bluuebunny/crossref_metadata_2025 huggingface dataset:
National ground-level NO2 predictions via satellite imagery driven convolutional neural networks
Authors: Cao Elton L.
Published: December 2023

Outdoor air pollution, specifically nitrogen dioxide (NO2), poses a global health risk. Land use regression (LUR) models are widely used to estimate ground-level NO2 concentrations by describing the satellite land use characteristics of a given location using buffer distance averages of variables. However, information may be leaked in this approach as averages ignore the variances within the averaged region. Therefore, in this study, we leverage a convolutional neural network (CNN) architecture to directly pass data grids of various satellite data for the prediction of U.S. national ground-level NO2. We designed CNN architectures of various complexity which inputs both satellite and meteorological reanalysis data, testing both high and low resolution data grids. Our resulting model accurately predicted NO2 concentrations at both daily (R2 = 0.892, RMSE = 2.259, MAE = 1.534) and annual (R2 = 0.952, RMSE = 0.988, MAE = 0.690) temporal scales, with coarse resolution imagery and simple CNN architectures displaying the best and most efficient performance. Furthermore, the CNN outperforms traditional buffer distance models, including random forest (RF), feedforward neural network (FNN), and multivariate linear regression (MLR) approaches, resulting in the MLR performing the poorest at daily (R2 = 0.625, RMSE = 4.281, MAE = 3.102) and annual (R2 = 0.758, RMSE = 2.218, MAE = 1.652) scales. With the success of the CNN in this approach, satellite land use variables continue to be useful for the prediction of NO2. Using this computationally inexpensive model, we encourage the globalization of advanced LUR models as a low-cost alternative to traditional NO2 monitoring.
Targeting colorectal cancer cells using AND-gated adaptor RevCAR T-cells
Authors: Soto Karla E. G. , Loureiro Liliana R. , Bartsch Tabea , Arndt Claudia , Kegler Alexandra , Mitwasi Nicola , Drewitz Laura , Hoffmann Lydia , Saleh Haidy A. , Crespo Eugenia , Mehnert Maria , Daglar Cansu , Abken Hinrich , Momburg Frank , Bachmann Michael , Feldmann Anja
Published: December 2023

Despite the success of chimeric antigen receptor (CAR) T-cells especially for treating hematological malignancies, critical drawbacks, such as “on-target, off-tumor” toxicities, need to be addressed to improve safety in translating to clinical application. This is especially true, when targeting tumor-associated antigens (TAAs) that are not exclusively expressed by solid tumors but also on hea9lthy tissues. To improve the safety profile, we developed switchable adaptor CAR systems including the RevCAR system. RevCAR T-cells are activated by cross-linking of bifunctional adaptor molecules termed target modules (RevTM). In a further development, we established a Dual-RevCAR system for an AND-gated combinatorial targeting by splitting the stimulatory and co-stimulatory signals of the RevCAR T-cells on two individual CARs. Examples of common markers for colorectal cancer (CRC) are the carcinoembryonic antigen (CEA) and the epithelial cell adhesion molecule (EpCAM), while these antigens are also expressed by healthy cells. Here we describe four novel structurally different RevTMs for targeting of CEA and EpCAM. All anti-CEA and anti-EpCAM RevTMs were validated and the simultaneous targeting of CEA+ and EpCAM+ cancer cells redirected specific in vitro and in vivo killing by Dual-RevCAR T-cells. In summary, we describe the development of CEA and EpCAM specific adaptor RevTMs for monospecific and AND-gated targeting of CRC cells via the RevCAR platform as an improved approach to increase tumor specificity and safety of CAR T-cell therapies.
Optimizing the cryopreservation and post-thaw recovery of natural killer cells is critical for the success of off-the-shelf platforms
Authors: Saultz Jennifer N. , Otegbeye Folashade
Published: December 2023

Natural killer (NK) cells are a promising allogeneic, off-the-shelf, cellular immunotherapy product. These cells can be manipulated ex vivo, genetically edited to enhance tumor targeting and expanded to produce large cell banks for multiple patient infusions. Therapeutic efficacy of these products depends on the recovery of viable and functional cells post-thaw. Post-thaw loss of viability and cytolytic activity results in large, and often variable, discrepancies between the intended cell dose (based on counts at cryopreservation) and the actual dose administered. Compared to their highly activated state in fresh culture, post-thaw NK cells demonstrate critical changes in cytokine production, cytotoxic activity, in vivo proliferation and migration. When these NK cells are introduced into the highly immunosuppressive tumor microenvironment, the functional changes induced by cryopreservation further limits the clinical potential of these products. This report will review the impact of cryopreservation on ex vivo expanded NK cells and outlines strategies described in published studies to recover post-thaw function.
Rapid screening for autoimmune diseases using Fourier transform infrared spectroscopy and deep learning algorithms
Authors: Wu Xue , Shuai Wei , Chen Chen , Chen Xiaomei , Luo Cainan , Chen Yi , Shi Yamei , Li Zhengfang , Lv Xiaoyi , Chen Cheng , Meng Xinyan , Lei Xin , Wu Lijun
Published: December 2023

Introduce

Ankylosing spondylitis (AS), rheumatoid arthritis (RA), and osteoarthritis (OA) are three rheumatic immune diseases with many common characteristics. If left untreated, they can lead to joint destruction and functional limitation, and in severe cases, they can cause lifelong disability and even death. Studies have shown that early diagnosis and treatment are key to improving patient outcomes. Therefore, a rapid and accurate method for rapid diagnosis of diseases has been established, which is of great clinical significance for realizing early diagnosis of diseases and improving patient prognosis.

