bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of Cystoid Macular Edema in Retinitis Pigmentosa: A Systematic Review and Meta-Analysis
Authors: Chen Chen , Liu Xia , Peng Xiaoyan
Published: May 2022

Background

To date, various treatments for cystoid macular edema (CME) in retinitis pigmentosa (RP) have been reported. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of current treatments for RP-CME.

Methods

PubMed, Embase and the Cochrane library were searched from inception to August 2021. ClinicalTrials.gov, WHO ICTRP and ISRCTN were also searched for relevant studies. Only studies published in English were included. The RoB 2 tool was used to evaluate the risk of bias of randomized controlled trials (RCTs), and the MINORS scale was used to assess the methodological quality of non-RCTs. Review manager (Revman) was used to pool the data. The primary outcomes included the change of central macular thickness (CMT) and best-corrected visual acuity (BCVA) from baseline. The secondary outcomes included fluorescein angiography (FA) leakage, rebound of CME and adverse effects.

Results

Thirty-two studies were included in the current systematic review and 7 studies were used for meta-analysis. Treatments for RP-CME included oral and topical carbonic anhydrase inhibitors (CAIs), systematic and local steroids, anti-VEGF therapy, NSAIDS, grid LASER photocoagulation, subliminal micropulse LASER, vitrectomy, lutein supplement and oral minocycline. CAIs and local steroids were proved to be effective in reducing CMT. The effects of anti-VEGF reagents varied among studies. Regarding other treatments, only one study for each method fitted the inclusion criteria, so the evidence was very limited.

Conclusion

Topical CAIs, oral CAIs and local steroids are effective in treating RP-CME. However, due to the overall inferior design and small patient number of the included studies, the quality of evidence was poor. Systematic steroids, LASER, NSAIDS and vitrectomy may also be effective, nevertheless, considering the limited number of studies, no conclusion could be drawn regarding these treatments. More well-designed and conducted studies are needed in this field.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021273979, identifier CRD42021273979.
Fungi and Archaea Control Soil N2O Production Potential in Chinese Grasslands Rather Than Bacteria
Authors: Zhong Lei , Qing Jinwu , Liu Min , Cai Xiaoxian , Li Gaoyuan , Li Frank yonghong , Chen Guanyi , Xu Xingliang , Xue Kai , Wang Yanfen
Published: May 2022

Nitrous oxide (N2O) is a powerful greenhouse gas and the predominant stratospheric ozone-depleting substance. Soil is a major source of N2O but remains largely uncertain due to the complicated processes of nitrification and denitrification performed by various groups of microbes such as bacteria, fungi, and archaea. We used incubation experiments to measure the total fungal, archaeal, and bacterial N2O production potential and the microbial functional genes in soils along 3,000 km Chinese grassland transect, including meadow steppe, typical steppe, desert steppe, alpine meadow, and alpine steppe. The results indicated that fungi, archaea, and bacteria contributed 25, 34, and 19% to nitrification and 46, 29, and 15% to denitrification, respectively. The AOA and AOB genes were notably correlated with the total nitrification enzyme activity (TNEA), whereas both narG and nirK genes were significantly correlated with total denitrification enzyme activity (TDEA) at p < 0.01. The correlations between AOA and ANEA (archaeal nitrification enzyme activity), AOB and BNEA (bacterial nitrification enzyme activity), and narG, nirK, and BDEA (bacterial denitrification enzyme activity) showed higher coefficients than those between the functional genes and TNEA/TDEA. The structural equation modeling (SEM) results showed that fungi are dominant in N2O production processes, followed by archaea in the northern Chinese grasslands. Our findings indicate that the microbial functional genes are powerful predictors of the N2O production potential, after distinguishing bacterial, fungal, and archaeal processes. The key variables of N2O production and the nitrogen (N) cycle depend on the dominant microbial functional groups in the N-cycle in soils.
Diversity of Microbial Eukaryotes Along the West Antarctic Peninsula in Austral Spring
Authors: Grattepanche Jean-David , Jeffrey Wade H. , Gast Rebecca J. , Sanders Robert W.
Published: May 2022

During a cruise from October to November 2019, along the West Antarctic Peninsula, between 64.32 and 68.37°S, we assessed the diversity and composition of the active microbial eukaryotic community within three size fractions: micro- (> 20 μm), nano- (20–5 μm), and pico-size fractions (5–0.2 μm). The communities and the environmental parameters displayed latitudinal gradients, and we observed a strong similarity in the microbial eukaryotic communities as well as the environmental parameters between the sub-surface and the deep chlorophyll maximum (DCM) depths. Chlorophyll concentrations were low, and the mixed layer was shallow for most of the 17 stations sampled. The richness of the microplankton was higher in Marguerite Bay (our southernmost stations), compared to more northern stations, while the diversity for the nano- and pico-plankton was relatively stable across latitude. The microplankton communities were dominated by autotrophs, mostly diatoms, while mixotrophs (phototrophs-consuming bacteria and kleptoplastidic ciliates, mostly alveolates, and cryptophytes) were the most abundant and active members of the nano- and picoplankton communities. While phototrophy was the dominant trophic mode, heterotrophy (mixotrophy, phagotrophy, and parasitism) tended to increase southward. The samples from Marguerite Bay showed a distinct community with a high diversity of nanoplankton predators, including spirotrich ciliates, and dinoflagellates, while cryptophytes were observed elsewhere. Some lineages were significantly related—either positively or negatively—to ice coverage (e.g., positive for Pelagophyceae, negative for Spirotrichea) and temperature (e.g., positive for Cryptophyceae, negative for Spirotrichea). This suggests that climate changes will have a strong impact on the microbial eukaryotic community.
Whole Genome Sequencing, Antibiotic Resistance, and Epidemiology Features of Nontyphoidal Salmonella Isolated From Diarrheic Children: Evidence From North China
Authors: Zhao Wei , Li Xin , Shi Xuening , Li Kewei , Shi Ben , Sun Jingyu , Zhao Chao , Wang Juan
Published: May 2022

