bluuebunny/crossref_metadata_2025_split huggingface dataset:
Asparagine synthetase and G‐protein coupled estrogen receptor are critical responders to nutrient supply in KRAS mutant colorectal cancer
Authors: Lu Lingeng , Zhang Qian , Aladelokun Oladimeji , Berardi Domenica , Shen Xinyi , Marin Audrey , Garcia‐Milian Rolando , Roper Jatin , Khan Sajid A. , Johnson Caroline H. 
Published: July 2024

AbstractSurvival differences exist in colorectal cancer (CRC) patients by sex and disease stage. However, the potential molecular mechanism(s) are not well understood. Here we show that asparagine synthetase (ASNS) and G protein‐coupled estrogen receptor‐1 (GPER1) are critical sensors of nutrient depletion and linked to poorer outcomes for females with CRC. Using a 3D spheroid model of isogenic SW48 KRAS wild‐type (WT) and G12A mutant (MT) cells grown under a restricted nutrient supply, we found that glutamine depletion inhibited cell growth in both cell lines, whereas ASNS and GPER1 expression were upregulated in KRAS MT versus WT. Estradiol decreased growth in KRAS WT but had no effect on MT cells. Selective GPER1 and ASNS inhibitors suppressed cell proliferation with increased caspase‐3 activity of MT cells under glutamine depletion condition particularly in the presence of estradiol. In a clinical colon cancer cohort from The Cancer Genome Atlas, both high GPER1 and ASNS expression were associated with poorer overall survival for females only in advanced stage tumors. These results suggest KRAS MT cells have mechanisms in place that respond to decreased nutrient supply, typically observed in advanced tumors, by increasing the expression of ASNS and GPER1 to drive cell growth. Furthermore, KRAS MT cells are resistant to the protective effects of estradiol under nutrient deplete conditions. The findings indicate that GPER1 and ASNS expression, along with the interaction between nutrient supply and KRAS mutations shed additional light on the mechanisms underlying sex differences in metabolism and growth in CRC, and have clinical implications in the precision management of KRAS mutant CRC.
Rapid development of neurological infection in a patient with human immunodeficiency virus following schistosomiasis: A case report
Authors: Liu Yan , Zhou Guoqiang , Jiang Wei , Kong Xianglong 
Published: July 2024

AbstractHIV‐1 and schistosomal infections present significant global health challenges, and neurological manifestations of these pathogens are easily misdiagnosed due to their rarity. Here, we report the case of a 36‐year‐old patient with acquired immunodeficiency syndrome who was initially diagnosed with human immunodeficiency virus‐1 (HIV‐1) infection 4 years earlier, although untreated for approximately 3 years until he began antiretroviral therapy (ART) following a tuberculosis diagnosis and hospitalization. Despite achieving virological suppression of HIV‐1 1 year after ART, he was readmitted with high fever and headache. Initial therapy for suspected tuberculosis based on clinical performance and brain imaging features failed, and further investigation confirmed an intracranial infection caused by schistosomiasis. Following anti‐schistosomal treatment and optimized ART, the patient recovered fully and was discharged. This case of a patient in Asia infected with human immunodeficiency virus (HIV) who rapidly developed a neurological infection subsequent to acquiring schistosomiasis highlights the need for awareness of such coinfections in patients with HIV.
Exploring the biodegradability of candidate metallic intravascular stent materials using X‐ray microfocus computed tomography: An in vitro study
Authors: Leyssens Lisa , Lapraille Noémie , Pyka Grzegorz , Jacques Pascal J. , Horman Sandrine , Goldman Jeremy , Kerckhofs Greet 
Published: July 2024

AbstractIn vitro testing for evaluating degradation mode and rate of candidate biodegradable metals to be used as intravascular stents is crucial before going to in vivo animal models. In this study, we show that X‐ray microfocus computed tomography (microCT) presents a key added value to visualize degradation mode and to evaluate degradation rate and material surface properties in 3D and at high resolution of large regions of interest. The in vitro degradation behavior of three candidate biodegradable stent materials was evaluated: pure iron (Fe), pure zinc (Zn), and a quinary Zn alloy (ZnAgCuMnZr). These metals were compared to a reference biostable cobaltchromium (CoCr) alloy. To compare the degradation mode and degradation rate evaluated with microCT, scanning electron microscopy (SEM) and inductively‐coupled plasma (ICP) were included. We confirmed that Fe degrades very slowly but with desirable uniform surface corrosion. Zn degrades faster but exhibits localized deep pitting corrosion. The Zn alloy degrades at a similar rate as the pure Zn, but more homogeneously. However, the formation of deep internal dendrites was observed. Our study provides a detailed microCT‐based comparison of essential surface and corrosion properties, with a structural characterization of the corrosion behavior, of different candidate stent materials in 3D in a non‐destructive way.
Long noncoding RNA LINC01550 inhibits colorectal cancer malignancy by suppressing the Wnt/β‐catenin signaling pathway
Authors: Wu Weiyun , Li Aiting , He Huanjin , Ye Shicai , Zhou Zhuliang , Quan Juan‐Hua , Tan Wenkai 
Published: July 2024

