bluuebunny/crossref_metadata_2025 huggingface dataset:
Bacterial, fungal, and interkingdom microbiome features of exclusively breastfeeding dyads are associated with infant age, antibiotic exposure, and birth mode
Authors: Heisel Timothy , Johnson Abigail J. , Gonia Sara , Dillon Abrielle , Skalla Emily , Haapala Jacob , Jacobs Katherine M. , Nagel Emily , Pierce Stephanie , Fields David , Demerath Ellen , Knights Dan , Gale Cheryl A.
Published: November 2022

The composition and function of early life gut bacterial communities (microbiomes) have been proposed to modulate health for the long term. In addition to bacteria, fungi (mycobiomes) also colonize the early life gut and have been implicated in health disorders such as asthma and obesity. Despite the potential importance of mycobiomes in health, there has been a lack of study regarding fungi and their interkingdom interactions with bacteria during infancy. The goal of this study was to obtain a more complete understanding of microbial communities thought to be relevant for the early life programming of health. Breastmilk and infant feces were obtained from a unique cohort of healthy, exclusively breastfeeding dyads recruited as part of the Mothers and Infants Linked for Healthy Growth (MILk) study with microbial taxa characterized using amplicon-based sequencing approaches. Bacterial and fungal communities in breastmilk were both distinct from those of infant feces, consistent with niche-specific microbial community development. Nevertheless, overlap was observed among sample types (breastmilk, 1-month feces, 6-month feces) with respect to the taxa that were the most prevalent and abundant. Self-reported antibacterial antibiotic exposure was associated with micro- as well as mycobiome variation, which depended upon the subject receiving antibiotics (mother or infant), timing of exposure (prenatal, peri- or postpartum), and sample type. In addition, birth mode was associated with bacterial and fungal community variation in infant feces, but not breastmilk. Correlations between bacterial and fungal taxa abundances were identified in all sample types. For infant feces, congruency between bacterial and fungal communities was higher for older infants, consistent with the idea of co-maturation of bacterial and fungal gut communities. Interkingdom connectedness also tended to be higher in older infants. Additionally, higher interkingdom connectedness was associated with Cesarean section birth and with antibiotic exposure for microbial communities of both breastmilk and infant feces. Overall, these results implicate infant age, birth mode, and antibiotic exposure in bacterial, fungal and interkingdom relationship variation in early-life-relevant microbiomes, expanding the current literature beyond bacteria.
Metabolites extracted from microorganisms as potential inhibitors of glycosidases (α-glucosidase and α-amylase): A review
Authors: Wang Xiaojing , Li Jiaying , Shang Jiaqi , Bai Jing , Wu Kai , Liu Jing , Yang Zhijun , Ou Hao , Shao Lei
Published: November 2022

α-Glucosidase and α-amylase are the two main glycosidases that participate in the metabolism of carbohydrates. Inhibitors of these two enzymes are considered an important medical treatment for carbohydrate uptake disorders, such as diabetes and obesity. Microbes are an important source of constituents that have the potential to inhibit glycosidases and can be used as sources of new drugs and dietary supplements. For example, the α-glucosidase inhibitor acarbose, isolated from Actinoplanes sp., has played an important role in adequately controlling type 2 diabetes, but this class of marketed drugs has many drawbacks, such as poor compliance with treatment and expense. This demonstrates the need for new microorganism-derived resources, as well as novel classes of drugs with better compliance, socioeconomic benefits, and safety. This review introduces the literature on microbial sources of α-glucosidase and α-amylase inhibitors, with a focus on endophytes and marine microorganisms, over the most recent 5 years. This paper also reviews the application of glycosidase inhibitors as drugs and dietary supplements. These studies will contribute to the future development of new microorganism-derived glycosidase inhibitors.
The microbial community and functional indicators response to flow restoration in gradient in a simulated water flume
Authors: Huang Wei , Wang Zhuowei , Liu Xiaobo , Zhu Dayu , Wang Yurong , Wu Leixiang
Published: November 2022

