bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and Laboratory Approach to Diagnose COVID-19 Using Machine Learning
Authors: Chadaga Krishnaraj , Chakraborty Chinmay , Prabhu Srikanth , Umakanth Shashikiran , Bhat Vivekananda , Sampathila Niranjana
Published: February 2022

Coronavirus 2 (SARS-CoV-2), often known by the name COVID-19, is a type of acute respiratory syndrome that has had a significant influence on both economy and health infrastructure worldwide. This novel virus is diagnosed utilising a conventional method known as the RT-PCR (Reverse Transcription Polymerase Chain Reaction) test. This approach, however, produces a lot of false-negative and erroneous outcomes. According to recent studies, COVID-19 can also be diagnosed using X-rays, CT scans, blood tests and cough sounds. In this article, we use blood tests and machine learning to predict the diagnosis of this deadly virus. We also present an extensive review of various existing machine-learning applications that diagnose COVID-19 from clinical and laboratory markers. Four different classifiers along with a technique called Synthetic Minority Oversampling Technique (SMOTE) were used for classification. Shapley Additive Explanations (SHAP) method was utilized to calculate the gravity of each feature and it was found that eosinophils, monocytes, leukocytes and platelets were the most critical blood parameters that distinguished COVID-19 infection for our dataset. These classifiers can be utilized in conjunction with RT-PCR tests to improve sensitivity and in emergency situations such as a pandemic outbreak that might happen due to new strains of the virus. The positive results indicate the prospective use of an automated framework that could help clinicians and medical personnel diagnose and screen patients.

Graphical abstract
Laplace Approximations for Capture–Recapture Models in the Presence of Individual Heterogeneity
Authors: Herliansyah Riki , King Ruth , King Stuart
Published: February 2022

Capture–recapture studies are common for collecting data on wildlife populations. Populations in such studies are often subject to different forms of heterogeneity that may influence their associated demographic rates. We focus on the most challenging of these relating to individual heterogeneity. We consider (i) continuous time-varying individual covariates and (ii) individual random effects. In general, the associated likelihood is not available in closed form but only expressible as an analytically intractable integral. The integration is specified over (i) the unknown individual covariate values (if an individual is not observed, its associated covariate value is also unknown) and (ii) the unobserved random effect terms. Previous approaches to dealing with these issues include numerical integration and Bayesian data augmentation techniques. However, as the number of individuals observed and/or capture occasions increases, these methods can become computationally expensive. We propose a new and efficient approach that approximates the analytically intractable integral in the likelihood via a Laplace approximation. We find that for the situations considered, the Laplace approximation performs as well as, or better, than alternative approaches, yet is substantially more efficient.Supplementary materials accompanying this paper appear on-line
Pathogens attributed to central-line–associated bloodstream infections in US acute-care hospitals during the first year of the coronavirus disease 2019 (COVID-19) pandemic
Authors: Weiner-Lastinger Lindsey M. , Haass Kathryn , Gross Cindy , Leaptrot Denise , Wong Emily , Wu Hsiu , Dudeck Margaret A.
Published: February 2022

To assess potential changes in the pathogens attributed to central-line–associated bloodstream infections between 2019 and 2020, hospital data from the National Healthcare Safety Network were analyzed. Compared to 2019, increases in the proportions of pathogens identified as Enterococcus faecalis and coagulase-negative staphylococci were observed during 2020.
Serum ferritin levels are associated with frequent consumption of iron- and ascorbate-rich foods among women of childbearing age in Nandi County, Kenya
Authors: Nyakundi Patrick Nyamemba , Kiio Juliana , Munyaka Ann Wambui
Published: February 2022

Information on consumption patterns of iron- and ascorbate-rich foods and their influence on iron status among women of childbearing age (WCA) is scarce in Kenya despite iron deficiency being rampant. The present study investigated consumption patterns of iron- and ascorbate-rich foods on iron status among WCA in Kapsabet Ward, Kenya. The study adopted a cross-sectional analytical design. A sample of 160 respondents was systematically selected proportionately in the eight villages. Consumption patterns of iron- and ascorbate-rich foods were assessed using a modified 7-d Food Frequency Questionnaire. Venous blood (2 ml) was drawn from participants. Serum ferritin and C-reactive proteins were measured by enzyme immunoassay. Consumption patterns of iron- and ascorbate-rich foods were analysed using descriptive statistics. Multivariable regression was conducted to investigate the association between iron- and ascorbate-rich foods consumption and iron status. Confounding variables such as consumption of foods high phytate levels, milk and milk products, recent major blood losses and parasitic infections were controlled for during analysis. The prevalence of iron deficiency among the WCA was 45⋅0 %. Iron-rich foods were rarely (<2 times/week) consumed by the respondents with the majority reporting infrequent consumption: meat (61⋅3 %), sardines (61⋅9 %), oranges (54⋅4 %) and fortified breakfast cereals (94⋅4 %), except for kale and beans. Iron- (iron-fortified porridge, meat, sardines, beans, amaranth and spider plants) and ascorbate- (oranges and mangoes) rich foods positively predicted (AOR = 4⋅851,P= 0⋅021) the normal iron status of WCA. WCA should consume above 2 intakes per week of each iron- and ascorbate-rich food for better iron status outcomes.
ON REPUNIT CULLEN NUMBERS
Authors: ALAHMADI ADEL , LUCA FLORIAN
Published: February 2022