Nontyphoidal Salmonella (NTS) in children remains a growing burden on public health and often causes children to be hospitalized with diarrheic symptoms. In this work, 260 strains of human Salmonella isolated from Jilin, China were characterized by serotypes and antimicrobial resistance using whole genome sequencing (WGS). The most prevalent serotype was Salmonella enteritidis (47.3%), followed by S. I 4,[5],12:i:- (33.1%), and Salmonella Typhimurium (7.3%). Furthermore, the consistency between resistance phenotype and genotype was confirmed. Similarly, strains harbored blaTEM−1B and tetA genes were detected, which verified the level of resistant phenotype in β-lactams and tetracyclines. The presence of a single mutation in parC, gyrA, and qnrS1 genes corresponding to quinolones was also observed. In our work, multilocus sequence typing (MLST) and core genome multilocus sequence typing (cgMLST) were found to have a high resolution to molecular traceability, and the combination of both was conducive to practical application in an actual situation. Taking all of this into account, we suggested that the comprehensive surveillance of Salmonella infection in children should be carried out to monitor antimicrobial-resistant trends from various sources and to alert on outbreaks of foodborne diseases to protect public health.
Immediate Effects of Functional Electrical Stimulation-Assisted Cycling on the Paretic Muscles of Patients With Hemiparesis After Stroke: Evidence From Electrical Impedance Myography
Authors: Li Le , Hu Chengpeng , Leung Kenry W. C. , Tong Raymond K. Y.
Published: May 2022

Background

Electrical impedance myography (EIM) has been applied to assess muscle health conditions in neuromuscular disorders. This study aimed to detect immediate muscle electrical impedance property alterations in lower extremity of chronic stroke survivors immediately after functional electrical stimulation (FES)-assisted cycling training.

Methods

Fourteen chronic stroke survivors were recruited for the current study. EIM measurements were conducted before and immediately after 40-min FES-assisted cycling training for each subject. Four interested muscle groups [rectus femoris (RF), biceps femoris (BF), tibialis anterior (TA), and the medial head of gastrocnemius (MG)] were selected. Correlation analysis was performed to reveal a significant correlation between changes in EIM parameters and clinical scales [Fugl–Meyer Assessment of the lower extremity (FMA-LE); 6-min walking test (6MWT)].

Results

Immediately after training, reactance (X) and phase angle (θ) values significantly increased on the TA and MG muscles. Significant correlation was observed between X value and FMA-LE scores (r = 0.649, p = 0.012) at MG as well as X and FMA scores of the ankle joint (r = 0.612, p = 0.02). Resistance (R) and θ were significantly correlated with 6MWT score (R-6MWT: r = 0.651, p = 0.012; θ-6MWT: r = 0.621, p = 0.018).

Conclusion

This brief report demonstrated that EIM can reveal the intrinsic property alteration in the paretic muscle of chronic stroke survivors immediately after FES-assisted cycling training. These alterations might be related to muscle hypertrophy (i.e., increases in muscle fiber size). This brief report might aid the understanding of the mechanism of electrical stimulation-assisted exercise in improving muscle function of stroke survivors.
Compound Heterozygous COX20 Variants Impair the Function of Mitochondrial Complex IV to Cause a Syndrome Involving Ophthalmoplegia and Visual Failure
Authors: Li Peizheng , Guo Dandan , Zhang Xiufang , Ji Kunqian , Lv Hongbo , Zhang Yanli , Chen Zhichao , Ma Jun , Fang Yaofeng , Liu Yiming
Published: May 2022

The cytochrome c oxidase 20 (COX20) gene encodes a protein with a crucial role in the assembly of mitochondrial complex IV (CIV). Mutations in this gene can result in ataxia and muscle hypotonia. However, ophthalmoplegia and visual failure associated with COX20 mutation have not been examined previously. Moreover, the mechanism causing the phenotype of patients with COX20 variants to differ from that of patients with mutations in other genes impairing CIV assembly is unclear. In this investigation, the aim was to assess the relation between COX20 variants and CIV assembly. We performed detailed clinical, physical, and biochemical investigations of affected individuals. Western blotting, reverse transcription-polymerase chain reaction, and blue native-polyacrylamide gel electrophoresis were used to analyze the expression level of COX20 and oxidative phosphorylation. A Seahorse XF Cell Mito Stress Test and enzymatic activity analysis were performed to evaluate mitochondrial function. Whole-exome sequencing revealed the same compound heterozygous mutations (c.41A > G and c.222G > T, NM_198076) in COX20 in two siblings. This is the first description of ophthalmoplegia and visual failure associated with COX20 variants. In vitro analysis confirmed that the COX20 protein level was significantly decreased, impairing the assembly and activity of CIV in patients' fibroblast. Overexpression of COX20 using a transduced adenovirus partially restored the function of the patients' fibroblasts. Early-onset complex movement disorders may be closely related to COX20 variants. Our results broaden the clinical phenotypes of patients with COX20 variants showing ophthalmoplegia and visual failure. Additionally, dysfunction of COX20 protein can impair the assembly and activity of CIV.
Troubleshooting Gait Disturbances in Parkinson’s Disease With Deep Brain Stimulation
Authors: Pozzi Nicoló G. , Palmisano Chiara , Reich Martin M. , Capetian Philip , Pacchetti Claudio , Volkmann Jens , Isaias Ioannis U.
Published: May 2022

