bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxytocin, but not vasopressin, decreases willingness to harm others by promoting moral emotions of guilt and shame
Authors: Zheng Xiaoxiao , Wang Jiayuan , Yang Xi , Xu Lei , Becker Benjamin , Sahakian Barbara J. , Robbins Trevor W. , Kendrick Keith M.
Published: May 2024

Prosocial and moral behaviors have overlapping neural systems and can both be affected in a number of psychiatric disorders, although whether they involve similar neurochemical systems is unclear. In the current registered randomized placebo-controlled trial on 180 adult male and female subjects, we investigated the effects of intranasal administration of oxytocin and vasopressin, which play key roles in influencing social behavior, on moral emotion ratings for situations involving harming others and on judgments of moral dilemmas where others are harmed for a greater good. Oxytocin, but not vasopressin, enhanced feelings of guilt and shame for intentional but not accidental harm and reduced endorsement of intentionally harming others to achieve a greater good. Neither peptide influenced arousal ratings for the scenarios. Effects of oxytocin on guilt and shame were strongest in individuals scoring lower on the personal distress subscale of trait empathy. Overall, findings demonstrate for the first time that oxytocin, but not vasopressin, promotes enhanced feelings of guilt and shame and unwillingness to harm others irrespective of the consequences. This may reflect associations between oxytocin and empathy and vasopressin with aggression and suggests that oxytocin may have greater therapeutic potential for disorders with atypical social and moral behavior.
Celastrol ameliorates hypoxic-ischemic brain injury in neonatal rats by reducing oxidative stress and inflammation
Authors: Hu Yingying , Nan Yan , Lin Hongzhou , Zhao Qianlei , Chen Tingting , Tao Xiaoyue , Ding Bingqing , Lu Liying , Chen Shangqin , Zhu Jianghu , Guo Xiaoling , Lin Zhenlang
Published: May 2024

Background

Hypoxic-ischemic encephalopathy (HIE) is caused by perinatal hypoxia and subsequent reductions in cerebral blood flow and is one of the leading causes of severe disability or death in newborns. Despite its prevalence, we currently lack an effective drug therapy to combat HIE. Celastrol (Cel) is a pentacyclic triterpene extracted from Tripterygium Wilfordi that can protect against oxidative stress, inflammation, and cancer. However, whether Cel can alleviate neonatal hypoxic-ischemic (HI) brain damage remains unclear.

Methods

Here, we established both in vitro and in vivo models of HI brain damage using CoCl2-treated PC12 cells and neonatal rats, respectively, and explored the neuroprotective effects of Cel in these models.

Results

Analyses revealed that Cel administration reduced brain infarction size, microglia activation, levels of inflammation factors, and levels of oxidative stress markers by upregulating levels of p-AMPKα, Nrf2, HO-1, and by downregulating levels of TXNIP and NLRP3. Conversely, these beneficial effects of Cel on HI brain damage were largely inhibited by AMPKα inhibitor Compound C and its siRNA.

Conclusions

We present compelling evidence that Cel decreases inflammation and oxidative stress through the AMPKα/Nrf2/TXNIP signaling pathway, thereby alleviating neonatal HI brain injury. Cel therefore represents a promising therapeutic agent for treating HIE.

Impact

We firstly report that celastrol can ameliorate neonatal hypoxic-ischemic brain injury both in in vivo and in vitro, which represents a promising therapeutic agent for treating related brain injuries.

Celastrol activates the AMPKα/Nrf2/TXNIP signaling pathway to relieve oxidative stress and inflammation and thereby alleviates neonatal hypoxic-ischemic brain injury.
Prevalence of hearing impairment in neonatal encephalopathy due to hypoxia-ischemia: a systematic review and meta-analysis
Authors: Pawale Dinesh , Fursule Anurag , Tan Jason , Wagh Deepika , Patole Sanjay , Rao Shripada
Published: May 2024

Background

This systematic review was undertaken to estimate the overall prevalence of hearing impairment in survivors of neonatal HIE.

Methods

PubMed, EMBASE, CINAHL, EMCARE and Cochrane databases, mednar (gray literature) were searched till January 2023. Randomized controlled trials and observational studies were included. The main outcome was estimation of overall prevalence of hearing impairment in survivors of HIE.

Results

A total of 71studies (5821 infants assessed for hearing impairment) were included of which 56 were from high income countries (HIC) and 15 from low- or middle-income countries (LMIC). Overall prevalence rate of hearing impairment in cooled infants was 5% (95% CI: 3–6%, n = 4868) and 3% (95% CI: 1–6%, n = 953) in non-cooled HIE infants. The prevalence rate in cooled HIE infants in LMICs was 7% (95% CI: 2–15%) and in HICs was 4% (95% CI: 3–5%). The prevalence rate in non-cooled HIE infants in LMICs was 8% (95% CI: 2–17%) and HICs was 2% (95% CI: 0–4%).

Conclusions

These results would be useful for counseling parents, and in acting as benchmark when comparing institutional data, and while monitoring future RCTs testing new interventions in HIE. There is a need for more data from LMICs and standardization of reporting hearing impairment.

Impact

The overall prevalence rate of hearing impairment in cooled infants with HIE was 5% (95% CI: 3–6%) and 3% (95% CI: 1–6%) in the non-cooled infants.

The prevalence rate in cooled HIE infants in LMICs was 7% (95% CI: 2–15%) and in HICs was 4% (95% CI: 3–5%).

The prevalence rate in non-cooled HIE infants in LMICs was 8% (95% CI: 2–17%) and HICs was 2% (95% CI: 0–4%).

