bluuebunny/crossref_metadata_2025 huggingface dataset:
Acquired port-wine stain: a case report and differential diagnosis
Authors: Lade Nitin , Mullaveettil Farhana , Nayak Prateek , Prakashey Arjun R
Published: September 2024

Port-wine stain (PWS) are vascular malformations characterised by dilated dermal capillaries with normal endothelial cells. Congenital PWS are the most prevalent vascular malformation affecting 0.3–1% of newborns while acquired PWS (APWS), though an uncommon entity, exhibit morphological and histological similarity to congenital PWS. We hereby report a case of APWS along with a comprehensive comparison of clinical, histopathological and dermoscopic findings of other acquired vascular malformations.
Refractory singultus and area postrema syndrome as a presentation of neurocysticercosis
Authors: Datta Amlan Kusum , Malakar Sudeshna , Mukherjee Adreesh
Published: September 2024

Neurocysticercosis (NCC) is the most common parasitic infection of the central nervous system, caused by the pork tapeworm,Taenia solium. Common presenting features are seizures, headaches and focal neurodeficits. The present report details the anecdote of a middle-aged Asian man, who presented with subacute onset of persistent nausea, vomiting and hiccups. Following unsuccessful trials with numerous prokinetic, antipsychotic, muscle relaxant and anticonvulsant medications, as well as an uneventful battery of gastrointestinal tests, he was referred for neurological evaluation. The constellation of symptoms was congruent with the diagnosis of area postrema syndrome. Although initial CT scan of brain was normal, MRI with contrast evaluation revealed a circumscribed, ring-enhancing lesion of the dorsal medulla oblongata, reminiscent of colloid vesicular stage of NCC. The patient was successfully treated with steroids and albendazole. The association of refractory singultus, nausea and vomiting and NCC is thus far, not reported in the literature.
Sex and gender reporting in UK emergency medicine trials from 2010 to 2023: a systematic review
Authors: Astin-Chamberlain Raine , Pott Jason , Cole Elaine , Bloom Benjamin Michael
Published: September 2024

Background

Female participants are underrepresented in randomised control trials conducted in urgent care settings. Although sex and gender are frequently reported within demographic data, it is less common for primary outcomes to be disaggregated by sex or gender. The aim of this review is to report sex and gender of participants in the primary papers published on research listed on the National Institute of Health and Care Research (NIHR) Trauma and Emergency Care (TEC) portfolio and how these data are presented.

Methods

This is a systematic review of the published outputs of interventional trials conducted in UK EDs. Interventional trials were eligible to be included in the review if they were registered on the NIHR TEC research portfolio from January 2010, if the primary paper was published before 31 December 2023 and if the research was delivered primarily in the ED. Trials were identified through the NIHR open data platform and the primary papers were identified through specific searches using MedLine, EMBASE and PubMed. The primary objective of the review is to quantify the proportion of sex-disaggregated or gender-disaggregated primary outcomes in clinical trials within UK emergency medicine.

Results

The initial search revealed 169 registered research projects on the NIHR TEC portfolio during the study period, of which 24 met the inclusion criteria. Overall, 76 719 participants were included, of which 31 374 (40%) were female. Only one trial (CRYOSTAT-2) reported a sex-disaggregated analysis of the effect of the intervention on either primary or secondary outcomes, and no sex-based difference in treatment effect was detected.

Conclusions

Fewer females than males were included in TEC trials from 2010 to 2023. One trial reported the primary outcome stratified by sex. There is significant scope to increase the scientific value of TEC trials to females by funders.
Subarachnoid haemorrhage in the emergency department (SHED): a prospective, observational, multicentre cohort study
Authors:   The Trainee Emergency Research Network (TERN)
Published: September 2024

Background

People presenting to the ED with acute severe headache often undergo investigation to exclude subarachnoid haemorrhage (SAH). International guidelines propose that brain imaging within 6 hours of headache onset can exclude SAH, in isolation. The safety of this approach is debated. We sought to externally validate this strategy and evaluate the test characteristics of CT-brain beyond 6 hours.

Methods

A prospective, multicentre, observational cohort study of consecutive adult patients with non-traumatic acute headache presenting to the ED within a UK National Health Service setting. Investigation, diagnosis and management of SAH were all performed within routine practice. All participants were followed up for 28 days using medical records and direct contact as necessary. Uncertain diagnoses were independently adjudicated.

Results

Between March 2020 and February 2023, 3663 eligible patients were enrolled from 88 EDs (mean age 45.8 (SD 16.6), 64.1% female). 3268 patients (89.2%) underwent CT-brain imaging. There were 237 cases of confirmed SAH, a prevalence of 6.5%. CT within 6 hours of headache onset (n=772) had a sensitivity of 97% (95% CI 92.5% to 99.2%) for the diagnosis of SAH and a negative predictive value of 99.6% (95% CI 98.9% to 99.9%). The post-test probability after a negative CT within 6 hours was 0.5% (95% CI 0.2% to 1.3%). The negative likelihood ratio was 0.03 (95% CI 0.01 to 0.08). CT within 24 hours of headache onset (n=2008) had a sensitivity of 94.6% (95% CI 91.0% to 97.0%). Post-test probability for SAH was consistently less than 1%. ForaneurysmalSAH, post-test probability was 0.1% (95% CI 0.0% to 0.4%) if the CT was performed within 24 hours of headache onset.

Conclusion

Our data suggest a very low likelihood of SAH after a negative CT-brain scan performed early after headache onset. These results can inform shared decision-making on the risks and benefits of further investigation to exclude SAH in ED patients with acute headache.
Management strategies and outcomes in pregnancy-related acute aortic dissection: a multicentre cohort study in China
Authors: Liu Hong , Yang Liu , Chen Cui-ying , Qian Si-chong , Ma Lu-yao , Diao Yi-fei , Wu Xiao-yu , Wu Shu-yan , Dong Zhi-qiang , Shao Yong-feng , Zhang Hong-jia , Sun Li-Zhong , Zhu Jun-ming , Zhang Jia-rong , Li Haiyang
Published: September 2024

Background

Acute aortic dissection (AD) in pregnancy poses a lethal risk to both mother and fetus. However, well-established therapeutic guidelines are lacking. This study aimed to investigate clinical features, outcomes and optimal management strategies for pregnancy-related AD.

