bluuebunny/crossref_metadata_2025 huggingface dataset:
Response times for reflexive saccades correlate with cognition in parkinson's disease, not disease severity or duration
Authors: Yu Yaqin , Yan Weihong , Xu Xin , Zhang Kaili , Si Lihong , Liu Xiaolei , Wang Jinyu , Song Junling , Sun Huanxin , Li Xinyi
Published: August 2022

Objective

Dementia is a common and serious non-motor symptom in Parkinson's disease (PD). We aimed to investigate the reflexive saccade in PD patients and explore its potential role as a biomarker for cognitive decline.

Methods

Using an infrared video-based eye tracker, we investigated reflexive saccades in 94 PD patients and 115 healthy controls (HCs). Saccadic parameters were compared between PD patients and HCs, and also among PD subgroups. The correlation of saccadic performance with disease duration, severity and cognition were further investigated.

Results

Compared with healthy controls, PD patients had prolonged and hypometric reflexive saccades even in early disease stage. Univariate and multivariate analysis showed that there was significant inverse relation between prolonged latency and MMSE in PD patients (P < 0.05); tremor dominant PD patients were more likely to have decreased velocity than non-tremor-dominant PD patients (P < 0.05); saccadic accuracy was found to have no significant relation with disease duration, H&Y staging or MMSE.

Conclusion

Reflexive saccadic performance was abnormal in PD and worsened with cognitive decline. The negative correlation between prolonged latency and MMSE scores may make the reflexive saccade a potential predictor for cognitive decline in Parkinson's disease.
Individualized CT image-guided free-hand catheter technique: A new and reliable method for minimally invasive evacuation of basal ganglia hematoma
Authors: Zhao Zhijie , Xiao Jinting , Wang Jianjun , Meng Xiangjing , Li Cuiling , Xin Tao , Li Shengjie
Published: August 2022

Objective

To validate the clinical reliability of an individualized CT image-guided‘ free-hand catheter technique (CTGFC) for basal ganglia hematoma (BGH) evacuation.

Methods

From January 2017 to December 2020, 58 cases of patients with BGH who underwent catheter evacuation were enrolled. The surgery was conducted using the CTGFC (n = 31) or stereotactic catheter technique (STC, n = 27). The authors evaluated the baseline characteristics, operation-related indicators, postoperative complications, hospitalization-related indicators, short-term and long-term functional outcomes, and mortality rate 1 year after surgery.

Results

All patients underwent BGH evacuation under non-general anesthesia in the CTGFC group. The operative time (p < 0.01) and operation costs (p < 0.05) were significantly shorter in the CTGFC group than that in the STC group (p < 0.01). Comparable results were found in the catheter indwelling duration, residual hematoma volume, hematoma evacuation rate, incidence of postoperative complications, hospital ICU stay, and hospital costs between these two groups (p > 0.05). The duration of hospital stay was remarkably shorter in the CTGFC group than that in the STC group (p < 0.01). There were no differences in terms of the short-time functional outcomes score at discharge, including the Glasgow outcome scale (GOS) score, the activities of daily living (ADL) score, and the Karnofsky performance score (KPS). Moreover, comparable findings were also found in the 1-year postoperative GOS score, ADL score, KPS score, and mortality rate between these two groups.

Conclusion

The simple CTGFC-assisted surgery was a safe and reliable option for BGH evacuation, especially in primary medical institutes and emergency situations with limited medical resources.
Dynamic spectral signatures of mirror movements in the sensorimotor functional connectivity network of patients with Kallmann syndrome
Authors: Di Nardo Federica , Manara Renzo , Canna Antonietta , Trojsi Francesca , Velletrani Gianluca , Sinisi Antonio Agostino , Cirillo Mario , Tedeschi Gioacchino , Esposito Fabrizio
Published: August 2022

In Kallmann syndrome (KS), the peculiar phenomenon of bimanual synkinesis or mirror movement (MM) has been associated with a spectral shift, from lower to higher frequencies, of the resting-state fMRI signal of the large-scale sensorimotor brain network (SMN). To possibly determine whether a similar frequency specificity exists across different functional connectivity SMN states, and to capture spontaneous transitions between them, we investigated the dynamic spectral changes of the SMN functional connectivity in KS patients with and without MM symptom. Brain MRI data were acquired at 3 Tesla in 39 KS patients (32 without MM, KSMM-, seven with MM, KSMM+) and 26 age- and sex-matched healthy control (HC) individuals. The imaging protocol included 20-min rs-fMRI scans enabling detailed spectro-temporal analyses of large-scale functional connectivity brain networks. Group independent component analysis was used to extract the SMN. A sliding window approach was used to extract the dynamic spectral power of the SMN functional connectivity within the canonical physiological frequency range of slow rs-fMRI signal fluctuations (0.01–0.25 Hz). K-means clustering was used to determine (and count) the most recurrent dynamic states of the SMN and detect the number of transitions between them. Two most recurrent states were identified, for which the spectral power peaked at a relatively lower (state 1) and higher (state 2) frequency. Compared to KS patients without MM and HC subjects, the SMN of KS patients with MM displayed significantly larger spectral power changes in the slow 3 canonical sub-band (0.073–0.198 Hz) and significantly fewer transitions between state 1 (less recurrent) and state 2 (more recurrent). These findings demonstrate that the presence of MM in KS patients is associated with reduced spontaneous transitions of the SMN between dynamic functional connectivity states and a higher recurrence and an increased spectral power change of the high-frequency state. These results provide novel information about the large-scale brain functional dynamics that could help to understand the pathologic mechanisms of bimanual synkinesis in KS syndrome and, potentially, other neurological disorders where MM may also occur.
Affective video recommender systems: A survey
Authors: Wang Dandan , Zhao Xiaoming
Published: August 2022

