bluuebunny/crossref_metadata_2025_split huggingface dataset:
Smart Galactosidase‐Responsive Antimicrobial Dendron: Towards More Biocompatible Membrane‐Disruptive Agents
Authors: Shao Zeyu , Xu You Dan , Luo Hao , Hakobyan Karen , Zhang Mengnan , Xu Jiangtao , Stenzel Martina H. , Wong Edgar H. H. 
Published: June 2024

AbstractAntimicrobial resistance is a global healthcare challenge that urgently needs the development of new therapeutic agents. Antimicrobial peptides and mimics thereof are promising candidates but mostly suffer from inherent toxicity issues due to the non‐selective binding of cationic groups with mammalian cells. To overcome this toxicity issue, this work herein reports the synthesis of a smart antimicrobial dendron with masked cationic groups (Gal‐Dendron) that could be uncaged in the presence of β‐galactosidase enzyme to form the activated Enz‐Dendron and confer antimicrobial activity. Enz‐Dendron show bacteriostatic activity toward Gram‐negative (P. aeruginosa and E. coli) and Gram‐positive (S. aureus) bacteria with minimum inhibitory concentration values of 96 µm and exerted its antimicrobial mechanism via a membrane disruption pathway, as indicated by inner and outer membrane permeabilization assays. Crucially, toxicity studies confirmed that the masked prodrug Gal‐Dendron exhibited low hemolysis and is at least 2.4 times less toxic than the uncaged cationic Enz‐Dendron, thus demonstrating the advantage of masking the cationic groups with responsive immolative linkers to overcome toxicity and selectivity issues. Overall, this study highlights the potential of designing new membrane‐disruptive antimicrobial agents that are more biocompatible via the amine uncaging strategy.
ZBTB7A interferes with the RPL5‐P53 feedback loop and reduces endoplasmic reticulum stress‐induced apoptosis of pancreatic cancer cells
Authors: Tang Jie , Chen Lingling , Chang Yunli , Hang Dongyun , Chen Guoyu , Wang Ying , Feng Lingmei , Xu Ming 
Published: June 2024

AbstractEndoplasmic reticulum (ER) stress is a primary mechanism leading to cell apoptosis, making it of great research interests in cancer management. This study delves into the function of ribosomal protein L5 (RPL5) in ER stress within pancreatic cancer (PCa) cells and investigates its regulatory mechanisms. Bioinformatics predictions pinpointed RPL5 as an ER stress‐related gene exhibiting diminished expression in PCa. Indeed, RPL5 was found to be poorly expressed in PCa tissues and cells, with this reduced expression correlating with an unfavorable prognosis. Moreover, RPL5 overexpression led to heightened levels of p‐PERK, p‐eIF2α, and CHOP, bolstering the proapoptotic effect of Tunicamycin, an ER stress activator, on PCa cells. Additionally, the RPL5 overexpression curbed cell proliferation, migration, and invasion. Tunicamycin enhanced the binding between RPL5 and murine double minute 2 (MDM2), thus suppressing MDM2‐mediated ubiquitination and degradation of P53. Consequently, P53 augmentation intensified ER stress, which further enhanced the binding between RPL5 and MDM2 through PERK‐dependent eIF2α phosphorylation, thereby establishing a positive feedback loop. Zinc finger and BTB domain containing 7A (ZBTB7A), conspicuously overexpressed in PCa samples, repressed RPL5 transcription, thereby reducing P53 expression. Silencing of ZBTB7A heightened ER stress and subdued the malignant attributes of PCa cells, effects counteracted upon RPL5 silencing. Analogous outcomes were recapitulated in vivo employing a xenograft tumor mouse model, where ZBTB7A silencing dampened the tumorigenic potential of PCa cells, an effect reversed by additional RPL5 silencing. In conclusion, this study suggests that ZBTB7A represses RPL5 transcription, thus impeding the RPL5‐P53 feedback loop and mitigating ER‐induced apoptosis in PCa cells.
Targeting RNA‐binding motif protein 39 for arginine reduction: unveiling metabolic vulnerability in arginine‐dependent liver cancer
Authors: Li Aoxue , Cui Hongjuan , Zhao Erhu 
Published: June 2024

