bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti-methicillin resistant Staphylococcus aureus (MRSA) activity of fermented apple peels kombucha and their chemical content
Authors: Fitriasari P D , Zahrotunisya D T
Published: March 2024

The production of kombucha using local apple peels is expected to reduce the production of apple peel waste while increasing the nutritional and functional value of kombucha products. This study aimed to determine the active compounds and antibacterial activity of kombucha apple peels against MRSA (Methicillin Resistant Staphylococcus aureus). This research was carried out experimentally in a completely randomised design with two factors: the apple varieties (Anna, Manalagi, and Romebeauty) and the concentration of the apple peel substrate (2.5%, 7.5% and 12.5%). The analyses comprised phytochemical screening and antimicrobial activity testing, both qualitative and quantitative. The results showed that the kombucha apple peel contains tannins, saponins, flavonoids, polyphenols, and organic acids. The average total phenolic, total acid, and antibacterial activities of Kombucha apple peels were significantly (α≤0.05) differently affected by apple cultivar and substrate concentration. Antimicrobial activity against MRSA showed a range of weak to moderate inhibition, with the highest inhibition zone diameter value of 6.58 ± 0.52 mm in the Anna variety treatment at 12.5% substrate concentration. The MIC of the best treated kombucha was found at a concentration of 85%, while the MBC could not be determined.
Influence of meridional circulation on extreme high temperature and weakened rainfall over the Yangtze River Valley in August 2022
Authors: Cang Chen , Liew Juneng , Cheng Jianbo , Zhao Yuheng , Xu Zhihang , Chen Honghui , Feng Guolin
Published: March 2024

The Yangtze River Valley (YRV) experienced record-breaking extreme high temperature and weakened rainfall events in August 2022, which resulted in severe disasters and large socioeconomic losses. The importance of the intensification and westward movement of the western Pacific subtropical high (WPSH) with abnormal subsidence has been emphasized in previous studies. However, the source of the abnormal subsidence remains unknown. This study investigates the source of the abnormal subsidence over the YRV and discusses its possible causes by adopting the three-pattern decomposition of the atmospheric circulation (3P-DGAC). Meridional circulation (MC) was the main contributor to the abnormal vertical velocity (114%), while the contribution of zonal circulation (ZC) was negative (–14%). Additionally, the negative rainfall anomaly over the YRV can be explained mainly by the MC. The anomalous MC was characterized as a ‘negative-positive-negative-positive-negative’ quintuple distribution with sinking motion over the YRV. Anomalous MC is closely related to the sea surface temperature anomaly (SSTA) over the three oceans. The negative phase of the Indian Ocean dipole (IOD) and La Niña SSTA leads to an anomalous rising motion of the ZC over the Maritime Continent, favoring the existence of the rising motion of the MC by the coupling effect. The positive phase of the North Atlantic triple (NAT) SSTA results in an anomalous Rossby wave train, which further leads to a sinking motion over the YRV.
Mechanical and morphological analysis of cellulose extracted from sisal fibers and their effect on bio-based composites mechanical properties
Authors: Zidi Samir , Miraoui Imed
Published: March 2024

This study aims to investigate the viability of untreated sisal fibers (N.F.), NaOH-treated sisal fibers (NaOH.F.) and cellulose extracted from sisal (CELL.F.) as an alternative to synthetic materials to produce biocomposites. The main objective was to conduct an in-depth study of the properties of these fibers whose aim is to limit matrix/fiber slippage and improve adhesion by modifying reinforcement surfaces, and to improve the efficiency of sisal fibers as reinforcements for composite materials using various analytical techniques including Fourier transform infrared spectroscopy, scanning electron microscopy, x-ray diffraction, and thermogravimetric analysis. In addition, the study aimed to produce a composite material by reinforcing plaster with the aforementioned fibers and then compare the mechanical and physical properties of the resulting material. The results showed that cellulose fibers exhibited higher mechanical strength and better compatibility with the plaster-matrix compared to sisal fibers by an increse of 324% in their tensil strength compared to natural sial fibers. In particular, the flexural strength showed a significant increase of 35% in the cellulose fiber reinforced composite. The reinforced composite material exhibited improved properties such as better flexural strength, increased absorption by 12.8% and descres the density by 21.3%, highlighting the promising prospects of cellulose fibers in advancing biocomposite technology.
Comparative analysis of cement-based bricks in India: a cradle-to-gate life cycle assessment
Authors: Sravani Tata , Ramani Prasanna Venkatesan , Anbu Madhumathi
Published: March 2024

The main aim of this study is to quantify the environmental impact caused by different types of bricks used in the Indian construction field. This study considered four brick types: Autoclave Aerated Concrete, Fly ash, and Cellular Foam bricks. The prime objectives of the investigation are to evaluate and compare the embodied energy and resource depletion by modelling the environmental impact of the bricks by Global Warming Potential (GWP) with the LCA software SimaPro. The study’s use of a cradle-to-gate approach provides a comprehensive understanding of the environmental implications associated with four types of bricks. Moreover, the analysis conducted using SimaPro 8.1 software with the life cycle ReCiPe 2016 v1.1 and IMPACT 2002 + v2.15 demonstrates the rigour and accuracy of the findings. The results indicate that cement bricks have the lowest Global Warming Potential, specific heat, and cost, making them a more environmentally and economically friendly option than other bricks. Furthermore, weight, water absorption, density, thermal conductivity, and compressive strength were also analyzed and showed other better-performing bricks.
Effect of source and drain electrode positions on the performance of bottom gate organic thin film transistor
Authors: Rathod Arun Pratap Singh , Dubey V P , Gowri R , Juneja P K
Published: March 2024