Traditional video recommendation provides the viewers with customized media content according to their historical records (e.g., ratings, reviews). However, such systems tend to generate terrible results if the data is insufficient, which leads to a cold-start problem. An affective video recommender system (AVRS) is a multidiscipline and multimodal human-robot interaction (HRI) system, and it incorporates physical, physiological, neuroscience, and computer science subjects and multimedia resources, including text, audio, and video. As a promising research domain, AVRS employs advanced affective analysis technologies in video resources; therefore, it can solve the cold-start problem. In AVRS, the viewers’ emotional responses can be obtained from various techniques, including physical signals (e.g., facial expression, gestures, and speech) and internal signals (e.g., physiological signals). The changes in these signals can be detected when the viewers face specific situations. The physiological signals are a response to central and autonomic nervous systems and are mostly involuntarily activated, which cannot be easily controlled. Therefore, it is suitable for reliable emotion analysis. The physical signals can be recorded by a webcam or recorder. In contrast, the physiological signals can be collected by various equipment, e.g., psychophysiological heart rate (HR) signals calculated by echocardiogram (ECG), electro-dermal activity (EDA), and brain activity (GA) from electroencephalography (EEG) signals, skin conductance response (SCR) by a galvanic skin response (GSR), and photoplethysmography (PPG) estimating users’ pulse. This survey aims to provide a comprehensive overview of the AVRS domain. To analyze the recent efforts in the field of affective video recommendation, we collected 92 relevant published articles from Google Scholar and summarized the articles and their key findings. In this survey, we feature these articles concerning AVRS from different perspectives, including various traditional recommendation algorithms and advanced deep learning-based algorithms, the commonly used affective video recommendation databases, audience response categories, and evaluation methods. Finally, we conclude the challenge of AVRS and provide the potential future research directions.
Efficacy and safety of sintilimab plus XELOX as a neoadjuvant regimen in patients with locally advanced gastric cancer: A single-arm, open-label, phase II trial
Authors: Guo Honghai , Ding Ping’an , Sun Chenyu , Yang Peigang , Tian Yuan , Liu Yang , Lowe Scott , Bentley Rachel , Li Yaru , Zhang Zhidong , Wang Dong , Li Yong , Zhao Qun
Published: August 2022

Background

Neoadjuvant chemotherapies have been widely recommended in patients with locally advanced gastric cancer (LAGC). However, the evidence of combining neoadjuvant chemotherapy with anti–programmed death 1 (anti–PD-1) antibody therapy for patients with LAGC is lacking. Thus, we conducted a single-arm phase II trial to evaluate the efficacy and safety of the anti–PD-1 antibody sintilimab plus XELOX regimen (capecitabine plus oxaliplatin) in patients with LAGC.

Methods

Patients with LAGC (cT3-4 N+ M0, CY0, P0) were enrolled and received four preoperative cycles of sintilimab (200 mg, IV, Q21d) plus XELOX (oxaliplatin 130 mg/m2, IV, d1 with capecitabine 1,000 mg/m2, bid, d1–d14, Q21d) therapy. The primary endpoint was the pathological complete response (pCR) rate. This clinical trial was registered at Chictr.org.cn (trial number: ChiCTR2000030414).

Results

Thirty patients were enrolled from March 2020 to July 2021, with a median age of 62 years (range, 30–72), and 18 (60.0%) were men. There were 19 (63.3%) patients with PD-L1 CPS ≥1.The pCR rate was 33.3% [95% confidence interval (CI), 17.3%–52.8%], and the major pathologic response (MPR) rate was 63.3% (95% CI, 43.9%–80.1%). All the patients underwent R0 resection. The objective response rate (ORR) and the disease control rate (DCR) were 70.0% (95% CI, 50.6%–85.3%) and 100% (95% CI, 88.4%–100%), respectively. Downstaging of the overall TNM stage was observed in 22 (73.3%) patients. The pCR rate in patients with PD-L1 CPS ≥1 and patients with PD-L1 CPS <1 was 42.1% vs. 18.2% (P = 0.246), whereas the MPR rate was 78.9% vs. 36.4% (P = 0.047). The potential immune-related adverse events (irAEs) were hypothyroidism (3.3%), pneumonia (10.0%), and dermatitis (6.7%). Grade3 common treatment-related adverse events (TRAEs) were ALT increase (3.3%), AST increase (3.3%), and dermatitis (3.3%) during the neoadjuvant therapy. There were no severe complications or death related to the surgery.

Conclusion

Sintilimab plus XELOX as neoadjuvant therapy showed an encouraging pCR rate, MPR rate, and manageable safety. This combination of regimens might provide a new option for patients with LAGC.

Clinical Trial Registration: Chictr.org.cn, identifier ChiCTR2000030414.
Socioeconomic status-based survival disparities and nomogram prediction for patients with multiple myeloma: Results from American and Chinese populations
Authors: Xu Jiaxuan , Xu Peipei , Han Qiaoyan , Sun Jingjing , Chen Bing , Dong Xiaoqing
Published: August 2022

Objective

This study aimed to comprehensively investigate the relationship between the survival differences and socioeconomic status (SES) in patients with multiple myeloma (MM) and construct a predictive nomogram to assess clinical outcomes of MM patients.

