bluuebunny/crossref_metadata_2025 huggingface dataset:
PepSim: T-cell cross-reactivity prediction via comparison of peptide sequence and peptide-HLA structure
Authors: Hall-Swan Sarah , Slone Jared , Rigo Mauricio M. , Antunes Dinler A. , Lizée Gregory , Kavraki Lydia E.
Published: April 2023

Introduction

Peptide-HLA class I (pHLA) complexes on the surface of tumor cells can be targeted by cytotoxic T-cells to eliminate tumors, and this is one of the bases for T-cell-based immunotherapies. However, there exist cases where therapeutic T-cells directed towards tumor pHLA complexes may also recognize pHLAs from healthy normal cells. The process where the same T-cell clone recognizes more than one pHLA is referred to as T-cell cross-reactivity and this process is driven mainly by features that make pHLAs similar to each other. T-cell cross-reactivity prediction is critical for designing T-cell-based cancer immunotherapies that are both effective and safe.

Methods

Here we present PepSim, a novel score to predict T-cell cross-reactivity based on the structural and biochemical similarity of pHLAs.

Results and discussion

We show our method can accurately separate cross-reactive from non-crossreactive pHLAs in a diverse set of datasets including cancer, viral, and self-peptides. PepSim can be generalized to work on any dataset of class I peptide-HLAs and is freely available as a web server at pepsim.kavrakilab.org.
Toward transplantation tolerance with adipose tissue-derived therapeutics
Authors: Cheng Hui-Yun , Anggelia Madonna Rica , Lin Cheng-Hung , Wei Fu-Chan
Published: April 2023

Solid organ and composite tissue allotransplanation have been widely applied to treat end-stage organ failure and massive tissue defects, respectively. Currently there are a lot of research endeavors focusing on induction of transplantation tolerance, to relieve the burden derived from long-term immunosuppressant uptake. The mesenchymal stromal cells (MSCs) have been demonstrated with potent immunomodulatory capacities and applied as promising cellular therapeutics to promote allograft survival and induce tolerance. As a rich source of adult MSCs, adipose tissue provides additional advantages of easy accessibility and good safety profile. In recent years, the stromal vascular fraction (SVF) isolated from adipose tissues following enzymatic or mechanical processing without in vitro culture and expansion has demonstrated immunomodulatory and proangiogenic properties. Furthermore, the secretome of AD-MSCs has been utilized in transplantation field as a potential “cell-free” therapeutics. This article reviews recent studies that employ these adipose-derived therapeutics, including AD-MSCs, SVF, and secretome, in various aspects of organ and tissue allotransplantation. Most reports validate their efficacies in prolonging allograft survival. Specifically, the SVF and secretome have performed well for graft preservation and pretreatment, potentially through their proangiogenic and antioxidative capacities. In contrast, AD-MSCs were suitable for peri-transplantation immunosuppression. The proper combination of AD-MSCs, lymphodepletion and conventional immunosuppressants could consistently induce donor-specific tolerance to vascularized composite allotransplants (VCA). For each type of transplantation, optimizing the choice of therapeutics, timing, dose, and frequency of administration may be required. Future progress in the application of adipose-derived therapeutics to induce transplantation tolerance will be further benefited by continued research into their mechanisms of action and the development of standardized protocols for isolation methodologies, cell culture, and efficacy evaluation.
Immune desert in MMR-deficient tumors predicts poor responsiveness of immune checkpoint inhibition
Authors: Zheng Guoxing , Lu Yingsi , Yang Zheng , Chen Hong , Liang Qian , Zhu Qingqing , Li Yan , Xiao Xing , He Zhuzhen , Zhu Yifan , Li Bo , Huang Leilei , Dong Nan , Hu Shuang , Pan Yihang , Zhang Changhua , Zhu Chengming
Published: April 2023

Background

Although many efforts have been devoted to identify biomarkers to predict the responsiveness of immune checkpoint inhibitors, including expression of programmed death-ligand 1 (PD-L1) and major histocompatibility complex (MHC) I, microsatellite instability (MSI), mismatch repair (MMR) defect, tumor mutation burden (TMB), tertiary lymphoid structures (TLSs), and several transcriptional signatures, the sensitivity of these indicators remains to be further improved.

Materials and methods

Here, we integrated T-cell spatial distribution and intratumor transcriptional signals in predicting the response to immune checkpoint therapy in MMR-deficient tumors including tumors of Lynch syndrome (LS).

Results

In both cohorts, MMR-deficient tumors displayed personalized tumor immune signatures, including inflamed, immune excluded, and immune desert, which were not only individual-specific but also organ-specific. Furthermore, the immune desert tumor exhibited a more malignant phenotype characterized by low differentiation adenocarcinoma, larger tumor sizes, and higher metastasis rate. Moreover, the tumor immune signatures associated with distinct populations of infiltrating immune cells were comparable to TLSs and more sensitive than transcriptional signature gene expression profiles (GEPs) in immunotherapy prediction. Surprisingly, the tumor immune signatures might arise from the somatic mutations. Notably, patients with MMR deficiency had benefited from the typing of immune signatures and later immune checkpoint inhibition.

