bluuebunny/crossref_metadata_2025 huggingface dataset:
Defining and targeting patterns of T cell dysfunction in inborn errors of immunity
Authors: Campos Jose S. , Henrickson Sarah E.
Published: September 2022

Inborn errors of immunity (IEIs) are a group of more than 450 monogenic disorders that impair immune development and function. A subset of IEIs blend increased susceptibility to infection, autoimmunity, and malignancy and are known collectively as primary immune regulatory disorders (PIRDs). While many aspects of immune function are altered in PIRDs, one key impact is on T-cell function. By their nature, PIRDs provide unique insights into human T-cell signaling; alterations in individual signaling molecules tune downstream signaling pathways and effector function. Quantifying T-cell dysfunction in PIRDs and the underlying causative mechanisms is critical to identifying existing therapies and potential novel therapeutic targets to treat our rare patients and gain deeper insight into the basic mechanisms of T-cell function. Though there are many types of T-cell dysfunction, here we will focus on T-cell exhaustion, a key pathophysiological state. Exhaustion has been described in both human and mouse models of disease, where the chronic presence of antigen and inflammation (e.g., chronic infection or malignancy) induces a state of altered immune profile, transcriptional and epigenetic states, as well as impaired T-cell function. Since a subset of PIRDs amplify T-cell receptor (TCR) signaling and/or inflammatory cytokine signaling cascades, it is possible that they could induce T-cell exhaustion by genetically mimicking chronic infection. Here, we review the fundamentals of T-cell exhaustion and its possible role in IEIs in which genetic mutations mimic prolonged or amplified T-cell receptor and/or cytokine signaling. Given the potential insight from the many forms of PIRDs in understanding T-cell function and the challenges in obtaining primary cells from these rare disorders, we also discuss advances in CRISPR-Cas9 genome-editing technologies and potential applications to edit healthy donor T cells that could facilitate further study of mechanisms of immune dysfunctions in PIRDs. Editing T cells to match PIRD patient genetic variants will allow investigations into the mechanisms underpinning states of dysregulated T-cell function, including T-cell exhaustion.
Acute exercise mobilizes NKT-like cells with a cytotoxic transcriptomic profile but does not augment the potency of cytokine-induced killer (CIK) cells
Authors: Zúñiga Tiffany M. , Baker Forrest L. , Smith Kyle A. , Batatinha Helena , Lau Branden , Gustafson Michael P. , Katsanis Emmanuel , Simpson Richard J.
Published: September 2022

CD3+/CD56+Natural killer (NK) cell-like T-cells (NKT-like cells) represent <5% of blood lymphocytes, display a cytotoxic phenotype, and can kill various cancers. NKT-like cells can be expandedex vivointo cytokine-induced killer (CIK) cells, however this therapeutic cell product has had mixed results against hematological malignancies in clinical trials. The aim of this study was to determine if NKT-like cells mobilized during acute cycling exercise could be used to generate more potent anti-tumor CIK cells from healthy donors. An acute exercise bout increased NKT-like cell numbers in blood 2-fold. Single cell RNA sequencing revealed that exercise mobilized NKT-like cells have an upregulation of genes and transcriptomic programs associated with enhanced anti-tumor activity, including cytotoxicity, cytokine responsiveness, and migration. Exercise, however, did not augment theex vivoexpansion of CIK cells or alter their surface phenotypes after 21-days of culture. CIK cells expanded at rest, during exercise (at 60% and 80% VO2max) or after (1h post) were equally capable of killing leukemia, lymphoma, and multiple myeloma target cells with and without cytokine (IL-2) and antibody (OKT3) primingin vitro. We conclude that acute exercise in healthy donors mobilizes NKT-like cells with an upregulation of transcriptomic programs involved in anti-tumor activity, but does not augment theex vivoexpansion of CIK cells.
Analysis of S gene characteristic sequences and changes in properties of protein expression in HBV ASCs with low-level HBsAg
Authors: Yu Yu , Zhang Yingqiang , Dai Yuzhu , Sun Qingyang , Jiang Chun , Xu Xujian , Mei Chuanzhong , Cheng Jun
Published: September 2022

Objective

We detected the serum HBsAg immune complex (HBsAg-CIC) and sequenced the HBV S gene in these patients to reveal the association between sustained low-level expression of HBsAg and mutated S gene sequence characteristics, protein function changes, and HBsAg immune complex formation.

Methods

A total of 204 samples were collected and divided into high-level (n = 60, HBsAg level >10 IU/ml) and low-level (n = 144, HBsAg level ≤ 10 IU/ml) HBsAg groups. The clinical and epidemiological data of the two groups were statistically compared. According to different serological patterns and genotypes, the HBsAg-CIC results of the high-level and low-level HBsAg groups were divided into different subgroups, and then the HBsAg-CIC positive rates among different subgroups were compared. We sequenced the S gene of HBV from the two groups and identified the relevant mutations in the MHR of the S gene. In addition, we compared the changes in HBsAg protein properties and functions after hot spot mutation in the MHR of the S gene.

Results

Comparing the positive rates of HBsAg-CIC under different serological patterns and genotypes in the two groups, the HBsAg-CIC positive rate was higher in the low-level HBsAg group. Moreover, there was weak correlation between HBsAg-CIC and HBsAg or HBV DNA in both groups (r = 0.32, 0.27, 0.41, 0.48; P < 0.05). Sequencing of S gene in the two groups, showed that the hot-spot mutations were T126A, M133L/T/S, and F134L/T/I in MHR of S gene of genotype B, and hot-spot mutations were Q101R and I126S/T in MHR of S gene of genotype C. Additionally, the positive rate of MHR mutation in the S gene from HBsAg-CIC positive patients was higher in the low-level HBsAg group.