These results would be useful for counseling parents, and in acting as benchmark when comparing institutional data, and while monitoring future RCTs testing new interventions in HIE.
DEPDC5 protects CD8+ T cells from ferroptosis by limiting mTORC1-mediated purine catabolism
Authors: Li Song , Ouyang Xinxing , Sun Hongxiang , Jin Jingsi , Chen Yao , Li Liang , Wang Qijun , He Yingzhong , Wang Jiwen , Chen Tongxin , Zhong Qing , Liang Yinming , Pierre Philippe , Zou Qiang , Ye Youqiong , Su Bing
Published: May 2024

Peripheral CD8+ T cell number is tightly controlled but the precise molecular mechanism regulating this process is still not fully understood. In this study, we found that epilepsy patients with loss of function mutation of DEPDC5 had reduced peripheral CD8+ T cells, and DEPDC5 expression positively correlated with tumor-infiltrating CD8+ T cells as well as overall cancer patient survival, indicating that DEPDC5 may control peripheral CD8+ T cell homeostasis. Significantly, mice with T cell-specific Depdc5 deletion also had reduced peripheral CD8+ T cells and impaired anti-tumor immunity. Mechanistically, Depdc5-deficient CD8+ T cells produced high levels of xanthine oxidase and lipid ROS due to hyper-mTORC1-induced expression of ATF4, leading to spontaneous ferroptosis. Together, our study links DEPDC5-mediated mTORC1 signaling with CD8+ T cell protection from ferroptosis, thereby revealing a novel strategy for enhancing anti-tumor immunity via suppression of ferroptosis.
Integrating single cell expression quantitative trait loci summary statistics to understand complex trait risk genes
Authors: Wang Lida , Khunsriraksakul Chachrit , Markus Havell , Chen Dieyi , Zhang Fan , Chen Fang , Zhan Xiaowei , Carrel Laura , Liu Dajiang. J. , Jiang Bibo
Published: May 2024

Transcriptome-wide association study (TWAS) is a popular approach to dissect the functional consequence of disease associated non-coding variants. Most existing TWAS use bulk tissues and may not have the resolution to reveal cell-type specific target genes. Single-cell expression quantitative trait loci (sc-eQTL) datasets are emerging. The largest bulk- and sc-eQTL datasets are most conveniently available as summary statistics, but have not been broadly utilized in TWAS. Here, we present a new method EXPRESSO (EXpression PREdiction with Summary Statistics Only), to analyze sc-eQTL summary statistics, which also integrates 3D genomic data and epigenomic annotation to prioritize causal variants. EXPRESSO substantially improves existing methods. We apply EXPRESSO to analyze multi-ancestry GWAS datasets for 14 autoimmune diseases. EXPRESSO uniquely identifies 958 novel gene x trait associations, which is 26% more than the second-best method. Among them, 492 are unique to cell type level analysis and missed by TWAS using whole blood. We also develop a cell type aware drug repurposing pipeline, which leverages EXPRESSO results to identify drug compounds that can reverse disease gene expressions in relevant cell types. Our results point to multiple drugs with therapeutic potentials, including metformin for type 1 diabetes, and vitamin K for ulcerative colitis.
Bright and durable scintillation from colloidal quantum shells
Authors: Guzelturk Burak , Diroll Benjamin T. , Cassidy James P. , Harankahage Dulanjan , Hua Muchuan , Lin Xiao-Min , Iyer Vasudevan , Schaller Richard D. , Lawrie Benjamin J. , Zamkov Mikhail
Published: May 2024

Efficient, fast, and robust scintillators for ionizing radiation detection are crucial in various fields, including medical diagnostics, defense, and particle physics. However, traditional scintillator technologies face challenges in simultaneously achieving optimal performance and high-speed operation. Herein we introduce colloidal quantum shell heterostructures as X-ray and electron scintillators, combining efficiency, speed, and durability. Quantum shells exhibit light yields up to 70,000 photons MeV−1 at room temperature, enabled by their high multiexciton radiative efficiency thanks to long Auger-Meitner lifetimes (>10 ns). Radioluminescence is fast, with lifetimes of 2.5 ns and sub-100 ps rise times. Additionally, quantum shells do not exhibit afterglow and maintain stable scintillation even under high X-ray doses (>109 Gy). Furthermore, we showcase quantum shells for X-ray imaging achieving a spatial resolution as high as 28 line pairs per millimeter. Overall, efficient, fast, and durable scintillation make quantum shells appealing in applications ranging from ultrafast radiation detection to high-resolution imaging.
Sex-specific developmental gene expression atlas unveils dimorphic gene networks in C. elegans
Authors: Haque Rizwanul , Kurien Sonu Peedikayil , Setty Hagar , Salzberg Yehuda , Stelzer Gil , Litvak Einav , Gingold Hila , Rechavi Oded , Oren-Suissa Meital
Published: May 2024

Sex-specific traits and behaviors emerge during development by the acquisition of unique properties in the nervous system of each sex. However, the genetic events responsible for introducing these sex-specific features remain poorly understood. In this study, we create a comprehensive gene expression atlas of pure populations of hermaphrodites and males of the nematode Caenorhabditis elegans across development. We discover numerous differentially expressed genes, including neuronal gene families like transcription factors, neuropeptides, and G protein-coupled receptors. We identify INS-39, an insulin-like peptide, as a prominent male-biased gene expressed specifically in ciliated sensory neurons. We show that INS-39 serves as an early-stage male marker, facilitating the effective isolation of males in high-throughput experiments. Through complex and sex-specific regulation, ins-39 plays pleiotropic sexually dimorphic roles in various behaviors, while also playing a shared, dimorphic role in early life stress. This study offers a comparative sexual and developmental gene expression database for C. elegans. Furthermore, it highlights conserved genes that may underlie the sexually dimorphic manifestation of different human diseases.
Absolute dating of the European Neolithic using the 5259 BC rapid 14C excursion
Authors: Maczkowski Andrej , Pearson Charlotte , Francuz John , Giagkoulis Tryfon , Szidat Sönke , Wacker Lukas , Bolliger Matthias , Kotsakis Kostas , Hafner Albert
Published: May 2024

