bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Adaptive Schemas and Sexual Wellbeing in Women: Exploring Differences in Menopausal Status
Authors: Allen Andrew , Tully-Wilson Colleen
Published: May 2023

There is limited research concerning the relationship between early adaptive schema, from Young’s Schema Theory, and women’s sexual wellbeing. Schema Theory posits that early adaptive schema start forming in early childhood from core emotional needs being met, and positively influence individuals’ concept of self, relationships with others, and their behaviours. Building on this theory, the current study explored the relationship of early adaptive schema and adult women’s sexual wellbeing at pre-, peri-, and post-menopause. Four hundred and sixty-seven women, mostly partnered and heterosexual, from over ten countries, participated in an online survey measuring relationships between early adaptive schema and sexual wellbeing, measured by sexual functioning and sexual satisfaction. The strength of association of early adaptive schema and sexual well-being were evaluated in addition to known predictors. The results showed higher early adaptive schema were associated with higher sexual wellbeing, measured by sexual satisfaction and sexual functioning, with medium-to-large effect sizes, at pre and peri-menopause, and produced a non-significant result for post-menopause. The association of early adaptive schema continued after known factors were accounted for. The results support the use of early adaptive schema to promote sexual wellbeing for women at pre- and peri-menopause.
Subtleties in the trainability of quantum machine learning models
Authors: Thanasilp Supanut , Wang Samson , Nghiem Nhat Anh , Coles Patrick , Cerezo Marco
Published: May 2023

A new paradigm for data science has emerged, with quantum data, quantum models, and quantum computational devices. This field, called quantum machine learning (QML), aims to achieve a speedup over traditional machine learning for data analysis. However, its success usually hinges on efficiently training the parameters in quantum neural networks, and the field of QML is still lacking theoretical scaling results for their trainability. Some trainability results have been proven for a closely related field called variational quantum algorithms (VQAs). While both fields involve training a parametrized quantum circuit, there are crucial differences that make the results for one setting not readily applicable to the other. In this work, we bridge the two frameworks and show that gradient scaling results for VQAs can also be applied to study the gradient scaling of QML models. Our results indicate that features deemed detrimental for VQA trainability can also lead to issues such as barren plateaus in QML. Consequently, our work has implications for several QML proposals in the literature. In addition, we provide theoretical and numerical evidence that QML models exhibit further trainability issues not present in VQAs, arising from the use of a training dataset. We refer to these as dataset-induced barren plateaus. These results are most relevant when dealing with classical data, as here the choice of embedding scheme (i.e., the map between classical data and quantum states) can greatly affect the gradient scaling.
Improved Power Control of DFIGs Driven by Wind Turbine under Unbalanced Grid Voltage
Authors: Shehata E. G.
Published: May 2023

Undesired oscillation components appear in active and reactive powers, electromagnetic torque and DC-link voltage of doubly fed induction generators (DFIGs) connected to unbalanced grid voltage. These components oscillate at double source frequency as a result of negative sequence components in voltage and current. Different direct power control (DPC) techniques were studied in literatures to damp these oscillations. However, these techniques require sequence decomposition process, axes transformation of stator voltage/current and estimation of different power components which complicate the overall control system. This paper presents a simplified DPC of DFIGs in stationary reference frame under normal and unbalanced grid voltage. Decomposition process, axes transformation and compensation power terms are totally eliminated. Vector proportional- integral (VPI) controllers are designed to regulate stator active and reactive powers. The performance of the proposed DPC scheme using VPI and proportional-integral-resonant (PIR) controllers is analyzed and compared under different operating conditions. Bode diagram of open loop and closed loop control using VPI and PIR are studied to illustrate stability, steady state and transient response of the two controllers. Also, the performance of proposed technique and previous DPCs designed in synchronous reference frame is compared to prove the validity of proposed one. The results show that proposed DPC using VPI has superior performance in steady state and transient conditions with simple implementation.
A Time-Free Assumption for Solving Signature-Free Asynchronous Multivalued Byzantine Consensus
Authors: Nezzar Abderafik , Moumen Hamouma , Arar Chafik
Published: May 2023

This paper tackles the asynchronous signature-free Byzantine consensus. One way to circumvent the FLP impossibility result consists in adding a Time-free assumption. This assumption is based on the pattern of messages that are exchanged. In the context of authenticated asynchronous Byzantine systems where at most t processes may exhibit a Byzantine behavior, Moumen and Mostéfaoui provide the main result. They assume at least one correct process $$p_i$$

p
i

, called $$\diamond \langle t+1\rangle \text {-winning}$$

⋄
⟨
t
+
1
⟩
-winning

, and a set Q of t correct processes such that, eventually, for each query issued by $$p_i$$

p
i

, any process $$p_j$$

p
j

of Q receives a response from $$p_i$$

p
i

among the $$(n-t)$$

(
n
-
t
)

first responses to that query. The main contribution of this paper is to show that a deterministic solution for the Signature-free Byzantine consensus problem is possible if the system model satisfies an additional assumption that relies on the pattern of exchanged messages. To solve the Consensus problem, we assume a correct process $$p_i$$

p
i

, called $$\diamond \langle 2t+1\rangle \text {-winning}$$

⋄
⟨
2
t
+
1
⟩
-winning

, and a set Q of $$(2t+1)$$

(
2
t
+
1
)

correct processes (including $$p_i$$

p
i

itself) such that, eventually, for each query issued by $$p_i$$

p
i

, any process $$p_j$$

p
j

of Q receives a response from $$p_i$$

p
i

among the $$(n - t)$$

(
n
-
t
)

first responses to that query. The processes of the set Q may change over time. Based on this assumption, a Signature-free Multivalued Byzantine consensus protocol is proposed. Whereas many time-free protocols have been designed for the consensus problem in the crash model and in the Byzantine Authenticated model, this is, to our knowledge, the first time-free deterministic solution to the Signature-free Byzantine consensus Problem.
Mistrust Among Rescue Workers After the Terrorist Attack in Berlin in 2016 – Gender-Specific Health Inequality
Authors: Wesemann Ulrich , Helms Christian , Polk Sarah , Mahnke Manuel , Bühler Antje , Muschner Patric , Willmund Gerd
Published: May 2023