Deep brain stimulation (DBS) of the subthalamic nucleus or the globus pallidus is an established treatment for Parkinson’s disease (PD) that yields a marked and lasting improvement of motor symptoms. Yet, DBS benefit on gait disturbances in PD is still debated and can be a source of dissatisfaction and poor quality of life. Gait disturbances in PD encompass a variety of clinical manifestations and rely on different pathophysiological bases. While gait disturbances arising years after DBS surgery can be related to disease progression, early impairment of gait may be secondary to treatable causes and benefits from DBS reprogramming. In this review, we tackle the issue of gait disturbances in PD patients with DBS by discussing their neurophysiological basis, providing a detailed clinical characterization, and proposing a pragmatic programming approach to support their management.
Effects of Dietary Indole-3-carboxaldehyde Supplementation on Growth Performance, Intestinal Epithelial Function, and Intestinal Microbial Composition in Weaned Piglets
Authors: Zhang Ruofan , Huang Guowen , Ren Yuting , Wang Haifeng , Ye Yanxin , Guo Jiaqing , Wang Mengting , Zhu Weiyun , Yu Kaifan
Published: May 2022

As a microbial tryptophan metabolite, indole-3-carboxaldehyde (ICA) has been suggested to confer benefits to host, such as regulation of intestinal barrier function. This study aimed to elucidate the role of ICA in modulating intestinal homeostasis via using a weaned pig model. Twenty-four weaned piglets were randomly allocated into three groups: the control group (a basal diet), ICA100 group (the basal diet supplemented with 100 mg/kg ICA), and ICA200 group (the basal diet supplemented with 200 mg/kg ICA). The experiment lasted 14 d, and pigs from the control and ICA100 groups were slaughtered. The results showed no significant differences in the average daily gain (ADG) and average daily feed intake (ADFI) among the three groups (P > 0.05). However, the ICA100 group had a lower feed to gain ratio (F:G) (P < 0.05). Dietary ICA supplementation did not alter the villus height, crypt depth, and villus height/crypt depth ratio in the small intestine, and did not change the intestinal permeability and antioxidant parameters (P > 0.05). Intriguingly, ICA treatment significantly increased the jejunal, ileal and colonic indexes in piglets (P < 0.05). Besides, the expression of proliferating cell nuclear antigen (PCNA) in the intestine was up-regulated by ICA treatment. Moreover, in vitro experiments demonstrated that 15 μM ICA significantly accelerated the proliferation activity of IPEC-J2 cells, and increased the expression of the ICA receptor aryl hydrocarbon receptor (AHR) and the proliferation markers PCNA and Cyclin D1 (P < 0.05). In addition, dietary ICA supplementation modulated the intestinal flora, increasing the richness estimators and diversity index, decreasing the abundances of phylum Fibrobacterota and genera Alloprevotella, Prevotella, and Parabacteroides, and enriching the abundance of genera Butyrivibrio. These data reveal a beneficial role for the microbial metabolite ICA on intestinal epithelial proliferation, rather than intestinal barrier function, in weaned piglets.
The Role of Feedback Loops in Targeted Therapy for Pancreatic Cancer
Authors: Gu Weigang , Shen HongZhang , Xie Lu , Zhang Xiaofeng , Yang Jianfeng
Published: May 2022

Pancreatic cancer is the leading cause of cancer-related deaths worldwide, with limited treatment options and low long-term survival rates. The complex and variable signal regulation networks are one of the important reasons why it is difficult for pancreatic cancer to develop precise targeted therapy drugs. Numerous studies have associated feedback loop regulation with the development and therapeutic response of cancers including pancreatic cancer. Therefore, we review researches on the role of feedback loops in the progression of pancreatic cancer, and summarize the connection between feedback loops and several signaling pathways in pancreatic cancer, as well as recent advances in the intervention of feedback loops in pancreatic cancer treatment, highlighting the potential of capitalizing on feedback loops modulation in targeted therapy for pancreatic cancer.
Development and Characterization of an HCMV Multi-Antigen Therapeutic Vaccine for Glioblastoma Using the UNITE Platform
Authors: Adhikari Amit S. , Macauley Juliete , Johnson Yoshimi , Connolly Mike , Coleman Timothy , Heiland Teri
Published: May 2022

Glioblastoma multiforme (GBM) is an aggressive form of brain cancer with a median survival of 15 months that has remained unchanged despite advances in the standard of care. GBM cells express human cytomegalovirus (HCMV) proteins, providing a unique opportunity for targeted therapy. We utilized our UNITE (UNiversal Intracellular Targeted Expression) platform to develop a multi-antigen DNA vaccine (ITI-1001) that codes for the HCMV proteins pp65, gB, and IE-1. The UNITE platform involves lysosomal targeting technology, fusing lysosome-associated membrane protein 1 (LAMP1) with target ntigens. We demonstrate evidence of increased antigen presentation by both MHC-I and -II, delivering a robust antigen-specific CD4 and CD8 T-cell response in addition to a strong humoral response. Using a syngeneic orthotopic GBM mouse model, therapeutic treatment with the ITI-1001 vaccine resulted in ~56% survival of tumor-bearing mice. Investigation of the tumor microenvironment showed significant CD4 infiltration as well as enhanced Th1 and cytotoxic CD8 T activation. Regulatory T cells were also upregulated after ITI-1001 vaccination. In addition, tumor burden negatively correlated with activated interferon (IFN)γ+ CD4 T cells, reiterating the importance of CD4 activation in ITI-1001 efficacy and in identifying treatment responders and non-responders. Further characterization of these two groups showed high infiltration of CD3+, CD4+, and CD8+ T cells in responders compared to non-responders. Thus, we show that vaccination with HCMV antigens using the ITI-1001-UNITE platform generates strong cellular and humoral immune responses, triggering significant antitumor activity, leading to enhanced survival in a mouse model of GBM.
Clinical Outcomes of BCMA CAR-T Cells in a Multiple Myeloma Patient With Central Nervous System Invasion
Authors: Wang Ting , He Ting , Ma Lie , Yang Yazi , Feng Ru , Ding Yanping , Shan Yueming , Bu Bing , Qi Feifei , Wu Fei , Lu Xin-an , Liu Hui
Published: May 2022

