bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-cell analysis of bronchoalveolar cells in inflammatory and fibrotic post-COVID lung disease
Authors: Mehta Puja , Sanz-Magallón Duque de Estrada Blanca , Denneny Emma K. , Foster Kane , Turner Carolin T. , Mayer Andreas , Milighetti Martina , Platé Manuela , Worlock Kaylee B. , Yoshida Masahiro , Brown Jeremy S. , Nikolić Marko Z. , Chain Benjamin M. , Noursadeghi Mahdad , Chambers Rachel C. , Porter Joanna C. , Tomlinson Gillian S.
Published: May 2024

Background

Persistent radiological lung abnormalities are evident in many survivors of acute coronavirus disease 2019 (COVID-19). Consolidation and ground glass opacities are interpreted to indicate subacute inflammation whereas reticulation is thought to reflect fibrosis. We sought to identify differences at molecular and cellular level, in the local immunopathology of post-COVID inflammation and fibrosis.

Methods

We compared single-cell transcriptomic profiles and T cell receptor (TCR) repertoires of bronchoalveolar cells obtained from convalescent individuals with each radiological pattern, targeting lung segments affected by the predominant abnormality.

Results

CD4 central memory T cells and CD8 effector memory T cells were significantly more abundant in those with inflammatory radiology. Clustering of similar TCRs from multiple donors was a striking feature of both phenotypes, consistent with tissue localised antigen-specific immune responses. There was no enrichment for known SARS-CoV-2-reactive TCRs, raising the possibility of T cell-mediated immunopathology driven by failure in immune self-tolerance.

Conclusions

Post-COVID radiological inflammation and fibrosis show evidence of shared antigen-specific T cell responses, suggesting a role for therapies targeting T cells in limiting post-COVID lung damage.
Neuroserpin, IL-33 and IL-17A as potential markers of mild symptoms of depressive syndrome in Toxoplasma gondii-infected pregnant women
Authors: Silva Zolder Marinho , Toledo Débora Nonato Miranda , Pio Sirlaine , Machado Bianca Alves Almeida , Santos Priscilla Vilela dos , Hó Flávia Galvão , Medina Yasmim Nogueira , Cordeiro Paulo Henrique de Miranda , Perucci Luiza Oliveira , Pinto Kelerson Mauro de Castro , Talvani André
Published: May 2024

Introduction

Depressive syndrome (DS) is a common complication during pregnancy and the postpartum period, and is triggered by multiple organic/genetic and environmental factors. Clinical and biochemical follow-up is essential for the early diagnosis and prognosis of DS. The protozoan Toxoplasma gondii causes infectious damage to the fetus during parasite primary-infection. However, in long-term infections, pregnant women develop immune protection to protect the fetus, although they remain susceptible to pathological or inflammatory effects induced by T. gondii. This study aimed to investigate plasma inflammatory biomarkers in pregnant women seropositive and seronegative for T. gondii, with diagnoses of minor and moderate/severe DS.

Methods

Pregnant women (n=45; age=18–39 years) were recruited during prenatal care at health centers in Ouro Preto, Minas Gerais, Brazil. Participants were asked to complete a socio-demographic questionnaire to be submitted to well-standardized DS scale calculators (Beck Depression Inventory Questionnaire, Edinburgh Postnatal Depression Scale, and Major Depressive Episode Module). Additionally, 4 mL of blood was collected for plasma neuroserpin, CCL2, IL-17A, and IL-33 analysis.

Results

Pregnant volunteers with chronic T. gondii contact were all IgG+ (44%; n=21) and exhibited increased plasma IL-33, IL-17A, and neuroserpin levels, but not CCL2, compared to uninfected pregnant women. Using Beck’s depression inventory, we observed an increase in plasma IL-17A and IL-33 in women with T. gondii infeCction diagnosed with mild DS, whereas neuroserpin was associated with minor and moderate/severe DS.

Discussion

Our data suggest a close relationship between DS in pregnant women with chronic T. gondii infection and neurological conditions, which may be partially mediated by plasma neuroserpin, IL-33, and IL-17A levels.
S1PR2 participates in intestinal injury in severe acute pancreatitis by regulating macrophage pyroptosis
Authors: Lin Tianjiao , Peng Mengyuan , Zhu Qingyun , Pan Xinting
Published: May 2024

Background

Severe acute pancreatitis (SAP) is an inflammatory disorder affecting the gastrointestinal system. Intestinal injury plays an important role in the treatment of severe acute pancreatitis. In this study, we mainly investigated the role of S1PR2 in regulating macrophage pyroptosis in the intestinal injury of severe acute pancreatitis.

Methods

The SAP model was constructed using cerulein and lipopolysaccharide, and the expression of S1PR2 was inhibited by JTE-013 to detect the degree of pancreatitis and intestinal tissue damage in mice. Meanwhile, the level of pyroptosis-related protein was detected by western blot, the level of related mRNA was detected by PCR, and the level of serum inflammatory factors was detected by ELISA. In vitro experiments, LPS+ATP was used to construct the pyroptosis model of THP-1. After knockdown and overexpression of S1PR2, the pyroptosis proteins level was detected by western blot, the related mRNA level was detected by PCR, and the level of cell supernatant inflammatory factors were detected by ELISA. A rescue experiment was used to verify the sufficient necessity of the RhoA/ROCK pathway in S1PR2-induced pyroptosis. Meanwhile, THP-1 and FHC were co-cultured to verify that cytokines released by THP-1 after damage could regulate FHC damage.