AbstractCancer is increasingly acknowledged as a metabolic disease, characterized by metabolic reprogramming as its hallmark. However, the precise mechanisms behind this phenomenon and the factors contributing to tumorigenicity are still poorly understood. In a recent publication in Cell, Mossmann and colleague reported a study unveiling arginine as a molecule with second messenger‐like properties that reshapes metabolism to facilitate the tumor development in hepatocellular carcinoma (HCC). Their research revealed that the RNA‐binding motif protein 39 (RBM39)‐mediated increase in asparagine synthesis results in increased arginine uptake. This establishes a positive feedback loop that sustains elevated levels of arginine and facilitates oncogenic metabolic reprogramming. Additionally, Mossmann et al. demonstrated that depleting RBM39 with indisulam effectively disrupts the proto‐oncogenic metabolic reprogramming in HCC. This discovery presents a novel treatment strategy for arginine‐dependent liver cancers.
No evidence of Fabry disease in a patient with the new p.Met70Val GLA gene variant
Authors: Capelli Irene , Di Costanzo Roberta , Aiello Valeria , Lerario Sarah , De Giovanni Paola , Montevecchi Marcello , Cerretani Davide , Donadio Vincenzo , La Manna Gaetano , Mignani Renzo 
Published: June 2024

AbstractBackgroundFabry disease (FD) is a rare X‐linked lysosomal storage disorder caused by variants in GLA gene leading to deficient α‐galactosidase A enzyme activity. This deficiency leads to the accumulation of glycosphingolipids, particularly globotriaosylceramide (Gb3), in various tissues and organs, which can result in life‐threatening complications. The clinical presentation of the disease can vary from the “classic” phenotype with pediatric onset and multi‐organ involvement to the “later‐onset” phenotype, which presents with predominantly cardiac symptoms. In recent years, advances in screening studies have led to the identification of an increasing number of variants of unknown significance that have not yet been described, and whose pathogenic role remains undetermined.MethodsIn this clinical report, we describe the case of an asymptomatic adult female who was found to have a new variant of unknown significance, p.Met70Val. Given the unknown pathogenic role of this variant, a thorough analysis of the potential organ involvement was conducted. The clinical data were analyzed retrospectively.ResultsThe analysis revealed that there were no signs of significant organ involvement, and the benignity of the variant was confirmed.ConclusionThis case underscores the importance of a comprehensive evaluation of new variants of unknown significance to establish their pathogenicity accurately.
Ultrafast T2 and T2* mapping using single‐shot spatiotemporally encoded MRI with reduced field of view and spiral out‐in‐out‐in trajectory
Authors: Jin Junxian , Zhou Yang , Chen Lin , Chen Zhong 
Published: June 2024

AbstractBackgroundT2 and T2* mapping are crucial components of quantitative magnetic resonance imaging, offering valuable insights into tissue characteristics and pathology. Single‐shot methods can achieve ultrafast T2 or T2* mapping by acquiring multiple readout echo trains. However, the extended echo trains pose challenges, such as compromised image quality and diminished quantification accuracy.PurposeIn this study, we develop a single‐shot method for ultrafast T2 and T2* mapping with reduced echo train length.MethodsThe proposed method is based on ultrafast single‐shot spatiotemporally encoded (SPEN) MRI combined with reduced field of view (FOV) and spiral out‐in‐out‐in (OIOI) trajectory. Specifically, a biaxial SPEN excitation scheme was employed to excite the spin signal into the spatiotemporal encoding domain. The OIOI trajectory with high acquisition efficiency was employed to acquire signals within targeted reduced FOV. Through non‐Cartesian super‐resolved (SR) reconstruction, 12 aliasing‐free images with different echo times were obtained within 150 ms. These images were subsequently fitted to generate T2 or T2* mapping simultaneously using a derived model.ResultsAccurate and co‐registered T2 and T2* maps were generated, closely resembling the reference maps. Numerical simulations demonstrated substantial consistency (R2 > 0.99) with the ground truth values. A mean difference of 0.6% and 1.7% was observed in T2 and T2*, respectively, in in vivo rat brain experiments compared to the reference. Moreover, the proposed method successfully obtained T2 and T2* mappings of rat kidney in free‐breathing mode, demonstrating its superiority over multishot methods lacking respiratory navigation.ConclusionsThe results suggest that the proposed method can achieve ultrafast and accurate T2 and T2* mapping, potentially facilitating the application of T2 and T2* mapping in scenarios requiring high temporal resolution.
Headache and Facial Pain/Pressure in the Chronic Rhinosinusitis Population: A Systematic Review and Meta‐analysis
Authors: Heiland Luke D. , Farmer Hannah G. , Nguyen Shaun A. , Soler Zachary M. , Schlosser Rodney J. 
Published: June 2024

