bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of the Thrombin Pathway Restores LTP in a Pilocarpine Mice Model of Status Epilepticus
Authors: Shavit-Stein Efrat , Berkowitz Shani , Davidy Tal , Fennig Uri , Gofrit Shani Guly , Dori Amir , Maggio Nicola
Published: May 2022

Background

Status epilepticus (SE) leads to memory impairment following a seizure, attributed to long-term potentiation (LTP) reduction. Thrombin, a coagulation factor that activates protease-activated receptor 1 (PAR1) is involved in cognitive impairment following traumatic brain injury by reducing hippocampal LTP and in seizures as seen in a SE pilocarpine-induced mice model. Thrombin pathway inhibition prevents this cognitive impairment. We evaluated the effect of thrombin pathway inhibition in the pilocarpine-induced SE mice model, on LTP, hippocampal, and serum markers for inflammation, the PAR1 pathway, and neuronal cell damage.

Methods

SE was induced by injecting C57BL/6J mice with pilocarpine. Before pilocarpine injection, mice were injected with either the specific thrombin inhibitor α-NAPAP [Nα-(2-naphthalene-sulfonylglycyl)-4-amidino-DL-phenylalaninepiperidide], the PAR1 antagonist SCH79797, or vehicle-only solution. Recordings of excitatory postsynaptic potentials (EPSP) were conducted from hippocampal slices 24 h following pilocarpine injection. Hippocampal real-time PCR for the quantification of the PAR1, prothrombin, and tumor necrosis factor α (TNF-α) mRNA expression levels was conducted. Serum levels of neurofilament light chain (NfL) and TNF-α were measured by a single molecule array assay.

Results

The EPSP was reduced in the pilocarpine-induced SE mice (p < 0.001). This reduction was prevented by both NAPAP and SCH79797 treatments (p < 0.001 for both treatments). Hippocampal expression of TNF-α was elevated in the pilocarpine-induced SE group compared to the control (p < 0.01), however, serum levels of TNF-α were not changed. NfL levels were elevated in the pilocarpine-induced SE group (p = 0.04) but not in the treated groups.

Conclusions

Pilocarpine-induced SE reduces LTP, in a thrombin PAR1-related mechanism. Elevation of serum NfL supports neuronal damage accompanying this functional abnormality which may be prevented by PAR1 pathway modulation.
Facial Nerve Function After Microsurgical Resection in Vestibular Schwannoma Under Neurophysiological Monitoring
Authors: Arlt Felix , Kasper Johannes , Winkler Dirk , Jähne Katja , Fehrenbach Michael Karl , Meixensberger Jürgen , Sander Caroline
Published: May 2022

Background

The use of intraoperative neurophysiological monitoring, including direct nerve stimulation (especially the facial nerve), acoustic evoked potentials (AEP) and somatosensory evoked potentials (SSEP), is a helpful tool in the microsurgery of vestibular schwannoma to prevent nerve injury. Patient characteristics and intraoperative and postoperative variables might also influence the postoperative facial nerve function. The study was performed to investigate these variables and the intraoperative neurophysiological monitoring values.

Methods

Seventy-nine patients with vestibular schwannoma were included consecutively into this study. Intraoperative neurophysiological monitoring, including SSEP, AEP, and direct nerve stimulation for facial and trigeminal nerve electromyography, was performed utilizing digital data storage in all cases. The intensity (in volts) of the direct stimulation and the latency (in ms) for the orbicularis oculi and the orbicularis oris muscle and the amplitude (in mV) was measured. Univariate and multivariate statistical analyses concerning the different parameters was performed directly after the operation and in the subsequent follow-ups 3 and 6 months after the operation.

Results

The mean intensity was 0.79 V (SD.29). The latency and amplitude for the oris muscle was 5.2 ms (SD 2.07) and 0.68 mV (SD.57), respectively. The mean latency for the occuli muscle was 5.58 ms (SD 2.2) and the amplitude was 0.58 mV (SD 1.04). The univariate and multivariate statistical analyses showed significance concerning the postoperative facial nerve function and the amplitude of the direct stimulation of the facial nerve in the orbicularis oris muscle (p = 0.03), so repeated direct nerve stimulation might show FN function deterioration. The mean diameter of the tumors was 24 mm (range 10–57 mm). Cross total resection and near total was achieved in 76 patients (96%) and subtotal in three patients (4%). The preoperative House–Brakeman score (HBS) 1 was constant in 65 (82%) cases. The mortality in our series was 0%; the overall morbidity was 10%. The HBS was not influenced concerning the extent of resection. The mean follow-up was 28 months (range 6 to 60 months). The limitations of the study might be a low number of patients and the retrospective character of the study.

Conclusion

Intraoperative neurophysiological monitoring is crucial in vestibular schwannoma surgery. Repeated direct nerve stimulation and a detected decreased amplitude might show facial nerve function deterioration.
Use of Novel Concussion Protocol With Infralow Frequency Neuromodulation Demonstrates Significant Treatment Response in Patients With Persistent Postconcussion Symptoms, a Retrospective Study
Authors: Legarda Stella B. , Lahti Caroline E. , McDermott Dana , Michas-Martin Andreas
Published: May 2022

Introduction

Concussion is a growing public health concern. No uniformly established therapy exists; neurofeedback studies report treatment value. We use infralow frequency neuromodulation (ILF) to remediate disabling neurological symptoms caused by traumatic brain injury (TBI) and noted improved outcomes with a novel concussion protocol. Postconcussion symptoms (PCS) and persistent postconcussion symptoms (PPCS; >3 months post head injury) are designated timelines for protracted neurological complaints following TBI. We performed a retrospective study to explore effectiveness of ILF in PCS/PPCS and investigated the value of using this concussion protocol.

