bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential effects of desvenlafaxine on hot flashes in women with breast cancer taking tamoxifen: a randomized controlled trial
Authors: Kim Yongjoo , Yeom Chan-Woo , Lee Hyun Jeong , Kim Jeong-Hyun , Lee Kwang-Min , Kim Tae-Yong , Lee Han-Byoel , Kim Hoon , Im Seock-Ah , Lee Kyung-Hun , Kim Miso , Han Wonsik , Moon Hyeong-Gon , Spiegel David , Hahm Bong-Jin , Son Kyung-Lak
Published: July 2024

Hot flashes (HF) are a common adverse event of prolonged tamoxifen use in women with estrogen receptor-positive breast cancer, impacting psychiatric health and quality of life. While desvenlafaxine does not interact with tamoxifen, its efficacy and safety in breast cancer patients remain unstudied. This phase 3, four-week, multi-center, three-arm, parallel-group, randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of desvenlafaxine for treating HF in women with breast cancer taking tamoxifen, assessing potential differential effects in patients with psychiatric and inflammatory conditions. Between December 2017 and February 2019, 57 women aged 19 or older, regularly taking tamoxifen as adjuvant therapy, experiencing moderate-to-severe HFs for more than a month, were randomized to receive desvenlafaxine 50 mg/day (D-50), desvenlafaxine 100 mg/day (D-100), or placebo for four weeks. The primary endpoint was the change rate in HF scores over four weeks, with adverse events as a secondary endpoint. Both desvenlafaxine arms demonstrated greater HF score reductions compared to placebo: D-50 (2.20 points/week, 95% CI: 0.71, 3.68) and D-100 (2.34 points/week, 95% CI: 0.92, 3.76). Notably, D-50 arm showed significantly greater efficacy in patients with depression or elevated inflammation. Desvenlafaxine offers an effective and safe treatment regimen for HF in women with breast cancer taking tamoxifen. The presence of depression and inflammation may guide optimal desvenlafaxine dosing. (Trial Registration: ClinicalTrials.gov Identifier: NCT02819921)
Learning together: Towards foundation models for machine learning interatomic potentials with meta-learning
Authors: Allen Alice E. A. , Lubbers Nicholas , Matin Sakib , Smith Justin , Messerly Richard , Tretiak Sergei , Barros Kipton
Published: July 2024

The development of machine learning models has led to an abundance of datasets containing quantum mechanical (QM) calculations for molecular and material systems. However, traditional training methods for machine learning models are unable to leverage the plethora of data available as they require that each dataset be generated using the same QM method. Taking machine learning interatomic potentials (MLIPs) as an example, we show that meta-learning techniques, a recent advancement from the machine learning community, can be used to fit multiple levels of QM theory in the same training process. Meta-learning changes the training procedure to learn a representation that can be easily re-trained to new tasks with small amounts of data. We then demonstrate that meta-learning enables simultaneously training to multiple large organic molecule datasets. As a proof of concept, we examine the performance of a MLIP refit to a small drug-like molecule and show that pre-training potentials to multiple levels of theory with meta-learning improves performance. This difference in performance can be seen both in the reduced error and in the improved smoothness of the potential energy surface produced. We therefore show that meta-learning can utilize existing datasets with inconsistent QM levels of theory to produce models that are better at specializing to new datasets. This opens new routes for creating pre-trained, foundation models for interatomic potentials.
A deep position-encoding model for predicting olfactory perception from molecular structures and electrostatics
Authors: Zhang Mengji , Hiki Yusuke , Funahashi Akira , Kobayashi Tetsuya J.
Published: July 2024

Predicting olfactory perceptions from odorant molecules is challenging due to the complex and potentially discontinuous nature of the perceptual space for smells. In this study, we introduce a deep learning model, Mol-PECO (Molecular Representation by Positional Encoding of Coulomb Matrix), designed to predict olfactory perceptions based on molecular structures and electrostatics. Mol-PECO learns the efficient embedding of molecules by utilizing the Coulomb matrix, which encodes atomic coordinates and charges, as an alternative of the adjacency matrix and its Laplacian eigenfunctions as positional encoding of atoms. With a comprehensive dataset of odor molecules and descriptors, Mol-PECO outperforms traditional machine learning methods using molecular fingerprints and graph neural networks based on adjacency matrices. The learned embeddings by Mol-PECO effectively capture the odor space, enabling global clustering of descriptors and local retrieval of similar odorants. This work contributes to a deeper understanding of the olfactory sense and its mechanisms.
Position-dependent function of human sequence-specific transcription factors
Authors: Duttke Sascha H. , Guzman Carlos , Chang Max , Delos Santos Nathaniel P. , McDonald Bayley R. , Xie Jialei , Carlin Aaron F. , Heinz Sven , Benner Christopher
Published: July 2024

