bluuebunny/crossref_metadata_2025 huggingface dataset:
A Practical Guide to Data Analysis Using R
Authors: Maindonald John H. , Braun W. John , Andrews Jeffrey L.
Published: May 2024

Using diverse real-world examples, this text examines what models used for data analysis mean in a specific research context. What assumptions underlie analyses, and how can you check them? Building on the successful 'Data Analysis and Graphics Using R,' 3rd edition (Cambridge, 2010), it expands upon topics including cluster analysis, exponential time series, matching, seasonality, and resampling approaches. An extended look at p-values leads to an exploration of replicability issues and of contexts where numerous p-values exist, including gene expression.
Developing practical intuition, this book assists scientists in the analysis of their own data, and familiarizes students in statistical theory with practical data analysis. The worked examples and accompanying commentary teach readers to recognize when a method works and, more importantly, when it doesn't. Each chapter contains copious exercises. Selected solutions, notes, slides, and R code are available online, with extensive references pointing to detailed guides to R.
Appropriateness of Antibiotic Prescribing in US Emergency Department Visits, 2016–2021
Authors: Ladines-Lim Joseph Benigno , Fischer Michael A. , Linder Jeffrey A. , Chua Kao-Ping
Published: May 2024

In this national analysis of US emergency department visits with antibiotic prescribing during 2016–2021, 27.6% of visits resulted in inappropriate antibiotic prescribing: 14.9% had diagnosis codes plausibly antibiotic-related (eg, acute bronchitis), suggesting actual inappropriate prescribing, and 12.6% had diagnosis codes not plausibly antibiotic-related (eg, hypertension), suggesting poor coding quality.
Powers of commutators in linear algebraic groups
Authors: Martin Benjamin
Published: May 2024

Let ${\mathcal G}$ be a linear algebraic group over k, where k is an algebraically closed field, a pseudo-finite field or the valuation ring of a non-archimedean local field. Let $G= {\mathcal G}(k)$. We prove that if $\gamma\in G$ such that γ is a commutator and $\delta\in G$ such that $\langle \delta\rangle= \langle \gamma\rangle$ then δ is a commutator. This generalises a result of Honda for finite groups. Our proof uses the Lefschetz principle from first-order model theory.
Laryngeal muscle tension in patients with sinonasal diseases: prevalence and clinical significance
Authors: Hamdan Abdul-Latif , Hosri Jad , Yammine Yara , Abou Raji Feghali Patrick , El Hadi Nadine , Alam Elie
Published: May 2024

Objective

To determine the prevalence of laryngeal muscle tension in patients with sinonasal diseases.

Methods

The medical records and video-recordings of patients with a history of sinonasal disease were reviewed to identify one of four muscle tension patterns during phonation. A control group with no history of sinonasal diseases was matched according to age and gender.

Results

Seventy-seven patients were divided into a study group (n = 47) and a control group (n = 30). In the study group, 29 patients had at least one muscle tension pattern compared with only 9 in the control group (p = 0.007). The most common muscle tension patterns observed in the study and control groups were muscle tension patterns II and III. In the study group, 79.3 per cent of patients with at least one muscle tension pattern reported dysphonia compared with only 33.3 per cent in the control group.

Conclusion

Patients with sinonasal diseases are more likely to exhibit laryngeal muscle tension and dysphonia in comparison with healthy subjects.
Report on Summer Conferences in England: Research in Movement and the International Council on Kinetography Laban.
Authors: de Laban Juana
Published: May 2024

The week-end conference on “Research in Movement” convened August 10-12, 1973, at Nonington College, near Dover, Kent, England. Five lectures beginning with an evening session on Friday, August 10, featured the paper on “Ergonomics,” by.Dr. Nigel Corbett (Industrial Engineer, Birmingham University), which was read and discussed by Mr. S. Madeley. He oriented the assembled movement researchers to the fact that “measurement of motion” is of particular concern to physiologists and scientists since the World War II demanded immediate practical solutions (how to survive in a jungle, speed and weightlessness in flying, etc.). Now it is vital that the job be fitted and programmed to the worker. He cited research by Alberg (1968) on tests and models of tasks (52 experiments); by Spitzer & Hethinger (1970) on static work involving large body movement and force factors; by Laban (1950) as utilized in Britain by Paddy McMasters who analyzed filmed worktasks.

The research at Birmingham University focused on three types of actions: weight, breath, reaction-time factors for which examples were set-up each with four tasks for eight different people. The pilot studies are continuing and yielding results, corroborating that movement actions can be successfully measured.

On Saturday, August 11, the next three lectures enthralled everyone. The Principal of Nonington College, Miss Ellinor Hinks, spoke on ”Educational Gymnastics”. Her invention of special equipment created and designed for the exploration of total body movement techniques, conceived and housed in a unique space-gymnasium, is highly effective in training young people who concentrate and inventively achieve far more than pure motor skills. Two films of her work “Movement in the Making, I & II”, demonstrated her new method. As films, they superbly illustrate the physical potentialities of movement with this new type of apparatus (the films can be rented or purchased).
Finite-element analysis case retrieval based on an ontology semantic tree
Authors: Xu Xuesong , Cheng Zhenbo , Xiao Gang , Zhang Yuanming , Zhang Haoxin , Meng Hangcheng
Published: May 2024