Methods

We conducted a retrospective multicentre cohort study including 67 women with acute AD during pregnancy or within 12 weeks postpartum from three major cardiovascular centres in China between 2003 and 2021. Patient characteristics, management strategies and short-term outcomes were analysed.

Results

Median age was 31 years, with AD onset at median 32 weeks gestation. Forty-six patients (68.7%) had type A AD, of which 41 underwent immediate surgery. Overall maternal mortality was 10.4% (7/67) and fetal mortality was 26.9% (18/67). Compared with immediate surgery, selective surgery was associated with higher risk of composite maternal and fetal death (adjusted RR: 12.47 (95% CI 3.26 to 47.73); p=0.0002) and fetal death (adjusted RR: 8.77 (95% CI 2.33 to 33.09); p=0.001).

Conclusions

Immediate aortic surgery should be considered for type A AD at any stage of pregnancy or postpartum. For pregnant women with AD before fetal viability, surgical treatment with the fetus in utero should be considered. Management strategies should account for dissection type, gestational age, and fetal viability.

Trial registration number

NCT05501145.
Regression of renal cell carcinoma by T cell receptor-engineered T cells targeting a human endogenous retrovirus
Authors: Barisic Stefan , Brahmbhatt Elizabeth M , Cherkasova Elena , Spear Timothy T , Savani Ujjawal , Pierre Stephanie , Scurti Gina M , Chen Long , Igboko Muna , Nadal Rosa , Zeng Gang , Parry Gordon , Stroncek David F , Highfill Steven , Dalheim Annika V , Reger Robert , Nishimura Michael I , Childs Richard W
Published: September 2024

Background

We discovered a novel human endogenous retrovirus (CT-RCC HERV-E) that was selectively expressed in most clear cell renal cell carcinomas (ccRCC) and served as a source of antigens for T cell-mediated killing. Here, we described the cloning of a novel T cell receptor (TCR) targeting a CT-RCC HERV-E-derived antigen specific to ccRCC and characterized antitumor activity of HERV-E TCR-transduced T cells (HERV-E T cells).

Methods

We isolated a CD8+T cell clone from a patient with immune-mediated regression of ccRCC post-allogeneic stem cell transplant that recognized the CT-RCC-1 HERV-E-derived peptide in an HLA-A11-restricted manner. We used 5’Rapid Amplification of cDNA Ends (RACE) to clone the full length HERV-E TCR and generated retrovirus encoding this TCR for transduction of T cells. We characterized HERV-E T cells for phenotype and function in vitro and in a murine xenograft model. Lastly, we implemented a good manufacturing practice-compliant method for scalable production of HERV-E T cells.

Results

The HLA-A11-restricted HERV-E-reactive TCR exhibited a CD8-dependent phenotype and demonstrated specific recognition of the CT-RCC-1 peptide. CD8+T cells modified to express HERV-E TCR displayed potent antitumor activity against HLA-A11+ccRCC cells expressing CT-RCC HERV-E compared with unmodified T cells. Killing by HERV-E T cells was lost when cocultured against HERV-E knockout ccRCC cells. HERV-E T cells induced regression of established ccRCC tumors in a murine model and improved survival of tumor-bearing mice. Large-scale production of HERV-E T cells under good manufacturing practice conditions generated from healthy donors retained specific antigen recognition and cytotoxicity against ccRCC.

Conclusions

This is the first report showing that human ccRCC cells can be selectively recognized and killed by TCR-engineered T cells targeting a HERV-derived antigen. These preclinical findings provided the foundation for evaluating HERV-E TCR-transduced T cell infusions in patients with metastatic ccRCC in a clinical trial (NCT03354390).
Circumventing resistance within the Ewing sarcoma microenvironment by combinatorial innate immunotherapy
Authors: Luo Wen , Hoang Hai , Zhu Hongwen , Miller Katherine , Mo Xiaokui , Eguchi Shiori , Tian Meijuan , Liao Yanling , Ayello Janet , Rosenblum Jeremy M , Marcondes Mario , Currier Mark , Mardis Elaine , Cripe Timothy , Lee Dean , Cairo Mitchell S
Published: September 2024

Background

Pediatric patients with recurrent/metastatic Ewing sarcoma (ES) have a dismal 5-year survival. Novel therapeutic approaches are desperately needed. Natural killer (NK) cell number and function are low in ES patient tumors, in large part due to the immunosuppressive tumor microenvironment (TME). Melanoma cell adhesion molecule (MCAM) is highly expressed on ES and associated with ES metastasis. NKTR-255 is a polymer-conjugated recombinant human interleukin-15 (IL-15) agonist improving NK cell activity and persistence. Magrolimab (MAG) is a CD47 blockade that reactivates the phagocytic activity of macrophages.

Methods

Transcriptome profiling coupled with CIBERSORT analyses in both ES mouse xenografts and human patient tumors were performed to identify mechanisms of NK resistance in ES TME. A chimeric antigen receptor (CAR) NK cell targeting MCAM was engineered by CAR mRNA electroporation into ex vivo expanded NK cells. In vitro cytotoxicity assays were performed to investigate the efficacy of anti-MCAM-CAR-NK cell alone or combined with NKTR-255 against ES cells. Interferon-γ and perforin levels were measured by ELISA. The effect of MAG on macrophage phagocytosis of ES cells was evaluated by in vitro phagocytosis assays. Cell-based and patient-derived xenograft (PDX)-based xenograft mouse models of ES were used to investigate the antitumor efficacy of CAR-NK alone and combined with NKTR-255 and MAG in vivo.

