bluuebunny/crossref_metadata_2025 huggingface dataset:
Myocarditis and myositis/myasthenia gravis overlap syndrome induced by immune checkpoint inhibitor followed by esophageal hiatal hernia: A case report and review of the literature
Authors: Yin Beibei , Xiao Junjuan , Wang Xuan , Li Xingyu , Guan Yaping , Chen Jinghua , Han Pengxi , Li Kun , Wang Jun
Published: November 2022

Immunotherapy with programmed death 1 (PD-1) inhibitor has shown activity as first- or second-line treatment for various metastatic human malignancies. Immune-related adverse events (irAEs) are now well-described, and most organ sites are potentially influenced, but the prevalence of myocarditis and myositis/myasthenia gravis (MG) overlap syndrome following esophageal hiatal hernia induced by immunotherapy is rarely reported. Here, we describe a 71-year-old woman with a progressed unresectable extrahepatic cholangiocarcinoma and biliary obstruction. She had no prior history of muscle weakness and neuromuscular disease with a normal body mass index. She was treated with sintilimab as a rescue regimen of immunotherapy. After the first cycle of treatment, she experienced a grade 4 myopathy including simultaneous myositis, myalgia, and myocarditis due to multiple injuries in her cardiac, skeletal, and ocular muscles. She had elevated levels of creatine kinase (CK), cardiac troponin I, and myoglobin (MYO), but MG and myositis-specific and myositis-related antibodies were negative. Immunotherapy was discontinued and pulse high-dose methylprednisolone with a slow tapering and intravenous immunoglobulin (IVIG) was initiated. Two weeks later, the patient’s clinical presentation improved significantly. A subsequent cardiac magnetic resonance (MR) examination revealed an old myocardial injury that may be a result of immune-related cardiac toxicity. In the third month following the PD-1 inhibitor therapy, she restarted systemic chemotherapy in combination with an anti-angiogenic agent but without immunotherapy. Half a year later, she complained of repeated abdominal distension and radiographic examinations and endoscopy showed a clinically confirmed diagnosis of sliding hiatal hernia of the esophagus and gastroesophageal reflux disease. Due to mild symptoms associated with gastroesophageal reflux, she was suggested close monitoring with acid secretion blockade rather than immediate surgical intervention. The severity for patients with myositis and myocarditis accompanied without MG is similar to those with MG. Considering the use of PD-1 inhibitors is increasing in cancer patients, physicians should therefore pay more attention to immunotherapy-induced myocarditis with myositis/MG overlap syndrome. Since we hypothesize diaphragmatic hiatal hernia as a potential consequence of immunotherapy-induced myositis, reports on hiatal hernias subsequent to immunotherapy-induced myositis are needed.
Endoscope ear pick: An emerging but neglected medical device
Authors: Huang Wendi , Li Ying , Huang Juan , Luo Yong , Huang Nanqu
Published: November 2022

Earwax (cerumen), a normal bodily secretion, can become a problem when it obstructs the ear canal. Earwax removal is a difficult task for specialists because of the ear's unique location and the ear canal's intricate structure. Using ear scoops or cotton swabs to dig out ear wax in daily life is like “a blind man walking on a cliff.” Improper operation may damage the ear canal or the eardrum. Thus, we need a pair of visible “eyes,” otoscopes, to help us see earwax intuitively. As opposed to traditional otoscopes, which only serve as a visual aid, the endoscopic ear pick allows us to not only view the ear canal but also remove wax or other obstructions from the ear. In this review, we discussed endoscope ear pick pros and cons and discussed their future role.
Frequency of HTLV-1 seroconversion between pregnancies in Nagasaki, Japan, 2011–2018
Authors: Komatsu Nahoko , Iwanaga Masako , Hasegawa Yuri , Miura Shoko , Fuchi Naoki , Moriuchi Hiroyuki , Yanagihara Katsunori , Miura Kiyonori
Published: November 2022

Background

Human T-cell leukemia virus type-1 (HTLV-1) is transmitted vertically from an infected mother to her child via breastfeeding during infancy or horizontally via sexual contact. However, little information is available on the HTLV-1 seroconversion rate in pregnant mothers and the impact of new HTLV-1 infection on mothers and babies during the perinatal period.

Methods

From the database of a prefecture-wide antenatal adult T-cell leukemia prevention program in Nagasaki, Japan, we extracted data on 57,323 pregnant women who were screened for anti-HTLV-1 antibody during 2011–2018. Data on the 16,863 subjects whose HTLV-1 proviral load (PVL) was measured more than twice were included in our analyses.

Results

In total, 133 (0.79%) pregnant women were HTLV-1-positive during their first pregnancy and nine (0.05%) seroconverted before or during subsequent pregnancies (between pregnancies). The median PVL (per 100 peripheral blood mononuclear cells) was significantly lower in the seroconverted mothers (0.10%) than in the initially seropositive mothers (0.15%). A repeated measures correlation analysis for the individual PVLs of the HTLV-1-positive pregnant women showed that PVL increased with parity number (rrm = 0.25) with no perinatal problems.