Conclusion

The host immune process of clearing HBV seems to have multiple site mutations in MHR, which changes the physicochemical properties and functions of HBsAg and intensifies the formation of HBsAg-CIC, thus avoiding the effective recognition of HBsAg by the host and resulting in immune tolerance between the host and HBV, which may be one of the formation mechanisms of sustained low-level expression of HBsAg in the serum of HBV-infected persons.
Splenic infarction during acute falciparum malaria: A case report
Authors: Lu Youguang , Zhang Shian , Jiang Chuanshen
Published: September 2022

Splenomegaly is common in malaria, but splenic infarction is a rare complication of malaria. We report a case of a patient with Plasmodium falciparum infection who developed abdominal pain, reappearance of fever, elevated D-dimer during treatment, and abdominal CT confirmed splenic infarction. The abdominal pain was relieved and the fever subsided by analgesic and anticoagulant therapy. Six months later, abdominal CT showed splenic recovery. As a result, splenic infarction should be considered when a patient with malaria developed abdominal pain, reappearance of fever and elevated blood D-dimer during treatment. In the absence of surgical indications, conservative medical treatment is effective.
Excessive fructose intake inhibits skeletal development in adolescent rats via gut microbiota and energy metabolism
Authors: Gao Tianlin , Tian Chunyan , Tian Ge , Ma Li , Xu Lili , Liu Wendong , Cai Jing , Zhong Feng , Zhang Huaqi , Ma Aiguo
Published: September 2022

Excessive fructose intake from desserts and beverages may influence bone development among adolescents. The gut microbiota (GM) and energy metabolism play important roles in bone development. In this study, 40 female adolescent rats were randomly assigned to the control group, the fructose group with two concentrations, and the glucose group as the positive control group. After 10 weeks, serum glucose and lipids were detected by means of an automatic analyzer, and the bone microstructure was analyzed by Micro-CT. Then, the GM was determined via 16S rRNA sequencing analysis, and energy metabolism was detected by measuring serum carbohydrate metabolites. At last, bone metabolism markers were measured via ELISA kits. The results showed that excessive fructose intake could increase body weight and influence the glucolipid metabolism of female adolescent rats. Meanwhile, the bone microstructures were impaired with excessive fructose intake. Mechanistically, excessive fructose intake shifted the GM of rats with the decrease of Lachnospiraceae, Ruminococcaceae, and increase of Allobaculum, Lachnospiraceae. Energy metabolism analysis suggested that most metabolites of fructose did not enter the tricarboxylic acid cycle to provide energy for the body’s development. Furthermore, serum bone metabolism markers showed that excessive fructose intake could decrease both bone formation and resorption. Our results suggested that excessive fructose intake could inhibit skeletal development in adolescents. One potential mechanism might be that it affected the intestinal microbiota homeostasis in the juvenile body, thus changing the energy metabolism level, and ultimately affecting the bone metabolic balance.
Niche differentiation among comammox (Nitrospira inopinata) and other metabolically distinct nitrifiers
Authors: Yang Xueqin , Yu Xiaoli , He Qiang , Deng Ting , Guan Xiaotong , Lian Yingli , Xu Kui , Shu Longfei , Wang Cheng , Yan Qingyun , Yang Yuchun , Wu Bo , He Zhili
Published: September 2022

Due to global change, increasing nutrient input to ecosystems dramatically affects the nitrogen cycle, especially the nitrification process. Nitrifiers including ammonia-oxidizing archaea (AOAs), ammonia-oxidizing bacteria (AOBs), nitrite-oxidizing bacteria (NOBs), and recently discovered complete ammonia oxidizers (comammoxs) perform nitrification individually or in a community. However, much remains to be learned about their niche differentiation, coexistence, and interactions among those metabolically distinct nitrifiers. Here, we used synthetic microbial ecology approaches to construct synthetic nitrifying communities (SNCs) with different combinations of Nitrospira inopinata as comammox, Nitrososphaera gargensis as AOA, Nitrosomonas communis as AOB, and Nitrospira moscoviensis as NOB. Our results showed that niche differentiation and potential interactions among those metabolically distinct nitrifiers were determined by their kinetic characteristics. The dominant species shifted from N. inopinata to N. communis in the N4 community (with all four types of nitrifiers) as ammonium concentrations increased, which could be well explained by the kinetic difference in ammonia affinity, specific growth rate, and substrate tolerance of nitrifiers in the SNCs. In addition, a conceptual model was developed to infer niche differentiation and possible interactions among the four types of nitrifiers. This study advances our understanding of niche differentiation and provides new strategies to further study their interactions among the four types of nitrifiers.
A decade after the first Pucciniales genomes: A bibliometric snapshot of (post) genomics studies in three model rust fungi
Authors: Petre Benjamin , Duplessis Sébastien
Published: September 2022

