bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variants in the WDR44 WD40-repeat domain cause a spectrum of ciliopathy by impairing ciliogenesis initiation
Authors: Accogli Andrea , Shakya Saurabh , Yang Taewoo , Insinna Christine , Kim Soo Yeon , Bell David , Butov Kirill R. , Severino Mariasavina , Niceta Marcello , Scala Marcello , Lee Hyun Sik , Yoo Taekyeong , Stauffer Jimmy , Zhao Huijie , Fiorillo Chiara , Pedemonte Marina , Diana Maria C. , Baldassari Simona , Zakharova Viktoria , Shcherbina Anna , Rodina Yulia , Fagerberg Christina , Roos Laura Sønderberg , Wierzba Jolanta , Dobosz Artur , Gerard Amanda , Potocki Lorraine , Rosenfeld Jill A. , Lalani Seema R. , Scott Tiana M. , Scott Daryl , Azamian Mahshid S. , Louie Raymond , Moore Hannah W. , Champaigne Neena L. , Hollingsworth Grace , Torella Annalaura , Nigro Vincenzo , Ploski Rafal , Salpietro Vincenzo , Zara Federico , Pizzi Simone , Chillemi Giovanni , Ognibene Marzia , Cooney Erin , Do Jenny , Linnemann Anders , Larsen Martin J. , Specht Suzanne , Walters Kylie J. , Choi Hee-Jung , Choi Murim , Tartaglia Marco , Youkharibache Phillippe , Chae Jong-Hee , Capra Valeria , Park Sung-Gyoo , Westlake Christopher J. 
Published: January 2024

AbstractWDR44 prevents ciliogenesis initiation by regulating RAB11-dependent vesicle trafficking. Here, we describe male patients with missense and nonsense variants within the WD40 repeats (WDR) of WDR44, an X-linked gene product, who display ciliopathy-related developmental phenotypes that we can model in zebrafish. The patient phenotypic spectrum includes developmental delay/intellectual disability, hypotonia, distinct craniofacial features and variable presence of brain, renal, cardiac and musculoskeletal abnormalities. We demonstrate that WDR44 variants associated with more severe disease impair ciliogenesis initiation and ciliary signaling. Because WDR44 negatively regulates ciliogenesis, it was surprising that pathogenic missense variants showed reduced abundance, which we link to misfolding of WDR autonomous repeats and degradation by the proteasome. We discover that disease severity correlates with increased RAB11 binding, which we propose drives ciliogenesis initiation dysregulation. Finally, we discover interdomain interactions between the WDR and NH2-terminal region that contains the RAB11 binding domain (RBD) and show patient variants disrupt this association. This study provides new insights into WDR44 WDR structure and characterizes a new syndrome that could result from impaired ciliogenesis.
Emergence of nodal Bogoliubov quasiparticles across the transition from the pseudogap metal to the d-wave superconductor
Authors: Christos Maine , Sachdev Subir 
Published: January 2024

AbstractWe model the pseudogap state of the hole- and electron-doped cuprates as a metal with hole and/or electron pocket Fermi surfaces. In the absence of long-range antiferromagnetism, such Fermi surfaces violate the Luttinger requirement of enclosing the same area as free electrons at the same density. Using the Ancilla theory of such a pseudogap state, we describe the onset of conventional d-wave superconductivity by the condensation of a charge e Higgs boson transforming as a fundamental under the emergent SU(2) gauge symmetry of a background π-flux spin liquid. In all cases, we find that the d-wave superconductor has gapless Bogoliubov quasiparticles at 4 nodal points on the Brillouin zone diagonals with significant velocity anisotropy, just as in the BCS state. This includes the case of the electron-doped pseudogap metal with only electron pockets centered at wavevectors (π, 0), (0, π), and an electronic gap along the zone diagonals. Remarkably, in this case, too, gapless nodal Bogoliubov quasiparticles emerge within the gap at 4 points along the zone diagonals upon the onset of superconductivity.
Sweet taste receptors play roles in artificial sweetener-induced enhanced urine output in mice
Authors: Cai Shuangfeng , Xie Ningning , Zheng Ling , Li Quan , Zhang Siyu , Huang Qinghua , Luo Wei , Wu Mei , Wang Yidan , Du Yilun , Deng Shao-ping , Cai Lei 
Published: January 2024