Conclusion

The HTLV-1 seroconversion rate between pregnancies was 0.05%, and their HTLV-1 PVL increased annually but no perinatal problems were noted.
Viral metagenomics combined with metabolomics reveals the role of gut viruses in mouse model of depression
Authors: Duan Jiajia , Wang Wei , Jiang Tao , Bai Xiaoyang , Liu Chuanxin
Published: November 2022

Depression is a heterogeneous mental disorder that has been linked to disturbances in the gut microbiome. As an essential part of the gut microbiome, gut virome may play critical roles in disease progression and development. However, the relationship between the effect of gut virome on neurotransmitter metabolism and depression is unknown. We evaluated the alterations of gut virome and neurotransmitters in chronic restraint stress (CRS)-induced mouse model of depression based on viral metagenomics and LC–MS/MS metabolomics analyses. The results reveal that the gut virome profile of CRS group differed significantly from CON group. Microviridae was the most abundant differential viral family in both groups, followed by Podoviridae, while Siphoviridae was only enriched in CRS group of the top 100 differential viruses. The differential viruses that predicted to Enterobacteriaceae phage, Gammaproteobacteria phage and Campylobacteraceae phage were enriched in CRS group. Furthermore, 12 differential neurotransmitters primarily involved in the tryptophan metabolism pathway were altered in depressive-like mice. Besides, tryptamine and 5-methoxytryptamine hydrochloride were strongly associated with differential viruses belonging to Podoviridae and Microviridae. Our findings provide new insight into understanding the potential role of the gut virome and metabolites in depression.
Microbial communities in the liver and brain are informative for postmortem submersion interval estimation in the late phase of decomposition: A study in mouse cadavers recovered from freshwater
Authors: Wang Linlin , Zhang Fuyuan , Zeng Kuo , Dong Wenwen , Yuan Huiya , Wang Ziwei , Liu Jin , Pan Jiaqing , Zhao Rui , Guan Dawei
Published: November 2022

Introduction

Bodies recovered from water, especially in the late phase of decomposition, pose difficulties to the investigating authorities. Various methods have been proposed for postmortem submersion interval (PMSI) estimation and drowning identification, but some limitations remain. Many recent studies have proved the value of microbiota succession in viscera for postmortem interval estimation. Nevertheless, the visceral microbiota succession and its application for PMSI estimation and drowning identification require further investigation.

Methods

In the current study, mouse drowning and CO2 asphyxia models were developed, and cadavers were immersed in freshwater for 0 to 14 days. Microbial communities in the liver and brain were characterized via 16S rDNA high-throughput sequencing.

Results

Only livers and brains collected from 5 to 14 days postmortem were qualified for sequencing. There was significant variation between microbiota from liver and brain. Differences in microbiota between the cadavers of mice that had drowned and those only subjected to postmortem submersion decreased over the PMSI. Significant successions in microbial communities were observed among the different subgroups within the late phase of the PMSI in livers and brains. Eighteen taxa in the liver which were mainly related to Clostridium_sensu_stricto and Aeromonas, and 26 taxa in the brain which were mainly belonged to Clostridium_sensu_stricto, Acetobacteroides, and Limnochorda, were selected as potential biomarkers for PMSI estimation based on a random forest algorithm. The PMSI estimation models established yielded accurate prediction results with mean absolute errors ± the standard error of 1.282 ± 0.189 d for the liver and 0.989 ± 0.237 d for the brain.

Conclusions

The present study provides novel information on visceral postmortem microbiota succession in corpses submerged in freshwater which sheds new light on PMSI estimation based on the liver and brain in forensic practice.
Metagenomic next-generation sequencing for identification of central nervous system pathogens in HIV-infected patients
Authors: Zhu Yunqi , Zhao Wenxuan , Yang Xihong , Zhang Yuanyuan , Lin Xiaoling , Weng Xing , Wang Yali , Cheng Cong , Chi Yun , Wei Hongxia , Peng Zhihang , Hu Zhiliang
Published: November 2022

Although considerable interest in metagenomic next-generation sequencing (mNGS) has been attracted in recent years, limited data are available regarding the performance of mNGS in HIV-associated central nervous system (CNS) infection. Here, we conducted a retrospectively analyzing of the cerebrospinal fluid (CSF) mNGS reports and other clinical data from 80 HIV-infected patients admitted to the Second Hospital of Nanjing, China from March, 2018 to March, 2022. In our study, CSF mNGS reported negative result, mono-infection, and mixed infection in 8.8, 36.2, and 55% of the patients, respectively. Epstein–Barr virus (EBV), positive in 52.5% of samples, was the most commonly reported pathogen, followed by cytomegalovirus (CMV), John Cunningham virus (JCV), torque teno virus (TTV), cryptococcus neoformans (CN), toxoplasma Gondii (TE), and mycobacterium tuberculosis (MTB). 76.2% of the EBV identification and 54.2% of the CMV identification were not considered clinically important, and relative less sequence reads were reported in the clinical unimportant identifications. The clinical importance of the presence of TTV in CSF was not clear. Detection of JCV, CN, or TE was 100% suggestive of specific CNS infection, however, 60% of the MTB reports were considered contamination. Moreover, of the 44 (55%) mixed infections reported by mNGS, only 4 (5%) were considered clinical important, and mNGS failed to identify one mixed infection. Additionally, except for MTB, CSF mNGS tended to have high sensitivity to identify the above-mentioned pathogens (almost with 100% sensitivity). Even all the diagnostic strategies were evaluated, the cause of neurological symptoms remained undetermined in 6 (7.5%) patients. Overall, our results suggest that mNGS is a very sensitive tool for detecting common opportunistic CNS pathogen in HIV-infected patients, although its performance in CNS tuberculosis is unsatisfactory. EBV and CMV are commonly detected by CSF mNGS, however, the threshold of a clinical important detection remains to be defined.
Single nuclei RNA sequencing investigation of the Purkinje cell and glial changes in the cerebellum of transgenic Spinocerebellar ataxia type 1 mice
Authors: Borgenheimer Ella , Hamel Katherine , Sheeler Carrie , Moncada Francisco Labrada , Sbrocco Kaelin , Zhang Ying , Cvetanovic Marija
Published: November 2022