Results

We found that NK cell infiltration and activity were negatively regulated by tumor-associated macrophages (TAM) in ES TME. Expression of anti-MCAM CAR significantly and specifically enhanced NK cytotoxic activity against MCAMhighbut not MCAM-knockout ES cells in vitro, and significantly reduced lung metastasis and extended animal survival in vivo. NKTR-255 and MAG significantly enhanced in vitro CAR-NK cytotoxicity and macrophage phagocytic activity against ES cells, respectively. By combining with NKTR-255 and MAG, the anti-MCAM-CAR-NK cell significantly decreased primary tumor growth and prolonged animal survival in both cell- and PDX-based ES xenograft mouse models.

Conclusions

Our preclinical studies demonstrate that immunotherapy via the innate immune system by combining tumor-targeting CAR-NK cells with an IL-15 agonist and a CD47 blockade is a promising novel therapeutic approach to targeting MCAMhighmalignant metastatic ES.
Smart mouthguards and contact sport: the data ethics dilemma
Authors: Gibson Richard B , Nelson Anna
Published: September 2024

The use of smart mouthguards in contact sports like rugby aims to enhance player safety by providing real-time data on head impacts. These devices, equipped with sensors, measure collision force and frequency, potentially identifying concussions that might go unnoticed during gameplay. The idea is that such enhanced monitoring will enable teams, physicians and other stakeholders to better protect players from the effects of on-pitch injury through immediate detection of head trauma and the long-term provision of player data. While we welcome the move towards a better understanding of the potential harm that contact sports athletes may experience, introducing a new avenue through which information about player performance and health can be collected brings several areas of ethical concern absent from traditional mouthguards. In this paper, we consider four noteworthy areas: device and data efficacy, player choice, the inherent issues of such data’s existence and the harmful consequences of this data’s usage and exposure. We argue that failing to identify and address the risks associated with smart mouthguards’ employment in the elite sporting sphere not only risks the mistreatment and misapplication of player data but may also jeopardise the acceptability of a novel health monitoring method that has the potential to prevent long-term debilitating diseases.
Distinct plasma lipids predict axonal injury and multiple sclerosis activity
Authors: Schoeps Vinicius A , Bhargava Pavan , Virupakshaiah Akash , Ladakis Dimitrios Christos , Moseley Carson , Chong Janet , Aaen Gregory , Graves Jennifer S , Benson Leslie , Gorman Mark P , Rensel Mary , Abrams Aaron , Mar Soe , Lotze Timothy E , Chitnis Tanuja , Waldman Amy , Krupp Lauren , Rodriguez Moses , Tillema Jan-Mendelt , Rose John , Schreiner Teri , Qureshi Ferhan , Peterson Skyler , Barcellos Lisa F , Casper T Charles , Newman John , Borkowski Kamil , Waubant Emmanuelle
Published: September 2024

Background

Lipids are of particular interest for the study of neuroinjury and neuroinflammation as structural lipids are major components of myelin, and a variety of lipid species modulate inflammation. In this study, we performed an in-depth lipidomics analysis to identify lipids associated with injury and disease activity.

Methods

Plasma samples were collected from paediatric-onset multiple sclerosis (MS) cases within 4 years of disease onset from 17 sites. The lipidome was measured using untargeted and targeted mass spectrometry. For cross-sectional analyses, the agreement between multiple machine learning models was used to predict neurofilament light chain (NfL) levels. In longitudinal analyses, the association between clinical (relapse count) and imaging (MRI count with ≥1 enhancing or new T2 lesion) outcomes with each metabolite was estimated using adjusted negative binomial regression.

Results

At sample collection, 68% of the 435 included individuals were treatment-naive, with a median disease duration of 0.8 years (IQR 0.3–1.7). For longitudinal analyses, 381 and 335 subjects had at least 1 year of clinical and imaging follow-up, respectively. In cross-sectional analyses, NfL chain levels identified structural lipids (phosphatidylcholines and phosphatidylethanolamines) as the highest-performing predictors, including external validation. In contrast, longitudinal analyses found polyunsaturated fatty acids (PUFAs) and their derivatives to be protective from subsequent disease activity (q<0.001, multiple outcomes).

Conclusion

There are two categories of lipids associated with MS processes. First, structural lipids strongly associated with NfL levels may result from cell lysis secondary to acute inflammation. In contrast, PUFAs, especially ω−3, had a protective effect on subsequent disease activity.
Distribution ofChlamydia trachomatis ompA-genotypes over three decades in Portugal
Authors: Lodhia Zohra , Cordeiro Dora , Correia Cristina , João Inês , Carreira Teresa , Vieira Luís , Nunes Alexandra , Ferreira Rita , Schäfer Sandra , Aliyeva Elzara , Portugal Clara , Monge Isabel , Pessanha Maria Ana , Toscano Cristina , Côrte-Real Rita , Antunes Marília , Gomes Joao Paulo , Borges Vítor , José Borrego Maria
Published: September 2024

Objectives

Chlamydia trachomatisis classified into 15 major genotypes, A to L3, based on the diversity ofompAgene. Here, we evaluated and characterised the distribution and diversity ofompA-genotypes over 32 years (1990–2021) in Portugal.

Methods

The collection of the Portuguese National Reference Laboratory for Sexually Transmitted Infections includes 5824C.trachomatis-positive samples that were successfullyompA-genotyped between 1990 and 2021. An in-depth analysis ofompA-genotypes distribution across the years, as well as by biological sex, age and anatomical site of infection was performed.

