bluuebunny/crossref_metadata_2025 huggingface dataset:
Auditory and Vestibular Characteristics of NLRP3 Inflammasome Related Autoinflammatory Disorders: Monogenic Hearing Loss Can Be Improved by Anti-interleukin-1 Therapy
Authors: Nakanishi Hiroshi , Yamada Satoshi , Kita Junya , Shinmura Daichi , Hosokawa Kumiko , Sahara Sosuke , Misawa Kiyoshi
Published: April 2022

Inflammasomes are large multimeric protein complexes which regulate the activation of the proinflammatory cytokines interleukins-1β and−18 and inflammatory cell death called pyroptosis. NLRP1, NLRP3, NLRC4, AIM2, and pyrin can induce the formation of inflammasomes. Of these, the NLRP3 inflammasome is the most well-characterized. Recent studies revealed that variants of the NLRP3 gene cause genetic diseases, including systemic inflammatory syndrome called cryopyrin-associated periodic syndrome (CAPS) and non-syndromic sensorineural hearing loss DFNA34. NLRP3 variants cause CAPS and DFNA34 by constitutively activating the NLRP3 inflammasome and increasing IL-1β release. Patients with CAPS show systemic inflammatory symptoms, and hearing loss is a characteristic feature. Patients with CAPS and DFNA34 show progressive bilateral sensorineural hearing loss. Hearing loss has unique characteristics that can be improved or stabilized by anti-interluekin-1 therapy, although it is usually difficult to alleviate genetic hearing loss by drugs. However, it should be noted that there is a window of opportunity to respond to treatment, and younger patients are most likely to respond. It is important to know the characteristics of CAPS and DFNA34 for early diagnosis, and mutation analysis of NLRP3 will lead to a definite diagnosis. In this review, we summarize the current understanding of the mechanisms of the NLRP3 inflammasome and characteristics of patients with CAPS and DFNA34, especially focused on auditory and vestibular findings.
Contralaterally Controlled Functional Electrical Stimulation Combined With Brain Stimulation for Severe Upper Limb Hemiplegia—Study Protocol for a Randomized Controlled Trial
Authors: Mohan Akhil , Knutson Jayme S. , Cunningham David A. , Widina Morgan , O'Laughlin Kyle , Arora Tarun , Li Xin , Sakaie Ken , Wang Xiaofeng , Uchino Ken , Plow Ela B.
Published: April 2022

Background

Approximately two-thirds of stroke survivors experience chronic upper limb paresis, and of them, 50% experience severe paresis. Treatment options for severely impaired survivors are often limited. Rehabilitation involves intensively engaging the paretic upper limb, and disincentivizing use of the non-paretic upper limb, with the goal to increase excitability of the ipsilesional primary motor cortex (iM1) and suppress excitability of the undamaged (contralesional) motor cortices, presumed to have an inhibitory effect on iM1. Accordingly, brain stimulation approaches, such as repetitive transcranial magnetic stimulation (rTMS), are also given to excite iM1 and/or suppress contralesional motor cortices. But such approaches aimed at ultimately increasing iM1 excitability yield limited functional benefit in severely impaired survivors who lack sufficient ipsilesional substrate.

Aim

Here, we test the premise that combining Contralaterally Controlled Functional Electrical Stimulation (CCFES), a rehabilitation technique that engages the non-paretic upper limb in delivery of neuromuscular electrical stimulation to the paretic upper limb, and a new rTMS approach that excites intact, contralesional higher motor cortices (cHMC), may have more favorable effect on paretic upper limb function in severely impaired survivors based on recruitment of spared, transcallosal and (alternate) ipsilateral substrate.

Methods

In a prospective, double-blind, placebo-controlled RCT, 72 chronic stroke survivors with severe distal hand impairment receive CCFES plus cHMC rTMS, iM1 rTMS, or sham rTMS, 2X/wk for 12wks. Measures of upper limb motor impairment (Upper Extremity Fugl Meyer, UEFM), functional ability (Wolf Motor-Function Test, WMFT) and perceived disability are collected at 0, 6, 12 (end-of-treatment), 24, and 36 wks (follow-up). TMS is performed at 0, 12 (end-of-treatment), and 36 wks (follow-up) to evaluate inter-hemispheric and ipsilateral mechanisms. Influence of baseline severity is also characterized with imaging.

Conclusions

Targeting of spared neural substrates and rehabilitation which engages the unimpaired limb in movement of the impaired limb may serve as a suitable combinatorial treatment option for severely impaired stroke survivors.

ClinicalTrials No

NCT03870672.
Attentional Prioritization of Complex, Naturalistic Stimuli Maintained in Working-Memory–A Dot-Probe Event-Related Potentials Study
Authors: Rutkowska Natalia , Doradzińska Łucja , Bola Michał
Published: April 2022

