bluuebunny/crossref_metadata_2025 huggingface dataset:
Human movement in simulated hypogravity—Bridging the gap between space research and terrestrial rehabilitation
Authors: De Martino Enrico , Green David A. , Ciampi de Andrade Daniel , Weber Tobias , Herssens Nolan
Published: February 2023

Human movement is optimized to Earth's gravity and based on highly complex interactions between sensory and neuro-muscular systems. Yet, humans are able to adapt—at least partially—to extreme environments upon and beyond Earth's surface. With upcoming Lunar Gateway and Artemis missions, it is crucial to increase our understanding of the impact of hypogravity—i.e., reduced vertical loading—on physiological and sensory-motor performances to improve countermeasure programs, and define crewmember's readiness to perform mission critical tasks. Several methodologies designed to reduce vertical loading are used to simulate hypogravity on Earth, including body weight support (BWS) devices. Countering gravity and offloading the human body is also used in various rehabilitation scenarios to improve motor recovery in neurological and orthopedic impairments. Thus, BWS-devices have the potential of advancing theory and practice of both space exploration and terrestrial rehabilitation by improving our understanding of physiological and sensory-motor adaptations to reduced vertical loading and sensory input. However, lack of standardization of BWS-related research protocols and reporting hinders the exchange of key findings and new advancements in both areas. The aim of this introduction paper is to review the role of BWS in understanding human movement in simulated hypogravity and the use of BWS in terrestrial rehabilitation, and to identify relevant research areas contributing to the optimization of human spaceflight and terrestrial rehabilitation. One of the main aims of this research topic is to facilitate standardization of hypogravity-related research protocols and outcome reporting, aimed at optimizing knowledge transfer between space research and BWS-related rehabilitation sciences.
Staged stenting strategy of acutely wide-neck ruptured intracranial aneurysms: A meta-analysis and systematic review
Authors: Wei Yanpeng , Zhang Xiaoxi , Zhang Renkun , Zhang Guanghao , Shang Chenghao , Chen Rundong , Li Dan , Huyan Meihua , Wu Congyan , Zong Kang , Feng Zhengzhe , Dai Dongwei , Li Qiang , Huang Qinghai , Xu Yi , Yang Pengfei , Zhao Rui , Zuo Qiao , Liu Jianmin
Published: February 2023

Objective

In the study, we explored the safety and effectiveness of staged stenting strategy for acutely wide-neck ruptured intracranial aneurysms.

Methods

Online databases, including PubMed, EMBASE, the Cochrane database, and Web of Science, were retrospectively and systematically searched. The main observation indicators were the procedure-related complication rate, complete occlusion rate, and favorable clinical outcome. Meta-analysis was performed using a random or fixed effect model based on heterogeneity.

Results

A total of 5 studies with 143 patients were included. The hemorrhagic complication rate of the initial coiling and staged stenting was 2.8% (4 of 143) and 0, respectively. The ischemic complication rate of the coiling and supplemental stenting was 3.5% (5 of 143) and 2.9% (4 of 139), respectively. There were no deaths due to procedure-related complications in two stages. The aneurysm complete occlusion rate was 25% (95% CI, 0.13–0.03; I2 = 4.4%; P = 0.168) after initial coiling, 54% (95% CI, 0.63–0.64; I2 = 0%; P = 0.872) after staged stenting, and 74% (95% CI, 0.66–0.81; I2 = 56.4%; P = 0.562) at follow-up, respectively. Favorable clinical outcome rate 74% (95% CI, 0.61–0.86; I2 = 50.5%; P = 0.133) after discharge of initial coiling treatment, and 86% (95% CI, 0.80–0.92; I2 = 0; P = 0.410) after discharge from stenting, and 97% (95% CI, 0.93–1.01; I2 = 43.8%; P = 0.130) at follow-up.

Conclusion

Staged stenting treatment of wide-neck RIA with coiling in the acute phase followed by delayed regular stent or flow-diverter stent had high aneurysm occlusion rate, favorable clinical outcome rate and low procedure-related complication rate. A more dedicated and well-designed controlled study is warranted for further evaluation of staged stenting treatment compared to SCA in wide-neck RIA.
Analyzing and predicting the risk of death in stroke patients using machine learning
Authors: Zhu Enzhao , Chen Zhihao , Ai Pu , Wang Jiayi , Zhu Min , Xu Ziqin , Liu Jun , Ai Zisheng
Published: February 2023

Background

Stroke is an acute disorder and dysfunction of the focal neurological system that has long been recognized as one of the leading causes of death and severe disability in most regions globally. This study aimed to supplement and exploit multiple comorbidities, laboratory tests and demographic factors to more accurately predict death related to stroke, and furthermore, to make inferences about the heterogeneity of treatment in stroke patients to guide better treatment planning.

Methods

We extracted data from the Medical Information Mart from the Intensive Care (MIMIC)-IV database. We compared the distribution of the demographic factors between the control and death groups. Subsequently, we also developed machine learning (ML) models to predict mortality among stroke patients. Furthermore, we used meta-learner to recognize the heterogeneity effects of warfarin and human albumin. We comprehensively evaluated and interpreted these models using Shapley Additive Explanation (SHAP) analysis.

Results

We included 7,483 patients with MIMIC-IV in this study. Of these, 1,414 (18.9%) patients died during hospitalization or 30 days after discharge. We found that the distributions of age, marital status, insurance type, and BMI differed between the two groups. Our machine learning model achieved the highest level of accuracy to date in predicting mortality in stroke patients. We also observed that patients who were consistent with the model determination had significantly better survival outcomes than the inconsistent population and were better than the overall treatment group.