Glial cells constitute half the population of the human brain and are essential for normal brain function. Most, if not all, brain diseases are characterized by reactive gliosis, a process by which glial cells respond and contribute to neuronal pathology. Spinocerebellar ataxia type 1 (SCA1) is a progressive neurodegenerative disease characterized by a severe degeneration of cerebellar Purkinje cells (PCs) and cerebellar gliosis. SCA1 is caused by an abnormal expansion of CAG repeats in the gene Ataxin1 (ATXN1). While several studies reported the effects of mutant ATXN1 in Purkinje cells, it remains unclear how cerebellar glia respond to dysfunctional Purkinje cells in SCA1. To address this question, we performed single nuclei RNA sequencing (snRNA seq) on cerebella of early stage Pcp2-ATXN1[82Q] mice, a transgenic SCA1 mouse model expressing mutant ATXN1 only in Purkinje cells. We found no changes in neuronal and glial proportions in the SCA1 cerebellum at this early disease stage compared to wild-type controls. Importantly, we observed profound non-cell autonomous and potentially neuroprotective reactive gene and pathway alterations in Bergmann glia, velate astrocytes, and oligodendrocytes in response to Purkinje cell dysfunction.
Non-invasive brain stimulation therapy on neurological symptoms in patients with multiple sclerosis: A network meta analysis
Authors: Zhang Xiaoyun , Huai Yaping , Wei Zhiqiang , Yang Weiwei , Xie Qizhi , Yi Li
Published: November 2022

Objective

The aim of the study was to evaluate non-invasive brain stimulation (NIBS) [including transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (tES)] on neurological symptoms in patients with multiple sclerosis (PwMS).

Method

We searched PubMed, Embase, Cochrane Library, Web of Science and Ovid MEDLINE until February 2022. And we evaluated the included studies for methodological quality by the Cochrane bias risk assessment tool and assessed the studies' certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. We performed network meta analysis (NMA) by using Stata 15 and ranked the results of the NMA by using the surface under the cumulative ranking curve (SUCRA) ranking chart.

Result

Twenty seven clinical trials were finally included (N = 596, 66.4% women). For the immediate effects, rTMS over M1 yielded the most optimal scheme for fatigue reduction among all the interventions compared to the sham stimulation groups [MD = −0.85, 95% CI (−1.57, −0.14)] (SUCRA = 82.6%). iTBS over M1 yielded the most signifcant reduced pain level than the sham groups did [MD = −1.26, 95% CI (−2.40, −0.11)] (SUCRA = 98.4%). tDCS over F3 was the best protocol of NIBS to improve quality of life (QOL) [MD = 1.41, 95% CI = (0.45,2.36)] (SUCRA = 76.7%), and iTBS over M1 may significantly reduce spasticity compared to sham stimulation [MD = −1.20, 95% CI = (−1.99, −0.41)] (SUCRA = 90.3%). Furthermore, rTMS, tRNS, and tDCS on certain areas may improve PwMS accuracy, response time, manual dexterity, pain relief and QOL, but does not show statistically significant differences. The evidence assessed using GRADE is very low.

Conclusion

Based on the NMA and SUCRA ranking, we can conclude that symptoms including fatigue, pain, spasticity, and QOL can be improved by following NIBS protocol after treatment. Nonetheless, most of the included studies lack a good methodology, and more high-quality randomized clinical trials are needed.
Elevated plasma D-dimer levels in patients with anti-N-methyl-D-aspartate receptor encephalitis
Authors: Shao Yingzhe , Du Juan , Song Yajun , Li Yanfei , Jing Lijun , Gong Zhe , Duan Ranran , Yao Yaobing , Jia Yanjie , Jiao Shujie
Published: November 2022

Purpose

We aimed to explore the difference in coagulation function between healthy individuals and patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis and its relationship with disease severity.

Methods

We retrospectively compared coagulation function in 161 patients with first-attack anti-NMDAR encephalitis and 178 healthy individuals. The association between D-dimer levels and disease severity was analyzed using binary logistic regression. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of D-dimer levels for the severity of anti-NMDAR encephalitis.

Results

Compared to control individuals, patients with anti-NMDAR encephalitis had higher D-dimer levels (median 0.14 vs. 0.05 mg/L, p < 0.001), blood white blood cell (WBC) count (median 8.54 vs. 5.95 × 109/L, p < 0.001), and neutrophil count (median 6.14 vs. 3.1 × 109/L, p < 0.001). D-dimers (median 0.22 vs. 0.10 mg/L, p < 0.001), blood WBC count (median 9.70 vs. 7.70 × 109/L, p < 0.001), neutrophil count (median 7.50 vs. 4.80 × 109/L, p < 0.001), and C-reactive protein (median 2.61 vs. 1.50 mg/l, p = 0.017) were higher; however, eosinophils (median 0.02 vs. 0.06 × 109/L, p < 0.001), and blood calcium (median 2.26 vs. 2.31 mmol/L, p = 0.003) were lower in patients with severe forms of anti-NMDAR encephalitis than in those with mild to moderate forms, and were associated with initial modified Rankin Scale scores. Multivariate analysis showed that D-dimer levels were significantly associated with severity [odds ratio =2.631, 95% confidence interval (CI) = 1.018–6.802, p = 0.046]. The ROC curve was used to analyze the predictive value of D-dimer levels for disease severity. The area under the curve was 0.716 (95% CI = 0.64–0.80, p < 0.001), and the best cut-off value was D-dimer = 0.147 mg/L (sensitivity 0.651; specificity, 0.705).