In recent years several novel technologies have emerged on commercial level. Organic electronics is one such technology that has created new avenues for the development of flexible, robust, and cost-effective electronic devices. Transistor developed using organic materials are called organic thin film transistors (OTFT). Transistor is elementary component of any electronic device, any variation in the size or performance of the transistors reflects directly on the overall performance of the electronic devices. Bottom gate bottom contact (BGBC) OTFT is commonly employed single gate organic transistor owing to its simple architecture and easy fabrications. Since in organic semiconductor material carrier mobility of charges is lower, hence its overall performance declines. As a result, its application in electronic circuits becomes limited. Therefore, to enhance the performance of BGBC OTFT and facilitate the optimal charge mobilisation inside organic semiconductor layer i.e., OSC, improvement in the architecture of BGBC is deemed necessary. In this research article the performance of BGBC OTFT is analysed for different positions of electrodes viz. source and drain embedded inside the OSC layer. The study signifies the effect of electrode positions on performance optimization of BGBC OTFT without changing the materials, dimensions, or the operating voltage regime. It has been found that for 30 nm thick OSC layer, the electrodes should ideally be placed between 5 nm to 10 nm above the junction of OSC and dielectric layer inside OSC layer for optimal results.
Actively learning costly reward functions for reinforcement learning
Authors: Eberhard André , Metni Houssam , Fahland Georg , Stroh Alexander , Friederich Pascal
Published: March 2024

Transfer of recent advances in deep reinforcement learning to real-world applications is hindered by high data demands and thus low efficiency and scalability. Through independent improvements of components such as replay buffers or more stable learning algorithms, and through massively distributed systems, training time could be reduced from several days to several hours for standard benchmark tasks. However, while rewards in simulated environments are well-defined and easy to compute, reward evaluation becomes the bottleneck in many real-world environments, e.g. in molecular optimization tasks, where computationally demanding simulations or even experiments are required to evaluate states and to quantify rewards. When ground-truth evaluations become orders of magnitude more expensive than in research scenarios, direct transfer of recent advances would require massive amounts of scale, just for evaluating rewards rather than training the models. We propose to alleviate this problem by replacing costly ground-truth rewards with rewards modeled by neural networks, counteracting non-stationarity of state and reward distributions during training with an active learning component. We demonstrate that using our proposed method, it is possible to train agents in complex real-world environments orders of magnitudes faster than would be possible when using ground-truth rewards. By enabling the application of RL methods to new domains, we show that we can find interesting and non-trivial solutions to real-world optimization problems in chemistry, materials science and engineering. We demonstrate speed-up factors of 50–3000 when applying our approach to challenges of molecular design and airfoil optimization.
Effects of extreme temperatures and recovery potential of Gongolaria barbata from a coastal lagoon in the northern Adriatic Sea: an ex situ approach
Authors: Bilajac Andrea , Gljušćić Edi , Smith Shannen , Najdek Mirjana , Iveša Ljiljana
Published: March 2024

Background and Aims

Globally, rising seawater temperatures contribute to the regression of marine macroalgal forests. Along the Istrian coastline (northern Adriatic), an isolated population of Gongolaria barbata persists in a coastal lagoon, representing one of the last marine macroalgal forests in the region. Our objective was to examine the impact of extreme temperatures on the morphology and physiology of G. barbata and test its potential for recovery after simulating marine heatwave (MHW) conditions.

Methods

We explored the occurrence of marine heatwaves in southern Istria, adjacent to the study area, in addition to extreme temperatures inside the area itself. Subsequently, we performed a thermotolerance experiment, consisting of a stress and recovery phase, in which we exposed G. barbata thalli to four extreme (28, 30, 32 and 34 °C) and one favourable (18 °C) temperature. We monitored morphological and physiological responses.

Key Results

Our findings indicate a significant rise in frequency, duration and intensity of MHWs over decades on the southern Istrian coast. Experimental results show that G. barbata demonstrates potential for both morphological and physiological recovery after exposure to temperatures as high as 32 °C. However, exposure to 34 °C led to thallus decay, with limited ability to regenerate.