Patterns of transcriptional activity are encoded in our genome through regulatory elements such as promoters or enhancers that, paradoxically, contain similar assortments of sequence-specific transcription factor (TF) binding sites1–3. Knowledge of how these sequence motifs encode multiple, often overlapping, gene expression programs is central to understanding gene regulation and how mutations in non-coding DNA manifest in disease4,5. Here, by studying gene regulation from the perspective of individual transcription start sites (TSSs), using natural genetic variation, perturbation of endogenous TF protein levels and massively parallel analysis of natural and synthetic regulatory elements, we show that the effect of TF binding on transcription initiation is position dependent. Analysing TF-binding-site occurrences relative to the TSS, we identified several motifs with highly preferential positioning. We show that these patterns are a combination of a TF’s distinct functional profiles—many TFs, including canonical activators such as NRF1, NFY and Sp1, activate or repress transcription initiation depending on their precise position relative to the TSS. As such, TFs and their spacing collectively guide the site and frequency of transcription initiation. More broadly, these findings reveal how similar assortments of TF binding sites can generate distinct gene regulatory outcomes depending on their spatial configuration and how DNA sequence polymorphisms may contribute to transcription variation and disease and underscore a critical role for TSS data in decoding the regulatory information of our genome.
In vivo single-cell CRISPR uncovers distinct TNF programmes in tumour evolution
Authors: Renz Peter F. , Ghoshdastider Umesh , Baghai Sain Simona , Valdivia-Francia Fabiola , Khandekar Ameya , Ormiston Mark , Bernasconi Martino , Duré Clara , Kretz Jonas A. , Lee Minkyoung , Hyams Katie , Forny Merima , Pohly Marcel , Ficht Xenia , Ellis Stephanie J. , Moor Andreas E. , Sendoel Ataman
Published: July 2024

The tumour evolution model posits that malignant transformation is preceded by randomly distributed driver mutations in cancer genes, which cause clonal expansions in phenotypically normal tissues. Although clonal expansions can remodel entire tissues1–3, the mechanisms that result in only a small number of clones transforming into malignant tumours remain unknown. Here we develop an in vivo single-cell CRISPR strategy to systematically investigate tissue-wide clonal dynamics of the 150 most frequently mutated squamous cell carcinoma genes. We couple ultrasound-guided in utero lentiviral microinjections, single-cell RNA sequencing and guide capture to longitudinally monitor clonal expansions and document their underlying gene programmes at single-cell transcriptomic resolution. We uncover a tumour necrosis factor (TNF) signalling module, which is dependent on TNF receptor 1 and involving macrophages, that acts as a generalizable driver of clonal expansions in epithelial tissues. Conversely, during tumorigenesis, the TNF signalling module is downregulated. Instead, we identify a subpopulation of invasive cancer cells that switch to an autocrine TNF gene programme associated with epithelial–mesenchymal transition. Finally, we provide in vivo evidence that the autocrine TNF gene programme is sufficient to mediate invasive properties and show that the TNF signature correlates with shorter overall survival of patients with squamous cell carcinoma. Collectively, our study demonstrates the power of applying in vivo single-cell CRISPR screening to mammalian tissues, unveils distinct TNF programmes in tumour evolution and highlights the importance of understanding the relationship between clonal expansions in epithelia and tumorigenesis.
Giant chiral magnetoelectric oscillations in a van der Waals multiferroic
Authors: Gao Frank Y. , Peng Xinyue , Cheng Xinle , Viñas Boström Emil , Kim Dong Seob , Jain Ravish K. , Vishnu Deepak , Raju Kalaivanan , Sankar Raman , Lee Shang-Fan , Sentef Michael A. , Kurumaji Takashi , Li Xiaoqin , Tang Peizhe , Rubio Angel , Baldini Edoardo
Published: July 2024

Helical spin structures are expressions of magnetically induced chirality, entangling the dipolar and magnetic orders in materials1–4. The recent discovery of helical van der Waals multiferroics down to the ultrathin limit raises prospects of large chiral magnetoelectric correlations in two dimensions5,6. However, the exact nature and magnitude of these couplings have remained unknown so far. Here we perform a precision measurement of the dynamical magnetoelectric coupling for an enantiopure domain in an exfoliated van der Waals multiferroic. We evaluate this interaction in resonance with a collective electromagnon mode, capturing the impact of its oscillations on the dipolar and magnetic orders of the material with a suite of ultrafast optical probes. Our data show a giant natural optical activity at terahertz frequencies, characterized by quadrature modulations between the electric polarization and magnetization components. First-principles calculations further show that these chiral couplings originate from the synergy between the non-collinear spin texture and relativistic spin–orbit interactions, resulting in substantial enhancements over lattice-mediated effects. Our findings highlight the potential for intertwined orders to enable unique functionalities in the two-dimensional limit and pave the way for the development of van der Waals magnetoelectric devices operating at terahertz speeds.
A hot-Jupiter progenitor on a super-eccentric retrograde orbit
Authors: Gupta Arvind F. , Millholland Sarah C. , Im Haedam , Dong Jiayin , Jackson Jonathan M. , Carleo Ilaria , Libby-Roberts Jessica , Delamer Megan , Giovinazzi Mark R. , Lin Andrea S. J. , Kanodia Shubham , Wang Xian-Yu , Stassun Keivan , Masseron Thomas , Dragomir Diana , Mahadevan Suvrath , Wright Jason , Alvarado-Montes Jaime A. , Bender Chad , Blake Cullen H. , Caldwell Douglas , Cañas Caleb I. , Cochran William D. , Dalba Paul , Everett Mark E. , Fernandez Pipa , Golub Eli , Guillet Bruno , Halverson Samuel , Hebb Leslie , Higuera Jesus , Huang Chelsea X. , Klusmeyer Jessica , Knight Rachel , Leroux Liouba , Logsdon Sarah E. , Loose Margaret , McElwain Michael W. , Monson Andrew , Ninan Joe P. , Nowak Grzegorz , Palle Enric , Patel Yatrik , Pepper Joshua , Primm Michael , Rajagopal Jayadev , Robertson Paul , Roy Arpita , Schneider Donald P. , Schwab Christian , Schweiker Heidi , Sgro Lauren , Shimizu Masao , Simard Georges , Stefánsson Guðmundur , Stevens Daniel J. , Villanueva Steven , Wisniewski John , Will Stefan , Ziegler Carl
Published: July 2024