Pucciniales (rust fungi) are one of the largest fungal order of plant pathogens. They collectively infect key crops such as wheat and soybean, and threaten global food security. In the early 2010s, the genome sequences of three rust fungi were released: Melampsora larici-populina (the poplar leaf rust fungus), Puccinia graminis f. sp. tritici (the wheat stem rust fungus), and Puccinia striiformis f. sp. triciti (the wheat stripe rust or wheat yellow rust fungus). The availability of those genomes has forwarded rust biology into the post-genomic era, sparking a series of genomics, transcriptomics, in silico, and functional studies. Here, we snapshot the last 10 years of post-genomics studies addressing M. larici-populina, P. graminis f. sp. tritici, and/or P. striiformis f. sp. tritici. This mini-review notably reveals the model species-centered structure of the research community, and highlights the drastic increase of the number of functional studies focused on effectors since 2014, which notably revealed chloroplasts as a central host compartment targeted by rust fungi. This mini-review also discusses genomics-facilitated studies in other rust species, and emerging post-genomic research trends related to fully-phased rust genomes.
Isobaric tags for relative and absolute quantification-based proteomic analysis of host-pathogen protein interactions in the midgut of Aedes albopictus during dengue virus infection
Authors: Wang Jiatian , Fan Peiyang , Wei Yong , Wang Jiaqi , Zou Weihao , Zhou Guofa , Zhong Daibin , Zheng Xueli
Published: September 2022

Aedes albopictus (Ae. albopictus), an important vector of dengue virus (DENV), is distributed worldwide. Identifying host proteins involved in flavivirus replication in Ae. albopictus and determining their natural antiviral mechanisms are critical to control virus transmission. Revealing the key proteins related to virus replication and exploring the host-pathogen interaction are of great significance in finding new pathways of the natural immune response in Ae. albopictus. Isobaric tags for relative and absolute quantification (iTRAQ) was used to perform a comparative proteomic analysis between the midgut of Ae. albopictus infected with DENV and the control. 3,419 proteins were detected, of which 162 were ≥ 1.2-fold differentially upregulated or ≤ 0.8-fold differentially downregulated (p < 0.05) during DENV infections. Differentially expressed proteins (DEPs) were mainly enriched in ubiquitin ligase complex, structural constituent of cuticle, carbohydrate metabolism, and lipid metabolism pathways. We found that one of the DEPs, a putative pupal cuticle (PC) protein could inhibit the replication of DENV and interact with the DENV-E protein. In addition, the result of immunofluorescence (IF) test showed that there was co-localization between ubiquitin carboxyl-terminal hydrolase (UCH) protein and the DENV-E protein, and virus infection reduced the level of this protein. iTRAQ-based proteomic analysis of the Ae. albopictus midgut identified dengue infection-induced upregulated and downregulated proteins. The interaction between the PC and UCH proteins in the midgut of Ae. albopictus might exert a natural antiviral mechanism in mosquito.
Diagnostic value of an algorithm for autoimmune epilepsy in a retrospective cohort
Authors: Sakamoto Mitsuhiro , Matsumoto Riki , Shimotake Akihiro , Togawa Jumpei , Takeyama Hirofumi , Kobayashi Katsuya , Leypoldt Frank , Wandinger Klaus-Peter , Kondo Takayuki , Takahashi Ryosuke , Ikeda Akio
Published: September 2022

Purpose

This study aims to propose a diagnostic algorithm for autoimmune epilepsy in a retrospective cohort and investigate its clinical utility.

Methods

We reviewed 60 patients with focal epilepsy with a suspected autoimmune etiology according to board-certified neurologists and epileptologists. To assess the involvement of the autoimmune etiology, we used the patients' sera or cerebrospinal fluid (CSF) samples to screen for antineuronal antibodies using rat brain immunohistochemistry. Positive samples were analyzed for known antineuronal antibodies. The algorithm applied to assess the data of all patients consisted of two steps: evaluation of clinical features suggesting autoimmune epilepsy and evaluation using laboratory and imaging findings (abnormal CSF findings, hypermetabolism on fluorodeoxyglucose-positron emission tomography, magnetic resonance imaging abnormalities, and bilateral epileptiform discharges on electroencephalography). Patients were screened during the first step and classified into five groups according to the number of abnormal laboratory findings. The significant cutoff point of the algorithm was assessed using a receiver-operating characteristic curve analysis.

Results

Fourteen of the 60 patients (23.3%) were seropositive for antineuronal antibodies using rat brain immunohistochemistry. Ten patients had antibodies related to autoimmune epilepsy/encephalitis. The cutoff analysis of the number of abnormal laboratory and imaging findings showed that the best cutoff point was two abnormal findings, which yielded a sensitivity of 78.6%, a specificity of 76.1%, and an area under the curve of 0.81.

Conclusion

The proposed algorithm could help predict the underlying autoimmune etiology of epilepsy before antineuronal antibody test results are available.
Continuous theta-burst stimulation over the left posterior inferior frontal gyrus induced compensatory plasticity in the language network
Authors: An HyunJung , Bashir Shahid , Cha Eunsil , Lee Jeongeun , Ohn Suk Hoon , Jung Kwang-Ik , Yoo Woo-Kyoung
Published: September 2022

Introduction

Continuous theta-burst stimulation (cTBS) has been used as an effective tool in inducing inhibitory aftereffect within a short time periods in the motor cortex; this has been demonstrated in the language network to a limited degree with controversial effect. In this study, we aimed to delineate the offline effect of cTBS-induced changes to the left posterior inferior frontal gyrus (pIFG) in healthy subjects using functional magnetic resonance imaging (fMRI).

Methods

Twenty healthy, normal subjects (mean age: 30.84 years) were recruited. They all were right-handed and had no contra-indications for fMRI or cTBS. They were randomly assigned into the treatment group or the sham control group.

Results

ANOVA showed that cTBS had a significant main effect only when the sham treatment was subtracted from the real stimulation in left superior temporal, left inferior frontal gyrus, thalamus, and right insular cortex (uncorrected p < 0.002). The subjects' post-cTBS condition differed significantly from their pre-cTBS condition in the left pIFG (uncorrected p < 0.002). There were interactions in the pIFG, bilateral superior parietal lobules, left superior temporal, left supramarginal, and left cuneus areas. The application of cTBS induced increased BOLD signals in language-related networks by stimulating the left pIFG (BA 44). This implies that inhibiting the pIFG led to increased use of language network resources.