We prove that if$s\ge 2$is a fixed integer, then the equation$ns^n+1=(b^m-1)/(b-1)$has only finitely many positive integer solutions$(n,b,m)$with$b\ge 2$and$m\ge 3$. When$s=2$, it has no solution.
Unravelling causes of poor crop response to applied N and P fertilizers on African soils
Authors: Sileshi Gudeta W. , Kihara Job , Tamene Lulseged , Vanlauwe Bernard , Phiri Elijah , Jama Bashir
Published: February 2022

A number of studies across sub-Saharan Africa have recently reported poor crop responses and low agronomic use efficiencies of applied nitrogen (AEN), phosphorus (AEP) and potassium (AEK). However, the conditions under which non-responsiveness occurs, its underlying causes and its probability of occurrence on different soil types are not well understood. Using data from 542 sites and 14 soil types in 23 African countries, we provide novel insights into the linkage between lack of response to applied N, P and K, the mineralogy of soils and their resilience to erosion. We estimated mean responses as well as the probabilities (ϕ) of no response in terms of response ratio (RR), yield gain (YG) and agronomic efficiency. Here we defined ‘no response’ as zero agronomic response to fertilizer inputs in a given site and year indexed by either RR ≤ 1, AEN ≤ 0, AEP ≤ 0 or AEK ≤ 0. The highest risks of no response were recorded on the iron-rich Plinthosols (ϕ = 0.26) followed by the aluminium-rich Alisols (ϕ = 0.16) and the erosion-prone Lixisols (ϕ = 0.16) and Leptosols (ϕ = 0.13). In terms of yield gains, the highest risk of low response (i.e., YG ≤ 0.5) was recorded on Alisols (ϕ = 0.47) and the lowest on Fluvisols (ϕ = 0.05). Cambisols, Fluvisols, Luvisols and Nitisols were deemed highly responsive to NPK fertilizer. The risks of no response were significantly higher on soils derived from siliceous than mafic parent materials, soil types with low resilience to erosion, soils with low-activity clays and high P fixation capacity. It is concluded that maize grain yields can exceed 3 t ha-1 with high probability (ϕ > 0.80) on Andosols, Nitisols and Vertisols, but with very low probability (ϕ < 0.30) on Alisols and Arenosols. It is also concluded that across soil types and agroecological zones, the risk of no response is up to two times more on farmers’ fields than on research stations. Here, we discuss the implications of these finding for the design and location of future agronomic trials. We also provide insights to guide the targeting of fertilizer subsidies where nutrients can be more efficiently used.
Field evaluation of a new third generation push-pull technology for control of striga weed, stemborers, and fall armyworm in western Kenya
Authors: Cheruiyot Duncan , Chidawanyika Frank , Midega Charles A. O. , Pittchar Jimmy O. , Pickett John A. , Khan Zeyaur R.
Published: February 2022

Production of cereal crops in sub-Saharan Africa is threatened by parasitic striga weeds and attack by stemborers and the invasive fall armyworm (FAW), compounded by increasing hot and dry conditions. A climate-smart push-pull technology (PPT) significantly reduces effects of these biotic challenges. To improve further resilience of the system to climate change, more adapted and suitable companion plants were identified and integrated in a new version of PPT, termed ‘third generation PPT’. Our study evaluates field performance and farmer opinions of this new version in comparison with the earlier version, climate-smart PPT, and farmers’ own practices of growing maize in controlling stemborers, FAW, and striga weeds. Trials were conducted across five locations in western Kenya for two cropping seasons in the year 2019 following a one-farm one-replicate completely randomized design. We assessed infestation on striga, stemborers, and FAW, and yield performance of the three cropping systems. We also sought the opinions of the hosting farmers through semi-structured questionnaires that were administered through individual interviews. Both PPT plots recorded significantly (P < 0.05) lower striga count, FAW, and stemborer damage, and higher grain yield than in plots that followed farmers’ own practices. There was no statistically significant difference between the two PPT plots except for stemborer damage for which the third generation PPT recorded higher damage than the climate-smart PPT. However, farmers preferred the third generation PPT for important traits possessed by its companion plants which their counterparts in climate-smart PPT are deficient. The cultivar Xaraes was rated as ‘very good’ for resistance to spider mites, biomass yield, and drought tolerance while Desmodium incanum was rated ‘very good’ for seed production and drought tolerance. The third generation PPT is based on companion crops that are more resilient to hot and dry conditions which are increasing rapidly in prevalence with climate change. This version therefore presents a better option to upscale the technology and meet different needs of farmers especially in arid and semi-arid conditions.
The long-term effect of over-supplementation on recovered populations: why restraint is a virtue
Authors: Adamski Paweł , Ćmiel Adam M.
Published: February 2022

We present a long-term analysis of the results of the Apollo butterflyParnassius apollorecovery project in the Pieniny National Park, southern Poland, using a classical population ecology model. Six possible theoretical models of changes in population abundance were constructed and their predictions compared with current data. Models that did not take into account supplementation with captive-reared individuals provided the best fit to the population growth pattern during recovery. This was probably because of the introduction of captive-reared specimens to sites while habitat reconstruction was taking place. In addition, we provide data supporting the hypothesis that a significant reduction in the habitat's carrying capacity occurred during the restoration project, probably as a result of the population being over-supplemented with captive-reared individuals. Our analysis shows that for a recovery project to be successful, captive breeding and habitat restoration should be properly coordinated.
A randomized controlled trial of supervised remotely-delivered attention bias modification for posttraumatic stress disorder
Authors: Alon Yaron , Azriel Omer , Pine Daniel S. , Bar-Haim Yair
Published: February 2022