Abrupt radiocarbon (14C) excursions, or Miyake events, in sequences of radiocarbon measurements from calendar-dated tree-rings provide opportunities to assign absolute calendar dates to undated wood samples from contexts across history and prehistory. Here, we report a tree-ring and14C-dating study of the Neolithic site of Dispilio, Northern Greece, a waterlogged archaeological site on Lake Kastoria. Findings secure an absolute, calendar-dated time using the 5259 BC Miyake event, with the final ring of the 303-year-long juniper tree-ring chronology dating to 5140 BC. While other sites have been absolutely dated to a calendar year through14C-signature Miyake events, Dispilio is the first European Neolithic site of these and it provides a fixed, calendar-year anchor point for regional chronologies of the Neolithic.
BRCA1/BARD1 ubiquitinates PCNA in unperturbed conditions to promote continuous DNA synthesis
Authors: Salas-Lloret Daniel , García-Rodríguez Néstor , Soto-Hidalgo Emily , González-Vinceiro Lourdes , Espejo-Serrano Carmen , Giebel Lisanne , Mateos-Martín María Luisa , de Ru Arnoud H. , van Veelen Peter A. , Huertas Pablo , Vertegaal Alfred C. O. , González-Prieto Román
Published: May 2024

Deficiencies in the BRCA1 tumor suppressor gene are the main cause of hereditary breast and ovarian cancer. BRCA1 is involved in the Homologous Recombination DNA repair pathway and, together with BARD1, forms a heterodimer with ubiquitin E3 activity. The relevance of the BRCA1/BARD1 ubiquitin E3 activity for tumor suppression and DNA repair remains controversial. Here, we observe that the BRCA1/BARD1 ubiquitin E3 activity is not required for Homologous Recombination or resistance to Olaparib. Using TULIP2 methodology, which enables the direct identification of E3-specific ubiquitination substrates, we identify substrates for BRCA1/BARD1. We find that PCNA is ubiquitinated by BRCA1/BARD1 in unperturbed conditions independently of RAD18. PCNA ubiquitination by BRCA1/BARD1 avoids the formation of ssDNA gaps during DNA replication and promotes continuous DNA synthesis. These results provide additional insight about the importance of BRCA1/BARD1 E3 activity in Homologous Recombination.
The sterol C-24 methyltransferase encoding gene, erg6, is essential for viability of Aspergillus species
Authors: Xie Jinhong , Rybak Jeffrey M. , Martin-Vicente Adela , Guruceaga Xabier , Thorn Harrison I. , Nywening Ashley V. , Ge Wenbo , Parker Josie E. , Kelly Steven L. , Rogers P. David , Fortwendel Jarrod R.
Published: May 2024

Triazoles, the most widely used class of antifungal drugs, inhibit the biosynthesis of ergosterol, a crucial component of the fungal plasma membrane. Inhibition of a separate ergosterol biosynthetic step, catalyzed by the sterol C-24 methyltransferase Erg6, reduces the virulence of pathogenic yeasts, but its effects on filamentous fungal pathogens like Aspergillus fumigatus remain unexplored. Here, we show that the lipid droplet-associated enzyme Erg6 is essential for the viability of A. fumigatus and other Aspergillus species, including A. lentulus, A. terreus, and A. nidulans. Downregulation of erg6 causes loss of sterol-rich membrane domains required for apical extension of hyphae, as well as altered sterol profiles consistent with the Erg6 enzyme functioning upstream of the triazole drug target, Cyp51A/Cyp51B. Unexpectedly, erg6-repressed strains display wild-type susceptibility against the ergosterol-active triazole and polyene antifungals. Finally, we show that erg6 repression results in significant reduction in mortality in a murine model of invasive aspergillosis. Taken together with recent studies, our work supports Erg6 as a potentially pan-fungal drug target.
Machine learning-aided first-principles calculations of redox potentials
Authors: Jinnouchi Ryosuke , Karsai Ferenc , Kresse Georg
Published: May 2024

We present a method combining first-principles calculations and machine learning to predict the redox potentials of half-cell reactions on the absolute scale. By applying machine learning force fields for thermodynamic integration from the oxidized to the reduced state, we achieve efficient statistical sampling over a broad phase space. Furthermore, through thermodynamic integration from machine learning force fields to potentials of semi-local functionals, and from semi-local functionals to hybrid functionals using Δ-machine learning, we refine the free energy with high precision step-by-step. Utilizing a hybrid functional that includes 25% exact exchange (PBE0), this method predicts the redox potentials of the three redox couples, Fe3+/Fe2+, Cu2+/Cu+, and Ag2+/Ag+, to be 0.92, 0.26, and 1.99 V, respectively. These predictions are in good agreement with the best experimental estimates (0.77, 0.15, 1.98 V). This work demonstrates that machine-learned surrogate models provide a flexible framework for refining the accuracy of free energy from coarse approximation methods to precise electronic structure calculations, while also facilitating sufficient statistical sampling.
A quantum coherent spin in hexagonal boron nitride at ambient conditions
Authors: Stern Hannah L. , M. Gilardoni Carmem , Gu Qiushi , Eizagirre Barker Simone , Powell Oliver F. J. , Deng Xiaoxi , Fraser Stephanie A. , Follet Louis , Li Chi , Ramsay Andrew J. , Tan Hark Hoe , Aharonovich Igor , Atatüre Mete
Published: May 2024