Conclusion

Serum D-dimer and neutrophil levels were independent predictors of disease severity in patients with first-attack anti-NMDAR encephalitis.
Association between the C-reactive protein to albumin ratio and adverse clinical prognosis in patients with young stroke
Authors: Du Yang , Zhang Jia , Li Ning , Guo Jiahuan , Liu Xinmin , Bian Liheng , Zhao Xingquan , Liu Yanfang
Published: November 2022

Background

The inflammatory response plays an important role in ischemic stroke, and the incidence of stroke in young adults has increased rapidly in recent years. The C-reactive protein-to-albumin ratio (CAR) is a new index that reflects the overall inflammatory status of patients with major diseases; however, no studies have reported the relationship between CAR and young stroke.

Methods

The participants' baseline characteristics and laboratory examination results, including CAR, were obtained at admission. The modified Rankin Scale (mRS) scores at the 30-day and 90-day follow-ups were obtained from all patients. All the participants included in the study were classified into four groups according to CAR quartiles (Q1–Q4). Logistic regression was used to analyze the relationship between different CAR levels and adverse outcomes (mRS 3–6 and mRS 2–6). We also plotted receiver operating characteristic curves of CAR for adverse clinical outcomes and calculated the area under the curve and cutoff values.

Results

A total of 630 patients with young stroke were enrolled in the study. In the multivariate logistic regression model, at the 30-day follow-up, the Q3 and Q4 (significantly increased CAR) groups showed an elevated risk of mRS score of 2–6 (odds ratio [OR]: 2.94; 95% confidence interval [CI]: 1.40–6.16, p < 0.01; OR: 4.01; 95% CI: 1.88–8.91, p < 0.01). At the 90-day follow-up, the Q3 and Q4 groups still showed an elevated risk of an mRS score of 2–6 (Q3, OR: 2.76; 95% CI: 1.30–5.86, p < 0.01; Q4, OR: 2.63; 95% CI: 1.22–5.65, p < 0.01).

Conclusion

A significantly increased CAR was independently associated with an increased risk of adverse outcomes in young patients with stroke.
Neuroimaging in schizophrenia: A review article
Authors: Dabiri Mona , Dehghani Firouzabadi Fatemeh , Yang Kun , Barker Peter B. , Lee Roland R. , Yousem David M.
Published: November 2022

In this review article we have consolidated the imaging literature of patients with schizophrenia across the full spectrum of modalities in radiology including computed tomography (CT), morphologic magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy (MRS), positron emission tomography (PET), and magnetoencephalography (MEG). We look at the impact of various subtypes of schizophrenia on imaging findings and the changes that occur with medical and transcranial magnetic stimulation (TMS) therapy. Our goal was a comprehensive multimodality summary of the findings of state-of-the-art imaging in untreated and treated patients with schizophrenia. Clinical imaging in schizophrenia is used to exclude structural lesions which may produce symptoms that may mimic those of patients with schizophrenia. Nonetheless one finds global volume loss in the brains of patients with schizophrenia with associated increased cerebrospinal fluid (CSF) volume and decreased gray matter volume. These features may be influenced by the duration of disease and or medication use. For functional studies, be they fluorodeoxyglucose positron emission tomography (FDG PET), rs-fMRI, task-based fMRI, diffusion tensor imaging (DTI) or MEG there generally is hypoactivation and disconnection between brain regions. However, these findings may vary depending upon the negative or positive symptomatology manifested in the patients. MR spectroscopy generally shows low N-acetylaspartate from neuronal loss and low glutamine (a neuroexcitatory marker) but glutathione may be elevated, particularly in non-treatment responders. The literature in schizophrenia is difficult to evaluate because age, gender, symptomatology, comorbidities, therapy use, disease duration, substance abuse, and coexisting other psychiatric disorders have not been adequately controlled for, even in large studies and meta-analyses.
Association between pre-diagnostic dietary copper, zinc, and copper-to-zinc ratio and severity of ovarian cancer
Authors: Yin Jia-Li , Tao Tao , Wen Zhao-Yan , Wang Ran , Sun Ming-Hui , Gao Chang , Chang Yu-Jiao , Yan Shi , Qin Xue , Zhao Yu-Hong , Wang Lan , Gao Song
Published: November 2022

Background

The impact of dietary trace elements intake on ovarian cancer (OC) severity is unknown.

Objective

We firstly explore the relationship between dietary copper (Cu), zinc (Zn), and copper-to-zinc (Cu/Zn) ratio and severity of OC.

Methods

This cross-sectional study included 701 women from the OC follow-up study between 2015 and 2020. Dietary information was collected by a validated food frequency questionnaire (FFQ). The severity information of OC including age at diagnosis, histological type, International Federation of Gynecology and Obstetrics (FIGO) stage, and histopathologic grade was ascertained from medical records. Logistic regression model was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of aforementioned associations.

Results

Among 701 participants, the number of patients age at diagnosis older than 50 were 443 (63.2%). The number of patients diagnosed as serous, III–IV stage, and poorly differentiation OC were 477 (68.05%), 336 (47.93%), and 597 (85.16%), respectively. In addition, compared with the lowest tertile intake, higher possibility of non-serous OC was associated with the pre-diagnosis dietary Cu (OR = 2.39, 95% CI = 1.28–4.47, p trend < 0.05) and Cu/Zn ratio (OR = 2.06, 95% CI = 1.26–3.39, P trend < 0.05) in the highest tertile intake. The risk of poorly differentiation OC at diagnosis was significant inversely related to dietary Cu intake (OR = 0.40, 95% CI = 0.18–0.88, P trend < 0.05). Besides, the results of subgroup analyses were consistent with the main findings but not all of them showed statistical significance.