Results

ompA-genotype E was consistently the most frequently detected across the years, with a median frequency of 34.6%, followed by D/Da (17.6%), F (14.3%) and G (10.7%). The prevalence of lymphogranuloma venereum (LGV) genotypes (mostly L2, 62.0%, followed by L2b, 32.1%) increased since 2016, reaching the highest value in 2019 (20.9%). LGV, G and Da genotypes were associated with biological sex, specifically with being male, and were the most frequent among anorectal specimens (37.7%, 19.4% and 17.7%, respectively). Notably, LGVompA-genotypes represented 38.9% of the male anorectal specimens since 2016, and were also detected among oropharynx and urogenital samples.ompA-genotype E was the most frequently detected at the oropharynx (28.6%) and urogenital (33.9%) sites during the study period, followed by D/Da (17.4%) and F (16.0%) in the urogenital specimens, and by G (26.1%) and D/Da (25.7%) in oropharynx specimens. Our data also highlight the emergence of the recombinant L2b/D-Da strain since 2017 (representing between 2.0% and 15.5% of LGV casesperyear) and the non-negligible detection ofompA-genotype B in urogenital and anorectal specimens.

Conclusions

This study provides a comprehensive landscape ofC. trachomatismolecular surveillance in Portugal, highlighting the continued relevance ofompA-genotyping as a complement to rapid LGV-specific detection tests. It also contributes to a deeper understanding ofC. trachomatisepidemiology, diversity and pathogenicity.
Impact of fungicide, IMI-herbicide, and cultivar on ascochyta blight severity and yield of chickpea in Saskatchewan, Canada
Authors: Hubbard Michelle , Luan Limin , Tar'an Bunyamin , Gossen Bruce D.
Published: September 2024

Ascochyta blight, caused by Ascochyta rabiei, is a serious constraint to chickpea production, managed primarily via foliar fungicides and genetic resistance. Imidazolinone (IMI) herbicides, used for in-crop weed management, can injure susceptible chickpea cultivars and so increase ascochyta risk. The impact of IMI application on susceptible and tolerant cultivars was assessed in combination with blight management options (starting fungicide application prior to symptom development, two versus four fungicide applications, genetic resistance) in small plot trials in Saskatchewan in 2019, 2021, and 2022. Two kabuli-type chickpea cultivars (CDC Orion, CDC Orkney) and two desi-types (CDC Vanguard, CDC Cory) were grown with or without IMI herbicide. CDC Orion and CDC Vanguard were susceptible to IMI herbicides, CDC Orkney and CDC Cory were tolerant. The severity of ascochyta blight (0–9 scale) was very low in 2019 and 2021 (1.3 in 2019, 0.5 in 2021) and generally did not differ among treatments. In 2022, the desi cultivars had less disease at the end of the season than kabuli cultivars (mean 3.1 vs. 4.3). In 2022, two applications of fungicide (starting before or after symptoms appeared) reduced severity relative to the control (3.5 vs. 4.6). Four applications did not provide additional reduction. IMI herbicides resulted in <15% injury on IMI-susceptible and none on IMI-tolerant cultivars. Waiting for ascochyta symptoms, rated 1, to apply fungicide was just as effective as applying fungicide before symptom development. Fungicides provide yield and disease management benefits when disease is moderate, but not when weather is hot and dry.
Lifetimes of excited states in $$^{16}$$C as a benchmark for ab initio developments
Authors: Mathy M. , Petri M. , Roth R. , Wagner L. , Heil S. , Ayangeakaa A. D. , Bottoni S. , Carpenter M. P. , Crawford H. L. , Fallon P. , Elson J. , Kinnison J. , Lauritsen T. , Lee I.-Y. , Macchiavelli A. O. , Paschalis S. , Reviol W. , Sarantites D. G. , Syndikus I. , L. Tabor S. , Wiedeking M. , Zhu S.
Published: September 2024

Lifetimes of higher-lying states ($$2_2^+$$

2
2
+

and $$4_1^+$$

4
1
+

) in $$^{16}$$

16

C have been measured, employing the Gammasphere and Microball detector arrays, as key observables to test and refine ab initio calculations based on interactions developed within chiral Effective Field Theory. The presented experimental constraints to these lifetimes of $$\tau ({2_2^+}) = [\,244, 446]\,~\textrm{fs}$$

τ

(

2
2
+

)

=

[

244
,
446
]

fs

and $$\tau ({4_1^+}) = [\,1.8, 4]\,~\textrm{ps}$$

τ

(

4
1
+

)

=

[

1.8
,
4
]

ps

, combined with previous results on the lifetime of the $$2_1^+$$

2
1
+

state of $$^{16}$$

16

C, provide a rather complete set of key observables to benchmark the theoretical developments. We present No-Core Shell-Model calculations using state-of-the-art chiral 2- (NN) and 3-nucleon (3N) interactions at next-to-next-to-next-to-leading order for both the NN and the 3N contributions and a generalized natural-orbital basis (instead of the conventional harmonic-oscillator single-particle basis) which reproduce, for the first time, the experimental findings remarkably well. The level of agreement of the new calculations as compared to the CD-Bonn meson-exchange NN interaction is notable and presents a critical benchmark for theory.
Investigating μ±μ−→μ±μ− collisions under the effect of scalar and vector unparticles in Randall–Sundrum model
Authors: Dung Le Mai , Thuy Dao Thi Le , Thuc Le Nhu
Published: September 2024

A theoretical attempt is made to present the unparticles contribution to the muon processes [Formula: see text], in Standard Model (SM), Randall–Sundrum (RS) model and RS model with unparticles (RS([Formula: see text])) including scalar and vector unparticles. We evaluated the cross-sections versus the scattering angle [Formula: see text], the kinetic energy [Formula: see text] of the outgoing muon beams, the collision energy [Formula: see text], the scaling dimension [Formula: see text] and the energy scale [Formula: see text]. The numerical results show that the cross-sections of two processes in RS([Formula: see text]) are much larger than in SM. The [Formula: see text] and [Formula: see text] beams can be accelerated and collided, producing the outgoing [Formula: see text] and [Formula: see text] beams as final states with large kinetic energy to probe new physics effects. The total cross-sections depend strongly on the polarization conditions of incoming muon and anti-muon beams, the scaling dimension [Formula: see text] and the energy scale [Formula: see text]. The final states of the muon collisions also depend on [Formula: see text] of colliders and unparticles parameter: ([Formula: see text], [Formula: see text]) if unparticle physics included. The results subsequently lead to the unparticle contribution as propagator significantly larger than SM and Higgs–radion propagator. Hence, it would be worthwhile probing at the future colliders when the muons become the accelerating candidates in the collisions we restricted.
Efficient Fault Detection and Analysis of Power System Distribution Networks by Integrating BP Data Mining
Authors: Liu Feiyu
Published: September 2024