Methods

The Surveillance, Epidemiology, and End Results (SEER) census tract-level SES database provides two specialized attributes: SES index and rurality. Using this database, 37,819 patients diagnosed with MM between January 2007 and December 2016 were enrolled. We evaluated the effects of SES index on overall survival (OS) and myeloma-specific survival (MSS) using Kaplan-Meier curves and Cox regression analyses. Thereafter, we included 126 patients with MM from two independent medical centers in China and divided them into training (Center 1) and validation (Center 2) cohorts. Univariate and multivariate Cox analyses were used in the training cohort to construct a nomogram for predicting clinical outcomes. Nomogram performance was assessed using the area under the curve (AUC) and calibration curves.

Results

In the SEER cohort, lower SES was significantly associated with worse OS rates and MSS rates (both P < 0.001). Multivariate analysis confirmed SES as an independent predictor of survival. Subgroup analysis indicated an increasing linear trend in survival benefits in non-Hispanic White, married, insured, and urban populations with increasing SES (all P < 0.001). In the training cohort, albumin, creatinine, rurality, and SES were confirmed as independent prognostic indicators. A nomogram for OS prediction was developed using these four factors, and it showed satisfactory discrimination and calibration. The 18- and 36-month AUC values of the nomogram were 0.79 and 0.82, respectively. Based on the total nomogram points, patients were categorized into two risk levels with good separation.

Conclusion

SES strongly influences survival disparities in patients with MM. Our nomogram consisting of clinical and sociodemographic characteristics can potentially predict survival outcomes.
MAC-spinal meningioma score: A proposal for a quick-to-use scoring sheet of the MIB-1 index in sporadic spinal meningiomas
Authors: Wach Johannes , Hamed Motaz , Lampmann Tim , Güresir Ági , Schmeel Frederic Carsten , Becker Albert J. , Herrlinger Ulrich , Vatter Hartmut , Güresir Erdem
Published: August 2022

Objective

MIB-1 index is an important predictor of meningioma progression. However, MIB-1 index is not available in the preoperative tailored medical decision-making process. A preoperative scoring sheet independently estimating MIB-1 indices in spinal meningioma (SM) patients has not been investigated so far.

Methods

Between 2000 and 2020, 128 patients with clinical data, tumor imaging data, inflammatory laboratory (plasma fibrinogen, serum C-reactive protein) data, and neuropathological reports (MIB-1, mitotic count, CD68 staining) underwent surgery for spinal WHO grade 1 and 2 meningioma.

Results

An optimal MIB-1 index cut-off value (≥5/<5) predicting recurrence was calculated by ROC curve analysis (AUC: 0.83; 95%CI: 0.71-0.96). An increased MIB-1 index (≥5%) was observed in 55 patients (43.0%) and multivariable analysis revealed significant associations with baseline Modified McCormick Scale ≥2, age ≥65, and absence of calcification. A four-point scoring sheet (MAC-Spinal Meningioma) based on Modified McCormick, Age, and Calcification facilitates prediction of the MIB-1 index (sensitivity 71.1%, specificity 60.0%). Among those patients with a preoperative MAC-Meningioma Score ≥3, the probability of a MIB-1 index ≥5% was 81.3%.

Conclusion

This novel score (MAC-Spinal Meningioma) supports the preoperative estimation of an increased MIB-1 index, which might support preoperative patient-surgeon consultation, surgical decision making and enable a tailored follow-up schedule or an individual watch-and-wait strategy.
3-Dimensional mesothelioma spheroids provide closer to natural pathophysiological tumor microenvironment for drug response studies
Authors: Shi Huaikai , Rath Emma M. , Lin Ruby C. Y. , Sarun Kadir Harun , Clarke Candice Julie , McCaughan Brian C. , Ke Helen , Linton Anthony , Lee Kenneth , Klebe Sonja , Maitz Joanneke , Song Kedong , Wang Yiwei , Kao Steven , Cheng Yuen Yee
Published: August 2022

Traditional studies using cancer cell lines are often performed on a two-dimensional (2D) cell culture model with a low success rate of translating to Phase I or Phase II clinical studies. In comparison, with the advent of developments three-dimensional (3D) cell culture has been championed as the latest cellular model system that better mimics in vivo conditions and pathological conditions such as cancer. In comparison to biospecimens taken from in vivo tissue, the details of gene expression of 3D culture models are largely undefined, especially in mesothelioma – an aggressive cancer with very limited effective treatment options. In this study, we examined the veracity of the 3D mesothelioma cell culture model to study cell-to-cell interaction, gene expression and drug response from 3D cell culture, and compared them to 2D cell and tumor samples. We confirmed via SEM analysis that 3D cells grown using the spheroid methods expressed highly interconnected cell-to-cell junctions. The 3D spheroids were revealed to be an improved mini-tumor model as indicated by the TEM visualization of cell junctions and microvilli, features not seen in the 2D models. Growing 3D cell models using decellularized lung scaffold provided a platform for cell growth and infiltration for all cell types including primary cell lines. The most time-effective method was growing cells in spheroids using low-adhesive U-bottom plates. However, not every cell type grew into a 3D model using the the other methods of hanging drop or poly-HEMA. Cells grown in 3D showed more resistance to chemotherapeutic drugs, exhibiting reduced apoptosis. 3D cells stained with H&E showed cell-to-cell interactions and internal architecture that better represent that of in vivo patient tumors when compared to 2D cells. IHC staining revealed increased protein expression in 3D spheroids compared to 2D culture. Lastly, cells grown in 3D showed very different microRNA expression when compared to that of 2D counterparts. In conclusion, 3D cell models, regardless of which method is used. Showed a more realistic tumor microenvironment for architecture, gene expression and drug response, when compared to 2D cell models, and thus are superior preclinical cancer models.
Autophagy in gastrointestinal cancers
Authors: Shao Bo-Zong , Chai Ning-Li , Yao Yi , Li Jin-Ping , Law Helen Ka Wai , Linghu En-Qiang
Published: August 2022