Conclusion

Our findings suggest that compared to PD-L1 expression, MMR, TMB, and GEPs, characterization of the tumor immune signatures in MMR-deficient tumors improves the efficiency of predicting the responsiveness of immune checkpoint inhibition.
Long COVID brain fog and muscle pain are associated with longer time to clearance of SARS-CoV-2 RNA from the upper respiratory tract during acute infection
Authors: Antar Annukka A. R. , Yu Tong , Demko Zoe O , Hu Chen , Tornheim Jeffrey A. , Blair Paul W. , Thomas David L. , Manabe Yukari C.
Published: April 2023

Introduction

The incidence of long COVID is substantial, even in people with mild to moderate acute COVID-19. The role of early viral kinetics in the subsequent development of long COVID is largely unknown, especially in individuals who were not hospitalized for acute COVID-19.

Methods

Seventy-three non-hospitalized adult participants were enrolled within approximately 48 hours of their first positive SARS-CoV-2 RT-PCR test, and mid-turbinate nasal and saliva samples were collected up to 9 times within the first 45 days after enrollment. Samples were assayed for SARS-CoV-2 using RT-PCR and additional SARS-CoV-2 test results were abstracted from the clinical record. Each participant indicated the presence and severity of 49 long COVID symptoms at 1-, 3-, 6-, 12-, and 18-months post-COVID-19 diagnosis. Time from acute COVID-19 illness onset to SARS-CoV-2 RNA clearance greater or less than 28 days was tested for association with the presence or absence of each of 49 long COVID symptoms at 90+ days from acute COVID-19 symptom onset.

Results

Self-reported brain fog and muscle pain at 90+ days after acute COVID-19 onset were negatively associated with viral RNA clearance within 28 days of acute COVID-19 onset with adjustment for age, sex, BMI ≥ 25, and COVID vaccination status prior to COVID-19 (brain fog: aRR 0.46, 95% CI 0.22-0.95; muscle pain: aRR 0.28, 95% CI 0.08-0.94). Participants reporting higher severity brain fog or muscle pain at 90+ days after acute COVID-19 onset were less likely to have cleared SARS-CoV-2 RNA within 28 days. The acute viral RNA decay trajectories of participants who did and did not later go on to experience brain fog 90+ days after acute COVID-19 onset were distinct.

Discussion

This work indicates that at least two long COVID symptoms - brain fog and muscle pain – at 90+ days from acute COVID-19 onset are specifically associated with prolonged time to clearance of SARS-CoV-2 RNA from the upper respiratory tract during acute COVID-19. This finding provides evidence that delayed immune clearance of SARS-CoV-2 antigen or greater amount or duration of viral antigen burden in the upper respiratory tract during acute COVID-19 are directly linked to long COVID. This work suggests that host-pathogen interactions during the first few weeks after acute COVID-19 onset have an impact on long COVID risk months later.
Identification of calcium and integrin-binding protein 1 as a reprogrammed glucose metabolism mediator to restrict immune cell infiltration in the stromal compartment of pancreatic ductal adenocarcinoma
Authors: Ma Junrui , Song Yue , Zhuang Tongtao , Yang Hao , Yang Xiaobao , Zheng Juanjuan , Luo Jiajun , Xia Yihan , Fei Xuefeng , Chan David W. , Wu Di , Xu Peiqing , Ni Peihua , Dai Jing , Xu Dakang , Hu Yiqun
Published: April 2023

An increasing body of evidence has suggested that reprogrammed metabolism plays a critical role in the progression of pancreatic ductal adenocarcinoma (PDAC) by affecting the tumor and stromal cellular components in the tumor microenvironment (TME). By analyzing the KRAS pathway and metabolic pathways, we found that calcium and integrin-binding protein 1 (CIB1) corresponded with upregulation of glucose metabolism pathways and was associated with poor prognosis in patients with PDAC from The Cancer Genome Atlas (TCGA). Elevated CIB1 expression combined with upregulated glycolysis, oxidative phosphorylation (Oxphos), hypoxia pathway activation, and cell cycle promoted PDAC tumor growth and increased tumor cellular com-ponents. Furthermore, we confirmed the mRNA overexpression of CIB1 and co-expression of CIB1 and KRAS mutation in cell lines from the Expression Atlas. Subsequently, immunohistochemistry staining from the Human Protein Atlas (HPA) showed that high expression of CIB1 in tumor cells was associated with an increased tumor compartment and reduced stromal cellular abundance. Furthermore, using multiplexed immunohistochemistry (mIHC), we verified that low stromal abundance was correlated with low infiltration of CD8+ PD-1− T cells which led to suppressed anti-tumor immunity. Overall, our findings identify CIB1 as a metabolic pathway-mediated factor for the restriction of immune cell infiltration in the stromal compartment of PDAC and highlight the potential value of CIB1 as a prognostic biomarker involved in metabolic reprogramming and immune modulation.
Inactivated ostreid herpesvirus-1 induces an innate immune response in the Pacific oyster, Crassostrea gigas, hemocytes
Authors: Delisle Lizenn , Rolton Anne , Vignier Julien
Published: April 2023