Recent studies suggest that a stimulus actively maintained in working memory (WM) automatically captures visual attention when subsequently perceived. Such a WM-based guidance effect has been consistently observed for stimuli defined by simple features, such as color or orientation, but studies using more complex stimuli provided inconclusive results. Therefore, we investigated whether the WM-based guidance effect occurs also for naturalistic stimuli, whose identity is defined by multiple features and relations among them, specifically for faces and houses. The experiment consisted of multiple blocks in which participants (N = 28) either memorized or merely saw (WM or exposure condition, respectively) a template stimulus and then performed several dot-probe trials, with pairs of stimuli (template and control) presented laterally as distractors and followed by a target-asterisk. Analysis of reaction-times (RT) in the dot-probe task shows that memorized stimuli were prioritized by attention and points toward attention-hold, rather than capture, as a mechanism of attentional prioritization. Consistent with this interpretation, memorized items did not evoke a lateralized N2pc ERP component, thought to indicate attention shifts. However, in an exploratory ERP analysis we found evidence for a very early (100–200 ms post-stimulus) prioritization specific to the memorized faces, which is in line with the sensory recruitment theory of WM. In conclusion, our data provide evidence that complex stimuli are prioritized by attention when maintained in WM, and that the mechanism of such prioritization is based on a prolonged hold of spatial attention.
Early Life Exposure to a Diet With a Supramolecular Lipid Structure Close to That of Mammalian Milk Improves Early Life Growth, Skeletal Development, and Later Life Neurocognitive Function in Individually and Socially Housed Male C57BL/6J Mice
Authors: van Heijningen Steffen , Karapetsas Giorgio , van der Beek Eline M. , van Dijk Gertjan , Schipper Lidewij
Published: April 2022

Breastfeeding (duration) can be positively associated with infant growth outcomes as well as improved cognitive functions during childhood and later life stages. (Prolonged) exposure to optimal lipid quantity and quality, i.e., the supramolecular structure of lipids, in mammalian milk, may contribute to these beneficial effects through nutritional early-life programming. In this pre-clinical study, we exposed male C57BL/6J mice from post-natal Days 16 to 42 (i.e., directly following normal lactation), to a diet with large lipid droplets coated with bovine milk fat globule membrane-derived phospholipids, which mimic more closely the supramolecular structure of lipid droplets in mammalian milk. We investigated whether exposure to this diet could affect growth and brain development-related parameters. As these outcomes are also known to be affected by the post-weaning social environment in mice, we included both individually housed and pair-wise housed animals and studied whether effects of diet were modulated by the social environment. After Day 42, all the animals were fed standard semi-synthetic rodent diet. Growth and body composition were assessed, and the mice were subjected to various behavioral tests. Individual housing attenuated adolescent growth, reduced femur length, and increased body fat mass. Adult social interest was increased due to individual housing, while cognitive and behavioral alterations as a result of different housing conditions were modest. The diet increased adolescent growth and femur length, increased lean body mass, reduced adolescent anxiety, and improved adult cognitive performance. These effects of diet exposure were comparable between individually and socially housed mice. Hence, early life exposure to a diet with lipid droplets that mimic the supramolecular structure of those in mammalian milk may improve adolescent growth and alters brain function in both socially and individually housed mice. These findings suggest that lipid structure in infant milk formula may be a relevant target for nutritional solutions, targeting both healthy infants and infants facing growth challenges.
Elevated Axonal Protein Markers Following Repetitive Blast Exposure in Military Personnel
Authors: Vorn Rany , Naunheim Rosanne , Lai Chen , Wagner Chelsea , Gill Jessica M.
Published: April 2022

Blast exposures that occur during training are common in military personnel; however, the biomarkers that relate to these subtle injuries is not well understood. Therefore, the purpose of this study is to identify the acute biomarkers related to blast injury in a cohort of military personnel exposure to blast-related training. Thirty-four military personnel who participated in the training program were included in this study. Blood samples were collected before and after repetitive blast-related training on days 2 (n = 19) and days 7 (n = 15). Serum concentration (pg/mL) of tau, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and phosphorylated tau181 (p-tau181) were measured using an ultrasensitive immunoassay platform. We observed that serum p-tau181 concentrations were elevated after exposed to repetitive blast on days 2 (z = −2.983, p = 0.003) and days 7 (z = −2.158, p = 0.031). Serum tau (z = −2.272, p = 0.023) and NfL (z = −2.158, p = 0.031) levels were significantly elevated after exposure to repetitive blasts on days 7. Our findings indicate that blast exposure affects serum biomarkers indicating axonal injury.
First Food and Drug Administration Cleared Thin-Film Electrode for Intracranial Stimulation, Recording, and Monitoring of Brain Activity—Part 1: Biocompatibility Testing
Authors: Kullmann Aura , Kridner Debra , Mertens Steve , Christianson Mark , Rosa Dave , Diaz-Botia Camilo A.
Published: April 2022

Subdural strip and grid invasive electroencephalography electrodes are routinely used for surgical evaluation of patients with drug-resistant epilepsy (DRE). Although these electrodes have been in the United States market for decades (first FDA clearance 1985), their fabrication, materials, and properties have hardly changed. Existing commercially available electrodes are made of silicone, are thick (>0.5 mm), and do not optimally conform to brain convolutions. New thin-film polyimide electrodes (0.08 mm) have been manufactured to address these issues. While different thin-film electrodes are available for research use, to date, only one electrode is cleared by Food and Drug Administration (FDA) for use in clinical practice. This study describes the biocompatibility tests that led to this clearance. Biocompatibility was tested using standard methods according to International Organization for Standardization (ISO) 10993. Electrodes and appropriate control materials were bent, folded, and placed in the appropriate extraction vehicles, or implanted. The extracts were used for in vitro and in vivo tests, to assess the effects of any potential extractable and leachable materials that may be toxic to the body. In vitro studies included cytotoxicity tested in L929 cell line, genotoxicity tested using mouse lymphoma assay (MLA) and Ames assay, and hemolysis tested in rabbit whole blood samples. The results indicated that the electrodes were non-cytotoxic, non-mutagenic, non-clastogenic, and non-hemolytic. In vivo studies included sensitization tested in guinea pigs, irritation tested in rabbits, acute systemic toxicity testing in mice, pyrogenicity tested in rabbits, and a prolonged 28-day subdural implant in sheep. The results indicated that the electrodes induced no sensitization and irritation, no weight loss, and no temperature increase. Histological examination of the sheep brain tissue showed no or minimal immune cell accumulation, necrosis, neovascularization, fibrosis, and astrocyte infiltration, with no differences from the control material. In summary, biocompatibility studies indicated that these new thin-film electrodes are appropriate for human use. As a result, the electrodes were cleared by the FDA for use in clinical practice [510(k) K192764], making it the first thin-film subdural electrode to progress from research to clinic. Its readiness as a commercial product ensures availability to all patients undergoing surgical evaluation for DRE.
Cerebral Metabolic Network in Patients With Anti-N-Methyl-D-Aspartate Receptor Encephalitis on 18F-FDG PET Imaging
Authors: Huang Gan , Xin Mei , Hao Yong , Bai Shuwei , Liu Jianjun , Zhang Chenpeng
Published: April 2022