Methods

This study was based on Fourier transform infrared spectroscopy (FTIR) combined with a deep learning model to achieve non-invasive, rapid, and accurate differentiation of AS, RA, OA, and healthy control group. In the experiment, 320 serum samples were collected, 80 in each group. AlexNet, ResNet, MSCNN, and MSResNet diagnostic models were established by using a machine learning algorithm.

Result

The range of spectral wave number measured by four sets of Fourier transform infrared spectroscopy is 700-4000 cm-1. Serum spectral characteristic peaks were mainly at 1641 cm-1(amide I), 1542 cm-1(amide II), 3280 cm-1(amide A), 1420 cm-1(proline and tryptophan), 1245 cm-1(amide III), 1078 cm-1(carbohydrate region). And 2940 cm-1 (mainly fatty acids and cholesterol). At the same time, AlexNet, ResNet, MSCNN, and MSResNet diagnostic models are established by using machine learning algorithms. The multi-scale MSResNet classification model combined with residual blocks can use convolution modules of different scales to extract different scale features and use resblocks to solve the problem of network degradation, reduce the interference of spectral measurement noise, and enhance the generalization ability of the network model. By comparing the experimental results of the other three models AlexNet, ResNet, and MSCNN, it is found that the MSResNet model has the best diagnostic performance and the accuracy rate is 0.87.

Conclusion

The results prove the feasibility of serum Fourier transform infrared spectroscopy combined with a deep learning algorithm to distinguish AS, RA, OA, and healthy control group, which can be used as an effective auxiliary diagnostic method for these rheumatic immune diseases.
Case report: Application of nonsurgical method in saving transplant renal vein thrombosis caused by acute diarrhea
Authors: Xia Liubing , Ye Yongrong , Luo You , Miao Bin , Na Ning
Published: December 2023

Transplant renal vein thrombosis is a rare complication after kidney transplantation, which can seriously threaten graft survival. Though the measures like thrombolytic therapy or operative intervention could be taken to deal with this complication, allograft loss is the most common outcome. Thus, early finding as well as decisive intervention is crucial to saving the graft. Here we present a 46-year-old male patient who underwent kidney transplantation from a cadaveric donor who developed a transplant renal venous thrombosis induced by acute diarrhea more than 1 year after renal transplantation with an initial symptom of sudden anuria and pain in the graft area. Subsequently, serum creatinine levels increased to 810.0 μmol/L. Pelvic CT showed increased vascular density of the transplanted kidney, and contrast-enhanced ultrasound confirmed venous thrombosis. The patient was treated with heparin sodium alone and diuresis gradually resumed. After more than 1 year of follow-up, serum creatinine returned to the baseline level prior to thrombosis. Our case indicates that quick ancillary examination and treatment without hesitation would be indispensable in rescuing allografts with renal vein thrombus. Unfractionated heparin can be recommended as an effective treatment for mid-long-term renal transplantation patients with renal vein thrombosis.
Incisional surface quality of electron-beam irradiated cornea-extracted lenticule for stromal keratophakia: high nJ-energy vs. low nJ-energy femtosecond laser
Authors: Chan Jian S. , Han Evelina , Lim Chris H. L. , Kurz Arthur C. , Shuman Jeremy , Liu Yu-Chi , Riau Andri K. , Mehta Jodhbir S.
Published: December 2023

Introduction

Corneal lenticules can be utilized as an additive material for stromal keratophakia. However, following extraction, they must be reimplanted almost immediately or cryopreserved in lenticule banks. Electron-beam (E-beam) irradiated corneas permit room-temperature storage for up to 2 years, enabling keratophakia to be performed on demand. This study aims to compare the performance of high nano Joule (nJ)-energy (VisuMax) and low nJ-energy (FEMTO LDV) femtosecond laser systems on the thickness consistency and surface quality and collagen morphology of lenticules produced from fresh and E-beamed corneas.

Methods

A total of 24 lenticules with −6.00 dioptre power were cut in fresh human donor corneas and E-beamed corneas with VisuMax and FEMTO LDV. Before extraction, the thickness of the lenticules was measured with anterior segment-optical coherence tomography (AS-OCT). The incisional surface roughness of extracted lenticules was analyzed using atomic force microscopy (AFM) and scanning electron microscopy (SEM). Multiphoton microscopy was then used to assess the surface collagen morphometry.

Results

The E-beamed lenticules that were cut using FEMTO LDV were significantly thicker than the fresh specimens as opposed to those created with VisuMax, which had a similar thickness as the fresh lenticules. On the vertex, they were ∼11% thicker than the fresh lenticules. The surface roughness (Rq) of E-beamed lenticules incised with FEMTO LDV did not differ significantly from the fresh lenticules. This contrasted with the VisuMax-fashioned lenticules, which showed notably smoother surfaces (∼36 and ∼20% lower Rq on anterior and posterior surfaces, respectively) on the E-beamed than the fresh lenticules. The FEMTO LDV induced less cumulative changes to the collagen morphology on the surfaces of both fresh and E-beamed lenticules than the VisuMax.

