bluuebunny/crossref_metadata_2025 huggingface dataset:
Persistent accelerated epigenetic ageing in a longitudinal cohort of vertically infected HIV-positive adolescents
Authors: Heany Sarah J. , Levine Andrew J. , Lesosky Maia , Phillips Nicole , Fouche Jean-Paul , Myer Landon , Zar Heather J. , Stein Dan J. , Horvath Steve , Hoare Jacqueline
Published: May 2023

We have previously shown accelerated ageing in adolescents perinatally infected with HIV (PHIV +), based on discrepancies between epigenetic and chronological age. The current study examines follow-up longitudinal patterns of epigenetic ageing and the association of epigenetic ageing with cognition as well as whole brain structure changes in PHIV + and healthy controls enrolled in the Cape Town Adolescent Antiretroviral Cohort Study (CTAAC). The Illumina EPIC array was used to generate blood DNA methylation data from 60 PHIV + adolescents and 36 age-matched controls aged 9–12 years old at baseline and again at a 36-month follow-up. Epigenetic clock software estimated two measures of epigenetic age acceleration: extrinsic epigenetic accelerated ageing (EEAA) and age acceleration difference (AAD) at both time points. At follow-up, each participant completed neuropsychological testing, structural magnetic resonance imaging, and diffusion tensor imaging. At follow-up, PHIV infection remains associated with increased EEAA and AAD. Accelerated epigenetic ageing remained positively associated with viral load and negatively associated with CD4 ratio. EEAA was positively associated with whole brain grey matter volume and alterations in whole brain white matter integrity. AAD and EEAA were not associated with cognitive function within the PHIV + group. Measures of epigenetic ageing, as detected in DNA methylation patterns, remain increased in PHIV + adolescents across a 36-month period. Associations between epigenetic ageing measures, viral biomarkers, and alterations in brain micro- and macrostructure also persist at 36-month follow-up. Further study should determine if epigenetic age acceleration is associated with cognitive functional changes due to brain alterations in later life.
MemeTector: enforcing deep focus for meme detection
Authors: Koutlis Christos , Schinas Manos , Papadopoulos Symeon
Published: May 2023

Image memes and specifically their widely known variation image macros are a special new media type that combines text with images and are used in social media to playfully or subtly express humor, irony, sarcasm and even hate. It is important to accurately retrieve image memes from social media to better capture the cultural and social aspects of online phenomena and detect potential issues (hate-speech, disinformation). Essentially, the background image of an image macro is a regular image easily recognized as such by humans but cumbersome for the machine to do so due to feature map similarity with the complete image macro. Hence, accumulating suitable feature maps in such cases can lead to deep understanding of the notion of image memes. To this end, we propose a methodology, called visual part utilization, that utilizes the visual part of image memes as instances of the regular image class and the initial image memes as instances of the image meme class to force the model to concentrate on the critical parts that characterize an image meme. Additionally, we employ a trainable attention mechanism on top of a standard ViT architecture to enhance the model’s ability to focus on these critical parts and make the predictions interpretable. Several training and test scenarios involving web-scraped regular images of controlled text presence are considered for evaluating the model in terms of robustness and accuracy. The findings indicate that light visual part utilization combined with sufficient text presence during training provides the best and most robust model, surpassing state of the art. Source code and dataset are available at https://github.com/mever-team/memetector.
Lifelong Learning in the Educational Setting: A Systematic Literature Review
Authors: Thwe Win Phyu , Kálmán Anikó
Published: May 2023

This systematic literature review aimed to provide updated information on lifelong learning in educational research by examining theoretical documents and empirical papers from 2000 to 2022. This review sought to identify concepts, theories, and research trends and methods linked to lifelong learning in educational research in different countries. Our review findings showed that theoretical papers, such as reports, policies, and concepts of lifelong learning, are generally much more extensive than empirical studies. Word cloud analysis revealed that the most prominent concepts were lifelong learning skills, lifelong learning competencies, and the three types of lifelong learning (formal, nonformal, and informal). Following the inductive analysis, this study investigated three common research trends: conceptual framework or policies of lifelong learning, lifelong learning abilities, and influencing factors of lifelong learning and/or lifelong learning abilities. Regarding methodology, this study identified only three studies that used mixed methods, which is insufficient in the field. In addition, heterogeneity was also observed between research instruments in lifelong learning. Different data analysis techniques can be applied in this field, including content analysis, descriptive analysis, and inferential analysis. Finally, the participants involved in the examined studies were students, primary and secondary school teachers, undergraduates, postgraduates, student teachers, European Union Lifelong Learning experts, young adults, teacher educators, administrators, and academic staff.
Effect of virtual running with exercise on functionality in pre-frail and frail elderly people: randomized clinical trial
Authors: Mollà-Casanova Sara , Muñoz-Gómez Elena , Sempere-Rubio Núria , Inglés Marta , Aguilar-Rodríguez Marta , Page Álvaro , López-Pascual Juan , Serra-Añó Pilar
Published: May 2023

Background

Virtual mirror therapies could increase the results of exercise, since the mirror neuron system produces an activation of motor execution cortical areas by observing actions performed by others. In this way, pre-frail and frail people could use this system to reach an exercise capacity threshold and obtain health benefits.

Aim

The aim of this study is to evaluate the effects of a virtual running (VR) treatment combined with specific physical gait exercise (PE) compared to placebo VR treatment combined with PE on functionality, pain, and muscular tone in pre-frail and frail older persons.