Method

Patients with PCS/PPCS seen for their first neurology office visit or received their first neurofeedback session between 1 August 2018 and 31 January 2021 were entered. Outcomes were compared following treatment as usual (TAU) vs. TAU with ILF neurotherapy (TAU+ILF). The study cohort was limited to PPCS patients; the TAU+ILF group was restricted further to PPCS patients receiving at least 10 neurotherapy sessions. Within the TAU+ILF group, comparisons were made between those who trained at least 10 sessions using concussion protocol (TAU+ILF+CP) and those who trained for at least 10 sessions of ILF regardless of protocol (TAU+ILF-CP).

Results

Among our resultant PPCS cohort (n = 59) leading persistent neurological complaints were headache (67.8%), memory impairment (57.6%), and brain fog (50.8%). PPCS patients in TAU+ILF+CP (n = 25) demonstrated greater net (p = 0.004) and percent (p = 0.026) improvement of symptoms compared to PPCS subjects in TAU (n = 26). PPCS patients in TAU+ILF-CP (n = 8) trended toward significant symptom improvements compared to TAU, and TAU+ILF+CP trended toward greater efficacy than TAU+ILF-CP.

Conclusion

PPCS patients who received TAU+ILF+CP demonstrated significantly greater improvement as a group when compared to TAU. When used as an integrative modality to treatment as usual in managing patients with PPCS, ILF neuromodulation with use of concussion protocol provided significant symptom improvements.
Dentate Granule Cells Are Hyperexcitable in the TgF344-AD Rat Model of Alzheimer's Disease
Authors: Smith Lindsey A. , Goodman Anthoni M. , McMahon Lori L.
Published: May 2022

The dentate gyrus is both a critical gatekeeper for hippocampal signal processing and one of the first brain regions to become dysfunctional in Alzheimer's disease (AD). Accordingly, the appropriate balance of excitation and inhibition through the dentate is a compelling target for mechanistic investigation and therapeutic intervention in early AD. Previously, we reported an increased long-term potentiation (LTP) magnitude at medial perforant path-dentate granule cell (MPP-DGC) synapses in slices from both male and acutely ovariectomized female TgF344-AD rats compared with wild type (Wt) as early as 6 months of age that is accompanied by an increase in steady-state postsynaptic depolarization during the high-frequency stimulation used to induce plasticity. Subsequently, we found that heightened function of β-adrenergic receptors (β-ARs) drives the increase in the LTP magnitude, but the increase in steady-state depolarization was only partially due to β-AR activation. As we previously reported no detectable difference in spine density or presynaptic release probability, we entertained the possibility that DGCs themselves might have modified passive or active membrane properties, which may contribute to the significant increase in charge transfer during high-frequency stimulation. Using brain slice electrophysiology from 6-month-old female rats acutely ovariectomized to eliminate variability due to fluctuating plasma estradiol, we found significant changes in passive membrane properties and active membrane properties leading to increased DGC excitability in TgF344-AD rats. Specifically, TgF344-AD DGCs have an increased input resistance and decreased rheobase, decreased sag, and increased action potential (AP) spike accommodation. Importantly, we found that for the same amount of depolarizing current injection, DGCs from TgF344-AD compared with Wt rats have a larger magnitude voltage response, which was accompanied by a decreased delay to fire the first action potential, indicating TgF344-AD DGCs membranes are more excitable. Taken together, DGCs in TgF344-AD rats are more excitable, which likely contributes to the heightened depolarization during high-frequency synaptic activation.
Dietary Succinate Impacts the Nutritional Metabolism, Protein Succinylation and Gut Microbiota of Zebrafish
Authors: Ding Qianwen , Lu Chenyao , Hao Qiang , Zhang Qingshuang , Yang Yalin , Olsen Rolf Erik , Ringo Einar , Ran Chao , Zhang Zhen , Zhou Zhigang
Published: May 2022