AbstractObjectiveTo evaluate the severity and prevalence of headache and facial pain/pressurere in the chronic rhinosinusitis (CRS) population.Data SourcesCINAHL, PubMed, Scopus.Review MethodsThe literature was searched from inception through June 2023 for English language articles documenting “headache” or “facial pain/pressure” and “chronic rhinosinusitis.” Data collected included Lund‐MacKay computed tomography score, Lund‐Kennedy endoscopy score, sinonasal outcome test, and visual analog scale. Meta‐analyses were performed on continuous measures (mean), proportions (%), and regression.ResultsA total of 69 studies were included with 8643 CRS patients and 703 control patients. The CRS group had a mean age of 44.1 (range: 16‐82; 95% confidence interval [CI]: 40.3‐48) and 86.1% [95% CI: 76.4‐93.5] with nasal polyposis. The control group had a mean age of 39.2 (range: 17‐88; 95% CI: 28.7‐49.8). All CRS subgroups had significantly more severe headache and facial pain/pressure when compared to the control (P < .0001). Patients without polyps had significantly more severe facial pain/pressure and headache when compared to patients with polyps (P < .0001). Facial pain/pressure is a moderate problem or worse in 29.8% of polypoid patients versus 56.4% of nonpolypoid patients; Δ26.6% [95% CI: 0.7‐50; P = .045].ConclusionsAcross all outcome metrics, CRS patients experience significantly more severe headache and facial pain/pressure when compared to a control population. Nonpolypoid patients experience significantly more severe facial pain/pressure and headache when compared to polypoid patients. The majority of nonpolypoid patients experience facial pain/pressure that is moderate in severity or worse.
ChatENT: Augmented Large Language Model for Expert Knowledge Retrieval in Otolaryngology–Head and Neck Surgery
Authors: Long Cai , Subburam Deepak , Lowe Kayle , dos Santos André , Zhang Jessica , Hwang Sang , Saduka Neil , Horev Yoav , Su Tao , Côté David W.J. , Wright Erin D. 
Published: June 2024

AbstractObjectiveThe recent surge in popularity of large language models (LLMs), such as ChatGPT, has showcased their proficiency in medical examinations and potential applications in health care. However, LLMs possess inherent limitations, including inconsistent accuracy, specific prompting requirements, and the risk of generating harmful hallucinations. A domain‐specific model might address these limitations effectively.Study DesignDevelopmental design.SettingVirtual.MethodsOtolaryngology–head and neck surgery (OHNS) relevant data were systematically gathered from open‐access Internet sources and indexed into a knowledge database. We leveraged Retrieval‐Augmented Language Modeling to recall this information and utilized it for pretraining, which was then integrated into ChatGPT4.0, creating an OHNS‐specific knowledge question & answer platform known as ChatENT. The model is further tested on different types of questions.ResultsChatENT showed enhanced performance in the analysis and interpretation of OHNS information, outperforming ChatGPT4.0 in both the Canadian Royal College OHNS sample examination questions challenge and the US board practice questions challenge, with a 58.4% and 26.0% error reduction, respectively. ChatENT generated fewer hallucinations and demonstrated greater consistency.ConclusionTo the best of our knowledge, ChatENT is the first specialty‐specific knowledge retrieval artificial intelligence in the medical field that utilizes the latest LLM. It appears to have considerable promise in areas such as medical education, patient education, and clinical decision support. The model has demonstrated the capacity to overcome the limitations of existing LLMs, thereby signaling a future of more precise, safe, and user‐friendly applications in the realm of OHNS and other medical fields.
Effects of dopamine‐modified ZnO and Ce‐Zr oxides on UV resistance and thermal stability of epoxy composites
Authors: Li Yi , Zhang Ning , Zhu Yanchao , Cheng Min , Gao Shuang 
Published: June 2024

