bluuebunny/crossref_metadata_2025 huggingface dataset:
Software techniques for training restricted Boltzmann machines on size-constrained quantum annealing hardware
Authors: Salmenperä Ilmo , Nurminen Jukka K.
Published: October 2023

Restricted Boltzmann machines are common machine learning models that can utilize quantum annealing devices in their training processes as quantum samplers. While this approach has shown promise as an alternative to classical sampling methods, the limitations of quantum annealing hardware, such as the number of qubits and the lack of connectivity between the qubits, still pose a barrier to wide-scale adoption. We propose the use of multiple software techniques such as dropout method, passive labeling, and parallelization techniques for addressing these hardware limitations. The study found that using these techniques along with quantum sampling showed comparable results to its classical counterparts in certain contexts, while in others the increased complexity of the sampling process hindered the performance of the trained models. This means that further research into the behavior of quantum sampling needs to be done to apply quantum annealing to training tasks of more complicated RBM models.
The value of cardiac magnetic resonance post-contrast T1 mapping in improving the evaluation of myocardial infarction
Authors: Xiang Chunlin , Zhang Hongyan , Li Haojie , Zhou Xiaoyue , Huang Lu , Xia Liming
Published: October 2023

Objective

To explore the additional value of cardiac magnetic resonance (CMR) post-contrast T1 mapping in the detection of myocardial infarction, compared with late gadolinium enhancement (LGE).

Materials and methods

A CMR database of consecutive patients with myocardial infarction was retrospectively analyzed. All patients were scanned at 3 T magnetic resonance; they underwent conventional CMR (including LGE) and post-contrast T1 mapping imaging. Two radiologists interpreted the CMR images using a 16-segment model. The first interpretation included only LGE images. After 30 days, the same radiologists performed a second analysis of random LGE images, with the addition of post-contrast T1 mapping images. Images were analyzed to diagnose myocardial scars, and the transmural extent of each scar was visually evaluated. Diagnoses retained after LGE were compared with diagnoses retained after the addition of post-contrast T1 mapping.

Results

In total, 80 patients (1,280 myocardial segments) were included in the final analysis. After the addition of post-contrast T1 mapping, eight previously unidentified subendocardial scars were detected. Compared with LGE images, the percentage of infarcted segments was higher after the addition of post-contrast T1 mapping images (21.7% vs. 22.3%, P = 0.008), the percentage of uncertain segments was lower after the addition of post-contrast T1 mapping (0.8% vs. 0.1%, P = 0.004), and the percentage of uncertain transmural extent of scarring was lower after the addition of post-contrast T1 mapping (0.9% vs. 0.1%, P = 0.001).

Conclusion

The addition of post-contrast T1 mapping after LGE helps to improve the detection of myocardial infarction, as well as the assessment of the transmural extent of scarring.
Sequence and directivity in cardiac muscle injury of COVID-19 patients: an observational study
Authors: Wang Yixuan , Chen Jianxiong , Jin Lin , Wu Lingheng , Zhang Mengjiao , Sun Jiali , Shen Cuiqin , Du Lianfang , Wang Bei , Li Zhaojun
Published: October 2023

Objective

To compare cardiac function indicators between mild and moderate to severe COVID-19 patients and to try to identify the sequence and directivity in cardiac muscle injury of COVID-19 patients.

Methods

From December 2022 to January 2023, all patients with laboratory-confirmed SARS-CoV-2 infection in Shanghai General Hospital Jiading Branch were enrolled. The clinical classification was stratified into mild, moderate, or severe groups. We collected the clinical and laboratory information, transthoracic echocardiographic and speckle-tracking echocardiographic parameters of patients and compared the differences among different groups.

Results

The values of echocardiographic parameters in mild group were lower than that in moderate or severe group (P < 0.05) except LVEF. The values of LVEF of mild and moderate group were higher than severe group (P < 0.05). There were no significant differences between moderate and severe group. Positive correlations were observed between left ventricular global longitudinal strain (LVGLS) and myoglobin (r = 0.72), E/e' and age (r = 0.79), E/e' and BNP (r = 0.67). The multivariate analysis shows that SpO2 (OR = 0.360, P = 0.02), LVGLS (OR = 3.196, P = 0.003) and E/e' (OR = 1.307, P = 0.036) were the independent risk factors for mild cases progressing to moderate or severe. According to the receiver operating characteristic (ROC) curves, when all the COVID-19 patients was taken as the sample size, the area under the curve (AUC) of the LVGLS was the highest (AUC = 0.861). The AUC of the LVGLS was higher than LVGCS (AUC = 0.565, P < 0.001).

Conclusion

When mild COVID-19 progresses to moderate or severe, both systolic and diastolic functions of the heart are impaired. LVGLS was the independent risk factor for mild cases progressing to moderate or severe cases. Longitudinal changes may manifest earlier than circumferential changes as myocardial disease progresses in COVID-19.
Supra-subduction melt modification of the fossil subcontinental lithospheric mantle: insights from ultra-depleted Khara-Nur ophiolitic peridotites (Eastern Sayan, central Asian orogenic belt)
Authors: Gornova Marina A. , Belyaev Vasiliy A. , Karimov Anas A. , Skuzovatov Sergei Yu. , Karmanov Nikolay S. , Medvedev Alexander Ya. , Bryanskiy Nikolay V.
Published: October 2023