Succinate is widely used in the food and feed industry as an acidulant, flavoring additive, and antimicrobial agent. This study investigated the effects of dietary succinate on growth, energy budget, nutritional metabolism, protein succinylation, and gut microbiota composition of zebrafish. Zebrafish were fed a control-check (0% succinate) or four succinate-supplemented diets (0.05, 0.10, 0.15, and 0.2%) for 4 weeks. The results showed that dietary succinate at the 0.15% additive amount (S0.15) can optimally promote weight gain and feed intake. Whole body protein, fat, and energy deposition increased in the S0.15 group. Fasting plasma glucose level decreased in fish fed the S0.15 diet, along with improved glucose tolerance. Lipid synthesis in the intestine, liver, and muscle increased with S0.15 feeding. Diet with 0.15% succinate inhibited intestinal gluconeogenesis but promoted hepatic gluconeogenesis. Glycogen synthesis increased in the liver and muscle of S0.15-fed fish. Glycolysis was increased in the muscle of S0.15-fed fish. In addition, 0.15% succinate-supplemented diet inhibited protein degradation in the intestine, liver, and muscle. Interestingly, different protein succinylation patterns in the intestine and liver were observed in fish fed the S0.15 diet. Intestinal proteins with increased succinylation levels were enriched in the tricarboxylic acid cycle while proteins with decreased succinylation levels were enriched in pathways related to fatty acid and amino acid degradation. Hepatic proteins with increased succinylation levels were enriched in oxidative phosphorylation while proteins with decreased succinylation levels were enriched in the processes of protein processing and transport in the endoplasmic reticulum. Finally, fish fed the S0.15 diet had a higher abundance of Proteobacteria but a lower abundance of Fusobacteria and Cetobacterium. In conclusion, dietary succinate could promote growth and feed intake, promote lipid anabolism, improve glucose homeostasis, and spare protein. The effects of succinate on nutritional metabolism are associated with alterations in the levels of metabolic intermediates, transcriptional regulation, and protein succinylation levels. However, hepatic fat accumulation and gut microbiota dysbiosis induced by dietary succinate suggest potential risks of succinate application as a feed additive for fish. This study would be beneficial in understanding the application of succinate as an aquatic feed additive.
Black Soldier Fly Larvae Meal in the Diet of Gilthead Sea Bream: Effect on Chemical and Microbiological Quality of Filets
Authors: Oteri Marianna , Chiofalo Biagina , Maricchiolo Giulia , Toscano Giovanni , Nalbone Luca , Lo Presti Vittorio , Di Rosa Ambra Rita
Published: May 2022

The chemical and microbiological characteristics of filets of Spaurus aurata L. specimens fed with diets containing a Hermetia illucens meal (HIM) at the 25, 35, and 50%, as a partial replacement for fish meal (FM) were evaluated. The diets, formulated to satisfy the nutritional needs of fish, were isoenergetic (22 MJ/kg gross energy), isonitrogenous (43 g/100 g, a.f.), and isolipidic (19 g/100 g, a.f.). Seventy-two specimens were randomly killed after 186 days of growing trials. Then, the filets were analyzed for chemical profile, fatty acids, amino acids, minerals, and microbial flora. Data were subjected to statistical analysis. No significant differences were observed in chemical composition. The sum of polyunsaturated fatty acids (PUFAs) showed a similar content in the filets; eicosapentaenoic acid was similar in the filets of HIM0, HIM35%, and HIM50%, whereas docosahexaenoic acid was higher in filets of the HIM0 group. n3/n6 PUFA ratio and the sum of EPA + DHA showed a high value (p < 0.001) in filets of the group fed with FM. No significant difference was observed in thrombogenic index and hypocholesterolaemic/hypercholesterolaemic ratio in the groups; the atherogenic index showed a higher value (p = 0.001) in the HIM50% group. Indispensable amino acids showed some significant (p < 0.0001) differences in the groups; arginine and phenylalanine content was higher in the filets of fish fed with FM; isoleucine and valine content was higher in the filets of HIM50%; leucine, lysine and methionine content was lower in the filets of HIM35%; histidine content was lower in the filets of HIM25%; tryptophan content was lower in filets of the HIM50% group. EAA/NEAA ratio showed highest value in the filets of the group that received FM. The presence of HIM in the three diets kept chromium, manganese, iron, copper, zinc, and nickel levels lower than those recommended by various authorities. Ca/P ratio showed a higher level (p < 0.0001) in the group fed with FM than those fed with diets containing HIM. The insect meal in the diets did not influence the microbiological profile of fish. Use of HIM as an unconventional feed ingredient in Sparus aurata diet looks promising, although the quality of filets may be affected.
Splenic Volume, an Easy-To-Use Predictor of HCC Late Recurrence for HCC Patients After Hepatectomy
Authors: Fang Tongdi , Long Guo , Mi Xingyu , Su Wenxin , Mo Lei , Zhou Ledu
Published: May 2022

Purpose

The high recurrence rate of hepatocellular carcinoma (HCC) has a poor impact on the quality of life and survival time of patients. Especially for late recurrence, poor data are available in analysis. We aim to evaluate whether the splenic volume (SV) measured from preoperative CT images could predict late recurrence in HCC patients after hepatectomy.

Patients and Methods

A cohort of 300 HCC patients hospitalized at Xiangya Hospital of Central South University between January 2015 and June 2018 was retrospectively analyzed. The SV was calculated by using automated volumetry software from preoperative CT images. A total of 300 HCC patients were separated into the early recurrence cohort (n=167), the late recurrence cohort (n=39), and the no recurrence cohort (n=94) according to whether there is a recurrence and the recurrence time. Univariate and multivariate Cox analyses were performed to identify the independent risk factors of both early and late recurrence.

Results

AFP, Microvascular invasion (MVI), satellitosis, and BCLC staging were independent risk factors of HCC early recurrence. Splenic volume (HR=1.003, 95%CI:1.001-1.005, P<0.001) was the only predictor of HCC late recurrence. Based on X-tile software, 133 non-early recurrence patients were divided into two groups according to SV: low SV (<165ml, n=45) and high SV (≥165ml, n= 88). The low SV group had a significantly better RFS compared with the high SV group (P=0.015). Nomogram was built on the base of SV to get the probability of 3-year RFS, 4-year RFS, and 5-year RFS.