Conclusion

It has been previously demonstrated that the low nJ-energy FEMTO LDV produced a smoother cutting surface compared to high nJ-energy VisuMax in fresh lenticules. Here, we showed that this effect was also seen in the E-beamed lenticules. In addition, lower laser energy conferred fewer changes to the lenticular surface collagen morphology. The smaller disparity in surface cutting quality and collagen disturbances on the E-beamed lenticules could be beneficial for the early visual recovery of patients who undergo stromal keratophakia.
Establishment of noncycloplegic methods for screening myopia and pre-myopia in preschool children
Authors: Yin Yao , Li Liping , Wang Ting , Lin Senlin , Wang Jia , Wang Hong , Jiang Minmin , Ma Yingyan , Zhu Jianfeng
Published: December 2023

Purpose

Pre-myopia, a non-myopic refractive state, is a key concern for myopia prevention because of its association with a significantly higher risk of myopia in children under 3 years of age. Amid the myopia pandemic, its onset at younger ages is increasing, yet research on screening methods for myopia and pre-myopia in preschool children remains limited. This study aimed to establish effective noncycloplegic screening methods for myopia and pre-myopia in preschool children.

Methods

This cross-sectional study included 16 kindergartens in Shanghai, China. Uncorrected distance visual acuity (UDVA) was recorded using a logMAR visual acuity chart. Pre- and post-cycloplegic refractions were obtained using an auto-refractor (TopconKR-800). Noncycloplegic axial length (AL) and corneal curvature radius (CR) were measured using the IOL Master-700. Logistic regression models were developed to establish accurate noncycloplegic screening methods for myopia and pre-myopia.

Results

A total of 1,308 children with a mean age of 4.3 ± 0.9 years were included; among them 640 (48.9%) were girls. The myopia prevalence rate was 2.8% (n = 36), and the prevalence of pre-myopia was 21.9% (n = 286). Pre-myopia screening (cycloplegic spherical equivalent [SE] ≤ −0.5 < SE ≤0.75 diopters [D]) using UDVA exhibited an area under the receiver operating curve (AUC) of 0.52, noncycloplegic SE had an AUC of 0.70 and AL had an AUC of 0.63. The accuracy of combining the SE and AL/CR ratio was among the best with the least number of checks used, and the AUC was 0.74 for pre-myopia screening and 0.94 for myopia screening (cycloplegic SE ≤ −0.5 D). The addition of UDVA did not further improve the accuracy.

Conclusion

Using UDVA alone did not achieve good accuracy in pre-myopia or myopia screening of young children. Under non-cycloplegic conditions, the combination of AL/CR and SE demonstrated favorable results for pre-myopia and myopia screening of preschool children.
Clinical trials for Chagas disease: etiological and pathophysiological treatment
Authors: Gonzaga Beatriz Matheus de Souza , Ferreira Roberto Rodrigues , Coelho Laura Lacerda , Carvalho Anna Cristina C. , Garzoni Luciana Ribeiro , Araujo-Jorge Tania C.
Published: December 2023

Chagas disease (CD) is caused by the flagellate protozoan Trypanosoma cruzi. It is endemic in Latin America. Nowadays around 6 million people are affected worldwide, and 75 million are still at risk. CD has two evolutive phases, acute and chronic. The acute phase is mostly asymptomatic, or presenting unspecific symptoms which makes it hard to diagnose. At the chronic phase, patients can stay in the indeterminate form or develop cardiac and/or digestive manifestations. The two trypanocide drugs available for the treatment of CD are benznidazole (BZ) and nifurtimox (NFX), introduced in the clinic more than five decades ago. WHO recommends treatment for patients at the acute phase, at risk of congenital infection, for immunosuppressed patients and children with chronic infection. A high cure rate is seen at the CD acute phase but better treatment schemes still need to be investigated for the chronic phase. There are some limitations within the use of the trypanocide drugs, with side effects occurring in about 40% of the patients, that can lead patients to interrupt treatment. In addition, patients with advanced heart problems should not be treated with BZ. This is a neglected disease, discovered 114 years ago that still has no drug effective for their chronic phase. Multiple social economic and cultural barriers influence CD research. The high cost of the development of new drugs, in addition to the low economical return, results in the lack of investment. More economic support is required from governments and pharmaceutical companies on the development of more research for CD treatment. Two approaches stand out: repositioning and combination of drugs, witch drastically decrease the cost of this process, when compared to the development of a new drug. Here we discuss the progress of the clinical trials for the etiological and pathophysiological treatment for CD. In summary, more studies are needed to propose a new drug for CD. Therefore, BZ is still the best option for CD. The trials in course should clarify more about new treatment regimens, but it is already possible to indicate that dosage and time of treatment need to be adjusted.
Vertical distribution and seasonal dynamics of planktonic cyanobacteria communities in a water column of deep mesotrophic Lake Geneva
Authors: Carratalà Anna , Chappelier Coralie , Selmoni Oliver , Guillaume Annie S. , Chmiel Hannah E. , Pasche Natacha , Weil Charlotte , Kohn Tamar , Joost Stéphane
Published: December 2023

Background

Temperate subalpine lakes recovering from eutrophication in central Europe are experiencing harmful blooms due to the proliferation of Planktothrix rubescens, a potentially toxic cyanobacteria. To optimize the management of cyanobacteria blooms there is the need to better comprehend the combination of factors influencing the diversity and dominance of cyanobacteria and their impact on the lake’s ecology. The goal of this study was to characterize the diversity and seasonal dynamics of cyanobacteria communities found in a water column of Lake Geneva, as well as the associated changes on bacterioplankton abundance and composition.