Mantle peridotites from the Mesoproterozoic forearc-type ophiolites in the Eastern Sayan range (Eastern Siberia) provide insights into the nature and formation processes of the supra-subduction mantle. The peridotites are represented by porphyroclastic harzburgites and dunites. The harzburgites have strongly refractory compositions recorded in high Mg# olivine (0.912-0.927) and orthopyroxene (0.916-0.935), high Cr# spinel (0.45-0.66), low Al2O3 and Cr2O3 abundances in orthopyroxene, the lack of residual clinopyroxene, low HREE abundances in orthopyroxene, clinopyroxene and whole-rocks. Some rocks are relatively enriched in SiO2, which is a common feature of supra-subduction (arc and forearc) peridotites and suggests hydrous melting, whereas the rest resemble the chemistry of residues from anhydrous melting of depleted mantle (DM). The whole-rock Al2O3 and Cr-spinel compositions reflect high degrees of partial melting, which initiated in the garnet facies. The Khara-Nur peridotites experienced modification by high-Mg, low-Ti hydrous (boninitic or tholeiitic) arc melts, which crystallized newly-formed minerals (clinopyroxene, Cr-spinel, olivine) in harzburgites. The trace-element composition of clinopyroxene (YbN = 0.5-1.0, La/YbN = 0.05-0.5) resembles that of clinopyroxene from the forearc peridotites and reflects low melt/rock ratio. In dunites, melt percolation resulted in growth of Cr-spinel hosting multiphase inclusions (olivine + clinopyroxene + orthopyroxene + amphibole + phlogopite). Clinopyroxenes from Cr-spinel-hosted inclusions exhibit considerable variations in trace element composition due to heterogeneity of parental melts. Remarkably low Fe3+/∑Fe ratios (0.02-0.12) of Cr-spinels in both harzburgites and dunites are uncommon in SSZ mantle rocks and cannot be explained in terms of the supra-subduction processes, such as partial melting and melt percolation. The whole-rock and mineral compositions of Khara-Nur peridotites, along with previously reported Paleo- to Mesoproterozoic Re-Os model ages, suggest an affinity to ultra-depleted Proterozoic subcontinental lithospheric mantle (SCLM). Overall, the Khara-Nur mantle rocks most likely represent a block of SCLM which underwent melt interaction in a supra-subduction tectonic setting that yielded boninitic and tholeiitic melts comprising now the crustal part of Eastern Sayan ophiolites.
Magnetic characteristics of Chinese archaeological bricks and their implications for archaeomagnetism
Authors: Chen Qiong , Sun Qirui , Liao Lishan , Wang Wei , Yang Xiaoqiang
Published: October 2023

Fired archaeological objects have been widely studied in palaeomagnetic research. However, the uneven heating during the firing process can affected the type, grain size and magnetic domain characteristics of the magnetic carrier, which in turn can led to notable discrepancies in the paleomagnetic information that they captured. In this study, we conducted a detailed rock magnetic study on two Chinese archaeological (one grey and one red) to reveal the properties of magnetic minerals subjected to different firing temperatures. Our results show that single domain (SD) magnetite with strong magnetostatic interactions is the dominant magnetic carrier in grey bricks, while SD magnetite with weak magnetostatic interactions is the dominant magnetic carrier in the red bricks. And stepwise heating results show that the firing temperature of the grey brick and the outer layers of red brick (R-1, R-3) is above 700°C, while the inner layer (R-2) of red brick shows a thermal transformation process at ∼ 350°C. This uneven heating may cause the spatial discrepancies in magnetic parameters such as the mass-normalized magnetic susceptibility (χ) and natural remanent magnetization (NRM) in red brick. Nevertheless, the direction of the geomagnetic field can be accurately obtained even if the brick is not heated evenly. However, more work is needed to explore the paleointensity behavior at different firing temperatures.
Comparison of prognosis after partial and total surgical resection for parathyroid carcinoma: an inverse probability of treatment weighting analysis of the SEER database
Authors: Jin Shuai , Cho William C. , Yang Jiaxi , Xia Kaide , Zhou Changxi
Published: October 2023

Background

Complete resection of the tumor and the ipsilateral thyroid lobe at the primary surgery is the “gold standard” for the treatment of parathyroid carcinoma (PC). However, differences in the overall survival (OS) of patients with PC who underwent partial and total surgical resection remain to be determined.

Methods

Data on patients with PC who underwent partial and total surgical resection were extracted from the Surveillance, Epidemiology and End Results (SEER) database (2000–2018). The X-tile software (https://medicine.yale.edu/lab/rimm/research/software/) was used to define the optimal cut-off values for continuous variables. The inverse probability of treatment weighting (IPTW) method was used to reduce the selection bias. IPTW-adjusted Kaplan–Meier curves and Cox proportional hazards models were used to compare the OS of patients with PC in the partial and total surgical resection groups.

Results

A total of 334 patients with PC were included in this study (183 and 151 in the partial and total surgical resection groups, respectively). The optimal cut-off values for age at diagnosis were 53 and 73 years, respectively, while that for tumor size was 34 mm. In both the Kaplan–Meier analysis and univariable Cox proportional hazards regression analysis before IPTW, the difference in OS between the partial and total surgical resection groups was not statistically significant (p>0.05). These findings were confirmed in the IPTW-adjusted Kaplan–Meier analysis and multivariate Cox proportional hazards regression analysis (p>0.05). Subgroup analysis revealed that total surgical resection was beneficial for OS only in the subgroup with unknown tumor size.