AbstractSweet taste receptors found in oral and extra oral tissues play important roles in the regulation of many physiological functions. Studies have shown that urine volume increases during the lifetime exposure to artificial sweeteners. However, the detailed molecular mechanism and the general effects of different artificial sweeteners exposure on urine volume remain unclear. In this study, we investigated the relationship between urinary excretion and the sweet taste receptor expression in mice after three artificial sweeteners exposure in a higher or lower concentration via animal behavioral studies, western blotting, and real-time quantitative PCR experiment in rodent model. Our results showed that high dose of acesulfame potassium and saccharin can significantly enhance the urine output and there was a positive correlation between K+ and urination volume. The acesulfame potassium administration assay of T1R3 knockout mice showed that artificial sweeteners may affect the urine output directly through the sweet taste signaling pathway. The expression of T1R3 encoding gene can be up-regulated specifically in bladder but not in kidney or other organs we tested. Through our study, the sweet taste receptors, distributing in many tissues as bladder, were indicated to function in the enhanced urine output. Different effects of long-term exposure to the three artificial sweeteners were shown and acesulfame potassium increased urine output even at a very low concentration.
Exploring chronic and transient tumor hypoxia for predicting the efficacy of hypoxia-activated pro-drugs
Authors: Mathur Shreya , Chen Shannon , Rejniak Katarzyna A. 
Published: January 2024

AbstractHypoxia, a low level of oxygen in the tissue, arises due to an imbalance between the vascular oxygen supply and oxygen demand by the surrounding cells. Typically, hypoxia is viewed as a negative marker of patients’ survival, because of its implication in the development of aggressive tumors and tumor resistance. Several drugs that specifically target the hypoxic cells have been developed, providing an opportunity for exploiting hypoxia to improve cancer treatment. Here, we consider combinations of hypoxia-activated pro-drugs (HAPs) and two compounds that transiently increase intratumoral hypoxia: a vasodilator and a metabolic sensitizer. To effectively design treatment protocols with multiple compounds we used mathematical micro-pharmacology modeling and determined treatment schedules that take advantage of heterogeneous and dynamically changing oxygenation in tumor tissue. Our model was based on data from murine pancreatic cancers treated with evofosfamide (as a HAP) and either hydralazine (as a vasodilator), or pyruvate (as a metabolic sensitizer). Subsequently, this model was used to identify optimal schedules for different treatment combinations. Our simulations showed that schedules of HAPs with the vasodilator had a bimodal distribution, while HAPs with the sensitizer showed an elongated plateau. All schedules were more successful than HAP monotherapy. The three-compound combination had three local optima, depending on the HAPs clearance from the tissue interstitium, each two-fold more effective than baseline HAP treatment. Our study indicates that the three-compound therapy administered in the defined order will improve cancer response and that designing complex schedules could benefit from the use of mathematical modeling.
Neoadjuvant atezolizumab plus chemotherapy in gastric and gastroesophageal junction adenocarcinoma: the phase 2 PANDA trial
Authors: Verschoor Yara L. , van de Haar Joris , van den Berg José G. , van Sandick Johanna W. , Kodach Liudmila L. , van Dieren Jolanda M. , Balduzzi Sara , Grootscholten Cecile , IJsselsteijn Marieke E. , Veenhof Alexander A. F. A. , Hartemink Koen J. , Vollebergh Marieke A. , Jurdi Adham , Sharma Shruti , Spickard Erik , Owers Emilia C. , Bartels-Rutten Annemarieke , den Hartog Peggy , de Miranda Noel F. C. C. , van Leerdam Monique E. , Haanen John B. A. G. , Schumacher Ton N. , Voest Emile E. , Chalabi Myriam 
Published: January 2024