The widespread use of finite-element analysis (FEA) in industry has led to a large accumulation of cases. Leveraging past FEA cases can improve accuracy and efficiency in analyzing new complex tasks. However, current engineering case retrieval methods struggle to measure semantic similarity between FEA cases. Therefore, this article proposed a method for measuring the similarity of FEA cases based on ontology semantic trees. FEA tasks are used as indexes for FEA cases, and an FEA case ontology is constructed. By using named entity recognition technology, pivotal entities are extracted from FEA tasks, enabling the instantiation of the FEA case ontology and the creation of a structured representation for FEA cases. Then, a multitree algorithm is used to calculate the semantic similarity of FEA cases. Finally, the correctness of this method was confirmed through an FEA case retrieval experiment on a pressure vessel. The experimental results clearly showed that the approach outlined in this article aligns more closely with expert ratings, providing strong validation for its effectiveness.
Calculation of Kinetic Fractionation of Open‐Water Evaporation Over an Upland Reservoir
Authors: Bui Tri Q. , Do Nga T. , Vu Thuy T. , Nguyen Dinh T. , Trinh Duc A.
Published: May 2024

Based on the fact that many water reservoirs built in headwater catchments receive no water input during dry season, we modified the Craig‐Gordon model and proposed an approach to calculate kinetic fractionation factors in open‐water evaporation taking into account isotopic compositions of precipitation and of lake water, lake volume, and land‐based meteorological data. The approach is centered around the determination of lake water isotope enrichment rate over time during dry periods. We then applied this approach for calculating kinetic fractionation factors, turbulence index, and open‐water evaporation for a small reservoir located in a sub‐tropical monsoonal climate. We found that the kinetic fractionation factors, εK,H and εK,O are, respectively 3.11‰ ± 0.41‰ and 2.50‰ ± 2.15‰, corresponding to the turbulence index of 0.43 ± 0.19. Evaporation rates in open‐water estimated by our approach is 1.55 times of the land‐based evaporation gauged in the nearby meteorological station. Wind speed, represented by turbulence index, is proved as an important climatic factor influencing kinetic fractionation. This study confirms that wind and surface area factors, which have been neglected in several isotope mass balance models, should be included into calculation process.
The Protracted Evolution of a Plate Boundary: Eastern Cuba Block and Old Bahamas Channel
Authors: Oliviera de Sá A. , Leroy S. , d’Acremont E. , Lafuerza S. , Granja‐Bruña J.‐L. , Moreno B. , Cabiativa Pico V. , Letouzey J.
Published: May 2024

The Eastern Cuban block has experienced a complex tectonic history characterized by plate interactions, resulting in a diverse array of geological features observable in the offshore sedimentary record. We investigate the tectonic evolution of offshore Eastern Cuba, specifically in the Old Bahamas Channel and its surrounding areas, by integrating multi‐channel seismic (MCS) reflection and published geological data. Our analysis employs stratigraphic frameworks and MCS data to assess deformation and key geological events in the region. We highlight the complex tectonic history of the Eastern Cuban block, marked by significant geodynamic events, such as rifting, the subduction of the oceanic Proto‐Caribbean plate, and syn‐orogenic and post‐orogenic phases. The seismic units observed in the majority of the study area reveal the early evolution of the Northern Proto‐Caribbean margin, subsequently impacted by the Cuban orogeny and the reactivation of the Cuban Transform Fault zone corresponding to a former plate boundary. We propose estimated ages for the seismic sequences, correlating them with available well data from neighboring regions. This study offers valuable insights into the tectonic history and geological evolution of offshore Eastern Cuba, contributing to a more comprehensive understanding of the region's geodynamic development.
Linking Upwelling Dynamics and Subsurface Nutrients to Projected Productivity Changes in the California Current System
Authors: Jacox Michael G. , Bograd Steven J. , Fiechter Jerome , Pozo Buil Mercedes , Alexander Michael , Amaya Dillon , Cordero Quiros Nathalí , Ding Hui , Rykaczewski Ryan R.
Published: May 2024

Given the importance of coastal upwelling systems to ocean productivity, fisheries, and biogeochemical cycles, their response to climate change is of great interest. However, there is no consensus on future productivity changes in these systems, which may be controlled by multiple drivers including wind‐driven and geostrophic transport, stratification, and source water properties. Here we use an ensemble of regional ocean projections and recently developed upwelling indices for the California Current System to disentangle these sometimes‐competing influences. Some changes are consistent among models (e.g., decreased mixed layer depth), while for others there is a lack of agreement even on the direction of future change (e.g., nitrate concentration in upwelled waters). Despite models' diverging projections of productivity changes, they agree that those changes are predominantly driven by subsurface nitrate concentrations, not by upwelling strength. Our results highlight the need for more attention to processes governing subsurface nutrient changes, not just upwelling strength.
Improvements on Phase Classification Using Atmospheric Melting and Refreezing Energy Based on Soundings
Authors: Shi Shangyong , Liu Guosheng
Published: May 2024