Solid-state spin–photon interfaces that combine single-photon generation and long-lived spin coherence with scalable device integration—ideally under ambient conditions—hold great promise for the implementation of quantum networks and sensors. Despite rapid progress reported across several candidate systems, those possessing quantum coherent single spins at room temperature remain extremely rare. Here we report quantum coherent control under ambient conditions of a single-photon-emitting defect spin in a layered van der Waals material, namely, hexagonal boron nitride. We identify that the carbon-related defect has a spin-triplet electronic ground-state manifold. We demonstrate that the spin coherence is predominantly governed by coupling to only a few proximal nuclei and is prolonged by decoupling protocols. Our results serve to introduce a new platform to realize a room-temperature spin qubit coupled to a multiqubit quantum register or quantum sensor with nanoscale sample proximity.
In vitro reconstitution of epigenetic reprogramming in the human germ line
Authors: Murase Yusuke , Yokogawa Ryuta , Yabuta Yukihiro , Nagano Masahiro , Katou Yoshitaka , Mizuyama Manami , Kitamura Ayaka , Puangsricharoen Pimpitcha , Yamashiro Chika , Hu Bo , Mizuta Ken , Tsujimura Taro , Yamamoto Takuya , Ogata Kosuke , Ishihama Yasushi , Saitou Mitinori
Published: May 2024

Epigenetic reprogramming resets parental epigenetic memories and differentiates primordial germ cells (PGCs) into mitotic pro-spermatogonia or oogonia. This process ensures sexually dimorphic germ cell development for totipotency1. In vitro reconstitution of epigenetic reprogramming in humans remains a fundamental challenge. Here we establish a strategy for inducing epigenetic reprogramming and differentiation of pluripotent stem-cell-derived human PGC-like cells (hPGCLCs) into mitotic pro-spermatogonia or oogonia, coupled with their extensive amplification (about >1010-fold). Bone morphogenetic protein (BMP) signalling is a key driver of these processes. BMP-driven hPGCLC differentiation involves attenuation of the MAPK (ERK) pathway and both de novo and maintenance DNA methyltransferase activities, which probably promote replication-coupled, passive DNA demethylation. hPGCLCs deficient in TET1, an active DNA demethylase abundant in human germ cells2,3, differentiate into extraembryonic cells, including amnion, with de-repression of key genes that bear bivalent promoters. These cells fail to fully activate genes vital for spermatogenesis and oogenesis, and their promoters remain methylated. Our study provides a framework for epigenetic reprogramming in humans and an important advance in human biology. Through the generation of abundant mitotic pro-spermatogonia and oogonia-like cells, our results also represent a milestone for human in vitro gametogenesis research and its potential translation into reproductive medicine.
Non-invasive spinal cord electrical stimulation for arm and hand function in chronic tetraplegia: a safety and efficacy trial
Authors: Moritz Chet , Field-Fote Edelle C. , Tefertiller Candace , van Nes Ilse , Trumbower Randy , Kalsi-Ryan Sukhvinder , Purcell Mariel , Janssen Thomas W. J. , Krassioukov Andrei , Morse Leslie R. , Zhao Kristin D. , Guest James , Marino Ralph J. , Murray Lynda M. , Wecht Jill M. , Rieger Markus , Pradarelli Jared , Turner Amanda , D’Amico Jessica , Squair Jordan W. , Courtine Gregoire
Published: May 2024

Cervical spinal cord injury (SCI) leads to permanent impairment of arm and hand functions. Here we conducted a prospective, single-arm, multicenter, open-label, non-significant risk trial that evaluated the safety and efficacy of ARCEX Therapy to improve arm and hand functions in people with chronic SCI. ARCEX Therapy involves the delivery of externally applied electrical stimulation over the cervical spinal cord during structured rehabilitation. The primary endpoints were safety and efficacy as measured by whether the majority of participants exhibited significant improvement in both strength and functional performance in response to ARCEX Therapy compared to the end of an equivalent period of rehabilitation alone. Sixty participants completed the protocol. No serious adverse events related to ARCEX Therapy were reported, and the primary effectiveness endpoint was met. Seventy-two percent of participants demonstrated improvements greater than the minimally important difference criteria for both strength and functional domains. Secondary endpoint analysis revealed significant improvements in fingertip pinch force, hand prehension and strength, upper extremity motor and sensory abilities and self-reported increases in quality of life. These results demonstrate the safety and efficacy of ARCEX Therapy to improve hand and arm functions in people living with cervical SCI. ClinicalTrials.gov identifier: NCT04697472.
The BELSAR dataset: Mono- and bistatic full-pol L-band SAR for agriculture and hydrology
Authors: Bouchat Jean , Tronquo Emma , Orban Anne , de Macedo Karlus A. C. , Davidson Malcolm , Verhoest Niko E. C. , Defourny Pierre
Published: May 2024

The BELSAR dataset consists of high-resolution multitemporal airborne mono- and bistatic fully-polarimetric synthetic aperture radar (SAR) data in L-band, alongside concurrent measurements of vegetation and soil biogeophysical variables measured in maize and winter wheat fields during the summer of 2018 in Belgium. Its collection was funded by the European Space Agency (ESA) to address the lack of publicly-accessible experimental datasets combining multistatic SAR and in situ measurements. As such, it offers an opportunity to advance the development of SAR remote sensing science and applications for agricultural monitoring and hydrology. This paper aims to facilitate its adoption and exploration by offering comprehensive documentation and integrating its multiple data sources into a unified, analysis-ready dataset.
A large and diverse brain organoid dataset of 1,400 cross-laboratory images of 64 trackable brain organoids
Authors: Schröter Julian , Deininger Luca , Lupse Blaz , Richter Petra , Syrbe Steffen , Mikut Ralf , Jung-Klawitter Sabine
Published: May 2024