Objectives:

In this single-case-by-group comparison, we examine whether previously found cisgender differences in paranoid ideation after a terror attack are also seen in a transgender male emergency worker.

Methods:

Sixty emergency personnel who were exposed to the 2016 terror attack in Berlin were evaluated 3 to 4 and 21-25 mo after the attack.

Results:

On paranoid ideation, the transgender male showed higher scores than cisgender males (+2 standard deviations [SD]) and the overall group (+1 SD).

Conclusions:

This underpins the previously identified gender effects. It would be useful to consider specified pre- and postdeployment modules that take cis- and transgender differences into account.
Status-impact assessment: is accuracy linked with status motivations?
Authors: Durkee Patrick K. , Lukaszewski Aaron W. , Buss David M.
Published: May 2023

Status hierarchies are ubiquitous across cultures and have been over deep time. Position in hierarchies shows important links with fitness outcomes. Consequently, humans should possess psychological adaptations for navigating the adaptive challenges posed by living in hierarchically organised groups. One hypothesised adaptation functions to assess, track, and store the status impacts of different acts, characteristics and events in order to guide hierarchy navigation. Although this status-impact assessment system is expected to be universal, there are several ways in which differences in assessment accuracy could arise. This variation may link to broader individual difference constructs. In a preregistered study with samples from India (N = 815) and the USA (N = 822), we sought to examine how individual differences in the accuracy of status-impact assessments covary with status motivations and personality. In both countries, greater overall status-impact assessment accuracy was associated with higher status motivations, as well as higher standing on two broad personality constructs: Honesty–Humility and Conscientiousness. These findings help map broad personality constructs onto variation in the functioning of specific cognitive mechanisms and contribute to an evolutionary understanding of individual differences.
The Asymptotic Statistics of Random Covering Surfaces
Authors: Magee Michael , Puder Doron
Published: May 2023

Let$\Gamma _{g}$be the fundamental group of a closed connected orientable surface of genus$g\geq 2$. We develop a new method for integrating over the representation space$\mathbb {X}_{g,n}=\mathrm {Hom}(\Gamma _{g},S_{n})$, where$S_{n}$is the symmetric group of permutations of$\{1,\ldots ,n\}$. Equivalently, this is the space of all vertex-labeled,n-sheeted covering spaces of the closed surface of genusg.

Given$\phi \in \mathbb {X}_{g,n}$and$\gamma \in \Gamma _{g}$, we let$\mathsf {fix}_{\gamma }(\phi )$be the number of fixed points of the permutation$\phi (\gamma )$. The function$\mathsf {fix}_{\gamma }$is a special case of a natural family of functions on$\mathbb {X}_{g,n}$called Wilson loops. Our new methodology leads to an asymptotic formula, as$n\to \infty $, for the expectation of$\mathsf {fix}_{\gamma }$with respect to the uniform probability measure on$\mathbb {X}_{g,n}$, which is denoted by$\mathbb {E}_{g,n}[\mathsf {fix}_{\gamma }]$. We prove that if$\gamma \in \Gamma _{g}$is not the identity andqis maximal such that$\gamma $is aqthpower in$\Gamma _{g}$, then$$\begin{align*}\mathbb{E}_{g,n}\left[\mathsf{fix}_{\gamma}\right]=d(q)+O(n^{-1}) \end{align*}$$

as$n\to \infty $, where$d\left (q\right )$is the number of divisors ofq. Even the weaker corollary that$\mathbb {E}_{g,n}[\mathsf {fix}_{\gamma }]=o(n)$as$n\to \infty $is a new result of this paper. We also prove that$\mathbb {E}_{g,n}[\mathsf {fix}_{\gamma }]$can be approximated to any order$O(n^{-M})$by a polynomial in$n^{-1}$.
The distribution of fossil pollen and charcoal in stalagmites
Authors: Dickson Bianca , Sniderman J.M. Kale , Korasidis Vera A. , Woodhead Jon
Published: May 2023

Pollen preserved in caves provides a little-appreciated opportunity to study past vegetation and climate changes in regions where conventional wetland sediments are either unavailable, contain little organic matter, and/or are difficult to date accurately. Most palynology in caves has focused on clastic infill sediments, but pollen preserved in growing speleothems provides important new opportunities to develop vegetation and climatic records that can be dated accurately with radiometric methods. However, when pollen is present in speleothems, concentrations can vary by orders of magnitude, highlighting how little we know about the processes that transport pollen into caves and onto speleothem surfaces, and that determine the pollen's preservation probability. To explore these aspects of speleothem pollen taphonomy, we investigated the distribution of pollen and microscopic charcoal within several stalagmites from southwest Australia. We examined spatial patterns in pollen and charcoal preservation in order to distinguish whether observed gradients result from preservation or are products of systematic transport processes working along stalagmite surfaces. We find that pollen grains and charcoal fragments are located preferentially on the flanks of most stalagmites. This suggests that pollen grain and charcoal deposition on speleothems is influenced by transport and accumulation of detrital debris on growing surfaces. These insights will assist in future sampling campaigns focusing on speleothem pollen and charcoal contents.
In search of Tabal, central Anatolia: Iron Age interaction at Alişar Höyük
Authors: Kealhofer Lisa , Grave Peter , Marsh Ben
Published: May 2023