Conclusions

Our results show that G. barbata has a remarkable resilience to long-term exposure to extreme temperatures ≤32 °C and suggest that short-term exposure to temperatures beyond this, as currently recorded inside the lagoon, do not notably affect the physiology or morphology of local G. barbata. With more MHWs expected in the future, such an adapted population might represent an important donor suitable for future restoration activities along the Istrian coast. These results emphasize the resilience of this unique population, but also warn of the vulnerability of marine macroalgal forests to rising seawater temperatures in rapidly changing climatic conditions.
The use of technology in case management in international investment arbitration: a realistic approach
Authors: Yıldırım Ahmet Cemil
Published: March 2024

Investment arbitration, with its unique demands for transparency due to the public interest, is an especially promising arena for AI technologies. This transparency push and the judicialization of processes make investment arbitration increasingly amenable to technological innovations. However, the full potential of artificial intelligence (AI) in streamlining international investment arbitration case management remains largely untapped. The key to unlocking this potential lies in digitalization of data and procedures, and inter-institutional collaboration to share data. The literature regarding the use of technology in international arbitration mainly focuses on AI and its potential use in international arbitration in the future. While much of this literature speculates about the future, a holistic understanding of the present state of technology in international investment arbitration is crucial. This article spotlights the advancements achievable in case management in international investment arbitration using today’s available technologies. The current state of AI technology is primed for handling straightforward procedural tasks. Yet, these modest tasks occupy significant bandwidth in the agendas of arbitral institutions and tribunals. Once comprehensive digitalization is achieved, and AI technologies are integrated into international investment arbitration case management adeptly, that will be a significant step towards more expeditious and cost-effective arbitration procedures.
Bayesian two-stage modeling of longitudinal and time-to-event data with an integrated fractional Brownian motion covariance structure
Authors: Palipana Anushka , Song Seongho , Gupta Nishant , Szczesniak Rhonda
Published: March 2024

It is difficult to characterize complex variations of biological processes, often longitudinally measured using biomarkers that yield noisy data. While joint modeling with a longitudinal submodel for the biomarker measurements and a survival submodel for assessing the hazard of events can alleviate measurement error issues, the continuous longitudinal submodel often uses random intercepts and slopes to estimate both between- and within-patient heterogeneity in biomarker trajectories. To overcome longitudinal submodel challenges, we replace random slopes with scaled integrated fractional Brownian motion (IFBM). As a more generalized version of integrated Brownian motion, IFBM reasonably depicts noisily measured biological processes. From this longitudinal IFBM model, we derive novel target functions to monitor the risk of rapid disease progression as real-time predictive probabilities. Predicted biomarker values from the IFBM submodel are used as inputs in a Cox submodel to estimate event hazard. This two-stage approach to fit the submodels is performed via Bayesian posterior computation and inference. We use the proposed approach to predict dynamic lung disease progression and mortality in women with a rare disease called lymphangioleiomyomatosis who were followed in a national patient registry. We compare our approach to those using integrated Ornstein-Uhlenbeck or conventional random intercepts-and-slopes terms for the longitudinal submodel. In the comparative analysis, the IFBM model consistently demonstrated superior predictive performance.
Accounting for network noise in graph-guided Bayesian modeling of structured high-dimensional data
Authors: Li Wenrui , Chang Changgee , Kundu Suprateek , Long Qi
Published: March 2024

There is a growing body of literature on knowledge-guided statistical learning methods for analysis of structured high-dimensional data (such as genomic and transcriptomic data) that can incorporate knowledge of underlying networks derived from functional genomics and functional proteomics. These methods have been shown to improve variable selection and prediction accuracy and yield more interpretable results. However, these methods typically use graphs extracted from existing databases or rely on subject matter expertise, which are known to be incomplete and may contain false edges. To address this gap, we propose a graph-guided Bayesian modeling framework to account for network noise in regression models involving structured high-dimensional predictors. Specifically, we use 2 sources of network information, including the noisy graph extracted from existing databases and the estimated graph from observed predictors in the dataset at hand, to inform the model for the true underlying network via a latent scale modeling framework. This model is coupled with the Bayesian regression model with structured high-dimensional predictors involving an adaptive structured shrinkage prior. We develop an efficient Markov chain Monte Carlo algorithm for posterior sampling. We demonstrate the advantages of our method over existing methods in simulations, and through analyses of a genomics dataset and another proteomics dataset for Alzheimer’s disease.
Underlining neighbourhood perception: a possible risk factor for dementia that deserves more attention
Authors: Sevi Barış , Gutiérrez Ángela , Muniz-Terrera Graciela
Published: March 2024

This essay highlights the interplay between the neighbourhood structural environment and neighbourhood perceptions on dementia by articulating how an individual’s perception of neighbourhood, with respect to their individual differences, may provide key insights to understand the link between the neighbourhood and dementia.
Peri-ictal activation of dorsomedial dorsal raphe serotonin neurons reduces mortality associated with maximal electroshock seizures
Authors: Petrucci Alexandra N , Jones Allysa R , Kreitlow Benjamin L , Buchanan Gordon F
Published: March 2024