Conclusion

Pre-diagnostic dietary Cu and Cu/Zn ratio were contributed to reducing the severity of OC at diagnosis, especially for the risk of serous OC and poorly differentiation OC.
Effects of an exogenous ketone ester using multi-omics in skeletal muscle of aging C57BL/6J male mice
Authors: Roberts Brandon M. , Deemer Sarah E. , Smith Daniel L. , Mobley James A. , Musi Nicolas , Plaisance Eric P.
Published: November 2022

Exogenous ketone ester supplementation provides a means to increase circulating ketone concentrations without the dietary challenges imposed by ketogenic diets. Our group has shown that oral R,S-1,3, butanediol diacetoacetate (BD-AcAc2) consumption results in body weight loss or maintenance with moderate increases in circulating ketones. We have previously shown a diet consisting of 25% BD-AcAc2 can maintain lean body mass (LBM) and induce fat mass (FM) loss in young, healthy male mice, but the underlying mechanisms are still unknown. Therefore, the purpose of this study was to determine if a diet consisting of 25% BD-AcAc2 (ketone ester, KE) would alter body composition, transcriptional regulation, the proteome, and the lipidome of skeletal muscle in aged mice. We hypothesized that the KE group would remain weight stable with improvements in body composition compared to controls, resulting in a healthy aging phenotype. Male C57BL/6J mice (n = 16) were purchased from Jackson Laboratories at 72 weeks of age. After 1 week of acclimation, mice were weighed and randomly assigned to one of two groups (n = 8 per group): control (CON) or KE. A significant group by time interaction was observed for body weight (P < 0.001), with KE fed mice weighing significantly less than CON. FM increased over time in the control group but was unchanged in the KE group. Furthermore, LBM was not different between CON and KE mice despite KE mice weighing less than CON mice. Transcriptional analysis of skeletal muscle identified 6 genes that were significantly higher and 21 genes that were significantly lower in the KE group compared to CON. Lipidomic analysis of skeletal muscle identified no differences between groups for any lipid species, except for fatty acyl chains in triacylglycerol which was 46% lower in the KE group. Proteomics analysis identified 44 proteins that were different between groups, of which 11 were lower and 33 were higher in the KE group compared to CON. In conclusion, 72-week-old male mice consuming the exogenous KE, BD-AcAc2, had lower age-related gains in body weight and FM compared to CON mice. Furthermore, transcriptional and proteomics data suggest a signature in skeletal muscle of KE-treated mice consistent with markers of improved skeletal muscle regeneration, improved electron transport chain utilization, and increased insulin sensitivity.
Maintaining the quality of postharvest broccoli by inhibiting ethylene accumulation using diacetyl
Authors: Li Xiaotong , Meng Zan , Malik Aman Ullah , Zhang Song , Wang Qingguo
Published: November 2022

Broccoli (Brassica oleracea L. var. Italic) is rich in nutrition. However, it is susceptible to yellowing after harvest, leading to nutritional and economic losses. In this study, diacetyl, a natural food additive compound, was selected to inhibit the yellowing of broccoli florets and maintain the nutrient quality during storage time. It was found that 20 μl L–1 diacetyl treatment for 12 h could significantly delay the yellowing and decrease the weight loss and lignin content of broccoli florets. Meanwhile, diacetyl could maintain higher contents of chlorophyll, vitamin C and flavonoids and suppress the transcript levels of chlorophyll degradation–related genes in broccoli florets. Moreover, accumulations of reactive oxygen species (ROS) were inhibited by diacetyl treatment. Under diacetyl treatment, the generation of ethylene was prevented by inhibiting the activities and related-gene expressions of 1-aminocyclopropane-1-carboxylic acid (ACC) synthase and ACC oxidase. Based on our findings, exogenous diacetyl could be employed as a novel bioactive molecule for retarding the yellowing and maintaining the quality of postharvest broccoli.
Epidermal growth factor receptor mutations and brain metastases in non-small cell lung cancer
Authors: Zhao Wei , Zhou Wei , Rong Li , Sun Mao , Lin Xing , Wang Lulu , Wang Shiqiang , Wang Ying , Hui Zhouguang
Published: November 2022

Studies have revealed that non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations has a high incidence of brain metastases (BMs). However, the association between EGFR mutations and BMs remains unknown. This review summarizes detailed information about the incidence of BMs, clinical and imaging characteristics of BMs, brain surveillance strategies, influence of treatments on BMs, prognosis after BMs, and differences in EGFR mutations between paired primary tumors and BMs in EGFR-mutated NSCLC. The prognostic results demonstrate that patients with mutated EGFR have a higher incidence of BMs, EGFR tyrosine kinase inhibitors (EGFR-TKIs) (afatinib and osimertinib) delay the development of BMs, and patients with mutated EGFR with synchronous or early BMs have better overall survival after BMs than those with wild-type EGFR. The EGFR mutation status of BM sites is not always in accordance with the primary tumors, which indicates that there is heterogeneity in EGFR gene status between paired primary tumors and BMs. However, the EGFR gene status of the primary site can largely represent that of BM sites. Among patients developing synchronous BMs, patients with mutated EGFR are less likely to have central nervous system (CNS) symptoms than patients with wild-type EGFR. However, the possibility of neuro-symptoms is high in patients with metachronous BMs. Patients with mutated EGFR tend to have multiple BMs as compared to patients with wild-type EGFR. Regarding very early-stage NSCLC patients without neuro-symptoms, regular neuroimaging follow-up is not recommended. Among advanced NSCLC patients with EGFR mutation, liberal brain imaging follow-up in the first several years showed more advantages in terms of cost.
Large-cell neuroendocrine carcinoma of the gynecologic tract: Prevalence, survival outcomes, and associated factors
Authors: Pang Li , Chen Jie , Chang Xiaohan
Published: November 2022

Background

We aimed to assess the clinical behavior of gynecologic large-cell neuroendocrine carcinoma (LCNEC) via a retrospective analysis of data from 469 patients.