Trajectories of social complexity following socio-political collapse have provided fertile ground for new theoretical and methodological perspectives in archaeology. Here we investigate ceramics from the site of Alişar Höyük, a settlement that was likely part of the Iron Age polity of Tabal. Best known from Assyrian texts, Tabal emerged in central Anatolia after the Late Bronze Age Hittite collapse, but its structure and operation remain enigmatic. Excavated in the 1920s and 1930s, a large sample of ceramics from Alişar has since been curated at the Oriental Institute, University of Chicago. Using multiple perspectives on this Middle Iron Age ceramic sample, we explore the political and economic structures at this site in terms of its interaction sphere. Our results suggest that if Alişar was part of Tabal, by the Middle Iron Age this polity was highly intra-regionally integrated, competitive and heterarchical.
Technology-enhanced language learning and pragmatics: Insights from digital game-based pragmatics instruction
Authors: Taguchi Naoko
Published: May 2023

Learning pragmatics involves learning linguistic forms and their communicative functions as well as the context where the form-function relationships are realized. Given its socially grounded, context-sensitive nature, pragmatics may be best learned in a technology-enhanced environment that provides direct access to contextualized communicative practice. Technology can help produce rich multimodal input, opportunities for interaction with consequences, and experience-based learning, which are all important elements of pragmatics learning. This lecture highlights these benefits of technology-enhanced pragmatics learning using a digital game as a sample platform. We created a digital game to teach request-making in English by having participants experience interpersonal consequences of their request as feedback (observing their interlocutor's reactions to their choice of request-making forms). Using the digital game with Chinese learners of English, a series of studies were conducted to investigate a variety of topics, such as the effects of different feedback conditions on learning outcomes, role of metapragmatic knowledge in learning, and transfer of request-making knowledge to a novel speech act. This lecture presents findings from these studies and concludes with future research directions on technology-enhanced pragmatics learning.
Screening the predictors for live birth failure in women after the first frozen embryo transfer based on the Lasso algorithm: a retrospective study
Authors: Jin Wumin , Lin Jia , Wang Peiyu , Yang Haiyan , Jin Congcong
Published: May 2023

This study aimed to screen factors related to live birth outcomes of women with first frozen embryo transfer (FET). The enrolled women were divided into training and validation cohorts. The least absolute shrinkage and selection operator (Lasso) regression algorithm of machine learning and the multiple regression model were then used to screen factors relevant to live birth failure (LBF) for the training dataset. A nomogram risk prediction model was established on the basis of the screened factors, and the consistency index (C-index) and calibration curve were derived for evaluating the model. The validation cohort was utilized to validate the nomogram model further. In total, 2083 women who accepted the first FET in our hospital were included and 44 factors were initially screened in this study. On the basis of the training cohort, the screened risk factors via multiple regression analysis with odds ratio (OR) values were female age (OR: 3.092, 95%CI: 1.065–4.852), body mass index (BMI; OR: 1.106, 95%CI: 1.015–1.546), caesarean section (OR: 1.909, 95%CI: 1.318–2.814), number of high-quality embryos (OR: 0.698, 95%CI: 0.599–0.812), and endometrial thickness (OR: 0.957, CI: 0.904–0.980). The nomogram model was generated based on five predictors. Furthermore, favourable results with C-indexes and calibration curves close to ideal curves indicated the accurate predictive ability of the nomogram. Female age, BMI, caesarean section, number of high-quality embryos, and endometrial thickness were independent predictors for LBF. The five factors of the risk assessment model may help to identify LBF with high accuracy in women who accept FET.
Determining sentiment views of verbal multiword expressions using linguistic features
Authors: Wiegand Michael , Schulder Marc , Ruppenhofer Josef
Published: May 2023

We examine the binary classification of sentiment views for verbal multiword expressions (MWEs). Sentiment views denote the perspective of the holder of some opinion. We distinguish between MWEs conveying the view of the speaker of the utterance (e.g., in “The company reinvented the wheel” the holder is the implicit speaker who criticizes the company for creating something already existing) and MWEs conveying the view of explicit entities participating in an opinion event (e.g., in “Peter threw in the towel” the holder is Peter having given up something). The task has so far been examined on unigram opinion words. Since many features found effective for unigrams are not usable for MWEs, we propose novel ones taking into account the internal structure of MWEs, a unigram sentiment-view lexicon and various information from Wiktionary. We also examine distributional methods and show that the corpus on which a representation is induced has a notable impact on the classification. We perform an extrinsic evaluation in the task of opinion holder extraction and show that the learnt knowledge also improves a state-of-the-art classifier trained on BERT. Sentiment-view classification is typically framed as a task in which only little labeled training data are available. As in the case of unigrams, we show that for MWEs a feature-based approach beats state-of-the-art generic methods.
Molecular cytology identification of 22 sugarcane germplasm clones from Sri Lanka
Authors: Li Xujuan , Mao Jun , Chen Xuekuan , Lin Xiuqin , Wang Xiaoyan , Xu Chaohua , Liu Xinlong , Lu Xin
Published: May 2023