Conclusion

We used several highly interpretive machine learning models to predict stroke prognosis with the highest accuracy to date and to identify heterogeneous treatment effects of warfarin and human albumin in stroke patients. Our interpretation of the model yielded a number of findings that are consistent with clinical knowledge and warrant further study and verification.
Large-scale organoid study suggests effects of trisomy 21 on early fetal neurodevelopment are more subtle than variability between isogenic lines and experiments
Authors: Czerminski Jan T. , King Oliver D. , Lawrence Jeanne B.
Published: February 2023

This study examines cortical organoids generated from a panel of isogenic trisomic and disomic iPSC lines (subclones) as a model of early fetal brain development in Down syndrome (DS). An initial experiment comparing organoids from one trisomic and one disomic line showed many genome-wide transcriptomic differences and modest differences in cell-type proportions, suggesting there may be a neurodevelopmental phenotype that is due to trisomy of chr21. To better control for multiple sources of variation, we undertook a highly robust study of ∼1,200 organoids using an expanded panel of six all-isogenic lines, three disomic, and three trisomic. The power of this experimental design was indicated by strong detection of the ∼1.5-fold difference in chr21 genes. However, the numerous expression differences in non-chr21 genes seen in the smaller experiment fell away, and the differences in cell-type representation between lines did not correlate with trisomy 21. Results suggest that the initial smaller experiment picked up differences between small organoid samples and individual isogenic lines, which “averaged out” in the larger panel of isogenic lines. Our results indicate that even when organoid and batch variability are better controlled for, variation between isogenic cell lines (even subclones) may obscure, or be conflated with, subtle neurodevelopmental phenotypes that may be present in ∼2nd trimester DS brain development. Interestingly, despite this variability between organoid batches and lines, and the “fetal stage” of these organoids, an increase in secreted Aβ40 peptide levels—an Alzheimer-related cellular phenotype—was more strongly associated with trisomy 21 status than were neurodevelopmental shifts in cell-type composition.
Dynamic spectral cues do not affect human sound localization during small head movements
Authors: McLachlan Glen , Majdak Piotr , Reijniers Jonas , Mihocic Michael , Peremans Herbert
Published: February 2023

Natural listening involves a constant deployment of small head movement. Spatial listening is facilitated by head movements, especially when resolving front-back confusions, an otherwise common issue during sound localization under head-still conditions. The present study investigated which acoustic cues are utilized by human listeners to localize sounds using small head movements (below ±10° around the center). Seven normal-hearing subjects participated in a sound localization experiment in a virtual reality environment. Four acoustic cue stimulus conditions were presented (full spectrum, flattened spectrum, frozen spectrum, free-field) under three movement conditions (no movement, head rotations over the yaw axis and over the pitch axis). Localization performance was assessed using three metrics: lateral and polar precision error and front-back confusion rate. Analysis through mixed-effects models showed that even small yaw rotations provide a remarkable decrease in front-back confusion rate, whereas pitch rotations did not show much of an effect. Furthermore, MSS cues improved localization performance even in the presence of dITD cues. However, performance was similar between stimuli with and without dMSS cues. This indicates that human listeners utilize the MSS cues before the head moves, but do not rely on dMSS cues to localize sounds when utilizing small head movements.
Variation of peripheral pulse transit time with internal vascular pressure changes induced by arm movement
Authors: Sun Zhiwei , Jiang Xinge , Wu Hua , Liu Feifei
Published: February 2023

Pulse transit time (PTT) and blood pressure (BP) are widely used to quantify arterial characteristics. Arm position influences arterial BP and peripheral PTT. This study aims to quantify the relationship between PTT changes with internal vascular pressure variations induced by the arm moving. With left arm at horizontal position as reference and the right arm moving from 90 to 45, 0, −45, and −90° respectively, PTT difference was calculated by the difference of the pulse foot between right arm and left arm within the same heartbeat. The change in the BP was calculated from the gravitational effect with the measured arm length. Our results showed that the change in PTT with arm elevating is more obvious than that with arm lowering, indicating the different relationship between PTT changes due to the internal BP changes. This can help in understanding the inherent physiological/pathological mechanism of cardiovascular system.
Development and validation of a radiomics-based nomogram for the prediction of postoperative malnutrition in stage IB1-IIA2 cervical carcinoma
Authors: Yu Wenke , Xu Hong’en , Chen Fangjie , Shou Huafeng , Chen Ying , Jia Yongshi , Zhang Hongwei , Ding Jieni , Xiong Hanchu , Wang Yiwen , Song Tao
Published: February 2023

Objective

In individuals with stage IB1-IIA2 cervical cancer (CC) who received postoperative radiotherapy ± chemotherapy (PORT/CRT), the interaction between sarcopenia and malnutrition remains elusive, let alone employing a nomogram model based on radiomic features of psoas extracted at the level of the third lumbar vertebra (L3). This study was set to develop a radiomics-based nomogram model to predict malnutrition as per the Patient-Generated Subjective Global Assessment (PG-SGA) for individuals with CC.