Determining precipitation as solid (snow) or liquid (rain) phase is crucial for remote sensing of precipitation. Most phase classification methods rely on near‐surface temperatures. Further attempts to incorporate atmospheric information aloft only achieved mixed level of success, particularly for precipitation with temperature inversion. In our study, we developed a phase classification scheme based on the upper‐level melting energy (ME) and refreezing energy (RE), which is proportional to the area enclosed by the temperature profile and the 0°C isotherm. We performed least squares fitting and linear discriminant analysis to derive phase separation functions using observed surface and sounding data in North America. We provided separation functions for snow conditional probabilities ranging from 30% to 80% for various applications. Compared to a previously published (Probsnow) method, our energy method achieved comparable performance for Type 1 soundings with one near‐surface melting layer, and significantly improves the phase classification scores for Type 2 soundings with an aloft melting layer and a near‐surface refreezing layer. We innovatively combined surface ice‐bulb temperature with the ratio between the ME and RE to represent Type 2 profiles. For Type 2 soundings, our energy method improves the Heidke skill score (HSS) from 0.25 to 0.47 and reduces false alarm rate (FAR) by 0.47 compared to the Probsnow method for 50% threshold. By applying the physically based method, we improved accuracy and HSS, and reduced FAR for more than two thirds of the evaluation stations across the North America. Finally, we tested the application of the new method in satellite snowfall retrievals.
A New Method for Size‐Resolved Aerosol CCN Activity Measurement at Low Supersaturation in Pristine Atmosphere
Authors: Tao Jiangchuan , Luo Biao , Meng Zixiang , Xie Linhong , Zhang Shaobin , Hong Juan , Zhou Yaqing , Kuang Ye , Wang Qiaoqiao , Huang Shan , Cheng Peng , Yuan Bin , Yu Pengfei , Su Hang , Cheng Yafang , Ma Nan
Published: May 2024

Understanding aerosol‐cloud interactions under pristine atmospheric conditions is crucial for meaningful global climate change predictions. However, ability of aerosol particles to act as cloud condensation nuclei (CCN) activity of aerosols in pristine atmosphere remains limited, mainly because of the difficulty of measuring it in pristine environments. Given the extremely low CCN number concentration under low supersaturations (SSs) and the complex impact of the kinetic limitation in CCN measurements, size‐resolved CCN activity measurements at low SSs cannot be achieved with traditional methods using differential mobility analyzers and a CCN counter (CCNC) because of the low sample efficiency and the impact of particles with multiple charges. To overcome this difficulty, we propose a new method for measuring size‐resolved CCN activity at low aerosol number concentrations. The new method is based on a combined system comprising an aerodynamic aerosol classifier (AAC) and a CCNC (AAC‐CCNC system). A control program was developed to achieve high‐resolution scans of the SS and particle size within a reasonable time frame. A data inversion scheme, including corrections for the transfer function and kinetic limitation, was developed to obtain accurate size‐resolved CCN activity. In July‐August 2022, the new method was used to measure the size‐resolved CCN activity on the Tibetan Plateau. This new method can advance the size‐resolved CCN measurements, thereby enhancing our understanding of aerosol‐cloud interactions in pristine atmosphere.
Causes of Past African Temperature Change in PMIP Simulations of the Mid‐Holocene
Authors: Marshall Charlie , Morrill Carrie , Dee Sylvia , Pausata Francesco S. R. , Russell James
Published: May 2024

Current‐generation climate models project that Africa will warm by up to 5°C in the coming century, severely stressing African populations. Past and ongoing work indicates, however, that the models used to create these projections do not match proxy records of past temperature in Africa during the mid‐Holocene (MH), raising concerns that their future projections may house large uncertainties. Rather than reproducing proxy‐based reconstructions of MH warming relative to the Pre‐Industrial (PI), models instead simulate MH temperatures very similar to or slightly colder than the PI. This data‐model mismatch could be due to a variety of factors, including biases in model surface energy budgets or inaccurate representation of the feedbacks between temperature and hydrologic change during the “Green Sahara.” We focus on the differences among model simulations in the Paleoclimate Modeling Intercomparison Project Phases 3 and 4 (PMIP3 and PMIP4), examining surface temperature and energy budgets to investigate controls on temperature and the potential model sources of this paleoclimate data‐model mismatch. Our results suggest that colder conditions simulated by PMIP3 and PMIP4 models during the MH are in large part due to the joint impacts of feedback uncertainties in response to increased precipitation, a strengthened West African Monsoon (WAM) in the Sahel, and the Green Sahara. We extend these insights into suggestions for model physics and boundary condition changes, and discuss implications for the accuracy of future climate model projections over Africa.
Cryospheric and Oceanographic Evolution in the Arctic Makarov Basin Since the Early Pleistocene Revealed by Bulk Mineral Assemblages
Authors: Park Kwangkyu , Nam Seung‐Il , Vogt Christoph , Frederichs Thomas , Kim Jung‐Hyun , Khim Boo‐Keun
Published: May 2024