Background

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common autoimmune encephalitis (AE), and the prognosis may significantly be improved if identified earlier and immune-related treated more effectively. This study evaluated the brain metabolic network using fluorodeoxyglucose positron emission tomography (FDG PET).

Material and methods

FDG PET imaging of patients with NMDAR encephalitis was used to investigate the metabolic connectivity network, which was analyzed using the graph theory. The results in patients were compared to those in age- and sex-matched healthy controls.

Results

The hub nodes were mainly in the right frontal lobe in patients with NMDAR encephalitis. The global and local efficiencies in most brain regions were significantly reduced, and the shortest characteristic path length was significantly longer, especially in the temporal and occipital lobes. Significant network functions of topology properties were enhanced in the right frontal, caudate nucleus, and cingulate gyrus. In addition, the internal connection integration in the left cerebral hemisphere was poor, and the transmission efficiency of Internet information was low.

Conclusion

The present findings indicate that those characteristic and connections of metabolic network were changed in the brain by graph theory analysis quantitatively, which is helpful to better understand neuropathological and physiological mechanisms in patients with anti-NMDAR encephalitis.
Dysfunction of the Hippocampal-Lateral Septal Circuit Impairs Risk Assessment in Epileptic Mice
Authors: Cao Yi , Sun Chongyang , Huang Jianyu , Sun Peng , Wang Lulu , He Shuyu , Liao Jianxiang , Lu Zhonghua , Lu Yi , Zhong Cheng
Published: April 2022

Temporal lobe epilepsy, a chronic disease of the brain characterized by degeneration of the hippocampus, has impaired risk assessment. Risk assessment is vital for survival in complex environments with potential threats. However, the underlying mechanisms remain largely unknown. The intricate balance of gene regulation and expression across different brain regions is related to the structure and function of specific neuron subtypes. In particular, excitation/inhibition imbalance caused by hyperexcitability of glutamatergic neurons and/or dysfunction of GABAergic neurons, have been implicated in epilepsy. First, we estimated the risk assessment (RA) by evaluating the behavior of mice in the center of the elevated plus maze, and found that the kainic acid-induced temporal lobe epilepsy mice were specifically impaired their RA. This experiment evaluated approach-RA, with a forthcoming approach to the open arm, and avoid-RA, with forthcoming avoidance of the open arm. Next, results from free-moving electrophysiological recordings showed that in the hippocampus, ∼7% of putative glutamatergic neurons and ∼15% of putative GABAergic neurons were preferentially responsive to either approach-risk assessment or avoid-risk assessment, respectively. In addition, ∼12% and ∼8% of dorsal lateral septum GABAergic neurons were preferentially responsive to approach-risk assessment and avoid-risk assessment, respectively. Notably, during the impaired approach-risk assessment, the favorably activated dorsal dentate gyrus and CA3 glutamatergic neurons increased (∼9%) and dorsal dentate gyrus and CA3 GABAergic neurons decreased (∼7%) in the temporal lobe epilepsy mice. Then, we used RNA sequencing and immunohistochemical staining to investigate which subtype of GABAergic neuron loss may contribute to excitation/inhibition imbalance. The results show that temporal lobe epilepsy mice exhibit significant neuronal loss and reorganization of neural networks. In particular, the dorsal dentate gyrus and CA3 somatostatin-positive neurons and dorsal lateral septum cholecystokinin-positive neurons are selectively vulnerable to damage after temporal lobe epilepsy. Optogenetic activation of the hippocampal glutamatergic neurons or chemogenetic inhibition of the hippocampal somatostatin neurons directly disrupts RA, suggesting that an excitation/inhibition imbalance in the dHPC dorsal lateral septum circuit results in the impairment of RA behavior. Taken together, this study provides insight into epilepsy and its comorbidity at different levels, including molecular, cell, neural circuit, and behavior, which are expected to decrease injury and premature mortality in patients with epilepsy.
Probiotic Mixture Containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum Affects Brain Responses Toward an Emotional Task in Healthy Subjects: A Randomized Clinical Trial
Authors: Rode Julia , Edebol Carlman Hanna M. T. , König Julia , Repsilber Dirk , Hutchinson Ashley N. , Thunberg Per , Andersson Pernilla , Persson Jonas , Kiselev Andrey , Lathrop Stern Lori , Salomon Benita , Mohammed Ahmed Abdulilah , Labus Jennifer S. , Brummer Robert J.
Published: April 2022

Background

Evidence from preclinical studies suggests that probiotics affect brain function via the microbiome-gut-brain axis, but evidence in humans remains limited.