Methods

In total, 120 individuals with CC underwent computed tomography (CT) scans before PORT/CRT. The radiomic features of psoas at L3 were obtained from non-enhanced CT images. Identification of the optimal features and construction of the rad-score formula were conducted utilizing the least absolute shrinkage and selection operator (LASSO) logistic regression to predict malnutrition in the training dataset (radiomic model). Identification of the major clinical factors in the clinical model was performed by means of binary logistic regression analysis. The radiomics-based nomogram was further developed by integrating radiomic signatures and clinical risk factors (combined model). The receiver operating characteristic (ROC) curves and decision curves analysis (DCA) were employed for the evaluation and comparison of the three models in terms of their predictive performance.

Results

Twelve radiomic features in total were chosen, and the rad-score was determined with the help of the non-zero coefficient from LASSO regression. Multivariate analysis revealed that besides rad-score, age and Eastern Cooperative Oncology Group performance status could independently predict malnutrition. As per the data of this analysis, a nomogram prediction model was constructed. The area under the ROC curves (AUC) values of the radiomic and clinical models were 0.778 and 0.847 for the training and 0.776 and 0.776 for the validation sets, respectively. An increase in the AUC was observed up to 0.972 and 0.805 in the training and validation sets, respectively, in the combined model. DCA also confirmed the clinical benefit of the combined model.

Conclusion

This radiomics-based nomogram model depicted potential for use as a marker for predicting malnutrition in stage IB1-IIA2 CC patients who underwent PORT/CRT and required further investigation with a large sample size.
Retrospective analysis of risk factors for distant metastasis of early-onset gastric cancer during the perioperative period
Authors: Bi Bo , Deng Guo-fei , Duan Yun-min , Huang Zhi-jian , Chen Xiao-yan , Zhang Chang-hua , He Yu-long
Published: February 2023

Background

Although the overall global incidence of gastric cancer has been declining, the number of new cases in people under the age of 50 is increasing, which is related to metastasis, late pathological stages, and poor prognosis. There is a scarcity of large-scale studies to evaluate and predict distant metastasis in patients with early-onset gastric cancer.

Methods

From January 2010 to December 2019, data on early-onset GC patients undergoing surgery were gathered from the Surveillance, Epidemiology, and End Results (SEER) database. We investigated the independent risk factors for distant metastasis in patients with early-onset gastric cancer. Based on these risk factors, we developed a nomogram to predict distant metastasis. The model underwent internal validation on the test set and external validation on 205 patients from the First Affiliated Hospital of Sun Yat-sen University and the seventh Affiliated Hospital of Sun Yat-sen University. The novel nomogram model was then evaluated using the receiver operating characteristic (ROC) curve, calibration, the area under the curve (AUC), and decision curve analysis (DCA). The training set nomogram score was used to classify the different risk clusters of distant metastasis.

Results

Our study enrolled 2217 patients after establishing the inclusion and exclusion criteria, with 1873 having no distant metastasis and 344 having distant metastasis. The tumor size, total lymph nodes, whether or not receiving radiotherapy and chemotherapy, T stage, and N stage were significant predictors of advanced distant metastasis (p < 0.05). The AUC of the ROC analysis demonstrated our model’s high accuracy. Simultaneously, the prediction model shows high stability and clinical practicability in the calibration curve and DCA analysis.

Conclusions

We developed an innovative nomogram containing clinical and pathological characteristics to predict distant metastasis in patients younger than 50 years old with gastric cancer. The tool can alert clinicians about distant metastasis and help them develop more effective clinical treatment plans.
The emerging applications and advancements of Raman spectroscopy in pediatric cancers
Authors: Li Chenbei , Feng Chengyao , Xu Ruiling , Jiang Buchan , Li Lan , He Yu , Tu Chao , Li Zhihong
Published: February 2023

Although the survival rate of pediatric cancer has significantly improved, it is still an important cause of death among children. New technologies have been developed to improve the diagnosis, treatment, and prognosis of pediatric cancers. Raman spectroscopy (RS) is a non-destructive analytical technique that uses different frequencies of scattering light to characterize biological specimens. It can provide information on biological components, activities, and molecular structures. This review summarizes studies on the potential of RS in pediatric cancers. Currently, studies on the application of RS in pediatric cancers mainly focus on early diagnosis, prognosis prediction, and treatment improvement. The results of these studies showed high accuracy and specificity. In addition, the combination of RS and deep learning is discussed as a future application of RS in pediatric cancer. Studies applying RS in pediatric cancer illustrated good prospects. This review collected and analyzed the potential clinical applications of RS in pediatric cancers.
MUC16 and TP53 family co-regulate tumor-stromal heterogeneity in pancreatic adenocarcinoma
Authors: Chirravuri-Venkata Ramakanth , Dam Vi , Nimmakayala Rama Krishna , Alsafwani Zahraa Wajih , Bhyravbhatla Namita , Lakshmanan Imayavaramban , Ponnusamy Moorthy P. , Kumar Sushil , Jain Maneesh , Ghersi Dario , Batra Surinder K.
Published: February 2023