Background

Multiple myeloma (MM) is the second most common hematological malignancy that still lacks effective clinical treatments. In particular, MM with central nervous system (CNS) invasion occurs rarely. Although B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor-T (CAR-T) cell therapy has shown great promise for the treatment of relapsed/refractory MM, few studies have reported whether BCMA CAR-T could inhibit MM with CNS invasion.

Case Presentation

In this study, we report a special case of a 63-year-old male patient who suffered MM with CNS invasion and presented rapid extramedullary disease (EMD) progression into multiple organs. Before CAR-T cell infusion, this patient received five cycles of bortezomib, Adriamycin, and dexamethasone (PAD) and an autologous transplant as the front-line treatment, followed by two cycles of bortezomib, lenalidomide, and dexamethasone (VRD) as the second-line regimen, and daratumumab, bortezomib, dexamethasone (DVD) as the third-line regimen. Since the patient still showed rapid progressive disease (PD), BCMA CAR-T cells were infused, and 1 month later, a stringent complete response (sCR) was achieved, and the response lasted for 4 months. Meanwhile, only grade 1 cytokine release syndrome (CRS) was observed.

Conclusion

This case report demonstrated that BCMA CAR-T could effectively eradicate CNS-involved MM with low adverse events, suggesting that CAR-T cell therapy could be a feasible therapeutic option for this kind of refractory disease.

Clinical Trial Registration

https://ClinicalTrials.gov, identifier: NCT04537442.a
Development and Validation of an Immune-Related Prognostic Signature in Cervical Cancer
Authors: Su Rongjia , Jin Chengwen , Bu Hualei , Xiang Jiangdong , Zhou Lina , Jin Chengjuan
Published: May 2022

Background

Cervical cancer is the fourth most frequent gynecological malignancy across the world. Immunotherapies have proved to improve prognosis of cervical cancer. However, few studies on immune-related prognostic signature had been reported in cervical cancer.

Methods

Raw data and clinical information of cervical cancer samples were downloaded from TCGA and UCSC Xena website. Immunophenoscore of immune infiltration cells in cervical cancer samples was calculated through the ssGSEA method using GSVA package. WGCNA, Cox regression analysis, LASSO analysis, and GSEA analysis were performed to classify cervical cancer prognosis and explore the biological signaling pathway.

Results

There were eight immune infiltration cells associated with prognosis of cervical cancer. Through WGCNA, 153 genes from 402 immune-related genes were significantly correlated with prognosis of cervical cancer. A 15-gene signature demonstrated powerful predictive ability in prognosis of cervical cancer. GSEA analysis showed multiple signaling pathways containing Programmed cell death ligand-1 (PD-L1) expression and PD-1 checkpoint pathway differences between high-risk and low-risk groups. Furthermore, the 15-gene signature was associated with multiple immune cells and immune infiltration in tumor microenvironment.

Conclusion

The 15-gene signature is an effective potential prognostic classifier in the immunotherapies and surveillance of cervical cancer.
MRI-Based Risk Assessment for Incomplete Resection of Brain Metastases
Authors: Rosenstock Tizian , Pöser Paul , Wasilewski David , Bauknecht Hans-Christian , Grittner Ulrike , Picht Thomas , Misch Martin , Onken Julia Sophie , Vajkoczy Peter
Published: May 2022

Object

Recent studies demonstrated that gross total resection of brain metastases cannot always be achieved. Subtotal resection (STR) can result in an early recurrence and might affect patient survival. We initiated a prospective observational study to establish a MRI-based risk assessment for incomplete resection of brain metastases.

Methods

All patients in whom ≥1 brain metastasis was resected were prospectively included in this study (DRKS ID: DRKS00021224; Nov 2020 – Nov 2021). An interdisciplinary board of neurosurgeons and neuroradiologists evaluated the pre- and postoperative MRI (≤48h after surgery) for residual tumor. Extensive neuroradiological analyses were performed to identify risk factors for an unintended STR which were integrated into a regression tree analysis to determine the patients’ individual risk for a STR.

Results

We included 150 patients (74 female; mean age: 61 years), in whom 165 brain metastases were resected. A STR was detected in 32 cases (19.4%) (median residual tumor volume: 1.36ml, median EORrel: 93.6%), of which 6 (3.6%) were intended STR (median residual tumor volume: 3.27ml, median EORrel: 67.3%) - mainly due to motor-eloquent location - and 26 (15.8%) were unintended STR (uSTR) (median residual tumor volume: 0.64ml, median EORrel: 94.7%). The following risk factors for an uSTR could be identified: subcortical metastasis ≥5mm distant from cortex, diffuse contrast agent enhancement, proximity to the ventricles, contact to falx/tentorium and non-transcortical approaches. Regression tree analysis revealed that the individual risk for an uSTR was mainly associated to the distance from the cortex (distance ≥5mm vs. <5mm: OR 8.0; 95%CI: 2.7 – 24.4) and the contrast agent patterns (diffuse vs. non-diffuse in those with distance ≥5mm: OR: 4.2; 95%CI: 1.3 – 13.7). The preoperative tumor volume was not substantially associated with the extent of resection.