Background

Many individuals with posttraumatic stress disorder (PTSD) have limited access to first-line treatments, warranting the development of remotely-delivered treatments. Attention bias modification (ABM), targeting perturbed threat-related attentional patterns, shows promise when delivered in-person. However, previous studies found ABM to be ineffective when delivered remotely. Randomized clinical trials usually applied two variations of ABM: ABM away from threat or attention control training (ACT) balancing attention between threat-related and neutral stimuli. We tested remotely-delivered ACT/ABM with tighter supervision and video-based interactions that resemble in-clinic protocols. We expected to replicate the results of in-clinic trials, in which ACT outperformed ABM for PTSD.

Methods

In this double-blinded, parallel-group randomized controlled trial, 60 patients diagnosed with PTSD were randomized (ABM n = 30; ACT n = 30). Patients performed eight bi-weekly remotely-delivered supervised ABM/ACT sessions. Symptoms were assessed pre- and post-treatment with Clinician-Administered PTSD Scale 5 (CAPS-5) severity score and PTSD diagnosis as the primary outcomes. Current depressive episode, current anxiety-related comorbidity, and time elapsed since the trauma were examined as potential moderators of treatment outcome.

Results

Significant decrease in CAPS-5 severity scores and PTSD diagnosis was observed following both ACT and ABM with no between-group difference. Patients without depression or whose trauma occurred more recently had greater symptom reduction in the ACT than the ABM group.

Conclusions

Contrary to our expectation, symptoms decreased similarly following ACT and ABM. Moderator analyses suggest advantage for ACT in non-depressed patients and patients whose trauma occurred more recently. Further refinements in remotely-delivered ABM/ACT may be needed.
AN ASYMPTOTIC THEORY FOR LEAST SQUARES MODEL AVERAGING WITH NESTED MODELS
Authors: Fang Fang , Yuan Chaoxia , Tian Wenling
Published: February 2022

Theoretical results of frequentist model averaging mainly focus on asymptotic optimality and asymptotic distribution of the model averaging estimator. However, even for basic least squares model averaging, many theoretical problems have not been well addressed yet. This article discusses asymptotic properties of a class of least squares model averaging methods with nested candidate models that includes the Mallows model averaging (MMA) of Hansen (2007, Econometrica 75, 1175–1189) as a special case. Two scenarios are considered: (i) all candidate models are under-fitted; and (ii) the true model is included in the candidate models. We find that in the first scenario, the least squares model averaging method asymptotically assigns weight one to the largest candidate model and the resulting model averaging estimator is asymptotically normal. In the second scenario with a slightly special weight space, if the penalty factor in the weight selection criterion is diverging with certain order, the model averaging estimator is asymptotically optimal by putting weight one to the true model. However, MMA with fixed model dimensions is not asymptotically optimal since it puts nonnegligible weights to over-fitted models. The theoretical results are clearly summarized with their restrictions, and some critical implications are discussed. Monte Carlo simulations confirm our theoretical results.
EXPLORING AN ELICITED IMITATION TASK AS A MEASURE OF HERITAGE LANGUAGE PROFICIENCY
Authors: Solon Megan , Park Hae In , Dehghan-Chaleshtori Marzieh , Carver Carly , Long Avizia Y.
Published: February 2022

This study examines a 30-item Spanish elicited imitation task (EIT) as a measure of global language proficiency for heritage language (HL) learners of Spanish. Results from Rasch modeling suggest that, while EIT scores demonstrated excellent reliability, the ability of much of the HL sample far exceeded the difficulty of the items. Differential item functioning analysis revealed that several items functioned differently for the present study’s HL sample than for the second language learners from a prior study. Additionally, although EIT scores were strongly correlated with another proficiency measure for the present HL sample (e.g., the Diploma de español como lengua extranjera or DELE), common-person equating suggested that the EIT and the DELE may measure different latent variables. Overall, the results provide evidence of the EIT’s utility as a proficiency assessment tool for research on HL learners, however, with limitations and the need for additional analyses discussed.
LEARNING ENGLISH IN TODAY’S GLOBAL WORLD
Authors: Köylü Zeynep , Tracy-Ventura Nicole
Published: February 2022

In comparative studies focusing on context of learning, the main contexts under investigation have been study abroad (SA), at-home formal instruction (AH), and domestic immersion (IM). With the global status of English and its burgeoning popularity as a medium of instruction in countries where English only holds the status of a lingua franca, a new SA context has emerged. This study compares the L2 learning of English in this new English as a lingua franca study abroad (ELFSA) context to Anglophone SA and AH in terms of oral and written complexity, accuracy, and fluency gains. Participants’ perceptions of contextual differences concerning the amount of language contact, use, development, and their views toward English are also explored qualitatively. Apart from indicating equal development on most CAF measures after a semester, the qualitative findings highlight ELFSA as providing a low-anxiety atmosphere that helps sojourners gain ownership of English. Thus, ELFSA emerges as an appealing study abroad context for future sojourners.
The Experience of Older Adults Socially Distancing during the Early Stages of the COVID-19 Pandemic
Authors: Nelson Heather , Ziefflie Beverlee , Norton Deborah , Page Susan , Unique Rhonda , Mayer Paula
Published: February 2022