Conclusion

In our study, we drew a conclusion that splenic volume was the only predictor of HCC late recurrence because of its association with portal hypertension and liver cirrhosis. High splenic volume often indicated a worse recurrence.
TaqMan Probe-Based Quantitative Real-Time PCR to Detect Panax notoginseng in Traditional Chinese Patent Medicines
Authors: Lou Qian , Xin Tianyi , Xu Wenjie , Li Ranjun , Song Jingyuan
Published: May 2022

Background: There has been global concern about the safety and accuracy of traditional Chinese patent medicines (TCPMs). Panax notoginseng, also known as sanqi, is an important constituent of TCPMs. However, identifying the species contained in TCPMs is challenging due to the presence of multiple ingredients and the use of various preparation processes.

Objective: To detect P. notoginseng in TCPMs.

Methods: A TaqMan probe-based qPCR assay was constructed and validated with DNA extracted from P. notoginseng and adulterants. In total, 75 samples derived from 25 batches of TCPMs were tested using the constructed qPCR method.

Results: A TaqMan probe-based qPCR assay targeting P. notoginseng was established. The constructed qPCR assay could specifically discriminate P. notoginseng from Panax ginseng, Panax quinquefolium and Curcuma aromatica Salisb. cv. Wenyujin. The sensitivity study showed that the detectable DNA template concentration of P. notoginseng for this qPCR assay was 0.001 ng/μl. All 75 samples from TCPMs were confirmed to contain P. notoginseng by the qPCR assay.

Conclusions: The qPCR method can accurately identify P. notoginseng in TCPMs and is promising as a powerful tool for quality control and market regulation.
S1PR3, as a Core Protein Related to Ischemic Stroke, is Involved in the Regulation of Blood–Brain Barrier Damage
Authors: Fan Xuehui , Chen Hongping , Xu Chen , Wang Yingju , Yin Pengqi , Li Meng , Tang Zhanbin , Jiang Fangchao , Wei Wan , Song Jihe , Li Guozhong , Zhong Di
Published: May 2022

Background: Ischemic stroke is the most common stroke incident. Sphingosine-1-phosphate (S1P) receptor 3 (S1PR3) is a member of the downstream G protein-coupled receptor family of S1P. The effect of S1PR3 on ischemic stroke remains elusive.

Methods: We downloaded two middle cerebral artery occlusion (MCAO) microarray datasets from the Gene Expression Omnibus (GEO) database and screened differentially expressed genes (DEGs). Then, we performed a weighted gene coexpression network analysis (WGCNA) and identified the core module genes related to ischemic stroke. We constructed a protein–protein interaction (PPI) network for the core genes in which DEGs and WGCNA intersected. Finally, we discovered that S1PR3 was involved as the main member of the red proteome. Then, we explored the mechanism of S1PR3 in the mouse tMCAO model. The S1PR3-specific inhibitor CAY10444 was injected into the abdominal cavity of mice after cerebral ischemia/reperfusion (I/R) injury, and changes in the expression of blood–brain barrier-related molecules were measured using PCR, western blotting, and immunofluorescence staining.

Results: Both GEO datasets showed that S1PR3 was upregulated during cerebral I/R in mice. WGCNA revealed that the light yellow module had the strongest correlation with the occurrence of IS. We determined the overlap with DEGs, identified 146 core genes that are potentially related to IS, and constructed a PPI network. Finally, S1PR3 was found to be the main member of the red proteome. In the mouse cerebral I/R model, S1PR3 expression increased 24 h after ischemia. After the administration of CAY10444, brain edema and neurological deficits in mice were ameliorated. CAY10444 rescued the decreased expression of the tight junction (TJ) proteins zonula occludens 1 (ZO1) and occludin after ischemia induced by transient MCAO (tMCAO) and reduced the increase in aquaporin 4 (AQP4) levels after tMCAO, preserving the integrity of the BBB. Finally, we found that S1PR3 is involved in regulating the mitogen-activated protein kinase (MAPK) and (phosphatidylinositol-3 kinase/serine-threonine kinase) PI3K-Akt signaling pathways.

Conclusion: S1PR3 participates in the regulation of blood–brain barrier damage after cerebral I/R. S1PR3 is expected to be an indicator and predictor of cerebral ischemia, and drugs targeting S1PR3 may also provide new ideas for clinical medications.
Exosome: The “Off-the-Shelf” Cellular Nanocomponent as a Potential Pathogenic Agent, a Disease Biomarker, and Neurotherapeutics
Authors: Ghosh Satyajit , Ghosh Surajit
Published: May 2022

Exosomes are nanosized “off-the-shelf” lipid vesicles released by almost all cell types and play a significant role in cell–cell communication. Exosomes have already been proven to carry cell-specific cargos of proteins, lipids, miRNA, and noncoding RNA (ribonucleic acid). These vesicles can be selectively taken up by the neighboring cell and can regulate cellular functions. Herein, we have discussed three different roles of exosomes in neuroscience. First, we have discussed how exosomes play the role of a pathogenic agent as a part of cell–cell communication and transmit pathogens such as amyloid-beta (Aβ), further helping in the propagation of neurodegenerative and other neurological diseases. In the next section, the review talks about the role of exosomes in biomarker discovery in neurological disorders. Toward the end, we have reviewed how exosomes can be harnessed and engineered for therapeutic purposes in different brain diseases. This review is based on the current knowledge generated in this field and our comprehension of this domain.
Resveratrol Attenuate Myocardial Injury by Inhibiting Ferroptosis Via Inducing KAT5/GPX4 in Myocardial Infarction
Authors: Liu Jing , Zhang Mingming , Qin Chaoshi , Wang Zikuan , Chen Jianghong , Wang Rui , Hu Jianqiang , Zou Qing , Niu Xiaolin
Published: May 2022