Conclusion

There was no significant difference in the prognosis of patients who underwent partial and total surgical resection. This finding may provide a useful reference for the treatment of PC.
Are all HCL systems the same? long term outcomes of three HCL systems in children with type 1 diabetes: real-life registry-based study
Authors: Santova Alzbeta , Plachy Lukas , Neuman Vit , Pavlikova Marketa , Petruzelkova Lenka , Konecna Petra , Venhacova Petra , Skvor Jaroslav , Pomahacova Renata , Neumann David , Vosahlo Jan , Strnadel Jiri , Kocourkova Kamila , Obermannova Barbora , Pruhova Stepanka , Cinek Ondrej , Sumnik Zdenek
Published: October 2023

Objective

To compare parameters of glycemic control among three types of hybrid closed loop (HCL) systems in children with T1D (CwD) using population-wide data from the national pediatric diabetes registry ČENDA.

Methods

CwD aged <19 years treated with Medtronic MiniMed 780G (780G), Tandem t:slim X2 (Control-IQ) or do-it-yourself AndroidAPS (AAPS) systems for >12 months and monitored by CGM >70% of the time were included. HbA1c, times in glycemic ranges, and Glycemia Risk Index (GRI) were used for cross-sectional comparison between the HCL systems.

Results

Data from 512 CwD were analyzed. 780G, Control-IQ and AAPS were used by 217 (42.4%), 211 (41.2%), and 84 (16.4%) CwD, respectively. The lowest HbA1c value was observed in the AAPS group (44 mmol/mol; IQR 8.0, p<0.0001 vs any other group), followed by Control-IQ and 780G groups (48 (IQR 11) and 52 (IQR 10) mmol/mol, respectively). All of the systems met the recommended criteria for time in range (78% in AAPS, 76% in 780G, and 75% in Control-IQ users). CwD using AAPS spent significantly more time in hypoglycemia (5% vs 2% in 780G and 3% in Control-IQ) and scored the highest GRI (32, IQR 17). The lowest GRI (27, IQR 15) was seen in 780G users.

Conclusion

Although all HCL systems proved effective in maintaining recommended long-term glycemic control, we observed differences that illustrate strengths and weaknesses of particular systems. Our findings could help in individualizing the choice of HCL systems.
Experimental study on helical tubes heat transfer characteristics considering corrosion products
Authors: Yulong Mao , Shuqi Meng , Xianghui Lu , Desheng Jin , Xiaoting Wang , Kejia Li , Yisong Hu , Yousen Hu , Min Rui
Published: October 2023

During the power operation of nuclear reactors, the corrosion products in the secondary circuit will deposit on the inside of Helical-coiled One-Through Steam Generator (H-OTSG) heat transfer tubes and form fouling. The main component of fouling is iron-based oxide, which generates from the heat exchangers made of cast iron. Fouling may change the local heat transfer characteristics of heat transfer tubes, and then affect the safety and economy of reactors. In order to obtain the distribution of fouling thickness and its action mechanism on helical tubes heat transfer characteristics, the heat transfer experiment under small pressurized reactors service environment was conducted. The experimental results indicate: corrosion products mainly deposit on onset of saturated boiling point with the maximum fouling thickness of 50 μm, and induce local wall temperature elevating about 773 K; fouling will increase the thermal equilibrium void fraction and hinder the heat transfer of helical tube, but has little impact on the onset position of saturated boiling point; corrosion products will release and re-deposit near dry-out point because of the flush of high speed vapor, causing the periodic fluctuation of thermal resistance of helical tube.
Trypanosoma cruzi P21 recombinant protein modulates Toxoplasma gondii infection in different experimental models of the human maternal–fetal interface
Authors: de Souza Guilherme , Teixeira Samuel Cota , Fajardo Martínez Aryani Felixa , Silva Rafaela José , Luz Luana Carvalho , Lima Júnior Joed Pires de , Rosini Alessandra Monteiro , dos Santos Natália Carine Lima , de Oliveira Rafael Martins , Paschoalino Marina , Barbosa Matheus Carvalho , Alves Rosiane Nascimento , Gomes Angelica Oliveira , da Silva Claudio Vieira , Ferro Eloisa Amália Vieira , Barbosa Bellisa Freitas
Published: October 2023

Introduction

Toxoplasma gondii is the etiologic agent of toxoplasmosis, a disease that affects about one-third of the human population. Most infected individuals are asymptomatic, but severe cases can occur such as in congenital transmission, which can be aggravated in individuals infected with other pathogens, such as HIV-positive pregnant women. However, it is unknown whether infection by other pathogens, such as Trypanosoma cruzi, the etiologic agent of Chagas disease, as well as one of its proteins, P21, could aggravate T. gondii infection.

Methods

In this sense, we aimed to investigate the impact of T. cruzi and recombinant P21 (rP21) on T. gondii infection in BeWo cells and human placental explants.

Results

Our results showed that T. cruzi infection, as well as rP21, increases invasion and decreases intracellular proliferation of T. gondii in BeWo cells. The increase in invasion promoted by rP21 is dependent on its binding to CXCR4 and the actin cytoskeleton polymerization, while the decrease in proliferation is due to an arrest in the S/M phase in the parasite cell cycle, as well as interleukin (IL)-6 upregulation and IL-8 downmodulation. On the other hand, in human placental villi, rP21 can either increase or decrease T. gondii proliferation, whereas T. cruzi infection increases T. gondii proliferation. This increase can be explained by the induction of an anti-inflammatory environment through an increase in IL-4 and a decrease in IL-6, IL-8, macrophage migration inhibitory factor (MIF), and tumor necrosis factor (TNF)-α production.

