bluuebunny/crossref_metadata_2025 huggingface dataset:
Preclinical Model of Stereotactic Ablative Lung Irradiation Using Arc Delivery in the Mouse: Is Fractionation Worthwhile?
Authors: Bertho Annaïg , Dos Santos Morgane , Braga-Cohen Sarah , Buard Valérie , Paget Vincent , Guipaud Olivier , Tarlet Georges , Milliat Fabien , François Agnès
Published: December 2021

Lung stereotactic body radiation therapy is characterized by a reduction in target volumes and the use of severely hypofractionated schedules. Preclinical modeling became possible thanks to rodent-dedicated irradiation devices allowing accurate beam collimation and focal lung exposure. Given that a great majority of publications use single dose exposures, the question we asked in this study was as follows: in incremented preclinical models, is it worth using fractionated protocols or should we continue focusing solely on volume limitation? The left lungs of C57BL/6JRj mice were exposed to ionizing radiation using arc therapy and 3 × 3 mm beam collimation. Three-fraction schedules delivered over a period of 1 week were used with 20, 28, 40, and 50 Gy doses per fraction. Lung tissue opacification, global histological damage and the numbers of type II pneumocytes and club cells were assessed 6 months post-exposure, together with the gene expression of several lung cells and inflammation markers. Only the administration of 3 × 40 Gy or 3 × 50 Gy generated focal lung fibrosis after 6 months, with tissue opacification visible by cone beam computed tomography, tissue scarring and consolidation, decreased club cell numbers and a reactive increase in the number of type II pneumocytes. A fractionation schedule using an arc-therapy-delivered three fractions/1 week regimen with 3 × 3 mm beam requires 40 Gy per fraction for lung fibrosis to develop within 6 months, a reasonable time lapse given the mouse lifespan. A comparison with previously published laboratory data suggests that, in this focal lung irradiation configuration, administering a Biological Effective Dose ≥ 1000 Gy should be recommended to obtain lung fibrosis within 6 months. The need for such a high dose per fraction challenges the appropriateness of using preclinical highly focused fractionation schedules in mice.
Longitudinal Analysis of Antibody Responses to the mRNA BNT162b2 Vaccine in Patients Undergoing Maintenance Hemodialysis: A 6-Month Follow-Up
Authors: Weigert André , Bergman Marie-Louise , Gonçalves Lígia A. , Godinho Iolanda , Duarte Nádia , Abrantes Rita , Borges Patrícia , Brennand Ana , Malheiro Vanessa , Matoso Paula , Akpogheneta Onome , Kosack Lindsay , Cruz Pedro , Nogueira Estela , Pereira Magda , Ferreira Ana , Marques Marco , Nunes Telmo , Faro-Viana João , Demengeot Jocelyne , Penha-Gonçalves Carlos
Published: December 2021

Background: Patients on hemodialysis (HD) are at higher risk for COVID-19, overall are poor responders to vaccines, and were prioritized in the Portuguese vaccination campaign.

Objective: This work aimed at evaluating in HD patients the immunogenicity of BTN162b2 after the two doses induction phase, the persistence of specific antibodies along time, and factors predicting these outcomes.

Methods: We performed a prospective, 6-month long longitudinal cohort analysis of 156 HD patients scheduled to receive BTN162b2. ELISA quantified anti-spike IgG, IgM, and IgA levels in sera were collected every 3 weeks during the induction phase (t0 before vaccine; t1, d21 post first dose; and t2 d21 post second dose), and every 3–4 months during the waning phase (t3, d140, and t4, d180 post first dose). The age-matched control cohort was similarly analyzed from t0 to t2.

Results: Upon exclusion of participants identified as previously exposed to SARS-CoV-2, seroconversion at t1 was lower in patients than controls (29 and 50%, respectively, p = 0.0014), while the second vaccine dose served as a boost in both cohorts (91 and 95% positivity, respectively, at t2, p = 0.2463). Lower response in patients than controls at t1 was a singularity of the participants ≤ 70 years (p = 2.01 × 10−05), associated with immunosuppressive therapies (p = 0.013), but not with lack of responsiveness to hepatitis B. Anti-spike IgG, IgM, and IgA levels decreased at t3, with IgG levels further waning at t4 and resulting in >30% seronegativity. Anti-spike IgG levels at t1 and t4 were correlated (ρ = 0.65, p < 2.2 × 10−16).

Conclusions: While most HD patients seroconvert upon 2 doses of BNT162b2 vaccination, anti-spike antibodies levels wane over the following 4 months, leading to early seroreversion in a sizeable fraction of the patients. These findings warrant close monitoring of COVID-19 infection in vaccinated HD patients, and advocate for further studies following reinforced vaccination schedules.
Management of Intraocular Pressure Elevation After CO2 Laser-Assisted Sclerectomy Surgery in Patients With Primary Open-Angle Glaucoma
Authors: Chen Min , Gu Yuxiang , Yang Yumei , Zhang Qi , Liu Xin , Wang Kaijun
Published: December 2021

Purpose: To report the safety and efficiency of carbon dioxide (CO2) laser-assisted sclerectomy surgery (CLASS) in Chinese patients with primary open-angle glaucoma (POAG) and the management of unexpected postoperative intraocular pressure (IOP) elevation.