Gastrointestinal cancers are a group of cancers occurred in gastrointestinal tissues with high morbidity and mortality rate. Although numerous studies were conducted on the investigation of gastrointestinal cancers, the real mechanisms haven’t been discovered, and no effective methods of prevention and treatment of gastrointestinal cancers have been developed. Autophagy, a vital catabolic process in organisms, have been proven to participate in various mechanisms and signaling pathways, thus producing a regulatory effect on various diseases. The role of autophagy in gastrointestinal cancers remains unclear due to its high complexity. In this review, firstly, the biological features of autophagy will be introduced. Secondly, the role of autophagy in three popular gastrointestinal cancers, namely esophageal cancer, gastric cancer, and colorectal cancer will be described and discussed by reviewing the related literature. We aimed to bring novel insights in exploring the real mechanisms for gastrointestinal cancers and developing effective and efficient therapeutic methods to treat gastrointestinal cancers.
Integrated analysis of the M2 macrophage-related signature associated with prognosis in ovarian cancer
Authors: Peng Caijiao , Li Licheng , Luo Guangxia , Tan Shanmei , Xia Ruming , Zeng Lanjuan
Published: August 2022

Background

M2 macrophages play an important role in cancer development. However, the underlying biological fator affecting M2 macrophages infiltration in ovarian cancer (OV) has not been elucidated.

Methods

R software v 4.0.0 was used for all the analysis. The expression profile and clinical information of OV patients enrolled in this study were all downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases.

Results

The CIBERSORT algorithm was used to quantify the M2 macrophage infiltration in OV tissue, which was found a risk factor for patients survival. Based on the limma package, a total of 196 DEGs were identified between OV patients with high and low M2 macrophage infiltration, which were defined as M2 macrophages related genes. Finally, the genes PTGFR, LILRA2 and KCNA1 were identified for prognosis model construction, which showed a great prediction efficiency in both training and validation cohorts (Training cohort, 1-year AUC = 0.661, 3-year AUC = 0.682, 8-year AUC = 0.846; Validation cohort, 1-year AUC = 0.642, 3-year AUC = 0.716, 5-year AUC = 0.741). Clinical correlation showed that the riskscore was associated with the worse clinical features. Pathway enrichment analysis showed that in high risk patients, the pathway of epithelial-mesenchymal transition (EMT), TNF-α signaling via NFKB, IL2/STAT5 signaling, apical junction, inflammatory response, KRAS signaling, myogenesis were activated. Moreover, we found that the PTGFR, LILRA2 and KCNA1 were all positively correlated with M2 macrophage infiltration and PTGFR was significantly associated with the pathway of autophagy regulation. Moreover, we found that the low risk patients might be more sensitive to cisplatin, while high risk patient might be more sensitive to axitinib, bexarotene, bortezomib, nilotinib, pazopanib.

Conclusions

In this study, we identified the genes associated with M2 macrophage infiltration and developed a model that could effectively predict the prognosis of OV patients.
Association of laboratory markers and cerebral blood flow among sickle cell anemia children
Authors: Adanho Corynne Stéphanie Ahouéfa , Yahouédéhou Sètondji Cocou Modeste Alexandre , Santana Sânzio Silva , Vieira Camilo , Santiago Rayra Pereira , de Santana Jeanne Machado , Pitanga Thassila Nogueira , Aleluia Milena Magalhães , Maffili Vítor Valério , Leite Ivana Paula Ribeiro , Zanette Dalila Luciola , Lyra Isa Menezes , Goncalves Marilda Souza
Published: August 2022

Background

Stroke is one of the highest complications of sickle-cell anemia (SCA). The Transcranial Doppler (TCD) has been adopted worldwide as a gold standard method for detecting alterations in the blood velocity in cerebral arteries. In this study, we investigated the association between laboratory parameters and increased cerebral blood flow velocity in Brazilian SCA pediatric patients.

Methods

The study included 159 pediatric patients with SCA, submitted to TCD velocity screening, and the time-averaged maximum mean velocity (TAMMV) was determined in the middle cerebral artery (MCA), anterior cerebral artery (ACA), and distal intracranial internal carotid artery (ICA). We compared cerebral blood flow in patients stratified by the following: TCD1—defined as normal, with TAMMV inferior to 170 cm/s; TCD2—conditional, with TAMMV above 170 cm/s, but less than 199 cm/s; TCD3—altered, with TAMMV greater than or equal to 200 cm/s.

Results

TAMMV was negatively correlated with age and weight (p < 0.05). Moreover, TAMMV was associated or correlated with reductions in HbF, RBC, hemoglobin, hematocrit, HDL, and haptoglobin and, increases in MCV, MCH, RDW, reticulocytes, WBC, lymphocytes, monocytes, eosinophils, total and indirect bilirubin, LDH, AST, ALT, glucose, ferritin, and AAT (p < 0.05).