Over one-third of patients with epilepsy will develop refractory epilepsy and continue to experience seizures despite medical treatment. These patients are at the greatest risk for sudden unexpected death in epilepsy. The precise mechanisms underlying sudden unexpected death in epilepsy are unknown, but cardiorespiratory dysfunction and arousal impairment have been implicated. Substantial circumstantial evidence suggests serotonin is relevant to sudden unexpected death in epilepsy as it modulates sleep/wake regulation, breathing and arousal. The dorsal raphe nucleus is a major serotonergic center and a component of the ascending arousal system. Seizures disrupt the firing of dorsal raphe neurons, which may contribute to reduced responsiveness. However, the relevance of the dorsal raphe nucleus and its subnuclei to sudden unexpected death in epilepsy remains unclear. The dorsomedial dorsal raphe may be a salient target due to its role in stress and its connections with structures implicated in sudden unexpected death in epilepsy. We hypothesized that optogenetic activation of dorsomedial dorsal raphe serotonin neurons in TPH2-ChR2-YFP (n = 26) mice and wild-type (n = 27) littermates before induction of a maximal electroshock seizure would reduce mortality. In this study, pre-seizure activation of dorsal raphe nucleus serotonin neurons reduced mortality in TPH2-ChR2-YFP mice with implants aimed at the dorsomedial dorsal raphe. These results implicate the dorsomedial dorsal raphe in this novel circuit influencing seizure-induced mortality. It is our hope that these results and future experiments will define circuit mechanisms that could ultimately reduce sudden unexpected death in epilepsy.
Parkinson’s disease impairs cortical sensori-motor decision-making cascades
Authors: Tomassini Alessandro , Cope Thomas E , Zhang Jiaxiang , Rowe James B
Published: March 2024

The transformation from perception to action requires a set of neuronal decisions about the nature of the percept, identification and selection of response options and execution of the appropriate motor response. The unfolding of such decisions is mediated by distributed representations of the decision variables—evidence and intentions—that are represented through oscillatory activity across the cortex. Here we combine magneto-electroencephalography and linear ballistic accumulator models of decision-making to reveal the impact of Parkinson’s disease during the selection and execution of action. We used a visuomotor task in which we independently manipulated uncertainty in sensory and action domains. A generative accumulator model was optimized to single-trial neurophysiological correlates of human behaviour, mapping the cortical oscillatory signatures of decision-making, and relating these to separate processes accumulating sensory evidence and selecting a motor action. We confirmed the role of widespread beta oscillatory activity in shaping the feed-forward cascade of evidence accumulation from resolution of sensory inputs to selection of appropriate responses. By contrasting the spatiotemporal dynamics of evidence accumulation in age-matched healthy controls and people with Parkinson’s disease, we identified disruption of the beta-mediated cascade of evidence accumulation as the hallmark of atypical decision-making in Parkinson’s disease. In frontal cortical regions, there was inefficient processing and transfer of perceptual information. Our findings emphasize the intimate connection between abnormal visuomotor function and pathological oscillatory activity in neurodegenerative disease. We propose that disruption of the oscillatory mechanisms governing fast and precise information exchanges between the sensory and motor systems contributes to behavioural changes in people with Parkinson’s disease.
Hierarchical functional differences between gyri and sulci at different scales
Authors: Zhao Lin , Dai Haixing , Wu Zihao , Jiang Xi , Zhu Dajiang , Zhang Tuo , Liu Tianming
Published: March 2024

Gyri and sulci are 2 fundamental cortical folding patterns of the human brain. Recent studies have suggested that gyri and sulci may play different functional roles given their structural and functional heterogeneity. However, our understanding of the functional differences between gyri and sulci remains limited due to several factors. Firstly, previous studies have typically focused on either the spatial or temporal domain, neglecting the inherently spatiotemporal nature of brain functions. Secondly, analyses have often been restricted to either local or global scales, leaving the question of hierarchical functional differences unresolved. Lastly, there has been a lack of appropriate analytical tools for interpreting the hierarchical spatiotemporal features that could provide insights into these differences. To overcome these limitations, in this paper, we proposed a novel hierarchical interpretable autoencoder (HIAE) to explore the hierarchical functional difference between gyri and sulci. Central to our approach is its capability to extract hierarchical features via a deep convolutional autoencoder and then to map these features into an embedding vector using a carefully designed feature interpreter. This process transforms the features into interpretable spatiotemporal patterns, which are pivotal in investigating the functional disparities between gyri and sulci. We evaluate the proposed framework on Human Connectome Project task functional magnetic resonance imaging dataset. The experiments demonstrate that the HIAE model can effectively extract and interpret hierarchical spatiotemporal features that are neuroscientifically meaningful. The analyses based on the interpreted features suggest that gyri are more globally activated, whereas sulci are more locally activated, demonstrating a distinct transition in activation patterns as the scale shifts from local to global. Overall, our study provides novel insights into the brain’s anatomy–function relationship.
Enhancement of weak signals by dynamic stochastic resonance in dark-field microscopy imaging
Authors: Zhang Bo , Xu Yue , Ma Yun Peng , Liu Hui , Li Yuan Fang , Huang Cheng Zhi
Published: March 2024

Enhancing weak signal acquisition is pivotal for bolstering analysis and detection capabilities. Herein, a dynamic stochastic resonance (DSR) algorithm for weak signal amplification that was identified to significantly improve the imaging visibility of dark-field microscopy nanoparticles under low illumination conditions is presented. When further combined with composite filed microscopy, DSR displays signal amplification much more effectively, showing high promise for detection purposes.
Association Between Social Vulnerability and Streptococcus pneumoniae Antimicrobial Resistance in US Adults
Authors: Mohanty Salini , Ye Gang , Sheets Charles , Cossrow Nicole , Yu Kalvin C , White Meghan , Klinker Kenneth P , Gupta Vikas
Published: March 2024

Background

Growing evidence indicates antimicrobial resistance disproportionately affects individuals living in socially vulnerable areas. This study evaluated the association between the CDC/ATSDR Social Vulnerability Index (SVI) and Streptococcus pneumoniae (SP) antimicrobial resistance (AMR) in the United States.