Discussion

In conclusion, in situations of coinfection, the presence of T. cruzi may favor the congenital transmission of T. gondii, highlighting the importance of neonatal screening for both diseases, as well as the importance of studies with P21 as a future therapeutic target for the treatment of Chagas disease, since it can also favor T. gondii infection.
Single-nuclei RNA-seq reveals skin cell responses to Aeromonas hydrophila infection in Chinese longsnout catfish Leiocassis longirostris
Authors: Mou Cheng-Yan , Zhang Lu , Zhao Han , Huang Zhi-Peng , Duan Yuan-Liang , Zhao Zhong-Meng , Ke Hong-Yu , Du Jun , Li Qiang , Zhou Jian
Published: October 2023

As the primary natural barrier that protects against adverse environmental conditions, the skin plays a crucial role in the innate immune response of fish, particularly in relation to bacterial infections. However, due to the diverse functionality and intricate anatomical and cellular composition of the skin, deciphering the immune response of the host is a challenging task. In this study, single nuclei RNA-sequencing (snRNA-seq) was performed on skin biopsies obtained from Chinese longsnout catfish (Leiocassis longirostris), comparing Aeromonas hydrophila-infected subjects to healthy control subjects. A total of 19,581 single nuclei cells were sequenced using 10x Genomics (10,400 in the control group and 9,181 in the treated group). Based on expressed unique transcriptional profiles, 33 cell clusters were identified and classified into 12 cell types including keratinocyte (KC), fibroblast (FB), endothelial cells (EC), secretory cells (SC), immune cells, smooth muscle cells (SMC), and other cells such as pericyte (PC), brush cell (BC), red blood cell (RBC), neuroendocrine cell (NDC), neuron cells (NC), and melanocyte (MC). Among these, three clusters of KCs, namely, KC1, KC2, and KC5 exhibited significant expansion after A. hydrophila infection. Analysis of pathway enrichment revealed that KC1 was primarily involved in environmental signal transduction, KC2 was primarily involved in endocrine function, and KC5 was primarily involved in metabolism. Finally, our findings suggest that neutrophils may play a crucial role in combating A. hydrophila infections. In summary, this study not only provides the first detailed comprehensive map of all cell types present in the skin of teleost fish but also sheds light on the immune response mechanism of the skin following A. hydrophila infection in Chinese longsnout catfish.
Single-cell RNAseq identifies clonally expanded antigen-specific T-cells following intradermal injection of gold nanoparticles loaded with diabetes autoantigen in humans
Authors: Hanna Stephanie J. , Thayer Terri C. , Robinson Emma J. S. , Vinh Ngoc-Nga , Williams Nigel , Landry Laurie G. , Andrews Robert , Siah Qi Zhuang , Leete Pia , Wyatt Rebecca , McAteer Martina A. , Nakayama Maki , Wong F. Susan , Yang Jennie H. M. , Tree Timothy I. M. , Ludvigsson Johnny , Dayan Colin M. , Tatovic Danijela
Published: October 2023

Gold nanoparticles (GNPs) have been used in the development of novel therapies as a way of delivery of both stimulatory and tolerogenic peptide cargoes. Here we report that intradermal injection of GNPs loaded with the proinsulin peptide C19-A3, in patients with type 1 diabetes, results in recruitment and retention of immune cells in the skin. These include large numbers of clonally expanded T-cells sharing the same paired T-cell receptors (TCRs) with activated phenotypes, half of which, when the TCRs were re-expressed in a cell-based system, were confirmed to be specific for either GNP or proinsulin. All the identified gold-specific clones were CD8+, whilst proinsulin-specific clones were both CD8+ and CD4+. Proinsulin-specific CD8+ clones had a distinctive cytotoxic phenotype with overexpression of granulysin (GNLY) and KIR receptors. Clonally expanded antigen-specific T cells remained in situ for months to years, with a spectrum of tissue resident memory and effector memory phenotypes. As the T-cell response is divided between targeting the gold core and the antigenic cargo, this offers a route to improving resident memory T-cells formation in response to vaccines. In addition, our scRNAseq data indicate that focusing on clonally expanded skin infiltrating T-cells recruited to intradermally injected antigen is a highly efficient method to enrich and identify antigen-specific cells. This approach has the potential to be used to monitor the intradermal delivery of antigens and nanoparticles for immune modulation in humans.
Innate lymphoid cells: a new key player in atopic dermatitis
Authors: Jia Haiping , Wan Huiying , Zhang Dingding
Published: October 2023

Atopic dermatitis (AD) is a common allergic inflammatory skin condition mainly caused by gene variants, immune disorders, and environmental risk factors. The T helper (Th) 2 immune response mediated by interleukin (IL)-4/13 is generally believed to be central in the pathogenesis of AD. It has been shown that innate lymphoid cells (ILCs) play a major effector cell role in the immune response in tissue homeostasis and inflammation and fascinating details about the interaction between innate and adaptive immunity. Changes in ILCs may contribute to the onset and progression of AD, and ILC2s especially have gained much attention. However, the role of ILCs in AD still needs to be further elucidated. This review summarizes the role of ILCs in skin homeostasis and highlights the signaling pathways in which ILCs may be involved in AD, thus providing valuable insights into the behavior of ILCs in skin homeostasis and inflammation, as well as new approaches to treating AD.
Proper development of long-lived memory CD4 T cells requires HLA-DO function
Authors: Song Nianbin , Welsh Robin A. , Sadegh-Nasseri Scheherazade
Published: October 2023