Infectious diseases are a major constraint to the expansion of shellfish production worldwide. Pacific oyster mortality syndrome (POMS), a polymicrobial disease triggered by the Ostreid herpesvirus-1 (OsHV-1), has devastated the global Pacific oyster (Crassostrea gigas) aquaculture industry. Recent ground-breaking research revealed that C. gigas possess an immune memory, capable of adaption, which improves the immune response upon a second exposure to a pathogen. This paradigm shift opens the door for developing ‘vaccines’ to improve shellfish survival during disease outbreaks. In the present study, we developed an in-vitro assay using hemocytes – the main effectors of the C. gigas immune system – collected from juvenile oysters susceptible to OsHV-1. The potency of multiple antigen preparations (e.g., chemically and physically inactivated OsHV-1, viral DNA, and protein extracts) to stimulate an immune response in hemocytes was evaluated using flow cytometry and droplet digital PCR to measure immune-related subcellular functions and gene expression, respectively. The immune response to the different antigens was benchmarked against that of hemocytes treated with Poly (I:C). We identified 10 antigen preparations capable of inducing immune stimulation in hemocytes (ROS production and positively expressed immune- related genes) after 1 h of exposure, without causing cytotoxicity. These findings are significant, as they evidence the potential for priming the innate immunity of oysters using viral antigens, which may enable cost-effective therapeutic treatment to mitigate OsHV-1/POMS. Further testing of these antigen preparations using an in-vivo infection model is essential to validate promising candidate pseudo-vaccines.
Host immune responses in aged rhesus macaques against BBV152, an inactivated SARS-CoV-2 vaccine, and cross-neutralization with beta and delta variants
Authors: Patil Dilip R. , Shete Anita M. , Yadav Pragya D. , Sapkal Gajanan N. , Deshpande Gururaj R. , Kaushal Himanshu , Mohandas Sreelekshmy , Fulari Siddharam , Jain Rajlaxmi , Kumar Ajay , Abraham Priya
Published: April 2023

The magnitude and duration of immune response to COVID-19 vaccination in older adults are known to be adversely affected due to immunosenescence and inflammaging. The threat of emerging variants warrants studies on immune response in older adults to primary vaccination and booster doses so as to understand the effectiveness of vaccines in countering the threat of emerging variants. Non-human primates (NHPs) are ideal translational models, as the immunological responses in NHPs are similar to those in humans, so it enables us to understand host immune responses to the vaccine. We initially studied humoral immune responses in aged rhesus macaques employing a three-dose regimen of BBV152, an inactivated SARS-CoV-2 vaccine. Initially, the study investigated whether the third dose enhances the neutralizing antibody (Nab) titer against the homologous virus strain (B.1) and variants of concern (Beta and Delta variants) in aged rhesus macaques immunized with BBV152, adjuvanted with Algel/Algel-IMDG (imidazoquinoline). Later, we also attempted to understand cellular immunity in terms of lymphoproliferation against γ-inactivated SARS-CoV-2 B.1 and delta in naïve and vaccinated rhesus macaques after a year of the third dose. Following the three-dose regimen with 6 µg of BBV152 with Algel-IMDG, animals had increased Nab responses across all SARS-CoV-2 variants studied, which suggested the importance of booster dose for the enhanced immune response against SARS-CoV-2-circulating variants. The study also revealed the pronounced cellular immunity against B.1 and delta variants of SARS-CoV-2 in the aged rhesus macaques even after a year of vaccination.
The inflammatory injury in the striatal microglia-dopaminergic-neuron crosstalk involved in Tourette syndrome development
Authors: Wang Xueming , Liu Xiumei , Chen Liangliang , Zhang Xiaoling
Published: April 2023

Background

Tourette syndrome (TS) is associated with immunological dysfunction. The DA system is closely related to TS development, or behavioral stereotypes. Previous evidence suggested that hyper-M1-polarized microglia may exist in the brains of TS individuals. However, the role of microglia in TS and their interaction with dopaminergic neurons is unclear. In this study, we applied iminodipropionitrile (IDPN) to establish a TS model and focused on the inflammatory injury in the striatal microglia-dopaminergic-neuron crosstalk.

Methods

Male Sprague–Dawley rats were intraperitoneally injected with IDPN for seven consecutive days. Stereotypic behavior was observed to verify the TS model. Striatal microglia activation was evaluated based on different markers and expressions of inflammatory factors. The striatal dopaminergic neurons were purified and co-cultured with different microglia groups, and dopamine-associated markers were assessed.

Results

First, there was pathological damage to striatal dopaminergic neurons in TS rats, as indicated by decreased expression of TH, DAT, and PITX3. Next, the TS group showed a trend of increased Iba-1 positive cells and elevated levels of inflammatory factors TNF-α and IL-6, as well as an enhanced M1-polarization marker (iNOS) and an attenuated M2-polarization marker (Arg-1). Finally, in the co-culture experiment, IL-4-treated microglia could upregulate the expression of TH, DAT, and PITX3 in striatal dopaminergic neurons vs LPS-treated microglia. Similarly, the TS group (microglia from TS rats) caused a decreased expression of TH, DAT, and PITX3 compared with the Sham group (microglia from control rats) in the dopaminergic neurons.

Conclusion

In the striatum of TS rats, microglia activation is M1 hyperpolarized, which transmits inflammatory injury to striatal dopaminergic neurons and disrupts normal dopamine signaling.
Live and inactivated Piscirickettsia salmonis activated nutritional immunity in Atlantic salmon (Salmo salar)
Authors: Martínez Danixa , Oyarzún-Salazar Ricardo , Quilapi Ana María , Coronado José , Enriquez Ricardo , Vargas-Lagos Carolina , Oliver Cristian , Santibañez Natacha , Godoy Marcos , Muñoz José Luis , Vargas-Chacoff Luis , Romero Alex
Published: April 2023