AbstractGastric and gastroesophageal junction (G/GEJ) cancers carry a poor prognosis, and despite recent advancements, most patients die of their disease. Although immune checkpoint blockade became part of the standard-of-care for patients with metastatic G/GEJ cancers, its efficacy and impact on the tumor microenvironment (TME) in early disease remain largely unknown. We hypothesized higher efficacy of neoadjuvant immunotherapy plus chemotherapy in patients with nonmetastatic G/GEJ cancer. In the phase 2 PANDA trial, patients with previously untreated resectable G/GEJ tumors (n = 21) received neoadjuvant treatment with one cycle of atezolizumab monotherapy followed by four cycles of atezolizumab plus docetaxel, oxaliplatin and capecitabine. Treatment was well tolerated. There were grade 3 immune-related adverse events in two of 20 patients (10%) but no grade 4 or 5 immune-related adverse events, and all patients underwent resection without treatment-related delays, meeting the primary endpoint of safety and feasibility. Tissue was obtained at multiple time points, allowing analysis of the effects of single-agent anti-programmed cell death ligand 1 (PD-L1) and the subsequent combination with chemotherapy on the TME. Twenty of 21 patients underwent surgery and were evaluable for secondary pathologic response and survival endpoints, and 19 were evaluable for exploratory translational analyses. A major pathologic response (≤10% residual viable tumor) was observed in 14 of 20 (70%, 95% confidence interval 46–88%) patients, including 9 (45%, 95% confidence interval 23–68%) pathologic complete responses. At a median follow-up of 47 months, 13 of 14 responders were alive and disease-free, and five of six nonresponders had died as a result of recurrence. Notably, baseline anti-programmed cell death protein 1 (PD-1)+CD8+ T cell infiltration was significantly higher in responders versus nonresponders, and comparison of TME alterations following anti-PD-L1 monotherapy versus the subsequent combination with chemotherapy showed an increased immune activation on single-agent PD-1/L1 axis blockade. On the basis of these data, monotherapy anti-PD-L1 before its combination with chemotherapy warrants further exploration and validation in a larger cohort of patients with nonmetastatic G/GEJ cancer. ClinicalTrials.gov registration: NCT03448835.
Changes in oscillatory patterns of microstate sequence in patients with first-episode psychosis
Authors: Zhou Dong-Dong , Li Hong-Zhi , Wang Wo , Kuang Li 
Published: January 2024

AbstractWe aimed to utilize chaos game representation (CGR) for the investigation of microstate sequences and explore its potential as neurobiomarkers for psychiatric disorders. We applied our proposed method to a public dataset including 82 patients with first-episode psychosis (FEP) and 61 control subjects. Two time series were constructed: one using the microstate spacing distance in CGR and the other using complex numbers representing the microstate coordinates in CGR. Power spectral features of both time series and frequency matrix CGR (FCGR) were compared between groups and employed in a machine learning application. The four canonical microstates (A, B, C, and D) were identified using both shared and separate templates. Our results showed the microstate oscillatory pattern exhibited alterations in the FEP group. Using oscillatory features improved machine learning performance compared with classical features and FCGR. This study opens up new avenues for exploring the use of CGR in analyzing EEG microstate sequences. Features derived from microstate sequence CGR offer fine-grained neurobiomarkers for psychiatric disorders.
Stress field disruption allows gas-driven microdeformation in bentonite to be quantified
Authors: Graham Caroline C. , Harrington Jon F. 
Published: January 2024

AbstractGeological disposal of radioactive waste is being planned by many countries. Bentonite clay is often included in facility design, providing a barrier to radionuclide migration. Gas, generated by the waste or corrosion of waste canisters, may disrupt the properties of the bentonite. Robust prediction of this interaction is, therefore, necessary to demonstrate safe facility evolution. In some cases, gas may deform the clay, resulting in localised flow; however, the nature of this deformation has been widely debated. Accurate numerical representation of this behaviour has been limited by a shortage of information on the degree/distribution of deformation. Using experimental data from gas injection tests in bentonite, we show that first order fluctuations in the stress field can provide this information. We show that hundreds of microdeformation events can be detected, with similar characteristics to established fracturing phenomena, including earthquakes and acoustic emissions. We also demonstrate that stress field disruption (i) is spatially localised and (ii) has characteristics consistent with gas pathway ‘opening’ and ‘closure’ as gas enters and exits the clay, respectively. This new methodology offers fundamental insight and a new opportunity to parameterise and constrain gas advection models in clays and shales, substantially improving our capacity for safe facility design.
The biogas upgrading from landfill leachate pretreated with low-frequency ultrasonic: anaerobic digestion performances and energy balance
Authors: Hosseinzadeh Ali , Gitipour Saeid , Mehrdadi Nasser 
Published: January 2024