Methods: This was a prospective case series study. A total of 23 eyes from 23 patients with POAG who underwent CLASS were involved and followed-up for 12 months. The primary outcomes included the changes in best corrected visual acuity (BCVA), IOP, and medications before and after CLASS. The secondary outcomes were success rate and postoperative laser interventions.

Results: The mean age of the patient was 42.6 ± 16.0 years. There was no significant change in BCVA and visual field at baseline and 12 months after CLASS. The number of medications was significantly reduced after CLASS. The IOP was also significantly decreased and remained well controlled during the follow-up period, except for a transient elevation at 1 month postoperatively, due to the occurrence of peripheral anterior synechiae (PAS). Generally, 17 patients (73.9%) were treated with neodymium-doped yttrium aluminum garnet (Nd:YAG) laser synechiolysis to remove iris obstruction in the filtration site and seven patients (30.4%) underwent Nd:YAG laser goniopuncture to deal with scleral reservoir reduction. Only one patient (4.3%) received surgical repositioning due to iris incarceration. The complete success rate and total success rate at 12 months were 69.6 and 95.7%, respectively.

Conclusion: CLASS was a safe and effective approach for Chinese patients with POAG. Peripheral anterior synechiae (PAS), iris incarceration, and scleral reservoir reduction were common causes of unexpected postoperative IOP elevation. Individualized Nd:YAG laser intervention helps to improve the long-term outcomes after CLASS.
COVID-19 Pandemic and Trends in Clinical Trials: A Multi-Region and Global Perspective
Authors: Nishiwaki Satoshi , Ando Yuichi
Published: December 2021

To evaluate the effect of the COVID-19 pandemic on clinical development, the number of newly started clinical trials in each geographical region between January 2018 and December 2020 were calculated based on data from the ClinicalTrials.gov database. Data regarding new drug applications were obtained from European Medicines Agency monthly reports, pharmaceutical company press releases, and the archives of the Drugs.com database. The mean percentage change in newly started clinical trials for diseases other than COVID-19 between each month in 2019 and the corresponding month in 2020 was −7.5%, with the maximum of −57.3% observed between April 2019 and April 2020. Similarly, the mean percentage change of reported results for each month in 2019 and 2020 was −5.1%, with the maximum of −27.4% observed in July 2020. The activity of clinical trials was decreased as the number of COVID-19 patients was increased, and a statistically negative correlation was observed between the prevalence of COVID-19 and the percentage decrease in the number of clinical trials stared or reported results. As for new drug submissions, decreases were observed in the latter half of 2020 compared with the same period during the previous year, for each indicator. A considerable decline in non-COVID-19 activity for all indicators regarding clinical developments was suggested during the first wave of the COVID-19 pandemic. It is important to recognize the situation and continue to make efforts to conduct clinical trials for both COVID-19 and no-COVID-19 for new medical developments in the future.
Do NSAIDs Take Us Away From Treatment Goals in Axial Spondyloarthritis: A Story About Dysbiosis or Just a Matter of Bias?
Authors: Queiro-Silva Rubén , García-Valle Andrea , Alonso-Castro Sara , Alperi-López Mercedes
Published: December 2021

Non-steroidal anti-inflammatory drugs (NSAIDs) remain the mainstay of treatment for spondyloarthritides (SpA), a group of entities with common clinical and pathophysiological aspects, but also with differential features. Although NSAIDs provide significant symptomatic relief, especially for joint pain and morning stiffness, their role in achieving and maintaining the treatment goals advocated by the treat to target strategy in SpA is not entirely clear. These agents can induce changes in the composition of the intestinal microbiota, also favoring an alteration of the barrier function in the gut epithelium. All of this, favored by a pre-disposing genetic background, could activate a specific type of aberrant immune response in the gut lamina propria, also known as type-3 immunity. This article offers a perspective on how NSAIDs, despite their undeniable value in the short-term SpA treatment, could hinder the achievement of medium and long-term treatment goals by compromising the barrier function of the gut mucosa and potentially altering the composition of the gut microbiota.
Microbial-Maximum Likelihood Estimation Tool for Microbial Quantification in Food From Left-Censored Data Using Maximum Likelihood Estimation for Microbial Risk Assessment
Authors: Bahk Gyung Jin , Lee Hyo Jung
Published: December 2021

In food microbial measurements, when most or very often bacterial counts are below to the limit of quantification (LOQ) or the limit of detection (LOD) in collected food samples, they are either ignored or a specified value is substituted. The consequence of this approach is that it may lead to the over or underestimation of quantitative results. A maximum likelihood estimation (MLE) or Bayesian models can be applied to deal with this kind of censored data. Recently, in food microbiology, an MLE that deals with censored results by fitting a parametric distribution has been introduced. However, the MLE approach has limited practical application in food microbiology as practical tools for implementing MLE statistical methods are limited. We therefore developed a user-friendly MLE tool (called “Microbial-MLE Tool”), which can be easily used without requiring complex mathematical knowledge of MLE but the tool is designated to adjust log-normal distributions to observed counts, and illustrated how this method may be implemented for food microbial censored data using an Excel spreadsheet. In addition, we used two case studies based on food microbial laboratory measurements to illustrate the use of the tool. We believe that the Microbial-MLE tool provides an accessible and comprehensible means for performing MLE in food microbiology and it will also be of help to improve the outcome of quantitative microbial risk assessment (MRA).
Comparison of Necroptosis With Apoptosis for OVX-Induced Osteoporosis
Authors: He Bin , Zhu Yongjun , Cui Hongwang , Sun Bo , Su Tian , Wen Peng
Published: December 2021