MUC16/CA125 is one of the few oldest cancer biomarkers still used in current clinical practice. As mesothelium is an abundant source of MUC16 and a major contributor to stromal heterogeneity in PDAC, we investigated the regulation of MUC16 in tumor and stromal compartments individually. The trajectories constructed using the single-cell transcriptomes of stromal cells from KPC tumors demonstrated continuity in the trajectory path between MUC16-expressing mesothelial cells and other CAF subsets. Further, the tumor tissues of MUC16 whole-body knockout (KPCM) showed dysregulation in the markers of actomyosin assembly and fibroblast differentiation (iCAF and myCAF), indicating that MUC16 has an extra-tumoral role in controlling CAF differentiation. Although we found mesothelium-derivative stromal cells to be bystanders in normal pancreas, the proportion of these cells was higher in invasive PDAC, particularly in TP53 deficient tumors. Moreover, we also detail the regulation of MUC16, KRAS, and SOX9 by TP53 family members (TP53 and TP63) using multi-omics data from knockout models, PDAC cell lines, and human PDAC tissues.
Preoperative individual-target transcranial magnetic stimulation demonstrates an effect comparable to intraoperative direct electrical stimulation in language-eloquent glioma mapping and improves postsurgical outcome: A retrospective fiber-tracking and electromagnetic simulation study
Authors: Li Sanzhong , Mu Yunfeng , Rao Yang , Sun Chuanzhu , Li Xiang , Liu Huan , Yu Xun , Yan Xiao , Ding Yunxia , Wang Yangtao , Fei Zhou
Published: February 2023

Background

Efforts to resection of glioma lesions located in brain-eloquent areas must balance the extent of resection (EOR) and functional preservation. Currently, intraoperative direct electrical stimulation (DES) is the gold standard for achieving the maximum EOR while preserving as much functionality as possible. However, intraoperative DES inevitably involves risks of infection and epilepsy. The aim of this study was to verify the reliability of individual-target transcranial magnetic stimulation (IT-TMS) in preoperative mapping relative to DES and evaluate its effectiveness based on postsurgical outcomes.

Methods

Sixteen language-eloquent glioma patients were enrolled. Nine of them underwent preoperative nTMS mapping (n=9, nTMS group), and the other seven were assigned to the non-nTMS group and did not undergo preoperative nTMS mapping (n=7). Before surgery, online IT-TMS was performed during a language task in the nTMS group. Sites in the cortex at which this task was disturbed in three consecutive trials were recorded and regarded as positive and designated nTMS hotspots (HSnTMS). Both groups then underwent awake surgery and intraoperative DES mapping. DES hotspots (HSDES) were also determined in a manner analogous to HSnTMS. The spatial distribution of HSnTMS and HSDES in the nTMS group was recorded, registered in a single brain template, and compared. The center of gravity (CoG) of HSnTMS (HSnTMS-CoG)-based and HSDES-CoG-based diffusion tensor imaging-fiber tracking (DTI-FT) was performed. The electromagnetic simulation was conducted, and the values were then compared between the nTMS and DES groups, as were the Western Aphasia Battery (WAB) scale and fiber-tracking values.

Results

HSnTMS and HSDES showed similar distributions (mean distance 6.32 ± 2.6 mm, distance range 2.2-9.3 mm, 95% CI 3.9-8.7 mm). A higher fractional anisotropy (FA) value in nTMS mapping (P=0.0373) and an analogous fiber tract length (P=0.2290) were observed. A similar distribution of the electric field within the brain tissues induced by nTMS and DES was noted. Compared with the non-nTMS group, the integration of nTMS led to a significant improvement in language performance (WAB scores averaging 78.4 in the nTMS group compared with 59.5 in the non-nTMS group, P=0.0321 < 0.05) as well as in brain-structure preservation (FA value, P=0.0156; tract length, P=0.0166).

Conclusion

Preoperative IT-TMS provides data equally crucial to DES and thus facilitates precise brain mapping and the preservation of linguistic function.
Syngeneic model of carcinogen-induced tumor mimics basal/squamous, stromal-rich, and neuroendocrine molecular and immunological features of muscle-invasive bladder cancer
Authors: Shah Shruti D. , Gillard Bryan M. , Wrobel Michelle M. , Karasik Ellen , Moser Michael T. , Mastri Michalis , Long Mark D. , Sule Norbert , Brackett Craig M. , Huss Wendy J. , Foster Barbara A.
Published: February 2023

Introduction

Bladder cancer is a heterogenous disease and the emerging knowledge on molecular classification of bladder tumors may impact treatment decisions based on molecular subtype. Pre-clinical models representing each subtype are needed to test novel therapies. Carcinogen-induced bladder cancer models represent heterogeneous, immune-competent, pre-clinical testing options with many features found in the human disease.

Methods

Invasive bladder tumors were induced in C57BL/6 mice when continuously exposed to N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) in the drinking water. Tumors were excised and serially passed by subcutaneous implantation into sex-matched syngeneic C57BL/6 hosts. Eight lines were named BBN-induced Urothelium Roswell Park (BURP) tumor lines. BURP lines were characterized by applying consensus molecular classification to RNA expression, histopathology, and immune profiles by CIBERSORT. Two lines were further characterized for cisplatin response.

Results

Eight BURP tumor lines were established with 3 male and 3 female BURP tumor lines, having the basal/squamous (BaSq) molecular phenotype and morphology. BURP-16SR was established from a male mouse and has a stromal-rich (SR) molecular phenotype and a sarcomatoid carcinoma morphology. BURP-19NE was established from a male mouse and has a neuroendocrine (NE)-like molecular phenotype and poorly differentiated morphology. The established BURP tumor lines have unique immune profiles with fewer immune infiltrates compared to their originating BBN-induced tumors. The immune profiles of the BURP tumor lines capture some of the features observed in the molecular classifications of human bladder cancer. BURP-16SR growth was inhibited by cisplatin treatment, while BURP-24BaSq did not respond to cisplatin.