AbstractColorectal cancer (CRC) is a common gastrointestinal malignancy. Long noncoding RNAs (lncRNAs) are associated with the progression of various cancers, including CRC. Herein, we explored the function of lncRNA LINC01550 in CRC. LINC01550 expression in CRC was analyzed using The Cancer Genome Atlas (TCGA). The diagnostic value of LINC01550 was evaluated using ROC curves. The relationship between clinicopathological variables and LINC01550 expression was explored, and its prognostic value was assessed using Kaplan–Meier and Cox regression analyses. The relationship between LINC01550 expression and immune cell infiltration was analyzed using CIBERSORT. Tumor‐associated mutations and drug sensitivity were compared between high and low LINC01550 expression groups. The effects of LINC01550 overexpression on CRC cells were investigated using CCK‐8, flow cytometry, wound healing, Transwell, qRT‐PCR, and western blot assays. LINC01550 was downregulated in CRC tissues, and the low expression of LINC01550 was correlated with advanced stage and metastasis. CRC patients with low LINC01550 expression had poorer overall survival. LINC01550 expression was an independent risk factor for CRC prognosis. APC and TP53 mutations were more frequent in the low LINC01550 expression group, while the high LINC01550 expression group was significantly more sensitive to 5‐fluorouracil, irinotecan, trametinib, gemcitabine, rapamycin, and XAV939. LINC01550 overexpression suppressed the proliferation, migration, invasion, and epithelial‐mesenchymal transition of HCT‐116 and HT‐29 cells and promoted apoptosis. LINC01550 exerted these effects by inhibiting Wnt/β‐catenin signaling. Our results suggest LINC01550 as a diagnostic and prognostic predictor in CRC that acts as a tumor suppressor and a potential therapeutic target.
Melatonin regulates endoplasmic reticulum stress in diverse pathophysiological contexts: A comprehensive mechanistic review
Authors: de Almeida Chuffa Luiz Gustavo , Seiva Fábio Rodrigues Ferreira , Silveira Henrique S. , Cesário Roberta Carvalho , da Silva Tonon Karolina , Simão Vinicius Augusto , Zuccari Debora Aparecida P. C. , Reiter Russel J. 
Published: July 2024

AbstractThe endoplasmic reticulum (ER) is crucial for protein quality control, and disruptions in its function can lead to various diseases. ER stress triggers an adaptive response called the unfolded protein response (UPR), which can either restore cellular homeostasis or induce cell death. Melatonin, a safe and multifunctional compound, shows promise in controlling ER stress and could be a valuable therapeutic agent for managing the UPR. By regulating ER and mitochondrial functions, melatonin helps maintain cellular homeostasis via reduction of oxidative stress, inflammation, and apoptosis. Melatonin can directly or indirectly interfere with ER‐associated sensors and downstream targets of the UPR, impacting cell death, autophagy, inflammation, molecular repair, among others. Crucially, this review explores the mechanistic role of melatonin on ER stress in various diseases including liver damage, neurodegeneration, reproductive disorders, pulmonary disease, cardiomyopathy, insulin resistance, renal dysfunction, and cancer. Interestingly, while it alleviates the burden of ER stress in most pathological contexts, it can paradoxically stimulate ER stress in cancer cells, highlighting its intricate involvement in cellular homeostasis. With numerous successful studies using in vivo and in vitro models, the continuation of clinical trials is imperative to fully explore melatonin's therapeutic potential in these conditions.
Safety of intravitreally delivered AAV2 vector‐mediated multi‐characteristic opsin genetic construct in wild type beagle dogs
Authors: Mohanty Samarendra , Batabyal Subrata , Ayyagari Ananta , Sharif Najam A. 
Published: July 2024