As one common kind of osteoporosis, postmenopausal osteoporosis (PMOP) is associated with the death and excessive loss of osteocytes. Estrogen deficiency of PMOP can cause osteocyte death by regulating necroptosis and apoptosis, but their roles in POMP have not been compared. In the present study, ovariectomy (OVX)-induced rat and murine long bone osteocyte Y4 (MLO-Y4) cells were used to compare the influence of necroptosis and apoptosis on osteocyte death and bone loss. Benzyloxycarbonyl-Val-Ala-Asp (zVAD) and necrostatin-1 (Nec-1) were used to specifically block cell apoptosis and necroptosis, respectively. OVX rats and MLO-Y4 cells were divided into zVAD group, Nec-1 group, zVAD + Nec-1 group, vehicle, and control group. The tibial plateaus of the rat model were harvested at 8 weeks after OVX and were analyzed by micro–computed tomography, transmission electron microscopy (TEM), the transferase dUTP nick end labeling assay, and western blot. The death of MLO-Y4 was stimulated by TNF-α and was measured by flow cytometry and TEM. The results found that necroptosis and apoptosis were both responsible for the death and excessive loss of osteocytes, as well as bone loss in OVX-induced osteoporosis, and furthermore necroptosis may generate greater impact on the death of osteocytes than apoptosis. Necroptotic death of osteocytes was mainly regulated by the receptor-interacting protein kinase 3 signaling pathway. Collectively, inhibition of necroptosis may produce better efficacy in reducing osteocyte loss than that of apoptosis, and combined blockade of necroptosis and apoptosis provide new insights into preventing and treating PMOP.
Treatment of Polarized Cystic Fibrosis Airway Cells With HGF Prevents VX-661-Rescued F508del-CFTR Destabilization Caused by Prolonged Co-exposure to VX-770
Authors: Matos Ana M. , Jordan Peter , Matos Paulo
Published: December 2021

Cystic fibrosis (CF), the most common inherited disease in Caucasians, is caused by mutations in CFTR, the most frequent of which is F508del. F508del causes ER retention and degradation of the mutant CFTR protein, but also defective channel gating and decreased half-life at the plasma membrane. Despite the recent successes with small-molecule CFTR modulator drugs, the folding-corrector/gating-potentiator drug combinations approved for CF individuals carrying F508del-CFTR have sometimes produced severe side effects. Previously, we showed that a prolonged, 15-days treatment of polarized bronchial epithelial monolayers with the VX-809+VX-770 combination resulted in epithelial dedifferentiation effects that we found were caused specifically by VX-809. Moreover, prolonged VX-770 exposure also led to the destabilization of VX-809-rescued F508del-CFTR. Notably, co-treatment with the physiological factor HGF prevented VX-809-mediated epithelial differentiation and reverted the destabilizing effect of VX-770 on VX-809-rescued CFTR. Here, we show that prolonged treatment with VX-661, a second-generation corrector developed based on VX-809 structure, does not perturb epithelial integrity of polarized bronchial epithelial monolayers. Yet, its efficacy is still affected by co-exposure to VX-770, the potentiator present in all VX-661-containing combination therapies approved in the United States and Europe for treatment of F508del-CFTR carriers. Importantly, we found that co-treatment with HGF still ameliorated the impact of VX-770 in F508del-CFTR functional rescue by VX-661, without increasing cell proliferation (Ki-67) or altering the overall expression of epithelial markers (ZO-1, E-cadherin, CK8, CK18). Our findings highlight the importance of evaluating the cellular effects of prolonged exposure to CFTR modulators and suggest that the benefits of adding HGF to current combination therapies should be further investigated.
Partial Volume Correction Increases the Sensitivity of 18F-Florbetapir-Positron Emission Tomography for the Detection of Early Stage Amyloidosis
Authors: Teipel Stefan J. , Dyrba Martin , Vergallo Andrea , Lista Simone , Habert Marie Odile , Potier Marie-Claude , Lamari Foudil , Dubois Bruno , Hampel Harald , Grothe Michel J.
Published: December 2021

Purpose: To test whether correcting for unspecific signal from the cerebral white matter increases the sensitivity of amyloid-PET for early stages of cerebral amyloidosis.

Methods: We analyzed 18F-Florbetapir-PET and cerebrospinal fluid (CSF) Aβ42 data from 600 older individuals enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI), including people with normal cognition, mild cognitive impairment (MCI), and Alzheimer’s disease (AD) dementia. We determined whether three compartmental partial volume correction (PVC-3), explicitly modeling signal spill-in from white matter, significantly improved the association of CSF Aβ42 levels with global 18F-Florbetapir-PET values compared with standard processing without PVC (non-PVC) and a widely used two-compartmental PVC method (PVC-2). In additional voxel-wise analyses, we determined the sensitivity of PVC-3 compared with non-PVC and PVC-2 for detecting early regional amyloid build-up as modeled by decreasing CSF Aβ42 levels. For replication, we included an independent sample of 43 older individuals with subjective memory complaints from the INveStIGation of AlzHeimer’s PredicTors cohort (INSIGHT-preAD study).