Germplasm innovation can provide materials for breeding sugarcane cultivars. Saccharum officinarum is the main source of high-sugar and high-yield genes in sugarcane breeding. ‘Nobilization’ is the theoretical basis for exploiting S. officinarum, and S. officinarum authenticity directly affects sugarcane nobility breeding efficiency. Herein, the authenticity of 22 SLC-series S. officinarum clones imported from Sri Lanka and preserved in the China National Germplasm Repository of Sugarcane (NGRS) was explored by four-primer amplification-arrested mutation PCR (ARMS PCR) and somatic chromosome number counting. The amplified bands from SLC 08 120 and SLC 08 131 were the same with those from S. officinarum clone Badila, i.e. a common band of 428 bp and a S. officinarum-specific band of 278 bp, hence they were tentatively assigned as S. officinarum clones. The other 20 SLC clones had both 278 bp (S. officinarum-specific) and 203 bp (S. spontaneum-specific) bands, which are hybrid characteristics. In addition, the chromosome numbers of SLC 08 120 and SLC 08 131 are both 80, belong to typical S. officinarum. While the chromosome numbers of the other 20 materials are ranging from 101 to 129, consistent with hybrids of S. officinarum and S. spontaneum. This molecular cytological characterization indicates that among the 22 introduced SLC-series clones, only two, SLC 08 120 and SLC 08 131, were S. officinarum. Future agronomic trait and resistance analyses could facilitate their use as crossing parents in sugarcane breeding.
Defending History? The Impact of Context and Speaker in Russia
Authors: Krawatzek Félix , Soroka George
Published: May 2023

Political attempts to control how the past may be represented have flourished in the twenty-first century. Russia participates in this trend, having taken steps to legislatively and juridically safeguard the legacy of the USSR’s involvement in World War II. This has institutionalized an interpretation of the fight against Nazism that was already widely held in society, making the Russian case a “hard test” for evaluating when the violation of a historical norm is deemed appropriate and what the impact of a memory law might be relative to other factors. Drawing on two vignette experiments conducted in 2021, our article demonstrates both that the discursive context in which a controversial statement about the past is made matters when respondents assess whether the person making it should be punished and that criticism of a historical norm is more likely to be accepted when it emanates from an in-group member. We also find that the state has limited ability to influence societal attitudes regarding history. Moreover, a willingness to defend state-led interventions into how the past is depicted aligns with support for the political system but the latter does not necessarily overlap with individuals’ historical views, underscoring the multidimensional nature of collective memory.
Rift Basins and Intraplate Earthquakes: New High‐Resolution Aeromagnetic Data Provide Insights Into Buried Structures of the Charleston, South Carolina Seismic Zone
Authors: Shah A. K. , Pratt T. L. , Horton J. W.
Published: May 2023

The delineation of faults that pose seismic risk in intraplate seismic zones and the mapping of features associated with failed rift basins can help our understanding of links between the two. We use new high‐resolution aeromagnetic data, previous borehole sample information, and reprocessed seismic reflection profiles to image subsurface structures and evaluate recent fault activity within the Charleston seismic zone, the associated Mesozoic South Georgia rift basin, and surrounds. The new aeromagnetic data provide an unprecedented view of buried basement structures. NE‐ and NW‐trending lineaments of various lengths throughout the survey area are interpreted as Paleozoic orogenic structures and Mesozoic dikes, respectively. Within the rift basin, 15‐ to 20‐km long ESE‐trending lineaments are associated with faults in pre‐Cretaceous strata of the reflection data and are interpreted as Mesozoic rift structures. Various intersections and terminations of interpreted faults suggest rift‐related reactivation of Paleozoic faults and corresponding inheritance for Mesozoic structures. The reflection data show that several Paleozoic and Mesozoic faults are associated with deformation in Cretaceous and younger sediments, suggesting reactivation in the more recent passive margin setting. Two of these faults, one NE‐striking and one ESE‐striking, are coincident with surficial landforms, suggesting Quaternary slip; the ESE‐striking fault is also well‐aligned with a plan‐view offset in modern seismicity. A favorable orientation for reverse motion on ESE‐striking Mesozoic faults, a possible sub‐basin, and potentially weakened lithosphere are failed rift basin features that may influence intraplate seismicity within the Charleston seismic zone.
Nanograin network memory with reconfigurable percolation paths for synaptic interactions
Authors: Lee Hoo-Cheol , Kim Jungkil , Kim Ha-Reem , Kim Kyoung-Ho , Park Kyung-Jun , So Jae-Pil , Lee Jung Min , Hwang Min-Soo , Park Hong-Gyu
Published: May 2023