AbstractBackgroundA novel adeno‐associated virus 2 (AAV2)‐carried multi‐characteristic opsin (MCO) (MCO‐010) is undergoing several clinical trials as a novel therapeutic modality for the treatment of degenerative retinal diseases including retinitis pigmentosa and Stargardt disease. The present study aimed to determine the ocular and systemic safety of MCO‐010 and the AAV2 vehicle in adult Beagle dogs following intravitreal (IVT) injection.MethodsThe current safety/toxicology studies spanning 13 weeks described here utilized well‐documented techniques to assess the effects of IVT injection of MCO‐010 up to 2.2 × 1011 genome copies (gc) per eye, or the AAV2 capsid (vehicle control) on gross behavioral and immunogenic changes, alterations in body weights, blood biochemistry, hematology, blood coagulation, gross necropsy lesions, organ weight changes and histopathology in the dogs (n = 4 per group; two males and two females per group). Immunohistochemical and functional electroretinogram studies were also conducted to determine MCO expression in the retina and determine any retinal toxicity associated with MCO‐010.ResultsThere were no significant deleterious effects of the MCO‐010 (or the AAV2 at the tested doses) on any of the examined parameters, including the absence of any severe ocular or systemic adverse events. However, as expected, inflammation after IVT delivery of AAV2 and MCO‐010 was observed in the conjunctivae of all groups of animals, although this self‐resolved within 1 week post‐injection. Quantitative immunohistochemical analyses of MCO‐010‐associated mCherry revealed successful delivery of the gene therapy within the inner retina.ConclusionsIn summary, MCO‐010 demonstrated a favorable safety profile when administered to the eyes of adult Beagle dogs of both sexes at dose levels up to 2.2 × 1011 gc per eye, with no adverse effects observed. This dose was identified as the No Observed Adverse Effect Level (i.e. NOAEL) and guided selection of safe doses for human clinical trials.
Synthesis of substituted 5,6,7,8‐tetrafluoro‐1H‐benzo[f]indol‐4,9‐diones based on the reaction of hexafluoro‐1,4‐napthoquinone with methyl 3‐aminocrotonates
Authors: Kudryavtseva Ekaterina N. , Lichitsky Boris V. , Komogortsev Andrey N. , Milyutin Constantine V. , Tretyakov Evgeny V. 
Published: July 2024

AbstractFor the first time, the possibility of using hexafluoro‐1,4‐naphthoquinone for the construction of condensed heterocyclic system was demonstrated. As a result, two‐step synthesis of previously unknown 5,6,7,8‐tetrafluoro‐1H‐benzo[f]indol‐4,9‐dione derivatives was elaborated. The suggested method includes initial interaction of hexafluoro‐1,4‐naphthoquinone with various methyl 3‐aminocrotonates and subsequent intramolecular cyclization into the target fluorinated benzo[f]indole‐4,9‐diones. The distinctive feature of considered protocol is regiospecific reaction of fluorine atoms in quinone fragment. Advantages of the presented approach are simple synthetic procedure avoiding chromatographic purification, atom economy and readily available starting materials. The structure of one of the synthesized compounds was established by x‐ray analysis.
Implementing a male‐specific ART counselling curriculum: a quality assessment with healthcare workers in Malawi
Authors: Robson Isabella , Mphande Misheck , Lee Jiyoung , Hubbard Julie Anne , Daniels Joseph , Phiri Khumbo , Chikuse Elijah , Coates Thomas J. , Cornell Morna , Dovel Kathryn 
Published: July 2024