Giant exoplanets orbiting close to their host stars are unlikely to have formed in their present configurations1. These ‘hot Jupiter’ planets are instead thought to have migrated inward from beyond the ice line and several viable migration channels have been proposed, including eccentricity excitation through angular-momentum exchange with a third body followed by tidally driven orbital circularization2,3. The discovery of the extremely eccentric (e = 0.93) giant exoplanet HD 80606 b (ref. 4) provided observational evidence that hot Jupiters may have formed through this high-eccentricity tidal-migration pathway5. However, no similar hot-Jupiter progenitors have been found and simulations predict that one factor affecting the efficacy of this mechanism is exoplanet mass, as low-mass planets are more likely to be tidally disrupted during periastron passage6–8. Here we present spectroscopic and photometric observations of TIC 241249530 b, a high-mass, transiting warm Jupiter with an extreme orbital eccentricity of e = 0.94. The orbit of TIC 241249530 b is consistent with a history of eccentricity oscillations and a future tidal circularization trajectory. Our analysis of the mass and eccentricity distributions of the transiting-warm-Jupiter population further reveals a correlation between high mass and high eccentricity.
Groundwater-dependent ecosystem map exposes global dryland protection needs
Authors: Rohde Melissa M. , Albano Christine M. , Huggins Xander , Klausmeyer Kirk R. , Morton Charles , Sharman Ali , Zaveri Esha , Saito Laurel , Freed Zach , Howard Jeanette K. , Job Nancy , Richter Holly , Toderich Kristina , Rodella Aude-Sophie , Gleeson Tom , Huntington Justin , Chandanpurkar Hrishikesh A. , Purdy Adam J. , Famiglietti James S. , Singer Michael Bliss , Roberts Dar A. , Caylor Kelly , Stella John C.
Published: July 2024

Groundwater is the most ubiquitous source of liquid freshwater globally, yet its role in supporting diverse ecosystems is rarely acknowledged1,2. However, the location and extent of groundwater-dependent ecosystems (GDEs) are unknown in many geographies, and protection measures are lacking1,3. Here, we map GDEs at high-resolution (roughly 30 m) and find them present on more than one-third of global drylands analysed, including important global biodiversity hotspots4. GDEs are more extensive and contiguous in landscapes dominated by pastoralism with lower rates of groundwater depletion, suggesting that many GDEs are likely to have already been lost due to water and land use practices. Nevertheless, 53% of GDEs exist within regions showing declining groundwater trends, which highlights the urgent need to protect GDEs from the threat of groundwater depletion. However, we found that only 21% of GDEs exist on protected lands or in jurisdictions with sustainable groundwater management policies, invoking a call to action to protect these vital ecosystems. Furthermore, we examine the linkage of GDEs with cultural and socio-economic factors in the Greater Sahel region, where GDEs play an essential role in supporting biodiversity and rural livelihoods, to explore other means for protection of GDEs in politically unstable regions. Our GDE map provides critical information for prioritizing and developing policies and protection mechanisms across various local, regional or international scales to safeguard these important ecosystems and the societies dependent on them.
Symbolic recording of signalling and cis-regulatory element activity to DNA
Authors: Chen Wei , Choi Junhong , Li Xiaoyi , Nathans Jenny F. , Martin Beth , Yang Wei , Hamazaki Nobuhiko , Qiu Chengxiang , Lalanne Jean-Benoît , Regalado Samuel , Kim Haedong , Agarwal Vikram , Nichols Eva , Leith Anh , Lee Choli , Shendure Jay
Published: July 2024

Measurements of gene expression or signal transduction activity are conventionally performed using methods that require either the destruction or live imaging of a biological sample within the timeframe of interest. Here we demonstrate an alternative paradigm in which such biological activities are stably recorded to the genome. Enhancer-driven genomic recording of transcriptional activity in multiplex (ENGRAM) is based on the signal-dependent production of prime editing guide RNAs that mediate the insertion of signal-specific barcodes (symbols) into a genomically encoded recording unit. We show how this strategy can be used for multiplex recording of the cell-type-specific activities of dozens to hundreds of cis-regulatory elements with high fidelity, sensitivity and reproducibility. Leveraging signal transduction pathway-responsive cis-regulatory elements, we also demonstrate time- and concentration-dependent genomic recording of WNT, NF-κB and Tet-On activities. By coupling ENGRAM to sequential genome editing via DNA Typewriter1, we stably record information about the temporal dynamics of two orthogonal signalling pathways to genomic DNA. Finally we apply ENGRAM to integratively record the transient activity of nearly 100 transcription factor consensus motifs across daily windows spanning the differentiation of mouse embryonic stem cells into gastruloids, an in vitro model of early mammalian development. Although these are proof-of-concept experiments and much work remains to fully realize the possibilities, the symbolic recording of biological signals or states within cells, to the genome and over time, has broad potential to complement contemporary paradigms for how we make measurements in biological systems.
Astrocytes require perineuronal nets to maintain synaptic homeostasis in mice
Authors: Tewari Bhanu P. , Woo AnnaLin M. , Prim Courtney E. , Chaunsali Lata , Patel Dipan C. , Kimbrough Ian F. , Engel Kaliroi , Browning Jack L. , Campbell Susan L. , Sontheimer Harald
Published: July 2024