Results

Our results demonstrated that JTE-013 effectively attenuated intestinal injury and inflammation in mice with SAP. Furthermore, we observed a significant reduction in the expression of pyroptosis-related proteins within the intestinal tissue of SAP mice upon treatment with JTE-013. We confirmed the involvement of S1PR2 in THP-1 cell pyroptosis in vitro. Specifically, activation of S1PR2 triggered pyroptosis in THP-1 cells through the RhoA/ROCK signaling pathway. Moreover, it was observed that inflammatory factors released during THP-1 cell pyroptosis exerted an impact on cohesin expression in FHC cells.

Conclusion

The involvement of S1PR2 in SAP-induced intestinal mucosal injury may be attributed to its regulation of macrophage pyroptosis.
OTULIN haploinsufficiency predisposes to environmentally directed inflammation
Authors: Staels Frederik , Bücken Leoni , De Vuyst Leana , Willemsen Mathijs , Van Nieuwenhove Erika , Gerbaux Margaux , Neumann Julika , Malviya Vanshika , Van Meerbeeck Lize , Haughton Jeason , Seldeslachts Laura , Gouwy Mieke , Martinod Kimberly , Vande Velde Greetje , Proost Paul , Yshii Lidia , Schlenner Susan , Schrijvers Rik , Liston Adrian , Humblet-Baron Stephanie
Published: May 2024

Recently, OTULIN haploinsufficiency was linked to enhanced susceptibility to Staphylococcus aureus infections accompanied by local necrosis and systemic inflammation. The pathogenesis observed in haploinsufficient patients differs from the hyperinflammation seen in classical OTULIN-related autoinflammatory syndrome (ORAS) patients and is characterized by increased susceptibility of dermal fibroblasts to S. aureus alpha toxin-inflicted cytotoxic damage. Immunological abnormalities were not observed in OTULIN haploinsufficient patients, suggesting a non-hematopoietic basis. In this research report, we investigated an Otulin+/− mouse model after in vivo provocation with lipopolysaccharide (LPS) to explore the potential role of hematopoietic-driven inflammation in OTULIN haploinsufficiency. We observed a hyperinflammatory signature in LPS-provoked Otulin+/− mice, which was driven by CD64+ monocytes and macrophages. Bone marrow-derived macrophages (BMDMs) of Otulin+/− mice demonstrated higher proinflammatory cytokine secretion after in vitro stimulation with LPS or polyinosinic:polycytidylic acid (Poly(I:C)). Our experiments in full and mixed bone marrow chimeric mice suggest that, in contrast to humans, the observed inflammation was mainly driven by the hematopoietic compartment with cell-extrinsic effects likely contributing to inflammatory outcomes. Using an OTULIN haploinsufficient mouse model, we validated the role of OTULIN in the regulation of environmentally directed inflammation.
An inclusive approach to designing a multi-epitope chimeric vaccine for Taenia infections by integrating proteomics and reverse vaccinology
Authors: Sharma Swati , Sharan Ujjawal , Kaur Rimanpreet , Chaudhary Anubha , Rawat Suraj S. , Keshri Anand K. , Arora Naina , Prasad Amit
Published: May 2024

Background

Soil- and water-transmitted helminths are a major concern in the developing world due to their high prevalence. More than a quarter of the population were estimated to be infected with helminths in these endemic zones.

Research design

An in silico approach was used to design a vaccine construct against the Taenia genus utilizing the proteomic information and evaluation of the construct using immune-informatics.

Results

Our study identified 451 conserved proteins in Taenia spp. using the existing proteome; out of these, 141 were found to be expressed in cysticerci. These proteins were screened for antigenic epitopes and a multi-subunit vaccine was constructed. The constructed vaccine was assessed for its efficacy in mounting the appropriate immune response. Our constructed vaccine showed stability and optimal performance against the TLR 4 receptor, which is reported to be upregulated in Taenia infections in hosts.

Conclusion

Immune-informatics tools help design vaccines for neglected diseases such as those attributed to helminths, which are known to cause widespread morbidity. Our vaccine construct holds tremendous potential in conferring protection against all Taenia spp. of clinical relevance to human.
Diversity and biogeography of dinoflagellates in the Kuroshio region revealed by 18S rRNA metabarcoding
Authors: Wu Yubei , Hirai Junya , Zhou Fanyu , Iwataki Mitsunori , Jiang Siyu , Ogawa Hiroshi , Inoue Jun , Hyodo Susumu , Saito Hiroaki
Published: May 2024

Dinoflagellate is one of the most diverse and pervasive protists and a fundamental player in the marine food web dynamics and biogeochemical cycles. While possessing different nutritional strategies from purely autotrophy or heterotrophy to mixotrophy, some of them are also known as toxic harmful algal bloom (HAB) formers over the world. Despite their ordinariness, their diversity and biogeography are understudied in the open ocean compared with coastal region. As the first metabarcoding survey covering the Kuroshio current region from the offshore of Okinawa to the south of Honshu, we investigated the distribution of free-living dinoflagellates using the hypervariable V4 and V9 regions on 18S rRNA and their relation to ambient environments influenced by this oligotrophic but highly productive current in the northwest Pacific Ocean. We observed community structures differentiated by depth and nutrient concentrations. Most species annotated are autotrophic or mixotrophic and had a distribution correlated to warmer surface water, whereas heterotrophic species correlated to high nutrient levels or deeper layer. Our results also confirmed the overall high genetic diversity of dinoflagellates that decreased with depth and onshore. Most species present at stations offshore, and the relative abundance of HAB assemblages was lower at nutrient-rich stations on the continental shelf than stations influenced by the Kuroshio current, exhibiting the role of the Kuroshio transporting dinoflagellates including HAB species. To fully understand the dynamics of dinoflagellate communities in marine ecosystems, further seasonal monitoring is foremost for correlating dinoflagellates and environmental factors while completing the reference genomic database.
Three-dimensional acoustic propagation of noise from impact pile driving in a complex costal environment and its effects on large yellow croaker (Pseudosciaena crocea)
Authors: Xie Jiarui , Xue Ruichao , Niu Fuqiang , Chen Benqing , Yang Yanming
Published: May 2024