Myocardial infarction (MI) is a coronary artery-related disease and ranks as the leading cause of sudden death globally. Resveratrol (Res) is a bioactive component and has presented antioxidant, anti-inflammatory and anti-microbial properties. However, the effect of Res on ferroptosis during MI progression remains elusive. Here, we aimed to explore the function of Res in the regulation of ferroptosis and myocardial injury in MI. We observed that the treatment of Res attenuated the MI-related myocardium injury and fibrosis in the rats. The expression of collagen 1 and α-SMA was induced in MI rats, in which the treatment of Res could decrease the expression. Treatment of Res suppressed the levels of IL-6 and IL-1β in MI rats. The GSH levels were inhibited and MDA, lipid ROS, and Fe2+ levels were induced in MI rats, in which the treatment of Res could reverse the phenotypes. Meanwhile, the expression of GPX4 and SLC7A11 was reduced in MI rats, while the treatment of Res could rescue the expression in the model. Meanwhile, Res relieved oxygen-glucose deprivation (OGD)-induced cardiomyocyte injury. Importantly, Res repressed OGD-induced cardiomyocyte ferroptosis in vitro. Mechanically, we identified that Res was able to enhance GPX4 expression by inducing KAT5 expression. We confirmed that KAT5 alleviated OGD-induced cardiomyocyte injury and ferroptosis. The depletion of KAT5 or GPX4 could reverse the effect of Res on OGD-induced cardiomyocyte injury. Thus, we concluded that Res attenuated myocardial injury by inhibiting ferroptosis via inducing KAT5/GPX4 in myocardial infarction. Our finding provides new evidence of the potential therapeutic effect of Res on MI by targeting ferroptosis.
Post-Translational Modifications of p53 in Ferroptosis: Novel Pharmacological Targets for Cancer Therapy
Authors: Zhang Le , Hou Ningning , Chen Bing , Kan Chengxia , Han Fang , Zhang Jingwen , Sun Xiaodong
Published: May 2022

The tumor suppressor p53 is a well-known cellular guardian of genomic integrity that blocks cell cycle progression or induces apoptosis upon exposure to cellular stresses. However, it is unclear how the remaining activities of p53 are regulated after the abrogation of these routine activities. Ferroptosis is a form of iron- and lipid-peroxide-mediated cell death; it is particularly important in p53-mediated carcinogenesis and corresponding cancer prevention. Post-translational modifications have clear impacts on the tumor suppressor function of p53. Here, we review the roles of post-translational modifications in p53-mediated ferroptosis, which promotes the elimination of tumor cells. A thorough understanding of the p53 functional network will be extremely useful in future strategies to identify pharmacological targets for cancer therapy.
Anomalous Temperature Interdicts the Reproductive Activity in Fish: Neuroendocrine Mechanisms of Reproductive Function in Response to Water Temperature
Authors: Zahangir Md. Mahiuddin , Rahman Mohammad Lutfar , Ando Hironori
Published: May 2022

Fish are poikilotherm and small changes in water temperature can greatly affect physiological processes including reproduction, which is regulated by complex neuroendocrine mechanisms that respond to climatic events. This review provides evidence that anomalous high and low temperature may directly affect reproduction in fish by suppressing the expression of genes in the reproductive neuroendocrine system. The grass puffer, Takifugu alboplumbeus, is an excellent animal model for studying the thermal regulation of reproduction, for they exhibit periodic spawning activities, which are synchronized with seasonal, lunar and daily cycles. In the grass puffer, the expression of the genes encoding gonadotropin-releasing hormone (GnRH) 1, kisspeptin, gonadotropin-inhibitory hormone (GnIH) and their receptors were markedly suppressed in the diencephalon of fish exposed to high temperature (28°C) when compared to normal temperature (21°C), followed by the decrease in the pituitary mRNA levels for follicle-stimulating hormone (FSH), luteinizing hormone (LH) and growth hormone (GH). On the other hand, the exposure to low temperature (14°C) also inhibited the expression of gnrh1, kiss2, gnih and their receptor genes in the brain and fshb, lhb, gh and prl in the pituitary. Taken together, it is plausible that anomalous high and low temperature may be a proximate driver of termination of reproduction by suppressing the activity of the reproductive GnRH/kisspeptin/GnIH system, possibly through direct action of temperature signals at transcription level.
Anatomical Characteristics and Variation Mechanisms on the Thick-Walled and Dwarfed Culm of Shidu Bamboo (Phyllostachys nidularia f. farcta)
Authors: Wang Yujun , Qiao Guirong , Xu Jing , Jin Kangming , Fan Minyuan , Ding Yulong , Wei Qiang , Zhuo Renying
Published: May 2022