Methods

A single blinded, two-arm, randomised controlled trial design was employed. Thirty-eight participants were divided into two intervention arms: Experimental Intervention (EI) group, in which VR and gait-specific physical exercises were administered and Control Intervention (CI) group, in which a placebo virtual gait and the same exercise programme was administered. Functionality, pain, and tone were assessed.

Results

EI group improved in aerobic capacity, functional lower-limb strength, reaction time, and pain, while CI group remained the same. Regarding static balance and muscle tone, no differences were found for either group. Further analysis is needed to asses VR effectiveness for improving gait, stand-up and sit-down performance and velocity.

Conclusions

Virtual running therapy appears to enhance capacities related with voluntary movements (i.e., aerobic capacity, functional lower-limb strength, and reaction time) and reduce pain.
Self-Generated Buried Submicrocavities for High-Performance Near-Infrared Perovskite Light-Emitting Diode
Authors: Li Jiong , Duan Chenghao , Zhang Qianpeng , Chen Chang , Wen Qiaoyun , Qin Minchao , Chan Christopher C. S. , Zou Shibing , Wei Jianwu , Xiao Zuo , Zuo Chuantian , Lu Xinhui , Wong Kam Sing , Fan Zhiyong , Yan Keyou
Published: May 2023

Embedding submicrocavities is an effective approach to improve the light out-coupling efficiency (LOCE) for planar perovskite light-emitting diodes (PeLEDs). In this work, we employ phenethylammonium iodide (PEAI) to trigger the Ostwald ripening for the downward recrystallization of perovskite, resulting in spontaneous formation of buried submicrocavities as light output coupler. The simulation suggests the buried submicrocavities can improve the LOCE from 26.8 to 36.2% for near-infrared light. Therefore, PeLED yields peak external quantum efficiency (EQE) increasing from 17.3% at current density of 114 mA cm−2 to 25.5% at current density of 109 mA cm−2 and a radiance increasing from 109 to 487 W sr−1 m−2 with low rolling-off. The turn-on voltage decreased from 1.25 to 1.15 V at 0.1 W sr−1 m−2. Besides, downward recrystallization process slightly reduces the trap density from 8.90 × 1015 to 7.27 × 1015 cm−3. This work provides a self-assembly method to integrate buried output coupler for boosting the performance of PeLEDs.
Production and therapeutic use of astaxanthin in the nanotechnology era
Authors: Abdelazim Karim , Ghit Amr , Assal Dina , Dorra Neamat , Noby Nehad , Khattab Sherine N. , El Feky Shaymaa Essam , Hussein Ahmed
Published: May 2023

Astaxanthin (AXT) is a red fat-soluble pigment found naturally in aquatic animals, plants, and various microorganisms and can be manufactured artificially using chemical catalysis. AXT is a xanthophyll carotenoid with a high potential for scavenging free radicals. Several studies have investigated AXT efficacy against diseases such as neurodegenerative, ocular, skin, and cardiovascular hypertension, diabetes, gastrointestinal and liver diseases, and immuno-protective functions. However, its poor solubility, low stability to light and oxygen, and limited bioavailability are major obstacles hindering its wide applications as a therapeutic agent or nutritional supplement. Incorporating AXT with nanocarriers holds great promise in enhancing its physiochemical properties. Nanocarriers are delivery systems with several benefits, including surface modification, bioactivity, and targeted medication delivery and release. Many approaches have been applied to enhance AXT’s medicinal effect, including solid lipid nanoparticles, nanostructured lipid carriers (NLCs) and polymeric nanospheres. AXT nano-formulations have demonstrated a high antioxidant and anti-inflammatory effect, significantly affecting cancer in different organs. This review summarizes the most recent data on AXT production, characterization, biological activity, and therapeutic usage, focusing on its uses in the nanotechnology era.

Graphical abstract
Statistical Considerations on the Use of RWD/RWE for Oncology Drug Approvals: Overview and Lessons Learned
Authors: Ro Sunhee K. , Zhang Weidong , Jiang Qi , Li Xiaoyun Nicole , Liu Rong , Lu Chengxing Cindy , Marchenko Olga , Sun Linda , Zhao Jing
Published: May 2023

Despite increasing utilization of real-world data (RWD)/real-world evidence (RWE) in regulatory submissions, their application to oncology drug approvals has seen limited success. Real-world data is most commonly summarized as a benchmark control for a single arm study or used to augment the concurrent control in a randomized clinical trial (RCT). While there has been substantial research on usage of RWD/RWE, our goal is to provide a comprehensive overview of their use in oncology drug approval submissions to inform future RWD/RWE study design. We will review examples of applications and summarize the strengths and weaknesses of each example identified by regulatory agencies. A few noteworthy case studies will be reviewed in detail. Operational aspects of RWD/RWE study design/analysis will be also discussed.
Intelligent Recommendation System Based on the Infusion Algorithms with Deep Learning, Attention Network and Clustering
Authors: Li Wenjun
Published: May 2023