AbstractIn this work, surface‐modified Ce‐Zr oxides and ZnO nanoparticles were conveniently prepared by dopamine (Dpa) treatment and then composited with epoxy (EP) by hot pressing. Thermogravimetric analysis (TGA) and UV‐shielding properties of the EP composites with surface modification with Dpa‐CZ and Dpa‐ZnO were measured. The TGA results showed that the modified treated fillers had no loss of heat resistance of the matrix and had an enhancement effect on the initial and maximum decomposition temperatures. In addition, the UV‐shielding properties of EP composites after Dpa‐CZ and Dpa‐ZnO modifications both showed a significant enhancement effect compared to pure EP. The T(UVA) of the 0.5 wt% Dpa‐ZnO modified composite decreased to less than 0.017%, and the T(UVB) decreased to less than 0.0059%. The T(UVA) of the 0.5 wt% Dpa‐CZ modified composite decreased to less than 15.98%, and the T(UVB) decreased to below 1.14%. The composites have both excellent thermal stability and UV‐shielding efficiency.
The effectiveness of an ultra‐brief intervention in 1 min for hazardous drinking in a general hospital setting: A quasi‐randomized pilot trial
Authors: Tezuka Yukio , So Ryuhei , Fukuda Takahiro 
Published: June 2024

AbstractObjectiveWe investigated the effectiveness of an ultra‐brief intervention (Ultra‐BI) for patients with hazardous drinking behaviors admitted to a general hospital.MethodIn a quasi‐randomized controlled trial at a general hospital in Japan, we assigned participants to intervention or control groups based on the last digit of their patient ID (odd for intervention, even for control). The study included inpatients with Alcohol Use Disorder Identification Test‐Consumption (AUDIT‐C) scores of ≥5 for men and ≥4 for women. The intervention involved providing advice and feedback within 1 min, accompanied by a leaflet on alcohol‐related issues (Ultra‐BI). The control group did not receive any intervention. The primary outcome was average weekly alcohol consumption at 3 months postintervention.ResultsThe study included 68 participants. The intervention group showed a reduction in average weekly alcohol consumption by −69.7 g/week compared to the control group (95% confidence interval [CI] −145.7 to 6.3 g/week, p = 0.07). Post‐hoc analysis, adjusting for baseline values, indicated a between‐group difference of −78.7 g/week (95% CI −135.2 to −22.2 g/week, p = 0.007).ConclusionThis pilot trial suggests the potential effectiveness of the Ultra‐BI in general hospital wards. Further large‐scale studies are required to confirm these findings.
A fast and sensitive size‐exclusion chromatography method for plasma extracellular vesicle proteomic analysis
Authors: Díaz Ludovico Ivo , Powell Samantha M. , Many Gina , Bramer Lisa , Sarkar Soumyadeep , Stratton Kelly , Liu Tao , Shi Tujin , Qian Wei‐Jun , Burnum‐Johnson Kristin E. , Melchior John T. , Nakayasu Ernesto S. 
Published: June 2024

AbstractExtracellular vesicles (EVs) carry diverse biomolecules derived from their parental cells, making their components excellent biomarker candidates. However, purifying EVs is a major hurdle in biomarker discovery since current methods require large amounts of samples, are time‐consuming and typically have poor reproducibility. Here we describe a simple, fast, and sensitive EV fractionation method using size exclusion chromatography (SEC) on a fast protein liquid chromatography (FPLC) system. Our method uses a Superose 6 Increase 5/150, which has a bed volume of 2.9 mL. The FPLC system and small column size enable reproducible separation of only 50 µL of human plasma in 15 min. To demonstrate the utility of our method, we used longitudinal samples from a group of individuals who underwent intense exercise. A total of 838 proteins were identified, of which, 261 were previously characterized as EV proteins, including classical markers, such as cluster of differentiation (CD)9 and CD81. Quantitative analysis showed low technical variability with correlation coefficients greater than 0.9 between replicates. The analysis captured differences in relevant EV proteins involved in response to physical activity. Our method enables fast and sensitive fractionation of plasma EVs with low variability, which will facilitate biomarker studies in large clinical cohorts.
Rheostatic contributions to protein stability can obscure a position's functional role
Authors: O'Neil Pierce T. , Swint‐Kruse Liskin , Fenton Aron W. 
Published: June 2024