Results: In the ADNI sample, PVC-3 18F-Florbetapir-PET values normalized to whole cerebellum signal showed significantly stronger associations with CSF Aβ42 levels than non-PVC or PVC-2, particularly in the lower range of amyloid levels. These effects were replicated in the INSIGHT-preAD sample. PVC-3 18F-Florbetapir-PET data detected regional amyloid build-up already at higher (less abnormal) CSF Aβ42 levels than non-PVC or PVC-2 data.

Conclusion: A PVC approach that explicitly models unspecific white matter binding improves the sensitivity of amyloid-PET for identifying the earliest stages of cerebral amyloid pathology which has implications for future primary prevention trials.
Intraoperative vs. Postoperative Side-Effects-Thresholds During Pallidal and Thalamic DBS
Authors: Geraedts Victor J. , van Ham Rogier A. P. , van Hilten Jacobus J. , Mosch Arne , Hoffmann Carel F. E. , van der Gaag Niels A. , Contarino Maria Fiorella
Published: December 2021

Background: It is currently unknown whether results from intraoperative test stimulation of two types of Deep Brain Stimulation (DBS), either during awake pallidal (GPi) or thalamic (Vim), are comparable to the results generated by chronic stimulation through the definitive lead.

Objective: To determine whether side-effects-thresholds from intraoperative test stimulation are indicative of postoperative stimulation findings.

Methods: Records of consecutive patients who received GPi or Vim were analyzed. Thresholds for the induction of either capsular or non-capsular side-effects were compared at matched depths and at group-level.

Results: Records of fifty-two patients were analyzed (20 GPis, 75 Vims). The induction of side-effects was not significantly different between intraoperative and postoperative assessments at matched depths, although a large variability was observed (capsular: GPi DBS: p = 0.79; Vim DBS: p = 0.68); non-capsular: GPi DBS: p = 0.20; and Vim DBS: p = 0.35). Linear mixed-effect models revealed no differences between intraoperative and postoperative assessments, although the Vim had significantly lower thresholds (capsular side-effects p = 0.01, non-capsular side-effects p < 0.01). Unpaired survival analyses demonstrated lower intraoperative than postoperative thresholds for capsular side-effects in patients under GPi DBS (p = 0.01), while higher intraoperative thresholds for non-capsular side-effects in patients under Vim DBS (p = 0.01).

Conclusion: There were no significant differences between intraoperative and postoperative assessments of GPi and Vim DBS, although thresholds cannot be directly extrapolated at an individual level due to high variability.
Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy Associated With Area Postrema Syndrome: A Case Report
Authors: Gao Xin , Tang Ying , Yang Guo-Dong , Wei Wu
Published: December 2021

Glial fibrillary acidic protein astrocytopathy is an immunotherapy-responsive autoimmune disease of the central nervous system with various clinical manifestations; among these, there are few reports about area postrema syndrome (APS). The authors present the case of a female patient admitted to the hospital with intractable nausea and vomiting as the predominant symptom. The patient's cerebrospinal fluid was tested by cell-based assays (CBA) and found positive for the presence of anti-glial fibrillary acidic protein (GFAP) antibody, in addition, serological testing showed elevated levels of thyroglobulin and thyroperoxidase-specific antibodies. Brain and cervical MRI showed abnormally high signal on the T2 sequence in the dorsal medulla oblongata and right pontine arm. Therefore, the patient was diagnosed with autoimmune GFAP astrocytopathy. The symptoms improved rapidly after treatment with corticosteroids, and no recurrence has been observed thus far. APS may be a relatively rare clinical manifestation of GFAP astrocytopathy. Importantly, such presentation is challenging to correctly diagnose without typical MRI imaging findings. However, the detection of antibodies in the cerebrospinal fluid or serum may be valuable. Systemic and neurological autoimmunity often coexist, comprehensive antibody screening should be conducted.
Electroencephalography Correlates of Well-Being Using a Low-Cost Wearable System
Authors: Cannard Cédric , Wahbeh Helané , Delorme Arnaud
Published: December 2021

Electroencephalography (EEG) alpha asymmetry is thought to reflect crucial brain processes underlying executive control, motivation, and affect. It has been widely used in psychopathology and, more recently, in novel neuromodulation studies. However, inconsistencies remain in the field due to the lack of consensus in methodological approaches employed and the recurrent use of small samples. Wearable technologies ease the collection of large and diversified EEG datasets that better reflect the general population, allow longitudinal monitoring of individuals, and facilitate real-world experience sampling. We tested the feasibility of using a low-cost wearable headset to collect a relatively large EEG database (N = 230, 22–80 years old, 64.3% female), and an open-source automatic method to preprocess it. We then examined associations between well-being levels and the alpha center of gravity (CoG) as well as trait EEG asymmetries, in the frontal and temporoparietal (TP) areas. Robust linear regression models did not reveal an association between well-being and alpha (8–13 Hz) asymmetry in the frontal regions, nor with the CoG. However, well-being was associated with alpha asymmetry in the TP areas (i.e., corresponding to relatively less left than right TP cortical activity as well-being levels increased). This effect was driven by oscillatory activity in lower alpha frequencies (8–10.5 Hz), reinforcing the importance of dissociating sub-components of the alpha band when investigating alpha asymmetries. Age was correlated with both well-being and alpha asymmetry scores, but gender was not. Finally, EEG asymmetries in the other frequency bands were not associated with well-being, supporting the specific role of alpha asymmetries with the brain mechanisms underlying well-being levels. Interpretations, limitations, and recommendations for future studies are discussed. This paper presents novel methodological, experimental, and theoretical findings that help advance human neurophysiological monitoring techniques using wearable neurotechnologies and increase the feasibility of their implementation into real-world applications.
Oculomotor Behavior Predict Professional Cricket Batting and Bowling Performance
Authors: Murray Nicholas P. , Lawton Josh , Rider Patrick , Harris Nathanial , Hunfalvay Melissa
Published: December 2021

Importance: A new, shorter version of cricket was introduced recently (Twenty20; T20). Since its inception, T20 cricket has rapidly become a popular and exciting format of cricket. However, there is little understanding of factors such as visual-motor control that influence expert performance.