The effects of high-intensity impulsive noise generated by pile driving on fish are a major concern in environmental impact assessments. Numerical acoustic models are essential for predicting underwater-acoustic-related problems in complex coastal environments prior to offshore construction. However, underwater noise modeling for impact pile driving has often been performed using simplistic propagation models that are inadequate for three-dimensional (3D) environments. A 3D parabolic equation method (PE) was established in this study to better predict broadband transmission loss (TL) from impact pile driving in complex coastal environments and its influence on the large yellow croaker (Pseudosciaena crocea). The effects of 3D propagation were investigated using two realistic scenarios with different bathymetric complexities. The values and attenuation rate of the broadband TL for the steeply sloped bottom were significantly greater than those for the flat and weakly varying bottoms over 3 km. At a water depth of 5 m, a difference of approximately 10 dB was observed between the two TL scenarios at a distance of 4.5 to 5 km. The simulation results are in reasonable agreement with the field measurement data, with a difference of less than 3 dB. The zones of behavioral response and injury in the large yellow croaker were estimated using the For3D model. The results showed that the effects of the noise generated by the impact pile driving on the large yellow croaker were evident and three-dimensional. Therefore, 3D propagation effects should be considered when analyzing the influence of underwater noise on marine animals.
Outcome of patients with different stages of acute-on-chronic liver failure treated with artificial liver support system
Authors: Ma Yuanji , Xu Yan , Du Lingyao , Bai Lang , Tang Hong
Published: May 2024

Background

Elevated international normalized ratio of prothrombin time (PT-INR) is one of the key characteristics of acute-on-chronic liver failure (ACLF). Whether the staging of PT-INR has the ability to screen out subgroups of ACLF patients who would be more eligible for artificial liver support system (ALSS) treatment has not been studied in detail.

Methods

A previous study enrolled patients receiving ALSS treatment with regional citrate anticoagulation from January 2018 to December 2019. Patients with different PT-INR intervals were retrospectively enrolled: 1.3 ≤ PT-INR < 1.5 (Pre-stage), 1.5 ≤ PT-INR < 2.0 (Early-stage), 2.0 ≤ PT-INR < 2.5 (Mid-stage), and PT-INR ≥ 2.5 (End-stage). The Cox proportional hazards models were used to estimate the association between stages of ACLF or sessions of ALSS treatment and 90 day mortality.

Results

A total of 301 ACLF patients were enrolled. The 90 day mortality risk of Early-stage ACLF patients (adjusted hazard ratio (aHR) (95% confidence interval (CI)), 3.20 (1.15–8.89), p = 0.026), Mid-stage ACLF patients (3.68 (1.34–10.12), p = 0.011), and End-stage ACLF patients (12.74 (4.52–35.91), p < 0.001) were higher than that of Pre-stage ACLF patients, respectively. The 90 day mortality risk of Mid-stage ACLF patients was similar to that of Early-stage ACLF patients (1.15 (0.69–1.94), p = 0.591). The sessions of ALSS treatment was an independent protective factor (aHR (95% CI), 0.81 (0.73–0.90), p < 0.001). The 90 day mortality risk in ACLF patients received 3–5 sessions of ALSS treatment was lower than that of patients received 1–2 sessions (aHR (95% CI), 0.34 (0.20–0.60), p < 0.001), whereas the risk in patients received ≥6 sessions of ALSS treatment was similar to that of patients received 3–5 sessions (0.69 (0.43–1.11), p = 0.128).

Conclusion

ACLF patients in Pre-, Early-, and Mid-stages might be more eligible for ALSS treatment. Application of 3–5 sessions of ALSS treatment might be reasonable.
Changes in soil organic carbon components and microbial community following spent mushroom substrate application
Authors: Yang Guiting , Ma Yan , Ma Xiaochi , Wang Xuanqing , Lu Chao , Xu Wenyi , Luo Jia , Guo Dejie
Published: May 2024

While spent mushroom substrate (SMS) has shown promise in increasing soil organic carbon (SOC) and improving soil quality, research on the interplay between SOC components and microbial community following the application of diverse SMS types remains scant. A laboratory soil incubation experiment was conducted with application of two types of SMSs from cultivation of Pleurotus eryngii (PE) and Agaricus bisporus (AB), each at three application rates (3, 5.5, and 8%). Advanced techniques, including solid-state 13C nuclear magnetic resonance (NMR) and high-throughput sequencing, were employed to investigate on SOC fractions and chemical structure, microbial community composition and functionality. Compared to SMS-AB, SMS-PE application increased the relative abundances of carbohydrate carbon and O-alkyl C in SOC. In addition, SMS-PE application increased the relative abundance of the bacterial phylum Proteobacteria and those of the fungal phyla Basidiomycota and Ascomycota. The relative abundances of cellulose-degrading bacterial (e.g., Flavisolibacter and Agromyces) and fungal genera (e.g., Myceliophthora, Thermomyces, and Conocybe) were increased as well. The application of SMS-AB increased the aromaticity index of SOC, the relative abundance of aromatic C, and the contents of humic acid and heavy fraction organic carbon. In addition, SMS-AB application significantly increased the relative abundances of the bacterial phyla Firmicutes and Actinobacteria. Notably, the genera Actinomadura, Ilumatobacter, and Bacillus, which were positively correlated with humic acid, experienced an increase in relative abundance. Functional prediction revealed that SMS-PE application elevated carbohydrate metabolism and reduced the prevalence of fungal pathogens, particularly Fusarium. The application of high-rate SMS-AB (8%) enhanced bacterial amino acid metabolism and the relative abundances of plant pathogenic fungi. Our research provides strategies for utilizing SMS to enrich soil organic carbon and fortify soil health, facilitating the achievement of sustainable soil management.
Disease spectrum and prognostic factors in patients treated for tuberculous meningitis in Shaanxi province, China
Authors: Wang Ting , Li Meng-yan , Cai Xin-shan , Cheng Qiu-sheng , Li Ze , Liu Ting-ting , Zhou Lin-fu , Wang Hong-hao , Feng Guo-dong , Marais Ben J. , Zhao Gang
Published: May 2024