Brain organoids represent a useful tool for modeling of neurodevelopmental disorders and can recapitulate brain volume alterations such as microcephaly. To monitor organoid growth, brightfield microscopy images are frequently used and evaluated manually which is time-consuming and prone to observer-bias. Recent software applications for organoid evaluation address this issue using classical or AI-based methods. These pipelines have distinct strengths and weaknesses that are not evident to external observers. We provide a dataset of more than 1,400 images of 64 trackable brain organoids from four clones differentiated from healthy and diseased patients. This dataset is especially powerful to test and compare organoid analysis pipelines because of (1) trackable organoids (2) frequent imaging during development (3) clone diversity (4) distinct clone development (5) cross sample imaging by two different labs (6) common imaging distractors, and (6) pixel-level ground truth organoid annotations. Therefore, this dataset allows to perform differentiated analyses to delineate strengths, weaknesses, and generalizability of automated organoid analysis pipelines as well as analysis of clone diversity and similarity.
The role of non-uniform magnetization texture for magnon–magnon coupling in an antidot lattice
Authors: Moalic Mathieu , Zelent Mateusz , Szulc Krzysztof , Krawczyk Maciej
Published: May 2024

We numerically study the spin-wave dynamics in an antidot lattice based on a Co/Pd multilayer structure with reduced perpendicular magnetic anisotropy at the edges of the antidots. This structure forms a magnonic crystal with a periodic antidot pattern and a periodic magnetization configuration consisting of out-of-plane magnetized bulk and in-plane magnetized rims. Our results show a different behavior of spin waves in the bulk and in the rims under varying out-of-plane external magnetic field strength, revealing complex spin-wave spectra and hybridizations between the modes of these two subsystems. A particularly strong magnon–magnon coupling, due to exchange interactions, is found between the fundamental bulk spin-wave mode and the second-order radial rim modes. However, the dynamical coupling between the spin-wave modes at low frequencies, involving the first-order radial rim modes, is masked by the changes in the static magnetization at the bulk–rim interface with magnetic field changes. The study expands the horizons of magnonic-crystal research by combining periodic structural patterning and non-collinear magnetization texture to achieve strong magnon–magnon coupling, highlighting the significant role of exchange interactions in the hybridization.
Machine learning-based model to predict delirium in patients with advanced cancer treated with palliative care: a multicenter, patient-based registry cohort
Authors: Kim Yu Jung , Lee Hayeon , Woo Ho Geol , Lee Si Won , Hong Moonki , Jung Eun Hee , Yoo Shin Hye , Lee Jinseok , Yon Dong Keon , Kang Beodeul
Published: May 2024

This study aimed to present a new approach to predict to delirium admitted to the acute palliative care unit. To achieve this, this study employed machine learning model to predict delirium in patients in palliative care and identified the significant features that influenced the model. A multicenter, patient-based registry cohort study in South Korea between January 1, 2019, and December 31, 2020. Delirium was identified by reviewing the medical records based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. The study dataset included 165 patients with delirium among 2314 patients with advanced cancer admitted to the acute palliative care unit. Seven machine learning models, including extreme gradient boosting, adaptive boosting, gradient boosting, light gradient boosting, logistic regression, support vector machine, and random forest, were evaluated to predict delirium in patients with advanced cancer admitted to the acute palliative care unit. An ensemble approach was adopted to determine the optimal model. For k-fold cross-validation, the combination of extreme gradient boosting and random forest provided the best performance, achieving the following accuracy metrics: 68.83% sensitivity, 70.85% specificity, 69.84% balanced accuracy, and 74.55% area under the receiver operating characteristic curve. The performance of the isolated testing dataset was also validated, and the machine learning model was successfully deployed on a public website (http://ai-wm.khu.ac.kr/Delirium/) to provide public access to delirium prediction results in patients with advanced cancer. Furthermore, using feature importance analysis, sex was determined to be the top contributor in predicting delirium, followed by a history of delirium, chemotherapy, smoking status, alcohol consumption, and living with family. Based on a large-scale, multicenter, patient-based registry cohort, a machine learning prediction model for delirium in patients with advanced cancer was developed in South Korea. We believe that this model will assist healthcare providers in treating patients with delirium and advanced cancer.
Exploring fluoropolymers for fabrication of femtoliter chamber arrays used in digital bioanalysis
Authors: Ando Jun , Murai Kazue , Mori Makiko , Michiyuki Tomoe , Iida Tatsuya , Makino Asami , Shinoda Hajime , Watanabe Rikiya
Published: May 2024

The global supply of fluoropolymers and fluorinated solvents is decreasing due to environmental concerns regarding polyfluoroalkyl substances. CYTOP has been used for decades primarily as a component of a femtoliter chamber array for digital bioanalysis; however, its supply has recently become scarce, increasing the urgency of fabricating a femtoliter chamber array using alternative materials. In this study, we investigated the feasibility of fabricating a femtoliter chamber array using four types of fluoropolymers in stable supply as candidate substitutes and verified their applicability for digital bioanalysis. Among these candidates, Fluorine Sealant emerged as a viable option for fabricating femtoliter chamber arrays using a conventional photolithography process. To validate its efficacy, we performed various digital bioanalysis using FP-A-based chamber arrays with model enzymes such as CRISPR–Cas, horseradish peroxidase, and β-galactosidase. The results demonstrated the similar performance to that of CYTOP, highlighting the broader utility of FP-A in digital bioanalysis. Our findings underscore the potential of FP-A to enhance the versatility of digital bioanalysis and foster the ongoing advancement of innovative diagnostic technologies.
Antibody longevity and waning following COVID-19 vaccination in a 1-year longitudinal cohort in Bangladesh
Authors: Haq Md. Ahsanul , Roy Anjan Kumar , Ahmed Razu , Kuddusi Rakib Ullah , Sinha Monika , Hossain Md. Shamim , Vandenent Maya , Islam Mohammad Zahirul , Zaman Rashid U. , Kibria Md. Golam , Razzaque Abdur , Raqib Rubhana , Sarker Protim
Published: May 2024