Methods

We used 16S rRNA amplicon high throughput sequencing on more than 200 water samples collected from surface to 100 meters deep monthly over 18 months. Bacterioplankton abundance was determined by quantitative PCR and PICRUSt predictions were used to explore the functional pathways present in the community and to calculate functional diversity indices.

Results

The obtained results confirmed that the most dominant cyanobacteria in Lake Geneva during autumn and winter was Planktothrix (corresponding to P. rubescens). Our data also showed an unexpectedly high relative abundance of picocyanobacterial genus Cyanobium, particularly during summertime. Multidimensional scaling of Bray Curtis dissimilarity revealed that the dominance of P. rubescens was coincident with a shift in the bacterioplankton community composition and a significant decline in bacterioplankton abundance, as well as a temporary reduction in the taxonomic and PICRUSt2 predicted functional diversity.

Conclusion

Overall, this study expands our fundamental understanding of the seasonal dynamics of cyanobacteria communities along a vertical column in Lake Geneva and the ecology of P. rubescens, ultimately contributing to improve our preparedness against the potential occurrence of toxic blooms in the largest lake of western Europe.
Sex moderates the association between age and myelin water fraction in the cingulum and fornix among older adults without dementia
Authors: Brenner Einat K. , Bangen Katherine J. , Clark Alexandra L. , Delano-Wood Lisa , Evangelista Nicole D. , Edwards Lauren , Sorg Scott F. , Jak Amy J. , Bondi Mark W. , Deoni Sean C. L. , Lamar Melissa
Published: December 2023

Background

Decreasing white matter integrity in limbic pathways including the fornix and cingulum have been reported in Alzheimer’s disease (AD), although underlying mechanisms and potential sex differences remain understudied. We therefore sought to explore sex as a moderator of the effect of age on myelin water fraction (MWF), a measure of myelin content, in older adults without dementia (N = 52).

Methods

Participants underwent neuropsychological evaluation and 3 T MRI at two research sites. Multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) quantified MWF in 3 a priori regions including the fornix, hippocampal cingulum (CgH), and cingulate cingulum (CgC). The California Verbal Learning Test-Second Edition assessed learning and delayed recall. Multiple linear regressions assessed for (1) interactions between age and sex on regional MWF and (2) associations of regional MWF and memory.

Results

(1) There was a significant age by sex interaction on MWF of the fornix (p = 0.002) and CgC (p = 0.005), but not the CgH (p = 0.192); as age increased, MWF decreased in women but not men. (2) Fornix MWF was associated with both learning and recall (ps < 0.01), but MWF of the two cingulum regions were not (p > 0.05). Results were unchanged when adjusting for hippocampal volume.

Conclusion

The current work adds to the literature by illuminating sex differences in age-related myelin decline using a measure sensitive to myelin and may help facilitate detection of AD risk for women.
PKCε activator protects hippocampal microvascular disruption and memory defect in 3×Tg-Alzheimer’s disease mice with cerebral microinfarcts
Authors: Wang Huaixing , Zhang Zongxiu , Hongpaisan Jarin
Published: December 2023

Background

Current evidence suggests that microvessel disease is involved in Alzheimer’s disease (AD). Cerebrovascular disease correlates with cardiovascular disease and is complicated in ≈40% of AD patients. The protein kinase C (PKC) ε activator DCPLA can stimulate human antigen (Hu) R that prevents degradation and promotes the translation of mitochondrial Mn-superoxide dismutase (MnSOD) and vascular endothelial growth factor-A (VEGF) mRNAs.

Methods

To induce brain microinfarcts, we injected triple transgenic (3×Tg) and wild-type (WT) control mice with microbeads (20 μm caliber) into common carotid arteries, with or without the DCPLA-ME (methyl-ester) for 2 weeks. After water maze training, mice at 16 months old were examined for confocal immunohistochemistry at a single cell or microvessel level in the hippocampal CA1 area, important for spatial memory storage, and in the dorsal hippocampus by western blots.

Results

In 3×Tg mice without cerebral microinfarcts, an accelerating age-related increase in (mild) oxidative stress and hypoxia inducible factor (HIF)-1α, but a reduction in VEGF, mitochondrial transcription factor A (TFAM), and MnSOD were associated with capillary loss. The change was less pronounced in arterioles. However, in 3×Tg mice with cerebral microinfarcts, increasing arteriolar diameter and their wall cells were related with the strong oxidative DNA damage 8-hydroxy-2′-deoxyguanosine (8-OHdG), apoptosis (cleaved caspase 3), and sustained hypoxia (increased HIF-1α and VEGF/PKCε/extracellular signal regulated kinase or ERK pathway). Microocclusion enhanced the loss of the synaptic marker spinophilin, astrocytic number, and astrocyte-vascular coupling areas and demyelination of axons. DCPLA-ME prevented spatial memory defect; strong oxidative stress-related apoptosis; sustained hypoxia (by reducing HIF-1α and VEGF); and exaggerated cell repair in arteriolar walls, pericapillary space dilation, neuro-glial-vascular disruption, and demyelination.