Conclusion

The current study highlights the importance of the investigation of hemolytic and inflammatory biomarkers for monitoring the clinical outcome of SCA pediatric patients, to avoid acute or chronic stroke. Moreover, glucose and HDL-C appear useful for predicting higher TAMMV.
Case report: A study on the de novo KMT2D variant of Kabuki syndrome with Goodpasture’s syndrome by whole exome sequencing
Authors: Li Shuolin , Liu Jing , Yuan Yuan , Lu Aizhen , Liu Fang , Sun Li , Shen Quanli , Wang Libo
Published: August 2022

Kabuki syndrome (KS) is a rare genetic disorder characterized by dysmorphic facial features, skeletal abnormalities, and intellectual disability. KMT2D and KDM6A were identified as the main causative genes. To our knowledge, there exist no cases of KS, which were reported with pneumorrhagia. In this study, a 10-month-old male was diagnosed to have KS with typical facial features, skeletal anomalies, and serious postnatal growth retardation. Whole exome sequencing of the trio family revealed the presence of a de novo KMT2D missense variant (c.15143G > A, p. R5048H). The child was presented to the pediatric emergency department several times because of cough, hypoxemia, and anemia. After performing chest CT and fiberoptic bronchoscopy, we found that the child had a pulmonary hemorrhage. During research on the cause of pulmonary hemorrhage, the patient’s anti-GBM antibodies gradually became positive, and the urine microalbumin level was elevated at the age of 12-month-old. After glucocorticoids and immunosuppressant therapy, the patient became much better. But he had recurrent pulmonary hemorrhage at the age of 16 months. Therefore, the patient underwent digital subtraction angiography (DSA). However, the DSA showed three abnormal bronchial arteries. This single case expands the phenotypes of patients with KS and Goodpasture’s syndrome, which were found to have a de novo KMT2D missense variant.
Case report: Novel SCN4A variant associated with a severe congenital myasthenic syndrome/myopathy phenotype
Authors: Berghold Veronika M. , Koko Mahmoud , Berutti Riccardo , Plecko Barbara
Published: August 2022

We present a now 18-year-old female patient with a severe congenital myopathy phenotype, originally diagnosed as mitochondrial myopathy, however later revealed to constitute a SCN4A-related myopathy based on genetic testing. After birth, floppiness, bradycardia and respiratory insufficiency ensued, and moderately reduced mitochondrial complex I activity was found in muscle tissue (tested at 3 weeks and 3 years of age, respectively). She was treated with riboflavin, carnitine, creatine and a ketogenic diet. At the age of 13 years, whole exome sequencing challenged the initial diagnosis by identifying two (compound heterozygous) SCN4A variants affecting the highly conserved voltage sensor and pore regions of the voltage-gated sodium channel NaV1.4: a known pathogenic loss of function (LOF) variant [c.4360C>T; p.(Arg1454Trp)] and a novel variant of uncertain significance [c.3615C>G; p.(Asn1205Lys)]. For this novel variant, a LOF effect was predicted by in silico, clinical and functional evidence from paralog human sodium channels, and the variant was accordingly classified as likely pathogenic. The patient's phenotype is in line with the few published cases of autosomal recessive SCN4A-related myopathy. There was limited benefit from treatment with salbutamol and acetazolamide, while pyridostigmine caused side effects at a minor dose. This report highlights the importance of genetic testing in severe myopathies particularly in regard to treatment options and the value of paralog information in evaluating ion channel variations.
Case report: Spindle cell neoplasm presenting as a spontaneous intestinal perforation in a term infant
Authors: Callaghan Lauren T. , Lafreniere Anthea , Onwuka Ekene A. , Beckman Ross M. , Foster Jennifer H. , Quintanilla Norma , Guillory Charleta , Lee Timothy C. , Cheng Lily S.
Published: August 2022

Spontaneous intestinal perforations in the neonatal population are mostly associated with low birth weight, prematurity, and necrotizing enterocolitis. Spontaneous intestinal perforation in the absence of these risk factors is extremely rare and should raise clinical concern for an underlying bowel pathology. Here we present a unique case of a normal-weight, full-term girl with spontaneous intestinal perforation due to a spindle cell neoplasm with a novel BRAF mutation and infantile fibrosarcoma-like morphology. Though rare, malignancy should be considered in the differential diagnosis for bowel perforation in an otherwise healthy, term infant as complete surgical excision can be curative.
Integrated analysis of inflammatory response subtype-related signature to predict clinical outcomes, immune status and drug targets in lower-grade glioma
Authors: Cao Yudong , Zhu Hecheng , Chen Quan , Huang Hailong , Xie Dongcheng , Li Xuewen , Jiang Xingjun , Ren Caiping , Peng Jiahui
Published: August 2022

Background: The inflammatory response in the tumor immune microenvironment has implications for the progression and prognosis in glioma. However, few inflammatory response-related biomarkers for lower-grade glioma (LGG) prognosis and immune infiltration have been identified. We aimed to construct and identify the prognostic value of an inflammatory response-related signature, immune infiltration, and drug targets for LGG.

Methods: The transcriptomic and clinical data of LGG samples and 200 inflammatory response genes were obtained from public databases. The LGG samples were separated into two inflammatory response-related subtypes based on differentially expressed inflammatory response genes between LGG and normal brain tissue. Next, inflammatory response-related genes (IRRGs) were determined through a difference analysis between the aforementioned two subtypes. An inflammatory response-related prognostic model was constructed using IRRGs by using univariate Cox regression and Lasso regression analyses and validated in an external database (CGGA database). ssGSEA and ESTIMATE algorithms were conducted to evaluate immune infiltration. Additionally, we performed integrated analyses to investigate the correlation between the prognostic signature and N 6-methyladenosine mRNA status, stemness index, and drug sensitivity. We finally selected MSR1 from the prognostic signature for further experimental validation.

Results: A total of nine IRRGs were identified to construct the prognostic signature for LGG. LGG patients in the high-risk group presented significantly reduced overall survival than those in the low-risk group. An ROC analysis confirmed the predictive power of the prognostic model. Multivariate analyses identified the risk score as an independent predictor for the overall survival. ssGSEA revealed that the immune status was definitely disparate between two risk subgroups, and immune checkpoints such as PD-1, PD-L1, and CTLA4 were significantly expressed higher in the high-risk group. The risk score was strongly correlated with tumor stemness and m6A. The expression levels of the genes in the signature were significantly associated with the sensitivity of tumor cells to anti-tumor drugs. Finally, the knockdown of MSR1 suppressed LGG cell migration, invasion, epithelial–mesenchymal transition, and proliferation.