Background

Tuberculous meningitis (TBM) is the most severe form of tuberculosis (TB) and can be difficult to diagnose and treat. We aimed to describe the clinical presentation, diagnosis, disease spectrum, outcome, and prognostic factors of patients treated for TBM in China.

Methods

A multicenter retrospective study was conducted from 2009 to 2019 enrolling all presumptive TBM patients referred to Xijing tertiary Hospital from 27 referral centers in and around Shaanxi province, China. Patients with clinical features suggestive of TBM (abnormal CSF parameters) were included in the study if they had adequate baseline information to be classified as “confirmed,” “probable,” or “possible” TBM according to international consensus TBM criteria and remained in follow-up. Patients with a confirmed alternative diagnosis or severe immune compromise were excluded. Clinical presentation, central nervous system imaging, cerebrospinal fluid (CSF) results, TBM score, and outcome—assessed using the modified Barthel disability index—were recorded and compared.

Findings

A total of 341 presumptive TBM patients met selection criteria; 63 confirmed TBM (25 culture positive, 42 Xpert-MTB/RIF positive), 66 probable TBM, 163 possible TBM, and 49 “not TBM.” Death was associated with BMRC grade III (OR = 5.172; 95%CI: 2.298–11.641), TBM score ≥ 15 (OR = 3.843; 95%CI: 1.372–10.761), age > 60 years (OR = 3.566; 95%CI: 1.022–12.442), and CSF neutrophil ratio ≥ 25% (OR = 2.298; 95%CI: 1.027–5.139). Among those with confirmed TBM, nearly one-third (17/63, 27.0%) had a TBM score < 12; these patients exhibited less classic meningitis symptoms and signs and had better outcomes compared with those with a TBM score ≥ 12. In this group, signs of disseminated/miliary TB (OR = 12.427; 95%CI: 1.138–135.758) and a higher TBM score (≥15, OR = 8.437; 95%CI: 1.328–53.585) were most strongly associated with death.

Conclusion

TBM patients who are older (>60 years) have higher TBM scores or CSF neutrophil ratios, have signs of disseminated/miliary TB, and are at greatest risk of death. In general, more effort needs to be done to improve early diagnosis and treatment outcome in TBM patients.
An investigation of the prevalence and diversity of Anisakis in China: marine food safety implications
Authors: Zeng Min-hao , Fang Chuan-tao , Wang Xiao-xu , Qadeer Abdul , Qiu Yang-yuan , Hong Xiao-mei , Mahmoud Mohamed H.
Published: May 2024

Anisakis can cause Anisakiasis in humans if raw or undercooked fish is consumed. Symptoms of infection may include vomiting, acute abdominal symptoms, or allergies. In this study, we collected 187 commercially available marine fish from the Yellow Sea, East China Sea, and South China Sea. Among them, 79 were found positive containing 520 Anisakis worms. The average prevalence rate was found 42% in this investigation. Ninety-two worms from different sea areas were selected and analyzed for identification, revealing the presence of five different species, which are Anisakis pegreffii, Hysterothylacium aduncum, Hysterothylacium zhoushanense, Hysterothylacium amoyense, and Hysterothylacium sp. In the meta-analysis, three databases: PubMed, CNKI, and BaiduXueshu were searched for surveys on the prevalence of Anisakis in Chinese waters from January 2000 to December 2023. A total of 26 studies were included in this analysis of which 25 publications were retrieved from different databases and one being the present study. The pooled prevalence of Anisakis was 45% among commercially available marine fish. Variances in the prevalence of Anisakis were noted among the four seas, with the highest rates in the East China Sea and the Bohai Sea, reaching 53% [0.38; 0.68] and 49% [0.36; 0.62], respectively. The Prevalence of Anisakis infection was significantly higher in astern parts such as Liaoning, Shanghai, and Zhejiang. Analysis of the host fish subgroups revealed that the orders of Anguilliformes, Scombriformes, and Gadiformes had high rates of infection. These findings suggest a significant prevalence of Anisakis, posing an increasing risk of infection for individuals. This study provides impactful information for implementing preventative measures against Anisakis.
Therapeutic role of voltage-gated potassium channels in age-related neurodegenerative diseases
Authors: Urrutia Janire , Arrizabalaga-Iriondo Ane , Sanchez-del-Rey Ana , Martinez-Ibargüen Agustín , Gallego Mónica , Casis Oscar , Revuelta Miren
Published: May 2024