Conclusion

This study demonstrated cTBS-induced changes in the language network caused by stimulation of the left pIFG. Based on these findings, future studies on the therapeutic effects of cTBS on the right Broca's homolog area are warranted.
White matter alterations in focal to bilateral tonic-clonic seizures
Authors: Maher Christina , D'Souza Arkiev , Zeng Rui , Barnett Michael , Kavehei Omid , Nikpour Armin , Wang Chenyu
Published: September 2022

We examined the white matter of patients with and without focal to bilateral tonic-clonic seizures (FBTCS), and control participants. A neural network based tract segmentation model (Tractseg) was used to isolate tract-specific, track-weighted tensor-based measurements from the tracts of interest. We compared the group differences in the track-weighted tensor-based measurements derived from whole and hemispheric tracts. We identified several regions that displayed significantly altered white matter in patients with focal epilepsy compared to controls. Furthermore, patients without FBTCS showed significantly increased white matter disruption in the inferior fronto-occipital fascicle and the striato-occipital tract. In contrast, the track-weighted tensor-based measurements from the FBTCS cohort exhibited a stronger resemblance to the healthy controls (compared to the non-FBTCS group). Our findings revealed marked alterations in a range of subcortical tracts considered critical in the genesis of seizures in focal epilepsy. Our novel application of tract-specific, track-weighted tensor-based measurements to a new clinical dataset aided the elucidation of specific tracts that may act as a predictive biomarker to distinguish patients likely to develop FBTCS.
Fragile X-associated tremor ataxia syndrome rating scale: Revision and content validity using a mixed method approach
Authors: Tosin Michelle H. S. , Stebbins Glenn T. , Goetz Christopher G. , Hagerman Randi J. , Hessl David , Zolecki Melissa A. , Todd Peter K. , Leehey Maureen A. , Hall Deborah A.
Published: September 2022

Background

The original Fragile X-associated Tremor Ataxia Syndrome Rating Scale (FXTAS-RS) contained 61 items, some requiring modifications to better meet recommendations for patient-focused rating scale development.

Purpose

Provide initial validation of a revised version of the FXTAS-RS for motor signs.

Method

We conducted a two-phase mixed-method approach. In Phase 1, revision, we implemented a Delphi technique identifying pertinent domains/subdomains and developing items through expert consensus. In Phase 2, content validation, we conducted cognitive pretesting assessing comprehensibility, comprehensiveness, and relevance of items to FXTAS motor signs.

Results

After five rounds of Delphi panel and two rounds of cognitive pretesting, the revised version of the FXTAS-RS was established with 18 items covering five domains and 13 subdomains of motor signs. Cognitive pretesting revealed adequate content validity for the assessment of FXTAS motor signs.

Conclusion

The revised FXTAS-RS has been successfully validated for content and it is now ready for large-scale field validation.
Post-mortem brain histological examination in the substantia nigra and subthalamic nucleus in Parkinson’s disease following deep brain stimulation
Authors: Mazumder Srestha , Bahar Anita Y. , Shepherd Claire E. , Prasad Asheeta A.
Published: September 2022

Parkinson’s disease (PD) is a progressive neurodegenerative disorder, pathologically hallmarked by the loss of dopamine neurons in the substantia nigra (SN) and alpha-synuclein aggregation. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a common target to treat the motor symptoms in PD. However, we have less understanding of the cellular changes in the STN during PD, and the impact of DBS on the STN and SN is limited. We examined cellular changes in the SN and STN in PD patients with and without STN-DBS treatment. Post-mortem brain tissues from 6 PD non-STN-DBS patients, 5 PD STN-DBS patients, and 6 age-matched controls were stained with markers for neurodegeneration (tyrosine hydroxylase, alpha-synuclein, and neuronal loss) and astrogliosis (glial fibrillary acidic protein). Changes were assessed using quantitative and semi-quantitative microscopy techniques. As expected, significant neuronal cell loss, alpha-synuclein pathology, and variable astrogliosis were observed in the SN in PD. No neuronal cell loss or astrogliosis was observed in the STN, although alpha-synuclein deposition was present in the STN in all PD cases. DBS did not alter neuronal loss, astrogliosis, or alpha-synuclein pathology in either the SN or STN. This study reports selective pathology in the STN with deposits of alpha-synuclein in the absence of significant neuronal cell loss or inflammation in PD. Despite being effective for the treatment of PD, this small post-mortem study suggests that DBS of the STN does not appear to modulate histological changes in astrogliosis or neuronal survival, suggesting that the therapeutic effects of DBS mechanism may transiently affect STN neural activity.
Chinese herbal formula (GCNY)-medicated serum alleviates peroxidation induced by H2O2 in human microglial cells
Authors: Chen Yong , Wang Baojiang , Lai Wing-Fu , Chen Yanjuan , Pan Rongbin , Tang Zhongsheng , Liu Dongzhou
Published: September 2022