Perineuronal nets (PNNs) are densely packed extracellular matrices that cover the cell body of fast-spiking inhibitory neurons. PNNs stabilize synapses inhibiting synaptic plasticity. Here we show that synaptic terminals of fast-spiking interneurons localize to holes in the PNNs in the adult mouse somatosensory cortex. Approximately 95% of holes in the PNNs contain synapses and astrocytic processes expressing Kir4.1, glutamate and GABA transporters. Hence, holes in the PNNs contain tripartite synapses. In the adult mouse brain, PNN degradation causes an expanded astrocytic coverage of the neuronal somata without altering the axon terminals. The loss of PNNs impairs astrocytic transmitter and potassium uptake, resulting in the spillage of glutamate into the extrasynaptic space. Our data show that PNNs and astrocytes cooperate to contain synaptically released signals in physiological conditions. Their combined action is altered in mouse models of Alzheimer’s disease and epilepsy where PNNs are disrupted.
Terahertz tunable three-dimensional photonic jets
Authors: Rezaei Behrooz , Yahyapour Babak , Darafsheh Arash
Published: July 2024

Highly localized electromagnetic field distributions near the “shadow-side” surface of certain transparent mesoscale bodies illuminated by light waves are called photonic jets. We demonstrated formation of three-dimensional (3D) tunable photonic jets in terahertz regime (terajets, TJs) by dielectric micro-objects -including spheres, cylinders, and cubes-coated with a bulk Dirac semimetal (BDS) layer, under uniform beam illumination. The optical characteristics of the produced TJs can be modulated dynamically through tuning the BDS layer’s index of refraction via changing its Fermi energy. It is demonstrated that the Fermi energy of BDS layer has a significant impact on tuning the optical characteristics of the produced photonic jets for both TE and TM polarizations. A notable polarization dependency of the characteristics of the TJs was also observed. The impact of obliquity of the incident beam was studied as well and it was demonstrated that electromagnetic field distributions corresponding to asymmetric photonic jets can be formed in which the intensity at the focal region is preserved in a wide angular range which could find potential application in scanning devices. It was found that the maximum intensity of the TJ occurs at a non-trivial morphology-dependent source-angle.
Characterization and application of LDH with chitosan composites investigated by positron annihilation lifetime spectroscopy and surface texture for the adsorption of methyl orange
Authors: Abdel-Hady E. E. , Hafez Sarah H. M. , Mohamed Hamdy F. M. , Elsharkawy Mohamed R. M.
Published: July 2024

With a rapid increase in industrial growth around the world, the demand for an entirely novel category of nanoparticles and technologies for wastewater treatment has become a key concern for environmental protection. Recently, hybrids of layered double hydroxides (LDH), particularly those containing LDH, have gained attention as potential nanoscale adsorbents for water treatment. Recent research has shown that LDH-containing composites are interesting versatile materials with the ability to be used in energy storage, photocatalysis, nanocomposites, and water treatment. In the current work, LDH-containing composites were utilized as adsorbents for the purpose of purifying water. The adsorbents investigated are Zn–Co–Fe/LDH/Chitosan-in situ sample preparation (LDH/CS1) and Zn–Co–Fe/LDH/Chitosan-ex situ sample preparation (LDH/CS2). Furthermore, LDH/CS1 and LDH/CS2 were investigated for wastewater treatment from methyl orange dye (MO) with various adsorption conditions. When the initial MO concentration was 20 mg/L and the amount of adsorbent was 0.1 g, the removal efficiency reached 72.8 and 91.7% for LDH/CS1 and LDH/CS2, respectively. The MO’s maximum adsorption capabilities are 160.78 and 165.89 mg/g for LDH/CS1 and LDH/CS2, respectively, which is much greater than that of comparable commercial adsorbents. MO adsorption onto LDH/CS1 and LDH/CS2 was best characterized by the pseudo-second-order kinetic model. The equilibrium adsorption data was followed by the Freundlich and Langmuir models. The adsorption is favorable as evidenced by the equilibrium parameter RL values for MO adsorption onto LDH/CS1 and LDH/CS2, which were 0.227 and 0.144, respectively. Using the free volume distribution method and the positron annihilation lifetime technique, the nanostructure of the materials was examined.
Novel insight into nicotinamide adenine dinucleotide and related metabolites in cancer patients undergoing surgery
Authors: Fujita Hiroaki , Wakiya Taiichi , Tatara Yota , Ishido Keinosuke , Sakamoto Yoshiyuki , Kimura Norihisa , Morohashi Hajime , Miura Takuya , Muroya Takahiro , Akasaka Harue , Yokoyama Hiroshi , Kanda Taishu , Kubota Shunsuke , Ichisawa Aika , Ogasawara Kenta , Kuwata Daisuke , Takahashi Yoshiya , Nakamura Akie , Yamazaki Keisuke , Yamada Takahiro , Matsuyama Ryo , Kanou Masanobu , Yamana Kei , Itoh Ken , Hakamada Kenichi
Published: July 2024