Introduction

HLA-DO (DO) is an accessory protein that binds DM for trafficking to MIIC and has peptide editing functions. DO is mainly expressed in thymic medulla and B cells. Using biochemical experiments, our lab has discovered that DO has differential effects on editing peptides of different sequences: DO increases binding of DM-resistant peptides and reduces the binding of DM-sensitive peptides to the HLA-DR1 molecules. In a separate line of work, we have established that appropriate densities of antigen presentation by B cells during the contraction phase of an infection, induces quiescence in antigen experienced CD4 T cells, as they differentiate into memory T cells. This quiescence phenotype helps memory CD4 T cell survival and promotes effective memory responses to secondary Ag challenge.

Methods

Based on our mechanistic understanding of DO function, it would be expected that if the immunodominant epitope of antigen is DM-resistant, presentation of decreased densities of pMHCII by B cells would lead to faulty development of memory CD4 T cells in the absence of DO. We explored the effects of DO on development of memory CD4 T cells and B cells utilizing two model antigens, H5N1-Flu Ag bearing DM-resistant, and OVA protein, which has a DM-sensitive immunodominant epitope and four mouse strains including two DO-deficient Tg mice. Using Tetramers and multiple antibodies against markers of memory CD4 T cells and B cells, we tracked memory development.

Results

We found that immunized DR1+DO-KO mice had fewer CD4 memory T cells and memory B cells as compared to the DR1+DO-WT counterpart and had compromised recall responses. Conversely, OVA specific memory responses elicited in HA immunized DR1+DO-KO mice were normal.

Conclusion

These results demonstrate that in the absence of DO, the presentation of cognate foreign antigens in the DO-KO mice is altered and can impact the proper development of memory cells. These findings provide new insights on vaccination design leading to better immune memory responses.
Understanding knowledge, perception, and willingness of non-invasive prenatal testing for fetal aneuploidy: a survey among Chinese high-risk pregnant women
Authors: Zhao Yi , Xue Zhu , Geng Yarui , Zhu Jie , Hu Maidan , Jiang Minmin
Published: October 2023

Objectives

Non-invasive prenatal testing (NIPT) is utilized for screening the likelihood of fetal aneuploidy, presenting the benefits of non-invasiveness, high sensitivity, and specificity. Its application in prenatal screening has become ubiquitous. The inquiry into how pregnant women comprehend and determine NIPT screening strategies is paramount. Regrettably, there has been a dearth of research on this subject in China. Consequently, this study scrutinizes pregnant women’s cognizance and perspectives concerning NIPT, furnishing a foundation for advancing its judicious implementation.

Methods

From February 2021 to December 2022, a questionnaire survey was conducted among pregnant women receiving prenatal care and screening at the Women’s Hospital, School of Medicine, Zhejiang University, who were randomly selected from a pool of individuals exhibiting a high risk of fetal aneuploidy on serological screening. The survey aimed to gather data on participant characteristics, knowledge, perception, and willingness concerning NIPT. The study employed chi-square and Kruskal Wallis tests to analyze subgroup differences.

Results

A total of 226 valid questionnaires were obtained. 83.2% of women pregnant women identified as high risk by serological screening would opt for NIPT, with 66.4% indicating that they would prefer NIPT for fetal aneuploidy screening in future pregnancies. These findings suggest a notable willingness among pregnant women to undergo NIPT. Additionally, the results suggest that various factors, including place of residence, educational level, family income, causes of abortion, and conception method, influence pregnant women’s knowledge about NIPT Accordingly, the level of NIPT knowledge varies among pregnant women.

Conclusion

The survey generally revealed that pregnant women were strongly inclined to select NIPT; however, expectant Chinese mothers possess limited knowledge and perception regarding this screening method for fetal aneuploidy. Therefore, the government must implement effective measures to augment public awareness of fetal aneuploidy screening and encourage the judicious utilization of NIPT.
Peripapillary choroidal vascularity index and thickness in patients with systemic sclerosis
Authors: Pieklarz Barbara , Gińdzieńska-Sieśkiewicz Ewa , Zawadzka Izabela , Bagrowska Magdalena , Daniluk Joanna , Sidorczuk Patryk , Kowal-Bielecka Otylia , Konopińska Joanna , Dmuchowska Diana Anna
Published: October 2023

Introduction

Patients with systemic sclerosis (SSc) present an increased risk of developing glaucomatous optic neuropathy (GON). We investigated peripapillary choroidal parameters and peripapillary retinal nerve fiber layer (RNFL) thickness using spectral domain optical coherence tomography (SD-OCT) to determine the relationships of these factors with clinical variables.

Methods

A total of 33 patients with SSc were enrolled and compared to 40 controls. After obtaining circular scans around the optic disc, the global and quadrant peripapillary choroidal thickness (pCT) and RNFL thickness were measured. Additionally, the peripapillary choroidal vascularity index (pCVI), which allows for a quantitative analysis of the choroidal vasculature, was determined.