Voltage-gated ion channels are essential for membrane potential maintenance, homeostasis, electrical signal production and controlling the Ca2+ flow through the membrane. Among all ion channels, the key regulators of neuronal excitability are the voltage-gated potassium channels (KV), the largest family of K+ channels. Due to the ROS high levels in the aging brain, K+ channels might be affected by oxidative agents and be key in aging and neurodegeneration processes. This review provides new insight about channelopathies in the most studied neurodegenerative disorders, such as Alzheimer Disease, Parkinson’s Disease, Huntington Disease or Spinocerebellar Ataxia. The main affected KV channels in these neurodegenerative diseases are the KV1, KV2.1, KV3, KV4 and KV7. Moreover, in order to prevent or repair the development of these neurodegenerative diseases, previous KV channel modulators have been proposed as therapeutic targets.
Decoding imagined speech with delay differential analysis
Authors: Carvalho Vinícius Rezende , Mendes Eduardo Mazoni Andrade Marçal , Fallah Aria , Sejnowski Terrence J. , Comstock Lindy , Lainscsek Claudia
Published: May 2024

Speech decoding from non-invasive EEG signals can achieve relatively high accuracy (70–80%) for strictly delimited classification tasks, but for more complex tasks non-invasive speech decoding typically yields a 20–50% classification accuracy. However, decoder generalization, or how well algorithms perform objectively across datasets, is complicated by the small size and heterogeneity of existing EEG datasets. Furthermore, the limited availability of open access code hampers a comparison between methods. This study explores the application of a novel non-linear method for signal processing, delay differential analysis (DDA), to speech decoding. We provide a systematic evaluation of its performance on two public imagined speech decoding datasets relative to all publicly available deep learning methods. The results support DDA as a compelling alternative or complementary approach to deep learning methods for speech decoding. DDA is a fast and efficient time-domain open-source method that fits data using only few strong features and does not require extensive preprocessing.
Bringing together multimodal and multilevel approaches to study the emergence of social bonds between children and improve social AI
Authors: Bonnaire Julie , Dumas Guillaume , Cassell Justine
Published: May 2024

This protocol paper outlines an innovative multimodal and multilevel approach to studying the emergence and evolution of how children build social bonds with their peers, and its potential application to improving social artificial intelligence (AI). We detail a unique hyperscanning experimental framework utilizing functional near-infrared spectroscopy (fNIRS) to observe inter-brain synchrony in child dyads during collaborative tasks and social interactions. Our proposed longitudinal study spans middle childhood, aiming to capture the dynamic development of social connections and cognitive engagement in naturalistic settings. To do so we bring together four kinds of data: the multimodal conversational behaviors that dyads of children engage in, evidence of their state of interpersonal rapport, collaborative performance on educational tasks, and inter-brain synchrony. Preliminary pilot data provide foundational support for our approach, indicating promising directions for identifying neural patterns associated with productive social interactions. The planned research will explore the neural correlates of social bond formation, informing the creation of a virtual peer learning partner in the field of Social Neuroergonomics. This protocol promises significant contributions to understanding the neural basis of social connectivity in children, while also offering a blueprint for designing empathetic and effective social AI tools, particularly for educational contexts.
The HER2 flip-HER2 amplification of tumor cells in the cerebrospinal fluid of breast cancer patients with leptomeningeal disease: implications for treating the LM tumor with anti-HER2 therapy
Authors: Kumthekar Priya U. , Blouw Barbara , Corkos Perry , Nagpal Seema , Tripathy Arushi , Piccioni David , Youssef Michael
Published: May 2024

Introduction

CNSide is a platform that detects and characterizes tumor cells in the cerebrospinal fluid (CSF) of patients with leptomeningeal disease (LMD). The platform was validated per College of American Pathologists (CAP) and Clinical Laboratories Improvement Amendment (CLIA) guidelines and run as a commercial Laboratory Developed Test (LDT) at Biocept in San Diego, CA. The platform allows CSF tumor cell (CSF-TC) enumeration and biomarker characterization by fluorescent in situ hybridization (FISH).

Methods

We performed a multicenter retrospective chart review of HER2 FISH CNSide test results that were commercially ordered on 26 patients by physicians for LMD breast cancer patients between April 2020 and October 2022.

Results

We show that HER2 is amplified on CSF tumor cells in 62% (16/26) of LMD breast cancer patients. 10/26 (38%) patients had discordant HER2-positivity between the primary tumor tissue and CSF-TC; of these, 35% (9/26) of the patients displayed HER2 amplification on the CSF-TCs, however were categorized as HER2 negative on the primary tumor. Of the 27% (7/26) patients with a HER2 positive primary tumor, one patient showed a HER2 negative LMD tumor. Two patients, 8% (2/26) had a HER2 equivocal primary tumor; of these, one demonstrated a HER2 negative, and one a HER2 positive LMD tumor. Serial analysis (at least 4 longitudinal tests) of HER2 status of the CSF-TC throughout therapy was available for 14 patients and demonstrated that HER2 status of the LMD changed in 29% (4/14) during their treatment course and impacted care decisions.

Conclusions

Our data suggests that CSF-TC HER2 FISH analysis in LMD breast cancer patients may be discordant to the primary tumor sample and the discovery of HER2 positivity in the CSF may open doors to anti-HER2 targeted therapy options for LMD patients.
Percutaneous triamcinolone injection for upper eyelid retraction in thyroid eye disease
Authors: Parsons Shaun R. , Wilson-Pogmore Ario , Sullivan Timothy J.
Published: May 2024

Purpose

To evaluate percutaneous triamcinolone (TA) injection efficacy in treating upper eyelid retraction (UER) for Australian thyroid eye disease (TED) patients.