We present the glacial history of the Makarov Basin (western Arctic Ocean) during the last ∼1.1 Myr, with sediment provenances using the newly refined chronostratigraphy of core ARA03B‐41GC02. According to the principal component analysis of the bulk mineral assemblages, felsic minerals were dominant, and their ratios (K‐feldspar/plagioclase and quartz/feldspars) indicated that sediment supply to the Makarov Basin was mainly from the Siberian margin and partly from northern North America, including the Canadian Arctic. However, their occurrence did not vary significantly between interglacials and glacials due to the mixed sources. In contrast, clinopyroxene and dolomite indicated specific sediment origins from the eastern Siberian margin and northern North America, respectively. The clinopyroxene content followed an eccentricity cycle (∼100‐Kyr) during the early to middle Pleistocene, suggesting that the eustatic sea level changes may have influenced its input from the eastern Siberian margin. The dolomite, transported primarily by icebergs from the Arctic sector of the Laurentide Ice Sheet (LIS) in northern North America, has also followed the same cycle since the early Pleistocene. Thus, the mineralogical signals highlight that sediment origins and transport processes in the Makarov Basin were related to ice sheet evolution at the eccentricity cycle. In addition, dolomite deposition in the Makarov Basin began by the early Pleistocene (∼790 ka), ∼150 ka earlier than in previous North Atlantic records (∼640 ka), indicating the earlier LIS calving in the Arctic sector than in the Atlantic sector.
Participants’ views of ultra-low dose combination therapy for high blood pressure: a mixed-methods study from the QUARTET trial
Authors: Kovoor Joshua G. , Chow Clara K. , Salam Abdul , Webster Ruth , Shiel Louise , Nelson Mark R. , Affandi Jacquita S. , Hay Peter , Burke Michael , Figtree Gemma A. , Usherwood Tim , Reid Christopher M. , Schlaich Markus P. , Rodgers Anthony , Atkins Emily R.
Published: May 2024

Single-pill combination therapy containing four quarter-dose medications for high blood pressure improves BP control compared to monotherapy, however patient-reported acceptance of the quadpill as a treatment strategy remains undescribed. We collected within-trial feedback and interviewed participants from the quadruple ultra-low-dose treatment for hypertension (QUARTET) trial to characterise patient attitudes to this intervention. All trial participants were asked about ease and preference for the quadpill and provided an opportunity to give further comments on the trial at 12 weeks (trial primary endpoint) and 52 weeks extended follow-up. Separately, we used purposive and quota sampling for the semi-structured telephone interviews, with the resultant verbatim transcripts analysed using an inductive thematic analysis approach. Themes were re-evaluated after each successive interview, and at suspected data saturation, an additional interview conducted for confirmation. At 12 weeks follow-up, 502 of 591 (85%) participants responded to acceptability questions, and 359 of 417 (86%) responded at week 52. Most reported the trial capsule easy or very easy to take. From eight sites, 16 participants were interviewed between 5 August 2020 and 19 November 2020. All described a positive experience, preferred once-daily morning dosing and found routine facilitated adherence. Participants valued individual responsibility for adherence, and involvement of the general practitioner in blood-pressure management. Most reported capsule size did not deter adherence but desired a smaller capsule. Participants described a preference for minimising number and dosage of medications, reduced capsule size, and once-daily morning dosing. These findings suggest a preference for single-pill combination therapy for blood pressure lowering.
Statistical assessment of reliability of anthropometric measurements in the multi-site South African National Dietary Intake Survey 2022
Authors: Nel Sanja , de Man Jeroen , van den Berg Louise , Wenhold Friedeburg Anna Maria
Published: May 2024

Background

Anthropometric data quality in large multicentre nutrition surveys is seldom adequately assessed. In preparation for the South African National Dietary Intake Survey (NDIS-2022), this study assessed site leads’ and fieldworkers’ intra- and inter-rater reliability for measuring weight, length/height, mid-upper arm circumference (MUAC), waist circumference (WC) and calf circumference (CC).

Methods

Standardised training materials and measurement protocols were developed, and new anthropometric equipment was procured. Following two training rounds (12 site lead teams, 46 fieldworker teams), measurement reliability was assessed for both groups, using repeated measurements of volunteers similar to the survey target population. Reliability was statistically assessed using the technical error of measurement (TEM), relative TEM (%TEM), intra-class correlation coefficient (ICC) and coefficient of reliability (R). Agreement was visualised with Bland-Altman analysis.

Results

By %TEM, the best reliability was achieved for weight (%TEM = 0.260–0.923) and length/height (%TEM = 0.434–0.855), and the poorest for MUAC by fieldworkers (%TEM = 2.592–3.199) and WC (%TEM = 2.353–2.945). Whole-sample ICC and R were excellent ( > 0.90) for all parameters except site leads’ CC inter-rater reliability (ICC = 0.896, R = 0.889) and fieldworkers’ inter-rater reliability for MUAC in children under two (ICC = 0.851, R = 0.881). Bland-Altman analysis revealed no significant bias except in fieldworkers’ intra-rater reliability of length/height measurement in adolescents/adults ( + 0.220 (0.042, 0.400) cm). Reliability was higher for site leads vs. fieldworkers, for intra-rater vs. inter-rater assessment, and for weight and length/height vs. circumference measurements.

Conclusion

NDIS-2022 site leads and fieldworkers displayed acceptable reliability in performing anthropometric measurements, highlighting the importance of intensive training and standardised measurement protocols. Ongoing reliability assessment during data collection is recommended.
Ecological divergence despite common mating sites: Genotypes and symbiotypes shed light on cryptic diversity in the black bean aphid species complex
Authors: Gimmi Elena , Wallisch Jesper , Vorburger Christoph
Published: May 2024