Conclusion

In conclusion, in 3×Tg mice with cerebral microinfarcts, sustained hypoxia (increased HIF-1α and VEGF signals) is dominant with arteriolar wall thickening, and DCPLA has a protective effect on sustained hypoxia.
Complications and outcomes of hospitalizations for patients with and without Parkinson disease
Authors: George Benjamin P. , Barbosa William A. , Sethi Anish , Richard Irene H.
Published: December 2023

Objective

To examine complications and outcomes of hospitalizations for common indications for hospitalization among patients with Parkinson disease (PD).

Methods

We identified and selected the ten most common indications for hospitalization among individuals ≥65 years of age using principal diagnoses from the California State Inpatient Database, 2018–2020. Patients with comorbid PD were identified using secondary diagnosis codes and matched one-to-one to patients without PD based on principal diagnosis (exact matching), age, gender, race and ethnicity, and Elixhauser comorbidity index (coarsened exact matching). We identified potentially preventable complications based on the absence of present on admission indicators among secondary diagnoses. In the matched cohort, we compared inpatient complications, early Do-Not-Resuscitate (DNR) orders (placed within 24 h of admission), use of life-sustaining therapies, new nursing facility requirement on discharge, and death or hospice discharge for patients with and without PD.

Results

We identified 35,457 patients with PD among the ten leading indications for hospitalization in older adults who were matched one-to-one to patients without PD (n = 70,914 in total). Comorbid PD was associated with an increased odds of developing aspiration pneumonia (OR 1.17 95% CI 1.02–1.35) and delirium (OR 1.11 95% CI 1.02–1.22) during admission. Patients with PD had greater odds of early DNR orders [placed within 24 h of admission] (OR 1.34 95% CI 1.29–1.39). While there was no difference in the odds of mechanical ventilation (OR 1.04 95% CI 0.98–1.11), patients with PD demonstrated greater odds of tracheostomy (OR 1.41 95% CI 1.12–1.77) and gastrostomy placement (OR 2.00 95% CI 1.82–2.20). PD was associated with greater odds of new nursing facility requirement upon discharge (OR 1.58 95% CI 1.53–1.64). Patients with PD were more likely to die as a result of their hospitalization (OR 1.11 95% CI 1.06–1.16).

Conclusion

Patients with PD are at greater risk of developing aspiration pneumonia and delirium as a complication of their hospitalization. While patients with PD more often have early DNR orders, they have greater utilization of life-sustaining therapies and experience worse outcomes of their hospitalization including new nursing facility requirement upon discharge and greater mortality.
Neuromyelitis optica spectrum disorder safely and successfully treated with satralizumab during pregnancy and breastfeeding: a case report
Authors: Yoshida Takashi , Watanabe Osamu , Nomura Miwa , Yoshimoto Yusuke , Maki Yoshimitsu , Takashima Hiroshi
Published: December 2023

Background

Satralizumab, a monoclonal antibody that recognizes interleukin-6 receptors, is known to reduce the relapse rate in neuromyelitis optica spectrum disorder (NMOSD), but its safety during pregnancy has not been established. We present the case of an NMOSD patient who safely completed pregnancy, parturition, and breastfeeding under satralizumab treatment. Importantly, satralizumab transfer to umbilical cord blood, infant serum, or breast milk was not observed.

Case presentation

A 37-year-old Japanese female developed anti-aquaporin 4 antibody-positive NMOSD with left optic neuritis. Despite responding to steroid and azathioprine therapy, she experienced moon face and weight gain and desired the prompt reduction of the steroid dosage. She also wanted to conceive a child with a safe and preferably early pregnancy and parturition. Because pregnancy and parturition after the onset of NMOSD elevate the risk of relapse and miscarriage, treatment with satralizumab was initiated with the patient's consent. She experienced normal parturition and continued with satralizumab, steroid, and azathioprine treatments while breastfeeding without experiencing any relapses. Concentrations of satralizumab in the umbilical cord blood, infant serum, and breast milk were below the detection sensitivity.

Conclusion

These findings suggest that satralizumab may be safe and effective for the perinatal management of NMOSD, especially when there are concerns about continuing pregnancy and the risk of relapse after parturition.
Urine-based point-of-care testing for factor-Xa-inhibitors in acute ischemic stroke patients: a feasibility study
Authors: Doeppner Thorsten R. , Olbricht Linus , Maxhuni Toska , Alhaj Omar Omar , Sachs Ulrich J. , Juenemann Martin B. , Huttner Hagen B. , Gerner Stefan T.
Published: December 2023

Introduction

Direct oral anticoagulants (DOACs) have become widely used in clinical practice for preventing thromboembolic events. Point-of-care testing methods, particularly those based on urine samples, offer a promising approach for rapid and accurate assessment of DOAC presence. This pilot study aims to evaluate the utility of a urine-based DOAC dipstick test as a point-of-care tool for identifying DOAB presence in acute ischemic stroke (AIS) or transient ischemic attack (TIA) patients.

Patients and methods

This prospective pilot study included patients with AIS/TIA eligible for DOAC-measurement. After exclusion of 3 patients, 23 patients with DOAC-intake (DOAC group; factor-Xa-inhibitors; n = 23) and 21 patients without DOAC-intake (control-group) remained for analyses. The urine-based DOAC dipstick test and parallel blood-based specific DOAC-level assessment were performed in all patients. Time-intervals of sampling urine/blood sampling and result of DOAC-test were recorded to analyze a potential time benefit based on dipstick evaluation.