Objective

The present proof-of-concept study investigated if a probiotic product containing a mixture of Bifidobacterium longum R0175, Lactobacillus helveticus R0052 and Lactiplantibacillus plantarum R1012 (in total 3 × 109 CFU/day) affected functional brain responses in healthy subjects during an emotional attention task.

Design

In this double-blinded, randomized, placebo-controlled crossover study (Clinicaltrials.gov, NCT03615651), 22 healthy subjects (24.2 ± 3.4 years, 6 males/16 females) were exposed to a probiotic intervention and a placebo for 4 weeks each, separated by a 4-week washout period. Subjects underwent functional magnetic resonance imaging while performing an emotional attention task after each intervention period. Differential brain activity and functional connectivity were assessed.

Results

Altered brain responses were observed in brain regions implicated in emotional, cognitive and face processing. Increased activation in the orbitofrontal cortex, a region that receives extensive sensory input and in turn projects to regions implicated in emotional processing, was found after probiotic intervention compared to placebo using a cluster-based analysis of functionally defined areas. Significantly reduced task-related functional connectivity was observed after the probiotic intervention compared to placebo. Fecal microbiota composition was not majorly affected by probiotic intervention.

Conclusion

The probiotic intervention resulted in subtly altered brain activity and functional connectivity in healthy subjects performing an emotional task without major effects on the fecal microbiota composition. This indicates that the probiotic effects occurred via microbe-host interactions on other levels. Further analysis of signaling molecules could give possible insights into the modes of action of the probiotic intervention on the gut-brain axis in general and brain function specifically. The presented findings further support the growing consensus that probiotic supplementation influences brain function and emotional regulation, even in healthy subjects. Future studies including patients with altered emotional processing, such as anxiety or depression symptoms are of great interest.

Clinical Trial Registration

[http://clinicaltrials.gov/], identifier [NCT03615651].
Anti-inflammatory Effect of a Novel Pectin Polysaccharide From Rubus chingii Hu on Colitis Mice
Authors: Kong Yuanfang , Hu Yulong , Li Jieming , Cai Juntao , Qiu Yuanhao , Dong Chunhong
Published: April 2022

Rubus chingii Hu has been used as a functional food for a long time. A novel pectin polysaccharide named RCHP-S from R. chingii Hu was structurally identified and explored its anti-inflammatory effect on colitis mice. RCHP-S was composed of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, and arabinose. NMR spectroscopy and methylation analysis showed that RCHP-S was mainly composed of HG-type pectin domains but also contains a small amount of RG-I. The anti-inflammatory tests indicated that the mouse macrophage RAW 264.7 cells pretreated with RCHP-S could show a significant inhibitory effect on the mRNA level of iNOS, IL-1β, IL-6, and TNF-α in vitro. Polysaccharide RCHP-S reduced the enteritis symptoms in dextran sulfate sodium (DSS)-induced colitis mice by inhibiting released inflammatory factors. These results indicated that the R. chingii Hu polysaccharide can be used as food additives for the treatment of intestinal inflammation.
Combined Straw and Plastic Film Mulching Can Increase the Yield and Quality of Open Field Loose-Curd Cauliflower
Authors: Xie Yandong , Li Jinwu , Jin Li , Wei Shouhui , Wang Shuya , Jin Ning , Wang Junwen , Xie Jianming , Feng Zhi , Zhang Guobin , Lyu Jian , Yu Jihua
Published: April 2022

To evaluate the impact of straw mulching on the production of open field loose-curd cauliflower, this study analyzed the “Feicui No.9” cauliflower variety, grown in field trials in Northwest China, in 2019 and 2020. Plots in an open field were prepared without mulch (CK1) and with plastic film mulch (CK2), as experimental controls, along with three experimental mulching methods, including dual straw and plastic film mulch (T1), inter-row straw mulch (T2), and full straw mulch (T3). The effects of the different ground cover alternatives on loose-curd cauliflower's dry matter accumulation, yield, quality, and volatile compounds, were explored. The results showed that, compared with CK2 treatment, T1 treatment promoted the accumulation of dry matter, and increased the economic and biological yield, by 12.98 and 6.51%, respectively. The soluble sugar and vitamin C content in loose-curd cauliflower heads, subjected to T1 treatment, increased by 18.46 and 8.12%, respectively, and the nitrate content decreased by 25.57%. Moreover, the T1, T2, and T3 treatments significantly increased the levels of macro-, meso-, and microelements. Headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) was used to determine the volatile substances in loose-curd cauliflower heads from the 2020 harvesting period. Detected compounds included 17 aldehydes, 15 ketones, 10 alcohols, 15 esters, 29 hydrocarbons, 12 nitrogen-containing compounds, and 17 other substances. T1, T2, and T3 treatments increased the volatile substance content, whereas T1 treatment increased the quantity of volatile substances. In summary, dual mulching with straw and plastic film could promote dry matter accumulation, significantly increase the yield and quality, and effectively improve the flavor of loose-curd cauliflower. This mulching technique can be applied to open field vegetable and corn production areas, providing technical and theoretical support for the realization of high-yield, high-quality production models and a new straw recycling method.
Identification and Characterization of the Bioactive Polyphenols and Volatile Compounds in Sea Buckthorn Leaves Tea Together With Antioxidant and α-Glucosidase Inhibitory Activities
Authors: Wang Ningning , Wen Xiufeng , Gao Yan , Lu Shunguang , Li Yimeng , Shi Yanbin , Yang Zhigang
Published: April 2022