Discussion

The BURP lines represent several molecular classifications, including basal/squamous, stroma-rich, and NE-like. The stroma-rich (BURP-16SR) and NE-like (BURP-19NE) represent unique immunocompetent models that can be used to test novel treatments in these less common bladder cancer subtypes. Six basal/squamous tumor lines were established from both male and female mice. Overall, the BURP tumor lines have less heterogeneity than the carcinogen-induced tumors and can be used to evaluate treatment response without the confounding mixed response often observed in heterogeneous tumors. Additionally, basal/squamous tumor lines were established and maintained in both male and female mice, thereby allowing these tumor lines to be used to compare differential treatment responses between sexes.
Volume change rate before and after neoadjuvant systemic therapy of breast cancer is an efficacious evaluation index to predict pathological complete response
Authors: Xu Yinggang , Zhang Weiwei , Wang Siqi , Xu Lu , Xu Haiping , Chen Rui , Shi Xiaoqing , Huang Xiaofeng , Wang Ye , He Jinzhi , Shi Wenjie , Wan Xinyu , Wang Jue , Zha Xiaoming
Published: February 2023

Neoadjuvant systemic therapy (NST) is widely applied in breast cancer treatment, but individuals respond differently to the same NST regimen. It is unclear which patients should adjust their NST regimen and what such an adjustment should be, especially for patients with radiologically partial response (PR). This study aimed to identify a quantitative efficacy evaluation index to evaluate the therapeutic effect of NST. 164 patients were enrolled in this study received four cycles of epirubicin and cyclophosphamide (EC), followed by four cycles of taxanes with trastuzumab [T(H)], if needed. Of patients with a volume change rate of EC treatment (δV1) below 0.80, more than half benefited from subsequent T(H) treatment compared with EC treatment. Importantly, for δV1 of 0.80 and higher, patients’ subsequent T(H) treatment was not as efficient as previous EC treatment and they have a lower pathological complete response (pCR) rate. Across all patients, nanoparticle albumin-bound paclitaxel had a numerically higher pCR rate over other taxanes in patients with triple-negative breast cancer. This study showed that the volume change rate is better than the diameter change rate in monitoring the therapeutic effect of NST. Furthermore, δV1 is a good quantitative efficacy evaluation index to distinguish patients resistant to EC treatment and predict the pCR rate and guide the adjustment of individualized NST regimens.
Early cochlear implantation in prelingual profound hearing loss in Italy, analyzed by means of a social media survey
Authors: Orzan Eva , Pizzamiglio Giulia , Magadle Jad , Bubbico Luciano , Cutler Jodi M. , Consolino Patrizia , Burdo Sandro , Zamagni Giulia , Magni Elena , Mariottini Claudio , Gambacorta Valeria , Ricci Giampietro , Brotto Davide
Published: February 2023

Objective

To assess newborn hearing screening (NHS) impact on timing of cochlear implant (CI) surgery of patients with prelingual bilateral profound hearing impairment (BPHI), in order to evaluate whether the NHS ultimately serves the needs of the target population in Italy.

Methods

An online questionnaire was created to survey subjects affected by prelingual BPHL born between 1990 and 2018. Questions focused on age at BPHI diagnosis, first and second CI surgery (if performed), and the region in which the surgery was performed. The survey was distributed to potential participants via social media communities used by hearing impaired people or their family members for sharing advice and offering support. Responses were analyzed using descriptive statistics.

Results

Among the 318 respondents who completed the questionnaire, 276 (87%) reported having chosen CI surgery, 2/3 of them bilaterally. In the vast majority (97%) of cases the CI is used on a daily basis. Most of the people residing in the center (65%) and southern Italy (71%) had to move from their region of residence to perform the surgery. Late CI surgery was associated with failure to perform NHS (p = 0.007), birth before 2011 (p = 0.009), definitive diagnosis of BPHI after 6 months of life (p = 0.002), and progressive hearing impairment (p < 0.001).

Conclusion

The worldwide scientific approval of the NHS as the current best opportunity for early diagnosis and CI treatment for prelingual BPHI is confirmed by what patients and families reported via the online questionnaire used for this study. In recent years, early bilateral cochlear implantation has become increasingly available in Italy, but late diagnosis, progressive hearing loss, failure to perform the NHS and lack of follow-up are still open questions. A large proportion of families had to move from the region of residence to have their child undergo CI surgery, revealing inequalities in terms of geographical disparities. Social media has proved to be a valuable, fast and inexpensive tool for gathering information on the effectiveness of health prevention programs, involving a large sample of individuals in a short amount of time.
Case Report: Recombinant human growth hormone therapy in a patient with spondyloepiphyseal dysplasia, Kondo-Fu type
Authors: Chen Congli , Wu Jin , Liu Ying
Published: February 2023

Background

Variants in membrane-bound transcription factor peptidase, site 1 (MBTPS1) gene, can result in clinically rare spondyloepiphyseal dysplasia of Kondo-fu type (OMIM #618392, SEDKF), Silver–Russell syndrome, and CAOP (cataract, alopecia, oral mucosal disorder, and psoriasis-like) syndrome.

Case presentation

A 6-year-old Chinese male child diagnosed with SEDKF underwent 3 years of growth hormone therapy. A genetic examination revealed two new nonsense variants in the MBTPS1 gene on chromosome 16q23-q24 with compound heterozygotes c.1589(exon12)A > G and c.163(exon2)G > A.