Objective: The purpose of this project is to determine if a series of oculomotor measures can predict batting and bowling performance in professional cricket players.

Design: This study used a cross-sectional design. Each participant took part in a suite of eye-tracking tests to measure oculomotor behavior compared to their performance data.

Participants: This study used a sample of 59 male T20 league professional cricket players (30 Bowlers and 29 Batsman).

Results: One-way univariate analyses of variance examined the differences in oculomotor behavior between batsman and bowlers. A series of multiple regression analyses was conducted to evaluate how well the visual variables predict bowling and batting performance variables. Results demonstrate that several oculomotor eye tracking measures were good predictors of run performance and strike rate, including sports total score, sports on-field score, and sports functional score. Likewise, several of the same metrics predicted Runs and Wicket performance for bowlers. Overall, results provided further validation to a growing body of literature supporting the use of eye-tracking technology in performance evaluation.
Remote Subthreshold Stimulation Enhances Skin Sensitivity in the Lower Extremity
Authors: Plater Emma B. , Seto Vivian S. , Peters Ryan M. , Bent Leah R.
Published: December 2021

Foot sole skin interfaces with the ground and contributes to successful balance. In situations with reduced sensitivity in the glabrous foot skin, stochastic resonance (SR) improves skin sensitivity by adding tactile noise. Some situations, however, involve an interface comprised of hairy skin, which has higher thresholds for sensitivity. For example, in lower extremity amputation the residual limb is comprised of hairy leg skin. The main objective of this study was to determine if SR improves skin sensitivity in hairy skin, and whether a specific intensity of noise is most effective. Secondary objectives were to compare the effect between locations, ages and modalities. In 60 healthy participants a vibrotactile (test) input was delivered at the lower extremity concurrently with a second, noisy stimulus applied more proximally. The presence of a remote SR effect was tested in 15 young participants using electrotactile noise at the calf. Secondary objectives were tested in separate groups of 15 subjects and differed by substituting for one of the three variables: vibrotactile noise, heel site, and with older participants. A forced-choice protocol was used to determine detection ability of the subthreshold vibration test input with varying noise levels applied simultaneously (0, 20, 40, 60, 80, and 100% of perceptual threshold). An SR effect was identified when increased detection of the input was obtained at any level of noise versus no noise. It was found that all four test groups demonstrated evidence of SR: 33–47% of individuals showed better detection of the input with added noise. The SR effect did not appear consistently at any specific noise level for any of the groups, and none of the variables showed a superior ability to evoke SR. Interestingly, in approximately 33% of cases, threshold values fluctuated throughout testing. While this work has provided evidence that SR can enhance the perception of a vibrotactile input in hairy skin, these data suggest that the ability to repeatably show an SR effect relies on maintaining a consistent threshold.
Seed Oil Quality and Cultivation of Sambucus williamsii Hance as a New Oil Crop
Authors: Wang Shuyue , Yu Yongxin , Cui Mingxiao , Liu Kehai , Liu Kewu
Published: December 2021

Natural edible oil derived from wild non-cultivated oil crops contributed to human daily nutritional diversity and disease prevention. It was important to investigate the nutritional value of these oils and the feasibility of crop cultivation. The present study focused on the assessment of seed oil quality of Sambucus williamsii Hance (SWH) and its molecular breeding. Wild SWH seed oil was extracted by supercritical CO2 technology and the composition of the oil was determined by using gas chromatography mass spectrometry (GC-MS) analysis. The oil content of SWH seeds reaches around 40%. Its seed oil was found to be rich in unsaturated fatty acids, such as 24.24% of linolenic acid and 50.56% of linoleic acid, and vitamin E (25.92 mg kg−1). The cytotoxicity and heavy metal analysis showed SWH seed oil was safe for consumption. In addition, the SWH strains with excellent characteristics were screened out for cultivation according to genetic diversity and morphological analysis. Amplified fragment length polymorphism (AFLP) markers were used to evaluate the genetic diversity of 28 accessions of wild SWH seeds and 5 accessions were selected to cultivate. Among them, two strains of SWH (sample 3 and 6) with high yielding (275.7 and 266.8 area yield kg−1) were suitable for dense planting and could be used to establish the raw material forest of SWH seed oil. The results of this study indicated the potential of development of selected SWH as novel oil crops and their wide cultivation.
Exploring the Effects of Greek Yogurt Supplementation and Exercise Training on Serum Lithium and Its Relationship With Musculoskeletal Outcomes in Men
Authors: Baranowski Ryan W. , Skelly Lauren E. , Josse Andrea R. , Fajardo Val A.
Published: December 2021