Results

The urine-based DOAC dipstick test demonstrated high sensitivity (100%) and specificity (100%), correctly identifying all patients with anticoagulatory activity due to DOAC intake (i.e., anti-Xalevel ≥30 ng/mL). Moreover, the visual readout of the test provided semiquantitative information on drug-specific anti-Xa levels, showing a sensitivity of 83% and specificity of 93% to detect anti-Xa levels ≥120 ng/mL. The dipstick test exhibited a median time-benefit of 2:25 h compared to standard blood-based DOAC-level testing.

Discussion

The results of this pilot study underline the efficacy of urine-based point-of-care testing as a rapid and reliable method for assessing DOAC presence in patients with acute ischemic stroke.

Conclusion

The value of this tool for clinical decision-making in stroke management needs to be established in future trials.

Clinical Trial Registration: Clinicaltrails.org identifier [NCT06037200].
The effect of gaze on EEG measures of multisensory integration in a cocktail party scenario
Authors: Ahmed Farhin , Nidiffer Aaron R. , Lalor Edmund C.
Published: December 2023

Seeing the speaker’s face greatly improves our speech comprehension in noisy environments. This is due to the brain’s ability to combine the auditory and the visual information around us, a process known as multisensory integration. Selective attention also strongly influences what we comprehend in scenarios with multiple speakers–an effect known as the cocktail-party phenomenon. However, the interaction between attention and multisensory integration is not fully understood, especially when it comes to natural, continuous speech. In a recent electroencephalography (EEG) study, we explored this issue and showed that multisensory integration is enhanced when an audiovisual speaker is attended compared to when that speaker is unattended. Here, we extend that work to investigate how this interaction varies depending on a person’s gaze behavior, which affects the quality of the visual information they have access to. To do so, we recorded EEG from 31 healthy adults as they performed selective attention tasks in several paradigms involving two concurrently presented audiovisual speakers. We then modeled how the recorded EEG related to the audio speech (envelope) of the presented speakers. Crucially, we compared two classes of model – one that assumed underlying multisensory integration (AV) versus another that assumed two independent unisensory audio and visual processes (A+V). This comparison revealed evidence of strong attentional effects on multisensory integration when participants were looking directly at the face of an audiovisual speaker. This effect was not apparent when the speaker’s face was in the peripheral vision of the participants. Overall, our findings suggest a strong influence of attention on multisensory integration when high fidelity visual (articulatory) speech information is available. More generally, this suggests that the interplay between attention and multisensory integration during natural audiovisual speech is dynamic and is adaptable based on the specific task and environment.
TSPNet: a time-spatial parallel network for classification of EEG-based multiclass upper limb motor imagery BCI
Authors: Bi Jingfeng , Chu Ming , Wang Gang , Gao Xiaoshan
Published: December 2023

The classification of electroencephalogram (EEG) motor imagery signals has emerged as a prominent research focus within the realm of brain-computer interfaces. Nevertheless, the conventional, limited categories (typically just two or four) offered by brain-computer interfaces fail to provide an extensive array of control modes. To address this challenge, we propose the Time-Spatial Parallel Network (TSPNet) for recognizing six distinct categories of upper limb motor imagery. Within TSPNet, temporal and spatial features are extracted separately, with the time dimension feature extractor and spatial dimension feature extractor performing their respective functions. Following this, the Time-Spatial Parallel Feature Extractor is employed to decouple the connection between temporal and spatial features, thus diminishing feature redundancy. The Time-Spatial Parallel Feature Extractor deploys a gating mechanism to optimize weight distribution and parallelize time-spatial features. Additionally, we introduce a feature visualization algorithm based on signal occlusion frequency to facilitate a qualitative analysis of TSPNet. In a six-category scenario, TSPNet achieved an accuracy of 49.1% ± 0.043 on our dataset and 49.7% ± 0.029 on a public dataset. Experimental results conclusively establish that TSPNet outperforms other deep learning methods in classifying data from these two datasets. Moreover, visualization results vividly illustrate that our proposed framework can generate distinctive classifier patterns for multiple categories of upper limb motor imagery, discerned through signals of varying frequencies. These findings underscore that, in comparison to other deep learning methods, TSPNet excels in intention recognition, which bears immense significance for non-invasive brain-computer interfaces.
Elucidating the Influence of MPT-driven necrosis-linked LncRNAs on immunotherapy outcomes, sensitivity to chemotherapy, and mechanisms of cell death in clear cell renal carcinoma
Authors: Huang Jinbang , Liu Mengtao , Chen Haiqing , Zhang Jinhao , Xie Xixi , Jiang Lai , Zhang Shengke , Jiang Chenglu , Zhang Jieying , Zhang Qinhong , Yang Guanhu , Chi Hao , Tian Gang
Published: December 2023

Background

Clear cell renal carcinoma (ccRCC) stands as the prevailing subtype among kidney cancers, making it one of the most prevalent malignancies characterized by significant mortality rates. Notably,mitochondrial permeability transition drives necrosis (MPT-Driven Necrosis) emerges as a form of cell death triggered by alterations in the intracellular microenvironment. MPT-Driven Necrosis, recognized as a distinctive type of programmed cell death. Despite the association of MPT-Driven Necrosis programmed-cell-death-related lncRNAs (MPTDNLs) with ccRCC, their precise functions within the tumor microenvironment and prognostic implications remain poorly understood. Therefore, this study aimed to develop a novel prognostic model that enhances prognostic predictions for ccRCC.