AbstractIntroductionThere is little HIV counselling that directly meets the needs of men in Eastern and Southern Africa, limiting men's knowledge about the benefits of HIV treatment and how to overcome barriers to engagement, contributing to poorer HIV‐related outcomes than women. Male‐specific approaches are needed to improve men's outcomes but may be difficult for healthcare workers (HCWs) to implement with fidelity and quality in low‐resource settings. We developed a male‐specific counselling curriculum which was implemented by male HCWs and then conducted a mixed‐methods quality assessment.MethodsWe audio‐recorded counselling sessions to assess the quality of implementation (n = 50) by male HCWs from two cadres (nurse, n = 10 and lay cadre, n = 10) and conducted focus group discussions (FGDs) with HCWs at 6 and 9 months after rollout to understand barriers and facilitators to implementation. Counselling sessions and FGDs were translated, transcribed and analysed using thematic analysis adapted from WHO Quality Counselling Guidelines. We assessed if sessions were respectful, informative, interactive, motivating and included tailored action plans for overcoming barriers to care. All data were collected September 2021−June 2022.ResultsAll sessions used respectful, non‐judgemental language. Sessions were highly interactive with most HCWs frequently asking open‐ended questions (n = 46, 92%) and often incorporating motivational explanations of how antiretroviral therapy contributes to life goals (n = 42, 84%). Few sessions included individually tailored action plans for clients to overcome barriers to care (n = 9, 18%). New counselling themes were well covered; however, occasionally themes of self‐compassion and safe sex were not covered during sessions (n = 16 and n = 11). HCWs believed that having male HCWs conduct counselling, ongoing professional development and keeping detailed counselling notes facilitated quality implementation. Perceived barriers included curriculum length and client hesitancy to participate in action plan development. Findings were similar across cadres.ConclusionsImplementing high‐quality male‐specific counselling using male nurses and/or lay cadre is feasible. Efforts to utilize lay cadres should be prioritized, particularly in low‐resource settings. Programmes should provide comprehensive job aids to support HCWs. Ongoing training and professional development are needed to (1) improve HCWs’ skills in tailored action plans, and (2) sensitize HCWs to the need for self‐compassion within male clients to promote holistic sexual health.
Incidences of new hepatitis B infection and anti‐hepatitis B core‐negative occult hepatitis B infection among Japanese blood donors in relation to anti‐hepatitis B surface antigen levels
Authors: Satake Masahiro , Sugiyama Masaya , Mizokami Masashi , Tanaka Junko 
Published: July 2024

AbstractA transfusion‐transmitted hepatitis B virus (HBV) infection caused by blood only positive for anti‐hepatitis B surface antigen (anti‐HBs) was reported. Occult HBV infection (OBI) with sole anti‐HBs among blood donors is an issue. The incidence of HBV infection among repeat blood donors was investigated with a detailed HBV infection phase, focusing on the influence of anti‐HBs level. This study followed 3 435 653 donors for HBV DNA conversion over 4 years and 9 months. Infection phase was determined based on marker changes over DNA conversion. This study identified 115 hepatitis B surface antigen (HBsAg) conversions, 72 DNA‐only conversions, and 15 DNA plus anti‐hepatitis B core (anti‐HBc) conversions among donors all negative for HBV DNA, HBsAg, and anti‐HBc. Total incidence was 2.38/100 000 person‐years (PY). None of these 202 new HBV infections arose in the group with anti‐HBs titer ≥ 10 mIU/mL. In total, 30 anti‐HBc‐negative OBIs were identified (incidence; 0.35/100 000 PY); 7 showed typical secondary anti‐HBs response, and 23 showed stable anti‐HBc and anti‐HBs levels at DNA conversion. The HBV infection‐protective ability of anti‐HBs ≥ 10 mIU/mL was reinforced. In addition to new infections, the blood donor population includes anti‐HBc‐positive‐ and negative OBI with immune reactions or abortive HBV infection.
The signature of the main modes of climatic variability as revealed by the Jenkinson‐Collison classification over Europe
Authors: Fernández‐Granja Juan A. , Bedia Joaquín , Casanueva Ana , Brands Swen , Fernández Jesús 
Published: July 2024

AbstractThe Jenkinson‐Collison Weather Typing (JC‐WT) method uses sea‐level pressure gradients to create 27 types based on the geostrophic flow and vorticity around any extratropical target location. Typically, JC‐WTs are applied over specific locations or limited domains, thus hampering the understanding of the impact of large‐scale mechanisms on regional climate. This study explores the links between regional climate variability, as represented by the JC‐WTs, and large‐scale phenomena, to describe the synoptic‐scale variability in the North Atlantic‐European region and evaluate the JC‐WT methodology. Large‐scale circulation is here characterized by major atmospheric low‐frequency modes, namely the North Atlantic Oscillation, the East Atlantic and the Scandinavian teleconnection indices, and by atmospheric blockings. Results show that JC‐WTs coherently capture the spatial and temporal variability of the large‐scale modes and yields a characteristic response to blocking events. Overall, our results underpin the exploratory potential of this method for the analysis of the near‐surface circulation. These findings endorse the use of JC‐WTs and support the reliability and utility of the JC‐WT classification for process‐based model assessments and model selection, a crucial task for climate impact studies.
Segmenting social media users in international tourism: Insights integrated from multi‐homing theory and international visitor survey data
Authors: Lee Kwang‐Ho , Yen Alan 
Published: July 2024