Methods

Adult patients ≥18 years with 30-day nonduplicate SP isolates from ambulatory/hospital settings from January 2011 to December 2022 with zip codes of residence were evaluated across 177 facilities in the BD Insights Research Database. Isolates were identified as SP AMR if they were non-susceptible to ≥1 antibiotic class (macrolide, tetracycline, extended-spectrum cephalosporins, or penicillin). Associations between SP AMR and SVI score (overall and themes) were evaluated using generalized estimating equations with repeated measurements within county to account for within-cluster correlations.

Results

Of 8008 unique SP isolates from 574 US counties across 39 states, the overall proportion of AMR was 49.9%. A significant association between socioeconomic status (SES) theme and SP AMR was detected with higher SES theme SVI score (indicating greater social vulnerability) associated with greater risk of AMR. On average, a decile increase of SES, indicating greater vulnerability, was associated with a 1.28% increased risk of AMR (95% confidence interval [CI], .61%, 1.95%; P = .0002). A decile increase of household characteristic score was associated with a 0.81% increased risk in SP AMR (95% CI, .13%, 1.49%; P = .0197). There was no association between racial/ethnic minority status, housing type and transportation theme, or overall SVI score and SP AMR.

Conclusions

SES and household characteristics were the SVI themes most associated with SP AMR.
Type 1 Human Immunodeficiency Virus (HIV-1) Incidence, Adherence, and Drug Resistance in Individuals Taking Daily Emtricitabine/Tenofovir Disoproxil Fumarate for HIV-1 Pre-exposure Prophylaxis: Pooled Analysis From 72 Global Studies
Authors: Landovitz Raphael J , Tao Li , Yang Juan , de Boer Melanie , Carter Christoph , Das Moupali , Baeten Jared M , Liu Albert , Hoover Karen W , Celum Connie , Grinsztejn Beatriz , Morris Sheldon , Wheeler Darrell P , Mayer Kenneth H , Golub Sarit A , Bekker Linda-Gail , Diabaté Souleymane , Hoornenborg Elske , Myers Janet , Leech Ashley A , McCormack Sheena , Chan Philip A , Sweat Michael , Matthews Lynn T , Grant Robert ,   the Global F/TDF PrEP Study Team, Beyrer Chris , Brown Joelle , Clark Jesse , Colson Paul , Eakle Robyn , Farley Jason , Flash Charlene A , Gallardo Jorge , Gottlieb Geoffrey , Grangeiro Alexandre , Heffron Renee , Hosek Sybil , Hull Mark , Idoko John , Inwani Irene , Koenig Helen , Kurth Ann , Lee Shui-shan , Mayer Kenneth , Mboup Souleymane , Meyer Jaimie , Mills Anthony , Mujugira Andrew , Pala Pietro , Phoenix John , Piatt Janice , Russell Darren , Sanders Eduard , Scott Rachel , Sevelius Jae , Shang Hong , Siegel Marc , Swaminathan Shobha , Tamayo Vivian , Tan Darrell , Taylor Allan , Vuylsteke Bea
Published: March 2024

Background

Oral pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (F/TDF) has high efficacy against HIV-1 acquisition. Seventy-two prospective studies of daily oral F/TDF PrEP were conducted to evaluate HIV-1 incidence, drug resistance, adherence, and bone and renal safety in diverse settings.

Methods

HIV-1 incidence was calculated from incident HIV-1 diagnoses after PrEP initiation and within 60 days of discontinuation. Tenofovir concentrations in dried blood spots (DBS), drug resistance, and bone/renal safety indicators were evaluated in a subset of studies.

Results

Among 17 274 participants, there were 101 cases with new HIV-1 diagnosis (.77 per 100 person-years; 95% confidence interval [CI]: .63–.94). In 78 cases with resistance data, 18 (23%) had M184I or V, 1 (1.3%) had K65R, and 3 (3.8%) had both mutations. In 54 cases with tenofovir concentration data from DBS, 45 (83.3%), 2 (3.7%), 6 (11.1%), and 1 (1.9%) had average adherence of <2, 2−3, 4−6, and ≥7 doses/wk, respectively, and the corresponding incidence was 3.9 (95% CI: 2.9–5.3), .24 (.060–.95), .27 (.12–.60), and .054 (.008–.38) per 100 person-years. Adherence was low in younger participants, Hispanic/Latinx and Black participants, cisgender women, and transgender women. Bone and renal adverse event incidence rates were 0.69 and 11.8 per 100 person-years, respectively, consistent with previous reports.