Sea buckthorn leaves have been used for tea making in food field gradually. This study was carried out to characterize the bioactive polyphenols and volatile compounds in sea buckthorn leaves (SL), sea buckthorn leaves green tea (SGT), and sea buckthorn leaves black tea (SBT) by using high-performance liquid chromatography with an UV detector (HPLC-UV), the liquid chromatography-mass spectrometry (LC-MS), and headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC-MS), in combination with multivariate analysis. A total of 48 non-volatile metabolites and 295 volatile metabolites were identified. Then, the total polyphenol and total flavonoid contents in SL, SGT, and SBT were also analyzed. Moreover, SL and SGT showed greater antioxidant activities based on 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), and oxygen radical absorbance capacity (ORAC) results. At the concentration of 0.1 mg/ml, their DPPH and ABTS radical scavenging ratios were 66 to 95%, while SBT exhibited lower antioxidant activity of 26 to 44%. SL, SGT, and SBT displayed moderate α-glucosidase inhibitory activity.
Comparison of Efficacy Between Transabdominal and Transthoracic Surgical Approaches for Siewert Type II Adenocarcinoma of the Esophagogastric Junction: A Systematic Review and Meta-Analysis
Authors: Li Zonglin , Jiang Huaiwu , Chen Jin , Jiang Yifan , Liu Yi , Xu Linxia
Published: April 2022

Background

The optimal surgical approach, whether transabdominal (TA) or transthoracic (TT), for Siewert type II adenocarcinoma of the esophagogastric junction (AEG) remains controversial. This study compares the efficacy of TA and TT surgical approaches for Siewert type II AEG.

Methods

Studies comparing the surgical and oncological outcomes of TA and TT surgical approaches for Siewert type II AEG up to June 2021 were systematically searched on the Web of Science, PubMed, Embase, and Cochrane Library. A pooled analysis was performed for the available data regarding the baseline features, surgical, and oncological outcomes. The RevMan 5.3 software was used to perform the statistical analysis. Quality evaluation and publication bias were also conducted.

Results

Twelve studies with a total of 2,011 patients, including 985 patients in the TA group and 1,026 patients in the TT group, were included in this study. In the pooled analysis, the surgical outcomes, namely, operative time (MD = −54.61, 95% CI = −123.76 to 14.54, P = 0.12), intraoperative blood loss (MD = −28.85, 95% CI = −71.15 to 13.46, P = 0.18), the number of dissected lymph nodes (MD = 1.90, 95% CI = −1.32 to 5.12, P = 0.25), postoperative complications (OR = 0.84, 95% CI = 0.65 to 1.07, p = 0.16), anastomotic leakage rate (OR = 1.02, 95% CI = 0.63 to 1.65, p = 0.93), and postoperative death rate (OR = 0.89, 95% CI = 0.46 to 1.72, p = 0.73), and the oncological outcomes, namely, overall recurrence rate (OR = 0.75, 95% CI = 0.37 to 1.50, p = 0.41), 3-year overall survival (OS) rate (OR = 1.19, 95% CI = 0.54 to 2.65, p = 0.66), and 5-year OS rate (OR = 1.21, 95% CI = 0.84 to 1.74, p = 0.30) of the two groups were all comparable.

Conclusions

Both TA and TT surgical approaches are appropriate for Siewert type II AEG, and neither has a significant advantage in terms of short- and long-term outcomes. However, more high-quality randomized controlled trials are needed to confirm this conclusion.
Generating Full-Field Digital Mammogram From Digitized Screen-Film Mammogram for Breast Cancer Screening With High-Resolution Generative Adversarial Network
Authors: Zhou Yuanpin , Wei Jun , Wu Dongmei , Zhang Yaqin
Published: April 2022

Purpose

Developing deep learning algorithms for breast cancer screening is limited due to the lack of labeled full-field digital mammograms (FFDMs). Since FFDM is a new technique that rose in recent decades and replaced digitized screen-film mammograms (DFM) as the main technique for breast cancer screening, most mammogram datasets were still stored in the form of DFM. A solution for developing deep learning algorithms based on FFDM while leveraging existing labeled DFM datasets is a generative algorithm that generates FFDM from DFM. Generating high-resolution FFDM from DFM remains a challenge due to the limitations of network capacity and lacking GPU memory.

Method

In this study, we developed a deep-learning-based generative algorithm, HRGAN, to generate synthesized FFDM (SFFDM) from DFM. More importantly, our algorithm can keep the image resolution and details while using high-resolution DFM as input. Our model used FFDM and DFM for training. First, a sliding window was used to crop DFMs and FFDMs into 256 × 256 pixels patches. Second, the patches were divided into three categories (breast, background, and boundary) by breast masks. Patches from the DFM and FFDM datasets were paired as inputs for training our model where these paired patches should be sampled from the same category of the two different image sets. U-Net liked generators and modified discriminators with two-channels output, one channel for distinguishing real and SFFDMs and the other for representing a probability map for breast mask, were used in our algorithm. Last, a study was designed to evaluate the usefulness of HRGAN. A mass segmentation task and a calcification detection task were included in the study.

Results

Two public mammography datasets, the CBIS-DDSM dataset and the INbreast dataset, were included in our experiment. The CBIS-DDSM dataset includes 753 calcification cases and 891 mass cases with verified pathology information, resulting in a total of 3568 DFMs. The INbreast dataset contains a total of 410 FFDMs with annotations of masses, calcifications, asymmetries, and distortions. There were 1784 DFMs and 205 FFDM randomly selected as Dataset A. The remaining DFMs from the CBIS-DDSM dataset were selected as Dataset B. The remaining FFDMs from the INbreast dataset were selected as Dataset C. All DFMs and FFDMs were normalized to 100μm × 100μm in our experiments. A study with a mass segmentation task and a calcification detection task was performed to evaluate the usefulness of HRGAN.