As the basic guarantee for people’s production and life, the safe operation of the power system has an important impact on the development and operation of society. To ensure the safe and stable operation of the power grid, predicting potential faults and taking reasonable preventive measures can effectively avoid the occurrence of power accidents. However, due to the difficulty in ensuring the prediction accuracy of traditional methods, there are issues of protection misoperation and rejection. Therefore, in order to achieve accurate prediction of power grid faults and avoid protection misoperation and rejection issues, a distribution network fault classification prediction model using a combination of three-layer data mining model (TLDM) and adaptive moment estimation (Adam) algorithm/random gradient descent algorithm improved backpropagation neural network (BPNN) is proposed. The implementation results showed that the classification accuracy of artificial fish school [Formula: see text] priori, [Formula: see text]-means clustering convolutional neural network model and TLDM for single-phase grounding faults was 93.2%, 91.5% and 96.6%, respectively. The classification accuracy for two-phase faults was 92.8%, 92.4% and 95.7%, respectively. The classification accuracy for two-phase grounding faults was 93.7%, 91.2% and 96.9%, respectively. The classification accuracy for three-phase faults was 93.3%, 92.1% and 97.1%, respectively. The TLDM had the highest classification accuracy. The average accuracy, average accuracy and average recall of the BPNN improved by the combination of the ADAM algorithm and random gradient descent algorithm were 94.1%, 90.9% and 88%, respectively, which were higher than the BPNN improved by the combination of ADAM algorithm and random gradient descent algorithm. The above results indicate that the proposed distribution network fault classification and prediction model has good performance and can achieve accurate prediction of distribution network faults.
A RAPIDLY COLORIMETRIC DETECTION OF ARSENIC AND MERCURY IONS BASED ON SURFACE PLASMON RESONANCE ABSORBANCES OF FUNCTIONALIZED AuNPs IN COSMETICS
Authors: LIU ZHE-NAN , LIU XIAO-YING , FAN XIAO-YUE , XUE JIN-PENG , LI GUO-NA , LI XING
Published: September 2024

In this study, a novel colorimetric method is developed for the detection of arsenic and mercury ions, utilizing the surface plasmon resonance (SPR) properties of AuNPs ([Formula: see text] nanoparticles) functionalized with APT ([Formula: see text]-(3-aminophenyl) tetrazole). Theoretical calculations confirm the findings from UV–Visible spectroscopy and transmission electron microscopy analyses, indicating that APT is electrostatically bound to the surfaces of the AuNPs. The introduction of [Formula: see text] and [Formula: see text] ions triggers a coordination reaction with APT, resulting in a reduced interparticle distance among the AuNPs. This change leads to a visible color shift of the solution from wine red to bluish-gray. The detection limits for [Formula: see text] and [Formula: see text] are determined to be 0.6 and 0.24 [Formula: see text] g⋅[Formula: see text], respectively, distinguishable to the naked eye. A robust linear correlation is observed between the absorbance ratios and the ion concentrations, with correlation coefficients ([Formula: see text]) of 0.990 for [Formula: see text] and 0.998 for [Formula: see text]. These findings demonstrate that AuNPs functionalized with APT are effective for the quantitative analysis of arsenic and mercury ions. The sensor exhibits high selectivity and excellent resistance to interference, indicating its potential applicability for monitoring [Formula: see text] and [Formula: see text] in tap water and cosmetic products.
The structure control of MoC optimizes charge transfer to improve solar cell performance
Authors: Yao Jixin , Wang Wen , Lu Shibin , Meng Ying , Li Guang
Published: September 2024

Highly active counter electrodes with controllable morphology create new opportunities for the development of dye-sensitized solar cells. Controllable morphology accompanied by maximization of the use of active substances is a vital challenge. Herein, Integrated MoC quantum dots (QD) on different carbon frameworks to form solid flower-like MoCQD@SCF, hollow flower-like MoCQD@HCF1 and MoCQD@HCF2 with varying degrees of hollowness. The as-prepared MoCQD@HCF2 counter electrode (CE) displays a splendid tri-iodide reduction reaction (T-IRR). The power conversion efficiency (PCE) of DSSCs with MoCQD@HCF2 reaches 9.03%, which is higher than that of Pt CE (8.41%), MoCQD@HCF1 (8.24%) and MoCQD@SCF (7.81%). This controllable morphology strategy shows potential applications and provides new insights into energy conversion and storage devices.
Optimization of polymer incorporation in MOF via solvent exchange activation
Authors: Hai Jianhang , Wei Shuli , Zou Jie , Wang Lele , Lu Yunqing , Wang Jin
Published: September 2024

In this work, we activate metal-organic frameworks (MOFs) by applying the general vacuum heating (VH) method or the solvent exchange (SE) method, and encapsulate PSt into the MOF channels by the in-situ polymerization. For the SE method, methanol is optimal to exchange the DMF molecules inside MOF. The effectiveness of these two activation methods is compared. The results show that the MOF activated via the SE method has a higher specific surface area and a larger pore volume than the MOF activated via the general VH method. Also, the SE method is more efficient for the removal of DMF from the MOF channels, and leaves more open metal sites. Specifically, the amounts of loaded monomers inside the MOF activated via the SE method and the general VH method are 4.58 and 2.67 mmol/cm3. Furthermore, the MOF activated via the SE method has better retention of the channel structure and more free volume in the channels. This can increase the mobility of the monomers. As a consequence, the conversion rate of 47.57% from St to PSt is achieved in the MOF activated via the SE method, which is 50.21% higher than that obtained via the general VH method.
Establishment and characterization of a mouse model for studying kidney repair in diabetes
Authors: Shu Shaoqun , Wang Hui , Cai Juan , Chen Anqun , Dong Zheng
Published: September 2024