Conclusions

Leveraging the largest pooled analysis of global PrEP studies to date, we demonstrate that F/TDF is safe and highly effective, even with less than daily dosing, in diverse clinical settings, geographies, populations, and routes of HIV-1 exposure.
Narrativity and literariness in receptions of Josephus’s teknophagia story
Authors: Binyam Yonatan
Published: March 2024

In this article, I present an analysis of the narrative discourses and literary elements found in the teknophagia story that originates with Josephus’s Bellum Judaicum and trace the development of those motifs in subsequent Latin, Hebrew, Arabic, and Ethiopic versions of the story. I first outline the reception history of Josephus within medieval Coptic and Ethiopic literary traditions, by way of the Hebrew Sefer Yosippon and one of its Latin sources, the De Excidio Hierosolymitano. I then illustrate how the literariness of the various authors who reworked the teknophagia story influences a reading of the narrative discourses of each text. In doing so, I emphasize the unique iteration of the account of the cannibalistic mother that appears in the Christian-Arabic and Ethiopic histories, showing how this version of the story develops out of not only earlier stylistic changes, but also from the literary elements introduced into the story by the redactor of the Arabic reworking of the Hebrew Yosippon.
The interpreter’s role and deaf students’ autonomy in mainstream classrooms
Authors: Prinzi Lisa M
Published: March 2024

This article explores the interpreter's role and approaches to working with deaf students as seen from deaf individuals' and interpreters' perspectives. A group of 41 formerly mainstreamed deaf individuals and interpreters offered insights into how the interpreter's role in mainstream classrooms influences deaf student autonomy and participation. This research illustrates the significance of autonomy for mainstreamed deaf students and suggests a correlation between the interpreter’s role and deaf students’ perceived autonomy in the classroom. In addition, the findings suggest that deaf students do not always know what an interpreter is supposed to do in K-12 classrooms. This study also finds that educational team members do not always explicitly communicate their roles and responsibilities to deaf students, leading to confusion that impacts their autonomy and overall experience. Finally, this research finds that deaf students are not trained with the ability to negotiate and renegotiate the interpreter’s role. This article concludes with considerations and recommendations for deaf education and interpreter education communities.
Motor adaptation in deaf and hearing native signers
Authors: Stroh Anna-Lena , Overvliet Krista E , Zierul Björn , Rösler Frank , Röder Brigitte
Published: March 2024

Previous studies have suggested that deafness could lead to deficits in motor skills and other body-related abilities. However, the literature regarding motor skills in deaf adults is scarce and existing studies often included participants with heterogeneous language backgrounds and deafness etiologies, thus making it difficult to delineate the effects of deafness. In this study, we investigated motor learning in deaf native signers and hearing nonsigners. To isolate the effects of deafness and those of acquiring a signed language, we additionally tested a group of hearing native signers. Two well-established paradigms of motor learning were employed, in which participants had to adapt their hand movements to a rotation of the visual feedback (Experiment 1) or to the introduction of a force field (Experiment 2). Proprioceptive estimates were assessed before and after adaptation. Like hearing nonsigners, deaf and hearing signers showed robust adaptation in both motor adaptation paradigms. No significant differences in motor adaptation and memory were observed between deaf signers and hearing nonsigners, as well as between hearing signers and hearing nonsigners. Moreover, no discernible group differences in proprioceptive accuracy were observed. These findings challenge the prevalent notion that deafness leads to deficits in motor skills and other body-related abilities.
Deceptive Features on Platforms
Authors: Johnen Johannes , Somogyi Robert
Published: March 2024

Many products sold on online platforms have additional features like fees for services, shipping, luggage, upgrades, and so on. We study when a two-sided platform shrouds additional features towards potentially naive buyers. We explore a novel mechanism according to which platforms shroud to manipulate network externalities between buyers and sellers. Exploring this mechanism, we argue the advent of online marketplaces led to less transparent markets. First, platforms have stronger incentives to shroud seller fees than sellers themselves. Second, platforms shroud their own fees less if they earn more revenue from sellers; so when sellers on the platform compete more fiercely, platforms—somewhat perversely—shroud more. We connect these results to many applications and the current debate on regulating online platforms.
Chromosomal Inversions and the Demography of Speciation in Drosophila montana and Drosophila flavomontana
Authors: Poikela Noora , Laetsch Dominik R , Hoikkala Ville , Lohse Konrad , Kankare Maaria
Published: March 2024

Chromosomal inversions may play a central role in speciation given their ability to locally reduce recombination and therefore genetic exchange between diverging populations. We analyzed long- and short-read whole-genome data from sympatric and allopatric populations of 2 Drosophila virilis group species, Drosophila montana and Drosophila flavomontana, to understand if inversions have contributed to their divergence. We identified 3 large alternatively fixed inversions on the X chromosome and one on each of the autosomes 4 and 5. A comparison of demographic models estimated for inverted and noninverted (colinear) chromosomal regions suggests that these inversions arose before the time of the species split. We detected a low rate of interspecific gene flow (introgression) from D. montana to D. flavomontana, which was further reduced inside inversions and was lower in allopatric than in sympatric populations. Together, these results suggest that the inversions were already present in the common ancestral population and that gene exchange between the sister taxa was reduced within inversions both before and after the onset of species divergence. Such ancestrally polymorphic inversions may foster speciation by allowing the accumulation of genetic divergence in loci involved in adaptation and reproductive isolation inside inversions early in the speciation process, while gene exchange at colinear regions continues until the evolving reproductive barriers complete speciation. The overlapping X inversions are particularly good candidates for driving the speciation process of D. montana and D. flavomontana, since they harbor strong genetic incompatibilities that were detected in a recent study of experimental introgression.
Background Selection From Unlinked Sites Causes Nonindependent Evolution of Deleterious Mutations
Authors: Matheson Joseph , Masel Joanna
Published: March 2024