Conclusion: The study constructed a novel signature composed of nine IRRGs to predict the prognosis, potential drug targets, and impact immune infiltration status in LGG, which hold promise for screening prognostic biomarkers and guiding immunotherapy for LGG.
Gynostemma pentaphyllum for dyslipidemia: A systematic review of randomized controlled trials
Authors: Dai Ning , Zhao Fang-fang , Fang Min , Pu Feng-lan , Kong Ling-yao , Liu Jian-ping
Published: August 2022

Objective: To evaluate the lipid-lowering effect and safety of Gynostemma pentaphyllum (GP) used alone or as adjunctive therapy for dyslipidemia.

Methods: Eight databases and three clinical trial registries were searched until January 2022. Randomized controlled trials (RCTs) assessing the effectiveness of GP for dyslipidemia were included. Trial quality was assessed using the Cochrane Risk of Bias Tool 2.0. Data were analyzed by RevMan 5.4 with effects estimated as risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI).

Results: Twenty-two RCTs involving 2,407 dyslipidemia participants were included. Regarding the risk of bias, 14 RCTs had some concerns, seven RCTs were high, and one trial was low. GP was comparable to n-3 fatty acids (RR 0.89, 95% CI 0.62–1.28) and red yeast rice (RR 0.33, 95% CI 0.1–1.12) on normalization of serum lipids. GP plus n-3 fatty acid was superior in normalization of triglycerides (TG) and total cholesterol (TC) than n-3 fatty acids (RR 1.34, 95% CI 1.01–1.77). GP was similar to lipid-lowering agents (statins, fibrates, and n-3 fatty acids) in regulating TG, TC, and high-density lipoprotein cholesterol (HDL-C). GP plus lipid-lowering agents were superior to lipid-lowering agents in TG (MD −0.65 mmol/L, 95% CI −1.03 to −0.28), LDL-C (MD −0.57 mmol/L, 95% CI −1.07 to −0.08), and HDL-C (MD 0.15 mmol/L, 95% CI 0.11–0.20). GP was inferior to red yeast rice in TC (MD 0.64 mmol/L, 95% CI 0.15–1.13), TG (MD 0.43 mmol/L, 95% CI 0.15–0.71), and HDL-C (MD −0.25 mmol/L, 95% CI −0.47 to −0.04). GP had fewer adverse events than lipid-lowering drugs.

Conclusion: Very low certainty evidence showed that GP’s effects on TC, TG, and HDL-C were comparable to that of lipid-lowering agents. Low certainty evidence showed that red yeast rice was superior to GP in TC, TG, and HDL-C. Low to moderate certainty evidence showed that the effects of GP plus lipid-lowering agents were superior to that of lipid-lowering agents on TG, LDL-C, and HDL-C. GP use for more than 8 weeks appears safe.

Systematic Review Registration:https://inplasy.com/, identifier INPLASY202210135.
Inhibition of the IRE1/JNK pathway in renal tubular epithelial cells attenuates ferroptosis in acute kidney injury
Authors: Liang Yan , Liu Zhenjie , Qu Lingyun , Wang Yingzi , Zhou Yali , Liang Lulu , Guo Yanhong , Tang Lin
Published: August 2022

Backgroud: Ferroptosis is a form of regulated cell death in ischemia-reperfusion (I/R) injury models. Acute kidney injury (AKI) induced by I/R injury can result in cell death, and subcellular structural changes, including expansion of the endoplasmic reticulum (ER), mitochondrial shrinkage, and other morphological changes. Inositol requiring enzyme 1 (IRE1) a proximal ER stress sensor, activates c-Jun NH2-terminal kinases (JNK) in response to ER stress, which is inextricably linked to ER.

Method: To determine the resulting damage and relationship between ferroptosis and the IRE1/JNK pathway in AKI, we modeled AKI in I/R renal injury mice and hypoxia/reoxygenation (H/R) HK-2 cells, as in vivo and in vitro experiments, respectively.

Results: In I/R renal injury mice, we found that abnormal renal function; damage of renal tubular epithelial cells; activation of the IRE1/JNK pathway and ferroptosis. Our in vitro study showed a large number of reactive oxygen species and more ferroptotic mitochondria in H/R HK-2 cells. By inhibiting IRE1/JNK in I/R renal injury mice, we observed decreased blood urea nitrogen, creatinine, and tissue injury, compared with the I/R group, we also found the markers of ferroptosis changed, including decreased 4-hydroxynonenal and increased glutathione peroxidase 4, as well as in H/R induced IRE1/JNK knock-down HK-2 cell lines (stable depletion). Furthermore, inhibition of ferroptosis could also attenuate the IRE1/JNK pathway in mice following I/R and HK-2 cells following H/R.