The creation and use of big data have driven the intelligent development of e-commerce. The information generated in e-commerce provides a good means to analyze the behavior of users. How to use this information to give customer recommendations, improve the accuracy of recommendations and protect information security is a topic worth studying. For improving the accuracy of recommendations, analysis of users and tagging of resources are key. The current popular session recommendation algorithms face many problems, such as user interest drift which is difficult to be handled by these algorithms, thus affecting the recommendation accuracy. Based on these problems, this paper proposes a recommendation model based on deep learning, applies it to the clustering analysis of user tagging system, and designs a personalized recommendation algorithm for the tagging system. The model proposed in this paper can effectively analyze not only the interests exhibited by users in the current session, but also their potential long-term interests. By comparing the different performances of different datasets, the experimental results of this paper show that the proposed algorithmic model in this paper helps to dig the interests of different users, thus improving the quality of the recommendation system.
Sensitivity analysis of volatile organic compounds to PM2.5 concentrations in a representative industrial city of Korea
Authors: Lee Byeong-Kyu , Choi Sung-Deuk , Shin Byeorie , Kim Seong-Joon , Lee Sang-Jin , Kim Dai-Gon , Lee Greem , Kang Hyun-Jung , Kim Hyo-Seon , Park Dae-Young
Published: May 2023

This study aims to analyze the sensitivity of volatile organic compounds (VOCs) to ambient concentrations of fine particles (PM2.5) in the representative industrial city of Ulsan, Korea. For the calculation of sensitivity coefficients between VOCs and PM2.5 (SVOCs-PM2.5), PM2.5 data were obtained from an air quality monitoring station, and their corresponding 6-h average concentrations of VOCs (alkanes, alkenes, aromatics, and total VOCs) were measured at the Yeongnam intensive air monitoring station. The air monitoring period was divided into the warm-hot season (May–October 2020) and the cold season (November 2020–January 2021). The sensitivity coefficients in the low pollution period of PM2.5 (5 < PM2.5 ≤ 15 μg/m3) were higher and much higher than those in the medium pollution period (15 < PM2.5 ≤ 35 μg/m3) and high pollution period (35 < PM2.5 ≤ 50 μg/m3), respectively. This result indicates that the change ratios of PM2.5 concentrations to the background (PM2.5 ≤ 5 μg/m3) per unit concentration change of VOCs (particularly alkenes) in the high PM2.5 pollution period were much higher than those in the low pollution period. This also indicates that PM2.5 concentrations above 35 μg/m3 were more easily affected by the unit concentration change of VOCs (particularly alkenes) than those below 15 μg/m3. The average sensitivity coefficients during the cold season increased in a range of 23–125% as compared to those during the warm-hot season, except the alkenes-PM2.5 sensitivity with a decrease of 7%. It means that the impact of VOCs (except alkenes) on PM2.5 concentrations was relatively low in the cold season. However, in the cold season, the alkenes might contribute more to PM2.5 formation, particularly over the high pollution period, having PM2.5 > 35 μg/m3, than other VOC groups. The result of this study can be a basis for establishing PM2.5 management plans in industrial cities with large VOC emissions.
Measles outbreak in American Samoa: Alarm to strengthen vaccination post COVID-19 pandemic
Authors: Zaman Kamran , Mishra Shailendra Kumar , Mohanty Aroop , Padhi Bijaya Kumar , Sah Ranjit
Published: May 2023

Highlights
Christianity and the Problem of Free Will
Authors: Vicens Leigh
Published: May 2023

Central to the teachings of Christianity is a puzzle: on the one hand, sin seems something that humans do not do freely and so cannot be not responsible for, since it is unavoidable; on the other hand, sin seems something that we must be responsible for and so do freely, since we are enjoined to repent of it, and since it makes us liable to divine condemnation and forgiveness. After laying out the puzzle in more depth, this Element considers three possible responses—libertarian, soft determinist, and free-will skeptic—and weighs the costs and benefits of each.
Split Phenomenon of Fasciculation between Antagonistic Muscles in Amyotrophic Lateral Sclerosis: An Ultrasound Study
Authors: Hu Nan , Li Yi , Liu Jingwen , Cui Liying , Liu Mingsheng
Published: May 2023

Objective:

Paresis of muscle groups in patients with amyotrophic lateral sclerosis (ALS) tends to present split phenomena. We explored the split phenomenon of fasciculation in multiple antagonistic muscle groups in ALS patients.

Methods:

One hundred and forty ALS patients and 66 non-ALS patients were included from a single ALS center. Muscle ultrasonography (MUS) was performed to detect fasciculation in elbow flexor-extensor, wrist flexor-extensor, knee flexor-extensor, and ankle flexor-extensor. Split phenomena of fasciculation between different antagonistic muscle groups were summarized, and the possible influence factors were analyzed through stratified analysis.

Results:

The frequency of split phenomenon of fasciculation intensity was significantly higher than those of muscle strength (26.1% vs. 7.1% for elbow flexor-extensor, 38.3% vs. 5.7% for wrist flexor-extensor, 37.9% vs. 3.0% for knee extensor-flexor, and 33.6% vs. 14.4% for ankle flexor-extensor) (P < 0.01). For muscles with 0–1 level of muscle strength (the Medical Research Council, MRC, score), significance difference in mean fasciculation intensity was observed only in ankle flexor-extensor. For muscles with 2–5 level of muscle strength, significant dissociation of fasciculation grade was common, especially among patients with slow rapid progression rate and both upper and lower motor neuron (UMN and LMN) involvement. As for non-ALS patients, no significant difference was observed in fasciculation intensity between antagonistic muscles.