During the early stages of the COVID-19 pandemic, individuals were asked to stay home and restrict outings to limit the spread of the virus. Physical isolation was particularly emphasized for older adults over the age of 60 who, because of their age and related medical conditions, were at increased risk of severe disease and death from the virus. This led to reduced spread of the virus but also to social and emotional health challenges for older adults. Protecting the physical health of older adults was of the utmost importance during the pandemic but supporting social and mental health must not be overlooked. This patient-oriented qualitative study involved 40 interviews with older adults, conducted in the early stages of the pandemic, followed by a thematic analysis. Three themes were derived from the findings: subverted life plan, emotional impacts, and creating a path forward. The findings from this study will help inform current physical and social distancing guidelines during the ongoing COVID-19 pandemic. Moreover, findings indicate that social and emotional challenges with ongoing physical and social isolation must be taken into consideration for future pandemics.
Chevalier mult estes guariz and the ‘pre-chansonnier’ vernacular lyric
Authors: JACOB URI
Published: February 2022

Chansonniers copied from the thirteenth and the fourteenth centuries are the earliest extant sources to include an extensive corpus of lyrics in European vernacular languages. However, contemporary literary sources refer to the existence of earlier books of vernacular lyrics, and a handful of notated lyrics survive from as early as the twelfth century. This article explores a certain type of notated song that predates the relatively well-documented chansonnier tradition by some decades, specifically focusing on the case study of the crusader recruitment song Chevalier mult estes guariz (RS 1548a), composed around the mid-1140s. Probably the earliest extant copy of an Old French lyric (with or without musical notation), this unicum is distinct from songs of the kind preserved in the chansonniers in several respects, especially in its musical form, its manuscript appearance and its intended use in the Middle Ages. I examine this song from several angles, including its crusading theme, provenance, authorship, manuscript presentation, musical construction, intended audience, and the broader contexts of its composition and copying. Such close examination of a single song not only offers insights into the context of an early tradition of written-out vernacular monophony but also casts new light on the origins of the later chansonnier tradition.
Command Responsibility in the Times ofTokhang: Defining Military-likeness under Article 28(a) of the Rome Statute
Authors: PANGALANGAN Raphael Lorenzo A.
Published: February 2022

President Rodrigo Duterte won on a law-and-order campaign promise to fatten the fish in Manila Bay with the corpses of criminals. By the time the Philippines withdrew from the Rome Statute, the body count stood at a reported 30,000, a fifth of whom were openly killed in Philippine National Police (PNP) anti-drug operations. Duterte has since been accused of Crimes Against Humanity,inter alia, as “a person effectively acting as a military commander” under Article 28(a) of the Rome Statute for failing to prevent, repress, and report the crimes of his police subordinates. This study tests the veracity of that claim. It seeks to determine whether Duterte, as the Chief Executive and overall superior of the PNP – statutorily, a civilian group – may be held liable as a military-like commander under the doctrine of command responsibility. At the core of this query lies a singular concern far from simple: the meaning of military-likeness.
Abnormal photoplethysmography waveforms are associated with	chemotherapy induced neuropathy
Authors: Bryce Yolanda , Santos-Martin Ernesto , Ziv Etay , Gonzalez-Aguirre Adrian , Moussa Amgad , Friedman Adie , Maybody Majid
Published: February 2022

Summary: Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-dependent adverse event of many chemotherapy agents that affects autonomic, motor, and sensory nerve fibers. The purpose of this study is to describe abnormal photoplethysmography waveforms (PPGs) in the setting of CIPN in cancer patients screened for peripheral arterial disease (PAD), which to our knowledge has not been previously described. Patients and methods: 147 patients who underwent vascular physiologic testing in evaluation for PAD with an ankle brachial index (ABI) or toe brachial index (TBI), segmental pressures, pulse volume recordings, and toe PPGs, in a tertiary cancer center’s vascular lab between January 1, 2019 and January 31, 2021 were included in the study. Results: Odds ratio analysis demonstrates 3 times increased odds of abnormal PPGs in patients with PAD (OR 3.2256 95% CI 1.523–6.832, p=0.002), 7 times increased odds of abnormal PPGs in patients with CIPN (OR 7.802 95% CI 3.606–16.880, p<0.001), 9 times increased odds of abnormal PPGs in patients with both CIPN and PAD (9.895 95% CI 2.643–37.043, p=0.001), and 7 times increased odds of abnormal PPGs in patients with chemotherapy agent known to cause CIPN (7.821 95% CI 3.619–16.902, p<0.001). Logistic regression demonstrated that PAD (coefficient 1.171 std. error 0.383 wald 9.354 p=0.002), CIPN (coefficient 2.054 std. error 0.394 wald 27.227 p<0.001), and chemo agent known to cause CIPN (coefficient 2.057 std. error 0.393 wald 27.370 p<0.001) were all predictors of abnormal PPGs. Conclusions: CIPN had greater odds for abnormal PPGs than PAD. Additional larger studies are needed to assess if PPG analysis could be utilized to assess for early diagnosis of CIPN.
Autonomous Wintertime Observations of Air‐Sea Exchange in the Gulf Stream Reveal a Perfect Storm for Ocean CO2 Uptake
Authors: Nickford S. , Palter J. B. , Donohue K. , Fassbender A. J. , Gray A. R. , Long J. , Sutton A. J. , Bates N. R. , Takeshita Y.
Published: February 2022