Conclusions

The proposed HRGAN can generate high-resolution SFFDMs from DFMs. Extensive experiments showed the SFFDMs were able to help improve the performance of deep-learning-based algorithms for breast cancer screening on DFM when the size of the training dataset is small.
Preoperative Concurrent Chemoradiotherapy Versus Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer: Phase II Randomized Study
Authors: Wang Xin , Zhao Dong-Bing , Yang Lin , Chi Yihebali , Zhao Hong , Jiang Li-Ming , Jiang Jun , Tang Yuan , Li Ning , Liu Wen-Yang , Dou Li-Zhou , Zou Shuang-Mei , Xue Li-Yan , Ren Jian-Song , Tian Yan-Tao , Che Xu , Guo Chun-Guang , Bai Xiao-Feng , Sun Yue-Min , Wang Shu-Lian , Song Yong-Wen , Liu Yue-Ping , Fang Hui , Li Ye-Xiong , Jin Jing
Published: April 2022

Objective

We evaluated and compared the efficacy and safety of neoadjuvant chemoradiotherapy (NACRT) versus neoadjuvant chemotherapy (NACT) for locally advanced gastric cancer (LAGC) in a single-center randomized phase II trial.

Methods

Patients with LAGC were enrolled and received either NACT or NACRT, followed by gastrectomy and adjuvant chemotherapy. The primary endpoint was an R0 resection rate.

Results

We enrolled 75 patients: 75.7% (NACT, 28/37 patients) and 76.3% (NACRT, 29/38 patients) underwent surgery; R0 resection rates were 73.0% (27/37) and 73.7% (28/38), respectively. The NACRT group had significantly better major pathological response than the NACT group (37.9% vs 17.9%, p = 0.019). Between-group postoperative complications were not significantly different. The median follow-up was 59.6 months; 5-year overall survival (OS) rate was 50.1% (NACT) and 61.9% (NACRT); neither group reached the median OS; median progression-free survival was 37.3 and 63.4 months, respectively.

Conclusions

S-1-based NACRT did not improve the R0 resection rate, although it presented better tumor regression with similar safety to NACT.

Trial registration

ClinicalTrial.gov NCT02301481
A Pyroptosis-Related Gene Panel for Predicting the Prognosis and Immune Microenvironment of Cervical Cancer
Authors: Hu Haoran , Yang Meiqin , Dong Wei , Yin Bo , Ding Jianyi , Huang Baoyou , Zheng Qingliang , Li Fang , Han Lingfei
Published: April 2022

Cervical cancer (CC) is one of the most common malignant tumors of the female reproductive system. And the immune system disorder in patients results in an increasing incidence rate and mortality rate. Pyroptosis is an immune system-related programmed cell death pathway that produces systemic inflammation by releasing pro-inflammatory intracellular components. However, the diagnostic significance of pyroptosis-related genes (PRGs) in CC is still unclear. Therefore, we identified 52 PRGs from the TCGA database and screened three Differentially Expressed Pyroptosis-Related Genes (DEPRGs) in the prognosis of cervical cancer: CHMP4C, GZMB, TNF. The least absolute shrinkage and selection operator (LASSO) regression analysis and multivariate COX regression analysis were then used to construct a gene panel based on the three prognostic DEPRGs. The patients were divided into high-and low-risk groups based on the median risk score of the panel. According to the Kaplan-Meier curve, there was a substantial difference in survival rates between the two groups, with the high-risk group’s survival rate being significantly lower than the low-risk group’s. The PCA and t-SNE analyses revealed that the panel was able to differentiate patients into high-and low-risk groups. The area under the ROC curve (AUC) shows that the prognostic panel has high sensitivity and specificity. The risk score could then be employed as an independent prognostic factor using univariate and multivariate COX regression analyses paired with clinical data. The analyses of GO and KEGG functional enrichment of differentially expressed genes (DEGs) in the high-and low-risk groups revealed that these genes were primarily engaged in immune response and inflammatory cell chemotaxis. To illustrate immune cell infiltration in CC patients further, we used ssGSEA to compare immune-related cells and immune pathway activation between the high-and low-risk groups. The link between three prognostic DEPRGs and immune-related cells was still being discussed after evaluating immune cell infiltration in the TCGA cohort with “CIBERSORT.” In addition, the GEPIA database and qRT-PCR analysis were used to verify the expression levels of prognostic DEPRGs. In conclusion, PRGs are critical in tumor immunity and can be utilized to predict the prognosis of CC.
PRL-3 and MMP9 Expression and Epithelial-Mesenchymal Transition Markers in Circulating Tumor Cells From Patients With Colorectal Cancer: Potential Value in Clinical Practice
Authors: Hong Xiao-Cui , Liang Qi-Lian , Chen Man , Yang Hai-Xia , Huang Jie , Yi Si-Lin , Wang Zhen-Wei , Liang Hai-Yan , Zhang Ding-Yue , Huang Zeng-Yi
Published: April 2022

Objective

To evaluate the clinical correlation of epithelial-mesenchymal transition (EMT) with PRL-3 and MMP9 expression in the circulating tumor cells (CTCs) of patients with colorectal cancer (CRC).

Materials and Methods

Between January 2016 and December 2018, the EMT phenotype-based subsets of CTCs and the expression levels of PRL-3 and MMP9 in CTCs were identified, and their clinical values in 172 patients were evaluated. The CTCs were isolated, classified, and counted using the CanPatrol™ CTC filtration system. The CTC subsets (epithelial cells, mesenchymal cells and biphenotypic cells), as well as PRL-3 and MMP9 expression, were detected by RNA in situ hybridization.