Nicotinamide adenine dinucleotide (NAD +) plays a pivotal role in numerous cellular functions. Reduced NAD + levels are postulated to be associated with cancer. As interest in understanding NAD + dynamics in cancer patients with therapeutic applications in mind grows, there remains a shortage of comprehensive data. This study delves into NAD + dynamics in patients undergoing surgery for different digestive system cancers. This prospective study enrolled 99 patients with eight different cancers. Fasting blood samples were obtained during the perioperative period. The concentrations of NAD + , nicotinamide mononucleotide (NMN), and nicotinamide riboside were analyzed using tandem mass spectrometry. After erythrocyte volume adjustment, NAD + remained relatively stable after surgery. Meanwhile, NMN decreased the day after surgery and displayed a recovery trend. Interestingly, liver and pancreatic cancer patients exhibited poor postoperative NMN recovery, suggesting a potential cancer type-specific influence on NAD + metabolism. This study illuminated the behavior of NAD + in surgically treated cancer patients. We identified which cancer types have particularly low levels and at what point depletion occurs during the perioperative period. These insights suggest the need for personalized NAD + supplementation strategies, calibrated to individual patient needs and treatment timelines. Clinical trial registration jRCT1020210066.
COVID-19 and Parkinson’s disease: a single-center study and Mendelian randomization study
Authors: Yin Jianhong , Zhang Song , Zheng Qian , Feng Zhanhui
Published: July 2024

To investigate the association between COVID-19 and Parkinson’s disease (PD) via a single-center study and a Mendelian randomization (MR) study. A questionnaire-based survey was conducted among PD patients at a single center from December 7, 2022, to March 10, 2023. Logistic regression analysis was performed to identify the infection-related risk factors. Subsequently, bidirectional two-sample Mendelian randomization was employed to explore the association between COVID-19 and PD. In the cross-sectional analysis, it was found that the prevalence of COVID-19 infection in PD patients was 65.7%. Forty-eight (35.3%) PD patients experienced exacerbation of motor symptoms following COVID-19 infection. Long PD disease duration (≥ 10 years) (OR: 3.327, P = 0.045) and long time since last vaccination (> 12 m) (OR: 4.916, P = 0.035) were identified as significant risk factors related to infection. The MR analysis results supported that PD increases the COVID-19 susceptibility (β = 0.081, OR = 1.084, P = 0.006). However, the MR analysis showed that PD did not increases the COVID-19 severity and hospitalization, and no significant association of COVID-19 on PD was observed. The findings from this cross-sectional study suggest that individuals with PD may experience worsened motor symptoms following COVID-19 infection. Long disease duration (≥10 years) and long time since last vaccination (> 12 m) are identified as important risk factors for infection in these patients. Furthermore, our MR study provides evidence supporting an association between PD and COVID-19 susceptibility.
Reliability of impedance spectroscopy versus digital radiograph and ICDAS-II in occlusal caries detection: a prospective clinical trial
Authors: R. AbdELkader Amr , Hafez Ibrahim Shereen , Elsayed Hassanein Olfat
Published: July 2024

The traditional methods in early caries detection had many limitations. So, this study aimed to evaluate the clinical performance of alternating current impedance spectroscopy ACIST in comparison with digital radiograph and ICDAS-II in detection of occlusal carious lesions. Occlusal surfaces of molar and premolar teeth from 40 adult participants were examined by two observers using three diagnostic methods: (1) international caries detection and assessment system (ICDAS-II) (2) digital radiograph (DR) and (3) Cariescan Pro device (ACIST). Agreement analysis and the difference in sensitivities and specificities were evaluated. The results showed an excellent agreement in the different groups. The difference from the visual tactile against ACIST scoring for enamel caries detection, was statistically significant (p = 0.012) and the agreement was moderate (k = 0.509). For dentinal caries the difference was not statistically significant (p > 0.05) and the agreement was similarly moderate (k < 0.6). The difference from the digital radiograph against ACIST scoring, for enamel caries, digital radiography had significantly higher sensitivity and specificity than ACIST (p < 0.001) while for dentinal caries detection and overall, ACIST had higher sensitivity and digital radiography had higher specificity and the difference was statistically significant (p < 0.001). Visual-tactile examination is a considered as feasible and valid technique for occlusal caries detection, digital radiography is superior to ACIST in diagnosing enamel caries, but it could underestimate the caries depth, ACIST is a reliable tool for detecting occlusal caries in dentin.
Resin-based dental pulp capping restoration enclosing silica and portlandite nanoparticles from natural resources
Authors: Elbatanony Mai M. , Safwat Engie M. , El-Sherif Sammar , Hassan Mohammad L.
Published: July 2024

Natural-based materials represent green choices for biomedical applications. In this study, resin pulp capping restoration enclosing strengthening silica and bioactive portlandite nanofillers were prepared from industrial wastes. Silica nanoparticles were isolated from rice husk by heat treatment, followed by dissolution/precipitation treatment. Portlandite nanoparticles were prepared by calcination of carbonated lime waste followed by ultrasonic treatment. Both were characterized using x-ray diffraction, energy dispersive x-ray, and transmission electron microscopy. For preparing pulp capping restoration, silica (after silanization) and/or portlandite nanoparticles were mixed with 40/60 weight ratio of bisphenol A-glycidyl methacrylate and triethylene glycol dimethacrylate. Groups A, B, and C enclosing 50 wt.% silica, 25 wt.% silica + 25 wt.% portlandite, and 50 wt.% portlandite, respectively, were prepared. All groups underwent microhardness, compressive strength, calcium release, pH, and apatite forming ability inspection in comparison to mineral trioxide aggregate (MTA) positive control. In comparison to MTA, all experimental groups showed significantly higher compressive strength, group B showed comparable microhardness, and group C showed significantly higher calcium release. Groups B and C showed prominent hydroxyapatite formation. Thus, the preparation of economic, silica-fortified, bioactive pulp capping material from under-utilized agricultural residues (rice husk) and zero-value industrial waste (carbonated lime from sugar industry) could be achieved.
Longitudinal experiences of Canadians receiving compassionate access to psilocybin-assisted psychotherapy
Authors: de la Salle Sara , Kettner Hannes , Thibault Lévesque Julien , Garel Nicolas , Dames Shannon , Patchett-Marble Ryan , Rej Soham , Gloeckler Sara , Erritzoe David , Carhart-Harris Robin , Greenway Kyle T.
Published: July 2024