Nutritional immunity regulates the homeostasis of micronutrients such as iron, manganese, and zinc at the systemic and cellular levels, preventing the invading microorganisms from gaining access and thereby limiting their growth. Therefore, the objective of this study was to evaluate the activation of nutritional immunity in specimens of Atlantic salmon (Salmo salar) that are intraperitoneally stimulated with both live and inactivated Piscirickettsia salmonis. The study used liver tissue and blood/plasma samples on days 3, 7, and 14 post-injections (dpi) for the analysis. Genetic material (DNA) of P. salmonis was detected in the liver tissue of fish stimulated with both live and inactivated P. salmonis at 14 dpi. Additionally, the hematocrit percentage decreased at 3 and 7 dpi in fish stimulated with live P. salmonis, unchanged in fish challenged with inactivated P. salmonis. On the other hand, plasma iron content decreased during the experimental course in fish stimulated with both live and inactivated P. salmonis, although this decrease was statistically significant only at 3 dpi. Regarding the immune-nutritional markers such as tfr1, dmt1, and ireg1 were modulated in the two experimental conditions, compared to zip8, ft-h, and hamp, which were down-regulated in fish stimulated with live and inactivated P. salmonis during the course experimental. Finally, the intracellular iron content in the liver increased at 7 and 14 dpi in fish stimulated with live and inactivated P. salmonis, while the zinc content decreased at 14 dpi under both experimental conditions. However, stimulation with live and inactivated P. salmonis did not alter the manganese content in the fish. The results suggest that nutritional immunity does not distinguish between live and inactivated P. salmonis and elicits a similar immune response. Probably, this immune mechanism would be self-activated with the detection of PAMPs, instead of a sequestration and/or competition of micronutrients by the living microorganism.
Rice stripe virus p2 protein interacts with ATG5 and is targeted for degradation by autophagy
Authors: Zhang Xiangxiang , Wan Qionglian , Rui Penghuan , Lu Yuwen , Sun Zongtao , Chen Jianping , Wang Yunyue , Yan Fei
Published: April 2023

Autophagy can be induced by viral infection and plays antiviral roles in plants, but the underlying mechanism is not well understood. In our previous reports, we have demonstrated that the plant ATG5 plays an essential role in activating autophagy in rice stripe virus (RSV)-infected plants. We also showed that eIF4A, a negative factor of autophagy, interacts with and inhibits ATG5. We here found that RSV p2 protein interacts with ATG5 and can be targeted by autophagy for degradation. Expression of p2 protein induced autophagy and p2 protein was shown to interfere with the interaction between ATG5 and eIF4A, while eIF4A had no effect on the interaction between ATG5 and p2. These results indicate an additional information on the induction of autophagy in RSV-infected plants.
Clinical-pathological features and muscle imaging findings in 36 Chinese patients with rimmed vacuolar myopathies: case series study and review of literature
Authors: Wei Xiao-jing , Sun Hui , Miao Jing , Qiu Ru-qing , Jiang Zong-zhi , Ma Zhen-wei , Sun Wei , Yu Xue-fan
Published: April 2023

Introduction

Rimmed vacuolar myopathies (RVMs) are a group of genetically heterogeneous diseases that share histopathological characteristics on muscle biopsy, including the aberrant accumulation of autophagic vacuoles. However, the presence of non-coding sequences and structural mutations, some of which remain undetectable, confound the identification of pathogenic mutations responsible for RVMs. Therefore, we assessed the clinical profiles and muscle magnetic resonance imaging (MRI) changes in 36 Chinese patients with RVMs, emphasizing the role of muscle MRI in disease identification and differential diagnosis to propose a comprehensive literature-based imaging pattern to facilitate improved diagnostic workup.

Methods

All patients presented with rimmed vacuoles with varying degrees of muscular dystrophic changes and underwent a comprehensive evaluation using clinical, morphological, muscle MRI and molecular genetic analysis. We assessed muscle changes in the Chinese RVMs and provided an overview of the RVMs, focusing on the patterns of muscle involvement on MRI.

Results

A total of 36 patients, including 24 with confirmed distal myopathy and 12 with limb-girdle phenotype, had autophagic vacuoles with RVMs. Hierarchical clustering of patients according to the predominant effect of the distal or proximal lower limbs revealed that most patients with RVMs could be distinguished. GNE myopathy was the most prevalent form of RVMs observed in this study. Moreover, MRI helped identify the causative genes in some diseases (e.g., desminopathy and hereditary myopathy with early respiratory failure) and confirmed the pathogenicity of a novel mutation (e.g., adult-onset proximal rimmed vacuolar titinopathy) detected using next-generation sequencing.

Discussion

Collectively, our findings expand our knowledge of the genetic spectrum of RVMs in China and suggest that muscle imaging should be an integral part of assisting genetic testing and avoiding misdiagnosis in the diagnostic workup of RVM.
MRI characteristics of lumbosacral dural arteriovenous fistulas
Authors: Zhu Jinyu , Zhu Wangshu , Li Minghua , Wei Xiaoer , Chen Zheyi , Li Yuehua
Published: April 2023

Background and purpose

Spinal dural arteriovenous fistulas located in the lumbosacral region are rare and present with nonspecific clinical signs. The purpose of this study was to find out the specific radiologic features of these fistulas.

Methods

We retrospectively reviewed the clinical and radiological data of 38 patients diagnosed with lumbosacral spinal dural arteriovenous fistulas in our institution from September 2016 to September 2021. All patients underwent time-resolved contrast-enhanced three-dimensional MRA and DSA examinations, and were treated with either endovascular or neurosurgical strategies.