Dairy products can act as a dietary source of lithium (Li), and a recent study in university-aged males demonstrated that Greek yogurt (GY) supplementation augmented gains in fat free mass, strength and bone formation after 12 weeks of resistance exercise training compared to carbohydrate (CHO) pudding supplementation. Here, we performed secondary analyses to explore whether GY would alter serum Li levels and whether changes in serum Li would associate with changes in body composition, strength, and bone turnover markers. Results show that the GY group maintained serum Li levels after exercise training, whereas the CHO group did not. Maintaining/elevating serum Li levels was also associated with greater gains in strength and reductions in bone resorption. However, controlling for other dietary factors in GY such as protein and calcium weakened these associations. Thus, future studies should assess the causative role, if any, of dietary Li alone on strength and bone resorption in humans.
Hepatoprotective Effect of Cereal Vinegar Sediment in Acute Liver Injury Mice and Its Influence on Gut Microbiota
Authors: Guan Qijie , Gong Tingting , Lu Zhen-Ming , Geng Yan , Duan Wenhui , Ren Yi-Lin , Zhang Xiao-Juan , Chai Li-Juan , Shi Jin-Song , Xu Zheng-Hong
Published: December 2021

Cereal vinegar sediment (CVS) is a natural precipitate formed during the aging process of traditional grain vinegar. It has been used as Chinese traditional medicine, while its composition and function are reported minimally. In this study, we measured CVS in terms of saccharide, protein, fat and water content, and polyphenol and flavonoid content. Furthermore, we determined the amino acids, organic acids, and other soluble metabolites in CVS using reverse-phase high-performance liquid chromatography (RP-HPLC), HPLC, and liquid chromatography with tandem mass spectrometry (LC-MS/MS) platforms. The hepatoprotective effect of CVS was evaluated in acute CCl4-induced liver injury mice. Administration of CVS for 7 days prior to the CCl4 treatment can significantly decrease liver alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and reactive oxygen species (ROS) levels, compared with those in the hepatic injury model group. The gut microbiota was changed by CCl4 administration and was partly shifted by the pretreatment of CVS, particularly the Muribaculaceae family, which was increased in CVS-treated groups compared with that in the CCl4 administration group. Moreover, the abundances of Alistipes genus and Muribaculaceae family were correlated with the liver ALT, AST, and malondialdehyde (MDA) levels. Our results illustrated the composition of CVS and its hepatoprotective effect in mice, suggested that CVS could be developed as functional food to prevent acute liver injury.
Effect of Polymorphisms of ABCB1 and MTHFR on Methotrexate-Related Toxicities in Adults With Hematological Malignancies
Authors: Han Jian , Liu Lu , Meng Li , Guo Huan , Zhang Jin , Han Zhi-Qiang , Hong Zhen-Ya
Published: December 2021

Study of the association between single nucleotide polymorphisms (SNPs) of methotrexate (MTX) pathway genes and MTX-related toxicity in the treatment of hematological malignancies is popular. Here, we studied the association between SNPs of MTHFR and ABCB1 and MTX-related toxicity in 157 adult Chinese patients diagnosed with hematological malignancies. Patients were genotyped for MTHFR rs1801131, MTHFR rs1801133, and ABCB1 rs1045642 by fluorescence in situ hybridization. Patients with MTHFR rs1801133T allele had a significantly higher risk of hematopoietic toxicity compared with those with CC genotype (p=0.003). With respect to MTHFR rs1801131, patients with CC and AC genotypes had significantly lower frequency of hematopoietic toxicity than patients with AA genotype (p=0.044). In conclusion, we identified an important influence of the SNPs of ABCB1 and MTHFR on MTX-related hematopoietic toxicity in adults with hematological malignancies. To optimize high-dose (HD)-MTX therapy and reduce related hematopoietic toxicity, it is necessary to detect the SNPs of MTHFR and ABCB1 before initiating HD-MTX and deciding the optimal dose of MTX and duration of leucovorin rescue, according to genetic tests and disease type in adults with hematological malignancies.
Biological Pathways Associated With the Development of Pulmonary Toxicities in Mesothelioma Patients Treated With Radical Hemithoracic Radiation Therapy: A Preliminary Study
Authors: Crovella Sergio , Revelant Alberto , Muraro Elena , Moura Ronald Rodrigues , Brandão Lucas , Trovò Marco , Steffan Agostino , Zacchi Paola , Zabucchi Giuliano , Minatel Emilio , Borelli Violetta
Published: December 2021

Radical hemithoracic radiotherapy (RHR), after lung-sparing surgery, has recently become a concrete therapeutic option for malignant pleural mesothelioma (MPM), an asbestos-related, highly aggressive tumor with increasing incidence and poor prognosis. Although the toxicity associated to this treatment has been reduced, it is still not negligible and must be considered when treating patients. Genetic factors appear to play a role determining radiotherapy toxicity. The aim of this study is the identification of biological pathways, retrieved through whole exome sequencing (WES), possibly associated to the development of lung adverse effects in MPM patients treated with RHR. The study included individuals with MPM, treated with lung-sparing surgery and chemotherapy, followed by RHR with curative intent, and followed up prospectively for development of pulmonary toxicity. Due to the strong impact of grade 3 pulmonary toxicities on the quality of life, compared with less serious adverse events, for genetic analyses, patients were divided into a none or tolerable pulmonary toxicity (NoSTox) group (grade ≤2) and a severe pulmonary toxicity (STox) group (grade = 3). Variant enrichment analysis allowed us to identify different pathway signatures characterizing NoSTox and Stox patients, allowing to formulate hypotheses on the protection from side effects derived from radiotherapy as well as factors predisposing to a worst response to the treatment. Our findings, being aware of the small number of patients analyzed, could be considered a starting point for the definition of a panel of pathways, possibly helpful in the management of MPM patients.
Extracorporeal Membrane Oxygenation Candidacy in Pediatric Patients Treated With Hematopoietic Stem Cell Transplant and Chimeric Antigen Receptor T-Cell Therapy: An International Survey
Authors: Ghafoor Saad , Fan Kimberly , Di Nardo Matteo , Talleur Aimee C. , Saini Arun , Potera Renee M. , Lehmann Leslie , Annich Gail , Wang Fang , McArthur Jennifer , Sandhu Hitesh
Published: December 2021