Conclusions

Subcortical metastases ≥5mm distant from cortex with diffuse contrast agent enhancement showed the highest incidence of uSTR. The proposed MRI-based assessment allows estimation of the individual risk for uSTR and can help indicating intraoperative imaging.
Relationship Between Neoadjuvant Chemotherapy and Log Odds of Positive Lymph Nodes and Their Prognostic Role in Advanced Ovarian Cancer Patients With Optimal Cytoreductive Surgery
Authors: Hou Yue-min , Xue Yan , Yao Jin-meng , Feng Fang , An Rui-fang
Published: May 2022

Purpose

To analyze the relationship between neoadjuvant chemotherapy (NACT) and log odds of positive lymph nodes (LODDS), as well as their prognostic role in advanced ovarian cancer (AOC) patients with optimal cytoreductive surgery.

Patients and Methods

From the SEER database during 2010-2016, we identified 1,012 AOC patients with optimal cytoreductive surgery. Univariable and multivariable logistic regression was performed to identify the relationship between NACT and LODDS. Overall survival (OS) and cancer-specific survival (CSS) were assessed using the Kaplan-Meier method and log-rank test. Univariable and multivariable Cox regression was conducted to determine the independent prognostic factors for OS and CSS.

Results

Factors associated with significantly higher NACT odds included older (≥60 years old), married, tumor size ≥ 15 cm, FIGO IV, and LODDS ≤ 0.1. Multivariable Cox regression model confirmed older (≥60 years old), unmarried, separated, divorced, widowed, mucinous histology type, tumor size ≥ 15 cm, and LODDS > 0.1 were correlated with increased risks of OS and CSS. NACT was not an independent prognostic factor for OS and CSS. In the subgroup analyses, LODDS was an independent prognostic factor for OS and CSS in patients with < 75 years old, married, unmarried, FIGO III, and tumor size < 15 cm.

Conclusion

NACT did not show any survival benefit in AOC patients with optimal cytoreductive surgery, but it may be beneficial in reducing LODDS. Meanwhile, clinicians can use grade of LODDS to predict the prognosis of AOC patients with optimal cytoreductive surgery.
Myosteatosis can Predict Unfavorable Outcomes in Advanced Hepatocellular Carcinoma Patients Treated With Hepatic Artery Infusion Chemotherapy and Anti-PD-1 Immunotherapy
Authors: Yi Xiaoping , Fu Yan , Long Qianyan , Zhao Yazhuo , Li Sai , Zhou Chunhui , Lin Huashan , Liu Xiaolian , Liu Chang , Chen Changyong , Shi Liangrong
Published: May 2022

Aim

To evaluate the feasibility of computed tomography (CT) - derived measurements of body composition parameters to predict the risk factor of non-objective response (non-OR) in patients with hepatocellular carcinoma (HCC) undergoing anti-PD-1 immunotherapy and hepatic artery infusion chemotherapy (immune-HAIC).

Methods

Patients with histologically confirmed HCC and treated with the immune-HAIC were retrospectively recruited between June 30, 2019, and July 31, 2021. CT-based estimations of body composition parameters were acquired from the baseline unenhanced abdominal CT images at the level of the third lumbar vertebra (L3) and were applied to develop models predicting the probability of OR. A myosteatosis nomogram was built using the multivariate logistic regression incorporating both myosteatosis measurements and clinical variables. Receiver operating characteristic (ROC) curves assessed the performance of prediction models, including the area under the curve (AUC). The nomogram’s performance was assessed by the calibration, discrimination, and decision curve analyses. Associations among predictors and gene mutations were also examined by correlation matrix analysis.

Results

Fifty-two patients were recruited to this study cohort, with 30 patients having a OR status after immune-HAIC treatment. Estimations of myosteatosis parameters, like SM-RA (skeletal muscle radiation attenuation), were significantly associated with the probability of predicting OR (P=0.007). The SM-RA combined nomogram model, including serum red blood cell, hemoglobin, creatinine, and the mean CT value of visceral fat (VFmean) improved the prediction probability for OR disease with an AUC of 0.713 (95% CI, 0.75 to 0.95) than the clinical model nomogram with AUC of 0.62 using a 5-fold cross-validation methodology. Favorable clinical potentials were observed in the decision curve analysis.

Conclusions

The CT-based estimations of myosteatosis could be used as an indicator to predict a higher risk of transition to the Non-OR disease state in HCC patients treated with immune-HAIC therapy. This study demonstrated the therapeutic relevance of skeletal muscle composition assessments in the overall prediction of treatment response and prognosis in HCC patients.
Ovarian Teratoma-Related Paraneoplastic Neurological Syndromes
Authors: Lin Jingfang , Wang Minjin , Wang Jierui , Li Jinmei
Published: May 2022