Traditional Chinese herbal medicine aiming at nourishing yin formed a distinctive school of thought in history to achieve anti-aging and longevity. In the formula Gancao nourishing yin (GCNY) decoction, all of the ingredients show antioxidant properties. However, in real clinical practice, extractions of herbs are rarely applied alone but are prescribed as the integrated formula. To investigate whether GCNY possesses anti-oxidation potential, we applied GCNY to treat rats to acquire medicated serum, which was then added on H2O2 (200 μM)-modeled human microglial cell line HMC-3 in comparison with its control serum. The results revealed that GCNY-medicated serum decreased reactive oxygen species (ROS) levels. Inflammatory cytokines such as pNF-κB p65 (ser536) and IL-6 were also decreased. Nrf2 and its pathway-related molecules, such as HO1, ABCC2, GLCM, ME1, NQO1, and TKT, were activated by H2O2 modeling while declined by treating with GCNY-medicated serum, which indicated attenuated oxidative stress of GCNY. Furthermore, mRNA-seq analysis showed 58 differential expressed genes (DEGs), which were enriched in pathways including antigen processing and presentation, longevity regulation, oxidative phosphorylation, and Parkinson’s disease progression. DEGs that were downregulated by H2O2 modeling but upregulated by GCNY treatment include CENPF, MKI67, PRR11, and TOP2A. Those targets were reported to be associated with the cell cycle and cell proliferation and belong to the category of growth factor genes. In conclusion, this study verified anti-oxidation effects of GCNY and indicated its promising application for cognitive degeneration and aging-related disorders.
TNAP—a potential cytokine in the cerebral inflammation in spastic cerebral palsy
Authors: Wang Xiao-Kun , Gao Chao , Zhong He-Quan , Kong Xiang-Yu , Qiao Rui , Zhang Hui-Chun , Chen Bai-Yun , Gao Yang , Li Bing
Published: September 2022

Objective: Several studies have shown the significance of neuroinflammation in the pathological progress of cerebral palsy (CP). However, the etiology of CP remains poorly understood. Spastic CP is the most common form of CP, comprising 80% of all cases. Therefore, identifying the specific factors may serve to understand the etiology of spastic CP. Our research aimed to find some relevant factors through protein profiling, screening, and validation to help understand the pathogenesis of cerebral palsy.

Materials and methods: In the current study, related clinical parameters were assessed in 18 children with spastic CP along with 20 healthy individuals of the same age. Blood samples of the spastic CP children and controls were analyzed with proteomics profiling to detect differentially expressed proteins. On the other hand, after hypoxic-ischemic encephalopathy (HIE) was induced in the postnatal day 7 rat pups, behavioral tests were performed followed by detection of the differentially expressed markers and inflammatory cytokines in the peripheral blood and cerebral cortex of the CP model rats by Elisa and Western blot. Independent sample t-tests, one-way analysis of variance, and the Pearson correlation were used for statistical analysis.

Results: Through proteomic analysis, differentially expressed proteins were identified. Among them, tissue-nonspecific alkaline phosphatase (TNAP), the gene expression product of alkaline phosphatase (ALPL), was downregulated in spastic CP. In addition, significantly lower TNAP levels were found in the children with CP and model rats. In contrast, compared with the sham rats, the model rats demonstrated a significant increase in osteopontin and proinflammatory biomarkers in both the plasma and cerebral cortex on the ischemic side whereas serum 25 hydroxyvitamin D and IL-10 were significantly decreased. Moreover, serum TNAP level was positively correlated with serum CRP and IL-10 in model rats.

Conclusion: These results suggest that TNAP is the potential molecule playing a specific and critical role in the neuroinflammation in spastic CP, which may provide a promising target for the diagnosis and treatment of spastic CP.
Sciatic nerve schwannoma complicated by nerve bundle membrane effusion: Two case reports and a literature review
Authors: He Lian , Zhang Yan-Ji , He Shi-Li , Zhang Jia-Ren , Wu Jun , Zhang Gao-Feng , Wang Da-Li
Published: September 2022

Schwannoma is a benign tumor that originates from Schwann cells in the peripheral nerve tunica or bundle of nerves and grows along the longitudinal axis of the nerve. Schwannoma can occur in multiple anatomic locations but rarely in the sciatic nerve. To our knowledge, there are no previous reports in the literature related to schwannoma combined with effusion of the nerve bundle membranes. Here, we report two cases of sciatic nerve schwannoma combined with nerve bundle membrane effusion, and the relationship between them is uncertain. We have boldly speculated about this uncertain relationship by combining the two patients’ imaging manifestations to help determine the mechanism of schwannoma or effusion generation as well as a clinical treatment.
Incidence, mortality, and survival analyses of patients with thymic lymphoma
Authors: Wang Li , Wang Zhile , Huo Lanqing , Zhao Ailin
Published: September 2022

Objectives

To explore the clinical and prognostic characteristics of thymic lymphoma and the effects of current treatments on the prognosis.

Methods

Patients diagnosed as primary thymic lymphoma between 1975 and 2018 from the nine states of the US were identified, including Atlanta, Connecticut, Detroit, Hawaii, Iowa, New Mexico, San Francisco-Oakland, Seattle–Puget Sound, and Utah. Incidence and mortality rates were analyzed using SEER*Stat 8.3.9 software. Univariate and multivariate Cox regressions were performed to identify prognostic factors. The Kaplan–Meier curve and log-rank test were used to compare overall survival (OS) among different treatments.

Results

A total of 233 patients diagnosed as thymic lymphoma were identified, and eight of them were lost to follow-up or died upon diagnosis. The incidence of thymic lymphoma was 2.032 per ten million (95% CI: 1.777–2.312), and the mortality rate was 0.649 per ten million (95% CI: 0.508–0.817). Among the 225 patients with definite follow-up, 98 were males and 127 were females, with a median age of 33 years. The Cox regression results showed that age and pathological type were independent risk prognostic factors. The 5-, 10-, and 20-year OS were 80.0%, 77.5%, and 70.9%, respectively. For Ann Arbor stage I and II patients, there was no significant difference between the surgical group (N = 78) and the non-operative group (N = 65; P = 0.270). The radiotherapy group (N = 79) had better OS than the non-radiotherapy group (N = 64) in the first 25 years, and the prognosis in the later years was not significantly different (P = 0.051). The chemotherapy group (N = 37) had a significantly better prognosis than the non-chemotherapy group (N = 37; P = 0.020). Patients who received postoperative radiotherapy (N = 45) or who only received radiotherapy (N = 34) seemed to have better OS than that of patients who only received surgery (N = 33), although the difference was not significant (P = 0.063).