Different host plants represent ecologically dissimilar environments for phytophagous insects. The resulting divergent selection can promote the evolution of specialized host races, provided that gene flow is reduced between populations feeding on different plants. In black bean aphids belonging to the Aphis fabae complex, several morphologically cryptic taxa have been described based on their distinct host plant preferences. However, host choice and mate choice are largely decoupled in these insects: they are host-alternating and migrate between specific summer host plants and shared winter hosts, with mating occurring on the shared hosts. This provides a yearly opportunity for gene flow among aphids using different summer hosts, and raises the question if and to what extent the ecologically defined taxa are reproductively isolated. Here, we analyzed a geographically and temporally structured dataset of microsatellite genotypes from A. fabae that were mostly collected from their main winter host Euonymus europaeus, and additionally from another winter host and fourteen summer hosts. The data reveals multiple, strongly differentiated genetic clusters, which differ in their association with different summer and winter hosts. The clusters also differ in the frequency of infection with two heritable, facultative endosymbionts, separately hinting at reproductive isolation and divergent ecological selection. Furthermore, we found evidence for occasional hybridization among genetic clusters, with putative hybrids collected more frequently in spring than in autumn. This suggests that similar to host races in other phytophagous insects, both prezygotic and postzygotic barriers including selection against hybrids maintain genetic differentiation among A. fabae taxa, despite a common mating habitat.
A burden of proof study on alcohol consumption and ischemic heart disease
Authors: Carr Sinclair , Bryazka Dana , McLaughlin Susan A. , Zheng Peng , Bahadursingh Sarasvati , Aravkin Aleksandr Y. , Hay Simon I. , Lawlor Hilary R. , Mullany Erin C. , Murray Christopher J. L. , Nicholson Sneha I. , Rehm Jürgen , Roth Gregory A. , Sorensen Reed J. D. , Lewington Sarah , Gakidou Emmanuela
Published: May 2024

Cohort and case-control data have suggested an association between low to moderate alcohol consumption and decreased risk of ischemic heart disease (IHD), yet results from Mendelian randomization (MR) studies designed to reduce bias have shown either no or a harmful association. Here we conducted an updated systematic review and re-evaluated existing cohort, case-control, and MR data using the burden of proof meta-analytical framework. Cohort and case-control data show low to moderate alcohol consumption is associated with decreased IHD risk – specifically, intake is inversely related to IHD and myocardial infarction morbidity in both sexes and IHD mortality in males – while pooled MR data show no association, confirming that self-reported versus genetically predicted alcohol use data yield conflicting findings about the alcohol-IHD relationship. Our results highlight the need to advance MR methodologies and emulate randomized trials using large observational databases to obtain more definitive answers to this critical public health question.
High-confidence 3D template matching for cryo-electron tomography
Authors: Cruz-León Sergio , Majtner Tomáš , Hoffmann Patrick C. , Kreysing Jan Philipp , Kehl Sebastian , Tuijtel Maarten W. , Schaefer Stefan L. , Geißler Katharina , Beck Martin , Turoňová Beata , Hummer Gerhard
Published: May 2024

Visual proteomics attempts to build atlases of the molecular content of cells but the automated annotation of cryo electron tomograms remains challenging. Template matching (TM) and methods based on machine learning detect structural signatures of macromolecules. However, their applicability remains limited in terms of both the abundance and size of the molecular targets. Here we show that the performance of TM is greatly improved by using template-specific search parameter optimization and by including higher-resolution information. We establish a TM pipeline with systematically tuned parameters for the automated, objective and comprehensive identification of structures with confidence 10 to 100-fold above the noise level. We demonstrate high-fidelity and high-confidence localizations of nuclear pore complexes, vaults, ribosomes, proteasomes, fatty acid synthases, lipid membranes and microtubules, and individual subunits inside crowded eukaryotic cells. We provide software tools for the generic implementation of our method that is broadly applicable towards realizing visual proteomics.
Crown ether decorated silicon photonics for safeguarding against lead poisoning
Authors: Ranno Luigi , Tan Yong Zen , Ong Chi Siang , Guo Xin , Koo Khong Nee , Li Xiang , Wang Wanjun , Serna Samuel , Liu Chongyang , Rusli  , Littlejohns Callum G. , Reed Graham T. , Hu Juejun , Wang Hong , Sia Jia Xu Brian
Published: May 2024

Lead (Pb2+) toxification is a concerning, unaddressed global public health crisis that leads to 1 million deaths annually. Yet, public policies to address this issue have fallen short. This work harnesses the unique abilities of crown ethers, which selectively bind to specific ions. This study demonstrates the synergistic integration of highly-scalable silicon photonics, with crown ether amine conjugation via Fischer esterification in an environmentally-friendly fashion. This realizes an integrated photonic platform that enables the in-operando, highly-selective and quantitative detection of various ions. The development dispels the existing notion that Fischer esterification is restricted to organic compounds, facilitating the subsequent amine conjugation for various crown ethers. The presented platform is specifically engineered for selective Pb2+ detection, demonstrating a large dynamic detection range, and applicability to field samples. The compatibility of this platform with cost-effective manufacturing indicates the potential for pervasive implementation of the integrated photonic sensor technology to safeguard against societal Pb2+ poisoning.
Operando Raman spectroscopy uncovers hydroxide and CO species enhance ethanol selectivity during pulsed CO2 electroreduction
Authors: Herzog Antonia , Lopez Luna Mauricio , Jeon Hyo Sang , Rettenmaier Clara , Grosse Philipp , Bergmann Arno , Roldan Cuenya Beatriz
Published: May 2024