Flow reduction has greatly affected the river ecological systems, and it has attracted much attention. However, less attention has been paid to response to flow restoration, especially flow restoration in gradient. Flow regime of rivers may affect river functional indicators and microbial community structure. This study simulated the ecological restoration of the flow-reduced river reach by gradiently controlling the water flow and explores the ecological response of environmental functional indicators and microbial community structure to the water flow. The results showed that gross primary productivity (GPP), ecosystem respiration rate (ER) and some water quality indices such as chemical oxygen demand, total nitrogen, and total phosphorus (TP), exhibited positive ecological responses to flow restoration in gradient. GPP and ER increased by 600.1% and 500.2%, respectively. The alpha diversity indices of the microbial community increased significantly with a flow gradient restoration. Thereinto, Shannon, Simpson, Chao1, and Ace indices, respectively, increased by 16.4%, 5.6%, 8.6%, and 6.2%. Canonical correspondence analysis indicated that water flow, Dissolved oxygen and TP were the main influencing factors for changes in bacterial community structure. Microbial community structure and composition present a positive ecological response to flow restoration in gradient. This study reveals that the main variable in the restoration of the flow-reduced river reach is the flow discharge, and it provides a feasible scheme for its ecological restoration.
Geographical patterns of Fejervarya limnocharis gut microbiota by latitude along mainland China’s coastline
Authors: Zhao Na , Ma Zhiwei , Jiang Yixin , Shi Yingying , Xie Yuning , Wang Yuting , Wu Siyu , Liu Shelan , Wang Supen
Published: November 2022

The gut microbiota affects many aspects of host biology and plays key roles in the coevolutionary association with its host. Geographical gradients may play a certain role on gut microbiota variation in the natural environment. However, the distribution pattern of amphibian gut microbiota in the latitudinal gradient remains largely unexplored. Here, we sampled six natural populations of Fejervarya limnocharis along the eastern coastline of mainland China (spanning 20°–30° N = 1,300 km) using 16S rRNA amplicon sequencing to characterize the gut microbiota. First of all, a significant correlation between gut microbial diversity and latitude was observed in our research system. Second, we discovered that latitude influenced the composition of the gut microbiota of F. limnocharis. Finally, we detected that geographical distance could not determine gut microbiota composition in F. limnocharis. These results indicate that latitude can play an important role in shaping the gut microbial diversity of amphibian. Our study offers the first evidence that gut microbial diversity of amphibian presents a latitudinal pattern and highlights the need for increased numbers of individuals to be sampled during microbiome studies in wild populations along environmental gradients.
Engineering of Burkholderia thailandensis strain E264 serves as a chassis for expression of complex specialized metabolites
Authors: Wang Zong-Jie , Liu Xiaotong , Zhou Haibo , Liu Yang , Zhong Lin , Wang Xue , Tu Qiang , Huo Liujie , Yan Fu , Gu Lichuan , Müller Rolf , Zhang Youming , Bian Xiaoying , Xu Xiaokun
Published: November 2022

Heterologous expression is an indispensable approach to exploiting natural products from phylogenetically diverse microbial communities. In this study, we constructed a heterologous expression system based on strain Burkholderia thailandensis E264 by deleting efflux pump genes and screening constitutive strong promoters. The biosynthetic gene cluster (BGC) of disorazol from Sorangium cellulosum So ce12 was expressed successfully with this host, and the yield of its product, disorazol F2, rather than A1, was improved to 38.3 mg/L by promoter substitution and insertion. In addition to the disorazol gene cluster, the BGC of rhizoxin from Burkholderia rhizoxinica was also expressed efficiently, whereas no specific peak was detected when shuangdaolide BGC from Streptomyces sp. B59 was transformed into the host. This system provides another option to explore natural products from different phylogenetic taxa.
CSPα in neurodegenerative diseases
Authors: Huang Liqin , Zhang Zhaohui
Published: November 2022