The development of memory devices with functions that simultaneously process and store data is required for efficient computation. To achieve this, artificial synaptic devices have been proposed because they can construct hybrid networks with biological neurons and perform neuromorphic computation. However, irreversible aging of these electrical devices causes unavoidable performance degradation. Although several photonic approaches to controlling currents have been suggested, suppression of current levels and switching of analog conductance in a simple photonic manner remain challenging. Here, we demonstrated a nanograin network memory using reconfigurable percolation paths in a single Si nanowire with solid core/porous shell and pure solid core segments. The electrical and photonic control of current percolation paths enabled the analog and reversible adjustment of the persistent current level, exhibiting memory behavior and current suppression in this single nanowire device. In addition, the synaptic behaviors of memory and erasure were demonstrated through potentiation and habituation processes. Photonic habituation was achieved using laser illumination on the porous nanowire shell, with a linear decrease in the postsynaptic current. Furthermore, synaptic elimination was emulated using two adjacent devices interconnected on a single nanowire. Therefore, electrical and photonic reconfiguration of the conductive paths in Si nanograin networks will pave the way for next-generation nanodevice technologies.
Drug-induced lactate confers ferroptosis resistance via p38-SGK1-NEDD4L-dependent upregulation of GPX4 in NSCLC cells
Authors: Cheng Feng , Dou Jintao , Yang Yi , Sun Shaojie , Chen Ruiqi , Zhang Zhijian , Wei Huijun , Li Jianhui , Wu Zhihao
Published: May 2023

Ferroptosis is a newly defined non-apoptotic programmed cell death resulting from the accumulation of lipid peroxides. Whether ferroptosis plays any role in chemotherapy remains to be established. Here, we reported that ferroptosis represents a part of the chemotherapeutic drug etoposide-induced cell death response in Small Cell Lung Cancer (SCLC) cells and adaptive signaling molecule lactate protects Non-Small Cell Lung Cancer (NSCLC) from etoposide-induced ferroptosis. Lactate derived from metabolic reprogramming increases the expression of glutathione peroxidase 4 (GPX4) to promote ferroptosis resistance in NSCLC. Furthermore, we identified E3-ubiquitin ligase NEDD4L as a major regulator of GPX4 stability. Mechanistically, Lactate increases mitochondrial ROS generation and drives activation of the p38-SGK1 pathway, which attenuates the interaction of NEDD4L with GPX4 and subsequent ubiquitination and degradation of GPX4. Our data implicated the role of ferroptosis in chemotherapeutic resistance and identified a novel post-translational regulatory mechanism for the key Ferroptosis mediator GPX4.
GalNAc-Lipid nanoparticles enable non-LDLR dependent hepatic delivery of a CRISPR base editing therapy
Authors: Kasiewicz Lisa N. , Biswas Souvik , Beach Aaron , Ren Huilan , Dutta Chaitali , Mazzola Anne Marie , Rohde Ellen , Chadwick Alexandra , Cheng Christopher , Garcia Sara P. , Iyer Sowmya , Matsumoto Yuri , Khera Amit V. , Musunuru Kiran , Kathiresan Sekar , Malyala Padma , Rajeev Kallanthottathil G. , Bellinger Andrew M.
Published: May 2023

Lipid nanoparticles have demonstrated utility in hepatic delivery of a range of therapeutic modalities and typically deliver their cargo via low-density lipoprotein receptor-mediated endocytosis. For patients lacking sufficient low-density lipoprotein receptor activity, such as those with homozygous familial hypercholesterolemia, an alternate strategy is needed. Here we show the use of structure-guided rational design in a series of mouse and non-human primate studies to optimize a GalNAc-Lipid nanoparticle that allows for low-density lipoprotein receptor independent delivery. In low-density lipoprotein receptor-deficient non-human primates administered a CRISPR base editing therapy targeting the ANGPTL3 gene, the introduction of an optimized GalNAc-based asialoglycoprotein receptor ligand to the nanoparticle surface increased liver editing from 5% to 61% with minimal editing in nontargeted tissues. Similar editing was noted in wild-type monkeys, with durable blood ANGPTL3 protein reduction up to 89% six months post dosing. These results suggest that GalNAc-Lipid nanoparticles may effectively deliver to both patients with intact low-density lipoprotein receptor activity as well as those afflicted by homozygous familial hypercholesterolemia.
Deep learning to estimate lung disease mortality from chest radiographs
Authors: Weiss Jakob , Raghu Vineet K. , Bontempi Dennis , Christiani David C. , Mak Raymond H. , Lu Michael T. , Aerts Hugo J.W.L.
Published: May 2023

Prevention and management of chronic lung diseases (asthma, lung cancer, etc.) are of great importance. While tests are available for reliable diagnosis, accurate identification of those who will develop severe morbidity/mortality is currently limited. Here, we developed a deep learning model, CXR Lung-Risk, to predict the risk of lung disease mortality from a chest x-ray. The model was trained using 147,497 x-ray images of 40,643 individuals and tested in three independent cohorts comprising 15,976 individuals. We found that CXR Lung-Risk showed a graded association with lung disease mortality after adjustment for risk factors, including age, smoking, and radiologic findings (Hazard ratios up to 11.86 [8.64–16.27]; p < 0.001). Adding CXR Lung-Risk to a multivariable model improved estimates of lung disease mortality in all cohorts. Our results demonstrate that deep learning can identify individuals at risk of lung disease mortality on easily obtainable x-rays, which may improve personalized prevention and treatment strategies.
3D-patterned inverse-designed mid-infrared metaoptics
Authors: Roberts Gregory , Ballew Conner , Zheng Tianzhe , Garcia Juan C. , Camayd-Muñoz Sarah , Hon Philip W. C. , Faraon Andrei
Published: May 2023