Conclusion:

Split phenomenon of fasciculation between antagonistic muscles was common and relatively specific in ALS patients. Muscle strength, progression rate, and UMN involvement were influence factors of the split phenomenon of fasciculation intensity.
Complex cardiac implantable electronic device infections in Alberta, Canada: An epidemiologic cohort study of validated administrative data
Authors: King Teagan L. , Chew Derek S. , Leal Jenine , Cannon Kristine , Exner Derek V. , Smith Stephanie , Larios Oscar , Bush Kathryn , Yuen Brian , Zhang Zuying , Rennert-May Elissa
Published: May 2023

Objective:

To establish the epidemiology of cardiac implantable electronic device (CIED) infections in Alberta, Canada, using validated administrative data.

Design:

Retrospective, population-based cohort study.

Setting:

Alberta Health Services is a province-wide health system that services all of Alberta, Canada.

Participants:

Adult patients who underwent first-time CIED implantation or generator replacement in Alberta, Canada, between January 1, 2011, and December 31, 2019.

Methods:

CIED implant patients were identified from the Paceart database. Patients who developed an infection within 1 year of the index procedure were identified through validated administrative data (International Classification of Diseases, Tenth Revision in Canada). Demographic characteristics of patients were summarized. Logistic regression models were used to analyze device type, comorbidities, and demographics associated with infection rates and mortality.

Results:

Among 27,830 CIED implants, there were 205 infections (0.74%). Having 2 or more comorbidities was associated with higher infection risk. Generator replacement procedures (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.34–0.84; P = .008), age increase of every 10 years (OR, 0.73; 95% CI, 0.66–0.82; P ≤ .001), and index procedure after 2014 were associated with decreased risk. Comparing the infected to uninfected groups, the hospitalization rates were 2.63 compared to 0.69, and the mortality rates were 10.73% compared to 3.49%, respectively (P < .001).

Conclusions:

There is a slightly lower overall rate of CIED infections Alberta, Canada compared to previously described epidemiology. Implants after 2014, and generator replacements showed a decreased burden of infection. Patients with younger age, and 2 or more comorbidities are at greatest risk of CIED infection. The burden of hospitalization and mortality is substantially higher in infected patients.
Shell and associated operculum inTeiichispira(Macluritidae: Gastropoda) from the Early/Middle Ordovician of the Argentine Precordillera
Authors: Bertero Verónica , Ferrari Mariel , Carrera Marcelo G.
Published: May 2023

Two species ofTeiichispiraYochelson and Jones reported from the Early/Middle Ordovician marine deposits of the San Juan Formation in the Argentine Precordillera are described. The new speciesTeiichispira teresaen. sp. is a component of the Early/Middle Ordovician marine gastropod assemblage in the studied region;Teiichispira argentina(Kayser), previously known from the San Juan Formation, is described with a complete teleoconch and associated operculum. The opercula of bothTeiichispiraspecies are complete and preserved in life position associated with the shell ofT.argentina. The unguiculate morphology of the operculum is here interpreted as a mechanism for increasing the shell weight and ensuring anchoring to the substrate in a more or less fixed mode of life forTeiichispira, and as protection. The new occurrence ofTeiichispiraprovides new taxonomic data on early Paleozoic marine gastropods in Argentina and testifies to a wide paleobiogeographical distribution for the genus, restricted to tropical and subtropical regions during the Early/Middle Ordovician.

UUID:http://zoobank.org/8ee48319-b17a-4d15-a7d4-99cc9bb1dc42
Exponential control of the trajectories of iterated function systems with application to semi-strong GARCH models
Authors: Kandji Baye Matar
Published: May 2023

We establish new results on the strictly stationary solution to an iterated function system. When the driving sequence is stationary and ergodic, though not independent, the strictly stationary solution may admit no moment but we show an exponential control of the trajectories. We exploit these results to prove, under mild conditions, the consistency of the quasi-maximum likelihood estimator of GARCH(p,q) models with non-independent innovations.
Masked orthographic neighbor priming effects in Chinese two-character words
Authors: Yang Huilan , Spinelli Giacomo , Li Lingling , Lupker Stephen J.
Published: May 2023

In masked priming lexical decision tasks in alphabetic or syllabic script languages, latencies are longer when a word target is primed by a higher frequency neighbor (e.g., blue–BLUR) than when primed by an unrelated word of equivalent frequency (e.g., care–BLUR) – an “inhibitory neighbor priming effect.” In contrast, Zhou et al. (1999) demonstrated facilitatory orthographic neighbor priming for two-character Chinese words (e.g., 华丽–华贵). However, Zhou et al. did not control for relative prime-target frequency, which has been shown to be important in experiments when examining languages with other scripts. In the present Experiment 1 word neighbor primes (e.g., 容易-容貌) produced an inhibitory neighbor priming effect when the prime was higher frequency than the target, paralleling effects in other script languages. In further experiments, paralleling those in other script languages, two-character targets primed by nonword neighbors (容待-容貌) or single constituent characters matching the target in either position (容-容貌) showed significant facilitation. These results suggest that lexical activation/competition processes for two-character Chinese words are reasonably similar to those for words in alphabetic/syllabic script languages.
THE FIRST COMBINED RADIOCARBON AND ARCHAEOLOGICAL DATING OF THE GREAT MIGRATION PERIOD MATERIALS IN NORTHERN ALTAI: THE NECROPOLIS OF KARBAN-I
Authors: Seregin N N , Svyatko S V , Barrett G T , Demin M A , Matrenin S S , Papin D V , Reimer P J
Published: May 2023