The prognosis of acute kidney injury (AKI) is markedly worse in diabetic patients. Diabetes not only exaggerates the severity of AKI but may also prevent kidney repair or recovery from AKI. Little is known about the cellular and molecular basis of defective kidney repair in diabetes. One obstacle in studying kidney repair in diabetes is the lack of suitable animal models. Specifically, diabetes increases AKI severity, making it difficult to induce the same level of AKI in diabetic and non-diabetic animals to compare their kidney repair. Here, we have identified a time-window of 4 days immediately after the completion of streptozotocin (STZ) treatment in mice when blood glucose has yet to rise. Within this time-window, renal ischemia-reperfusion injury (IRI) induced the same level of AKI in STZ-treated mice [127.2±12.82 mg/dL blood urea nitrogen (BUN), 2.275±0.4728 serum creatinine] and vehicle solution-treated mice (128.6±11.83 mg/dL BUN, 2.087±0.4748 mg/dL serum creatinine]. By day 5-6, the post-AKI kidney entered into the phase of kidney repair when diabetic hyperglycemia started in STZ-treated mice, providing the opportunity to study the effect of diabetes on kidney repair without affecting initial AKI. In this model, kidney repair was indeed impaired by diabetes (116.5±8.052 mg/dL BUN and 1.382±0.2732 mg/dL serum creatinine in IR+vehicle group; 136.6±8.740 mg/dL BUN and 1.916±0.3756 mg/dL serum creatinine in IR+STZ group). The impairment was associated with decreased tubular cell proliferation and increased tubular cell senescence, peritubular capillary (PTC) rarefaction, inflammation, and 40.90% more interstitial fibrosis.
Spns1 is an iron transporter essential for megalin-dependent endocytosis.
Authors: Beenken Andrew , Shen Tian , Jin Guangchun , Ghotra Aryan , Xu Katherine , Nesanir Kivanc , Sturley Rachel E. , Vijayakumar Soundarapandian , Kahn Atlas , Levitman Abraham , Stauber Jacob , Chavez Estefania Y. , Robbins-Juarez Shelief Y. , Hao Luke , Field Thomas B. , Erdjument-Bromage Hediye , Neubert Thomas A. , Shapiro Lawrence , Qiu Andong , Barasch Jonathan
Published: September 2024

Proximal tubule endocytosis is essential to produce protein free urine as well as to regulate system wide metabolic pathways, such as the activation of Vitamin D. We have determined that the proximal tubule expresses an endolysosomal membrane protein, protein spinster homolog1 (Spns1), which engenders a novel iron conductance that is indispensable during embryonic development. Conditional knockout of Spns1 with a novel Cre-LoxP construct specific to megalin-expressing cells led to the arrest of megalin receptor-mediated endocytosis as well as dextran pinocytosis in proximal tubules. The endocytic defect was accompanied by changes in megalin phosphorylation as well as enlargement of lysosomes confirming previous findings in Drosophila and Zebrafish. The endocytic defect was also accompanied by iron overload in proximal tubules. Remarkably, iron levels regulated the Spns1 phenotypes, because feeding an iron deficient diet or mating Spns1 knockout with divalent metal transporter1 (DMT1) knockout rescued the phenotypes. Conversely, iron loading wild type mice reproduced the endocytic defect, These data demonstrate a reversible, negative feedback for apical endocytosis, and raise the possibility that regulation of endocytosis, pinocytosis, megalin activation, and organellar size and function is nutrient-responsive.
miR-199a-5p aggravates renal ischemia-reperfusion and transplant injury by targeting AKAP1 to disrupt mitochondrial dynamics
Authors: Shi Lang , Zha Hongchu , Huang Hua , Xia Yao , Li Huimin , Huang Jing , Yue Ruchi , Li Chenglong , Zhu Jiefu , Song Zhixia
Published: September 2024

This study identifies miR-199a-5p as a key regulator in renal ischemia-reperfusion injury through microRNA sequencing in mouse models and human delayed graft function. miR-199a-5p worsens renal IRI by aggravating graft dysfunction, tubular injury, and immune response, while its inhibition shows protective effects. miR-199a-5p downregulates A-kinase anchoring protein 1 (AKAP1), reducing dynamin-related protein 1 (Drp1)-s637 phosphorylation, increasing mitochondrial fission, and causing dysfunction. Targeting the miR-199a-5p/AKAP1/Drp1 axis offers therapeutic potential for renal IRI, as AKAP1 overexpression preserves mitochondrial integrity by maintaining Drp1-s637 phosphorylation.
Fingolimod, a sphingosine-1-phosphate receptor modulator, prevents neonatal bronchopulmonary dysplasia and subsequent airway remodeling in a murine model
Authors: Sudhadevi Tara , Annadi Akanksha , Basa Prathima , Jafri Anjum , Natarajan Viswanathan , Harijith Anantha
Published: September 2024

The role of the S1P receptor1 modulator, fingolimod, as an FDA-approved drug in preventing the recurrence of multiple sclerosis is established. Fingolimod prevented bronchopulmonary dysplasia (BPD) and its sequela of airway remodeling in a neonatal murine model. This protection was associated with the downregulation of lysyl oxidase signaling pathway. Fingolimod could be repurposed for the therapy of BPD.
Middle cerebral artery blood velocity and end-tidal carbon dioxide responses to moderate intensity cycling in children, adolescents, and adults
Authors: Weston Max E. , Barker Alan R. , Tomlinson Owen W. , Coombes Jeff S. , Bailey Tom G. , Bond Bert
Published: September 2024