AbstractThis study utilizes multi‐homing theory to assess international travelers' usage of social media platforms, revealing insights into their gender, country of origin, generation cohorts, and travel purposes. These insights can guide the development of effective social media marketing strategies for national destination management organizations (DMOs). Data from South Korea's 2019 International Visitor Survey (with 12,194 participants) was analyzed using chi‐square and correspondence analysis techniques. The results revealed distinctive preferences of international visitors among generational cohorts with different travel purposes across 19 countries in the usage of online travel communities, social network platforms, video‐sharing platforms, and travel blogs. Understanding the dynamics of social media platforms helps national DMOs enhance their social media marketing strategies for international visitors, based on the multi‐sided platform usage paradigm. Nevertheless, acknowledging the study's limitations points towards potential avenues for future research.
An evaluation of potential inbreeding depression in wild Mexican wolves
Authors: Clement Matthew J. , Oakleaf John K. , Heffelfinger James R. , Gardner Colby , deVos Jim , Rubin Esther S. , Greenleaf Allison R. , Dilgard Bailey , Gipson Philip S. 
Published: July 2024

AbstractEstimates of the influence of inbreeding on the fitness of wild animals can guide genetic conservation in rare species. Conservation genetics is important in Mexican wolves (Canis lupus baileyi) because the current population descended from 7 founders and mean inbreeding is relatively high. As an endangered subspecies, Mexican wolves are actively managed using select conflict avoidance measures and by placing captive‐born foster pups into wild litters. We obtained data on inbreeding coefficients of wolf pups and adults based on a pedigree dating to 1957 and data on reproduction for wild wolf packs during 1998–2022. We estimated trends in inbreeding coefficients and the associations between dam, sire, and pup inbreeding coefficients and pup recruitment to age 9 months, and assessed 3 components of recruitment: probability of producing a litter, number of pups produced, and recruitment conditional on successful reproduction. We generated estimates using generalized linear mixed models and bootstrapped estimates of confidence intervals. Mean inbreeding coefficients were high (0.227, SD = 0.047) in the wild population, but we detected no significant evidence of an increase during 2010–2022. Overall, the net associations of dam, sire, and pup inbreeding coefficients with our primary fitness metric, pup recruitment to age 9 months, did not differ from zero. While high inbreeding coefficients are a concern for the long‐term recovery of the subspecies, the stable level of inbreeding, lack of evidence for inbreeding depression, high pup production (5.1 pups/litter, SD = 1.64), and rapid population growth (384% increase from 2010–2022) indicate that inbreeding has not prevented rapid progress towards recovery goals under current management practices.
Tough Self‐Healing Materials via In Situ Growth of Zeolitic Imidazolate Framework‐8 Nanocrystals in Polymers
Authors: Xiao Weiye , Song Yan , Li Chao , Yao Qiwen , Li Guo Liang 
Published: July 2024

AbstractConstruction of self‐healing materials with improved mechanical performance is a great challenge. A strong and tough self‐healing composite is fabricated via in situ growth of zeolitic imidazole framework‐8 (ZIF‐8) nanocrystals in imidazole‐containing polymer networks. By adjusting the stoichiometric ratio of the zinc salt to 2‐methylimidazole, composites with various mechanical performances are obtained. The existence of ZIF‐8 nanocrystals via in situ growth in the polymer networks is confirmed by X‐ray diffraction (XRD), transmission electron microscopy (TEM), and atomic force microscopy (AFM). The zinc–imidazole interactions between the ZIF‐8 nanocrystals and the polymer are confirmed by attenuated total reflection Fourier transform infrared (ATR‐FTIR) spectroscopy. The composites can repair themselves under mild conditions owing to dynamic zinc–imidazole interactions. The self‐healing efficiency of composites can reach up to 91% under the condition of 60 °C for 48 h. In contrast to the pure zinc cation crosslinking system, the composite containing ZIF‐8 nanocrystals prepared via in situ growth exhibited enhanced tensile strength and toughness by 43% and 100%, respectively. This study proves that incorporating the metal‐organic frameworks (MOFs) materials into a self‐healing system via an in situ growth strategy is highly promising for designing self‐healing materials with improved mechanical performance.