The lack of systematic chronologies is a key problem for the archaeological sites of Altai and adjacent territories during the Great Migration Period. Here we present an attempt to establish the chronology of the Bulan-Koby culture objects of the Karban-I necropolis by correlation of accelerator mass spectrometry radiocarbon (AMS 14C) data from human remains with data from archaeological dating methods. This is the first application of such a combined targeted 14C and archaeological approach to the chronology of the Great Migration Period materials of northern Altai, and in particular the Bulan-Koby culture. Systematic analysis of the mutual occurrence of dated types of certain grave goods and 14C dating of a series of samples supports a predominant period of use for the site that spans the 2nd–3rd c. AD, which corresponds to the early Xianbei period. This study demonstrates strong agreement between the indicators obtained by archaeological and radiocarbon methods, suggesting chronological consistency of the necropolis which functioned at the beginning of the Great Migration Period. The very combination of the two techniques will allow more precise and detailed chronologies for other archaeological complexes of Altai and adjacent territories from the first centuries of the 1st mil. AD, which is the basis of historical reconstructions.
Misclassification and Bias in Predictions of Individual Ethnicity from Administrative Records
Authors: ARGYLE LISA P. , BARBER MICHAEL
Published: May 2023

We show that a common method of predicting individuals’ race in administrative records, Bayesian Improved Surname Geocoding (BISG), produces misclassification errors that are strongly correlated with demographic and socioeconomic factors. In addition to the high error rates for some racial subgroups, the misclassification rates are correlated with the political and economic characteristics of a voter’s neighborhood. Racial and ethnic minorities who live in wealthy, highly educated, and politically active areas are most likely to be misclassified as white by BISG. Inferences about the relationship between sociodemographic factors and political outcomes, like voting, are likely to be biased in models using BISG to infer race. We develop an improved method in which the BISG estimates are incorporated into a machine learning model that accounts for class imbalance and incorporates individual and neighborhood characteristics. Our model decreases the misclassification rates among non-white individuals, in some cases by as much as 50%.
Zoonotic helminths of dogs and risk factors associated with polyparasitism in Grenada, West Indies
Authors: Macpherson Maxine L.A. , Zendejas-Heredia Patsy A. , Sylvester Wayne , Gasser Robin B. , Traub Rebecca J. , Colella Vito , Macpherson Calum N.L.
Published: May 2023

Canine soil-transmitted helminths (STHs) cause important zoonoses in the tropics, with varying degrees of intensity of infection in humans and dogs. This study aimed to investigate the prevalence and associated risk factors for STHs in community dogs residing in Grenada, West Indies. In May 2021, 232 canine fecal samples were examined for zoonotic helminths by microscopy (following flotation), and genomic DNA from a subset of 211 of these samples were subjected to multiplex qPCR for the detection and specific identification of hookworms, Toxocara spp. and Strongyloides. Microscopic examination revealed that 46.5% (108/232, 95% CI 40–52.9), 9% (21/232, 95% CI 5.35–12.7) and 5.2% (12/232, 95% CI 2.3–8) of the samples contained eggs of Ancylostoma spp., Toxocara spp. and Trichuris vulpis, respectively. Multiplex qPCR revealed that, 42.2% (89/211, 95% CI 35.5–48.8) were positive for at least 1 zoonotic parasite. Of these, 40.8% (86/211, 95% CI 34.1–47.3) of samples tested positive for Ancylostoma spp., 36% (76/211, 95% CI 29.5–42.9) were positive for A. caninum, 13.3% (28/211, 95% CI 9–18.6) for A. ceylanicum, 5.7% for T. canis (12/211, 95% CI 2.97–8.81) and 1% (2/211, 95% CI 0–2.26) for Strongyloides spp. (identified as S. stercoralis and S. papillosus by conventional PCR-based Sanger sequencing). Using a multiple logistic regression model, a low body score and free-roaming behaviour were significant predictors of test-positivity for these parasitic nematodes in dogs (P < 0.05). Further studies of zoonotic STHs in humans should help elucidate the public health relevance of these parasites in Grenada.
Reliquary crosses from Middle Byzantine Aphrodisias: intimacy and archaeology
Authors: Jeffery Hugh G.
Published: May 2023

Worn constantly on the chest, reliquary crosses were intimately implicated in the lives of medieval people. Previous studies of such crosses have tended to consider them as tools through which people achieved specific ends, either as prophylactics against disease or as signifiers of hierarchical status. An alternative and complementary interpretation would emphasise intimacy: the prolonged rapport of particular crosses with particular bodies. This paper assembles and publishes 14 reliquary crosses from Aphrodisias in Caria, presented with commentary in an appendix. The body of the article addresses the archaeological contexts in which these crosses were found and explores the funerary use of reliquary crosses across Middle Byzantine Asia Minor from this novel perspective.
An investigation of the seasonal relationships between meteorological factors, water quality, and sporadic cases of Legionnaires’ disease in Washington, DC
Authors: Kirpich Alexander , Shishkin Aleksandr , Lhewa Pema , Yang Chen , von Fricken Michael E. , Norris Michael H. , Weppelmann Thomas A.
Published: May 2023