A scarcity of wintertime observations of surface ocean carbon dioxide partial pressure (pCO2) in and near the Gulf Stream creates uncertainty in the magnitude of the regional carbon sink and its controlling mechanisms. Recent observations from an Uncrewed Surface Vehicle (USV), outfitted with a payload to measure surface ocean and lower atmosphere pCO2, revealed sharp gradients in ocean pCO2 across the Gulf Stream. Surface ocean pCO2 was lower by ∼50 μatm relative to the atmosphere in the subtropical mode water (STMW) formation region. This undersaturation combined with strong wintertime winds allowed for rapid ocean uptake of CO2, averaging −11.5 mmol m−2 day−1 during the February 2019 USV mission. The unique timing of this mission revealed active STMW formation. The USV proved to be a useful tool for CO2 flux quantification in the poorly observed, dynamic western boundary current environment.
Earthquake‐Derived Seismic Velocity Changes During the 2018 Caldera Collapse of Kīlauea Volcano
Authors: Hotovec‐Ellis Alicia J. , Shiro Brian R. , Shelly David R. , Anderson Kyle R. , Haney Matthew M. , Thelen Weston A. , Montgomery‐Brown Emily K. , Johanson Ingrid A.
Published: February 2022

The 2018 Kīlauea caldera collapse produced extraordinary sequences of seismicity and deformation, with 62 episodic collapse events which significantly altered the landscape of the summit region. Despite decades of focused scientific studies at Kīlauea, detailed information about the internal structure of the volcano is limited. Recently developed techniques in seismic interferometry can be used to monitor the internal structure of an active volcano more directly by detecting subtle spatiotemporal changes in seismic wave velocity, but their utility relies on accurate interpretations of the underlying phenomena causing those velocity changes. Here, we retrospectively apply repeating‐earthquake‐based seismic interferometry to the 2018 Kīlauea eruption sequence. We find that seismic velocities changed over two distinct time scales: a sudden increase followed by a slower decrease in velocity in the hours following each collapse event, and a gradual, long‐term decrease in velocity over several weeks that ceased approximately 1 month prior to the end of the eruption. Modeling suggests that short‐term changes can be explained by magma reservoir pressurization which specifically closed vertical ring fractures. Long‐term changes are related to subsidence of the caldera and likely include the influence of inelastic strain from the formation of new fractures. These observations provide new insights into the evolution of Kīlauea during its progressive collapse and will inform future interpretations for near‐real‐time monitoring at hazardous volcanoes around the world using similar techniques, especially where a dominant fracture orientation is present.
Using Hematite to Decipher Past Climates and Environments
Authors: Jiang Zhaoxia , Liu Qingsong
Published: February 2022

The magnetic and color properties of the mineral hematite give clues to past environmental conditions and is being used for paleoclimatic reconstruction.
Why do humans undergo an adiposity rebound? Exploring links with the energetic costs of brain development in childhood using MRI-based 4D measures of total cerebral blood flow
Authors: Aronoff Jacob E. , Ragin Ann , Wu Can , Markl Michael , Schnell Susanne , Shaibani Ali , Blair Clancy , Kuzawa Christopher W.
Published: February 2022

Background

Individuals typically show a childhood nadir in adiposity termed the adiposity rebound (AR). The AR serves as an early predictor of obesity risk, with early rebounders often at increased risk; however, it is unclear why this phenomenon occurs, which could impede understandings of weight gain trajectories. The brain’s energy requirements account for a lifetime peak of 66% of the body’s resting metabolic expenditure during childhood, around the age of the AR, and relates inversely to weight gain, pointing to a potential energy trade-off between brain development and adiposity. However, no study has compared developmental trajectories of brain metabolism and adiposity in the same individuals, which would allow a preliminary test of a brain-AR link.

Methods

We used cubic splines and generalized additive models to compare age trajectories of previously collected MRI-based 4D flow measures of total cerebral blood flow (TCBF), a proxy for cerebral energy use, to the body mass index (BMI) in a cross-sectional sample of 82 healthy individuals (0–60 years). We restricted our AR analysis to pre-pubertal individuals (0–12 years,n = 42), predicting that peak TCBF would occur slightly after the BMI nadir, consistent with evidence that lowest BMI typically precedes the nadir in adiposity.

Results

TCBF and the BMI showed inverse trajectories throughout childhood, while the estimated age at peak TCBF (5.6 years) was close but slightly later than the estimated age of the BMI nadir (4.9 years).