AbstractThe efficient biogas production from landfill leachate (LL) is one of hot topics in anaerobic digestion systems. Higher bioavailability of LL can be achieved by application a feasible and promising pretreatment technologies in order to utilize as a substrate for anaerobic reactors. Here, the enhanced bioavailabity of LL using the low-frequency ultrasonic process and energy balance in anaerobic digestion process was estimated within incubation period of 24 days. The optimal performance of low-frequency ultrasonic for LL biodegradability index: sCOD and TVFA were estimated under influencing parameters: ultrasonic density (UD) (0.02–0.14 W/mL) and Ultrasonic time (UT) (0–12 min). Moreover, the effects of low-frequency ultrasonic pretreatment process on biogas production in batch mode anaerobic reactors operated at 37 ± 1 °C were surveyed for daily and cumulative methane production, operational performance and energy balance. An increased sCOD (820 mg/L) and TVFA (659 mg/L) were observed under optimum codition: UD (0.1 W/mL) and UT (10 min). The highest methane production (430 mL) was found in reactor 4, where %15 volume ratio of LL pretreated with low frequency ultrasonic were feed in. Energy balance assessment indicated that output energy for anaerobic reactors assissted with ultrasonic in range of + 6.99 and + 7.98 kJ/g VS removed. Therefore, incorporation the low-frequency ultrasonic and digestion process revealed a promising and economic technique to improve biomethane potential and energy balance from LL.
In silico anti-alzheimer study of phytochemicals from Lamiaceae family through GSK3-β inhibition
Authors: Zareei Sara , Pourmand Saeed , Eskandarzadeh Marzieh , Massahi Shokoufeh 
Published: January 2024

AbstractGlycogen synthase kinase 3-beta (GSK3-β) is a serine-threonine protease expressed in the brain, and its hyperactivity is considered the underlying cause of Alzheimer’s disease. This enzyme requires an ATP molecule in its N-terminal lobe to phosphorylate its substrates, with the most important substrate being the Tau protein. This study focuses on the inhibitory mechanism of four naturally occurring compounds—apigenin, luteolin, rosmarinic acid, and salvianolic acid—from the Laminaceae family against GSK3-β. The orientation of the ligands within the ATP-binding pocket of GSK3-β and their binding energy were determined through molecular docking. Additionally, molecular dynamics simulations was conducted to study the conformational changes induced by the ligands in the protein structure. The results showed that apigenin and salvianolic acid achieved deeper parts of the cavity compared to luteolin and rosmarinic acid and formed stable complexes with the enzyme. In the rosmarinic acid complex, the enzyme exhibited the most exposed conformation. On the other hand, luteolin binding caused a small closure of the opening, suggesting a potentially ATP-competitive role. Our results suggest these compounds as lead candidates for the design of GSK3-β inhibitors.
Investigation of ternary Zn–Co–Fe layered double hydroxide as a multifunctional 2D layered adsorbent for moxifloxacin and antifungal disinfection
Authors: Mahmoud Rehab , Kotb Nada M. , GadelHak Yasser , El-Ela Fatma I. Abo , Shehata Ayman Z. , Othman Sarah I. , Allam Ahmed A. , Rudayni Hassan Ahmed , Zaher Amal 
Published: January 2024

AbstractLayered double hydroxides have recently gained wide interest as promising multifunctional nanomaterials. In this work, a multifunctional ternary Zn–Co–Fe LDH was prepared and characterized using XRD, FTIR, BET, TEM, SEM, and EDX. This LDH showed a typical XRD pattern with a crystallite size of 3.52 nm and a BET surface area of 155.9 m2/g. This LDH was investigated, for the first time, as an adsorbent for moxifloxacin, a common fluoroquinolones antibiotic, showing a maximum removal efficiency and equilibrium time of 217.81 mg/g and 60 min, respectively. Its antifungal activity, for the first time, was investigated against Penicillium notatum, Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, and Mucor fungi at various concentrations (1000–1.95 µg/mL). This LDH was found to be effective against a variety of fungal strains, particularly Penicillium and Mucor species and showed zones of inhibition of 19.3 and 21.6 mm for Penicillium and Mucor, respectively, with an inhibition of 85% for Penicillium species and 68.3% for Mucormycosis. The highest antifungal efficacy results were obtained at very low MIC concentrations (33.3 and 62 µg/ml) against Penicillium and Mucor, respectively. The results of this study suggest a promising multifunctional potential of this LDH for water and wastewater treatment and disinfection applications.
Biomarkers of axonal damage to favor early diagnosis in variant transthyretin amyloidosis (A-ATTRv)
Authors: González-Moreno Juan , Gragera-Martínez Álvaro , Rodríguez Adrián , Borrachero-Garro Cristina , García-Garrido Sandra , Barceló Carles , Manovel-Sánchez Ana , Ribot-Sansó Maria Antonia , Ibargüen-González Lesly , Gomila Rosa , Muñoz-Beamud Francisco , Losada-López Inés , Cisneros-Barroso Eugenia 
Published: January 2024