Results

No significant differences were found in pCT and RNFL thickness between patients with SSc and controls, or within SSc subtypes (diffuse cutaneous systemic sclerosis (dcSSc) compared to limited cutaneous systemic sclerosis (lcSSc)) (p > 0.05). The pCVI was significantly lower in patients with SSc than in control subjects (64.25 ± 1.94 vs.65.73 ± 2.12, p < 0.001).

Conclusion

Our results suggest that the statistically significant decrease in pCVI in patients with SSc compared to the control group is probably due to a decrease in the vascular layer, which would partially explain an increased risk of GON in patients with SSc.
Finding and treating both tuberculosis disease and latent infection during population-wide active case finding for tuberculosis elimination
Authors: Coleman Mikaela , Nguyen Thu-Anh , Luu Boi Khanh , Hill Jeremy , Ragonnet Romain , Trauer James M. , Fox Greg J. , Marks Guy B. , Marais Ben J.
Published: October 2023

In recognition of the high rates of undetected tuberculosis in the community, the World Health Organization (WHO) encourages targeted active case finding (ACF) among “high-risk” populations. While this strategy has led to increased case detection in these populations, the epidemic impact of these interventions has not been demonstrated. Historical data suggest that population-wide (untargeted) ACF can interrupt transmission in high-incidence settings, but implementation remains lacking, despite recent advances in screening tools. The reservoir of latent infection—affecting up to a quarter of the global population –complicates elimination efforts by acting as a pool from which future tuberculosis cases may emerge, even after all active cases have been treated. A holistic case finding strategy that addresses both active disease and latent infection is likely to be the optimal approach for rapidly achieving sustainable progress toward TB elimination in a durable way, but safety and cost effectiveness have not been demonstrated. Sensitive, symptom-agnostic community screening, combined with effective tuberculosis treatment and prevention, should eliminate all infectious cases in the community, whilst identifying and treating people with latent infection will also eliminate tomorrow’s tuberculosis cases. If real strides toward global tuberculosis elimination are to be made, bold strategies are required using the best available tools and a long horizon for cost-benefit assessment.
Modified N-acyl-L-homoserine lactone compounds abrogate Las-dependent quorum-sensing response in human pathogen Pseudomonas aeruginosa
Authors: Ballante Flavio , Turkina Maria V. , Ntzouni Maria , Magnusson Karl-Eric , Vikström Elena
Published: October 2023

Quorum sensing (QS) is a mode of cell–cell communication that bacteria use to sense population density and orchestrate collective behaviors. The common opportunistic human pathogen Pseudomonas aeruginosa employs QS to regulate a large set of genes involved in virulence and host–pathogen interactions. The Las circuit positioned on the top of the QS hierarchy in P. aeruginosa makes use of N-acyl-L-homoserine lactones (AHLs) as signal molecules, like N-3-oxo-dodecanoyl-L-homoserine lactone (3O-C12-HSL). Disabling QS circuits by certain small-molecule compounds, known as quorum-sensing inhibitors (QSIs), has been proposed as a strategy to attenuate bacterial pathogenicity. In this study, four new AHL analogs were designed by incorporating a tert-butoxycarbonyl Boc group in amide and β-keto (3-oxo) moiety. Compounds were evaluated on a molecular and phenotypic basis as a QSI using the screening strategy linked to the assignment of the Las QS system in P. aeruginosa. Using a LasR-based bioreporter, we found that the compounds decreased LasR-controlled light activity and competed efficiently with natural 3O-C12-HSL. The compounds reduced the production of the cognate 3O-C12-HSL and certain virulence traits, like total protease activity, elastase activity, pyocyanin production, and extracellular DNA release. Furthermore, a quantitative proteomic approach was used to study the effect of the compounds on QS-regulated extracellular proteins. Among the four compounds tested, one of them showed the most significant difference in the appearance of the 3O-C12-HSL-responsive reference proteins related to QS communication and virulence, i.e., a distinct activity as a QSI. Moreover, by combining experimental data with computational chemistry, we addressed the effect of LasR protein flexibility on docking precision and assessed the advantage of using a multi-conformational docking procedure for binding mode prediction of LasR modulators. Thus, the four new AHL compounds were tested for their interaction with the AHL-binding site in LasR to identify the key interferences with the activity of LasR. Our study provides further insight into molecular features that are required for small-molecule modulation of LasR-dependent QS communication in P. aeruginosa. This should facilitate rational design of the next generation of antivirulence tools to study and manipulate QS-controlled fitness in bacteria and, thereby, handle bacterial infections in a new way.
Past and present experience shifts audiovisual temporal perception in rats
Authors: Al-youzbaki Mohammed U. , Schormans Ashley L. , Allman Brian L.
Published: October 2023