This is the first study to find that children have smaller increases in Δ%MCAv (∼12%) during moderate-intensity exercise compared with adolescents and adults (∼18%–20%). Furthermore, MCAv kinetics were significantly faster in children and adolescents, compared with adults. MCAv kinetic responses were significantly and positively associated with [Formula: see text] kinetics in adults, but not in children. These novel data also suggest that the regulatory role of [Formula: see text] on MCAv during exercise begins to strengthen during adolescence.
Gross Hematuria and Hemolytic Anemia in Infectious Mononucleosis
Authors: Sharma Chinmayi , Venugopal Navneet , Balachandra Shivaiah
Published: September 2024

Introduction. Infectious mononucleosis (IM), caused by the Epstein–Barr virus (EBV), typically presents with fever, tonsillopharyngitis, and lymphadenopathy while rare, renal, and hematological complications such as gross hematuria and hemolytic anemia can occur, particularly in children. Case Presentation. We describe a 15‐year‐old male with infectious mononucleosis presenting with abdominal pain, sore throat, and red‐colored urine for three days. Laboratory findings revealed leukocytosis, elevated liver enzymes, and hemoglobinuria. Serological testing confirmed EBV infection. Despite intravascular hemolysis, the patient’s anemia was mild, and he responded well to supportive care. Discussion. Gross hematuria and hemolytic anemia are uncommon in IM, with limited reports. Proposed mechanisms include viral‐induced renal injury and autoimmune hemolysis. Differential diagnosis should consider other causes of hematuria, which can be differentiated through urine microscopy and serological tests. IM should be considered in patients with pharyngitis and hematuria, especially when other causes are excluded.
Effect of Nanoencapsulated Pistachio Green Hull Extract in the Carboxymethyl Cellulose and Soy Protein Isolate Edible Coatings on Shelf‐Life Quality of Fresh Pistachio
Authors: Ebrahimian Parisa , Najafi Ali , Abedinia Ahmadreza
Published: September 2024

This research was aimed at investigating the effect of edible coatings based on the combination of carboxymethyl cellulose (CMC) and soy protein isolate (SPI) containing 0.0%, 1.0%, 2.0%, and 3.0% w/v of nanoencapsulated pistachio green peel extract (PGPE) on the chemical and microbiological properties of raw pistachio of Kale Ghoochi variety during 18 weeks of storage at 27 ± 1°C. Moisture content (MC), acid value (AV), peroxide value (PV), total phenol content (TPC), total viable count (TVC), and total fungi count (TFC) were tested at 21‐day intervals. PGPE contains phenolic compounds (48.73 mg GAE/g) with antioxidant activity (IC50 = 10.83) which increased MC (19.51%) and TPC (75.62%) of coated samples with 3% PGPE compared with control, whereas AV (41.12%), PV (53.16%), TVC (44.64%), and TFC (35.01%) reduced (p < 0.05). The results of this research suggested that the edible coatings based on the combination of CMC and SPI containing nanoencapsulated PGPE have the ability to reduce the oil oxidation reactions and microbial growth in raw pistachio. Therefore, the concentration of 2.0% nanoencapsulated PGPE due to its better properties can be used to extend the shelf life of raw pistachio.
Static Equilibrium Characteristics of Full‐Flow Staged Combustion Cycle Engine Under Different Propellants
Authors: He Haodong , Yu Nanjia , Di Sihan , Cai Guobiao , Zhou Chuang , Zheng Lihao
Published: September 2024

The full‐flow staged combustion cycle (FFSC) engine is a promising liquid rocket propulsion system owing to its capacity for high specific impulse. The present study introduces an equilibrium model of the FFSC engine, utilizing the Raptor engine as a reference point and employing the discrete Newton iteration method to resolve the equilibrium equations in a fixed‐point format. Under different propellants (LOX‐LH2, LOX‐LCH4, and LOX‐kerosene), the static equilibrium characteristics of the FFSC engine were analyzed, and the following conclusions were drawn. The FFSC engine exhibited similar equilibrium results on the oxidizer side, with differences concentrated on the fuel side. Significant differences were identified between the three propellants in the regulation range of the FFSC engine. The regulation range of LOX‐LH2 was wider than that of LOX‐LCH4 primarily because of the variance in the molecular weight of the fuel‐rich gas. Conversely, LOX‐kerosene exhibited the narrowest regulatory range, which was attributed to the extremely low value of the oxidizer excess coefficient. The temperature management of preburners relies on regulating the oxidizer excess coefficient, necessitating adjustments to the valve components (main fuel valve (MFV), oxidizer preburner fuel valve (OPFV), and fuel preburner oxidizer valve). The differences among the three propellants were mainly concentrated on the MFV and OPFV.
Simultaneous Targeting of NQO1 and SOD1 Eradicates Breast Cancer Stem Cells via Mitochondrial Futile Redox Cycling
Authors: Luo Ming , Shen Na , Shang Li , Fang Zeng , Xin Ying , Ma Yuxi , Du Min , Yuan Yuan , Hu Chenchen , Tang Yun , Huang Jing , Wei Wei , Lee Myung Ryul , Hergenrother Paul J. , Wicha Max S.
Published: September 2024

