construction materials are responsible for a large amount of energy and natural resource consumption. In light of the current challenges of resource scarcity and global climate change, the circular economy (CE) is a promising strategy to mitigate pressure on the environment, improve supplying of raw materials, and increase new market and employment opportunities. Developing eco-friendly thermal insulation materials based on agro-waste is a new waste management trend to achieve the sustainability of the resource and energy consumption in the construction sectors. In this work, banana-polystyrene composites were prepared by mixing the banana peels powder (BP) with polystyrene (PS) in different weight ratios (90:10, 80:20, 70:30, and 60:40). The physical and thermal properties such as thermal conductivity, electrical conductivity, Fourier Transform Infrared (FTIR), crystallographic structures of the fibers, X-Ray Diffraction (XRD), Thermogravimetric Analysis (TGA), and Differential Scanning Calorimetry (DSC) were carried out on BP and BP-PS1 that were prepared with ten wt.% and 20 wt.% of polystyrene powder (BP-PS2). The bio-composites results showed low thermal conductivity ranging from 0.028 to 0.030 W/m.K. The BP-PS2 exhibited a lower thermal conductivity of 0.027 W/m.K, while the pure peel powder demonstrated notable thermal stability, indicated by a total weight loss of 66.4% and a high crystallinity value of 56.1%. Furthermore, the thermal analysis (TGA) and X-Ray Diffraction (XRD) demonstrated that the pure banana peel has the highest thermal stability and crystallinity. These findings indicate that using banana peel-polystyrene composites represents an innovative solution for thermal insulation in buildings as an alternative to conventional materials to reduce energy and resource consumption.
Imaging-based study demonstrates how the DEK nanoscale distribution differentially correlates with epigenetic marks in a breast cancer model
Authors: Pierzynska-Mach Agnieszka , Cainero Isotta , Oneto Michele , Ferrando-May Elisa , Lanzanò Luca , Diaspro Alberto
Published: August 2023

Epigenetic dysregulation of chromatin is one of the hallmarks of cancer development and progression, and it is continuously investigated as a potential general bio-marker of this complex disease. One of the nuclear factors involved in gene regulation is the unique DEK protein—a histone chaperon modulating chromatin topology. DEK expression levels increase significantly from normal to cancer cells, hence raising the possibility of using DEK as a tumor marker. Although DEK is known to be implicated in epigenetic and transcriptional regulation, the details of these interactions and their relevance in cancer development remain largely elusive. In this work, we investigated the spatial correlation between the nuclear distribution of DEK and chromatin patterns—alongside breast cancer progression—leveraging image cross-correlation spectroscopy (ICCS) coupled with Proximity Ligation Assay (PLA) analysis. We performed our study on the model based on three well-established human breast cell lines to consider this tumor's heterogeneity (MCF10A, MCF7, and MDA-MB-231 cells). Our results show that overexpression of DEK correlates with the overall higher level of spatial proximity between DEK and histone marks corresponding to gene promoters regions (H3K9ac, H3K4me3), although it does not correlate with spatial proximity between DEK and gene enhancers (H3K27ac). Additionally, we observed that colocalizing fractions of DEK and histone marks are lower for the non-invasive cell subtype than for the highly invasive cell line (MDA-MB-231). Thus, this study suggests that the role of DEK on transcriptionally active chromatin regions varies depending on the subtype of the breast cancer cell line.
Modified generalized Weibull distribution: theory and applications
Authors: Shama Mustafa S. , Alharthi Amirah Saeed , Almulhim Fatimah A. , Gemeay Ahmed M. , Meraou Mohammed Amine , Mustafa Manahil SidAhmed , Hussam Eslam , Aljohani Hassan M.
Published: August 2023