Background selection describes the reduction in neutral diversity caused by selection against deleterious alleles at other loci. It is typically assumed that the purging of deleterious alleles affects linked neutral variants, and indeed simulations typically only treat a genomic window. However, background selection at unlinked loci also depresses neutral diversity. In agreement with previous analytical approximations, in our simulations of a human-like genome with a realistically high genome-wide deleterious mutation rate, the effects of unlinked background selection exceed those of linked background selection. Background selection reduces neutral genetic diversity by a factor that is independent of census population size. Outside of genic regions, the strength of background selection increases with the mean selection coefficient, contradicting the linked theory but in agreement with the unlinked theory. Neutral diversity within genic regions is fairly independent of the strength of selection. Deleterious genetic load among haploid individuals is underdispersed, indicating nonindependent evolution of deleterious mutations. Empirical evidence for underdispersion was previously interpreted as evidence for global epistasis, but we recover it from a non-epistatic model.
Locations and characteristics of pharmacy deserts in the United States: a geospatial study
Authors: Wittenauer Rachel , Shah Parth D , Bacci Jennifer L , Stergachis Andy
Published: March 2024

Pharmacies are important health care access points, but no national map currently exists of where pharmacy deserts are located. This cross-sectional study used pharmacy address data and Census Bureau surveys to define pharmacy deserts at the census tract level in all 50 US states and the District of Columbia. We also compared sociodemographic characteristics of pharmacy desert vs non-pharmacy desert communities. Nationally, 15.8 million (4.7%) of all people in the United States live in pharmacy deserts, spanning urban and rural settings in all 50 states. On average, communities that are pharmacy deserts have a higher proportion of people who have a high school education or less, have no health insurance, have low self-reported English ability, have an ambulatory disability, and identify as a racial or ethnic minority. While, on average, pharmacies are the most accessible health care setting in the United States, many people still do not have access to them. Further, the people living in pharmacy deserts are often marginalized groups who have historically faced structural barriers to health care. This study demonstrates a need to improve access to pharmacies and pharmacy services to advance health equity.
m6A RNA methylation regulates mitochondrial function
Authors: Kahl Michael , Xu Zhaofa , Arumugam Saravanan , Edens Brittany M , Fischietti Mariafausta , Zhu Allen C , Platanias Leonidas C , He Chuan , Zhuang Xiaoxi , Ma Yongchao C
Published: March 2024

RNA methylation of N6-methyladenosine (m6A) is emerging as a fundamental regulator of every aspect of RNA biology. RNA methylation directly impacts protein production to achieve quick modulation of dynamic biological processes. However, whether RNA methylation regulates mitochondrial function is not known, especially in neuronal cells which require a high energy supply and quick reactive responses. Here we show that m6A RNA methylation regulates mitochondrial function through promoting nuclear-encoded mitochondrial complex subunit RNA translation. Conditional genetic knockout of m6A RNA methyltransferase Mettl14 (Methyltransferase like 14) by Nestin-Cre together with metabolomic analysis reveals that Mettl14 knockout-induced m6A depletion significantly downregulates metabolites related to energy metabolism. Furthermore, transcriptome-wide RNA methylation profiling of wild type and Mettl14 knockout mouse brains by m6A-Seq shows enrichment of methylation on mitochondria-related RNA. Importantly, loss of m6A leads to a significant reduction in mitochondrial respiratory capacity and membrane potential. These functional defects are paralleled by the reduced expression of mitochondrial electron transport chain complexes, as well as decreased mitochondrial super-complex assembly and activity. Mechanistically, m6A depletion decreases the translational efficiency of methylated RNA encoding mitochondrial complex subunits through reducing their association with polysomes, while not affecting RNA stability. Together, these findings reveal a novel role for RNA methylation in regulating mitochondrial function. Given that mitochondrial dysfunction and RNA methylation have been increasingly implicate in neurodegenerative disorders, our findings not only provide insights into fundamental mechanisms regulating mitochondrial function, but also open up new avenues for understanding the pathogenesis of neurological diseases.
Common single-base insertions in the VNTR of the carboxyl ester lipase (CEL) gene are benign and also likely to arise somatically in the exocrine pancreas
Authors: Brekke Ranveig S , Gravdal Anny , El Jellas Khadija , Curry Grace E , Lin Jianguo , Wilhelm Steven J , Steine Solrun J , Mas Eric , Johansson Stefan , Lowe Mark E , Johansson Bente B , Xiao Xunjun , Fjeld Karianne , Molven Anders
Published: March 2024