Paraneoplastic neurological syndromes (PNSs) are a group of neurological disorders triggered by an underlying remote tumor. Ovarian teratoma (OT) is the most common histologic type of germ cell tumor in females. The most common PNSs associated with OT is anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. However, with the increasing number of new antibodies reported over the last decade, the clinical spectrum of OT-related PNSs is also expanding. Our knowledge of OT-related PNSs is still far from complete. Here, we provide a comprehensive review of the most recent findings in the field of OT-related PNSs, with a particular focus on their clinical and pathological characteristics. Overall, the description of neuronal antibodies in PNSs associated with OT strongly suggests that antibodies may be responsible for the clinical symptoms in some cases. OT-related PNSs are associated with various clinical manifestations, including anti-NMDAR encephalitis, limbic encephalitis, encephalomyelitis, progressive cerebellar syndrome and opsoclonus-myoclonus syndrome. The pathological characteristics of the OT suggest that the mechanism of PNSs is probably due to heteromorphic neurons in the tumor tissue, the ectopic expression of the antigens in neural tissue within the teratomas and patients’ unusual immune response. Despite the severity of the neurological syndromes, most patients with OT-related PNSs showed good neurologic response to early tumor resection combined with immunotherapy. To further advance the management of OT-related PNSs, additional studies are needed to explore this complex topic.
Translational Research in Cystic Fibrosis: From Bench to Beside
Authors: Garcia Laura de Castro e , Petry Lucas Montiel , Germani Pedro Augusto Van Der Sand , Xavier Luiza Fernandes , Barros Paula Barros de , Meneses Amanda da Silva , Prestes Laura Menestrino , Bittencourt Luana Braga , Pieta Marina Puerari , Friedrich Frederico , Pinto Leonardo Araújo
Published: May 2022

Cystic fibrosis is the most common life-limiting recessive genetic disorder in Caucasian populations, characterized by the involvement of exocrine glands, causing multisystemic comorbidities. Since the first descriptions of pancreatic and pulmonary involvement in children, technological development and basic science research have allowed great advances in the diagnosis and treatment of cystic fibrosis. The great search for treatments that acted at the genetic level, despite not having found a cure for this disease, culminated in the creation of CFTR modulators, highly effective medications for certain groups of patients. However, there are still many obstacles behind the treatment of the disease to be discussed, given the wide variety of mutations and phenotypes involved and the difficulty of access that permeate these new therapies around the world.
Case Report: MIS-C With Prominent Hepatic and Pancreatic Involvement in a Vaccinated Adolescent – A Critical Reasoning
Authors: Consolini Rita , Costagliola Giorgio , Spada Erika , Colombatto Piero , Orsini Alessandro , Bonuccelli Alice , Brunetto Maurizia R. , Peroni Diego G.
Published: May 2022

Multisystem inflammatory syndrome in children (MIS-C) is a pathologic condition that has emerged during the coronavirus disease 2019 (COVID-19) pandemic. Although the epidemiological evidence of association between MIS-C and SARS-CoV-2 infection has been demonstrated, its pathogenic mechanism is still undefined. We describe the case of a 17-year old female, previously vaccinated against SARS-CoV-2, presenting with a history of asthenia, fever, cough, anorexia, abdominal pain, and vomiting. During the hospitalization, the patient developed bilateral conjunctivitis, hand vasculitis, cutaneous rash, and multiple pulmonary nodules, following by hepatitis and pancreatitis. As she reported a high-risk contact with a SARS-CoV-2 positive patient 10 days before admission, the epidemiological link and the clinical picture characterized by multi-system organ disfunction and inflammatory biomarkers increase led us to the diagnosis of MIS-C. Therefore, the patient was treated with intravenous immunoglobulin and corticosteroids, resulting in a rapid resolution of fever, cutaneous, and pulmonary involvement, while the recovery of hepatitis and pancreatitis was observed in the following weeks. This case leads to the discussion on whether SARS-CoV-2 immunized children and adolescents should be considered at risk of developing MIS-C and on their possible presentation with non-classic clinical features. Additionally, due to the increasing number of vaccinated children and adolescents, the issues resulting either from the diagnostic suspect of MIS-C or from the consequent need of an early therapeutic approach are discussed.
Agonist-Promoted Phosphorylation and Internalization of the Kappa Opioid Receptor in Mouse Brains: Lack of Connection With Conditioned Place Aversion
Authors: Chen Chongguang , Huang Peng , Bland Kathryn , Li Mengchu , Zhang Yan , Liu-Chen Lee-Yuan
Published: May 2022

Selective kappa opioid receptor (KOR) agonists are promising antipruritic agents and analgesics. However, clinical development of KOR agonists has been limited by side effects, including psychotomimetic effects, dysphoria, and sedation, except for nalfurafine, and recently. CR845 (difelikefalin). Activation of KOR elicits G protein- and β-arrestin-mediated signaling. KOR-induced analgesic and antipruritic effects are mediated by G protein signaling. However, different results have been reported as to whether conditioned place aversion (CPA) induced by KOR agonists is mediated by β-arrestin signaling. In this study, we examined in male mice if there was a connection between agonist-promoted CPA and KOR phosphorylation and internalization, proxies for β-arrestin recruitment in vivo using four KOR agonists. Herein, we demonstrated that at doses producing maximal effective analgesic and antiscratch effects, U50,488H, MOM-SalB, and 42B, but not nalfurafine, promoted KOR phosphorylation at T363 and S369 in mouse brains, as detected by immunoblotting with phospho-KOR-specific antibodies. In addition, at doses producing maximal effective analgesic and antiscratch effects, U50,488H, MOM-SalB, and 42B, but not nalfurafine, caused KOR internalization in the ventral tegmental area of a mutant mouse line expressing a fusion protein of KOR conjugated at the C-terminus with tdTomato (KtdT). We have reported previously that the KOR agonists U50,488H and methoxymethyl salvinorin B (MOM-SalB) cause CPA, whereas nalfurafine and 42B do not, at doses effective for analgesic and antiscratch effects. Taken together, these data reveal a lack of connection between agonist-promoted KOR-mediated CPA with agonist-induced KOR phosphorylation and internalization in male mice.
Role of Selective Histone Deacetylase 6 Inhibitor ACY-1215 in Cancer and Other Human Diseases
Authors: Li Jianglei , Yu Meihong , Fu Shifeng , Liu Deliang , Tan Yuyong
Published: May 2022