AbstractEarly identification of ATTRv amyloidosis disease onset is still often delayed due to the lack of validated biomarkers of this disease. Light chain neurofilament (NfL) have shown promising results in early diagnosis in this disease, but data is still needed, including with alternative measuring methods. Our aim was to study the levels of NfL measured by ELISA. Furthermore, interstitial matrix metalloproteinase type 1 (MMP-1) serum levels were measured as a potential new biomarker in ATTRv. Serum NfL and MMP-1 were measured using ELISA assays in 90 participants (29 ATTR-V30M patients, 31 asymptomatic V30M-TTR variant carriers and 30 healthy controls). Median NfL levels among ATTRv amyloidosis patients were significantly higher (116 pg/mL vs 0 pg/mL in both comparison groups). The AUC comparing ATTRv amyloidosis patients and asymptomatic carriers was 0.90 and the NfL concentration of 93.55 pg/mL yielded a sensitivity of 79% and a specificity of 87%. NfL levels had a significant positive correlation with NIS values among patients. We found a negative significant correlation between eGFR and NfL levels. Finally, MMP1 levels were not different between groups. Evidence of NfL use for early diagnosis of ATTR-PN amyloidosis is growing. ELISA seems a reliable and available technique for it quantification. Decreased GFR could influence NfL plasma levels.
Boil water notices as health-risk communication: risk perceptions, efficacy, and compliance during winter storm Uri
Authors: Day Ashleigh M. , O’Shay Sydney , Islam Khairul , Seeger Matthew W. , Sperone F. Gianluca , McElmurry Shawn P. 
Published: January 2024

AbstractWinter Storm Uri was a disaster that impacted much of the United States during February of 2021. During and after the storm, Texas and Oklahoma experienced massive power grid failures. This led to cascading impacts, including water system disruptions and many boil water notices (BWNs). The breakdown of some communication channels and the inability to enact protective actions due to power outages, as well as travel limitations on public roads, complicated the dissemination and implementation of notifications. This research examined individuals’ perceptions of risk, water quality, and BWNs during Uri. Additionally, this study sought to understand if previous experience with a BWN influenced compliance during Uri and how perceived efficacy impacted these variables. Surveying 893 Texans and Oklahomans revealed that most Uri-affected respondents believed the risks associated with BWNs were severe. Income and race were two factors that influenced BWN compliance. Age, gender, and level of education did not influence compliance. Previous experience with BWNs did not increase risk perceptions. Higher levels of perceived efficacy correlated to higher levels of compliance, perceptions of risk, and water quality, much of which support propositions of the Extended Parallel Process Model. Results suggest that pre-disaster planning and communication are imperative to helping reduce risk(s) and enhancing efficacy during a disaster, especially for novel disasters that have cascading risks, like Winter Storm Uri.
A SINE-VNTR-Alu at the LRIG2 locus is associated with proximal and distal gene expression in CRISPR and population models
Authors: Hall Ashley , Middlehurst Ben , Cadogan Max A. M. , Reed Xylena , Billingsley Kimberley J. , Bubb Vivien J. , Quinn John P. 
Published: January 2024

AbstractSINE-VNTR-Alu (SVA) retrotransposons represent mobile regulatory elements that have the potential to influence the surrounding genome when they insert into a locus. Evolutionarily recent mobilisation has resulted in loci in the human genome where a given retrotransposon might be observed to be present or absent, termed a retrotransposon insertion polymorphism (RIP). We previously observed that an SVA RIP ~ 2 kb upstream of LRIG2 on chromosome 1, the ‘LRIG2 SVA’, was associated with differences in local gene expression and methylation, and that the two were correlated. Here, we have used CRISPR-mediated deletion of the LRIG2 SVA in a cell line model to validate that presence of the retrotransposon is directly affecting local expression and provide evidence that is suggestive of a modest role for the SVA in modulating nearby methylation. Additionally, in leveraging an available Hi-C dataset we observed that the LRIG2 SVA was also involved in long-range chromatin interactions with a cluster of genes ~ 300 kb away, and that expression of these genes was to varying degrees associated with dosage of the SVA in both CRISPR cell line and population models. Altogether, these data support a regulatory role for SVAs in the modulation of gene expression, with the latter potentially involving chromatin looping, consistent with the model that RIPs may contribute to interpersonal differences in transcriptional networks.