The CEL gene encodes carboxyl ester lipase, a pancreatic digestive enzyme. CEL is extremely polymorphic due to a variable number tandem repeat (VNTR) located in the last exon. Single-base deletions within this VNTR cause the inherited disorder MODY8, whereas little is known about VNTR single-base insertions in pancreatic disease. We therefore mapped CEL insertion variants (CEL-INS) in 200 Norwegian patients with pancreatic neoplastic disorders. Twenty-eight samples (14.0%) carried CEL-INS alleles. Most common were insertions in repeat 9 (9.5%), which always associated with a VNTR length of 13 repeats. The combined INS allele frequency (0.078) was similar to that observed in a control material of 416 subjects (0.075). We performed functional testing in HEK293T cells of a set of CEL-INS variants, in which the insertion site varied from the first to the 12th VNTR repeat. Lipase activity showed little difference among the variants. However, CEL-INS variants with insertions occurring in the most proximal repeats led to protein aggregation and endoplasmic reticulum stress, which upregulated the unfolded protein response. Moreover, by using a CEL-INS-specific antibody, we observed patchy signals in pancreatic tissue from humans without any CEL-INS variant in the germline. Similar pancreatic staining was seen in knock-in mice expressing the most common human CEL VNTR with 16 repeats. CEL-INS proteins may therefore be constantly produced from somatic events in the normal pancreatic parenchyma. This observation along with the high population frequency of CEL-INS alleles strongly suggests that these variants are benign, with a possible exception for insertions in VNTR repeats 1–4.
Hypoxic Functional Regulation Pathways in the GI Tract: Focus on the HIF-1α and Microbiota’s Crosstalk
Authors: Di Mattia Miriam , Sallese Michele , Neri Matteo , Lopetuso Loris Riccardo
Published: March 2024

Hypoxia is an essential gastrointestinal (GI) tract phenomenon that influences both physiologic and pathologic states. Hypoxia-inducible factors (HIFs), the primary drivers of cell adaptation to low-oxygen environments, have been identified as critical regulators of gut homeostasis: directly, through the induction of different proteins linked to intestinal barrier stabilization (ie, adherent proteins, tight junctions, mucins, integrins, intestinal trefoil factor, and adenosine); and indirectly, through the regulation of several immune cell types and the modulation of autophagy and inflammatory processes. Furthermore, hypoxia and HIF-related sensing pathways influence the delicate relationship existing between bacteria and mammalian host cells. In turn, gut commensals establish and maintain the physiologic hypoxia of the GI tract and HIF-α expression. Based on this premise, the goals of this review are to (1) highlight hypoxic molecular pathways in the GI tract, both in physiologic and pathophysiologic settings, such as inflammatory bowel disease; and (2) discuss a potential strategy for ameliorating gut-related disorders, by targeting HIF signaling, which can alleviate inflammatory processes, restore autophagy correct mechanisms, and benefit the host-microbiota equilibrium.
A data-driven framework for fast building energy demand estimation across future climate conditions
Authors: Zou Yukai , Chen Zhuoxi , Guo Jialiang , Zheng Yingsheng , Yang Xiaolin
Published: March 2024

The rapid and precise forecasting of building energy requirements plays a crucial role in decision-making processes for architects during the early design phase. This study introduces a data-driven framework capable of projecting energy demands in the context of evolving climate conditions. We evaluated four widely-used machine learning algorithms. Our results indicated that a hybrid approach, integrating Catboost and Bayesian optimization, excelled in both accuracy and efficiency for predicting building energy demand under climate change conditions. The framework proposed herein has potential applications in fostering sustainability in early-stage architectural design.
Microallopatric speciation in the relict dung beetle genus Grebennikovius (Coleoptera: Scarabaeidae) in the Eastern Arc Mountains
Authors: Montanaro Giulio , Grebennikov Vasily V , Rossini Michele , Grapputo Alessandro , Ruzzier Enrico , Tarasov Sergei
Published: March 2024

The Eastern Arc Mountains (EAMs) in Tanzania and Kenya are renowned for their exceptional species endemism often restricted to isolated mountain blocks. Forest fragmentation during the Pliocene–Pleistocene played a significant role in shaping the EAMs’ biodiversity by facilitating allopatric speciation between different mountains. However, only a few studies focused on species diversification within the same mountain block. In this article, we investigated the taxonomy and evolution of the dung beetle genus Grebennikovius, endemic to the Uluguru Mountains. Our goal was to unravel factors promoting allopatric speciation within a confined geographic area like the Ulugurus. We used an integrative taxonomic approach, combining phenotypic data and COI barcodes to delimit species and reconstructed a timetree of the genus. Molecular and morphological evidence consistently recovered 4 distinct Grebennikovius species, of which 3 are new to science: G. armiger n. sp., G. basilewskyi (Balthasar, 1960), G. lupanganus n. sp., and G. pafelo n. sp. Grebennikovius represents a rare case of microallopatry, with all species occurring in close proximity within different regions of the limited Uluguru forest (∼230 km2). We infer that speciation was driven by the interplay between climate fluctuations during the Miocene and mid-Pleistocene, Uluguru topography, and the stability of rainforest ecological conditions. The latter factor probably favored the loss of wings and a specialization for Uluguru microhabitats, reinforcing population isolation and divergence. This study highlights a unique instance of diversification resulting from small-scale speciation events, providing valuable insights into the evolution of Eastern African rainforest arthropods and underscoring the importance of microhabitats conservation.