Pulsed CO2 electroreduction (CO2RR) has recently emerged as a facile way to in situ tune the product selectivity, in particular toward ethanol, without re-designing the catalytic system. However, in-depth mechanistic understanding requires comprehensive operando time-resolved studies to identify the kinetics and dynamics of the electrocatalytic interface. Here, we track the adsorbates and the catalyst state of pre-reduced Cu2O nanocubes ( ~ 30 nm) during pulsed CO2RR using sub-second time-resolved operando Raman spectroscopy. By screening a variety of product-steering pulse length conditions, we unravel the critical role of co-adsorbed OH and CO on the Cu surface next to the oxidative formation of Cu-Oad or CuOx/(OH)y species, impacting the kinetics of CO adsorption and boosting the ethanol selectivity. However, a too low OHad coverage following the formation of bulk-like Cu2O induces a significant increase in the C1 selectivity, while a too high OHad coverage poisons the surface for C-C coupling. Thus, we unveil the importance of co-adsorbed OH on the alcohol formation under CO2RR conditions and thereby, pave the way for improved catalyst design and operating conditions.
Enabling 3D CT-scanning of cultural heritage objects using only in-house 2D X-ray equipment in museums
Authors: Bossema Francien G. , Palenstijn Willem Jan , Heginbotham Arlen , Corona Madeline , van Leeuwen Tristan , van Liere Robert , Dorscheid Jan , O’Flynn Daniel , Dyer Joanne , Hermens Erma , Batenburg K. Joost
Published: May 2024

Visualizing the internal structure of museum objects is a crucial step in acquiring knowledge about the origin, state, and composition of cultural heritage artifacts. Among the most powerful techniques for exposing the interior of museum objects is computed tomography (CT), a technique that computationally forms a 3D image using hundreds of radiographs acquired in a full circular range. However, the lack of affordable and versatile CT equipment in museums, combined with the challenge of transporting precious collection objects, currently keeps this technique out of reach for most cultural heritage applications. We propose an approach for creating accurate CT reconstructions using only standard 2D radiography equipment already available in most larger museums. Specifically, we demonstrate that a combination of basic X-ray imaging equipment, a tailored marker-based image acquisition protocol, and sophisticated data-processing algorithms, can achieve 3D imaging of collection objects without the need for a costly CT imaging system. We implemented this approach in the British Museum (London), the J. Paul Getty Museum (Los Angeles), and the Rijksmuseum (Amsterdam). Our work paves the way for broad facilitation and adoption of CT technology across museums worldwide.
Drosophila Evi5 is a critical regulator of intracellular iron transport via transferrin and ferritin interactions
Authors: Soltani Sattar , Webb Samuel M. , Kroll Thomas , King-Jones Kirst
Published: May 2024

Vesicular transport is essential for delivering cargo to intracellular destinations. Evi5 is a Rab11-GTPase-activating protein involved in endosome recycling. In humans, Evi5 is a high-risk locus for multiple sclerosis, a debilitating disease that also presents with excess iron in the CNS. In insects, the prothoracic gland (PG) requires entry of extracellular iron to synthesize steroidogenic enzyme cofactors. The mechanism of peripheral iron uptake in insect cells remains controversial. We show that Evi5-depletion in the Drosophila PG affected vesicle morphology and density, blocked endosome recycling and impaired trafficking of transferrin-1, thus disrupting heme synthesis due to reduced cellular iron concentrations. We show that ferritin delivers iron to the PG as well, and interacts physically with Evi5. Further, ferritin-injection rescued developmental delays associated with Evi5-depletion. To summarize, our findings show that Evi5 is critical for intracellular iron trafficking via transferrin-1 and ferritin, and implicate altered iron homeostasis in the etiology of multiple sclerosis.
Severe outcomes of malaria in children under time-varying exposure
Authors: De Salazar Pablo M. , Kamau Alice , Cavelan Aurelien , Akech Samuel , Mpimbaza Arthur , Snow Robert W. , Penny Melissa A.
Published: May 2024

In malaria epidemiology, interpolation frameworks based on available observations are critical for policy decisions and interpreting disease burden. Updating our understanding of the empirical evidence across different populations, settings, and timeframes is crucial to improving inference for supporting public health. Here, via individual-based modeling, we evaluate a large, multicountry, contemporary Plasmodium falciparum severe malaria dataset to better understand the relationship between prevalence and incidence of malaria pediatric hospitalizations - a proxy of malaria severe outcomes- in East-Africa. We find that life-long exposure dynamics, and subsequent protection patterns in children, substantially determine the likelihood of malaria hospitalizations relative to ongoing prevalence at the population level. Unsteady transmission patterns over a lifetime in children -increasing or decreasing- lead to an exponential relationship of hospitalization rates versus prevalence rather than the asymptotic pattern observed under steady transmission. Addressing this increase in the complexity of malaria epidemiology is crucial to update burden assessments via inference models that guide current and future policy decisions.
Long-read powered viral metagenomics in the oligotrophic Sargasso Sea
Authors: Warwick-Dugdale Joanna , Tian Funing , Michelsen Michelle L. , Cronin Dylan R. , Moore Karen , Farbos Audrey , Chittick Lauren , Bell Ashley , Zayed Ahmed A. , Buchholz Holger H. , Bolanos Luis M. , Parsons Rachel J. , Allen Michael J. , Sullivan Matthew B. , Temperton Ben
Published: May 2024