The deacetylation process regulated by histone deacetylases (HDACs) plays an important role in human health and diseases. HDAC6 belongs to the Class IIb of HDACs family, which mainly modifies non-histone proteins located in the cytoplasm. HDAC6 plays a key role in tumors, neurological diseases, and inflammatory diseases. Therefore, targeting HDAC6 has become a promising treatment strategy in recent years. ACY-1215 is the first orally available highly selective HDAC6 inhibitor, and its efficacy and therapeutic effects are being continuously verified. This review summarizes the research progress of ACY-1215 in cancer and other human diseases, as well as the underlying mechanism, in order to guide the future clinical trials of ACY-1215 and more in-depth mechanism researches.
Based on Network Pharmacology and Gut Microbiota Analysis to Investigate the Mechanism of the Laxative Effect of Pterostilbene on Loperamide-Induced Slow Transit Constipation in Mice
Authors: Yao Zhiwei , Fu Siqi , Ren Bingbing , Ma Lushun , Sun Daqing
Published: May 2022

Background: Pterostilbene (PTE) is a natural polyphenol compound that has been proven to improve intestinal inflammation, but its laxative effect on slow transit constipation (STC) has never been studied. This study aims to investigate the laxative effect of PTE on loperamide (LOP)-induced STC mice and its influence on intestinal microbes through a combination of network pharmacological analysis and experimental verification.

Material and Methods: PTE was used to treat LOP-exposed mice, and the laxative effect of PTE was evaluated by the total intestinal transit time and stool parameters. The apoptosis of Cajal interstitial cells (ICCs) was detected by immunofluorescence. The mechanism of PTE’s laxative effect was predicted by network pharmacology analysis. We used western blot technology to verify the predicted hub genes and pathways. Malondialdehyde (MDA) and GSH-Px were tested to reflect oxidative stress levels and the changes of gut microbiota were detected by 16S rDNA high-throughput sequencing.

Results: PTE treatment could significantly improve the intestinal motility disorder caused by LOP. Apoptosis of ICCs increased in the STC group, but decreased significantly in the PTE intervention group. Through network pharmacological analysis, PTE might reduce the apoptosis of ICCs by enhancing PI3K/AKT and Nrf2/HO-1 signaling, and improve constipation caused by LOP. In colon tissues, PTE improved the Nrf2/HO-1 pathway and upregulated the phosphorylation of AKT. The level of MDA increased and GSH-Px decreased in the STC group, while the level of oxidative stress was significantly reduced in the PTE treatment groups. PTE also promoted the secretion of intestinal hormone and restored the microbial diversity caused by LOP.

Conclusion: Pterostilbene ameliorated the intestinal motility disorder induced by LOP, this effect might be achieved by inhibiting oxidative stress-induced apoptosis of ICCs through the PI3K/AKT/Nrf2 signaling pathway.
Micro-Movement Measured by Laser Heterodyne Interferometer Based on Acousto-Optic Effect
Authors: Lin Bailin , Dai Wei , Sun Jun , Xiao Mengting , He Zihan , Wu Jianjian , Chen Xinqi
Published: May 2022

In this experiment, the stable output of a dual-frequency laser source is obtained by an acousto-optic modulator due to the Bragg diffraction effect. Furthermore, the non-polarized dual-laser heterodyne interferometer is designed to measure the micro-movement of stacked piezoelectric (PZT) ceramic. This micro-movement can be dynamically determined by comparing the phase difference between the conference beam and measuring beam. The results indicate that the micro-movement of PZT ceramic changes linearly with the driven-voltage in the range of 0–30 V and the sensitivity of movement to voltage is 58.3 nm/V, which is very close to the theoretical value and this laser heterodyne interferometer can be applied for calibrating parameters of PZT ceramic.
Raman Spectroscopy Enables Non-invasive and Confirmatory Diagnostics of Aluminum and Iron Toxicities in Rice
Authors: Higgins Samantha , Biswas Sudip , Goff Nicolas K. , Septiningsih Endang M. , Kurouski Dmitry
Published: May 2022

Metal toxicities can be detrimental to a plant health, as well as to the health of animals and humans that consume such plants. Metal content of plants can be analyzed using colorimetric, atomic absorption- or mass spectroscopy-based methods. However, these techniques are destructive, costly and laborious. In the current study, we investigate the potential of Raman spectroscopy (RS), a modern spectroscopic technique, for detection and identification of metal toxicities in rice. We modeled medium and high levels of iron and aluminum toxicities in hydroponically grown plants. Spectroscopic analyses of their leaves showed that both iron and aluminum toxicities can be detected and identified with ∼100% accuracy as early as day 2 after the stress initiation. We also showed that diagnostics accuracy was very high not only on early, but also on middle (day 4–day 8) and late (day 10–day 14) stages of the stress development. Importantly this approach only requires an acquisition time of 1 s; it is non-invasive and non-destructive to plants. Our findings suggest that if implemented in farming, RS can enable pre-symptomatic detection and identification of metallic toxins that would lead to faster recovery of crops and prevent further damage.
Spatial Mapping of Plant N-Glycosylation Cellular Heterogeneity Inside Soybean Root Nodules Provided Insights Into Legume-Rhizobia Symbiosis
Authors: Veličković Dušan , Liao Yen-Chen , Thibert Stephanie , Veličković Marija , Anderton Christopher , Voglmeir Josef , Stacey Gary , Zhou Mowei
Published: May 2022