Methods

Patients diagnosed with gynecologic LCNEC from 1988 to 2015 were identified using the Surveillance, Epidemiology, and End Results database. Univariate and multivariate Cox hazard regression analyses were performed to assess independent predictors of overall survival (OS) and cancer-specific survival (CSS). OS and CSS were also evaluated using the Kaplan–Meier method, and the effects of different treatment regimens on prognosis were compared according to disease stage.

Results

Cervical, ovarian, and endometrial LCNEC were observed in 169, 219, and 79 patients, respectively. The 5-year OS rates for patients with cervical, ovarian, and endometrial LCNEC were 35.98%, 17.84%, and 23.21%, respectively, and the median duration of overall survival was 26, 11, and 11 months in each group. The 5-year CSS rates for the three groups were 45.23%, 19.23%, and 31.39%, respectively, and the median duration of CSS was 41, 12, and 11 months in each group. Multivariate analysis revealed that American Joint Committee on Cancer stage, lymph node metastasis, and chemotherapy were independent prognostic factors for OS and CSS in patients with cervical LCNEC. Lymph node metastasis, surgery, and chemotherapy were independent prognostic factors for OS and CSS in the ovarian group and for OS in the endometrial group. Lymph node metastasis and surgery were also independent prognostic factors for CSS in the endometrial group.

Conclusion

Surgery alone may help to improve overall survival and CSS in patients with early-stage cervical LCNEC. In contrast, surgery+chemotherapy and surgery+radiotherapy may help to improve survival in those with early-stage ovarian and endometrial LCNEC, respectively. Regardless of subtype, comprehensive treatment involving surgery, CTX, and RT should be considered to improve prognosis in patients with advanced-stage gynecologic LCNEC.
Central nervous system germ cell tumor, an archetypal AYA tumor and a model for pediatric and neuro-oncology collaboration, review from the EURACAN domain 10 group
Authors: Faure Conter Cecile , Calaminus Gabriele , Nicholson James , Idbaih Ahmed , Hoang Xuan Khê , Vasiljevic Alexandre , Morana Giovanni , Szathmari Alexandru , Ajithkumar Thankamma , Frappaz Didier
Published: November 2022

Simple Summary: Adolescents and young adults (AYA) with cancer often fall through gaps between children’s and adults’ cancer services. They are consequently under-represented in clinical trials, and their survival is often inferior to that of children or adults with the same tumor type; in this paper, we use the example of central nervous system germ cell tumors (CNS-GCT), as a model of AYA tumor to illustrate this challenge. We describe how we have built bridges between pediatric and adult oncology, how this can apply to other types of brain tumors, and discuss ways to promote cancer care in the AYA population.

Adolescents and young adults (AYA) with cancer are under-represented in clinical trials and have thus not benefited from the same improvement in outcomes as either younger or older patients. Central nervous system germ cell tumors (CNS-GCT) represent an ideal model of AYA tumor as their incidence peaks during adolescence and young adulthood. Since the early 90’s, SIOP (International Society of Pediatric Oncology) has launched two successive European trials: SIOP CNS-GCT96 (January 1996 to December 2005) and SIOP CNS-GCTII protocols (October 2011 to July 2018), for CNS-GCTs. With the removal of the upper age limit in the SIOP CNS-GCTII trial, and closer collaboration between pediatric and adult oncologists within AYA multidisciplinary tumor boards, the proportion of adults enrolled in France has dramatically increased over time. The current article will use the example of CNS-GCT to illustrate how to build a bridge between pediatric and adult oncology, how this can apply to other types of brain tumors, and how to promote cancer care in the AYA population.
Alagille syndrome due to a de novo NOTCH2 mutation presenting as prenatal oligohydramnios and congenital bilateral renal hypodysplasia: A case report
Authors: Xu Fengdan , Peng Qi , He Xiaoguang , Chen Xiaolan , Jiang Shuanglan , Lu Xiaomei , Li Ning
Published: November 2022

Introduction

Here, we report the case of an infant suffering from Alagille syndrome (ALGS), manifesting with the atypical clinical manifestations of prenatal oligohydramnios and renal lesions. To the best of our knowledge, this is the first case of ALGS presenting as prenatal oligohydramnios and renal lesions caused by a de novo variant of the NOTCH2 gene.

Case presentation

A 3-month-old male infant was hospitalized for severe malnutrition. He presented with prenatal oligohydramnios from 28+4 weeks of gestation. After birth, he failed to thrive and suffered from impaired motor development, thermoregulation disorders, congenital bilateral renal hypodysplasia, which initially manifested as stage 5 before improving to stage 3 chronic renal impairment, slightly elevated levels of transaminases, cholestasis, and dysmorphic facial features. We used a diagnostic screening panel of 4,047 pathogenic genes and whole exome sequencing (WES) to analyze the proband and his parents (who had normal kidneys). We found that the proband carried a de novo heterozygous splicing variant (c.5930-2A > G) in intron 33 of the NOTCH2 gene. Transcriptome sequencing confirmed that the mutation of this gene site would affect the splicing of NOTCH2 mRNA and lead to exon 33 skipping.

Conclusions

Our case expands the spectrum of pathogenic variants of the NOTCH2 gene that are known to be associated with ALGS and characterized by prenatal oligohydramnios and renal lesions. It also reminds us of the necessity to monitor the liver and kidney function of the infant if a mother has oligohydramnios during pregnancy and we recommend ALGS as an additional differential diagnosis in prenatal renal abnormalities.
Using ear molding to correct auricular helix adhesion deformity
Authors: Chen Lili , Li Chenlong , He Aijuan , Chen Ying , Tong Hua , Fu Yaoyao , Zhang Tianyu
Published: November 2022

Objectives

This study examined the effectiveness of Byrd's EarWell system for the treatment of auricular helix adhesion.