Introduction

Pediatric patients who undergo hematopoietic cell transplant (HCT) or chimeric antigen receptor T-cell (CAR-T) therapy are at high risk for complications leading to organ failure and the need for critical care resources. Extracorporeal membrane oxygenation (ECMO) is a supportive modality that is used for cardiac and respiratory failure refractory to conventional therapies. While the use of ECMO is increasing for patients who receive HCT, candidacy for these patients remains controversial. We therefore surveyed pediatric critical care and HCT providers across North America and Europe to evaluate current provider opinions and decision-making and institutional practices regarding ECMO use for patients treated with HCT or CAR-T.

Methods

An electronic twenty-eight question survey was distributed to pediatric critical care and HCT providers practicing in North America (United States and Canada) and Europe through the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network and individual emails. Responses to the survey were recorded in a REDCap®database.

Results

Two-hundred and ten participants completed the survey. Of these, 159 (76%) identified themselves as pediatric critical care physicians and 47 (22%) as pediatric HCT physicians or oncologists. The majority (99.5%) of survey respondents stated that they would consider patients treated with HCT or CAR-T therapy as candidates for ECMO support. However, pediatric critical care physicians identified more absolute and relative contraindications for ECMO than non-pediatric critical care physicians. While only 0.5% of respondents reported that they consider HCT as an absolute contraindication for ECMO, 6% of respondents stated that ECMO is contraindicated in HCT patients within their institution and only 23% have an institutional protocol or policy to guide the evaluation for ECMO candidacy of these patients. Almost half (49.1%) of respondents would accept a survival to hospital discharge of 20-30% for pediatric HCT patients requiring ECMO as adequate.

Conclusions

ECMO use for pediatric patients treated with HCT and CAR-T therapy is generally acceptable amongst physicians. However, there are differences in the evaluation and decision-making regarding ECMO candidacy amongst providers across medical specialties and institutions. Therefore, multidisciplinary collaboration is an essential component in establishing practice guidelines and advancing ECMO outcomes for these patients.
Antenatal Antibiotic Exposure Affects Enteral Feeding, Body Growth, and Neonatal Infection in Preterm Infants: A Retrospective Study
Authors: Luo Ping , Zhang Kun , Chen You , Geng Xiuwen , Wu Tong , Li Li , Zhou Ping , Jiang Ping-Ping , Ma Liya
Published: December 2021

Background: Antibiotics are widely prescribed by obstetricians, which exposes a large number of infants to antenatal antibiotics (AAB). The effect of AAB on various aspects of neonatal development of preterm infants remains unclear.

Methods: In this retrospective study, infants born with gestational age (GA) between 22 +0 and 36 +6 weeks at our unit from 2017 to 2019 were included. Multivariable analysis was adopted to examine the associations between AAB exposure and various outcomes related to enteral feeding process, body growth, and neonatal infection after adjusting for potential confounders. Further subanalysis on the exposure level of AAB and stratified analysis by GA (<34 vs. ≥34 weeks) were also conducted.

Results: In this cohort comprising 2,543 preterm infants, AAB was associated with decreased risks of feeding intolerance (odds ratio [OR]: 0.63, 95% confidence interval [CI]: 0.48–0.82) and neonatal infection (OR: 0.63, 95% CI: 0.41–0.94). Higher AAB exposure level was associated with higher Z scores of birth weight (β = 0.37, 95% CI: 0.27–0.47), but lower Δbodyweight Z-scores (β = −0.20, 95% CI: −0.27 to −0.13). AAB was positively associated with the parameters related to body growth in infants with GA <34 weeks but negatively associated in those with GA ≥34 weeks.

Conclusions: AAB exposure affects the enteral feeding process and neonatal infection. The effects on body growth vary by the exposure level of AAB and GA of infants. A well-designed prospective and preferably multi-centre study with predefined parameters is required to confirm our findings.
Liraglutide Improves Cognitive and Neuronal Function in 3-NP Rat Model of Huntington’s Disease
Authors: Shawki Samar M. , Saad Mohammed A. , Rahmo Rania M. , Wadie Walaa , El-Abhar Hanan S.
Published: December 2021