Results

CTCs were detected in 93.0% (160/172) of the included patients with CRC. Positive PRL-3 and MMP9 expression in CTC and M-CTC was found in 75.0% (102/136) and 80.8% (97/120) of the patients, respectively. The proportion of patients with positive PRL-3 and MMP9 expression in M-CTC was significantly associated with distant metastasis (p<0.05). The patients with ≥6 CTCs tended to show poorer progression-free survival (PFS) and overall survival (OS) rates (p=0.016, 0.02, respectively), and the patients with ≥3 M-CTC also showed poor PFS (p=0.0013). Additionally, the patients with positive PRL-3 and MMP9 expression in CTCs had significantly poorer PFS (p=0.0024) and OS (p=0.095) than the patients with negative PRL-3 and MMP9 expression. Multivariate Cox analysis uncovered that positive PRL-3 and MMP9 expression in CTCs may be an independent prognostic factor for worse PFS.

Conclusion

EMT phenotypes and CTC numbers can be used as prognostic indicators for metastasis and survival in patients with CRC, and the combination of PRL-3 and MMP9 expression in CTCs is a promising clinical marker for patients with CRC.
Using Restricted Cubic Splines to Study the Duration of Antibiotic Use in the Prognosis of Ventilator-Associated Pneumonia
Authors: Xu Yixian , Han Didi , Xu Fengshuo , Shen Si , Zheng Xinkai , Wang Hao , Lyu Jun
Published: April 2022

Background: Ventilator-associated pneumonia (VAP) is the most widespread and life-threatening nosocomial infection in intensive care units (ICUs). The duration of antibiotic use is a good predictor of prognosis in patients with VAP, but the ideal duration of antibiotic therapy for VAP in critically ill patients has not been confirmed. Research is therefore needed into the optimal duration of antibiotic use and its impact on VAP.

Methods: The Medical Information Mart for Intensive Care database included 1,609 patients with VAP. Chi-square or Student’s t-tests were used to compare groups, and Cox regression analysis was used to investigate the factors influencing the prognoses of patients with VAP. Nonlinear tests were performed on antibiotic use lasting <7, 7–10, and >10 days. Significant factors were included in the model for sensitivity analysis. For the subgroup analyses, the body mass indexes (BMIs) of patients were separated into BMI <30 kg/m2 and BMI ≥30 kg/m2, with the criterion of statistical significance set at p < 0.05. Restricted cubic splines were used to analyze the relationship between antibiotic use duration and mortality risk in patients with VAP.

Results: In patients with VAP, the effects of antibiotic use duration on the outcomes were nonlinear. Antibiotic use for 7–10 days in models 1–3 increased the risk of antibiotic use by 2.6020-, 2.1642-, and 2.3263-fold relative to for >10 days, respectively. The risks in models 1–3 for <7 days were 2.6510-, 1.9933-, and 2.5151-fold higher than those in models with >10 days of antibiotic use, respectively. These results were robust across the analyses.

Conclusions: The duration of antibiotic treatment had a nonlinear effect on the prognosis of patients with VAP. Antibiotic use durations of <7 days and 7–10 days both presented risks, and the appropriate duration of antibiotic use can ensure the good prognosis of patients with VAP.
Studying Cardiac Neural Network Dynamics: Challenges and Opportunities for Scientific Computing
Authors: Gurel Nil Z. , Sudarshan Koustubh B. , Tam Sharon , Ly Diana , Armour J. Andrew , Kember Guy , Ajijola Olujimi A.
Published: April 2022

Neural control of the heart involves continuous modulation of cardiac mechanical and electrical activity to meet the organism’s demand for blood flow. The closed-loop control scheme consists of interconnected neural networks with central and peripheral components working cooperatively with each other. These components have evolved to cooperate control of various aspects of cardiac function, which produce measurable “functional” outputs such as heart rate and blood pressure. In this review, we will outline fundamental studies probing the cardiac neural control hierarchy. We will discuss how computational methods can guide improved experimental design and be used to probe how information is processed while closed-loop control is operational. These experimental designs generate large cardio-neural datasets that require sophisticated strategies for signal processing and time series analysis, while presenting the usual large-scale computational challenges surrounding data sharing and reproducibility. These challenges provide unique opportunities for the development and validation of novel techniques to enhance understanding of mechanisms of cardiac pathologies required for clinical implementation.
Prescribing Intensity in Resistance Training Using Rating of Perceived Effort: A Randomized Controlled Trial
Authors: Boxman-Zeevi Yael , Schwartz Hadar , Har-Nir Itai , Bordo Nadia , Halperin Israel
Published: April 2022

Introduction: Rating of perceived effort (RPE) scales are used to prescribe intensity in resistance training (RT) in several ways. For instance, trainees can reach a specific RPE value by modifying the number of repetitions, lifted loads, or other training variables. Given the multiple approaches of prescribing intensity using RPE and its growing popularity, we compared the effects of two RPE prescription approaches on adherence rates, body composition, performance and psychological outcomes, in an online RT intervention.

Methods: We randomly assigned 57 healthy participants without RT experience (60% females, age range: 18–45) to one of two groups that received two weekly RT sessions using a resistance-band for 8 weeks. In the fixed-repetition group, participants adjusted the band resistance with the goal of completing 10 repetitions and reaching a 7-RPE on a 0–10 scale by the 10th repetition. In the open-repetition group, participants selected their preferred band resistance and completed repetitions until reaching a 7-RPE by the final repetition. We measured body composition, performance, and program satisfaction rates.