Stable culm variants are valuable and important material for the study of culm development in bamboo plants. However, to date, there are few reports on the mechanism of variation of these bamboo variants. Phyllostachys nidularia f. farcta (Shidu bamboo) is a bamboo variant with stable phenotypes such as a dwarf culm with a thickened wall. In this study, we systematically investigated the cytological characteristics and underlying mechanism of morphological variation in culms of this variant using anatomical, mathematical statistical, physiological, and genomic methods. The anatomical observation and statistical results showed that the lateral increase of ground tissue in the inner layer of culm wall and the enlargement of vascular bundles are the anatomical essence of the wall thickening of Shidu bamboo; the limited elongation of fiber cells and the decrease in the number of parenchyma cells longitudinally are probably the main causes of the shortening of its internodes. A number of genes involved in the gibberellin synthesis pathway and in the synthesis of cell wall components are differentially expressed between the variant and its prototype, Ph. nidularia, and may play an important role in determining the phenotype of internode shortening in Shidu bamboo. The decrease in gibberellin content and the content of the major chemical components of the cell wall of Shidu bamboo confirmed the results of the above transcriptome. In addition, the variation in culm morphology in Shidu bamboo had little effect on the volume of the culm wall of individual internodes, suggesting that the decrease in the total number of internodes and the decrease in dry matter content (lignin, cellulose, etc.) may be the main factor for the sharp decline in culm biomass of Shidu bamboo.
Utilization of Plant Architecture Genes in Soybean to Positively Impact Adaptation to High Yield Environments
Authors: Kim Jeong-Hwa , Scaboo Andrew , Pantalone Vincent , Li Zenglu , Bilyeu Kristin
Published: May 2022

Optimization of plant architecture by modifying stem termination and timing of flowering and maturity of soybean is a promising strategy to improve its adaptability to specific production environments. Therefore, it is important to choose a proper stem termination type and to understand morphological differences between each stem termination type under various environmental conditions. Variations in abruptness of stem termination have been generally classified into three classical genetic types, indeterminate (Dt1), determinate (dt1), and semi-determinate (Dt2). However, an additional stem termination type, termed tall determinate, and its genetic symbol, dt1-t, were introduced about 25 years ago. The tall determinate soybean lines show delayed cessation of apical stem growth and about 50% taller plant heights than the typical determinate soybeans, even though the genetic control of the tall determinate phenotype was found to be allelic to dt1. Despite the potential agronomic merits of the alternative stem termination type, knowledge about the tall determinate soybean remains limited. We clarified the molecular basis of the tall determinate stem termination type and examined potential agronomic merits of the alternative stem type under three different production environments in the US. Sequence analysis of the classical tall determinate soybean lines revealed that the dt1-t allele responsible for tall determinate stem architecture is caused by two of the identified independent missense alleles of dt1, dt1-t1 (R130K), and dt1-t2 (R62S). Also, from the comparison among soybean accessions belonging to each of the genotype categories for stem termination types, soybean accessions with tall determinate alleles were found to have a high discrepancy rate in phenotyping. Newly developed tall determinate late-maturing soybean germplasm lines had taller plant heights and a greater number of nodes with a similar stem diameter and similar pod density at the apical stem compared to typical determinate soybeans having dt1 (R166W) alleles in Southern environments in the US. The phenotype of increased pod-bearing nodes with lodging resistance has the potential to improve yield, especially grown in high yield environments. This study suggests an alternative strategy to remodel the shape of soybean plants, which can possibly lead to yield improvement through the modification of soybean plant architecture.
English Phrase Learning With Multimodal Input
Authors: Huang Yuanlin , Zhang Zina , Yu Jia , Liu Xiaobin , Huang Yuhong
Published: May 2022

Although multimodal input has the potential to lead to more sound learning outcomes, it carries the risk of causing cognitive overload, making it difficult to determine the exact effects of multimodal input on the second language (L2) phrase learning. This study tests the efficacy of multimodal input on L2 phrase learning. It adopts a mixed-method approach by utilizing both quantitative and qualitative data. The experimental design is a 2 × 3 mixed model, with a group [the experimental group (EG) and the control group (CG)] as the between-subject factor and time (pretest, midtest, and posttest) as the within-subject factor. A total of 66 participants were divided into two groups. All materials incorporated three aspects of phrase knowledge (form, meaning, and use), but the materials of the CG were unimodal in that they were offered only on paper, and of the EG were multimodal in that they included pictures, audio recordings, and video clips. After the treatment, a questionnaire and a semi-structured interview were given to the EG learners to explore their perceptions of using multimodal materials to learn L2 phrases. The results indicate that both groups had significant gains in learning phrases, but students with the multimodal input achieved significantly better results than those with the unimodal input. Moreover, the EG students had a generally positive attitude toward the use of multimodal resources. This study validates the efficacy of multimodal input on the acquisition of English phrases and shows that cognitive overload was avoided by sequencing the information.
Detection of Depression and Suicide Risk Based on Text From Clinical Interviews Using Machine Learning: Possibility of a New Objective Diagnostic Marker
Authors: Shin Daun , Kim Kyungdo , Lee Seung-Bo , Lee Changwoo , Bae Ye Seul , Cho Won Ik , Kim Min Ji , Hyung Keun Park C. , Chie Eui Kyu , Kim Nam Soo , Ahn Yong Min
Published: May 2022

Background

Depression and suicide are critical social problems worldwide, but tools to objectively diagnose them are lacking. Therefore, this study aimed to diagnose depression through machine learning and determine whether it is possible to identify groups at high risk of suicide through words spoken by the participants in a semi-structured interview.

Methods

A total of 83 healthy and 83 depressed patients were recruited. All participants were recorded during the Mini-International Neuropsychiatric Interview. Through the suicide risk assessment from the interview items, participants with depression were classified into high-suicide-risk (31 participants) and low-suicide-risk (52 participants) groups. The recording was transcribed into text after only the words uttered by the participant were extracted. In addition, all participants were evaluated for depression, anxiety, suicidal ideation, and impulsivity. The chi-square test and student’s T-test were used to compare clinical variables, and the Naive Bayes classifier was used for the machine learning text model.