Dominant microorganisms of the Sargasso Sea are key drivers of the global carbon cycle. However, associated viruses that shape microbial community structure and function are not well characterised. Here, we combined short and long read sequencing to survey Sargasso Sea phage communities in virus- and cellular fractions at viral maximum (80 m) and mesopelagic (200 m) depths. We identified 2,301 Sargasso Sea phage populations from 186 genera. Over half of the phage populations identified here lacked representation in global ocean viral metagenomes, whilst 177 of the 186 identified genera lacked representation in genomic databases of phage isolates. Viral fraction and cell-associated viral communities were decoupled, indicating viral turnover occurred across periods longer than the sampling period of three days. Inclusion of long-read data was critical for capturing the breadth of viral diversity. Phage isolates that infect the dominant bacterial taxa Prochlorococcus and Pelagibacter, usually regarded as cosmopolitan and abundant, were poorly represented.
Tracking nuclear motion in single-molecule magnets using femtosecond X-ray absorption spectroscopy
Authors: Barlow Kyle , Phelps Ryan , Eng Julien , Katayama Tetsuo , Sutcliffe Erica , Coletta Marco , Brechin Euan K. , Penfold Thomas J. , Johansson J. Olof
Published: May 2024

The development of new data storage solutions is crucial for emerging digital technologies. Recently, all-optical magnetic switching has been achieved in dielectrics, proving to be faster than traditional methods. Despite this, single-molecule magnets (SMMs), which are an important class of magnetic materials due to their nanometre size, remain underexplored for ultrafast photomagnetic switching. Herein, we report femtosecond time-resolved K-edge X-ray absorption spectroscopy (TR-XAS) on a Mn(III)-based trinuclear SMM. Exploiting the elemental specificity of XAS, we directly track nuclear dynamics around the metal ions and show that the ultrafast dynamics upon excitation of a crystal-field transition are dominated by a magnetically active Jahn-Teller mode. Our results, supported by simulations, reveal minute bond length changes from 0.01 to 0.05 Å demonstrating the sensitivity of the method. These geometrical changes are discussed in terms of magneto-structural relationships and consequently our results illustrate the importance of TR-XAS for the emerging area of ultrafast molecular magnetism.
Transfer learning enables identification of multiple types of RNA modifications using nanopore direct RNA sequencing
Authors: Wu You , Shao Wenna , Yan Mengxiao , Wang Yuqin , Xu Pengfei , Huang Guoqiang , Li Xiaofei , Gregory Brian D. , Yang Jun , Wang Hongxia , Yu Xiang
Published: May 2024

Nanopore direct RNA sequencing (DRS) has emerged as a powerful tool for RNA modification identification. However, concurrently detecting multiple types of modifications in a single DRS sample remains a challenge. Here, we develop TandemMod, a transferable deep learning framework capable of detecting multiple types of RNA modifications in single DRS data. To train high-performance TandemMod models, we generate in vitro epitranscriptome datasets from cDNA libraries, containing thousands of transcripts labeled with various types of RNA modifications. We validate the performance of TandemMod on both in vitro transcripts and in vivo human cell lines, confirming its high accuracy for profiling m6A and m5C modification sites. Furthermore, we perform transfer learning for identifying other modifications such as m7G, Ψ, and inosine, significantly reducing training data size and running time without compromising performance. Finally, we apply TandemMod to identify 3 types of RNA modifications in rice grown in different environments, demonstrating its applicability across species and conditions. In summary, we provide a resource with ground-truth labels that can serve as benchmark datasets for nanopore-based modification identification methods, and TandemMod for identifying diverse RNA modifications using a single DRS sample.
Three-dimensional liquid metal-based neuro-interfaces for human hippocampal organoids
Authors: Wu Yan , Cheng Jinhao , Qi Jie , Hang Chen , Dong Ruihua , Low Boon Chuan , Yu Hanry , Jiang Xingyu
Published: May 2024

Human hippocampal organoids (hHOs) derived from human induced pluripotent stem cells (hiPSCs) have emerged as promising models for investigating neurodegenerative disorders, such as schizophrenia and Alzheimer’s disease. However, obtaining the electrical information of these free-floating organoids in a noninvasive manner remains a challenge using commercial multi-electrode arrays (MEAs). The three-dimensional (3D) MEAs developed recently acquired only a few neural signals due to limited channel numbers. Here, we report a hippocampal cyborg organoid (cyb-organoid) platform coupling a liquid metal-polymer conductor (MPC)-based mesh neuro-interface with hHOs. The mesh MPC (mMPC) integrates 128-channel multielectrode arrays distributed on a small surface area (~2*2 mm). Stretchability (up to 500%) and flexibility of the mMPC enable its attachment to hHOs. Furthermore, we show that under Wnt3a and SHH activator induction, hHOs produce HOPX+ and PAX6+ progenitors and ZBTB20+PROX1+ dentate gyrus (DG) granule neurons. The transcriptomic signatures of hHOs reveal high similarity to the developing human hippocampus. We successfully detect neural activities from hHOs via the mMPC from this cyb-organoid. Compared with traditional planar devices, our non-invasive coupling offers an adaptor for recording neural signals from 3D models.
Children exhibit superior memory for attended but outdated information compared to adults
Authors: Fu Yingtao , Guo Tingyu , Zheng Jiewei , He Jie , Shen Mowei , Chen Hui
Published: May 2024