Triple-negative breast cancer (TNBC) contains the highest proportion of cancer stem-like cells (CSC), which display intrinsic resistance to currently available cancer therapies. This therapeutic resistance is partially mediated by an antioxidant defense coordinated by the transcription factor NRF2 and its downstream targets that include NAD(P)H quinone oxidoreductase 1 (NQO1). In this study, we identified the antioxidant enzymes NQO1 and superoxide dismutase 1 (SOD1) as therapeutic vulnerabilities of ALDH+ epithelial-like CSCs and CD24−/loCD44+/hi mesenchymal-like CSCs in TNBC. Effective targeting of these CSC states was achieved by using isobutyl-deoxynyboquinone (IB-DNQ), a potent and specific NQO1-bioactivatable futile redox cycling molecule, which generated large amounts of reactive oxygen species including superoxide and hydrogen peroxide. Furthermore, the CSC killing effect was specifically enhanced by genetic or pharmacologic inhibition of SOD1, a copper-containing superoxide dismutase highly expressed in TNBC. Mechanistically, a significant portion of NQO1 resides in the mitochondrial intermembrane space, catalyzing futile redox cycling from IB-DNQ to generate high levels of mitochondrial superoxide, and SOD1 inhibition markedly potentiated this effect, resulting in mitochondrial oxidative injury, cytochrome c release, and activation of the caspase-3–mediated apoptotic pathway. Treatment with IB-DNQ alone or together with SOD1 inhibition effectively suppressed tumor growth, metastasis, and tumor-initiating potential in xenograft models of TNBC expressing different levels of NQO1. This futile oxidant-generating strategy, which targets CSCs across the epithelial–mesenchymal continuum, could be a promising therapeutic approach for treating patients with TNBC.

Significance: Combining NQO1-bioactivatable futile oxidant generators with SOD1 inhibition eliminates breast cancer stem cells, providing a therapeutic strategy that may have wide applicability, as NQO1 and SOD1 are overexpressed in several cancers.
Neighborhood Disadvantage and Prostate Tumor Aggressiveness among African American and European American Men
Authors: Boyle Joseph , Yau Jessica , Slade Jimmie L. , Butts Derrick A. , Wimbush Jessica , Park Jong Y. , Hussain Arif , Onukwugha Eberechukwu , Knott Cheryl L. , Wheeler David C. , Barry Kathryn Hughes
Published: September 2024

Background:

Studies have identified associations between neighborhood disadvantage (ND), which is more likely to affect African American (AA) individuals, and aggressive prostate cancer. Thus, ND may contribute to prostate cancer disparities. However, it is unknown what ND components drive aggressive disease and whether associations vary by race.

Methods:

We evaluated associations between aggressive prostate cancer and four ND metrics—Area Deprivation Index (ADI), validated Bayesian Neighborhood Deprivation Index (NDI), racial isolation (RI) index, and historical redlining, and whether these factors interacted with race, among men with prostate cancer treated at the University of Maryland Greenebaum Comprehensive Cancer Center (2004–2021).

Results:

We included 1,458 men (698 European American and 760 AA). AA men were more likely to experience ND. In adjusted models, the ADI, RI, and redlining were significantly associated with aggressive versus nonaggressive prostate cancer overall [ADI, OR for one SD increase = 1.14, 95% confidence interval (CI), 1.00–1.30; RI, OR = 1.27, CI, 1.07–1.51; redlining, OR = 1.77; CI, 1.23–2.56] and among AA men. The NDI was associated with aggressive prostate cancer among AA men (OR = 1.32, 95% credible interval: 1.13–1.57); percent in poverty received the largest importance weight. The ADI (P heterogeneity = 0.002) and NDI (exceedance probability heterogeneity = 98.1%) significantly interacted with race, such that associations were significantly stronger for AA men.

Conclusions:

We identified novel significant positive associations for racial segregation and historical redlining with aggressive prostate cancer and significant interactions between ND indices and race.

Impact:

Findings inform specific ND components that are associated with aggressive prostate cancer and suggest the ND effect is stronger for AA men, which has implications for interventions to reduce disparities.
A First-in-Human Phase I Study of BXQ-350, a First-in-Class Sphingolipid Metabolism Regulator, in Patients with Advanced/Recurrent Solid Tumors or High-Grade Gliomas
Authors: Rixe Olivier , Villano John L. , Wesolowski Robert , Noonan Anne M. , Puduvalli Vinay K. , Wise-Draper Trisha M. , Curry Richard , Yilmaz Emrullah , Cruze Charlie , Ogretmen Besim , Tapolsky Gilles , Takigiku Ray
Published: September 2024

Purpose:

BXQ-350, a nanovesicle formulation of saposin C, is an allosteric sphingolipid metabolism regulator that increases proapoptotic ceramide and decreases oncogenic sphingosine-1-phosphate levels. We conducted a first-in-human phase I study of BXQ-350.

Patients and Methods:

Adults (≥18 years old) with advanced/recurrent, treatment-refractory solid tumors or high-grade gliomas received BXQ-350 intravenously in five dose cohorts (0.7–2.4 mg/kg) in a 3+3 dose escalation and expansion design. The primary endpoints during dose escalation were dose-limiting toxicities and maximum tolerated dose; the primary objective in expansion parts was assessment of antitumor activity (RECIST v1.1/Response Assessment in Neuro-Oncology criteria).

Results:

Eighty-six patients were enrolled. Dose-limiting toxicities were not observed during dose escalation (n = 18), and a maximum tolerated dose was not identified. An additional 68 patients received the 2.4 mg/kg dose. Nine patients (10%) discontinued due to adverse events. The most common treatment-related adverse events were nausea (24%) and fatigue (23%). Eight patients had a progression-free survival of ≥6 months. Two of these achieved a partial response, and six had stable disease, among whom three had a reduction in ≥1 target lesion. Of those with progression-free survival of ≥6 months, seven remained on study for >12 months, five for >24 months, and after 7 years, two remained on study without disease progression.

Conclusions:

BXQ-350 was well-tolerated as monotherapy at doses up to 2.4 mg/kg. It provided some lasting clinical benefit in patients with recurrent solid malignancies across several tumor types, consistent with a decreased systemic sphingosine-1-phosphate/ceramide metabolic rheostat. BXQ-350 warrants further clinical investigation alone and combined with standard of care for advanced solid tumors.