Results: We assessed 46 participants at post-test, 24 from the fixed-repetition group and 22 from the open-repetition group. We observed non-significant and trivial differences between groups in all outcomes (p > 0.05). We then combined the pre-post change scores of the two groups. We found that adherence rates began at 89% and gradually decreased to 42%. On average, participants increased their fat-free mass [0.3 kg (95% CI: 0.1–0.6)], isometric mid-thigh pull [5.5 kg (95% CI: 0.8–10.4)], isometric knee-extension [2.2 kg (95% CI: 0.8–3.7)], and push-ups [6.3 repetitions (95% CI: 4.5–8.2)]. We observed non-significant and trivial changes in bodyweight, grip-force, and countermovement jump. Participants reported high satisfaction rates with all components of the program.

Conclusion: Participants in both groups improved their body composition and physical capacity to a similar extent, and reported comparable satisfaction rates with the programs they followed. Accordingly, either prescription approach can be used to deliver online RT sessions based on personal preferences and logistical constraints. However, since adherences rates declined over the course of the study, future research should test additional strategies aiming to maintain adherence rates.
BUMPY STEM Is an Arabidopsis Choline/Ethanolamine Kinase Required for Normal Development and Chilling Responses
Authors: Rabeler Christina , Chen Mingjie , Kaplinsky Nick
Published: April 2022

Phospholipid biosynthesis is a core metabolic pathway that affects all aspects of plant growth and development. One of the earliest step in this pathway is mediated by choline/ethanolamine kinases (CEKs), enzymes in the Kennedy pathway that catalyze the synthesis of the polar head groups found on the most abundant plant phospholipids. The Arabidopsis genome encodes four CEKs. CEK1-3 have been well characterized using viable mutants while CEK4 encodes an essential gene, making it difficult to characterize its effects on plant development and responses to the environment. We have isolated an EMS-induced allele of CEK4 called bumpy stem (bst). bst plants are viable, allowing the effects of decreased CEK4 function to be characterized throughout the Arabidopsis life cycle. bst mutants have a range of developmental defects including ectopic stem growths at the base of their flowers, reduced fertility, and short roots and stems. They are also sensitive to cold temperatures. Supplementation with choline, phosphocholine, ethanolamine, and phosphoethanolamine rescues bst root phenotypes, highlighting the flow of metabolites between the choline and ethanolamine branches of the Kennedy pathway. The identification of bst and characterization of its phenotypes defines new roles for CEK4 that go beyond its established biochemical function as an ethanolamine kinase.
Strategies and Bottlenecks in Hexaploid Wheat to Mobilize Soil Iron to Grains
Authors: Kumar Anil , Kaur Gazaldeep , Singh Palvinder , Meena Varsha , Sharma Shivani , Tiwari Manish , Bauer Petra , Pandey Ajay Kumar
Published: April 2022

Our knowledge of iron (Fe) uptake and mobilization in plants is mainly based on Arabidopsis and rice. Although multiple players of Fe homeostasis have been elucidated, there is a significant gap in our understanding of crop species, such as wheat. It is, therefore, imperative not only to understand the different hurdles for Fe enrichment in tissues but also to address specifically the knowns/unknowns involved in the plausible mechanism of Fe sensing, signaling, transport, and subsequent storage in plants. In the present review, a unique perspective has been described in light of recent knowledge generated in wheat, an economically important crop. The strategies to boost efficient Fe uptake, transcriptional regulation, and long-distance mobilization in grains have been discussed, emphasizing recent biotechnological routes to load Fe in grains. This article also highlights the new elements of physiological and molecular genetics that underpin the mechanistic insight for the identified Fe-related genes and discusses the bottlenecks in unloading the Fe in grains. The information presented here will provide much-needed resources and directions to overcome challenges and design efficient strategies to enhance the Fe density in wheat grains.
Dynamics of Deep Water and N Uptake of Oilseed Rape (Brassica napus L.) Under Varied N and Water Supply
Authors: Chen Guanying , Rasmussen Camilla Ruø , Dresbøll Dorte Bodin , Smith Abraham George , Thorup-Kristensen Kristian
Published: April 2022

Enhanced nitrogen (N) and water uptake from deep soil layers may increase resource use efficiency while maintaining yield under stressed conditions. Winter oilseed rape (Brassica napus L.) can develop deep roots and access deep-stored resources such as N and water to sustain its growth and productivity. Less is known of the performance of deep roots under varying water and N availability. In this study, we aimed to evaluate the effects of reduced N and water supply on deep N and water uptake for oilseed rape. Oilseed rape plants grown in outdoor rhizotrons were supplied with 240 and 80 kg N ha−1, respectively, in 2019 whereas a well-watered and a water-deficit treatment were established in 2020. To track deep water and N uptake, a mixture of 2H2O and Ca(15NO3)2 was injected into the soil column at 0.5- and 1.7-m depths. δ2H in transpiration water and δ15N in leaves were measured after injection. δ15N values in biomass samples were also measured. Differences in N or water supply had less effect on root growth. The low N treatment reduced water uptake throughout the soil profile and altered water uptake distribution. The low N supply doubled the 15N uptake efficiency at both 0.5 and 1.7 m. Similarly, water deficit in the upper soil layers led to compensatory deep water uptake. Our findings highlight the increasing importance of deep roots for water uptake, which is essential for maintaining an adequate water supply in the late growing stage. Our results further indicate the benefit of reducing N supply for mitigating N leaching and altering water uptake from deep soil layers, yet at a potential cost of biomass reduction.