Results

A total of 21,376 words were extracted from all participants and the model for diagnosing patients with depression based on this text confirmed an area under the curve (AUC) of 0.905, a sensitivity of 0.699, and a specificity of 0.964. In the model that distinguished the two groups using statistically significant demographic variables, the AUC was only 0.761. The DeLong test result (p-value 0.001) confirmed that the text-based classification was superior to the demographic model. When predicting the high-suicide-risk group, the demographics-based AUC was 0.499, while the text-based one was 0.632. However, the AUC of the ensemble model incorporating demographic variables was 0.800.

Conclusion

The possibility of diagnosing depression using interview text was confirmed; regarding suicide risk, the diagnosis accuracy increased when demographic variables were incorporated. Therefore, participants’ words during an interview show significant potential as an objective and diagnostic marker through machine learning.
A Randomized Controlled Trial Comparing Videoconference vs. Face-to-Face Delivery of Behavior Therapy for Youths With Tourette Syndrome in the Time of COVID-19
Authors: Prato Adriana , Maugeri Nicoletta , Chiarotti Flavia , Morcaldi Lucia , Vicario Carmelo M. , Barone Rita , Rizzo Renata
Published: May 2022

Objective

To evaluate the clinical effectiveness of online remote behavior therapy, compared with face-to-face therapy in reducing tics and co-occurring disorders associated with the tics in a sample of youths with Tourette Syndrome.

Design

A randomized controlled trial. TS patients were randomized to receive face-to-face or online remote behavior therapy.

Participants

40 children aged between 9 and 16 years affected by Tourette Syndrome.

Results

Online remote and face-to-face behavior therapy are equally effective in the treatment of tics and co-occurring disorders in children and adolescents affected by Tourette Syndrome. Both groups showed an improvement in the severity of tics, obsessive-compulsive symptoms, and anxiety symptoms, as assessed by neuropsychological findings. Online remote behavior therapy was more effective for reducing depressive symptoms than face-to-face behavior therapy.

Conclusions

Online remote behavior therapy is a promising tool for behavioral therapies for patients with Tourette Syndrome and may represents an alternative treatment option.
The Feasibility and Effectiveness of a Novel, On-Line Social Skills Intervention for Individuals With Prader-Willi Syndrome
Authors: Dykens Elisabeth M. , Roof Elizabeth , Hunt-Hawkins Hailee , McDonald Charles
Published: May 2022

Introduction

People with neurodevelopmental disabilities, including Prader-Willi syndrome (PWS), are at heightened risk for the negative sequalae of loneliness, including depression and anxiety. While societal factors such as stigma or limited social opportunities contribute to loneliness, so too do deficits in social cognition and social skills. People with PWS have specific difficulties recognizing affect in others, accurately interpreting social interactions, and taking the perspectives of others. These features, combined with hyperphagia, rigidity, and insistence on sameness conspire to impede the abilities of people with PWS to make and sustain friendships and reduce feelings of loneliness.

Methods

We developed and administered an intervention, Building Our Social Skills (BOSS), that aimed to improve social skill deficits in PWS. The 10-week intervention was administered on-line via Zoom to 51 young people with PWS in the U.S. (M age = 20.8, SD = 6.42). Two clinicians co-led groups of 6–8 participants in 30-min sessions, 3 times per week, and also trained 4 graduate students to co-lead groups with high fidelity. We used a pre-post intervention and 3-month follow-up design, with no control group, and mitigated this design limitation by triangulating across informants and methodologies. Specifically, parents completed the widely used Social Responsiveness Scale (SRS) and Child Behavior Checklist (CBCL), and participants were individually interviewed about their friendships and loneliness. Interview responses were reliably coded by independent raters.

Results

Repeated measure multivariate analyses, with baseline values entered as covariates, revealed significant pre-to post-test improvements in the SRS's social cognition, motivation and communication subscales (p's < 0.001), with large effect sizes (np2 = 0.920, 0.270, and 0.204, respectively). Participant and parental reports of loneliness were correlated with the CBCL's Internalizing domain, specifically the Anxiety/Depressed subdomain. Over time, parents reported getting along better with peers, increased contact with friends, more friends and less loneliness. Participants also reported significantly less loneliness and more friends.

Conclusions

This mixed method, proof-of-concept study demonstrated the feasibility of delivering an on-line social skills intervention to young people with PWS. As no differences were found between clinician vs. graduate student outcomes, the BOSS curriculum holds considerable promise for wider dissemination and implementation in the PWS community.
The Association Between Antipsychotics and Weight Gain and the Potential Role of Metformin Concomitant Use: A Retrospective Cohort Study
Authors: Hakami Alqassem Y. , Felemban Razaz , Ahmad Rami Ghazi , Al-Samadani Abdulrahman H. , Salamatullah Hassan K. , Baljoon Jamil M. , Alghamdi Loay J. , Ramadani Sindi Mostafa H. , Ahmed Mohamed Eldigire
Published: May 2022

Background

Obesity and its complications are associated with several adverse effects that may cause a serious impact on health. Antipsychotics-induced weight gain (AIWG) is one of the major, yet often neglected side effects of first and second generations antipsychotics. Importantly, several researches have shown metformin to be effective in managing weight gain especially, with AIWG. This study investigated the effect of antipsychotics use on weight gain and the theory of metformin concomitant use on the prevention of AIWG.