Methods

The newborns with helix adhesion were treated with ear molding. The photos of pinna were taken before, during, and after the treatment. The immediate and long-term outcomes, as well as the complications, were assessed by two independent plastic surgeons.

Study design

A retrospective study. Data on family history, neonatal weight, gestational age, delivery method, laterality, gender, age of initiating treatment, medical comorbidities, duration of treatment, and follow-up time were collected.

Study site and period

From 2019 to 2021, infants treated with the EarWell System in the Eye and ENT Hospital of Fudan University were enrolled in this study.

Results

A total of 46 newborns (66 ears) with helix adhesion were included. The average onset time of treatment was 4.57 ± 3.63 weeks. The average duration of treatment was 7.40 ± 2.05 weeks. 97.0% ears’ (64/66) immediate results were excellent or good. During long-term follow-up, 95.5% ears achieved excellent or good outcomes. Age of initiation treatment significantly affected immediate (p = 0.001) and long-term (p = 0.004) outcomes.

Conclusions

EarWell System was an effective method to correct auricular helix adhesion. Using this approach, patients with helix adhesion could avoid surgeries. Age of initiation treatment was the predictor of successful correction.
Pharmacophore-based virtual screening approaches to identify novel molecular candidates against EGFR through comprehensive computational approaches and in-vitro studies
Authors: Opo F A Dain Md , Moulay Mohammed , Zari Ali , Alqaderi Afnan , Alkarim Saleh , Zari Talal , Bhuiyan Mohiuddin Ahmed , Mahmoud Maged Mostafa , Aljoud Fadwa , Suhail Mohd , Edris Sherif , Ramadan Wafaa S. , Kamal Mohammad Amjad , Nemmiche Saïd , Ahammad Foysal
Published: November 2022

Alterations to the EGFR (epidermal growth factor receptor) gene, which primarily occur in the axon 18–21 position, have been linked to a variety of cancers, including ovarian, breast, colon, and lung cancer. The use of TK inhibitors (gefitinib, erlotinib, lapatinib, and afatinib) and monoclonal antibodies (cetuximab, panitumumab, and matuzumab) in the treatment of advanced-stage cancer is very common. These drugs are becoming less effective in EGFR targeted cancer treatment and developing resistance to cancer cell eradication, which sometimes necessitates stopping treatment due to the side effects. One in silico study has been conducted to identify EGFR antagonists using other compounds, databases without providing the toxicity profile, comparative analyses, or morphological cell death pattern. The goal of our study was to identify potential lead compounds, and we identified seven compounds based on the docking score and four compounds that were chosen for our study, utilizing toxicity analysis. Molecular docking, virtual screening, dynamic simulation, and in-vitro screening indicated that these compounds’ effects were superior to those of already marketed medication (gefitinib). The four compounds obtained, ZINC96937394, ZINC14611940, ZINC103239230, and ZINC96933670, demonstrated improved binding affinity (−9.9 kcal/mol, −9.6 kcal/mol, −9.5 kcal/mol, and −9.2 kcal/mol, respectively), interaction stability, and a lower toxicity profile. In silico toxicity analysis showed that our compounds have a lower toxicity profile and a higher LD50 value. At the same time, a selected compound, i.e., ZINC103239230, was revealed to attach to a particular active site and bind more tightly to the protein, as well as show better in-vitro results when compared to our selected gefitinib medication. MTT assay, gene expression analysis (BAX, BCL-2, and β-catenin), apoptosis analysis, TEM, cell cycle assay, ELISA, and cell migration assays were conducted to perform the cell death analysis of lung cancer and breast cancer, compared to the marketed product. The MTT assay exhibited 80% cell death for 75 µM and 100µM; however, flow cytometry analysis with the IC50 value demonstrated that the selected compound induced higher apoptosis in MCF-7 (30.8%) than in A549.
Effects of isolation, crowding, and different psychological countermeasures on crew behavior and performance
Authors: Shved Dmitry , Kuznetsova Polina , Rozanov Ivan A. , Lebedeva Svetlana A. , Vinokhodova Alla , Savinkina Alexandra , Shishenina Ksenia , Rey Nicole Diaz , Gushin Vadim
Published: November 2022

Studies conducted by I. Altman in the 1960–70s revealed the increase in the individual stress level under isolation and confinement. Altman introduced the term “privacy” as a desired level of personal space that humans need to feel psychologically comfortable. The author also mentioned the dynamic process of boundary regulation that can be accompanied by the increase in conflict tension in the confined groups. In our study with short-term chamber isolation ESKIS, we analyzed behavior, crew interactions, and psychological state of a mixed-gender crew with none or minimal previous isolation experience (4 males and 2 females) who spent 14 days in a small chamber of 50 m3. The study confirmed that the pre-isolation period was particularly stressful for the subjects who felt also significant anxiety during the first days of isolation. Also, some mood and sleep disturbances were detected under isolation and crowding. Psychological stress made the crew more cohesive; they demonstrated the increase in common values. Extraverted subjects who could obtain social support from their partners and Mission Control’s duty teams were less interested in psychological support via VR.
Nitrogen fertilizer application rates and ratios promote the biochemical and physiological attributes of winter wheat
Authors: Kubar Muhammad Saleem , Wang Chao , Noor Rana Shahzad , Feng Meichen , Yang Wude , Kubar Kashif Ali , Soomro Khalilullah , Yang Chen , Sun Hui , Hasan Mohamed E. , Mosa Walid F. A.
Published: November 2022