Methods

We conducted a retrospective analysis across 8 years and multiple diverse Australian centres identified UER patients who received TA injections. A single operator administered 40mg/1ml TA through upper eyelid skin. Assessments at 4-6 weeks and subsequent eyelid measurements gauged treatment response and complications.

Results

24 patients and 25 eyelids were included in the study. 91.6% were female, mean age 40.8 ± 10.3 years with mean follow-up of 17.5 months (± 18.5). Pre-treatment MRD1 was 6.2mm ± 1.4, and we observed a mean improvement of 2.2mm from pre-treatment to post-treatment (p<0.001). The mean UER measurement before treatment (defined as MRD1 - 4.0mm) was 3.0mm ± 1.3 (range, 0-6mm). After treatment, the mean UER measurement was -0.1mm. Quality of life (QOL) assessment improved significantly, from pre-treatment score of 4.13 ± 2.4 to post-treatment 8.0 ±1.7 (p<0.001).

Conclusions

Percutaneous injection of TA is an effective and safe treatment option for UER in patients with TED. This technique can be performed without upper eyelid eversion, which makes it more tolerable for patients and less complex for the operator compared to the transconjunctival injection approach. Our results show a significant improvement in MRD1 and UER, as well as patient QOL. Moreover, we found a low rate of complications (4.2% induced ptosis) and no cases of raised intraocular pressure. Percutaneous TA injection can greatly reduce the need for eyelid lowering surgery in this patient population.
To elucidate the mechanism of “Scrophulariae Radix–Fritillaria” in goiter by integrated metabolomics and serum pharmaco-chemistry
Authors: Chen Lixin , Liang Wei , Zhang Kun , Wang Zishuo , Cheng Wei , Li Wenlan
Published: May 2024

The pharmacodynamic substances in “Scrophulariae Radix–Fritillaria” and the molecular mechanisms underlying its therapeutic effects against goiter were analyzed through metabolomics and serum pharmaco-chemistry. A rat model of goiter was established using propylthiouracil (PTU), and the animals were treated using “Scrophulariae Radix–Fritillaria.” The efficacy of the drug pair was evaluated in terms of thyroid gland histopathology and blood biochemical indices. Serum and urine samples of the rats were analyzed by UPLC-Q-TOF/MS. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were performed to screen potential biomarkers in urine and the corresponding metabolic pathways. The blood components of “Scrophulariae Radix–Fritillaria” were also identified, and their correlation with urine biomarkers was analyzed in order to screen for potential bioactive compounds. “Scrophulariae Radix–Fritillaria” mitigated injury to thyroid tissues and normalized the levels of the thyroid hormones FT3, FT4, and TSH. We also identified 22 urine biomarkers related to goiter, of which 19 were regulated by “Scrophulariae Radix–Fritillaria.” Moreover, urine biomarkers are involved in tryptophan metabolism, steroid hormone biosynthesis, and beta-alanine metabolism, and these pathways may be targeted by the drug pair. In addition, 47 compounds of “Scrophulariae Radix–Fritillaria” were detected by serum pharmacochemistry, of which nine components, namely, syringic acid, paeonol, cedrol, and cis-ferulic acid, fetisinine, aucubigenin, linolenic acid, ussuriedine, and 5-(methylsulfanyl)pentanenitrile, were identified as potential effective substances against goiter. To summarize, we characterized the chemical components and mechanisms of “Scrophulariae Radix–Fritillaria” involved in the treatment of goiter, and our findings provide an experimental basis for its clinical application.
Efficacy and safety of FLT3 inhibitors in monotherapy of hematological and solid malignancies: a systemic analysis of clinical trials
Authors: Zhao Yuying , Zhang Xuedi , Ding Xiaoyan , Wang Ying , Li Zhenpeng , Zhao Ronglan , Cheng Hai-En , Sun Yanli
Published: May 2024

Introduction: FLT3 mutations are closely associated with the occurrence of hematological and solid malignancies, especially with acute myeloid leukemia. Currently, several FLT3 inhibitors are in clinical trials, and some have been applied in clinic. However, the safety, efficacy and pharmacodynamics of these FLT3 inhibitors have not been systemically analyzed before.

Methods: We searched and reviewed clinical trial reports on the monotherapy of 13 FLT3 inhibitors, including sorafenib, lestaurtinib, midostaurin, gilteritinib, quizartinib, sunitinib, crenolanib, tandutinib, cabozantinib, pexidartinib, pacritinib, famitinib, and TAK-659 in patients with hematological and solid malignancies before May 31, 2023.

Results: Our results showed the most common adverse events (AEs) were gastrointestinal adverse reactions, including diarrhea, hand-foot syndrome and nausea, while the most common hematological AEs were febrile neutropenia, anemia, and thrombocytopenia. Based on the published data, the mean overall survival (OS) and the mean progression-free survival (PFS) were 9.639 and 5.905 months, respectively. The incidence of overall response rate (ORR), complete remission (CR), partial response (PR), and stable disease (SD) for all these FLT3 inhibitors was 29.0%, 8.7%, 16.0%, and 42.3%, respectively. The ORRs of FLT3 inhibitors in hematologic malignancies and solid tumors were 40.8% and 18.8%, respectively, indicating FLT3 inhibitors were more effective for hematologic malignancies than for solid tumors. In addition, time to maximum plasma concentration (Tmax) in these FLT3 inhibitors ranged from 0.7-12.0 hours, but the elimination half-life (T1/2) range was highly variable, from 6.8 to 151.8 h.