Recent clinical trials have found that the serotonergic psychedelic psilocybin effectively alleviates anxiodepressive symptoms in patients with life-threatening illnesses when given in a supportive environment. These outcomes prompted Canada to establish legal pathways for therapeutic access to psilocybin, coupled with psychological support. Despite over one-hundred Canadians receiving compassionate access since 2020, there has been little examination of these ‘real-world’ patients.

We conducted a prospective longitudinal survey which focused on Canadians who were granted Section 56 exemptions for legal psilocybin-assisted psychotherapy. Surveys assessing various symptom dimensions were conducted at baseline, two weeks following the session (endpoint), and optionally one day post-session. Participant characteristics were examined using descriptive statistics, and paired sample t-tests were used to quantify changes from baseline to the two-week post-treatment endpoint. Eight participants with Section 56 exemptions (four females, Mage = 52.3 years), all with cancer diagnoses, fully completed baseline and endpoint surveys. Significant improvements in anxiety and depression symptoms, pain, fear of COVID-19, quality of life, and spiritual well-being were observed. Attitudes towards death, medical assistance in dying, and desire for hastened death remained unchanged. While most participants found the psilocybin sessions highly meaningful, if challenging, one reported a substantial decrease in well-being due to the experience. These preliminary data are amongst the first to suggest that psilocybin-assisted psychotherapy can produce psychiatric benefits in real-world patients akin to those observed in clinical trials. Limited enrollment and individual reports of negative experiences indicate the need for formal real-world evaluation programs to surveil the ongoing expansion of legal access to psychedelics.
Tool skill impacts the archaeological evidence across technological primates
Authors: Luncz Lydia V. , Slania Nora E. , Almeida-Warren Katarina , Carvalho Susana , Falótico Tiago , Malaivijitnond Suchinda , Arroyo Adrián , de la Torre Ignacio , Proffitt Tomos
Published: July 2024

The archaeological record offers insights into our evolutionary past by revealing ancient behaviour through stone and fossil remains. Percussive foraging is suggested to be particularly relevant for the emergence of tool-use in our lineage, yet early hominin percussive behaviours remain largely understudied compared to flaked technology. Stone tool-use of extant primates allows the simultaneous investigation of their artefacts and the associated behaviours. This is important for understanding the development of tool surface modification, and crucial for interpreting damage patterns in the archaeological record. Here, we compare the behaviour and the resulting material record across stone tool-using primates. We investigate the relationship of nut-cracking technique and stone tool modification across chimpanzees, capuchins, and long-tailed macaques by conducting standardized field experiments with comparable raw materials. We show that different techniques likely emerged in response to diverse nut hardness, leading to variation in foraging success across species. Our experiments further demonstrate a correlation between techniques and the intensity of visible percussive damage on the tools. Tools used with more precision and efficiency as demonstrated by macaques, show fewer use wear traces. This suggests that some percussive techniques may be less readily identified in the archaeological record.
Metaheuristic integrated machine learning classification of colon cancer using STFT LASSO and EHO feature extraction from microarray gene expressions
Authors: Nair Ajin R. , Rajaguru Harikumar , Karthika M. S. , Keerthivasan C.
Published: July 2024

The microarray gene expression data poses a tremendous challenge due to their curse of dimensionality problem. The sheer volume of features far surpasses available samples, leading to overfitting and reduced classification accuracy. Thus the dimensionality of microarray gene expression data must be reduced with efficient feature extraction methods to reduce the volume of data and extract meaningful information to enhance the classification accuracy and interpretability. In this research, we discover the uniqueness of applying STFT (Short Term Fourier Transform), LASSO (Least Absolute Shrinkage and Selection Operator), and EHO (Elephant Herding Optimisation) for extracting significant features from lung cancer and reducing the dimensionality of the microarray gene expression database. The classification of lung cancer is performed using the following classifiers: Gaussian Mixture Model (GMM), Particle Swarm Optimization (PSO) with GMM, Detrended Fluctuation Analysis (DFA), Naive Bayes classifier (NBC), Firefly with GMM, Support Vector Machine with Radial Basis Kernel (SVM-RBF) and Flower Pollination Optimization (FPO) with GMM. The EHO feature extraction with the FPO-GMM classifier attained the highest accuracy in the range of 96.77, with an F1 score of 97.5, MCC of 0.92 and Kappa of 0.92. The reported results underline the significance of utilizing STFT, LASSO, and EHO for feature extraction in reducing the dimensionality of microarray gene expression data. These methodologies also help in improved and early diagnosis of lung cancer with enhanced classification accuracy and interpretability.
Innovative graph neural network approach for predicting soil heavy metal pollution in the Pearl River Basin, China
Authors: Zha Yannan , Yang Yao
Published: July 2024