Results

Most of the patients (89.5%) had motor or sensory disorders in both lower limbs as the first symptoms. On MRA, the dilated filum terminale vein or radicular vein was seen in 23/30 (76.7%) patients with lumbar spinal dural arteriovenous fistulas and 8/8 (100%) patients with sacral spinal dural arteriovenous fistulas. T2W intramedullary abnormally high signal intensity areas were found in all lumbosacral spinal dural arteriovenous fistula patients, with involvement of the conus present in 35/38 (92.1%) patients. The “missing piece sign” in the intramedullary enhancement area was seen in 29/38 (76.3%) patients.

Conclusion

Dilatation of the filum terminale vein or radicular vein is powerful evidence for diagnosis of lumbosacral spinal dural arteriovenous fistulas, especially for sacral spinal dural arteriovenous fistulas. T2W intramedullary hyperintensity in the thoracic spinal cord and conus, and the missing-piece sign could be indicative of lumbosacral spinal dural arteriovenous fistula.
Is repetitive systemic corticosteroid therapy effective for idiopathic sudden sensorineural hearing loss? a retrospective study
Authors: Yamamoto Kengo , Kurioka Takaomi , Ohki Motofumi , Sano Hajime , Yamashita Taku
Published: April 2023

Introduction

Some idiopathic sudden sensorineural hearing loss (ISSHL) cases experience repetitive systemic corticosteroid treatment, but studies focusing on repetitive systemic corticosteroid administration have not been reported. Thus, we investigated the clinical characteristics and usefulness of repetitive systemic corticosteroid treatment in ISSHL cases.

Methods

We reviewed the medical records of 103 patients who received corticosteroids only in our hospital (single-treatment group), and 46 patients who presented at our hospital after receiving corticosteroids in a nearby clinic and were subsequently treated with corticosteroids again in our hospital (repetitive-treatment group). Clinical backgrounds, hearing thresholds, and hearing prognosis were assessed.

Results

The final hearing outcomes were not different between the two groups. Further, in the repetitive-treatment group, statistical differences were found between the good and poor prognosis groups in the number of days to start corticosteroid administration (p = 0.03), the dose of corticosteroid (p = 0.02), and the duration of corticosteroid administration (p = 0.02) at the previous facility. Multivariate analysis revealed a significant difference in the dose of corticosteroids administered by the previous clinic (p = 0.004).

Conclusion

The repetitive systemic corticosteroid administration might play a supplementary role in hearing improvement, and initial sufficient corticosteroid administration would lead to good hearing outcomes in an early phase of ISSHL.
Effects of 12 weeks of Tai Chi on neuromuscular responses and postural control in elderly patients with sarcopenia: a randomized controlled trial
Authors: Huang Dunbing , Ke Xiaohua , Jiang Cai , Song Wei , Feng Jing , Zhou Huiting , Zhang Rui , Zhang Anren , Lan Fujun
Published: April 2023

Objective

To explore the effect of 12 weeks of Tai Chi on neuromuscular responses and postural control in elderly patients with sarcopenia.

Methods

One hundred and twenty-four elderly patients with sarcopenia from ZheJiang Hospital and surrounding communities were selected, however, 64 were later disqualified. Sixty elderly patients with sarcopenia were randomly assigned to the Tai Chi group (n = 30) and the control group (n = 30). Both groups received 45-min health education sessions once every 2 weeks for 12 weeks, and the Tai Chi group engaged in 40-min simplified eight-style Tai Chi exercise sessions 3 times per week for 12 weeks. Two assessors who had received professional training and were unaware of the intervention allocation assessed the subjects within 3 days prior to the intervention and within 3 days after completion of the intervention. They chose the unstable platform provided by the dynamic stability test module in ProKin 254 to evaluate the patient’s postural control ability. Meanwhile, surface EMG was utilized to assess the neuromuscular response during this period.

Results

After 12 weeks of intervention, the Tai Chi group showed a significant decrease in neuromuscular response times of the rectus femoris, semitendinosus, anterior tibialis, and gastrocnemius and overall stability index (OSI) compared to before the intervention (p < 0.05), while there was no significant difference in the control group for these indicators before and after intervention (p > 0.05). In addition, these indicators in the Tai Chi group were significantly lower than those in the control group (p < 0.05). The changes in neuromuscular response times of the rectus femoris, semitendinosus, anterior tibialis, and gastrocnemius were positively correlated with the changes in OSI (p < 0.05) in the Tai Chi group, but there were no significant correlations between changes in neuromuscular response times of the aforementioned muscles and changes in OSI in the control group (p < 0.05).

Conclusion

Twelve-weeks of Tai Chi exercise can improve the neuromuscular response of the lower extremities in elderly patients with sarcopenia, shorten their neuromuscular response time when balance is endangered, enhance their dynamic posture control ability, and ultimately reduce the risk of falls.
PD-1 inhibitor combined with radiotherapy and GM-CSF in MSS/pMMR metastatic colon cancer: a case report
Authors: Yang Jiabao , Xing Pengfei , Kong Yuehong , Xu Meiling , Zhang Liyuan
Published: April 2023