Modern imaging systems can be enhanced in efficiency, compactness, and application through the introduction of multilayer nanopatterned structures for manipulation of light based on its fundamental properties. High transmission multispectral imaging is elusive due to the commonplace use of filter arrays which discard most of the incident light. Further, given the challenges of miniaturizing optical systems, most cameras do not leverage the wealth of information in polarization and spatial degrees of freedom. Optical metamaterials can respond to these electromagnetic properties but have been explored primarily in single-layer geometries, limiting their performance and multifunctional capacity. Here we use advanced two-photon lithography to realize multilayer scattering structures that achieve highly nontrivial optical transformations intended to process light just before it reaches a focal plane array. Computationally optimized multispectral and polarimetric sorting devices are fabricated with submicron feature sizes and experimentally validated in the mid-infrared. A final structure shown in simulation redirects light based on its angular momentum. These devices demonstrate that with precise 3-dimensional nanopatterning, one can directly modify the scattering properties of a sensor array to create advanced imaging systems.
Functional variants identify sex-specific genes and pathways in Alzheimer’s Disease
Authors: Bourquard Thomas , Lee Kwanghyuk , Al-Ramahi Ismael , Pham Minh , Shapiro Dillon , Lagisetty Yashwanth , Soleimani Shirin , Mota Samantha , Wilhelm Kevin , Samieinasab Maryam , Kim Young Won , Huh Eunna , Asmussen Jennifer , Katsonis Panagiotis , Botas Juan , Lichtarge Olivier
Published: May 2023

The incidence of Alzheimer’s Disease in females is almost double that of males. To search for sex-specific gene associations, we build a machine learning approach focused on functionally impactful coding variants. This method can detect differences between sequenced cases and controls in small cohorts. In the Alzheimer’s Disease Sequencing Project with mixed sexes, this approach identified genes enriched for immune response pathways. After sex-separation, genes become specifically enriched for stress-response pathways in male and cell-cycle pathways in female. These genes improve disease risk prediction in silico and modulate Drosophila neurodegeneration in vivo. Thus, a general approach for machine learning on functionally impactful variants can uncover sex-specific candidates towards diagnostic biomarkers and therapeutic targets.
Peripheral modulation of antidepressant targets MAO-B and GABAAR by harmol induces mitohormesis and delays aging in preclinical models
Authors: Costa-Machado Luis Filipe , Garcia-Dominguez Esther , McIntyre Rebecca L. , Lopez-Aceituno Jose Luis , Ballesteros-Gonzalez Álvaro , Tapia-Gonzalez Andrea , Fabregat-Safont David , Eisenberg Tobias , Gomez Jesús , Plaza Adrian , Sierra-Ramirez Aranzazu , Perez Manuel , Villanueva-Bermejo David , Fornari Tiziana , Loza María Isabel , Herradon Gonzalo , Hofer Sebastian J. , Magnes Christoph , Madeo Frank , Duerr Janet S. , Pozo Oscar J. , Galindo Maximo-Ibo , del Pino Isabel , Houtkooper Riekelt H. , Megias Diego , Viña Jose , Gomez-Cabrera Mari Carmen , Fernandez-Marcos Pablo J.
Published: May 2023

Reversible and sub-lethal stresses to the mitochondria elicit a program of compensatory responses that ultimately improve mitochondrial function, a conserved anti-aging mechanism termed mitohormesis. Here, we show that harmol, a member of the beta-carbolines family with anti-depressant properties, improves mitochondrial function and metabolic parameters, and extends healthspan. Treatment with harmol induces a transient mitochondrial depolarization, a strong mitophagy response, and the AMPK compensatory pathway both in cultured C2C12 myotubes and in male mouse liver, brown adipose tissue and muscle, even though harmol crosses poorly the blood–brain barrier. Mechanistically, simultaneous modulation of the targets of harmol monoamine-oxidase B and GABA-A receptor reproduces harmol-induced mitochondrial improvements. Diet-induced pre-diabetic male mice improve their glucose tolerance, liver steatosis and insulin sensitivity after treatment with harmol. Harmol or a combination of monoamine oxidase B and GABA-A receptor modulators extend the lifespan of hermaphrodite Caenorhabditis elegans or female Drosophila melanogaster. Finally, two-year-old male and female mice treated with harmol exhibit delayed frailty onset with improved glycemia, exercise performance and strength. Our results reveal that peripheral targeting of monoamine oxidase B and GABA-A receptor, common antidepressant targets, extends healthspan through mitohormesis.
Spatial metabolomics reveals glycogen as an actionable target for pulmonary fibrosis
Authors: Conroy Lindsey R. , Clarke Harrison A. , Allison Derek B. , Valenca Samuel Santos , Sun Qi , Hawkinson Tara R. , Young Lyndsay E. A. , Ferreira Juanita E. , Hammonds Autumn V. , Dunne Jaclyn B. , McDonald Robert J. , Absher Kimberly J. , Dong Brittany E. , Bruntz Ronald C. , Markussen Kia H. , Juras Jelena A. , Alilain Warren J. , Liu Jinze , Gentry Matthew S. , Angel Peggi M. , Waters Christopher M. , Sun Ramon C.
Published: May 2023