Conclusion: We observed cross-talk between the IRE1/JNK pathway and ferroptosis in I/R or H/R induced AKI. Our findings suggest that ferroptosis plays an important role in I/R induced AKI, and that inhibition of the IRE1/JNK pathway can protect against I/R induced renal injury by inhibiting ferroptosis. The inhibition of the IRE1/JNK pathway could therefore be a feasible therapeutic target for treatment of AKI.
Modulation of type 1 cannabinoid receptor activity by cannabinoid by-products from Cannabis sativa and non-cannabis phytomolecules
Authors: Zagzoog Ayat , Cabecinha Ashley , Abramovici Hanan , Laprairie Robert B.
Published: August 2022

Cannabis sativa contains more than 120 cannabinoids and 400 terpene compounds (i.e., phytomolecules) present in varying amounts. Cannabis is increasingly available for legal medicinal and non-medicinal use globally, and with increased access comes the need for a more comprehensive understanding of the pharmacology of phytomolecules. The main transducer of the intoxicating effects of Cannabis is the type 1 cannabinoid receptor (CB1R). ∆9-tetrahydrocannabinolic acid (∆9-THCa) is often the most abundant cannabinoid present in many cultivars of Cannabis. Decarboxylation converts ∆9-THCa to ∆9-THC, which is a CB1R partial agonist. Understanding the complex interplay of phytomolecules—often referred to as “the entourage effect”—has become a recent and major line of inquiry in cannabinoid research. Additionally, this interest is extending to other non-Cannabis phytomolecules, as the diversity of available Cannabis products grows. Here, we chose to focus on whether 10 phytomolecules (∆8-THC, ∆6a,10a-THC, 11-OH-∆9-THC, cannabinol, curcumin, epigallocatechin gallate, olivetol, palmitoylethanolamide, piperine, and quercetin) alter CB1R-dependent signaling with or without a co-treatment of ∆9-THC. Phytomolecules were screened for their binding to CB1R, inhibition of forskolin-stimulated cAMP accumulation, and βarrestin2 recruitment in Chinese hamster ovary cells stably expressing human CB1R. Select compounds were assessed further for cataleptic, hypothermic, and anti-nociceptive effects on male mice. Our data revealed partial agonist activity for the cannabinoids tested, as well as modulation of ∆9-THC-dependent binding and signaling properties of phytomolecules in vitro and in vivo. These data represent a first step in understanding the complex pharmacology of Cannabis- and non-Cannabis-derived phytomolecules at CB1R and determining whether these interactions may affect the physiological outcomes, adverse effects, and abuse liabilities associated with the use of these compounds.
Natural phytochemicals that affect autophagy in the treatment of oral diseases and infections: A review
Authors: Cheng Xi , Chen Qianming , Sun Ping
Published: August 2022

Autophagy is a critical factor in eukaryotic evolution. Cells provide nutrition and energy during autophagy by destroying non-essential components, thereby allowing intracellular material conversion and managing temporary survival stress. Autophagy is linked to a variety of oral disorders, including the type and extent of oral malignancies. Furthermore, autophagy is important in lymphocyte formation, innate immunity, and the regulation of acquired immune responses. It is also required for immunological responses in the oral cavity. Knowledge of autophagy has aided in the identification and treatment of common oral disorders, most notably cancers. The involvement of autophagy in the oral immune system may offer a new understanding of the immune mechanism and provide a novel approach to eliminating harmful bacteria in the body. This review focuses on autophagy creation, innate and acquired immunological responses to autophagy, and the status of autophagy in microbial infection research. Recent developments in the regulatory mechanisms of autophagy and therapeutic applications in oral illnesses, particularly oral cancers, are also discussed. Finally, the relationship between various natural substances that may be used as medications and autophagy is investigated.
Insensitivity to T790M mutation? A pooled analysis of outcomes following osimertinib for the treatment of NSCLC patients harboring uncommon epidermal growth factor receptor mutation
Authors: Hu Shanliang , Wang Congjie , Wang Chunsheng , Zhao Kewei , Wang Zhen , Dong Wei
Published: August 2022

Background: In this pooled analysis, the aim was to investigate the clinicopathological characteristics of patients with uncommon epidermal growth factor receptor (EGFR) (ucm-EGFRms) along with their treatment responses and survival following osimertinib treatment.

Methods: Univariate chi-square analysis was conducted to analyze the correlation between clinical characteristics, EGFR mutation type, and treatment response, and the Kaplan-Meier method was applied for survival analysis. Univariate logistic regression model and Cox proportional hazards model were performed to compare the efficacy and prognosis in subgroup analysis.

Results: Seventy-two NSCLC patients in total were included in this pooled analysis. The objective response rate (ORR) for osimertinib treatment was 57.0%, with a median PFS of 7.1 months. Twenty-eight patients received osimertinib as first-line therapy with an ORR of 67.9%, which was higher than that in patients who received osimertinib as second- or later-line therapy, and their response rate was 50%, nevertheless, no statistically significant differences were found (p = 0.139). However, patients who received first-line osimertinib showed a more significant PFS benefit than those who received second- or later-line therapy (mPFS: 16.8 months vs 6.0 months HR: 2.453, 95%CI: 1.285-4.682, p =0.004). Subgroup analysis showed that patients with a single, non-ex20ins, ucm-EGFRm displayed a superior efficacy advantage and favorable survival benefit following osimertinib treatment, with an ORR of 68.8% and an mPFS at 15.1 months. By contrast, patients with a multiple ucm-EGFRm that contain T790M exhibited the worst outcome of osimertinib treatment, with an ORR of 47.6% and an mPFS of only 3.6 months, respectively.