Patients with chemo-refractory metastatic colorectal cancer (mCRC) have poor prognoses. The application of programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors encouragingly improved the survival of mCRC patients with microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR). Unfortunately, it was ineffective for mCRC with microsatellite-stable (MSS)/proficient mismatch repair (pMMR), which accounted for 95% of mCRC. Radiotherapy can promote local control by directly killing tumor cells and inducing positive immune activities, which might help synergistically with immunotherapy. We present the report of an advanced MSS/pMMR mCRC patient who had progressive disease (PD) after first-line chemotherapy, palliative surgery and second-line chemotherapy combined with targeted therapy. Then the patient received the therapy of PD-1 inhibitor combined with radiotherapy and granulocyte-macrophage colony-stimulating factor (GM-CSF). According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST1.1), the patient showed a complete response (CR) after triple-combined therapy with progression-free survival (PFS) for more than 2 years so far. The patient had no other significant adverse reactions except for fatigue (Grade 1). The triple-combination therapy provided a promising strategy for metastatic chemo-refractory MSS/pMMR mCRC patients.
Efficacy and safety of CT-guided 125I seed implantation by coplanar template as a salvage therapy for vertebral metastases after failure of external beam radiation therapy: a retrospective study
Authors: Li Peishun , Bai Yunling , Yuan Qianqian , Man Qirong , Xing Chao , Ren Yanchen , Zhang Kaixian
Published: April 2023

Purpose

To evaluate the efficacy safety of computed tomography (CT)-guided 125I seed implantation by coplanar template for vertebral metastases after failure of external beam radiation therapy (EBRT).

Material and methods

Retrospective analysis of the clinical outcomes of 58 patients with vertebral metastases after failure of EBRT, who underwent 125I seed implantation as a salvage treatment with a CT-guided coplanar template-assisted technique from January 2015 to January 2017.

Results

The mean post-operative NRS score decreased significantly at T4w (3.5 ± 0.9, p<0.01), T8w (2.1 ± 0.9, p<0.01), T12w (1.5 ± 0.7, p< 0.01) and T6m (1.2 ± 0.6, p< 0.01) respectively. The local control rates after 3, 6, 9 and 12 months were 100% (58/58), 93.1% (54/58), 87.9% (51/58), and 81% (47/58), respectively. The median overall survival time was 18.52months (95% CI, 16.24-20.8), and 1- and 2-year survival rates were 81% (47/58) and 34.5% (20/58), respectively. By performing a paired t-test analysis, there was no significant difference in D90, V90, D100, V100, V150, V200, GTV volume, CI, EI and HI between preoperative and postoperative (p>0.05).

Conclusions

125I seed implantation can be used as a salvage treatment for patients with vertebral metastases after failure of EBRT.
Risk factors for cardiovascular adverse events from immune checkpoint inhibitors
Authors: Luo Lingli , Liu Yuxin , Lu Jingfen , Zhang Yifei , Fan Gang , Tang Xiaojun , Guo Weiming
Published: April 2023

Immune-related adverse events (irAEs), including skin injury, liver and kidney injury, colitis, as well as cardiovascular adverse events, are a series of complications arising during the treatment of immune checkpoint inhibitors (ICIs). Cardiovascular events are the most urgent and the most critical, as they can end life in a short period of time. With the widespread use of ICIs, the number of immune-related cardiovascular adverse events (irACEs) induced by ICIs has increased. More attention has been paid to irACEs, especially regarding cardiotoxicity, the pathogenic mechanism, diagnosis and treatment. This review aims to assess the risk factors for irACEs, to raise awareness and help with the risk assessment of irACEs at an early stage.
Ion channel gene GJB2 influences the intercellular communication by Up-regulating the SPP1 signaling pathway identified by the single-cell RNA sequencing in lung adenocarcinoma
Authors: Liu Zuo , Xiao Zengtuan , Wang Xiaofei , Zhang Lianmin , Zhang Zhenfa
Published: April 2023

Objective

Firstly, observe the prognostic significance and the biological functional effects of gap junction protein beta 2 (GJB2 or Cx26) in lung adenocarcinoma (LUAD). Subsequently, explore the role played by GJB2 in intercellular communication by single-cell RNA sequencing.

Method

We made a differential analysis of GJB2 expression through public databases and investigated the clinical characteristics and prognostic significance. ESTIMATE analysis and Tumor Immune Estimation Resource (TIMER) database were utilized to illustrate the association of GJB2 with immune infiltration and components of the tumor microenvironment. Gene Ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and Gene set enrichment analysis (GSEA) were performed to study the biological function of GJB2. Cell-cell communication was analyzed using the CellChat R package through sc-RNA data.

Results

GJB2 has an outstanding prognosis value in LUAD and a close relationship was found between GJB2 and immune infiltration in LUAD. GJB2 could participate in several tumor biological processes, including extracellular matrix remodeling and upregulation of multiple cancer-related active pathways. GJB2 related hub-genes influence intercellular communication through the SPP1 signaling pathway.

Conclusion

Our study illustrates one mechanism by which GJB2 exerts its cancer-specific relevant effects, that is, causing changes in intercellular communication through the SPP1 signaling pathway. Blockade of this pathway may limit the functional role of GJB2 and provide us with promising new perceptions for LUAD treatment.
Formulation and validation of a baseline prognostic score for osteosarcoma treated uniformly with a non-high dose methotrexate-based protocol from a low middle income healthcare setting: a single centre analysis of 594 patients
Authors: Ganguly Shuvadeep , Sasi Archana , Khan Shah Alam , Kumar Venkatesan Sampath , Kapoor Love , Sharma Mehar Chand , Mridha Asit , Barwad Adarsh , Thulkar Sanjay , Pushpam Deepam , Bakhshi Sameer
Published: April 2023

Introduction

The outcomes of osteosarcoma in low middle income countries (LMICs) are different due to patients presenting in advanced stages, resource constraints and the use of non-high-dose-methotrexate (HDMTX)-based regimens. This study derived and validated a prognostic score for osteosarcoma that integrates biologic and social factors and is tailored for patients from an LMIC setting using a non-HDMTX-based protocol.