COVID-19 vaccines have been effective in preventing severe illness, hospitalization and death, however, the effectiveness diminishes with time. Here, we evaluated the longevity of antibodies generated by COIVD-19 vaccines and the risk of (re)infection in Bangladeshi population. Adults receiving two doses of AstraZeneca, Pfizer, Moderna or Sinopharm vaccines were enrolled at 2–4 weeks after second dosing and followed-up at 4-monthly interval for 1 year. Data on COVID-like symptoms, confirmed COVID-19 infection, co-morbidities, and receipt of booster dose were collected; blood was collected for measuring spike (S)- and nucleocapsid (N)-specific antibodies. S-specific antibody titers reduced by ~ 50% at 1st follow-up visit and continued to decline unless re-stimulated by booster vaccine dose or (re)infection. Individuals infected between follow-up visits showed significantly lower S-antibody titers at preceding visits compared to the uninfected individuals. Pre-enrolment infection between primary vaccination dosing exhibited 60% and 50% protection against reinfection at 5 and 9 months, respectively. mRNA vaccines provided highest odds of protection from (re)infection up to 5 months (Odds Ratio (OR) = 0.08), however, protection persisted for 9 months in AstraZeneca vaccine recipients (OR = 0.06). In conclusion, vaccine-mediated protection from (re)infection is partially linked to elevated levels of S-specific antibodies. AstraZeneca vaccine provided the longest protection.
Movement trajectories as a window into the dynamics of emerging neural representations
Authors: Koenig-Robert Roger , Quek Genevieve L. , Grootswagers Tijl , Varlet Manuel
Published: May 2024

The rapid transformation of sensory inputs into meaningful neural representations is critical to adaptive human behaviour. While non-invasive neuroimaging methods are the de-facto method for investigating neural representations, they remain expensive, not widely available, time-consuming, and restrictive. Here we show that movement trajectories can be used to measure emerging neural representations with fine temporal resolution. By combining online computer mouse-tracking and publicly available neuroimaging data via representational similarity analysis (RSA), we show that movement trajectories track the unfolding of stimulus- and category-wise neural representations along key dimensions of the human visual system. We demonstrate that time-resolved representational structures derived from movement trajectories overlap with those derived from M/EEG (albeit delayed) and those derived from fMRI in functionally-relevant brain areas. Our findings highlight the richness of movement trajectories and the power of the RSA framework to reveal and compare their information content, opening new avenues to better understand human perception.
Group 2i Isochrysidales thrive in marine and lacustrine systems with ice cover
Authors: Wang Karen J. , Huang Yongsong , Kartzinel Tyler , Majaneva Markus , Richter Nora , Liao Sian , Andresen Camilla S. , Vermassen Flor
Published: May 2024

Global warming is causing rapid changes to the cryosphere. Predicting the future trajectory of the cryosphere requires quantitative reconstruction of its past variations. A recently identified sea-ice-associated haptophyte, known as Group 2i Isochrysidales, has given rise to a new sea-ice proxy with its characteristic alkenone distributions. However, apart from the occurrence of Group 2i Isochrysidales in regions with sea ice, and the empirical relationship between C37:4 alkenone abundance and sea-ice concentration, little is known about the ecology of these haptophyte species. Here, we systematically mapped the spatial and temporal occurrence of known Group 2i Isochrysidales based on environmental DNA in both marine and lacustrine environments. Our results indicate Group 2i is widely distributed in icy marine and lacustrine environments in both Northern and Southern Hemisphere, but is absent in warm environments. Temporally, Group 2i is part of the sea-ice algae bloom during the cold seasons, in contrast to other Isochrysidales that bloom in open waters during warm seasons. Our results indicate that ice is a prerequisite for the occurrence of the psychrophilic Group 2i haptophytes in marine and lacustrine ecosystems and further affirms its value for past ice reconstructions.
Comparison between contact diode laser with 980 nm and 1470 nm wavelengths for posterior laryngofissure in pigs
Authors: Rodrigues Isaac de Faria Soares , Guerreiro Cardoso Paulo Francisco , Nepomuceno da Silva Natalia Aparecida , Correia Aristides Tadeu , Minamoto Helio , Bibas Benoit Jacques , Xavier Costa Natalia de Souza , Mancini Marilia Wellichan , Dolhnikoff Marisa , Pego-Fernandes Paulo Manuel
Published: May 2024