Improper optimization of the rates and ratios of nitrogen application reduces grain yields and increases the nitrogen loss, thereby affecting environmental quality. In addition, scarcer evidence exists on the integrative approach of nitrogen, which could have effects on the biochemical and physiological characteristics of wheat. Treatments were arranged as nitrogen (N) rates of 00, 75, 150, 225, and 300 kg ha−1 in the main plots, and different nitrogen ratios were organized in subplots at 5:5:0:0 and 6:4:0:0, which were applied at the sowing, jointing, flowering, and grain filling stages. The results revealed that 225 kg N ha−1 significantly enhanced the stomatal conductance (Gs), photosynthetic rate (Pn), intercellular CO2 (Ci), transpiration rate (Tr), and total chlorophyll by 28.5%, 42.3%, 10.0%, 15.2%, and 50%, receptively, at the jointing stage in comparison to the control (0 kg N ha−1). Nitrogen application of 225 kg ha−1 increased the soil–plant analysis development (SPAD) value and the chlorophyll a, chlorophyll b, and carotenoid contents of winter wheat under the 6:4:0:0 ratio. The trend of the photosynthetic characteristics was observed to be greater at the 6:4:0:0 fertilization ratio compared to that at 5:5:0:0. The photosynthetic rate was significantly associated with the biochemical and physiological characteristics of winter wheat. In conclusion, the nitrogen dose of 225 kg ha−1 and the ratio of 6:4:0:0 (quantity applied at the sowing, jointing, flowering, and grain filling stages) effectively promoted the photosynthetic and other physiological characteristics of winter wheat.
QTL analysis identified two major all-internodes solidness loci from a completely solid-stemmed spring wheat line
Authors: Dhariwal Raman , Hiebert Colin W. , Randhawa Harpinder S.
Published: November 2022

The culms of solid-stemmed wheat cultivars are filled with “pith” – a parenchymatous tissue largely composed of soft, spongy, and compact parenchyma cells. Breeding solid-stemmed cultivars is the most effective way to decrease the detrimental impact of wheat stem sawfly (WSS), Cephus cinctus Norton (Hymenoptera: Cephidae) on wheat production. Although a major solid stem gene has been previously identified from durum wheat, it produces an intermediate level of stem solidness in common wheat which is insufficient to provide the required level of WSS resistance. The maximum resistance is achieved when stems are totally filled with pith. Thus, to identify a secondary source of solidness in common wheat, we developed three mapping populations from wheat cvs. Sadash, ‘AAC Innova’ and ‘AAC Cameron’, each crossed separately with P2711, a completely solid-stemmed hexaploid wheat breeding line. All populations were genotyped using either wheat 15K or 90K Infinium iSelect SNP Assay and high-density linkage maps were generated from individual populations along with consensus maps for chromosomes 3B and 3D from all populations. ‘Sadash/P2711’ and ‘AAC Innova/P2711’ populations were subjected to extensive phenotyping in ≥3 environments followed by quantitative trait loci (QTL) analyses using population-specific and consensus linkage maps. We identified two major solid stem QTLs in the distal regions of chromosome arms 3BL and 3DL in both populations in addition to several population-specific or common minor QTLs. Internode-specific QTL analyses detected both major QTLs of chromosomes 3B and 3D across internodes, from top to bottom of the stalk, but minor QTLs were largely detected in upper or middle internodes. Our results suggest that both major QTLs are sufficient to develop highly solid-stemmed cvs; however, the minor loci, which additively enhance the pith expression, can be coupled with major genes to achieve a complete solid stem phenotype in common wheat. Comparative and haplotype analyses showed that the 3B locus is homoeologous to 3D, the former being mapped to a 1.1 Mb genomic region. Major QTLs identified in this study can be incorporated in modern wheat cultivars to achieve maximum WSS resistance from high pith expression.
DhMYB2 and DhbHLH1 regulates anthocyanin accumulation via activation of late biosynthesis genes in Phalaenopsis-type Dendrobium
Authors: Wang Yachen , Yin Hantai , Long Zongxing , Zhu Wenjuan , Yin Junmei , Song Xiqiang , Li Chonghui
Published: November 2022

Phalaenopsis-type Dendrobium is a popular orchid with good ornamental and market value. Despite their popularity, molecular regulation of anthocyanin biosynthesis during flower development remains poorly understood. In this study, we systematically investigated the regulatory roles of the transcription factors DhMYB2 and DhbHLH1 in anthocyanins biosynthesis. Gene expression analyses indicated that both DhMYB2 and DhbHLH1 are specifically expressed in flowers and have similar expression patterns, showing high expression in purple floral tissues with anthocyanin accumulation. Transcriptomic analyses showed 29 differentially expressed genes corresponding to eight enzymes in anthocyanin biosynthesis pathway have similar expression patterns to DhMYB2 and DhbHLH1, with higher expression in the purple lips than the yellow petals and sepals of Dendrobium ‘Suriya Gold’. Further gene expression analyses and Pearson correlation matrix analyses of Dendrobium hybrid progenies revealed expression profiles of DhMYB2 and DhbHLH1 were positively correlated with the structural genes DhF3’H1, DhF3’5’H2, DhDFR, DhANS, and DhGT4. Yeast one-hybrid and dual‐luciferase reporter assays revealed DhMYB2 and DhbHLH1 can bind to promoter regions of DhF3’H1, DhF3’5’H2, DhDFR, DhANS and DhGT4, suggesting a role as transcriptional activators. These results provide new evidence of the molecular mechanisms of DhMYB2 and DhbHLH1 in anthocyanin biosynthesis in Phalaenopsis-type Dendrobium.