Conclusions

Age and pathological type were independent prognostic factors for thymic lymphoma. Surgical treatment had limited effects on OS, while both radiotherapy and chemotherapy could significantly improve the survival outcome.
Does the shape of the electric pulse matter in electroporation?
Authors: Novickij Vitalij , Rembiałkowska Nina , Szlasa Wojciech , Kulbacka Julita
Published: September 2022

Electric pulses are widely used in biology, medicine, industry, and food processing. Numerous studies indicate that electroporation (EP) is a pulse-dependent process, and the electric pulse shape and duration strongly determine permeabilization efficacy. EP protocols are precisely planned in terms of the size and charge of the molecules, which will be delivered to the cell. In reversible and irreversible EP applications, rectangular or sine, polar or bipolar pulses are commonly used. The usage of pulses of the asymmetric shape is still limited to high voltage and low voltage (HV/LV) sequences in the context of gene delivery, while EP-based applications of ultra-short asymmetric pulses are just starting to emerge. This review emphasizes the importance and role of the pulse shape for membrane permeabilization by EP.
The combined role of PET/CT metabolic parameters and inflammatory markers in detecting extensive disease in small cell lung cancer
Authors: Hu Yao , Sun Jin , Li Danming , Li Yangyang , Li Tiannv , Hu Yuxiao
Published: September 2022

The combined role of inflammatory markers [including neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), and systemic immune-inflammation index (SII)] and PET/CT metabolic parameters [including maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and TLG (total lesion glycolysis)] at baseline in evaluating the binary stage [extensive-stage disease (ED) and limited-stage disease (LD)] of small cell lung cancer (SCLC) is unclear. In this study, we verified that high metabolic parameters and inflammatory markers were related to the binary stage of SCLC patients, respectively (p < 0.05). High inflammatory markers were also associated with high MTV and TLG in patients with SCLC (p < 0.005). Moreover, the incidences of co-high metabolic parameters and inflammatory markers were higher in ED-SCLC (p < 0.05) than those in LD-SCLC. Univariate logistic regression analysis demonstrated that Co-high MTV/NLR, Co-high MTV/MLR, Co-high MTV/SII, Co-high TLG/NLR, Co-high TLG/MLR, and Co-high TLG/SII were significantly related to the binary stage of SCLC patients (p = 0.00). However, only Co-high MTV/MLR was identified as an independent predictor for ED-SCLC (odds ratio: 8.67, 95% confidence interval CI: 3.51–21.42, p = 0.000). Our results suggest that co-high metabolic parameters and inflammatory markers could be of help for predicting ED-SCLC at baseline. Together, these preliminary findings may provide new ideas for more accurate staging of SCLC.
Breast metastasis of cervical cancer: A case report and systematic literature review
Authors: Jian-yong Zhang , Guang-ping Zeng , Xue Wang , Shi-min Zhang , Zhen-guo Zhao
Published: September 2022

It has been reported that extramammary malignant tumors metastasize to the breast, but cervical cancer metastasis to the breast is very rare. At present, there are only dozens of reports about cervical cancer metastasis to breast in the world. It is difficult to distinguish between primary breast cancer and metastatic breast cancer. We report a 44-year-old woman who underwent surgery, chemotherapy, and radiotherapy for cervical cancer 5 years ago. Then, she was hospitalized for finding a left breast mass measured 2.9 × 2.7 cm in chest CT. Pathological examination combined with immunohistochemical staining showed that the mass came from the cervix. Then, the patient received systematic chemotherapy and interstitial brachytherapy (IB) for the breast mass and got a great result. Cervical cancer rarely metastasizes to the breast. In this case, we confirmed the diagnosis of breast mass by histopathological examination and immunohistochemistry. IB achieved a good result in the treatment of the breast mass. We hope to provide reference of prognosis and treatment when facing this situation by presenting this case.
Patients with melanoma treated with immune checkpoint inhibitors who had non-thyroid endocrine and skin immune-related adverse events have better prognosis: A systematic review and meta-analysis
Authors: Sun Qian , Sun Hongyan , Wu Nan , Hu Yue , Zhang Fangqing , Cong Xianling
Published: September 2022

Background

Several studies have reported an association between the occurrence of immune-related adverse events (irAEs) and prognosis in patients with melanoma treated with immune checkpoint inhibitors (ICIs), but the results remain controversial. We conducted a systematic review and meta-analysis to investigate the association between irAEs and survival in patients with melanoma treated with ICIs.

Methods

We searched the PubMed, Web of Science, and China National Knowledge Infrastructure databases through May 5, 2022 for clinical studies evaluating the association between irAEs and in melanoma patients treated with ICIs. Combined hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were calculated using fixed- or random-effects models based on heterogeneity.