Conclusion: Patients with um-EGFRms exhibit favorable but inconsistent responses and survival outcomes following osimertinib treatment, which is closely related to the mutation pattern and cooccurring partner mutant genes. Administering osimertinib for the treatment of patients with um-EGFRm might be considered an effective treatment option in some circumstances.
Differential immune responses in new and old fruit fly-parasitoid associations: Implications for their management
Authors: Gwokyalya Rehemah , Herren Jeremy K. , Weldon Christopher W. , Khamis Fathiya M. , Ndlela Shepard , Mohamed Samira Abuelgasim
Published: August 2022

The oriental fruit fly, Bactrocera dorsalis (Hendel), and marula fruit fly, Ceratitis cosyra (Walker), are major fruit-infesting tephritids across sub-Saharan Africa. Biological control of these pests using parasitic wasps has been widely adopted but with varying levels of success. Most studies investigating host-parasitoid models have focused on functional and evolutionary aspects leaving a knowledge gap about the physiological mechanisms underpinning the efficacy of parasitoids as biocontrol agents of tephritids. To better understand these physiological mechanisms, we investigated changes in the cellular immune responses of C. cosyra and B. dorsalis when exposed to the parasitic wasps, Diachasmimorpha longicaudata (Ashmaed) and Psyttalia cosyrae (Wilkinson). We found that B. dorsalis was more resistant to parasitisation, had a higher hemocyte count, and encapsulated more parasitoid eggs compared to C. cosyra, achieving up to 100% encapsulation when exposed to P. cosyrae. Exposing B. dorsalis to either parasitoid species induced the formation of a rare cell type, the giant multinucleated hemocyte, which was not observed in C. cosyra. Furthermore, compared to P. cosyrae-parasitized larvae, those of both host species parasitized by D. longicaudata had lower encapsulation rates, hemocyte counts and spreading abilities and yielded a higher number of parasitoid progeny with the highest parasitoid emergence (72.13%) recorded in C. cosyra. These results demonstrate that cellular immune responses are central to host-parasitoid interaction in tephritid fruit flies and further suggest that D. longicaudata presents greater potential as a biocontrol agent of B. dorsalis and C. cosyra in horticultural cropping systems.
Dynamic modeling of ABA-dependent expression of the Arabidopsis RD29A gene
Authors: Ndathe Ruth , Dale Renee , Kato Naohiro
Published: August 2022

The abscisic acid (ABA) signaling pathway is the key defense mechanism against drought stress in plants. In the pathway, signal transduction among four core proteins, pyrabactin resistance (PYR), protein phosphatase 2C (PP2C), sucrose-non-fermenting-1-related protein kinase 2 (SnRK2), and ABRE binding factor (ABF) leads to altered gene expression kinetics that is driven by an ABA-responsive element (ABRE). A most recent and comprehensive study provided data suggesting that ABA alters the expression kinetics in over 6,500 genes through the ABF-ABRE associations in Arabidopsis. Of these genes, termed ABA gene regulatory network (GRN), over 50% contain a single ABRE within 4 kb of the gene body, despite previous findings suggesting that a single copy of ABRE is not sufficient to drive the gene expression. To understand the expression system of the ABA GRN by the single ABRE, a dynamic model of the gene expression for the desiccation 29A (RD29A) gene was constructed with ordinary differential equations. Parameter values of molecular-molecular interactions and enzymatic reactions in the model were implemented from the data obtained by previously conducted in vitro experiments. On the other hand, parameter values of gene expression and translation were determined by comparing the kinetics of gene expression in the model to the expression kinetics of RD29A in real plants. The optimized model recapitulated the trend of gene expression kinetics of RD29A in ABA dose–response that were previously investigated. Further analysis of the model suggested that a single ABRE controls the time scale and dynamic range of the ABA-dependent gene expression through the PP2C feedback regulation even though an additional cis-element is required to drive the expression. The model construed in this study underpins the importance of a single ABRE in the ABA GRN.
Metabolome and RNA-seq Analysis of Responses to Nitrogen Deprivation and Resupply in Tea Plant (Camellia sinensis) Roots
Authors: Xu Wenluan , Li Jing , Zhang Luyu , Zhang Xuyang , Zhao Hua , Guo Fei , Wang Yu , Wang Pu , Chen Yuqiong , Ni Dejiang , Wang Mingle
Published: August 2022

Nitrogen (N) is an important contributor in regulating plant growth and development as well as secondary metabolites synthesis, so as to promote the formation of tea quality and flavor. Theanine, polyphenols, and caffeine are important secondary metabolites in tea plant. In this study, the responses of Camellia sinensis roots to N deprivation and resupply were investigated by metabolome and RNA-seq analysis. N deficiency induced content increase for most amino acids (AAs) and reduction for the remaining AAs, polyphenols, and caffeine. After N recovery, the decreased AAs and polyphenols showed a varying degree of recovery in content, but caffeine did not. Meanwhile, theanine increased in content, but its related synthetic genes were down-regulated, probably due to coordination of the whole N starvation regulatory network. Flavonoids-related pathways were relatively active following N stress according to KEGG enrichment analysis. Gene co-expression analysis revealed TCS2, AMT1;1, TAT2, TS, and GOGAT as key genes, and TFs like MYB, bHLH, and NAC were also actively involved in N stress responses in C. sinensis roots. These findings facilitate the understanding of the molecular mechanism of N regulation in tea roots and provide genetic reference for improving N use efficiency in tea plant.
Effect of product-based pedagogy on students’ project management skills, learning achievement, creativity, and innovative thinking in a high-school artificial intelligence course
Authors: Zhan Zehui , Shen Wenyao , Lin Wenkai
Published: August 2022

The purpose of this study is to explore the effectiveness of product-based pedagogy (PBP) on students’ creativity and innovative thinking in artificial intelligence (AI) education. A seven-step model (i.e., phenomenon, problem, plan, prototype, product, presentation, price) in accordance with PBP was proposed, in which the key function of the product as a linkage between creativity and innovation was emphasized. A total of 209 students from a major high school in South China were randomly assigned to a treatment group with PBP and a control group with direct instruction. Results indicated no significant difference was found in students’ learning performance; however, students in the treatment group performed significantly better than the control group in terms of students’ project management skills, creativity, and innovative thinking. This research validates the feasibility and effectiveness of the PBP and highlights its advantages for high-school AI education, which indicates a new direction for cultivating creative and innovative talents.