Methods

A retrospective cohort review of the medical records of patients from the psychiatry outpatient clinics in the King Abdulaziz Medical city, a tertiary hospital in Jeddah from May 2016 to August 2021. The population of patients in Psychiatry section was 4,141. The sampling technique was a non-random consecutive sampling technique. Moreover, the included patients’ records were divided to group 1 (patients on antipsychotics) and group 2 (patients using antipsychotics with Metformin).

Results

According to the study criteria, 395 patients’ records were included. A total of 309 (78%) patients were using antipsychotics without metformin, which in this study were depicted as group 1. In addition, a total of 86 (22%) were using antipsychotics with metformin, which in this study were assigned as group 2. Out of Group 1 patients (n= 309), only 67 patients experienced weight loss (21.68%), 43 remained with no weight change (13.92%), and 199 experienced weight gain (64.4%). Out of Group 2 patients (n= 86), 35 patients experienced weight loss (40.7%), 18 patients remained with no weight change (20.93%), and 33 experienced weight gain (38.37%). In addition, group 1 had a mean weight change of 2.5 kg, whereas group 2 had a mean weight change of −0.04 kg.

Conclusion

Statistical analysis revealed that patients on antipsychotics alone experienced weight gain, whereas the concomitant use of metformin showed reduction in the weight gain tendency. Thus, study outcomes indicate that concomitant use of metformin with antipsychotics might significantly reduce the AIWG.
A Restructured Hospital Into a One-Building Organization for COVID-19 Patients: A Resilient and Effective Response to the Pandemic
Authors: Bessis Simon , Dinh Aurélien , Gautier Sylvain , Davido Benjamin , Levy Jonathan , Lawrence Christine , Lot Anne-Sophie , Bensmail Djamel , Rech Célia , Farcy-Afif Muriel , Bouchand Frédérique , de Truchis Pierre , Herrmann Jean-Louis , Barbot Frédéric , Orlikowski David , Moine Pierre , Perronne Christian , Josseran Loïc , Prigent Hélène , Annane Djillali
Published: May 2022

The COVID-19 pandemic is a unique crisis challenging healthcare institutions as it rapidly overwhelmed hospitals due to a large influx of patients. This major event forced all the components of the healthcare systems to adapt and invent new workflows. Thus, our tertiary care hospital was reorganized entirely. During the cruising phase, additional staff was allocated to a one-building organization comprising an intensive care unit (ICU), an acute care unit, a physical medicine and rehabilitation unit, and a COVID-19 screening area. The transfer of patients from a ward to another was more efficient due to these organizations and pavilion structure. The observed mortality was low in the acute care ward, except in the palliative unit. No nosocomial infection with SARS-CoV-2 was reported in any other building of the hospital since this organization was set up. This type of one-building organization, integrating all the components for comprehensive patient care, seems to be the most appropriate response to pandemics.
Assessing Real-World Racial Differences Among Patients With Metastatic Triple-Negative Breast Cancer in US Community Practices
Authors: Tan Ruoding , Cassoli Lourenia , Yan Ying , Shen Vincent , Day Bann-mo , Mitchell Edith P.
Published: May 2022

Objective

Real-world data characterizing differences between African American (AA) and White women with metastatic triple-negative breast cancer (mTNBC) are limited. Using 9 years of data collected from community practices throughout the United States, we assessed racial differences in the proportion of patients with mTNBC, and their characteristics, treatment, and overall survival (OS).

Methods

This retrospective study analyzed de-identified data from 2,116 patients with mTNBC in the Flatiron Health database (January 2011 to March 2020). Characteristics and treatment patterns between AA and White patients with mTNBC were compared using descriptive statistics. OS was examined using Kaplan-Meier analysis and a multivariate Cox proportional hazards regression model.

Results

Among patients with metastatic breast cancer, more AA patients (23%) had mTNBC than White patients (12%). This difference was particularly pronounced in patients who lived in the Northeast, were aged 45–65, had commercial insurance, and had initial diagnosis at stage II. AA patients were younger and more likely to have Medicaid. Clinical characteristics and first-line treatments were similar between AA and White patients. Unadjusted median OS (months) was shorter in AA (10.3; 95% confidence interval [CI]: 9.1, 11.7) vs. White patients (11.9; 95% CI: 10.9, 12.8) but not significantly different. After adjusting for potential confounders, the hazard ratio for OS was 1.09 (95% CI: 0.95, 1.25) for AA vs. White patients.

Conclusions

The proportion of patients with mTNBC was higher in AA than White mBC patients treated in community practices. Race did not show an association with OS. Both AA and White patients with mTNBC received similar treatments. OS was similarly poor in both groups, particularly in patients who had not received any documented anti-cancer treatment. Effective treatment remains a substantial unmet need for all patients with mTNBC.
Physician Burnout Through the Female Lens: A Silent Crisis
Authors: Yeluru Hemasree , Newton Heather L. , Kapoor Rupa
Published: May 2022

Physician burnout, the emotional exhaustion and depersonalization that arises from job fatigue and dissatisfaction, is a rapidly growing problem. Although burnout has been a recognized problem for decades, our healthcare system has yet to devise a sustainable solution. Additionally, burnout does not affect all physicians in the same way- women physicians have disproportionately higher rates of burnout than male physicians. Burnout poses a tremendous risk to our public's health with its severe and debilitating effects on both physician and patient health alike. We must intervene as early as medical school and residency at both the systemic and individual levels to combat burnout. Clinical leadership training might be one sustainable approach to begin addressing burnout in female physicians.