Conclusion

The MBTPS1 gene c.1589(exon12)A > G and c.163(exon2)G > A on chromosome 16q23-q24 is associated with SEDKF. Growth hormone therapy can repair growth retardation in patients with spondyloepiphyseal dysplasia, Kondo-Fu type; however, more evidence of such patient cases is required to support this hypothesis.
Shu-Xie decoction alleviates oxidative stress and colon injury in acute sleep-deprived mice by suppressing p62/KEAP1/NRF2/HO1/NQO1 signaling
Authors: Wang Mengyuan , Li Bo , Liu Yijiang , Zhang Mengting , Huang Caoxin , Cai Teng , Jia Yibing , Huang Xiaoqing , Ke Hongfei , Liu Suhuan , Yang Shuyu
Published: February 2023

Introduction: Sleep disorders are common clinical psychosomatic disorders that can co-exist with a variety of conditions. In humans and animal models, sleep deprivation (SD) is closely related with gastrointestinal diseases. Shu-Xie Decoction (SX) is a traditional Chinese medicine (TCM) with anti-nociceptive, anti-inflammatory, and antidepressant properties. SX is effective in the clinic for treating patients with abnormal sleep and/or gastrointestinal disorders, but the underlying mechanisms are not known. This study investigated the mechanisms by which SX alleviates SD-induced colon injury in vivo.

Methods: C57BL/6 mice were placed on an automated sleep deprivation system for 72 h to generate an acute sleep deprivation (ASD) model, and low-dose SX (SXL), high-dose SX (SXH), or S-zopiclone (S-z) as a positive control using the oral gavage were given during the whole ASD-induced period for one time each day. The colon length was measured and the colon morphology was visualized using hematoxylin and eosin (H&E) staining. ROS and the redox biomarkers include reduced glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) were detected. Quantitative real-time PCR (qRT-PCR), molecular docking, immunofluorescence and western blotting assays were performed to detect the antioxidant signaling pathways.

Results: ASD significantly increased FBG levels, decreased colon length, moderately increased the infiltration of inflammatory cells in the colon mucosa, altered the colon mucosal structure, increased the levels of ROS, GSH, MDA, and SOD activity compared with the controls. These adverse effects were significantly alleviated by SX treatment. ASD induced nuclear translocation of NRF2 in the colon mucosal cells and increased the expression levels of p62, NQO1, and HO1 transcripts and proteins, but these effects were reversed by SX treatment.

Conclusion: SX decoction ameliorated ASD-induced oxidative stress and colon injury by suppressing the p62/KEAP1/NRF2/HO1/NQO1 signaling pathway. In conclusion, combined clinical experience, SX may be a promising drug for sleep disorder combined with colitis.
Sodium/(calcium + potassium) exchanger NCKX4 optimizes KLK4 activity in the enamel matrix microenvironment to regulate ECM modeling
Authors: Chan Barry , Cheng Ieong Cheng , Rozita Jalali , Gorshteyn Ida , Huang Yulei , Shaffer Ida , Chang Chih , Li Wu , Lytton Jonathan , Den Besten Pamela , Zhang Yan
Published: February 2023

Enamel development is a process in which extracellular matrix models from a soft proteinaceous matrix to the most mineralized tissue in vertebrates. Patients with mutant NCKX4, a gene encoding a K+-dependent Na+/Ca2+—exchanger, develop a hypomineralized and hypomature enamel. How NCKX4 regulates enamel protein removal to achieve an almost protein-free enamel is unknown. We characterized the upregulation pattern of Nckx4 in the progressively differentiating enamel-forming ameloblasts by qPCR, and as well as confirmed NCKX4 protein to primarily localize at the apical surface of wild-type ruffle-ended maturation ameloblasts by immunostaining of the continuously growing mouse incisors, posing the entire developmental trajectory of enamel. In contrast to the normal mature enamel, where ECM proteins are hydrolyzed and removed, we found significant protein retention in the maturation stage of Nckx4−/− mouse enamel. The Nckx4−/− enamel held less Ca2+ and K+ but more Na+ than the Nckx4+/+ enamel did, as measured by EDX. The alternating acidic and neutral pH zones at the surface of mineralizing Nckx4+/+ enamel were replaced by a largely neutral pH matrix in the Nckx4−/− enamel. In situ zymography revealed a reduced kallikrein-related peptidase 4 (KLK4) activity in the Nckx4−/− enamel. We showed that KLK4 took on 90% of proteinase activity in the maturation stage of normal enamel, and that recombinant KLK4 as well as native mouse enamel KLK4 both performed less effectively in a buffer with increased [Na+] and pH, conditions found in the Nckx4−/− developing enamel. This study, for the first time to our knowledge, provides evidence demonstrating the impaired in situ KLK4 activity in Nckx4−/− enamel and suggests a novel function of NCKX4 in facilitating KLK4-mediated hydrolysis and removal of ECM proteins, warranting the completion of enamel matrix modeling.
Characterization of HAK protein family in Casuarina equisetifolia and the positive regulatory role of CeqHAK6 and CeqHAK11 genes in response to salt tolerance
Authors: Wang Yujiao , Zhang Yong , Wei Yongcheng , Meng Jingxiang , Zhong Chonglu , Fan Chunjie
Published: February 2023