Since the discovery of Legionnaires’ disease (LD), limited progress has been made in understanding the epidemiology of sporadic cases of LD. Outbreaks have confirmed that air conditioning and potable water systems can be sources of community-acquired LD. However, studying the association between water quality and LD incidence has been challenging due to the heterogeneity of water systems across large geographic areas. Furthermore, although seasonal trends in incidence have been linked to increased rainfall and temperatures, the large geographic units have posed similar difficulties. To address this issue, a retrospective ecological study was conducted in Washington, DC, from 2001 to 2019. The study identified aseasonal pattern of LD incidence, with the majority of cases occurring between June and December, peaking in August, October, and November. Increased temperature was found to be associated with LD incidence. In surface water, higher concentrations of manganese, iron, and strontium were positively associated with LD, while aluminum and orthophosphate showed a negative association. Intreatment plant water, higher concentrations of total organic carbon, aluminum, barium, and chlorine were positively associated with LD, while strontium, zinc, and orthophosphate showed a negative association. The results for orthophosphates and turbidity were inconclusive, indicating the need for further research.
Oceanic Primary Production Estimation Based On Machine Learning
Authors: Ping Bo , Meng Yunshan , Xue Cunjin , Su Fenzhen
Published: May 2023

Oceanic primary production (OPP) is crucial for ecosystem services and global carbon cycle. However, sensitivity to geographic and environmental characteristics limits the application of semi‐empirical OPP estimate models, such as the vertically generalized productivity model (VGPM) and its modified version, particularly in coastal regions. In addition, the difficulty in collecting necessary parameters also hampers long‐term OPP estimates. Data‐driven machine learning (ML) methods can automatically capture the relationships between the input parameters and the objective; hence, they may become new methods for global OPP estimates. In this study, the effectiveness of ML methods to estimate OPP and the key attributes influencing ML performance in different regions and seasons are discussed. First, the ML models obtain a lower root mean square error than the VGPM and Eppley‐VGPM. In addition, the random forest (RF) model achieves the best performance among the four selected ML models. The enhancement in the accuracy of OPP estimates based on the RF model is more obvious in coastal regions than in the open ocean. In the four seasons, the RF model obtains better estimates of OPP than the Eppley‐VGPM, especially for summer. Moreover, input attributes, including sea surface temperature (SST), photosynthetic active radiation (PAR), and chlorophyll‐a concentration (Chlor‐a), achieve the best performance. The suitable alternative input attributes are SST/Chlor‐a in the coastal regions, and single Chlor‐a, SST/Chlor‐a, and PAR/Chlor‐a in the open ocean. Except for the SST/PAR/Chlor‐a combination, input with Chlor‐a, that is, SST/Chlor‐a and PAR/Chlor‐a, result a relatively acceptable performance in the four seasons.
Financial strain and depression in the U.S.: a scoping review
Authors: Ettman Catherine K. , Fan Alice Y. , Philips Alexander P. , Adam Gaelen P. , Ringlein Grace , Clark Melissa A. , Wilson Ira B. , Vivier Patrick M. , Galea Sandro
Published: May 2023

While the association between assets and depression has been established, less is known about the link between financial strain and depression. Given rising financial strain and economic inequity due to the COVID-19 pandemic, understanding the role that financial strain plays in shaping population depression in the United States is particularly salient. We conducted a scoping review of the peer-reviewed literature on financial strain and depression published from inception through January 19, 2023, in Embase, Medline via PubMed, and PsycINFO, PsycArticles, SocINDEX, and EconLit via Ebsco. We searched, reviewed, and synthesized the literature on longitudinal studies on financial strain and depression conducted in the United States. Four thousand and four unique citations were screened for eligibility. Fifty-eight longitudinal, quantitative articles on adults in the United States were included in the review. Eighty-three percent of articles (n = 48) reported a significant, positive association between financial strain and depression. Eight articles reported mixed results, featuring non-significant associations for some sub-groups and significant associations for others, one article was unclear, and one article reported no significant association between financial strain and depression. Five articles featured interventions to reduce depressive symptoms. Effective interventions included coping mechanisms to improve one’s financial situation (e.g., mechanisms to assist in finding employment), to modify cognitive behavior (e.g., reframing mindset), and to engage support (e.g., engaging social and community support). Successful interventions were tailored to participants, were group-based (e.g., they included family members or other job seekers), and occurred over multiple sessions. While depression was defined consistently, financial strain was defined variably. Gaps in the literature included studies featuring Asian populations in the United States and interventions to reduce financial strain. There is a consistent, positive association between financial strain and depression in the United States. More research is needed to identify and test interventions that mitigate the ill effects of financial strain on population’s mental health.
Diagnostic yield and clinical relevance of expanded germline genetic testing for nearly 7000 suspected HBOC patients
Authors: Henkel Jan , Laner Andreas , Locher Melanie , Wohlfrom Tobias , Neitzel Birgit , Becker Kerstin , Neuhann Teresa , Abicht Angela , Steinke-Lange Verena , Holinski-Feder Elke
Published: May 2023