Results

A total of 60 articles were included, with 16,520 patients. In patients with melanoma treated with ICIs, the occurrence of irAEs was significantly associated with better OS (HR, 0.58; 95% confidence interval [CI], 0.51–0.66; P<0.00001) and PFS (HR, 0.61; 95%CI, 0.51–0.72; P<0.00001). Endocrine irAEs (OS, HR, 0.81; 95%CI, 0.72–0.92; P=0.001; PFS: HR, 0.84; 95%CI, 0.73–0.96, P=0.009), skin irAEs (OS, HR, 0.59; 95%CI, 0.41–0.85; P=0.004; PFS: HR, 0.43; 95%CI, 0.36–0.52; P<0.00001), vitiligo (OS, HR, 0.22; 95%CI, 0.15–0.31; P<0.00001; PFS, HR, 0.33; 95%CI, 0.25–0.44; P<0.00001), and grade 1–2 irAEs (OS, HR, 0.67; 95%CI, 0.58–0.78; P<0.00001; PFS, HR, 0.62; 95%CI, 0.51–0.76; P<0.00001) showed similar results. However, thyroid, lung, gastrointestinal, liver, and grade 3–4 irAEs were not significantly associated with OS and PFS. The occurrence of non-thyroid endocrine irAEs was significantly associated with better OS (HR, 0.22; 95%CI, 0.15–0.31; P<0.00001). In patients with melanoma treated with anti-programmed cell death protein 1 (OS, HR, 0.61; 95%CI, 0.51–0.72; P<0.00001; PFS, HR, 0.59; 95%CI, 0.47–0.74; P<0.00001), the association between irAEs and clinical benefit was clearer than in patients treated with anti-cytotoxic T-lymphocyte-associated protein 4 (OS, HR, 0.68; 95%CI, 0.52–0.89; P=0.005; PFS, HR, 0.93; 95%CI, 0.49–1.78; P=0.83).

Conclusion

Among patients with melanoma treated with ICIs, those who developed non-thyroid endocrine irAEs and cutaneous irAEs have better prognosis. This suggests that non-thyroid endocrine irAEs and cutaneous irAEs may be a prognostic biomarker for patients with melanoma treated with ICIs.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022338308.
Clinical features and prognostic factors in patients with microvascular infiltration of hepatocellular carcinoma: Development and validation of a nomogram and risk stratification based on the SEER database
Authors: Yang Dashuai , Zhu Mingqiang , Xiong Xiangyun , Su Yang , Zhao Fangrui , Hu Yong , Zhang Guo , Pei Junpeng , Ding Youming
Published: September 2022

Background

The goal is to establish and validate an innovative prognostic risk stratification and nomogram in patients of hepatocellular carcinoma (HCC) with microvascular invasion (MVI) for predicting the cancer-specific survival (CSS).

Methods

1487 qualified patients were selected from the Surveillance, Epidemiology and End Results (SEER) database and randomly assigned to the training cohort and validation cohort in a ratio of 7:3. Concordance index (C-index), area under curve (AUC) and calibration plots were adopted to evaluate the discrimination and calibration of the nomogram. Decision curve analysis (DCA) was used to quantify the net benefit of the nomogram at different threshold probabilities and compare it to the American Joint Committee on Cancer (AJCC) tumor staging system. C-index, net reclassification index (NRI) and integrated discrimination improvement (IDI) were applied to evaluate the improvement of the new model over the AJCC tumor staging system. The new risk stratifications based on the nomogram and the AJCC tumor staging system were compared.

Results

Eight prognostic factors were used to construct the nomogram for HCC patients with MVI. The C-index for the training and validation cohorts was 0.785 and 0.776 respectively. The AUC values were higher than 0.7 both in the training cohort and validation cohort. The calibration plots showed good consistency between the actual observation and the nomogram prediction. The IDI values of 1-, 3-, 5-year CSS in the training cohort were 0.17, 0.16, 0.15, and in the validation cohort were 0.17, 0.17, 0.17 (P<0.05). The NRI values of the training cohort were 0.75 at 1-year, 0.68 at 3-year and 0.67 at 5-year. The DCA curves indicated that the new model more accurately predicted 1-year, 3-year, and 5-year CSS in both training and validation cohort, because it added more net benefit than the AJCC staging system. Furthermore, the risk stratification system showed the CSS in different groups had a good regional division.

Conclusions

A comprehensive risk stratification system and nomogram were established to forecast CSS for patients of HCC with MVI.
Mutational signature and clonal relatedness of recurrent urothelial carcinomas with aristolochic acid
Authors: Zhu Jie , Ai Qing , Cheng Qiang , Shen Dan , Dong Zhouhuan , Li Jie , Shen Donglai , Wang Wei , Zhang Xu , Li Hongzhao
Published: September 2022

Urothelial carcinomas (UCs) are malignant tumors that arise from the lower and upper urinary tract and are characterized by multiple recurrences. Aristolochic acid (AA) is a potent nephrotoxin and human carcinogen associated with UC. East Asian populations with a high UC prevalence have an unusual genome-wide AA-induced mutational pattern. To address the genomic differences and clonal relatedness between primary and recurrent tumors in the UCs with AA pattern, we investigated the genomic differences and tumor microenvironment (TME) of AA and non-AA UCs. 17 UC patients were recruited, with nine documented AA exposure. Eleven of them showed recurrence. After-surgery tissues of primary and paired recurrent tumors were collected. Capture-based targeted deep sequencing was performed using a commercial panel consisting of 520 cancer-related genes. Tumor-infiltrating lymphocytes (TILs) were identified with an immunofluorescence-based microenvironment analysis panel (MAP). Hierarchical clustering based on the COSMIC signatures confirmed two significant subtypes: AA Sig and non-AA Sig. AA Sig was associated with AA-containing herbal drug intake, recurrence, and higher tumor mutation burden (TMB). The clonal architecture of UCs revealed three types of clonal evolution patterns. Non-AA Sig cohort showed shared clonal origin of primary and recurrent tumors. AA Sig showed heterogeneity and had multiple independent origins. Recurrent tumors as second primary tumors in AA Sig showed immunoreactive TME, indicating a better response with immune checkpoint inhibitor therapy. The AA mutational signature and unique immune profiles are helpful molecular markers to distinguish AA exposure from other carcinogens. These results also provide new insights into the origin of recurrent UCs that could affect treatment strategies.
Allowing access to parents/caregivers into COVID-19 hospitalization areas does not increase infections among health personnel in a pediatric hospital
Authors: De la Rosa-Zamboni Daniela , Adame-Vivanco María José , Luque-Coqui Mercedes , Jaramillo-Esparza Carlos Mauricio , Ortega-Riosvelasco Fernando , Reyna-Trinidad Irineo , Guerrero-Díaz Ana Carmen , Ortega-Ruiz Sergio Gabriel , Saldívar-Salazar Sergio , Villa-Guillen Mónica , Nieto-Zermeño Jaime , Bonilla-Pellegrini Sergio René , Jamaica Balderas Lourdes María del Carmen
Published: September 2022