The potassium transporter group of the HAK/KUP/KT (high-affinity K+)/KUP (K+ uptake)/KT (K+ transporter) family plays a crucial role in plant growth and development as well as in environmental adaptation such as tolerance to salt stress. HAK/KUP/KT genes and their functions have been characterized for a number of plant species, but they remain unknown for Casuarina equisetifolia, an important tree species for coastal protection in southern China and many other countries. In this study, 25 HAK genes were identified in the C. equisetifolia genome. Their gene structure, conserved motif, phylogeny, and expression were comprehensively and systematically analyzed to understand their functions. All HAK genes were relatively conserved and could be divided into four clusters. The expression level of two particular genes, CeqHAK11 and CeqHAK6, increased significantly with the duration of salt treatment. To further elucidated their function in response to salt stress, subcellular localization, and their functional analysis were developed. Results revealed that CeqHAK11 and CeqHAK6 were localized on the plasma membrane, which mainly mediated high-affinity K+ uptake. Overexpression of CeqHAK6 or CeqHAK11 in Arabidopsis showed higher germination and survival rates and longer root length than wild-type (WT) under salt stress, suggesting that both genes improve tolerance to salt stress. Moreover, CeqHAK6 and CeqHAK11 improved their ability to tolerate salt stress by increasing the K+/Na+ ratio and antioxidant enzyme activities (CAT, POD, and SOD), and decreasing reactive oxygen species (ROS) accumulation. Consequently, CeqHAK6 and CeqHAK11 were verified as potassium transport proteins and could be applied for further molecular breeding for salt tolerance in C. equisetifolia or other crops to increasing salt tolerance.
Silicon in action: Between iron scarcity and excess copper
Authors: Nikolić Dragana , Bosnić Dragana , Samardžić Jelena
Published: February 2023

Essential micronutrients belonging to the transition metals, such as Fe and Cu, are indispensable for plant growth and stress tolerance; however, when present in excess, they can become potentially dangerous producers of reactive oxygen species. Therefore, their homeostases must be strictly regulated. Both microelement deficiencies and elevated concentrations of heavy metals in the soil are global problems that reduce the nutritional value of crops and seriously affect human health. Silicon, a beneficial element known for its protective properties, has been reported to alleviate the symptoms of Cu toxicity and Fe deficiency stress in plants; however, we are still far from a comprehensive understanding of the underlying molecular mechanisms. Although Si-mediated mitigation of these stresses has been clearly demonstrated for some species, the effects of Si vary depending on plant species, growing conditions and experimental design. In this review, the proposed mechanistic models explaining the effect of Si are summarized and discussed. Iron and copper compete for the common metal transporters and share the same transport routes, hence, inadequate concentration of one element leads to disturbances of another. Silicon is reported to beneficially influence not only the distribution of the element supplied below or above the optimal concentration, but also the distribution of other microelements, as well as their molar ratios. The influence of Si on Cu immobilization and retention in the root, as well as Si-induced Fe remobilization from the source to the sink organs are of vital importance. The changes in cellular Cu and Fe localization are considered to play a crucial role in restoring homeostasis of these microelements. Silicon has been shown to stimulate the accumulation of metal chelators involved in both the mobilization of deficient elements and scavenging excess heavy metals. Research into the mechanisms of the ameliorative effects of Si is valuable for reducing mineral stress in plants and improving the nutritional value of crops. This review aims to provide a thorough and critical overview of the current state of knowledge in this field and to discuss discrepancies in the observed effects of Si and different views on its mode of action.
Phylogenetic and AlphaFold predicted structure analyses provide insights for A1 aspartic protease family classification in Arabidopsis
Authors: Duan Yanling , Tang Hao , Yu Xiaobo
Published: February 2023

Aspartic proteases are widely distributed in animals, plants, fungi and other organisms. In land plants, A1 aspartic protease family members have been implicated to play important and varied roles in growth, development and defense. Thus a robust classification of this family is important for understanding their gene function and evolution. However, current A1 family members in Arabidopsis are less well classified and need to be re-evaluated. In this paper, 70 A1 aspartic proteases in Arabidopsis are divided into four groups (group I-IV) based on phylogenetic and gene structure analyses of 1200 A1 aspartic proteases which are obtained from 12 Embryophyta species. Group I-III members are further classified into 2, 4 and 7 subgroups based on the AlphaFold predicted structures. Furthermore, unique insights of A1 aspartic proteases have been unraveled by AlphaFold predicted structures. For example, subgroup II-C members have a unique II-C specific motif in the C-extend domain, and subgroup IV is a Spermatophyta conserved group without canonical DTGS/DSGT active sites. These results prove that AlphaFold combining phylogenetic analysis is a promising solution for complex gene family classification.
Deep learning for crown profile modelling of Pinus yunnanensis secondary forests in Southwest China
Authors: Chen Yuling , Wang Jianming
Published: February 2023

Accurate information concerning crown profile is critical in analyzing biological processes and providing a more accurate estimate of carbon balance, which is conducive to sustainable forest management and planning. The similarities between the types of data addressed with LSTM algorithms and crown profile data make a compelling argument for the integration of deep learning into the crown profile modeling. Thus, the aim was to study the application of deep learning method LSTM and its variant algorithms in the crown profile modeling, using the crown profile database from Pinus yunnanensis secondary forests in Yunnan province, in southwest China. Furthermore, the SHAP (SHapley Additive exPlanations) was used to interpret the predictions of ensemble or deep learning models. The results showed that LSTM’s variant algorithms was competitive with traditional Vanila LSTM, but substantially outperformed ensemble learning model LightGBM. Specifically, the proposed Hybrid LSTM-LightGBM and Integrated LSTM-LightGBM have achieved a best forecasting performance on training set and testing set respectively. Furthermore, the feature importance analysis of LightGBM and Vanila LSTM presented that there were more factors that contribute significantly to Vanila LSTM model compared to LightGBM model. This phenomenon can explain why deep learning outperforms ensemble learning when there are more interrelated features.
Energetic considerations for engineering novel biochemistries in photosynthetic organisms
Authors: Strand Deserah D. , Walker Berkley J.
Published: February 2023