This article presents and investigates a modified version of the Weibull distribution that incorporates four parameters and can effectively represent a hazard rate function with a shape resembling a bathtub. Its significance in the fields of lifetime and reliability stems from its ability to model both increasing and decreasing failure rates. The proposed distribution encompasses several well-known models such as the Weibull, extreme value, exponentiated Weibull, generalized Rayleigh, and modified Weibull distributions. The paper derives key mathematical statistics of the proposed distribution, including the quantile function, moments, moment-generating function, and order statistics density. Various mathematical properties of the proposed model are established, and the unknown parameters of the distribution are estimated using different estimation techniques. Furthermore, the effectiveness of these estimators is assessed through numerical simulation studies. Finally, the paper applies the new model and compares it with various existing distributions by analyzing two real-life time data sets.
Management of perimesencephalic nonaneurysmal subarachnoid hemorrhage: a national survey
Authors: Wolfert Christina , Maurer Christoph J. , Sommer Björn , Steininger Kathrin , Motov Stefan , Bonk Maximilian-Niklas , Krauss Philipp , Berlis Ansgar , Shiban Ehab
Published: August 2023

Perimesencephalic nonaneurysmal subarachnoid hemorrhage (NASAH) is a rare type of subarachnoid hemorrhage (SAH), usually associated with minor complications compared to aneurysmal SAH. Up to date, data is scarce and consensus on therapeutic management and follow-up diagnostics of NASAH is often missing. This survey aims to evaluate the clinical management among neurosurgical departments in Germany. 135 neurosurgical departments in Germany received a hardcopy questionnaire. Encompassing three case vignettes with minor, moderate and severe NASAH on CT-scans and questions including the in-hospital treatment with initial observation, blood pressure (BP) management, cerebral vasospasm (CV) prophylaxis and the need for digital subtraction angiography (DSA). 80 departments (59.2%) answered the questionnaire. Whereof, centers with a higher caseload state an elevated complication rate (Chi2 < 0.001). Initial observation on the intensive care unit is performed in 51.3%; 47.5%, 70.0% in minor, moderate and severe NASAH, respectively. Invasive BP monitoring is performed more often in severe NASAH (52.5%, 55.0%, 71.3% minor, moderate, severe). CV prophylaxis and transcranial doppler ultrasound (TCD) are performed in 41.3%, 45.0%, 63.8% in minor, moderate and severe NASAH, respectively. Indication for a second DSA is set in the majority of centers, whereas after two negative ones, a third DSA is less often indicated (2nd: 66.2%, 72.5%, 86.2%; 3rd: 3.8%, 3.8%, 13.8% minor, moderate, severe). This study confirms the influence of bleeding severity on treatment and follow-up of NASAH patients. Additionally, the existing inconsistency of treatment pathways throughout Germany is highlighted. Therefore, we suggest to conceive new treatment guidelines including this finding.
Combining atomic force microscopy and fluorescence-based techniques to explore mechanical properties of naive and ischemia-affected brain regions in mice
Authors: Fuhs Thomas , Flachmeyer Bianca , Krueger Martin , Blietz Alexandra , Härtig Wolfgang , Michalski Dominik
Published: August 2023

Knowledge of the brain’s structure and function is essential for understanding processes in health and disease. Histochemical and fluorescence-based techniques have proven beneficial in characterizing brain regions and cellular compositions in pre-clinical research. Atomic force microscopy (AFM) has been introduced for mechanical tissue characterization, which may also help investigate pathophysiological aspects in disease-related models such as stroke. While combining AFM and fluorescence-based techniques, this study explored the mechanical properties of naive and ischemic brain regions in mice. Ischemia-affected regions were identified by the green signal of fluorescein isothiocyanate-conjugated albumin. A semi-automated protocol based on a brain atlas allowed regional allocations to the neocortex, striatum, thalamus, hypothalamus, hippocampus, and fiber tracts. Although AFM led to varying measurements, intra-individual analyses indicated a gradually increased tissue stiffness in the neocortex compared to subcortical areas, i.e., the striatum and fiber tracts. Regions affected by ischemia predominantly exhibited an increased tissue stiffness compared to those of the contra-lateral hemisphere, which might be related to cellular swelling. This study indicated intra-individual differences in mechanical properties among naive and ischemia-affected brain regions. The combination of AFM, semi-automated regional allocations, and fluorescence-based techniques thus qualifies for mechanical characterizations of the healthy and disease-affected brain in pre-clinical research.