Conclusions

The timing of peak TCBF in this sample points to a likely concordance between peak brain energetics and the nadir in adiposity. Inverse age trajectories between TCBF and BMI support the hypothesis that brain metabolism is a potentially important influence on early life adiposity. These findings also suggest that experiences influencing the pattern of childhood brain energy use could be important predictors of body composition trajectories.
Pharmacological inhibition of Ref-1 enhances the therapeutic sensitivity of papillary thyroid carcinoma to vemurafenib
Authors: Hu Linfei , Zhang Jun , Tian Mengran , Kang Ning , Xu Guangwei , Zhi Jingtai , Ruan Xianhui , Hou Xiukun , Zhang Wei , Yi Jiaoyu , Ma Weike , Chang Luchen , Tang Tao , Zheng Xiangqian , Wei Xi , Gao Ming
Published: February 2022

The use of the BRAF inhibitor vemurafenib exhibits drug resistance in the treatment of thyroid cancer (TC), and finding more effective multitarget combination therapies may be an important solution. In the present study, we found strong correlations between Ref-1 high expression and BRAF mutation, lymph node metastasis, and TNM stage. The oxidative stress environment induced by structural activation of BRAF upregulates the expression of Ref-1, which caused intrinsic resistance of PTC to vemurafenib. Combination inhibition of the Ref-1 redox function and BRAF could enhance the antitumor effects of vemurafenib, which was achieved by blocking the action of Ref-1 on BRAF proteins. Furthermore, combination treatment could cause an overload of autophagic flux via excessive AMPK protein activation, causing cell senescence and cell death in vitro. And combined administration of Ref-1 and vemurafenib in vivo suppressed PTC cell growth and metastasis in a cell-based lung metastatic tumor model and xenogeneic subcutaneous tumor model. Collectively, our study provides evidence that Ref-1 upregulation via constitutive activation of BRAF in PTC contributes to intrinsic resistance to vemurafenib. Combined treatment with a Ref-1 redox inhibitor and a BRAF inhibitor could make PTC more sensitive to vemurafenib and enhance the antitumor effects of vemurafenib by further inhibiting the MAPK pathway and activating the excessive autophagy and related senescence process.
Increased MCL-1 synthesis promotes irradiation-induced nasopharyngeal carcinoma radioresistance via regulation of the ROS/AKT loop
Authors: Liang Ying-Ying , Niu Fei-Yu , Xu An-An , Jiang Li-Li , Liu Chun-shan , Liang Hui-ping , Huang Yu-Fan , Shao Xun-Fan , Mo Zhi-Wen , Yuan Ya-Wei
Published: February 2022

Worldwide, nasopharyngeal carcinoma (NPC) is a rare head and neck cancer; however, it is a common malignancy in southern China. Radiotherapy is the most important treatment strategy for NPC. However, although radiotherapy is a strong tool to kill cancer cells, paradoxically it also promotes aggressive phenotypes. Therefore, we mimicked the treatment process in NPC cells in vitro. Upon exposure to radiation, a subpopulation of NPC cells gradually developed resistance to radiation and displayed cancer stem-cell characteristics. Radiation-induced stemness largely depends on the accumulation of the antiapoptotic myeloid cell leukemia 1 (MCL-1) protein. Upregulated MCL-1 levels were caused by increased stability and more importantly, enhanced protein synthesis. We showed that repeated ionizing radiation resulted in persistently enhanced reactive oxygen species (ROS) production at a higher basal level, further promoting protein kinase B (AKT) signaling activation. Intracellular ROS and AKT activation form a positive feedback loop in the process of MCL-1 protein synthesis, which in turn induces stemness and radioresistance. AKT/MCL-1 axis inhibition attenuated radiation-induced resistance, providing a potential target to reverse radiation therapy-induced radioresistance.
The regulation, function, and role of lipophagy, a form of selective autophagy, in metabolic disorders
Authors: Zhang Sheng , Peng Xueqiang , Yang Shuo , Li Xinyu , Huang Mingyao , Wei Shibo , Liu Jiaxing , He Guangpeng , Zheng Hongyu , Yang Liang , Li Hangyu , Fan Qing
Published: February 2022

Autophagy is a conserved method of quality control in which cytoplasmic contents are degraded via lysosomes. Lipophagy, a form of selective autophagy and a novel type of lipid metabolism, has recently received much attention. Lipophagy is defined as the autophagic degradation of intracellular lipid droplets (LDs). Although much remains unknown, lipophagy appears to play a significant role in many organisms, cell types, metabolic states, and diseases. It participates in the regulation of intracellular lipid storage, intracellular free lipid levels (e.g., fatty acids), and energy balance. However, it remains unclear how intracellular lipids regulate autophagy. Impaired lipophagy can cause cells to become sensitive to death stimuli and may be responsible for the onset of a variety of diseases, including nonalcoholic fatty liver disease and metabolic syndrome. Like autophagy, the role of lipophagy in cancer is poorly understood, although analysis of specific autophagy receptors has helped to expand the diversity of chemotherapeutic targets. These studies have stimulated increasing interest in the role of lipophagy in the pathogenesis and treatment of cancer and other human diseases.
MYC-activated RNA N6-methyladenosine reader IGF2BP3 promotes cell proliferation and metastasis in nasopharyngeal carcinoma
Authors: Du Mingyu , Peng Yi , Li Yang , Sun Wenyue , Zhu Huanfeng , Wu Jing , Zong Dan , Wu Lirong , He Xia
Published: February 2022