Matrix assisted laser desorption/ionization imaging has greatly improved our understanding of spatial biology, however a robust bioinformatic pipeline for data analysis is lacking. Here, we demonstrate the application of high-dimensionality reduction/spatial clustering and histopathological annotation of matrix assisted laser desorption/ionization imaging datasets to assess tissue metabolic heterogeneity in human lung diseases. Using metabolic features identified from this pipeline, we hypothesize that metabolic channeling between glycogen and N-linked glycans is a critical metabolic process favoring pulmonary fibrosis progression. To test our hypothesis, we induced pulmonary fibrosis in two different mouse models with lysosomal glycogen utilization deficiency. Both mouse models displayed blunted N-linked glycan levels and nearly 90% reduction in endpoint fibrosis when compared to WT animals. Collectively, we provide conclusive evidence that lysosomal utilization of glycogen is required for pulmonary fibrosis progression. In summary, our study provides a roadmap to leverage spatial metabolomics to understand foundational biology in pulmonary diseases.
Microbiota-assisted iron uptake promotes immune tolerance in the intestine
Authors: Zhu Lizhen , Li Geng , Liang Zhixin , Qi Tuan , Deng Kui , Yu Jiancheng , Peng Yue , Zheng Jusheng , Song Yan , Chang Xing
Published: May 2023

Iron deficiencies are the most common nonenteric syndromes observed in patients with inflammatory bowel disease, but little is known about their impacts on immune tolerance. Here we show that homeostasis of regulatory T cells in the intestine was dependent on high cellular iron levels, which were fostered by pentanoate, a short-chain fatty acid produced by intestinal microbiota. Iron deficiencies in Treg caused by the depletion of Transferrin receptor 1, a major iron transporter, result in the abrogation of Treg in the intestine and lethal autoimmune disease. Transferrin receptor 1 is required for differentiation of c-Maf+ Treg, major constituents of intestinal Treg. Mechanistically, iron enhances the translation of HIF-2α mRNA, and HIF-2α in turn induces c-Maf expression. Importantly, microbiota-produced pentanoate promotes iron uptake and Treg differentiation in the intestine. This subsequently restores immune tolerance and ameliorated iron deficiencies in mice with colitis. Our results thus reveal an association between nutrient uptake and immune tolerance in the intestine.
Complex phase transitions and phase engineering in the aqueous solution of an isopolyoxometalate cluster
Authors: Wang Zhi-Da , Liang Song , Yang Yuqing , Liu Zhen-Ning , Duan Xiao-Zheng , Li Xinpei , Liu Tianbo , Zang Hong-Ying
Published: May 2023

Inorganic salts usually demonstrate simple phasal behaviors in dilute aqueous solution mainly involving soluble (homogeneous) and insoluble (macrophase separation) scenarios. Herein, we report the discovery of complex phase behavior involving multiple phase transitions of clear solution – macrophase separation – gelation – solution – macrophase separation in the dilute aqueous solutions of a structurally well-defined molecular cluster [Mo7O24]6− macroanions with the continuous addition of Fe3+. No chemical reaction was involved. The transitions are closely related to the strong electrostatic interaction between [Mo7O24]6− and their Fe3+ counterions, the counterion-mediated attraction and the consequent charge inversion, leading to the formation of linear/branched supramolecular structures, as confirmed by experimental results and molecular dynamics simulations. The rich phase behavior demonstrated by the inorganic cluster [Mo7O24]6− expands our understanding of nanoscale ions in solution.
Glutamatergic cerebellar neurons differentially contribute to the acquisition of motor and social behaviors
Authors: van der Heijden Meike E. , Rey Hipolito Alejandro G. , Kim Linda H. , Kizek Dominic J. , Perez Ross M. , Lin Tao , Sillitoe Roy V.
Published: May 2023

Insults to the developing cerebellum can cause motor, language, and social deficits. Here, we investigate whether developmental insults to different cerebellar neurons constrain the ability to acquire cerebellar-dependent behaviors. We perturb cerebellar cortical or nuclei neuron function by eliminating glutamatergic neurotransmission during development, and then we measure motor and social behaviors in early postnatal and adult mice. Altering cortical and nuclei neurons impacts postnatal motor control and social vocalizations. Normalizing neurotransmission in cortical neurons but not nuclei neurons restores social behaviors while the motor deficits remain impaired in adults. In contrast, manipulating only a subset of nuclei neurons leaves social behaviors intact but leads to early motor deficits that are restored by adulthood. Our data uncover that glutamatergic neurotransmission from cerebellar cortical and nuclei neurons differentially control the acquisition of motor and social behaviors, and that the brain can compensate for some but not all perturbations to the developing cerebellum.
Machine learning-guided discovery of ionic polymer electrolytes for lithium metal batteries
Authors: Li Kai , Wang Jifeng , Song Yuanyuan , Wang Ying
Published: May 2023

As essential components of ionic polymer electrolytes (IPEs), ionic liquids (ILs) with high ionic conductivity and wide electrochemical window are promising candidates to enable safe and high-energy-density lithium metal batteries (LMBs). Here, we describe a machine learning workflow embedded with quantum calculation and graph convolutional neural network to discover potential ILs for IPEs. By selecting subsets of the recommended ILs, combining with a rigid-rod polyelectrolyte and a lithium salt, we develop a series of thin (~50 μm) and robust (>200 MPa) IPE membranes. The Li|IPEs|Li cells exhibit ultrahigh critical-current-density (6 mA cm−2) at 80 °C. The Li|IPEs|LiFePO4 (10.3 mg cm−2) cells deliver outstanding capacity retention in 350 cycles (>96% at 0.5C; >80% at 2C), fast charge/discharge capability (146 mAh g−1 at 3C) and excellent efficiency (>99.92%). This performance is rarely reported by other single-layer polymer electrolytes without any flammable organics for LMBs.
Structure and sucrose binding mechanism of the plant SUC1 sucrose transporter
Authors: Bavnhøj Laust , Driller Jan Heiner , Zuzic Lorena , Stange Amanda Dyrholm , Schiøtt Birgit , Pedersen Bjørn Panyella
Published: May 2023