Here we report the results of a retrospective germline analysis of 6941 individuals fulfilling the criteria necessary for genetic testing of hereditary breast- and ovarian cancer (HBOC) according to the German S3 or AGO Guidelines. Genetic testing was performed by next-generation sequencing using 123 cancer-associated genes based on the Illumina TruSight® Cancer Sequencing Panel. In 1431 of 6941 cases (20.6%) at least one variant was reported (ACMG/AMP classes 3–5). Of those 56.3% (n = 806) were class 4 or 5 and 43.7% (n = 625) were a class 3 (VUS). We defined a 14 gene HBOC core gene panel and compared this to a national and different internationally recommended gene panels (German Hereditary Breast and Ovarian Cancer Consortium HBOC Consortium, ClinGen expert Panel, Genomics England PanelsApp) in regard of diagnostic yield, revealing a diagnostic range of pathogenic variants (class 4/5) from 7.8 to 11.6% depending on the panel evaluated. With the 14 HBOC core gene panel having a diagnostic yield of pathogenic variants (class 4/5) of 10.8%. Additionally, 66 (1%) pathogenic variants (ACMG/AMP class 4 or 5) were found in genes outside the 14 HBOC core gene set (secondary findings) that would have been missed with the restriction to the analysis of HBOC genes. Furthermore, we evaluated a workflow for a periodic re-evaluation of variants of uncertain clinical significance (VUS) for the improvement of clinical validity of germline genetic testing.
A step-for-step main-group replica of the Fischer carbene synthesis at a borylene carbonyl
Authors: Härterich Marcel , Matler Alexander , Dewhurst Rian D. , Sachs Andreas , Oppel Kai , Stoy Andreas , Braunschweig Holger
Published: May 2023

The Fischer carbene synthesis, involving the conversion of a transition metal (TM)-bound CO ligand to a carbene ligand of the form [=C(OR’)R] (R, R’ = organyl groups), is one of the seminal reactions in the history of organometallic chemistry. Carbonyl complexes of p-block elements, of the form [E(CO)n] (E = main-group fragment), are much less abundant than their TM cousins; this scarcity and the general instability of low-valent p-block species means that replicating the historical reactions of TM carbonyls is often very difficult. Here we present a step-for-step replica of the Fischer carbene synthesis at a borylene carbonyl involving nucleophilic attack at the carbonyl carbon followed by electrophilic quenching at the resultant acylate oxygen atom. These reactions provide borylene acylates and alkoxy-/silyloxy-substituted alkylideneboranes, main-group analogues of the archetypal transition metal acylate and Fischer carbene families, respectively. When either the incoming electrophile or the boron center has a modest steric profile, the electrophile instead attacks at the boron atom, leading to carbene-stabilized acylboranes – boron analogues of the well-known transition metal acyl complexes. These results constitute faithful main-group replicas of a number of historical organometallic processes and pave the way to further advances in the field of main-group metallomimetics.
Spatial analysis with SPIAT and spaSim to characterize and simulate tissue microenvironments
Authors: Feng Yuzhou , Yang Tianpei , Zhu John , Li Mabel , Doyle Maria , Ozcoban Volkan , Bass Greg T. , Pizzolla Angela , Cain Lachlan , Weng Sirui , Pasam Anupama , Kocovski Nikolce , Huang Yu-Kuan , Keam Simon P. , Speed Terence P. , Neeson Paul J. , Pearson Richard B. , Sandhu Shahneen , Goode David L. , Trigos Anna S.
Published: May 2023

Spatial proteomics technologies have revealed an underappreciated link between the location of cells in tissue microenvironments and the underlying biology and clinical features, but there is significant lag in the development of downstream analysis methods and benchmarking tools. Here we present SPIAT (spatial image analysis of tissues), a spatial-platform agnostic toolkit with a suite of spatial analysis algorithms, and spaSim (spatial simulator), a simulator of tissue spatial data. SPIAT includes multiple colocalization, neighborhood and spatial heterogeneity metrics to characterize the spatial patterns of cells. Ten spatial metrics of SPIAT are benchmarked using simulated data generated with spaSim. We show how SPIAT can uncover cancer immune subtypes correlated with prognosis in cancer and characterize cell dysfunction in diabetes. Our results suggest SPIAT and spaSim as useful tools for quantifying spatial patterns, identifying and validating correlates of clinical outcomes and supporting method development.
Structural basis for breadth development in the HIV-1 V3-glycan targeting DH270 antibody clonal lineage
Authors: Henderson Rory , Zhou Ye , Stalls Victoria , Wiehe Kevin , Saunders Kevin O. , Wagh Kshitij , Anasti Kara , Barr Maggie , Parks Robert , Alam S. Munir , Korber Bette , Haynes Barton F. , Bartesaghi Alberto , Acharya Priyamvada
Published: May 2023

Antibody affinity maturation enables adaptive immune responses to a wide range of pathogens. In some individuals broadly neutralizing antibodies develop to recognize rapidly mutating pathogens with extensive sequence diversity. Vaccine design for pathogens such as HIV-1 and influenza has therefore focused on recapitulating the natural affinity maturation process. Here, we determine structures of antibodies in complex with HIV-1 Envelope for all observed members and ancestral states of the broadly neutralizing HIV-1 V3-glycan targeting DH270 antibody clonal B cell lineage. These structures track the development of neutralization breadth from the unmutated common ancestor and define affinity maturation at high spatial resolution. By elucidating contacts mediated by key mutations at different stages of antibody development we identified sites on the epitope-paratope interface that are the focus of affinity optimization. Thus, our results identify bottlenecks on the path to natural affinity maturation and reveal solutions for these that will inform immunogen design aimed at eliciting a broadly neutralizing immune response by vaccination.
A general model to predict small molecule substrates of enzymes based on machine and deep learning
Authors: Kroll Alexander , Ranjan Sahasra , Engqvist Martin K. M. , Lercher Martin J.
Published: May 2023