Although ubiquitously present, information on the function of complex N-glycan posttranslational modification in plants is very limited and is often neglected. In this work, we adopted an enzyme-assisted matrix-assisted laser desorption/ionization mass spectrometry imaging strategy to visualize the distribution and identity of N-glycans in soybean root nodules at a cellular resolution. We additionally performed proteomics analysis to probe the potential correlation to proteome changes during symbiotic rhizobia-legume interactions. Our ion images reveal that intense N-glycosylation occurs in the sclerenchyma layer, and inside the infected cells within the infection zone, while morphological structures such as the cortex, uninfected cells, and cells that form the attachment with the root are fewer N-glycosylated. Notably, we observed different N-glycan profiles between soybean root nodules infected with wild-type rhizobia and those infected with mutant rhizobia incapable of efficiently fixing atmospheric nitrogen. The majority of complex N-glycan structures, particularly those with characteristic Lewis-a epitopes, are more abundant in the mutant nodules. Our proteomic results revealed that these glycans likely originated from proteins that maintain the redox balance crucial for proper nitrogen fixation, but also from enzymes involved in N-glycan and phenylpropanoid biosynthesis. These findings indicate the possible involvement of Lewis-a glycans in these critical pathways during legume-rhizobia symbiosis.
The Effects of Brief Heat During Early Booting on Reproductive, Developmental, and Chlorophyll Physiological Performance in Common Wheat (Triticum aestivum L.)
Authors: Xu Jiemeng , Lowe Claudia , Hernandez-Leon Sergio G. , Dreisigacker Susanne , Reynolds Matthew P. , Valenzuela-Soto Elisa M. , Paul Matthew J. , Heuer Sigrid
Published: May 2022

Rising temperatures due to climate change threaten agricultural crop productivity. As a cool-season crop, wheat is heat-sensitive, but often exposed to high temperatures during the cultivation period. In the current study, a bread wheat panel of spring wheat genotypes, including putatively heat-tolerant Australian and CIMMYT genotypes, was exposed to a 5-day mild (34°C/28°C, day/night) or extreme (37°C/27°C) heat stress during the sensitive pollen developmental stage. Worsening effects on anther morphology were observed, as heat stress increased from mild to extreme. Even under mild heat, a significant decrease in pollen viability and number of grains per spike from primary spike was observed compared with the control (21°C/15°C), with Sunstar and two CIMMYT breeding lines performing well. A heat-specific positive correlation between the two traits indicates the important role of pollen fertility for grain setting. Interestingly, both mild and extreme heat induced development of new tillers after the heat stress, providing an alternative sink for accumulated photosynthates and significantly contributing to the final yield. Measurements of flag leaf maximum potential quantum efficiency of photosystem II (Fv/Fm) showed an initial inhibition after the heat treatment, followed by a full recovery within a few days. Despite this, model fitting using chlorophyll soil plant analysis development (SPAD) measurements showed an earlier onset or faster senescence rate under heat stress. The data presented here provide interesting entry points for further research into pollen fertility, tillering dynamics, and leaf senescence under heat. The identified heat-tolerant wheat genotypes can be used to dissect the underlying mechanisms and breed climate-resilient wheat.
Coupling Effects of Nitrogen and Irrigation Levels on Growth Attributes, Nitrogen Use Efficiency, and Economics of Cotton
Authors: Kumar Rakesh , Pareek Narendra Kumar , Kumar Uttam , Javed Talha , Al-Huqail Asma A. , Rathore Vijay Singh , Nangia Vinay , Choudhary Ashok , Nanda Gangadhar , Ali Hayssam M. , Siddiqui Manzer H. , Youesf Ahmed F. , Telesiński Arkadiusz , Kalaji Hazem M.
Published: May 2022

Nitrogen (N) fertilization plays a pivotal role in physiomorphological attributes and yield formation of field-grown cotton (Gossypium hirsutumL.), but little is known of its interaction with irrigation levels. Therefore, this study was conducted with an objective of evaluating the impact of irrigation and nitrogen levels on growth attributes and nitrogen use efficiency ofBtcotton (Gossypiumspp.) in the hot arid region. The experiment consisted of a factorial arrangement of three irrigation levels (200, 400, and 600 mm) and four nitrogen rates (0, 75, 150, and 225 kg ha–1) in a split-plot design with three replications. Nitrogen fertilization and irrigation levels influenced cotton growth attributes and yield. The highest leaf area index, dry matter accumulation, crop growth rate, and relative growth rate were achieved at 225 kg N ha–1and irrigation level 600 mm as compared to other experimental treatments. Similarly, nitrogen uptake and content by seed, lint, and stalk and total nitrogen uptake recorded maximum at 225 kg N ha–1and irrigation level 600 mm. Interestingly, the treatment of 600 mm of irrigation and 150 kg N ha–1displayed significant increase in nitrogen use efficiency indices such as agronomic efficiency of nitrogen (AEN) and recovery efficiency of nitrogen (REN), while partial factor productivity of nitrogen (PFPN) and internal nitrogen use efficiency (iNUE) were significantly higher with application of 600 mm of irrigation and nitrogen application rate of 75 kg ha–1. Application of 600 mm of irrigation along with 225 kg N ha–1resulted in significant increase in gross return, net return, and B:C ratio than any other treatment combinations. So, application of 600 mm of irrigation along with 225 kg N ha–1could be recommended for achieving higher growth and yield, as well as profitability ofBtcotton under hot arid region and similar agroecologies.