N6-Methyladenosine (m6A) modification is the most abundant RNA modification in eukaryotic cells. IGF2BP3, a well-known m6A reader, is deregulated in many cancers, but its role in nasopharyngeal carcinoma (NPC) remains unclear. In this work, IGF2BP3 was upregulated in NPC tissues and cells. The high level of IGF2BP3 was positively related to late clinical stages, node metastasis, and poor outcomes. Moreover, IGF2BP3 accelerated NPC cell tumor progression and metastasis in vitro and vivo. Upstream mechanism analyses indicated that the high expression of IGF2BP3 in head and neck tumors was mainly due to mRNA level amplification. Luciferase assay and chromatin immunoprecipitation assay (CHIP) depicted that MYC was effectively bound to the promoter of IGF2BP3, thereby improving its transcriptional activity. Results also showed that IGF2BP3 was not only positively correlated with KPNA2 expression but also modulated the expression of KPNA2. m6A RNA immunoprecipitation (MeRIP) and RNA stability experiments verified that silencing IGF2BP3 significantly inhibited the m6A modification level of KPNA2, thereby stabilizing the mRNA stability of KPNA2. Rescue experiments proved that the effect of inhibiting or overexpressing IGF2BP3 on NPC cells was partly reversed by KPNA2. Collectively, MYC-activated IGF2BP3 promoted NPC cell proliferation and metastasis by influencing the stability of m6A-modified KPNA2. Our findings offer new insights that IGF2BP3 may serve as a new molecular marker and potential therapeutic target for NPC treatment.
Single-cell RNA sequencing identifies an Il1rn+/Trem1+ macrophage subpopulation as a cellular target for mitigating the progression of thoracic aortic aneurysm and dissection
Authors: Liu Xuanyu , Chen Wen , Zhu Guoyan , Yang Hang , Li Wenke , Luo Mingyao , Shu Chang , Zhou Zhou
Published: February 2022

Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening condition characterized by medial layer degeneration of the thoracic aorta. A thorough understanding of the regulator changes during pathogenesis is essential for medical therapy development. To delineate the cellular and molecular changes during the development of TAAD, we performed single-cell RNA sequencing of thoracic aortic cells from β-aminopropionitrile-induced TAAD mouse models at three time points that spanned from the early to the advanced stages of the disease. Comparative analyses were performed to delineate the temporal dynamics of changes in cellular composition, lineage-specific regulation, and cell–cell communications. Excessive activation of stress-responsive and Toll-like receptor signaling pathways contributed to the smooth muscle cell senescence at the early stage. Three subpopulations of aortic macrophages were identified, i.e., Lyve1+ resident-like, Cd74high antigen-presenting, and Il1rn+/Trem1+ pro-inflammatory macrophages. In both mice and humans, the pro-inflammatory macrophage subpopulation was found to represent the predominant source of most detrimental molecules. Suppression of macrophage accumulation in the aorta with Ki20227 could significantly decrease the incidence of TAAD and aortic rupture in mice. Targeting the Il1rn+/Trem1+ macrophage subpopulation via blockade of Trem1 using mLR12 could significantly decrease the aortic rupture rate in mice. We present the first comprehensive analysis of the cellular and molecular changes during the development of TAAD at single-cell resolution. Our results highlight the importance of anti-inflammation therapy in TAAD, and pinpoint the macrophage subpopulation as the predominant source of detrimental molecules for TAAD. Targeting the IL1RN+/TREM1+ macrophage subpopulation via blockade of TREM1 may represent a promising medical treatment.
Versatile metal-wire waveguides for broadband terahertz signal processing and multiplexing
Authors: Dong Junliang , Tomasino Alessandro , Balistreri Giacomo , You Pei , Vorobiov Anton , Charette Étienne , Le Drogoff Boris , Chaker Mohamed , Yurtsever Aycan , Stivala Salvatore , Vincenti Maria A. , De Angelis Costantino , Kip Detlef , Azaña José , Morandotti Roberto
Published: February 2022

Waveguides play a pivotal role in the full deployment of terahertz communication systems. Besides signal transporting, innovative terahertz waveguides are required to provide versatile signal-processing functionalities. Despite fundamental components, such as Bragg gratings, have been recently realized, they typically rely on complex hybridization, in turn making it extremely challenging to go beyond the most elementary functions. Here, we propose a universal approach, in which multiscale-structured Bragg gratings can be directly etched on metal-wires. Such an approach, in combination with diverse waveguide designs, allows for the realization of a unique platform with remarkable structural simplicity, yet featuring unprecedented signal-processing capabilities. As an example, we introduce a four-wire waveguide geometry, amenable to support the low-loss and low-dispersion propagation of polarization-division multiplexed terahertz signals. Furthermore, by engraving on the wires judiciously designed Bragg gratings based on multiscale structures, it is possible to independently manipulate two polarization-division multiplexed terahertz signals. This platform opens up new exciting perspectives for exploiting the polarization degree of freedom and ultimately boosting the capacity and spectral efficiency of future terahertz networks.
Hippocampal ensembles represent sequential relationships among an extended sequence of nonspatial events
Authors: Shahbaba Babak , Li Lingge , Agostinelli Forest , Saraf Mansi , Cooper Keiland W. , Haghverdian Derenik , Elias Gabriel A. , Baldi Pierre , Fortin Norbert J.
Published: February 2022