For most proteins annotated as enzymes, it is unknown which primary and/or secondary reactions they catalyze. Experimental characterizations of potential substrates are time-consuming and costly. Machine learning predictions could provide an efficient alternative, but are hampered by a lack of information regarding enzyme non-substrates, as available training data comprises mainly positive examples. Here, we present ESP, a general machine-learning model for the prediction of enzyme-substrate pairs with an accuracy of over 91% on independent and diverse test data. ESP can be applied successfully across widely different enzymes and a broad range of metabolites included in the training data, outperforming models designed for individual, well-studied enzyme families. ESP represents enzymes through a modified transformer model, and is trained on data augmented with randomly sampled small molecules assigned as non-substrates. By facilitating easy in silico testing of potential substrates, the ESP web server may support both basic and applied science.
The NELF pausing checkpoint mediates the functional divergence of Cdk9
Authors: DeBerardine Michael , Booth Gregory T. , Versluis Philip P. , Lis John T.
Published: May 2023

Promoter-proximal pausing by RNA Pol II is a rate-determining step in gene transcription that is hypothesized to be a prominent point at which regulatory factors act. The pausing factor NELF is known to induce and stabilize pausing, but not all kinds of pausing are NELF-mediated. Here, we find that NELF-depleted Drosophila melanogaster cells functionally recapitulate the NELF-independent pausing we previously observed in fission yeast (which lack NELF). Critically, only NELF-mediated pausing establishes a strict requirement for Cdk9 kinase activity for the release of paused Pol II into productive elongation. Upon inhibition of Cdk9, cells with NELF efficiently shutdown gene transcription, while in NELF-depleted cells, defective, non-productive transcription continues unabated. By introducing a strict checkpoint for Cdk9, the evolution of NELF was likely critical to enable increased regulation of Cdk9 in higher eukaryotes, as Cdk9 availability can be restricted to limit gene transcription without inducing wasteful, non-productive transcription.
Deep learning to estimate lithium-ion battery state of health without additional degradation experiments
Authors: Lu Jiahuan , Xiong Rui , Tian Jinpeng , Wang Chenxu , Sun Fengchun
Published: May 2023

State of health is a critical state which evaluates the degradation level of batteries. However, it cannot be measured directly but requires estimation. While accurate state of health estimation has progressed markedly, the time- and resource-consuming degradation experiments to generate target battery labels hinder the development of state of health estimation methods. In this article, we design a deep-learning framework to enable the estimation of battery state of health in the absence of target battery labels. This framework integrates a swarm of deep neural networks equipped with domain adaptation to produce accurate estimation. We employ 65 commercial batteries from 5 different manufacturers to generate 71,588 samples for cross-validation. The validation results indicate that the proposed framework can ensure absolute errors of less than 3% for 89.4% of samples (less than 5% for 98.9% of samples), with a maximum absolute error of less than 8.87% in the absence of target labels. This work emphasizes the power of deep learning in precluding degradation experiments and highlights the promise of rapid development of battery management algorithms for new-generation batteries using only previous experimental data.
Computational study on the catalytic control of endo/exo Diels-Alder reactions by cavity quantum vacuum fluctuations
Authors: Pavošević Fabijan , Smith Robert L. , Rubio Angel
Published: May 2023

Achieving control over chemical reaction’s rate and stereoselectivity realizes one of the Holy Grails in chemistry that can revolutionize chemical and pharmaceutical industries. Strong light-matter interaction in optical or nanoplasmonic cavities might provide the knob to reach such control. In this work, we demonstrate the catalytic and selectivity control of an optical cavity for two selected Diels-Alder cycloaddition reactions using the quantum electrodynamics coupled cluster (QED-CC) method. Herein, we find that by changing the molecular orientation with respect to the polarization of the cavity mode the reactions can be significantly inhibited or selectively enhanced to produce major endo or exo products on demand. This work highlights the potential of utilizing quantum vacuum fluctuations of an optical cavity to modulate the rate of Diels-Alder cycloaddition reactions and to achieve stereoselectivity in a practical and non-intrusive way. We expect that the present findings will be applicable to a larger set of relevant reactions, including the click chemical reactions.
Turn air-captured CO2 with methanol into amino acid and pyruvate in an ATP/NAD(P)H-free chemoenzymatic system
Authors: Liu Jianming , Zhang Han , Xu Yingying , Meng Hao , Zeng An-Ping
Published: May 2023

The use of gaseous and air-captured CO2 for technical biosynthesis is highly desired, but elusive so far due to several obstacles including high energy (ATP, NADPH) demand, low thermodynamic driving force and limited biosynthesis rate. Here, we present an ATP and NAD(P)H-free chemoenzymatic system for amino acid and pyruvate biosynthesis by coupling methanol with CO2. It relies on a re-engineered glycine cleavage system with the NAD(P)H-dependent L protein replaced by biocompatible chemical reduction of protein H with dithiothreitol. The latter provides a higher thermodynamic driving force, determines the reaction direction, and avoids protein polymerization of the rate-limiting enzyme carboxylase. Engineering of H protein to effectively release the lipoamide arm from a protected state further enhanced the system performance, achieving the synthesis of glycine, serine and pyruvate at g/L level from methanol and air-captured CO2. This work opens up the door for biosynthesis of amino acids and derived products from air.