To compare two different wavelengths of the surgical contact diode laser (CDL) for producing a posterior laryngofissure in in-vivo pigs. Anesthetized pigs underwent a tracheostomy and an anterior laryngofissure through a cervicotomy. They were randomly selected for the CDL wavelength and Power, according to the peak of Power set at device (980nm wavelength: Ppeak power of 10 W, 15 W, and 20 W, or 1470 nm wavelength: Ppeak 3 W, 5 W, 7 W, 10 W). At the end of the experiment, the laryngotracheal specimen was extracted and sent for histology and morphometry measurements (incision size, depth, area, and lateral thermal damage). Hemodynamic data and arterial blood gases were recorded during the incisions. Statistical analysis of the comparisons between the parameters and groups had a level of significance of p < 0.05. Twenty-six pigs were divided into CDL 980 nm (n = 11) and 1470 nm (n = 15). There was a greater incision area at the thyroid level in the 980 nm CDL and a wider incision at the trachea level, with a larger distance between mucosa borders. There were no significant differences in the area of lateral thermal damage between the two groups and neither difference among the power levels tested. Both wavelengths tested showed similar results in the various combinations of power levels without significant differences in the lateral thermal damage. The posterior laryngofissure incision can be performed by either of the wavelengths at low and medium power levels without great difference on lateral thermal damage.
Dynamic characterization of water hammer in gangue fly ash slurry pipelines during valve closure
Authors: Hao Yuxin , Song Xuepeng , Wang Chengshuai , Fan Bowen , Yang Kai
Published: May 2024

In the process of coal-filling mining, the gangue fly-ash slurry (GFS) needs to be transported over a long distance to reach the gobs. The abrupt closure of the valve during the transportation of GFS can result in a water hammer that significantly endangers the stability and safety of the pipeline transport system. To study the fluctuations in pressure induced by abrupt closure of the valve, experiments on the rheological parameters of gangue-coal ash slurry were conducted. Transient numerical simulations were carried out using the computational fluid dynamics method for various valve closing times. The results indicate that, with the increase of slurry concentration, the yield stress of the slurry significantly increases. When the concentration exceeds 76%, the increase in yield stress reaches 38.4% and 35.1%, respectively. Upon valve closure, the internal pressure of the slurry in the pipeline exhibits periodic dynamic oscillations. As the duration of valve closure increases, the frequency of periodic water hammer events decreases. The maximum water hammer pressure caused by valve closure decreases with the increasing distance between the valve and the closure point. At the same time, the intensity of maximum water hammer pressure fluctuations increases with the increase in slurry concentration and flow velocity in the pipeline. The results can provide references for water hammer protection and pipeline selection during the transportation of backfill slurry in mining.
Genome-wide association analysis uncovers rice blast resistance alleles of Ptr and Pia
Authors: Greenwood Julian R. , Lacorte-Apostol Vanica , Kroj Thomas , Padilla Jonas , Telebanco-Yanoria Mary Jeanie , Glaus Anna N. , Roulin Anne , Padilla André , Zhou Bo , Keller Beat , Krattinger Simon G.
Published: May 2024

A critical step to maximize the usefulness of genome-wide association studies (GWAS) in plant breeding is the identification and validation of candidate genes underlying genetic associations. This is of particular importance in disease resistance breeding where allelic variants of resistance genes often confer resistance to distinct populations, or races, of a pathogen. Here, we perform a genome-wide association analysis of rice blast resistance in 500 genetically diverse rice accessions. To facilitate candidate gene identification, we produce de-novo genome assemblies of ten rice accessions with various rice blast resistance associations. These genome assemblies facilitate the identification and functional validation of novel alleles of the rice blast resistance genes Ptr and Pia. We uncover an allelic series for the unusual Ptr rice blast resistance gene, and additional alleles of the Pia resistance genes RGA4 and RGA5. By linking these associations to three thousand rice genomes we provide a useful tool to inform future rice blast breeding efforts. Our work shows that GWAS in combination with whole-genome sequencing is a powerful tool for gene cloning and to facilitate selection of specific resistance alleles for plant breeding.
A vegetable fat-based diet delays psychomotor and cognitive development compared with maternal dairy fat intake in infant gray mouse lemurs
Authors: Chaudron Yohann , Boyer Constance , Marmonier Corinne , Plourde Mélanie , Vachon Annick , Delplanque Bernadette , Taouis Mohammed , Pifferi Fabien
Published: May 2024

Dairy fat has a unique lipid profile; it is rich in short- and medium-chain saturated fatty acids that induce ketone production and has a balanced ω6/ω3 ratio that promotes cognitive development in early life. Moreover, the high consumption of vegetable oils in pregnant and lactating women raises concerns regarding the quality of lipids provided to offspring. Here, we investigate maternal dairy fat intake during gestation and lactation in a highly valuable primate model for infant nutritional studies, the gray mouse lemur (Microcebus murinus). Two experimental diets are provided to gestant mouse lemurs: a dairy fat-based (DF) or vegetable fat-based diet (VF). The psychomotor performance of neonates is tested during their first 30 days. Across all tasks, we observe more successful neonates born to mothers fed a DF diet. A greater rate of falls is observed in 8-day-old VF neonates, which is associated with delayed psychomotor development. Our findings suggest the potential benefits of lipids originating from a lactovegetarian diet compared with those originating from a vegan diet for the psychomotor development of neonates.
Enhanced emergent electromagnetic inductance in Tb5Sb3 due to highly disordered helimagnetism
Authors: Kitaori Aki , White Jonathan S. , Ukleev Victor , Peng Licong , Nakajima Kiyomi , Kanazawa Naoya , Yu Xiuzhen , Ōnuki Yoshichika , Tokura Yoshinori
Published: May 2024