Our brains have a propensity to integrate closely-timed auditory and visual stimuli into a unified percept; a phenomenon that is highly malleable based on prior sensory experiences, and is known to be altered in clinical populations. While the neural correlates of audiovisual temporal perception have been investigated using neuroimaging and electroencephalography techniques in humans, animal research will be required to uncover the underlying cellular and molecular mechanisms. Prior to conducting such mechanistic studies, it is important to first confirm the translational potential of any prospective animal model. Thus, in the present study, we conducted a series of experiments to determine if rats show the hallmarks of audiovisual temporal perception observed in neurotypical humans, and whether the rat behavioral paradigms could reveal when they experienced perceptual disruptions akin to those observed in neurodevelopmental disorders. After training rats to perform a temporal order judgment (TOJ) or synchrony judgment (SJ) task, we found that the rats’ perception was malleable based on their past and present sensory experiences. More specifically, passive exposure to asynchronous audiovisual stimulation in the minutes prior to behavioral testing caused the rats’ perception to predictably shift in the direction of the leading stimulus; findings which represent the first time that this form of audiovisual perceptual malleability has been reported in non-human subjects. Furthermore, rats performing the TOJ task also showed evidence of rapid recalibration, in which their audiovisual temporal perception on the current trial was predictably influenced by the timing lag between the auditory and visual stimuli in the preceding trial. Finally, by manipulating either experimental testing parameters or altering the rats’ neurochemistry with a systemic injection of MK-801, we showed that the TOJ and SJ tasks could identify when the rats had difficulty judging the timing of audiovisual stimuli. These findings confirm that the behavioral paradigms are indeed suitable for future testing of rats with perceptual disruptions in audiovisual processing. Overall, our collective results highlight that rats represent an excellent animal model to study the cellular and molecular mechanisms underlying the acuity and malleability of audiovisual temporal perception, as they showcase the perceptual hallmarks commonly observed in humans.
Ecological validity of a deep learning algorithm to detect gait events from real-life walking bouts in mobility-limiting diseases
Authors: Romijnders Robbin , Salis Francesca , Hansen Clint , Küderle Arne , Paraschiv-Ionescu Anisoara , Cereatti Andrea , Alcock Lisa , Aminian Kamiar , Becker Clemens , Bertuletti Stefano , Bonci Tecla , Brown Philip , Buckley Ellen , Cantu Alma , Carsin Anne-Elie , Caruso Marco , Caulfield Brian , Chiari Lorenzo , D'Ascanio Ilaria , Del Din Silvia , Eskofier Björn , Fernstad Sara Johansson , Fröhlich Marceli Stanislaw , Garcia Aymerich Judith , Gazit Eran , Hausdorff Jeffrey M. , Hiden Hugo , Hume Emily , Keogh Alison , Kirk Cameron , Kluge Felix , Koch Sarah , Mazzà Claudia , Megaritis Dimitrios , Micó-Amigo Encarna , Müller Arne , Palmerini Luca , Rochester Lynn , Schwickert Lars , Scott Kirsty , Sharrack Basil , Singleton David , Soltani Abolfazl , Ullrich Martin , Vereijken Beatrix , Vogiatzis Ioannis , Yarnall Alison , Schmidt Gerhard , Maetzler Walter
Published: October 2023

Introduction

The clinical assessment of mobility, and walking specifically, is still mainly based on functional tests that lack ecological validity. Thanks to inertial measurement units (IMUs), gait analysis is shifting to unsupervised monitoring in naturalistic and unconstrained settings. However, the extraction of clinically relevant gait parameters from IMU data often depends on heuristics-based algorithms that rely on empirically determined thresholds. These were mainly validated on small cohorts in supervised settings.

Methods

Here, a deep learning (DL) algorithm was developed and validated for gait event detection in a heterogeneous population of different mobility-limiting disease cohorts and a cohort of healthy adults. Participants wore pressure insoles and IMUs on both feet for 2.5 h in their habitual environment. The raw accelerometer and gyroscope data from both feet were used as input to a deep convolutional neural network, while reference timings for gait events were based on the combined IMU and pressure insoles data.

Results and discussion

The results showed a high-detection performance for initial contacts (ICs) (recall: 98%, precision: 96%) and final contacts (FCs) (recall: 99%, precision: 94%) and a maximum median time error of −0.02 s for ICs and 0.03 s for FCs. Subsequently derived temporal gait parameters were in good agreement with a pressure insoles-based reference with a maximum mean difference of 0.07, −0.07, and <0.01 s for stance, swing, and stride time, respectively. Thus, the DL algorithm is considered successful in detecting gait events in ecologically valid environments across different mobility-limiting diseases.
RETRACTED: Spermatogonial stem-cell-derived neural-like cell transplantation enhances the functional recovery of a rat spinal cord injury model: characterization of evoked potentials
Authors: Guo Xinyu , Jiang Chao , Zhang Yongjie , Chen Zhe , Hao Dingjun , Zhang Haihong
Published: October 2023

Severe spinal cord injuries (SCIs) usually result in the temporary or permanent impairment of strength, sensation or autonomic functions below the sites of injuries. To date, a large number of therapeutic approaches have been used to ameliorate SCIs, and subsequent stem cell transplantation appears to be a promising strategy. The aim of this study was to evaluate the therapeutic effect of stem cells by changes in the evoked potentials at different time points after a transplantation of spermatogonial stem cells (SSCs) to differentiate the source neurons in a rat model with SCIs, as well as through histopathology. A modified Plemel spinal cord lateral compression model was used. The experiment was divided into a blank, a control and a SSC transplantation group. Motor activity scores, sensory evoked potentials (SEPs) and motor evoked potentials (MEPs) were assessed through motor resuscitation as well as histologic evaluation on each experimental group to determine the improvement. Consistent with our results, motor scores and evoked potentials were significantly improved in the SSC transplantation group. In addition, a histologic assessment showed that the transplanted stem cells had a significant restorative effect on the reconstruction of tissue cells. 1 week after the stem cell transplantation, the SSC transplantation group showed improvement in spinal cord functions and spinal cord pathologic injuries. After 2 weeks and beyond, the SSC transplantation group showed significant improvement in spinal cord functions and spinal cord pathology compared to the control group, meanwhile the evoked potentials and motor function of the hind limbs of rats in the SSC transplantation group were significantly improved. Therefore, the therapeutic strategies for spermatogonial stem cells will be an effective program in the study on SCIs, and we suggest the somatosensory evoked potentials as a tool to assess the degree of recovery from SCIs after the transplantation of stem cells.
Limosilactobacillus reuteri DSM 17938 reverses gut metabolic dysfunction induced by Western diet in adult rats
Authors: Abuqwider Jumana , Di Porzio Angela , Barrella Valentina , Gatto Cristina , Sequino Giuseppina , De Filippis Francesca , Crescenzo Raffaella , Spagnuolo Maria Stefania , Cigliano Luisa , Mauriello Gianluigi , Iossa Susanna , Mazzoli Arianna
Published: October 2023