Humans have been harnessing biology to make valuable compounds for generations. From beer and biofuels to pharmaceuticals, biology provides an efficient alternative to industrial processes. With the continuing advancement of molecular tools to genetically modify organisms, biotechnology is poised to solve urgent global problems related to environment, increasing population, and public health. However, the light dependent reactions of photosynthesis are constrained to produce a fixed stoichiometry of ATP and reducing equivalents that may not match the newly introduced synthetic metabolism, leading to inefficiency or damage. While photosynthetic organisms have evolved several ways to modify the ATP/NADPH output from their thylakoid electron transport chain, it is unknown if the native energy balancing mechanisms grant enough flexibility to match the demands of the synthetic metabolism. In this review we discuss the role of photosynthesis in the biotech industry, and the energetic considerations of using photosynthesis to power synthetic biology.
The chickpea root rot complex in Saskatchewan, Canada- detection of emerging pathogens and their relative pathogenicity
Authors: Armstrong-Cho Cheryl , Sivachandra Kumar Nimllash Thangam , Kaur Ramanpreet , Banniza Sabine
Published: February 2023

Chickpea fields in Saskatchewan, one of the three Canadian prairie provinces, have suffered from major health issues since 2019, but no definitive cause has been determined. Field surveys were conducted in Saskatchewan in 2020 and 2021 in order to develop a better understanding of root rot pathogens associated with chickpea. Root samples were analyzed for the presence of 11 potential chickpea root rot pathogens using end-point PCR. Fusarium redolens, F. solani and F. avenaceum were the most prevalent pathogen species detected in both survey years. The cause of Fusarium wilt in chickpea, F. oxysporum f. sp. ciceris, was not detected in either year, nor were Phytophthora spp. and Verticillium albo-atrum. Berkeleyomyces sp. was detected in one field in each year, and Verticillium dahliae was detected in several fields sampled in 2021. These two pathogens have not been reported previously on chickpea in Saskatchewan. The prevalence of Fusarium species obtained from 2021 root isolations was similar to that determined by molecular tests, with frequent isolation of F. redolens, F. oxysporum, F. avenaceum and F. solani. A series of indoor pathogenicity testing compared root disease severity caused by a selection of 16 isolates of six Fusarium species and single isolates of V. dahliae, Berkeleyomyces sp. and Macrophomina phaseolina. Results showed that select isolates of F. avenaceum were the most aggressive of the Fusarium isolates on chickpea. Despite relatively low inoculum density, a highly aggressive isolate of F. avenaceum caused severe stunting and more root rot symptoms than single isolates of V. dahliae, Berkeleyomyces sp. and M. phaseolina under the test conditions.
Genomic identification of cotton SAC genes branded ovule and stress-related key genes in Gossypium hirsutum
Authors: Shuya Ma , Le Liu , Huiyun Shi , Yu Gu , Yujun Li , Qanmber Ghulam
Published: February 2023

SAC genes have been identified to play a variety of biological functions and responses to various stresses. Previously, SAC genes have been recognized in animals and Arabidopsis. For the very first time, we identified 157 SAC genes in eight cotton species including three diploids and five tetraploids with 23 SAC members in G. hirsutum. Evolutionary analysis classified all cotton SAC gene family members into five distinct groups. Cotton SAC genes showed conserved sequence logos and WGD or segmental duplication. Multiple synteny and collinearity analyses revealed gene family expansion and purifying selection pressure during evolution. G. hirsutum SAC genes showed uneven chromosomal distribution, multiple exons/introns, conserved protein motifs, and various growth and stress-related cis-elements. Expression pattern analysis revealed three GhSAC genes (GhSAC3, GhSAC14, and GhSAC20) preferentially expressed in flower, five genes (GhSAC1, GhSAC6, GhSAC9, GhSAC13, and GhSAC18) preferentially expressed in ovule and one gene (GhSAC5) preferentially expressed in fiber. Similarly, abiotic stress treatment verified that GhSAC5 was downregulated under all stresses, GhSAC6 and GhSAC9 were upregulated under NaCl treatment, and GhSAC9 and GhSAC18 were upregulated under PEG and heat treatment respectively. Overall, this study identified key genes related to flower, ovule, and fiber development and important genetic material for breeding cotton under abiotic stress conditions.
Socioeconomic status and problem behaviors in young Chinese children: A moderated mediation model of parenting styles and only children
Authors: Lin Xunyi , Zhang Yifan , Liao Yutong , Xie Wanlin
Published: February 2023

Introduction

This study tested a moderated mediation model of child number (CN) and parenting styles (PS) in the relationships between family socioeconomic status (SES) and young children’s problem behaviors (PB).

Methods

A sample of 1,101 children (Mage = 4.90 years, SD = 1.07) and their parents participated in this study. Parents reported on PS, SES, and children’s PB.

Results and Discussion

The results show SES was positively related to authoritative parenting and negatively related to authoritarian parenting; problem behaviors were negatively related to authoritative parenting and positively related to authoritarian parenting; authoritative parenting and authoritarian parenting mediated the relationship between SES and PB; and singleton moderated the relationship between SES and PB. The combination of only children and low levels of SES could lead to high PB levels, while the combination of non-only children and high levels of SES could lead to high PB levels. At the same SES, only children had higher PB levels than non-only children.