Background

At the beginning of the current COVID-19 pandemic, it became critical to isolate all infected patients, regardless of their age. Isolating children has a negative effect on both, them and their parents/caregivers. Nevertheless isolation was mandatory because of the potential risk that visitation might have on COVID-19 dissemination mostly among health personnel.

Methods

From the starting of the COVID-19 pandemic in our pediatric hospital visits were forbidden. This 2 months period (April–May) was called P1. In June parents were allowed to visit (P2), under a visiting protocol previously published. Hospital workers were monitored for the presence of COVID-19 symptoms and tested for the infection when clinically justified. The positivity proportion and the relative risk (RR) of COVID-19 among the health personnel between periods were calculated. The caregivers were also followed up by phone calls.

Results

Since April 2020 to November 2020, 2,884 health personnel were studied for 234 days, (318,146 workers days). Although the COVID-19/1,000 health personnel days rate decreased from one period to another (1.43 vs 1.23), no statistically significant differences were found. During P1, 16 patients with COVID-19 were treated. During the follow up none of the family members were infected/symptomatic in P1, while in P2, 6/129 (4.65%) were symptomatic or had a positive test. All of them initiated between 2 and 4 days after the patient's admission. As they also had some other infected family members it was not possible to ensure the source of infection. There were no statistically significant differences in the RR of COVID-19 in health personnel, (RR 1, 95% CI 0.69–1.06, p = 0.162).

Conclusions

When safely implemented, allowing parents/caregivers to spend time with their hospitalized COVID-19 children does not increase the contagion risk for hospital workers or among themselves.
Case report: Removal of a subcutaneous implantable cardiac defibrillator in a pediatric patient with hypertrophic cardiomyopathy after a septal myectomy. Insights on current indications of type of ICD in children with hypertrophic cardiomyopathy and left ventricular tract obstruction
Authors: Dolader Paola , Alegria Iosune , Martínez Olorón Patricia , Fernandez-Doblas Joaquin , Gran Ferran , Roses-Noguer Ferran
Published: September 2022

Hypertrophic cardiomyopathy is a heart muscle disease with an annual incidence between 0.24 and 0.47/100000 in childhood. Sudden cardiac death is the most common cause of death in this population. Although some medical treatment can decrease the risk of sudden cardiac death, implantable cardioverter defibrillator continues to be the most reliable treatment. Different types of devices and programming strategies can be used in patients with hypertrophic cardiomyopathy depending on each center and specific patient condition. We report a pediatric patient affected with hypertrophic cardiomyopathy who had and ICD implantation in primary prevention. Four years later he developed symptomatic left ventricular outflow tract obstruction and a surgical septal myectomy was performed. After the myectomy the patient developed complete left bundle branch block on his 12 lead ECG, and unfortunately none of the S-ICD vectors were suitable after the myectomy and it had to be explanted and replaced for a new transvenous ICD.
Inhibitory effects of total triterpenoids isolated from the Hedyotis diffusa willd on H1975 cells
Authors: Wu Kenan , Wu Xue , Liang Yanni , Wang Ting , Wu Dongzhi , Li Luhan , Wang Zheng
Published: September 2022

It is estimated that non-small-cell lung cancer (NSCLC) is responsible for 80% of human deaths related to lung cancer worldwide. Currently, it has been discovered that two transcription factors. Nuclear factor-κB (NF-κB) and Signal transducer and activator of transcription 3 (STAT3) were the main factors affecting inflammation and cancer, and their activation promoted lung cancer cell proliferation. Hedyotis diffusa Willd. (H. diffusa) is an herbal Chinese medicine, which has always been used for the treatment of malignant tumors in clinical. Previous research found that H. diffusa could inhibit the proliferation of H1975 cells, but the specific mechanisms remain elusive. We investigated the effects of total triterpenes extracted from H. diffusa (TTH) on the migration, proliferation and apoptosis of H1975 cells. Cell-cycle and immunofluorescence analysis showed that TTH could block H1975 cells at G0/G1 phase and induce apoptosis of experimental cells. The protein levels of Bcl-2 were decreased, while the levels of pro-apoptotic Bax were increased. In addition, TTH could also inhibit the migration of H1975 cells through downregulated MMP-2 and MMP-9 and upregulated TIMP-2. Further research found that the level of phospho-STAT3 was significantly decreased after administration of TTH. And protein expression level of NF-κB in nucleus was decreased after TTH treatment, while NF-κB in cytoplasm increased. These results suggested that TTH could inhibit the proliferation and migration of H1975 cells, and also could induce cell apoptosis. These effects were closely connected to the activation of NF-κB and the phosphorylation of STAT3.