AbstractRheostat positions, which can be substituted with various amino acids to tune protein function across a range of outcomes, are a developing area for advancing personalized medicine and bioengineering. Current methods cannot accurately predict which proteins contain rheostat positions or their substitution outcomes. To compare the prevalence of rheostat positions in homologs, we previously investigated their occurrence in two pyruvate kinase (PYK) isozymes. Human liver PYK contained numerous rheostat positions that tuned the apparent affinity for the substrate phosphoenolpyruvate (Kapp‐PEP) across a wide range. In contrast, no functional rheostat positions were identified in Zymomonas mobilis PYK (ZmPYK). Further, the set of ZmPYK substitutions included an unusually large number that lacked measurable activity. We hypothesized that the inactive substitution variants had reduced protein stability, precluding detection of Kapp‐PEP tuning. Using modified buffers, robust enzymatic activity was obtained for 19 previously‐inactive ZmPYK substitution variants at three positions. Surprisingly, both previously‐inactive and previously‐active substitution variants all had Kapp‐PEP values close to wild‐type. Thus, none of the three positions were functional rheostat positions, and, unlike human liver PYK, ZmPYK's Kapp‐PEP remained poorly tunable by single substitutions. To directly assess effects on stability, we performed thermal denaturation experiments for all ZmPYK substitution variants. Many diminished stability, two enhanced stability, and the three positions showed different thermal sensitivity to substitution, with one position acting as a “stability rheostat.” The differences between the two PYK homologs raises interesting questions about the underlying mechanism(s) that permit functional tuning by single substitutions in some proteins but not in others.
Basic immunologic study as a foundation for engineered therapeutic development
Authors: DeStefano Sabrina , Fertil Daphna , Faust Mondreakest , Sadtler Kaitlyn 
Published: June 2024

AbstractBioengineering and drug delivery technologies play an important role in bridging the gap between basic scientific discovery and clinical application of therapeutics. To identify the optimal treatment, the most critical stage is to diagnose the problem. Often these two may occur simultaneously or in parallel, but in this review, we focus on bottom‐up approaches in understanding basic immunologic phenomena to develop targeted therapeutics. This can be observed in several fields; here, we will focus on one of the original immunotherapy targets—cancer—and one of the more recent targets—regenerative medicine. By understanding how our immune system responds in processes such as malignancies, wound healing, and medical device implantation, we can isolate therapeutic targets for pharmacologic and bioengineered interventions.
Spatial poverty dynamics and social mobility in rural America
Authors: Connor Dylan S. , Xie Siqiao , Uhl Johannes H. , Talbot Catherine , Hester Cyrus , Jaworski Taylor , Gutmann Myron , Leyk Stefan , Hunter Lori 
Published: June 2024

AbstractRural America is often depicted as a distressed and left‐behind place, with limited opportunities for the children growing up there. This paper addresses this topic by examining the dynamics of rural places over the past four decades and how these changes impact the economic mobility of children raised in poor rural households. Employing a place‐based framework, we utilise sequence analysis to identify dominant trajectories of change for more than 8000 rural communities. Our analysis reveals highly diverse community trajectories that connect deindustrialisation and racial inequality to elevated and rising poverty rates in certain places, while also documenting more favourable poverty trends elsewhere. These diverging local outcomes shed new light on the conflicting narratives surrounding rural America. We then demonstrate that, among children from poorer households, exposure to community poverty is predictive of adult economic mobility, patterns which are partly mediated by family stability and child poverty. Our finding that poor children face additional disadvantages when they also grow up in poor places suggests a potential role for place‐based policies and redistribution to help ameliorate these disparities.
Non‐Hermitian Control of Multimode Duan‐PPT Criteria and Steering in Energy‐Level Cascaded Four‐Wave Mixing Processes
Authors: Wei Jiajia , Huang Cheng , He Yandong , Wei Jiaxuan , Qin Wenqiang , Tang Haitian , Li Ning , Li Feng , Cai Yin , Li Bo , Zhang Yanpeng 
Published: June 2024

AbstractThe non‐Hermitian singularity control of multimode entanglement in the energy‐level cascaded four‐wave mixing system within a single atomic vapor is of great significance and importance. In this study, a non‐Hermiticity system by means of quasi‐quantization of energy‐band based on non‐Hermiticity systems is constructed. By employing atomic coherence in the non‐Hermiticity system, high‐dimensional quantized photon correlations underdressed field‐induced parity‐time (PT) symmetry and symmetry breaking through the quantization of energy levels are studied. Such a phenomenon happens at microscopic (nanoscale) when the eigenvalues of dressed energy‐level and multimode entanglement are considered for both real and imaginary parts symmetry breaking. Double dressing effect is observed with more coherent channels and larger information capacity than single dressing in the energy‐level cascaded four‐wave mixing system. The study found that the splitting of the real part is larger than an imaginary part in a second‐order system, and the imaginary part splitting is also greater than the real part splitting in a third‐order system. The real part (in phase) is constructive dressing quantization, and the imaginary (out of phase) is destructive dressing quantization. Exceptional points (EP points) can be used to enhance sensitivity detection of entanglement quantum state.