Methods

Employing both univariate Cox proportional hazards and Lasso regression methodologies, this investigation distinguished genes with differential expression that are intimately linked to prognosis.Furthermore, a comprehensive prognostic risk assessment model was established using multiple Cox proportional hazards regression. Additionally, a thorough evaluation was conducted to explore the associations between the characteristics of MPTDNLs and clinicopathological features, tumor microenvironment, and chemotherapy sensitivity, thereby providing insights into their interconnectedness.The model constructed based on the signatures of MPTDNLs was verified to exhibit excellent prediction performance by Cell Culture and Transient Transfection, Transwell and other experiments.

Results

By analyzing relevant studies, we identified risk scores derived from MPTDNLs as an independent prognostic determinant for ccRCC, and subsequently we developed a Nomogram prediction model that combines clinical features and associated risk assessment. Finally, the application of experimental techniques such as qRT-PCR helped to compare the expression of MPTDNLs in healthy tissues and tumor samples, as well as their role in the proliferation and migration of renal clear cell carcinoma cells. It was found that there was a significant correlation between CDK6-AS1 and ccRCC results, and CDK6-AS1 plays a key role in the proliferation and migration of ccRCC cells. Impressive predictive results were generated using marker constructs based on these MPTDNLs.

Conclusions

In this research, we formulated a new prognostic framework for ccRCC, integrating mitochondrial permeability transition-induced necrosis. This model holds significant potential for enhancing prognostic predictions in ccRCC patients and establishing a foundation for optimizing therapeutic strategies.
Detection of lymph node metastasis in colon cancer by ectopically expressed fibroblast markers FOXQ1 and THBS2
Authors: Ali Haytham , AbdelMageed Manar , Olsson Lina , Lindmark Gudrun , Hammarström Marie-Louise , Hammarström Sten , Sitohy Basel
Published: December 2023

Introduction

Approximately 25% of colon cancer (CC) patients having curative surgery will relapse. Therefore, it is crucial to identify patients with increased recurrence risk to offer them adjuvant chemotherapy. Three markers with prominent expression in fibroblasts: forkhead box Q1 (FOXQ1), matrix metalloproteinase-11 (MMP11), and thrombospondin-2 (THBS2), and the fibroblast expressed chemokine CXCL12 were selected for studies because of the critical role of fibroblasts in the microenvironment of the tumor.

Methods

The expression levels of the biomarkers were assessed in primary CC tumors, lymph nodes of CC patients and controls, and CC cell lines at mRNA and protein levels by real-time qRT-PCR and immunohistochemistry, respectively.

Results

FOXQ1, MMP11, and THBS2 mRNAs were expressed at significantly higher levels in primary tumors compared to normal colon (P=0.002, P<0.0001, and P<0.0001, respectively). In contrast, CXCL12 mRNA levels were higher in normal colon tissue. FOXQ1, MMP11, and THBS2 levels were also expressed at significantly higher levels in metastasis-positive lymph nodes compared to both metastasis-negative- and control nodes (P<0.0001/P=0.002, P<0.0001/P<0.0001, and P<0.0001/P<0.0001, respectively). Immuno-morphometry revealed that 30–40% of the tumor cells expressed FOXQ1, MMP11, and THBS2. FOXQ1 and THBS2 were barely detected in normal colon epithelium (P<0.0001), while MMP11 was expressed in normal colon epithelium at high levels.

Discussion

We conclude that CC tumor cells show ectopic expression of FOXQ1 and THBS2 possibly making these tumor cells independent of fibroblast cell support. The high expression levels of these two biomarkers in metastatic lymph nodes suggest that they are potential indicators of patients at risk for recurrence.
Lung cancer mortality and associated predictors: systematic review using 32 scientific research findings
Authors: Tesfaw Lijalem Melie , Dessie Zelalem G. , Mekonnen Fenta Haile
Published: December 2023

Background

Cancer is a chronic disease brought on by mutations to the genes that control our cells’ functions and become the most common cause of mortality and comorbidities. Thus, this study aimed to assess the comprehensive and common mortality-related risk factors of lung cancer using more than thirty scientific research papers.

Methods

Possible risk factors contributing to lung cancer mortality were assessed across 201 studies sourced from electronic databases, including Google Scholar, Cochrane Library, Web of Science (WOS), EMBASE, Medline/PubMed, the Lung Cancer Open Research Dataset Challenge, and Scopus. Out of these, 32 studies meeting the eligibility criteria for meta-analysis were included. Due to the heterogeneous nature of the studies, a random-effects model was applied to estimate the pooled effects of covariates.

Results

The overall prevalence of mortality rate was 10% with a 95% confidence interval of 6 and 16%. Twenty studies (62.50%) studies included in this study considered the ages of lung cancer patients as the risk factors for mortality. Whereas, eighteen (56.25%) and thirteen (40.63%) studies incorporated the gender and smoking status of patients respectively. The comorbidities of lung cancer mortality such as cardiovascular disease, hypertension, diabetes, and pneumonia were also involved in 7 (21.90%), 6 (18.75%), 5 (15.63%), and 2 (6.25%) studies, respectively. Patients of older age are more likely to die as compared to patients of younger age. Similarly, lung patients who had smoking practice were more likely to die as compared to patients who hadn’t practiced smoking