The hippocampus is critical to the temporal organization of our experiences. Although this fundamental capacity is conserved across modalities and species, its underlying neuronal mechanisms remain unclear. Here we recorded hippocampal activity as rats remembered an extended sequence of nonspatial events unfolding over several seconds, as in daily life episodes in humans. We then developed statistical machine learning methods to analyze the ensemble activity and discovered forms of sequential organization and coding important for order memory judgments. Specifically, we found that hippocampal ensembles provide significant temporal coding throughout nonspatial event sequences, differentiate distinct types of task-critical information sequentially within events, and exhibit theta-associated reactivation of the sequential relationships among events. We also demonstrate that nonspatial event representations are sequentially organized within individual theta cycles and precess across successive cycles. These findings suggest a fundamental function of the hippocampal network is to encode, preserve, and predict the sequential order of experiences.
Optical charge injection and coherent control of a quantum-dot spin-qubit emitting at telecom wavelengths
Authors: Dusanowski Łukasz , Nawrath Cornelius , Portalupi Simone L. , Jetter Michael , Huber Tobias , Klembt Sebastian , Michler Peter , Höfling Sven
Published: February 2022

Solid-state quantum emitters with manipulable spin-qubits are promising platforms for quantum communication applications. Although such light-matter interfaces could be realized in many systems only a few allow for light emission in the telecom bands necessary for long-distance quantum networks. Here, we propose and implement an optically active solid-state spin-qubit based on a hole confined in a single InAs/GaAs quantum dot grown on an InGaAs metamorphic buffer layer emitting photons in the C-band. We lift the hole spin-degeneracy using an external magnetic field and demonstrate hole injection, initialization, read-out and complete coherent control using picosecond optical pulses. These results showcase a solid-state spin-qubit platform compatible with preexisting optical fiber networks.
SMAP is a pipeline for sample matching in proteogenomics
Authors: Li Ling , Niu Mingming , Erickson Alyssa , Luo Jie , Rowbotham Kincaid , Guo Kai , Huang He , Li Yuxin , Jiang Yi , Hur Junguk , Liu Chunyu , Peng Junmin , Wang Xusheng
Published: February 2022

The integration of genomics and proteomics data (proteogenomics) holds the promise of furthering the in-depth understanding of human disease. However, sample mix-up is a pervasive problem in proteogenomics because of the complexity of sample processing. Here, we present a pipeline for Sample Matching in Proteogenomics (SMAP) to verify sample identity and ensure data integrity. SMAP infers sample-dependent protein-coding variants from quantitative mass spectrometry (MS), and aligns the MS-based proteomic samples with genomic samples by two discriminant scores. Theoretical analysis with simulated data indicates that SMAP is capable of uniquely matching proteomic and genomic samples when ≥20% genotypes of individual samples are available. When SMAP was applied to a large-scale dataset generated by the PsychENCODE BrainGVEX project, 54 samples (19%) were corrected. The correction was further confirmed by ribosome profiling and chromatin sequencing (ATAC-seq) data from the same set of samples. Our results demonstrate that SMAP is an effective tool for sample verification in a large-scale MS-based proteogenomics study. SMAP is publicly available at https://github.com/UND-Wanglab/SMAP, and a web-based version can be accessed at https://smap.shinyapps.io/smap/.
Differential activation mechanisms of lipid GPCRs by lysophosphatidic acid and sphingosine 1-phosphate
Authors: Liu Shian , Paknejad Navid , Zhu Lan , Kihara Yasuyuki , Ray Manisha , Chun Jerold , Liu Wei , Hite Richard K. , Huang Xin-Yun
Published: February 2022

Lysophospholipids are bioactive lipids and can signal through G-protein-coupled receptors (GPCRs). The best studied lysophospholipids are lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P). The mechanisms of lysophospholipid recognition by an active GPCR, and the activations of lysophospholipid GPCR–G-protein complexes remain unclear. Here we report single-particle cryo-EM structures of human S1P receptor 1 (S1P1) and heterotrimeric Gi complexes formed with bound S1P or the multiple sclerosis (MS) treatment drug Siponimod, as well as human LPA receptor 1 (LPA1) and Gi complexes in the presence of LPA. Our structural and functional data provide insights into how LPA and S1P adopt different conformations to interact with their cognate GPCRs, the selectivity of the homologous lipid GPCRs for S1P versus LPA, and the different activation mechanisms of these GPCRs by LPA and S1P. Our studies also reveal specific optimization strategies to improve the MS-treating S1P1-targeting drugs.
On-skin ultrathin and stretchable multifunctional sensor for smart healthcare wearables
Authors: Zhang Shipeng , Chhetry Ashok , Zahed Md. Abu , Sharma Sudeep , Park Chani , Yoon Sanghyuk , Park Jae Y.
Published: February 2022

The flexible and stretchable multifunctional sensors for the precise monitoring of the human physiological health indicators is an emerging requirement of next-generation electronics. However, the integration of multifunctional sensors into a common substrate for simultaneous detection of such signals without interfering with each other is the most challenging work. Here, we propose MXene-Ti3C2Tx and 3, 4-ethylene dioxythiophene (EDOT) deposited on laser-induced graphene (LIG/MXene-Ti3C2Tx@EDOT) composite-based flexible and stretchable multifunctional sensors for strain, temperature, and electrocardiogram (ECG) monitoring. In-situ electrophoretic deposition (EPD) of MXene-Ti3C2Tx@EDOT composite into LIG outperforms high strain sensitivity of 2,075, temperature coefficient of resistance (TCR) of 0.86%, and low skin-contact impedance. The sensor platform is integrated into an ultrathin and highly resilient polystyrene-block-poly(ethylene-ran-butylene)-block-polystyrene (SEBS). Finally, we demonstrate on-site detection of human body-induced deformations and physiological health indicators, such as temperature and ECG. The proposed approach paves a promising route to future wearables for smart skin and healthcare applications.