Materials and methods

A retrospective study including osteosarcoma patients enrolled for treatment at a single tertiary care centre in India between 2003-19 was conducted. Baseline biologic and social characteristics were extracted from medical records and survival outcomes were noted. The cohort was randomised into a derivation and validation cohort. Multivariable Cox regression was used to identify baseline characteristics that were independently prognostic for survival outcomes in the derivation cohort. A score was derived from the prognostic factors identified in the derivation cohort and further validated in the validation cohort with estimation of its predictive ability.

Results

594 patients with osteosarcoma were eligible for inclusion in the study. Around one-third of the cohort had metastatic disease with 59% of the patients residing in rural areas. The presence of metastases at baseline (HR 3.39; p<0.001; score=3), elevated serum alkaline phosphatase (SAP) >450 IU/L (HR 1.57; p=0.001; score=1) and baseline tumour size > 10 cm (HR 1.68; p<0.001; score=1) were identified to be independent factors predicting inferior event free survival (EFS) and were included in development of the prognostic score. Patients were categorized as low risk (score 0), intermediate risk (score 1-3) and high risk (4-5). Harrell’s c-indices for the score were 0.682, 0.608 and 0.657 respectively for EFS in the derivation, validation and whole cohort respectively. The timed AUC of ROC was 0.67 for predicting 18-month EFS in the derivation, validation and whole cohorts while that for 36-month EFS were 0.68, 0.66 and 0.68 respectively.

Conclusions

The study describes the outcomes among osteosarcoma patients from an LMIC treated uniformly with a non-HDMTX-based protocol. Tumor size, baseline metastases and SAP were prognostic factors used to derive a score with good predictive value for survival outcomes. Social factors did not emerge as determinants of survival.
Case Report: An NTRK1 fusion-positive embryonal rhabdomyosarcoma: clinical presentations, pathological characteristics and genotypic analyses
Authors: Li Na-Mei , Jiang Shi-He , Zhou Peng , Li Xiao-Hong
Published: April 2023

Rhabdomyosarcoma (RMS) is a prevalent form of soft tissue sarcoma that primarily affects children. Pediatric RMS is characterized by two distinct histological variants: embryonal (ERMS) and alveolar (ARMS). ERMS is a malignant tumor with primitive characteristics resembling the phenotypic and biological features of embryonic skeletal muscles. With the widespread and growing application of advanced molecular biological technologies, such as next-generation sequencing (NGS), it has been possible to determine the oncogenic activation alterations of many tumors. Specifically for soft tissue sarcomas, the determination of tyrosine kinase gene and protein related changes can be used as diagnostic aids and may be used as predictive markers for targeted tyrosine kinase inhibition therapy. Our study reports a rare and exceptional case of an 11-year-old patient diagnosed with ERMS, who tested positive for MEF2D-NTRK1 fusion. The case report presents a comprehensive overview of the clinical, radiographic, histopathological, immunohistochemical, and genetic characteristics of a palpebral ERMS. Furthermore, this study sheds light on an uncommon occurrence of NTRK1 fusion-positive ERMS, which may provide theoretical basis for therapy and prognosis.
Case Report: Successful treatment of external beam radiation-induced optic papillopathy with intravitreal anti-VEGF
Authors: Carey Andrew R.
Published: April 2023

Three cases of optic disc edema arising from radiation optic neuropathy isolated to the intra-ocular optic nerve following external beam radiation for head and neck squamous cell carcinoma are presented. A literature review of the etiology, presentation, and treatment is included for discussion, along with proposed diagnostic criteria.
Surface electromyographic characteristics of forearm muscles after ulnar and radius fracture inchildren
Authors: Qiu Hailing , Li Fanling , Zhang Siqi , Xiao Sheng , Liu Haobo , Chen Shuangxi , Li Xin , Fang Ke , Wen Jie , Li Tingzhi
Published: April 2023

Objective

To evaluate the characteristics of forearm muscle activity in children with ulnar and radius fractures during different follow-up periods by surface electromyography.

Methods

A retrospective analysis was performed on 20 children with ulnar and radius fractures treated with an elastic intramedullary nail from October 2020 to December 2021. All children were treated with transcubital casts after surgery. At 2 months and before taking out the elastic intramedullary nail, surface electromyographic signals were collected on the flexor/extension of the wrist and the maximum arbitrary isometric contraction of the grip strength in the forearm flexor and extensor muscles of the forearm. The root-mean-square values and integrated EMG values of the superficial flexor and extensor digitalis of the healthy side and the affected side were collected at the last follow-up and 2 months after surgery, and the co-systolic ratio was calculated. The root-mean-square values and co-systolic ratio were compared and analyzed, and the Mayo wrist function score was evaluated.

Results

The mean follow-up time was (8.4 ± 2.85) months. Mayo scores were (87.42 ± 13.01) and (97.69 ± 4.50) points at the last follow-up and two months after surgery, respectively (p < 0.05). In the test of grip strength, 2 months after surgery, the grip strength of the affected side was lower than that of the healthy side (p < 0.05), and the maximum and mean values of the superficial flexor of the affected side were lower than those of the healthy side (p < 0.05). At the last follow-up, there was no difference in the grip strength between the affected side and the healthy side (p > 0.05), and no difference in the maximum RMS, mean RMS and cooperative contraction ratio of the superficial flexor and digital extensor muscles between the affected side and the healthy side (p > 0.05).