In helimagnetic metals, ac current-driven spin motions can generate emergent electric fields acting on conduction electrons, leading to emergent electromagnetic induction (EEMI). Recent experiments reveal the EEMI signal generally shows a strongly current-nonlinear response. In this study, we investigate the EEMI of Tb5Sb3, a short-period helimagnet. Using small angle neutron scattering we show that Tb5Sb3 hosts highly disordered helimagnetism with a distribution of spin-helix periodicity. The current-nonlinear dynamics of the disordered spin helix in Tb5Sb3 indeed shows up as the nonlinear electrical resistivity (real part of ac resistivity), and even more clearly as a nonlinear and huge EEMI (imaginary part of ac resistivity) response. The magnitude of the EEMI reaches as large as several tens of μH for Tb5Sb3 devices on the scale of several tens of μm, originating to noncollinear spin textures possibly even without long-range helimagnetic order.
Metal mobilization from thawing permafrost to aquatic ecosystems is driving rusting of Arctic streams
Authors: O’Donnell Jonathan A. , Carey Michael P. , Koch Joshua C. , Baughman Carson , Hill Kenneth , Zimmerman Christian E. , Sullivan Patrick F. , Dial Roman , Lyons Timothy , Cooper David J. , Poulin Brett A.
Published: May 2024

Climate change in the Arctic is altering watershed hydrologic processes and biogeochemistry. Here, we present an emergent threat to Arctic watersheds based on observations from 75 streams in Alaska’s Brooks Range that recently turned orange, reflecting increased loading of iron and toxic metals. Using remote sensing, we constrain the timing of stream discoloration to the last 10 years, a period of rapid warming and snowfall, suggesting impairment is likely due to permafrost thaw. Thawing permafrost can foster chemical weathering of minerals, microbial reduction of soil iron, and groundwater transport of metals to streams. Compared to clear reference streams, orange streams have lower pH, higher turbidity, and higher sulfate, iron, and trace metal concentrations, supporting sulfide mineral weathering as a primary mobilization process. Stream discoloration was associated with dramatic declines in macroinvertebrate diversity and fish abundance. These findings have considerable implications for drinking water supplies and subsistence fisheries in rural Alaska.
A framework for small satellite deployable structures and how to deploy them reliably
Authors: Sauder Jonathan , Gebara Christine , Reddy Narravula Harshavardhan , García-Mora Carlos J.
Published: May 2024

Because of the miniaturization of small satellites, most of them have deployables to expand effective areas. However, Small Satellites are not only required to miniaturize systems, but often have a reduced budget, timeline, and employ teams with less experience. The goal of this paper is to provide a starting point for those new to deloyables, and working on small satellites, to understand the approaches available for deployable mechanisms and provide design practices which can improve success rates. To do so, this paper develops a framework for small satellite deployable structures, categorizing them into distinct deployment stages. It investigates the approaches that can be utilized for each stage, focusing on the stow, restrain, actuate, and locate stages. This review paper discusses the advantages and disadvantages of each approach, supported by examples provided in the references. It then highlights best practices for deployable mechanisms, and describes key challenges and future directions. By offering a comprehensive analysis of small deployable systems, this paper aims to guide engineers and researchers in implementing successful design practices for small satellite deployable structures.
Alzheimer’s disease as a women’s health challenge: a call for action on integrative precision medicine approaches
Authors: Miramontes S. , Pereda Serras C. , Woldemariam S. R. , Khan U. , Li Y. , Tang A. S. , Tsoy E. , Oskotsky T. T. , Sirota M.
Published: May 2024

Alzheimer’s Disease (AD) is marked by pronounced sex differences in pathophysiology and progression. However, the field has yet to fully recognize AD as a women’s health issue, delaying the development of targeted preventative strategies and treatments. This perspective explores the elements impacting AD in women, identifying sex specificity in risk factors, highlighting new diagnostic approaches with electronic health records, and reviewing key molecular studies to underscore the need for integrative precision medicine approaches. Established AD risk factors such as advancing age, the apolipoprotein E4 allele, and poorer cardiovascular health affect women differently. We also shed light on sociocultural risk factors, focusing on the gender disparities that may play a role in AD development. From a biological perspective, sex differences in AD are apparent in biomarkers and transcriptomics, further emphasizing the need for targeted diagnostics and treatments. The convergence of novel multiomics data and cutting-edge computational tools provides a unique opportunity to study the molecular underpinnings behind sex dimorphism in AD. Thus, precision medicine emerges as a promising framework for understanding AD pathogenesis through the integration of genetics, sex, environment, and lifestyle. By characterizing AD as a women’s health challenge, we can catalyze a transformative shift in AD research and care, marked by improved diagnostic accuracy, targeted interventions, and ultimately, enhanced clinical outcomes.
Design, clinical applications and post-surgical assessment of bioresorbable 3D-printed craniofacial composite implants
Authors: Targońska Sara , Dobrzyńska-Mizera Monika , Di Lorenzo Maria Laura , Knitter Monika , Longo Alessandra , Dobrzyński Maciej , Rutkowska Monika , Barnaś Szczepan , Czapiga Bogdan , Stagraczyński Maciej , Mikulski Michał , Muzalewska Małgorzata , Wyleżoł Marek , Rewak-Soroczyńska Justyna , Nowak Nicole , Andrzejewski Jacek , Reeks John , Wiglusz Rafal J.
Published: May 2024

This paper describes in detail the design, fabrication, clinical trial evaluation and post clinical application analysis of 3D-printed bone implants made from the nHAp@PLDLLA [nanohydroxyapatite; poly(l-lactide-co-d,l-lactide)] biomaterial.
PdFe alloy nanoparticles supported on nitrogen-doped carbon nanotubes for electrocatalytic upcycling of poly(ethylene terephthalate) plastics into formate coupled with hydrogen evolution
Authors: Zhang Heng , Liu Zhenzhen , Li Huaimeng , Fu Zhen , Zhang Guofeng , Zhang Haimin , Wang Guozhong , Zhang Yunxia
Published: May 2024

PdFe alloy nanoparticles supported on nitrogen-doped carbon nanotubes, is proposed for the electrochemical upcycling of polyethylene terephthalate waste at the anode with simultaneous generation of hydrogen at the cathode.