Discussion: FLT3 inhibitors monotherapy has shown significant anti-tumor effect in clinic, and the effectiveness may be further improved through combination medication.
Treating refractory obsessive compulsive disorder with cathodal transcranial direct current stimulation over the supplementary motor area: a large multisite randomized sham-controlled double-blind study
Authors: Harika-Germaneau Ghina , Heit Damien , Drapier Dominique , Sauvaget Anne , Bation Remy , Chatard Armand , Doolub Damien , Wassouf Issa , Langbour Nicolas , Jaafari Nematollah
Published: May 2024

Background

The present study evaluated the therapeutic efficacy and tolerability of 10 transcranial direct current stimulation (tDCS) sessions in treatment-resistance obsessive-compulsive disorder (OCD) patients using a multisite double-blind sham-controlled design.

Methods

Eighty treatment-resistance outpatients suffering from obsessive-compulsive disorder were randomized to receive either active or sham transcranial direct current stimulation. The cathode was positioned over the supplementary motor area and the anode over the right supraorbital area. Patients were evaluated at baseline, end of treatment (day 14), one-month follow-up (day 45), and three-month follow-up (day 105) on the Yale-Brown Obsessive Compulsive Scale.

Results

Although a significant interaction between time and treatment was observed, the primary endpoint—measuring the change in Yale-Brown obsessive compulsive scale scores after two weeks—was not achieved. Conversely, the secondary endpoint, which concerned the change in Yale-Brown obsessive compulsive scale scores after three months, was successfully met. It is important to note, however, that there were no significant differences in the percentage of responders and remitters at any of the post-treatment assessments. This suggests that the treatment may not have had a clinically relevant impact. Patients well received the transcranial direct current stimulation treatment, indicating its good tolerability.

Conclusion

This is the largest controlled trial using transcranial direct current stimulation in treatment-resistance obsessive-compulsive disorder patients. Our results indicate the importance of studying the placebo effect in transcranial direct current stimulation and the necessity to consider a long follow-up time to best evaluate the effects of the intervention.

Clinical trial registration

ClinicalTrials.gov, identifier NCT03304600.
The relationship between mobile phone dependence and academic burnout in Chinese college students: a moderated mediator model
Authors: Li Na , Fu Linxi , Yang Hewen , Zhao Wanting , Wang Xingbo , Yan Yingchun , Fu Yangyang
Published: May 2024

Objective

The aim of this study was to examine the correlation between the level of mobile phone dependence among college students and their experience of academic burnout. Additionally, the study sought to explore the potential mediating effect of study engagement and the moderating role of love.

Methods

During October and December 2023, a cross-sectional study measuring mobile phone dependence, academic burnout, and study engagement among Chinese college students, using the UtrechtWork Engagement Scale-student (UWES-S), College Student Mobile Phone Dependence Questionnaire (CSMPDQ), and Academic Burnout Questionnaire (ABQ). To examine the hypothesis of mediating and moderating effect, SPSS PROCESS was utilized.

Results

The predictive effect of mobile phone dependence on academic burnout was significant (β = 0.410, t = 14.236, p < 0.001), and the predictive effect of mobile phone dependence on academic burnout remained significant when the mediating variable study engagement was introduced (β = 0.308, t = 10.288, p < 0.001), mobile phone dependence had a significant predictive effect on study engagement (β = -0.292, t = -11.639, p < 0.001), and study engagement had a significant positive predictive effect on academic burnout (β = -0.270, t = -9.028, p < 0.001). Love significantly negatively predicted study engagement (β = -0.564, t = -9.641, p < 0.001); and the interaction term for mobile phone dependence and love was significant (β = -0.211, t = -3.688, p < 0.001), indicating a significant moderating effect of love between mobile phone dependence and study engagement.

Conclusion

Mobile phones among college students has been found to have a direct correlation with academic burnout. It can also indirectly contribute to academic burnout by diminishing levels of academic engagement. This indirect relationship is further influenced by love. These findings can help researchers and educators better understand the underlying mechanisms between smartphone dependence and learning burnout in undergraduates.
A one health approach for monitoring antimicrobial resistance: developing a national freshwater pilot effort
Authors: Franklin Alison M. , Weller Daniel L. , Durso Lisa M. , Bagley Mark , Davis Benjamin C. , Frye Jonathan G. , Grim Christopher J. , Ibekwe Abasiofiok M. , Jahne Michael A. , Keely Scott P. , Kraft Autumn L. , McConn Betty R. , Mitchell Richard M. , Ottesen Andrea R. , Sharma Manan , Strain Errol A. , Tadesse Daniel A. , Tate Heather , Wells Jim E. , Williams Clinton F. , Cook Kim L. , Kabera Claudine , McDermott Patrick F. , Garland Jay L.
Published: May 2024

Antimicrobial resistance (AMR) is a world-wide public health threat that is projected to lead to 10 million annual deaths globally by 2050. The AMR public health issue has led to the development of action plans to combat AMR, including improved antimicrobial stewardship, development of new antimicrobials, and advanced monitoring. The National Antimicrobial Resistance Monitoring System (NARMS) led by the United States (U.S) Food and Drug Administration along with the U.S. Centers for Disease Control and U.S. Department of Agriculture has monitored antimicrobial resistant bacteria in retail meats, humans, and food animals since the mid 1990’s. NARMS is currently exploring an integrated One Health monitoring model recognizing that human, animal, plant, and environmental systems are linked to public health. Since 2020, the U.S. Environmental Protection Agency has led an interagency NARMS environmental working group (EWG) to implement a surface water AMR monitoring program (SWAM) at watershed and national scales. The NARMS EWG divided the development of the environmental monitoring effort into five areas: (i) defining objectives and questions, (ii) designing study/sampling design, (iii) selecting AMR indicators, (iv) establishing analytical methods, and (v) developing data management/analytics/metadata plans. For each of these areas, the consensus among the scientific community and literature was reviewed and carefully considered prior to the development of this environmental monitoring program. The data produced from the SWAM effort will help develop robust surface water monitoring programs with the goal of assessing public health risks associated with AMR pathogens in surface water (e.g., recreational water exposures), provide a comprehensive picture of how resistant strains are related spatially and temporally within a watershed, and help assess how anthropogenic drivers and intervention strategies impact the transmission of AMR within human, animal, and environmental systems.
Training a Filter-Based Model of the Cochlea in the Context of Pre-Trained Acoustic Models
Authors: Coppieters de Gibson Louise , Garner Philip N.
Published: May 2024