Conclusion

Satisfactory results can be obtained after elastic intramedullary napping in children with ulnar and radius fractures. However, 2 months after surgery, the grip strength of the affected side is small, and the electrical activity of the forearm muscle is low during flexion and extension activities of the wrist joint, which has not returned to normal, suggesting that children orthopaedic clinicians should remind children to conduct timely and effective rehabilitation training after the removal of the cast.
Population pharmacokinetic analysis and dosing regimen optimization of teicoplanin in critically ill patients with sepsis
Authors: Chen Chao‐Yang , Xie Min , Gong Jun , Yu Ning , Wei Ran , Lei Li‐Li , Zhao Si‐Miao , Li Ruo‐Ming , Dong Xiu , Zhang Xiang‐Lin , Zhou Ying , Li Shuang‐Ling , Cui Yi‐Min
Published: April 2023

Objectives: Teicoplanin has been extensively used in the treatment for infections caused by gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). However, current teicoplanin treatment is challenging due to relatively low and variable concentrations under standard dosage regimens. This study aimed to investigate the population pharmacokinetics (PPK) characteristics of teicoplanin in adult sepsis patients and provide recommendations for optimal teicoplanin dosing regimens.

Methods: A total of 249 serum concentration samples from 59 septic patients were prospectively collected in the intensive care unit (ICU). Teicoplanin concentrations were detected, and patients’ clinical data were recorded. PPK analysis was performed using a non-linear, mixed-effect modeling approach. Monte Carlo simulations were performed to evaluate currently recommended dosing and other dosage regimens. The optimal dosing regimens were defined and compared by different pharmacokinetic/pharmacodynamic parameters, including trough concentration (Cmin), the ratio of 24-h area under the concentration-time curve to the minimum inhibitory concentration (AUC0-24/MIC), as well as the probability of target attainment (PTA) and the cumulative fraction of response (CFR) against MRSA.

Results: A two-compartment model adequately described the data. The final model parameter estimates for clearance, central compartment volume of distribution, intercompartmental clearance and peripheral compartment volume were 1.03 L/h, 20.1 L, 3.12 L/h and 101 L, respectively. Glomerular filtration rate (GFR) was the only covariate that significantly affected teicoplanin clearance. Model-based simulations revealed that 3 or 5 loading doses of 12/15 mg/kg every 12 h followed by a maintenance dose of 12/15 mg/kg every 24 h–72 h for patients with different renal functions were required to achieve a target Cmin of 15 mg/L and a target AUC0-24/MIC of 610. For MRSA infections, PTAs and CFRs were not satisfactory for simulated regimens. Prolonging the dosing interval may be easier to achieve the target AUC0-24/MIC than reducing the unit dose for renal insufficient patients.

Conclusion: A PPK model for teicoplanin in adult septic patients was successfully developed. Model-based simulations revealed that current standard doses may result in undertherapeutic Cmin and AUC, and a single dose of at least 12 mg/kg may be needed. AUC0-24/MIC should be preferred as the PK/PD indicator of teicoplanin, if AUC estimation is unavailable, in addition to routine detection of teicoplanin Cmin on Day 4, follow-up therapeutic drug monitoring at steady-state is recommended.
Saponins of ginseng products: a review of their transformation in processing
Authors: Ye Xian-Wen , Li Chun-Shuai , Zhang Hai-Xia , Li Qian , Cheng Shui-Qing , Wen Jia , Wang Xuan , Ren Hong-Min , Xia Liang-Jing , Wang Xu-Xing , Xu Xin-Fang , Li Xiang-Ri
Published: April 2023

The primary processed product of Panax ginseng C.A. Meyer (P. ginseng) is red ginseng. As technology advances, new products of red ginseng have arisen. Red ginseng products, e.g., traditional red ginseng, sun ginseng, black ginseng, fermented red ginseng, and puffed red ginseng, are commonly used in herbal medicine. Ginsenosides are the major secondary metabolites of P. ginseng. The constituents of P. ginseng are significantly changed during processing, and several pharmacological activities of red ginseng products are dramatically increased compared to white ginseng. In this paper, we aimed to review the ginsenosides and pharmacological activities of various red ginseng products, the transformation law of ginsenosides in processing, and some clinical trials of red ginseng products. This article will help to highlight the diverse pharmacological properties of red ginseng products and aid in the future development of red ginseng industrialization.
Neutron generation enhanced by a femtosecond laser irradiating on multi-channel target
Authors: Yang Yanlei , Lv Chong , Sun Wei , Ban Xiaona , Liu Qiushi , Deng Zhigang , Qi Wei , Yang Guoqing , Zhang Xiaohua , Wan Feng , Wang Zhao , Zhao Baozhen , Li Jianxing , Zhou Weimin
Published: April 2023

A novel scheme has been proposed to enhance neutron yields, in which a multi-channel target consisting of a row of parallel micro-wires and a plane substrate is irradiated by a relativistic femtosecond laser. Two-dimensional particle-in-cell simulations show that the multi-channel target can significantly enhance the neutron yield, which is about 4 orders of magnitude greater than the plane target. Different from the case of nanowire target, we find that when the laser penetrates into the channel, the excited transverse sheath electric field can effectively accelerate the D+ ions in the transverse direction. When these energetic D+ ions move towards the nearby wire, they will collide with the bulk D+ ions to trigger D-D fusion reaction and produce neutrons, which is much more effective than the plane target case. Due to the unique trajectory of the incident D+ ions, the angular distribution of the produced neutrons is modulated from isotropic to two peaks around ±90°. Meanwhile, this enhancement and modulation is further verified in a wide range of target parameters.