Predicting soil heavy metal (HM) content is crucial for monitoring soil quality and ensuring ecological health. However, existing methods often neglect the spatial dependency of data. To address this gap, our study introduces a novel graph neural network (GNN) model, Multi-Scale Attention-based Graph Neural Network for Heavy Metal Prediction (MSA-GNN-HMP). The model integrates multi-scale graph convolutional network (MS-GCN) and attention-based GNN (AGNN) to capture spatial relationships. Using surface soil samples from the Pearl River Basin, we evaluate the MSA-GNN-HMP model against four other models. The experimental results show that the MSA-GNN-HMP model has the best predictive performance for Cd and Pb, with a coefficient of determination (R2) of 0.841 for Cd and 0.886 for Pb, and the lowest mean absolute error (MAE) of 0.403 mg kg−1 for Cd and 0.670 mg kg−1 for Pb, as well as the lowest root mean square error (RMSE) of 0.563 mg kg−1for Cd and 0.898 mg kg−1 for Pb. In feature importance analysis, latitude and longitude emerged as key factors influencing the heavy metal content. The spatial distribution prediction trend of heavy metal elements by different prediction methods is basically consistent, with the high-value areas of Cd and Pb respectively distributed in the northwest and northeast of the basin center. However, the MSA-GNN-HMP model demonstrates superior detail representation in spatial prediction. MSA-GNN-HMP model has excellent spatial information representation capabilities and can more accurately predict heavy metal content and spatial distribution, providing a new theoretical basis for monitoring, assessing, and managing soil pollution.
Analysis of glycoalkaloid distribution in the tissues of mealworm larvae (Tenebrio molitor)
Authors: Winkiel Magdalena Joanna , Chowański Szymon , Sulli Maria , Diretto Gianfranco , Słocińska Małgorzata
Published: July 2024

Solanine (SOL) and chaconine (CHA) are glycoalkaloids (GAs) produced mainly by Solanum plants. These plant secondary metabolites affect insect metabolism; thus, they have the potential to be applied as natural plant protection products. However, it is not known which GA concentration induces physiological changes in animals. Therefore, the aim of this study was to perform a quantitative analysis of SOL and CHA in the larvae of Tenebrio molitor using LC‒MS to assess how quickly they are eliminated or metabolised. In this experiment, the beetles were injected with 2 μL of 10−5 M SOL or CHA solution, which corresponds to a dosage range of 0.12–0.14 ng/mg body mass. Then, 0.5, 1.5, 8, and 24 h after GA application, the haemolymph (H), gut (G), and the remainder of the larval body (FB) were isolated. GAs were detected in all samples tested for 24 h, with the highest percentage of the amount applied in the FB, while the highest concentration was measured in the H sample. The SOL and CHA concentrations decreased in the haemolymph over time, while they did not change in other tissues. CHA had the highest elimination rate immediately after injection, while SOL slightly later. None of the GA hydrolysis products were detected in the tested samples. One possible mechanism of the detoxification of GAs may be oxidation and/or sequestration. They may be excreted by Malpighian tubules, with faeces or with cuticles during moulting. The results presented are significant because they facilitate the interpretation of studies related to the effects of toxic substances on insect metabolism.
Light wavelength modulates search behavior performance in zebrafish
Authors: Waalkes Matthew R. , Leathery Maegan , Peck Madeline , Barr Allison , Cunill Alexander , Hageter John , Horstick Eric J.
Published: July 2024

Visual systems have evolved to discriminate between different wavelengths of light. The ability to perceive color, or specific light wavelengths, is important as color conveys crucial information about both biotic and abiotic features in the environment. Indeed, different wavelengths of light can drive distinct patterns of activity in the vertebrate brain, yet what remains incompletely understood is whether distinct wavelengths can invoke etiologically relevant behavioral changes. To address how specific wavelengths in the visible spectrum modulate behavioral performance, we use larval zebrafish and a stereotypic light-search behavior. Prior work has shown that the cessation of light triggers a transitional light-search behavior, which we use to interrogate wavelength-dependent behavioral modulation. Using 8 narrow spectrum light sources in the visible range, we demonstrate that all wavelengths induce motor parameters consistent with search behavior, yet the magnitude of search behavior is spectrum sensitive and the underlying motor parameters are modulated in distinct patterns across short, medium, and long wavelengths. However, our data also establishes that not all motor features of search are impacted by wavelength. To define how wavelength modulates search performance, we performed additional assays with alternative wavelengths, dual wavelengths, and variable intensity. Last, we also tested blind larvae to resolve which components of wavelength dependent behavioral changes potentially include signaling from non-retinal photoreception. These findings have important implications as organisms can be exposed to varying wavelengths in laboratory and natural settings and therefore impose unique behavioral outputs.
Silencing sensory neuron membrane protein RferSNMPu1 impairs pheromone detection in the invasive Asian Palm Weevil
Authors: Johny Jibin , Nihad Mohammad , Alharbi Hattan A. , AlSaleh Mohammed Ali , Antony Binu
Published: July 2024