Sucrose import from photosynthetic tissues into the phloem is mediated by transporters from the low-affinity sucrose transporter family (SUC/SUT family). Furthermore, sucrose redistribution to other tissues is driven by phloem sap movement, the product of high turgor pressure created by this import activity. Additionally, sink organs such as fruits, cereals and seeds that accumulate high concentrations of sugar also depend on this active transport of sucrose. Here we present the structure of the sucrose–proton symporter, Arabidopsis thaliana SUC1, in an outward open conformation at 2.7 Å resolution, together with molecular dynamics simulations and biochemical characterization. We identify the key acidic residue required for proton-driven sucrose uptake and describe how protonation and sucrose binding are strongly coupled. Sucrose binding is a two-step process, with initial recognition mediated by the glucosyl moiety binding directly to the key acidic residue in a stringent pH-dependent manner. Our results explain how low-affinity sucrose transport is achieved in plants, and pinpoint a range of SUC binders that help define selectivity. Our data demonstrate a new mode for proton-driven symport with links to cation-driven symport and provide a broad model for general low-affinity transport in highly enriched substrate environments.
Ocular conditions and injuries, detection and management in spaceflight
Authors: Meer Elana , Grob Seanna , Antonsen Erik L. , Sawyer Aenor
Published: May 2023

Ocular trauma or other ocular conditions can be significantly debilitating in space. A literature review of over 100 articles and NASA evidence books, queried for eye related trauma, conditions, and exposures was conducted. Ocular trauma and conditions during NASA space missions during the Space Shuttle Program and ISS through Expedition 13 in 2006 were reviewed. There were 70 corneal abrasions, 4 dry eyes, 4 eye debris, 5 complaints of ocular irritation, 6 chemical burns, and 5 ocular infections noted. Unique exposures on spaceflight, such as foreign bodies, including celestial dust, which may infiltrate the habitat and contact the ocular surface, as well as chemical and thermal injuries due to prolonged CO2 and heat exposure were reported. Diagnostic modalities used to evaluate the above conditions in space flight include vision questionnaires, visual acuity and Amsler grid testing, fundoscopy, orbital ultrasound, and ocular coherence tomography. Several types of ocular injuries and conditions, mostly affecting the anterior segment, are reported. Further research is necessary to understand the greatest ocular risks that astronauts face and how better we can prevent, but also diagnose and treat these conditions in space.
Global economic burden per episode for multiple diseases caused by group A Streptococcus
Authors: Lee Jung-Seok , Kim Sol , Excler Jean-Louis , Kim Jerome H. , Mogasale Vittal
Published: May 2023

Considering the lack of existing evidence on economic burden for diseases caused by group A Streptococcus, we estimated the economic burden per episode for selected diseases. Each cost component of direct medical costs (DMCs), direct non-medical costs (DNMCs), and indirect costs (ICs) was separately extrapolated and aggregated to estimate the economic burden per episode by income group as classified by the World Bank. Adjustment factors for DMC and DNMC were generated to overcome related data insufficiencies. To address uncertainty surrounding input parameters, a probabilistic multivariate sensitivity was carried out. The average economic burden per episode ranged from $22 to $392 for pharyngitis, $25 to $2,903 for impetigo, $47 to $2,725 for cellulitis, $662 to $34,330 for invasive and toxin-mediated infections, $231 to $6,332 for acute rheumatic fever (ARF), $449 to $11,717 for rheumatic heart disease (RHD), and $949 to $39,560 for severe RHD across income groups. The economic burden for multiple Group A Streptococcus diseases underscores an urgent need to develop effective prevention strategies including vaccines.
Sympathetic modulation of hindlimb muscle contractility is altered in aged rats
Authors: Hotta Harumi , Iimura Kaori , Watanabe Nobuhiro , Suzuki Harue , Sugie Masamitsu , Shigemoto Kazuhiro
Published: May 2023

It has recently been demonstrated that reflex excitation of muscle sympathetic nerves triggered by muscle contraction contributes to the maintenance of tetanic force (TF) in rat hindlimb muscles. We hypothesized that this feedback mechanism between the contraction of hindlimb muscles and the lumbar sympathetic nerves declines during aging. In this study, we examined the contribution of sympathetic nerves on skeletal muscle contractility in young adult (4–9 months old, n = 11) and aged (32–36 months old, n = 11) male and female rats. The tibial nerve was electrically stimulated to measure the TF of the triceps surae muscles resulting from motor nerve activation before and after cutting or stimulating (at 5–20 Hz) the lumbar sympathetic trunk (LST). The TF amplitude decreased by cutting the LST in the young and aged groups; however, the magnitude of the decrease in TF following transection of the LST in the aged rats (6.2%) was significantly (P = 0.02) smaller compared with that in the young rats (12.9%). The TF amplitude was increased by LST stimulation at ≥ 5 Hz in the young and ≥ 10 Hz in the aged groups. The overall TF response to LST stimulation was not significantly different between the two groups; however, an increase in muscle tonus resulting from LST stimulation, independent of motor nerve stimulation, was significantly (P = 0.03) greater in aged compared with young rats. The sympathetic contribution to support motor nerve-induced muscle contraction declined, whereas sympathetic-mediated muscle tonus, independent of motor nerve activity, was augmented in aged rats. These changes in sympathetic modulation of hindlimb muscle contractility may underlie the reduction of skeletal muscle strength during voluntary contraction and rigidity of motion during senescence.