Auditory research aims in general to lead to understanding of physiological processes. By contrast, the state of the art in automatic speech processing (notably recognition) is dominated by large pre-trained models that are meant to be used as black-boxes. In this work, we integrate a physiologically plausible (albeit simple filter-based) model of the cochlea into a much larger pre-trained acoustic model for speech recognition. We show that the hybrid system can be trained and evaluated with various combinations of fine-tuning and self-supervision. The results broadly show that the system automatically yields structures that are known to work well. Moreover, these structures lack artifacts that were apparent in (our) previous work using less sophisticated neural models. We conclude that the hybrid structure is an appropriate way to proceed in auditory research, more generally allowing the work to take advantage of larger models and databases from which it would not otherwise benefit.
The Development and Validation of a Tool to Evaluate the Determinants of Iron-Rich Food Intake among Adolescent Girls of Senegal
Authors: Ndiaye Aminata Ndene , Dupuis Jérémie B. , Lo Nafissatou Ba , Thiam El Hadj Momar , Sall Mohamadou , Blaney Sonia
Published: May 2024

To reduce anemia among adolescent girls, factors that influence the consumption of iron-rich foods/IRF have not been investigated, and neither has a tool been developed to assess its determinants. Using the extended version of the theory of planned behaviour/eTPB, this study aims to develop and validate a questionnaire assessing individual and environmental factors that could influence IRF intake among Senegalese adolescent girls aged 10–19 years old. First, eight focus group discussions (FGDs) were held in different regions to identify salient beliefs related to each of the four constructs of the eTPB. Information from FGDs was used to develop a questionnaire that was administered to the first group (n = 200) of girls. Principal component and exploratory factorial analyses were then performed to identify latent factors for each construct. A modified version of the tool was administered to the second sample of girls (n = 400), and confirmatory factorial analyses were conducted. Hancock and Muller’s H reliability index was computed on the final model. Most metrics for fit indices were respected, and the H value was satisfactory. This study proposes a tool that could be used to explore determinants of the consumption of IRF among adolescent girls.
Workload Measurement Method for Manned Vehicles in Multitasking Environments
Authors: Yang Chenyuan , Pang Liping , Zhang Jie , Cao Xiaodong
Published: May 2024

Workload (WL) measurement is a crucial foundation for human–machine collaboration, particularly in high-stress multitasking environments such as manned vehicle operations during emergencies, where operators often experience High Workload (HWL) levels, increasing the risk of human error. To address this challenge, this study introduces a novel WL measurement method that combines Task Demand Load (TDL) and Subject Load Capacity (SLC) to quantitatively assess operator workload. This method was validated through experiments with 45 subjects using the Environmental Control and Atmospheric Regeneration (ECAR) system. The statistical results showed that as the designed WL levels increased, the Average Workload (AWL), the NASA-TLX score, and the work time percentage increased significantly, while the task accuracy and the fixation duration decreased significantly. These results also revealed the impact of WL levels on human responses (such as subjective feeling, work performance, and eye movement). In addition, very strong correlations were found between AWL measurements and NASA-TLX scores (r = 0.75, p < 0.01), task accuracy (r = −0.73, p < 0.01), and work time percentage (r = 0.97, p < 0.01). Overall, these results proved the effectiveness of the proposed method for measuring WL. On this basis, this study defined WL thresholds by integrating task accuracy with AWL calculations, providing a framework for the dynamic management of task allocation between humans and machines to maintain operators within optimal WL ranges.
Distributed Hybrid Electric Propulsion Aircraft Design Based on Convex Optimized Power Allocation Management
Authors: Xiao Lingfei , Tan Yushuo , Zhang Xiaole , Han Zirui
Published: May 2024

In order to ensure that aircraft have medium and long-range flights, enhanced aerodynamic performance, and reduced fuel consumption, this paper presents an original Distributed Hybrid Electric Propulsion Aircraft (DHEPA) design scheme and proposes a novel power allocation management method based on convex optimization. Firstly, by taking the Tecnam P2006T general-purpose aircraft as a reference, key components of DHEPA are selected and modeled. Then, a power allocation management method for DHEPA is proposed on the basis of convex optimization, which takes the minimum fuel consumption as the performance index to realize the reasonable power allocation of the battery and engine, while avoiding sliding into the local optimum of allocation. Finally, momentum theory and numerical simulation methods are used to analyze the aerodynamic enhancement effect of the propeller on the wing in the DHEPA, and a dynamics method is utilized to calculate the dynamics performance of the aircraft at several important stages. The results show that, compared with the reference aircraft, the lift of the DHEPA is increased by 46%. Under typical sectors, the DHEPA has a higher rate of climb and maximum leveling off speed at cruise, and a significantly lower fuel consumption.