Huntington’s disease (HD) is an autosomal dominant inherited neurodegenerative disease characterized by progressive motor, psychiatric, and cognitive abnormalities. The antidiabetic drug liraglutide possesses a neuroprotective potential against several neurodegenerative disorders; however, its role in Huntington’s disease (HD) and the possible mechanisms/trajectories remain elusive, which is the aim of this work. Liraglutide (200 μg/kg, s.c) was administered to rats intoxicated with 3-nitropropionic acid (3-NP) for 4 weeks post HD model induction. Liraglutide abated the 3-NP-induced neurobehavioral deficits (open field and elevated plus maze tests) and histopathological changes. Liraglutide downregulated the striatal mRNA expression of HSP 27, PBR, and GFAP, while it upregulated that of DARPP32. On the molecular level, liraglutide enhanced striatal miR-130a gene expression and TrKB protein expression and its ligand BDNF, while it reduced the striatal protein content and mRNA expression of the death receptors sortilin and p75NTR, respectively. It enhanced the neuroprotective molecules cAMP, p-PI3K, p-Akt, and p-CREB, besides modulating the p-GSK-3β/p-β-catenin axis. Liraglutide enhanced the antioxidant transcription factor Nrf2, abrogated TBARS, upregulated both Bcl2 and Bcl-XL, and downregulated Bax along with decreasing caspase-3 activity. Therefore, liraglutide exerts a neurotherapeutic effect on 3-NP-treated rats that is, besides the upturn of behavioral and structural findings, it at least partially, increased miR-130a and modulated PI3K/Akt/CREB/BDNF/TrKB, sortilin, and p75NTR, and Akt/GSK-3β/p-β-catenin trajectories besides its capacity to decrease apoptosis and oxidative stress, as well as its neurotrophic activity.
Targeting Proteinase Activated Receptor-4 Reduces Mechanonociception During the Acute Inflammatory Phase but not the Chronic Neuropathic Phase of Osteoarthritis in Rats
Authors: O’Brien Melissa S. , McDougall Jason J.
Published: December 2021

Serine proteases are elevated in arthritic joints where they can cleave protease activated receptors (PARs) to modulate pain and inflammation. Activation of protease-activated receptor 4 (PAR4) has been implicated in inflammatory joint pain. Whether PAR4 is involved in osteoarthritis (OA) pain has not yet been explored. The aim of this study was to compare the role of PAR4 in modulating early versus late stage OA pain using two models of OA viz. monoiodoacetate (MIA) and medial meniscal transection (MMT). G-ratio calculation and electron microscopy analysis revealed saphenous nerve demyelination and structural damage during late stage but not early OA in both models. Using immunohistochemistry, neuronal expression of PAR4 was higher in early versus late OA. Systemic administration of the PAR4 antagonist pepducin P4pal10 reduced both secondary allodynia (von Frey hair algesiometry) and joint nociceptor firing (single unit recordings) in MMT and MIA animals compared to vehicle-treated animals in early OA. The PAR4 antagonist was ineffective at altering pain or joint afferent firing in post-inflammatory OA. During the acute phase of the models, joint inflammation as determined by laser speckle contrast analysis and intravital microscopy could be partially blocked by pepducin P4pal10. Compared to late-stage disease, inflammatory cytokines were elevated in early MIA and MMT rats. These findings suggest that PAR4 may be a viable target to treat the pain of early onset OA or during episodic inflammatory flares.
Modeling of Gate Tunable Synaptic Device for Neuromorphic Applications
Authors: Shen Yang , Tian He , Liu Yanming , Wu Fan , Yan Zhaoyi , Hirtz Thomas , Wang Xuefeng , Ren Tian-Ling
Published: December 2021

The emerging memories are great candidates to establish neuromorphic computing challenging non-Von Neumann architecture. Emerging non-volatile resistive random-access memory (RRAM) attracted abundant attention recently for its low power consumption and high storage density. Up to now, research regarding the tunability of the On/Off ratio and the switching window of RRAM devices remains scarce. In this work, the underlying mechanisms related to gate tunable RRAMs are investigated. The principle of such a device consists of controlling the filament evolution in the resistive layer using graphene and an electric field. A physics-based stochastic simulation was employed to reveal the mechanisms that link the filament size and the growth speed to the back-gate bias. The simulations demonstrate the influence of the negative gate voltage on the device current which in turn leads to better characteristics for neuromorphic computing applications. Moreover, a high accuracy (94.7%) neural network for handwritten character digit classification has been realized using the 1-transistor 1-memristor (1T1R) crossbar cell structure and our stochastic simulation method, which demonstrate the optimization of gate tunable synaptic device.
Leptin in the Respiratory Tract: Is There a Role in SARS-CoV-2 Infection?
Authors: Bruno Andreina , Ferrante Giuliana , Di Vincenzo Serena , Pace Elisabetta , La Grutta Stefania
Published: December 2021

Leptin is a pleiotropic adipocytokine involved in several physiologic functions, with a known role in innate and adaptive immunity as well as in tissue homeostasis. Long- and short-isoforms of leptin receptors are widely expressed in many peripheral tissues and organs, such as the respiratory tract. Similar to leptin, microbiota affects the immune system and may interfere with lung health through the bidirectional crosstalk called the “gut-lung axis.” Obesity leads to impaired protective immunity and altered susceptibility to pulmonary infections, as those by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although it is known that leptin and microbiota link metabolism and lung health, their role within the SARS-CoV2 coronavirus disease 2019 (COVID-19) deserves further investigations. This review aimed to summarize the available evidence about: (i) the role of leptin in immune modulation; (ii) the role of gut microbiota within the gut-lung axis in modulating leptin sensitivity; and (iii) the role of leptin in the pathophysiology of COVID-19.