Research on the development of cognitive selectivity predominantly focuses on attentional selection. The present study explores another facet of cognitive selectivity—memory selection—by examining the ability to filter attended yet outdated information in young children and adults. Across five experiments involving 130 children and 130 adults, participants are instructed to use specific information to complete a task, and then unexpectedly asked to report this information in a surprise test. The results consistently demonstrate a developmental reversal-like phenomenon, with children outperforming adults in reporting this kind of attended yet outdated information. Furthermore, we provide evidence against the idea that the results are due to different processing strategies or attentional deployments between adults and children. These results suggest that the ability of memory selection is not fully developed in young children, resulting in their inefficient filtering of attended yet outdated information that is not required for memory retention.
Regulation of cerebral blood flow boosts precise brain targeting of vinpocetine-derived ionizable-lipidoid nanoparticles
Authors: Bian Xufei , Yang Ling , Jiang Dingxi , Grippin Adam J. , Ma Yifan , Wu Shuang , Wu Linchong , Wang Xiaoyou , Tang Zhongjie , Tang Kaicheng , Pan Weidong , Dong Shiyan , Kim Betty Y. S. , Jiang Wen , Yang Zhaogang , Li Chong
Published: May 2024

Despite advances in active drug targeting for blood-brain barrier penetration, two key challenges persist: first, attachment of a targeting ligand to the drug or drug carrier does not enhance its brain biodistribution; and second, many brain diseases are intricately linked to microcirculation disorders that significantly impede drug accumulation within brain lesions even after they cross the barrier. Inspired by the neuroprotective properties of vinpocetine, which regulates cerebral blood flow, we propose a molecular library design centered on this class of cyclic tertiary amine compounds and develop a self-enhanced brain-targeted nucleic acid delivery system. Our findings reveal that: (i) vinpocetine-derived ionizable-lipidoid nanoparticles efficiently breach the blood-brain barrier; (ii) they have high gene-loading capacity, facilitating endosomal escape and intracellular transport; (iii) their administration is safe with minimal immunogenicity even with prolonged use; and (iv) they have potent pharmacologic brain-protective activity and may synergize with treatments for brain disorders as demonstrated in male APP/PS1 mice.
Structural basis of human NOX5 activation
Authors: Cui Chenxi , Jiang Meiqin , Jain Nikhil , Das Sourav , Lo Yu-Hua , Kermani Ali A. , Pipatpolkai Tanadet , Sun Ji
Published: May 2024

NADPH oxidase 5 (NOX5) catalyzes the production of superoxide free radicals and regulates physiological processes from sperm motility to cardiac rhythm. Overexpression of NOX5 leads to cancers, diabetes, and cardiovascular diseases. NOX5 is activated by intracellular calcium signaling, but the underlying molecular mechanism of which — in particular, how calcium triggers electron transfer from NADPH to FAD — is still unclear. Here we capture motions of full-length human NOX5 upon calcium binding using single-particle cryogenic electron microscopy (cryo-EM). By combining biochemistry, mutagenesis analyses, and molecular dynamics (MD) simulations, we decode the molecular basis of NOX5 activation and electron transfer. We find that calcium binding to the EF-hand domain increases NADPH dynamics, permitting electron transfer between NADPH and FAD and superoxide production. Our structural findings also uncover a zinc-binding motif that is important for NOX5 stability and enzymatic activity, revealing modulation mechanisms of reactive oxygen species (ROS) production.
Chemical manipulation of an activation/inhibition switch in the nuclear receptor PXR
Authors: Garcia-Maldonado Efren , Huber Andrew D. , Chai Sergio C. , Nithianantham Stanley , Li Yongtao , Wu Jing , Poudel Shyaron , Miller Darcie J. , Seetharaman Jayaraman , Chen Taosheng
Published: May 2024

Nuclear receptors are ligand-activated transcription factors that can often be useful drug targets. Unfortunately, ligand promiscuity leads to two-thirds of receptors remaining clinically untargeted. PXR is a nuclear receptor that can be activated by diverse compounds to elevate metabolism, negatively impacting drug efficacy and safety. This presents a barrier to drug development because compounds designed to target other proteins must avoid PXR activation while retaining potency for the desired target. This problem could be avoided by using PXR antagonists, but these compounds are rare, and their molecular mechanisms remain unknown. Here, we report structurally related PXR-selective agonists and antagonists and their corresponding co-crystal structures to describe mechanisms of antagonism and selectivity. Structural and computational approaches show that antagonists induce PXR conformational changes incompatible with transcriptional coactivator recruitment. These results guide the design of compounds with predictable agonist/antagonist activities and bolster efforts to generate antagonists to prevent PXR activation interfering with other drugs.
Enabling nucleophilic reactivity in molecular calcium fluoride complexes
Authors: Struijs Job J. C. , Ellwanger Mathias A. , Crumpton Agamemnon E. , Gouverneur Véronique , Aldridge Simon
Published: May 2024

Calcium fluoride is the ultimate source of all fluorochemicals. Current synthetic approaches rely on the use of HF, generated from naturally occurring fluorspar and sulfuric acid. Methods for constructing E–F bonds directly from CaF2 have long been frustrated by its high lattice energy, low solubility and impaired fluoride ion nucleophilicity. Little fundamental understanding of the reactivity of Ca–F moieties is available to guide methodology development; well-defined molecular species containing Ca–F bonds are extremely rare, and existing examples are strongly aggregated and evidence no nucleophilic fluoride delivery. Here, by contrast, we show that by targeting anionic systems of the type [Ln(X)2CaF]−, monomeric calcium fluoride complexes containing single Ca–F bonds can be synthesized, including via routes involving fluoride abstraction from existing C–F bonds. Comparative structural and spectroscopic studies of mono- and dinuclear systems allow us to define structure–activity relationships for E–F bond formation from molecular calcium fluorides.