The red palm weevil (RPW), Rhynchophorus ferrugineus (Olivier), also known as the Asian palm weevil, is an invasive pest that causes widespread damage to palm trees around the globe. As pheromone communication is crucial for their mass attack and survival on palm trees, the olfactory concept of pest control strategies has been widely explored recently. We aim to understand the molecular basis of olfaction in RPW by studying one of the key olfactory proteins in insect pheromone communication, sensory neuron membrane proteins (SNMPs). SNMPs belong to the CD36 (cluster of differentiation 36) family that perform two distinct olfactory roles in insects, either in pheromone (odorant) transfer to the odorant receptors (SNMP1) or in the pheromone clearing process (SNMP2). In this study, we performed antennal transcriptomic screening and identified six SNMPs, mapping them on the R. ferrugineus genome, and confirmed four distinct SNMPs. Both SNMP1 proteins in RPW, viz., RferSNMPu1 and RferSNMPu2, were mapped onto the same scaffold in different loci in the RPW genome. To further understand the function of these proteins, we first classified them using phylogenetic analysis and checked their tissue-specific expression patterns. Further, we measured the relative transcript abundance of SNMPs in laboratory-reared, field-collected adults and pheromone-exposure experiments, ultimately identifying RferSNMPu1 as a potential candidate for functional analysis. We mapped RferSNMPu1 expression in the antennae and found that expression patterns were similar in both sexes. We used RNAi-based gene silencing to knockdown RferSNMPu1 and tested the changes in the RPW responses to aggregation pheromone compounds, 4-methyl-5-nonanol (ferrugineol) and 4-methyl-5-nonanone (ferrugineone), and a kairomone, ethyl acetate using electroantennogram (EAG) recordings. We found a significant reduction in the EAG recordings in the RferSNMPu1 knockdown strain of adult RPWs, confirming its potential role in pheromone detection. The structural modelling revealed the key domains in the RferSNMPu1 structure, which could likely be involved in pheromone detection based on the identified ectodomain tunnels. Our studies on RferSNMPu1 with a putative role in pheromone detection provide valuable insight into understanding the olfaction in R. ferrugineus as well as in other Curculionids, as SNMPs are under-explored in terms of its functional role in insect olfaction. Most importantly, RferSNMPu1 can be used as a potential target for the olfactory communication disruption in the R. ferrugineus control strategies.
Pulmonary function trajectories in COVID-19 survivors with and without pre-existing respiratory disease
Authors: Gach Debbie , Beijers Rosanne J. H. C. G. , van Zeeland Roel , van Kampen-van den Boogaart Vivian , Posthuma Rein , Schols Annemie M. W. J. , van den Bergh Joop P. , van Osch Frits H. M.
Published: July 2024

A significant proportion of COVID-19 survivors still experience a reduced diffusion capacity three and twelve months after discharge. We aimed to compare pulmonary function trajectories between hospitalized COVID-19 patients with pre-existing respiratory disease (PRD) and patients without pre-existing respiratory disease (Non-PRD) at three and twelve months after hospital discharge. This single-centre retrospective cohort study included COVID-19 patients admitted to the VieCuri Medical Centre (Venlo, the Netherlands) between February and December 2020 that were invited to the outpatient clinic at three and twelve months after discharge. During this visit, pulmonary function tests were performed and impairments were based on lower limit of normal. Data of 239 patients were analysed (65% male, 66 ± 10 years, and 26% with a history of respiratory disease). Three months after discharge, 49% and 64% of the Non-PRD patients (n = 177) and PRD patients (n = 62) had a low diffusion capacity, respectively. This improved over time in Non-PRD patients (p = 0.003), but not in PRD patients (p = 0.250). A low diffusion capacity was still observed in 34% and 57% of the Non-PRD and PRD group, respectively, twelve months after discharge. Pulmonary function impairments, mainly a reduced diffusion capacity, are observed among hospitalized COVID-19 patients with PRD and Non-PRD, at three and twelve months follow-up. Although diffusion capacity impairments restore over time in Non-PRD patients, poor recovery was observed among PRD patients.
The response of sea turtles to vocalizations opens new perspectives to reduce their bycatch
Authors: Chevallier Damien , Maucourt Léo , Charrier Isabelle , Lelong Pierre , Le Gall Yves , Menut Eric , Wallace Bryan , Delvenne Cyrielle , Vincze Orsolya , Jeantet Lorène , Girondot Marc , Martin Jordan , Bourgeois Ouvéa , Lepori Muriel , Fournier Pascal , Fournier-Chambrillon Christine , Régis Sidney , Lecerf Nicolas , Lefebvre Fabien , Aubert Nathalie , Arthus Mosiah , Pujol Matthieu , Nalovic Michel Anthony , Nicolas Moulanier , Burg Marie-Clémence , Chevallier Pascale , Chevallier Tao , Landreau Antony , Meslier Stéphane , Larcher Eugène , Le Maho Yvon
Published: July 2024

Incidental capture of non-target species poses a pervasive threat to many marine species, with sometimes devastating consequences for both fisheries and conservation efforts. Because of the well-known importance of vocalizations in cetaceans, acoustic deterrents have been extensively used for these species. In contrast, acoustic communication for sea turtles has been considered negligible, and this question has been largely unexplored. Addressing this challenge therefore requires a comprehensive understanding of sea turtles’ responses to sensory signals. In this study, we scrutinized the avenue of auditory cues, specifically the natural sounds produced by green turtles (Chelonia mydas) in Martinique, as a potential tool to reduce bycatch. We recorded 10 sounds produced by green turtles and identified those that appear to correspond to alerts, flight or social contact between individuals. Subsequently, these turtle sounds—as well synthetic and natural (earthquake) sounds—were presented to turtles in known foraging areas to assess the behavioral response of green turtles to these sounds. Our data highlighted that the playback of sounds produced by sea turtles was associated with alert or increased the vigilance of individuals. This therefore suggests novel opportunities for using sea turtle sounds to deter them from fishing gear or other potentially harmful areas, and highlights the potential of our research to improve sea turtles populations’ conservation.