Conclusion

The mortality rate of lung cancer patients is considerably high. Older age, gender, stage, and comorbidities such as cardiovascular, hypertension, and diabetes have a significant positive effect on lung cancer mortality. The study results will contribute to future research, management, and prevention strategies for lung cancer.
Physical fitness and motor competence performance characteristics of Chinese elite youth athletes from four track and field throwing disciplines—a cross-sectional study
Authors: Zhao Kewei , Siener Maximilian , Zhao Yifan , Hohmann Andreas
Published: December 2023

Purpose: For systematic athletic training and targeted talent development, it is essential to know the physical fitness and motor competencies of top athletes in detail. However, it can be difficult to identify differences in performance requirements and thus to provide adequate support, especially for sports that at first glance appear to have similar demands—such as track and field throwing disciplines. Therefore, the aim of the study was to examine the physical fitness and motor competence of top athletes from different throwing disciplines and to check whether the athletes’ performance parameters match the specific requirements of the respective sport.

Methods: The study involved 289 male youth athletes (aged 14–18 years) across four distinct throwing disciplines: shot put (n = 101), hammer throw (n = 16), discus throw (n = 63), and javelin throw (n = 109). The performance evaluation comprised three anthropometric measurements and twelve motor performance prerequisites applicable to the throwing disciplines. Discriminant analysis and neural networks (Multilayer Perceptron) were implemented to determine the possibility of distinguishing among athletes from the four sports.

Results: The study’s findings indicate that in male throwing athletes, disparities in general physical fitness and motor proficiency assessments discern the majority of talented young athletes based on their specific sport (discriminant analysis: 68.2%; multilayer perceptron analysis: 72.2%). This remains applicable irrespective of the classification method employed. Discus throwers possessed a height advantage, while shot putters and hammer throwers exhibited superior arm strength. Javelin throwers displayed better explosive strength and sprinting speed. Except for the hammer throwers, all events demonstrated a high level of explosive power in the medicine ball forward or backward throw test, which was especially crucial for shot put and discus athletes.

Conclusion: The significance of physical fitness and motor competence tests in identifying and transferring talented athletes in track and field throwing disciplines has been affirmed. Using linear and non-linear classification methods, most athletes could be assigned to their correct sport. However, this also shows that slightly different training and talent identification is required for each of these sports. Furthermore, non-linear analysis methods can provide useful support for the development processes in junior competitive sports.
Population structure and genetic diversity in Eucalyptus pellita based on SNP markers
Authors: Wang Chubiao , Lan Jun , Wang Jianzhong , He Wenliang , Lu Wanhong , Lin Yan , Luo Jianzhong
Published: December 2023

Eucalyptus pellita has the characteristics of rapid growth and high resistance. However, there is little research on molecular breeding of E. pellita, which is essential to shortening breeding life and selecting quality varieties. Therefore, a crucial step before selective breeding can be carried out to increase the wood quality of E. pellita is identifying genetic diversity and population structure using single nucleotide polymorphism (SNP) markers. In this study, the genetic diversity of 1st generation 196 E. pellita families from 23 geographically defined was assessed using 1,677,732 SNP markers identified by whole genome resequencing. SNP annotation showed that the ratio of non-synonymous to synonymous coding mutations was 0.83. Principal component analysis (PCA), phylogenetic tree, and population structure analysis permitted the families to be categorized into three groups, one of which (G2) contains most of the Indonesian (IDN) and Papua New Guinea (PNG) families. Genetic relationship analysis showed that IDN was closely related to PNG. Genetic diversity analysis showed that He, PIC, I, and H mean values were 0.2502, 0.2027, 0.3815, and 0.2680, respectively. PCA analysis classified various provenances in QLD into two categories (G1 and G3). The genetic diversity of G3 was higher than that of G2. The results of genetic differentiation (Fst) showed that PNG region was divided into two groups (PNG1 and PNG2), the Fst (0.172) between QLD and PNG2 region was higher than QLD and PNG1, and the Fst (0.024) between IDN and PNG1 is smaller than IDN and PNG2. A Mantel test revealed a positive correlation between the genetic and geographic distance of E. pellita. This study has a certain reference value for genetic identification, germplasm preservation, and breeding of E. pellita. Also, it provides a basis for subsequent association analysis to explore excellent alleles and introduction.
Multifaceted roles of WRKY transcription factors in abiotic stress and flavonoid biosynthesis
Authors: Zhang Jinnan , Zhao Haiqing , Chen Lu , Lin Jiacheng , Wang Zhile , Pan Jiaqi , Yang Fan , Ni Xiaoli , Wang Yiang , Wang Yuhua , Li Rui , Pi Erxu , Wang Shang
Published: December 2023

Increasing biotic and abiotic stresses are seriously impeding the growth and yield of staple crops and threatening global food security. As one of the largest classes of regulators in vascular plants, WRKY transcription factors play critical roles governing flavonoid biosynthesis during stress responses. By binding major W-box cis-elements (TGACCA/T) in target promoters, WRKYs modulate diverse signaling pathways. In this review, we optimized existing WRKY phylogenetic trees by incorporating additional plant species with WRKY proteins implicated in stress tolerance and flavonoid regulation. Based on the improved frameworks and documented results, we aim to deduce unifying themes of distinct WRKY subfamilies governing specific stress responses and flavonoid metabolism. These analyses will generate experimentally testable hypotheses regarding the putative functions of uncharacterized WRKY homologs in tuning flavonoid accumulation to enhance stress resilience.