Introduction

Microencapsulation of probiotic bacteria is an efficient and innovative new technique aimed at preserving bacterial survival in the hostile conditions of the gastrointestinal tract. However, understanding whether a microcapsule preserves the effectiveness of the bacterium contained within it is of fundamental importance.

Methods

Male Wistar rats aged 90 days were fed a control diet or a Western diet for 8 weeks, with rats fed the Western diet divided into three groups: one receiving the diet only (W), the second group receiving the Western diet and free L. reuteri DSM 17938 (WR), and the third group receiving the Western diet and microencapsulated L. reuteri DSM 17938 (WRM). After 8 weeks of treatment, gut microbiota composition was evaluated, together with occludin, one of the tight junction proteins, in the ileum and the colon. Markers of inflammation were also quantified in the portal plasma, ileum, and colon, as well as markers for gut redox homeostasis.

Results

The Western diet negatively influenced the intestinal microbiota, with no significant effect caused by supplementation with free and microencapsulated L. reuteri. However, L. reuteri, in both forms, effectively preserved the integrity of the intestinal barrier, thus protecting enterocytes from the development of inflammation and oxidative stress.

Conclusion

From these whole data, it emerges that L. reuteri DSM 17938 can be an effective probiotic in preventing the unhealthy consequences of the Western diet, especially in the gut, and that microencapsulation preserves the probiotic effects, thus opening the formulation of new preparations to be able to improve gut function independent of dietary habits.
Combined deep-learning MRI-based radiomic models for preoperative risk classification of endometrial endometrioid adenocarcinoma
Authors: Yang Jin , Cao Yuying , Zhou Fangzhu , Li Chengyao , Lv Jiabei , Li Pu
Published: October 2023

Background

Differences exist between high- and low-risk endometrial cancer (EC) in terms of whether lymph node dissection is performed. Factors such as tumor grade, myometrial invasion (MDI), and lymphovascular space invasion (LVSI) in the European Society for Medical Oncology (ESMO), European SocieTy for Radiotherapy & Oncology (ESTRO) and European Society of Gynaecological Oncology (ESGO) guidelines risk classification can often only be accurately assessed postoperatively. The aim of our study was to estimate the risk classification of patients with endometrial endometrioid adenocarcinoma before surgery and offer individualized treatment plans based on their risk classification.

Methods

Clinical information and last preoperative pelvic magnetic resonance imaging (MRI) of patients with postoperative pathologically determined endometrial endometrioid adenocarcinoma were collected retrospectively. The region of interest (ROI) was subsequently plotted in T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and diffusion-weighted imaging (DWI) MRI scans, and the traditional radiomics features and deep-learning image features were extracted. A final radiomics nomogram model integrating traditional radiomics features, deep learning image features, and clinical information was constructed to distinguish between low- and high-risk patients (based on the 2020 ESMO-ESGO-ESTRO guidelines). The efficacy of the model was evaluated in the training and validation sets of the model.

Results

We finally included 168 patients from January 1, 2020 to July 29, 2021, of which 95 patients in 2021 were classified as the training set and 73 patients in 2020 were classified as the validation set. In the training set, the area under the curve (AUC) of the radiomics nomogram was 0.923 (95%CI: 0.865–0.980) and in the validation set, the AUC of the radiomics nomogram was 0.842 (95%CI: 0.762–0.923). The nomogram had better predictions than both the traditional radiomics model and the deep-learning radiomics model.

Conclusion

MRI-based radiomics models can be useful for preoperative risk classification of patients with endometrial endometrioid adenocarcinoma.
SET-CAN/NUP214 fusion gene in leukemia: general features and clinical advances
Authors: Song Jingyu , Li Huibo , Fan Shengjin
Published: October 2023

SET-CAN/NUP214 fusion is a recurrent event commonly observed in adult male patients diagnosed with T-cell acute lymphoblastic leukemia (T-ALL) and has occasionally been reported in other diseases such as acute myeloid leukemia (AML), myeloid sarcoma (MS), acute undifferentiated leukemia (AUL), chronic myeloid leukemia (CML) and B-cell acute lymphoblastic leukemia (B-ALL). This fusion gene is derived from chromosome del(9)(q34.11;q34.13) or t(9;9)(q34;q34) and may have an inhibitory effect on primitive progenitor differentiation. The prognosis of the reported patients is varied, with these patients often show resistance to chemotherapy regimens that include high doses of glucocorticoids. The optional treatment has not been determined, more cases need to be accumulated and evaluated. The scope of this review is to summarize the general features and prognostic significance in leukemia associated with the SET-CAN/NUP214 fusion gene and to discuss the methods of detection and treatment, aiming at providing some useful references for relevant researchers in the field of blood tumor.