Adult-onset neuronal ceroid lipofuscinosis (ANCL) is a rare neurodegenerative disease characterized by epilepsy, cognitive degeneration, and motor disorders caused by mutations in the DNAJC5 gene. In addition to being associated with ANCL disease, the cysteine string proteins α (CSPα) encoded by the DNAJC5 gene have been implicated in several neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease. However, the pathogenic mechanism responsible for these neurodegenerative diseases has not yet been elucidated. Therefore, this study examines the functional properties of the CSPα protein and the related mechanisms of neurodegenerative diseases.
Hippocampal adaptation to high altitude: a neuroanatomic profile of hippocampal subfields in Tibetans and acclimatized Han Chinese residents
Authors: Zhang Lianqing , Meng Jinli , Li Hailong , Tang Mengyue , Zhou Zan , Zhou Xingning , Feng Li , Li Xiangwei , Guo Yongyue , He Yuanyuan , He Wanlin , Huang Xiaoqi
Published: November 2022

The hippocampus is highly plastic and vulnerable to hypoxia. However, it is unknown whether and how it adapts to chronic hypobaric hypoxia in humans. With a unique sample of Tibetans and acclimatized Han Chinese individuals residing on the Tibetan plateau, we aimed to build a neuroanatomic profile of the altitude-adapted hippocampus by measuring the volumetric differences in the whole hippocampus and its subfields. High-resolution T1-weighted magnetic resonance imaging was performed in healthy Tibetans (TH, n = 72) and healthy Han Chinese individuals living at an altitude of more than 3,500 m (HH, n = 27). In addition, healthy Han Chinese individuals living on a plain (HP, n = 72) were recruited as a sea-level reference group. Whereas the total hippocampal volume did not show a significant difference across groups when corrected for age, sex, and total intracranial volume, subfield-level differences within the hippocampus were found. Post hoc analyses revealed that Tibetans had larger core hippocampal subfields (bilateral CA3, right CA4, right dentate gyrus); a larger right hippocampus–amygdala transition area; and smaller bilateral presubiculum, right subiculum, and bilateral fimbria, than Han Chinese subjects (HH and/or HP). The hippocampus and all its subfields were found to be slightly and non-significantly smaller in HH subjects than in HP subjects. As a primary explorational study, our data suggested that while the overall hippocampal volume did not change, the core hippocampus of Tibetans may have an effect of adaptation to chronic hypobaric hypoxia. However, this adaptation may have required generations rather than mere decades to accumulate in the population.
A protocol to analyze the global literature on the clinical benefit of interlimb-coordinated intervention in gait recovery and the associated neurophysiological changes in patients with stroke
Authors: Li Shijue , Zhang Haojie , Leng Yan , Lei Di , Yu Qiuhua , Li Kai , Ding Minghui , Lo Wai Leung Ambrose
Published: November 2022

Background

Stroke is among the leading causes of disability of worldwide. Gait dysfunction is common in stroke survivors, and substantial advance is yet to be made in stroke rehabilitation practice to improve the clinical outcome of gait recovery. The role of the upper limb in gait recovery has been emphasized in the literature. Recent studies proposed that four limbs coordinated interventions, coined the term “interlimb-coordinated interventions,” could promote gait function by increasing the neural coupling between the arms and legs. A high-quality review is essential to examine the clinical improvement and neurophysiological changes following interlimb-coordinated interventions in patients with stroke.

Methods

Systematic review and meta-analysis will be conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The literature will be retrieved from the databases of OVID, MEDLINE, PubMed, Web of Science, EMBASE, and PsycINFO. Studies published in English over the past 15 years will be included. All of the clinical studies (e.g., randomized, pseudorandomized and non-randomized controlled trials, uncontrolled trials, and case series) that employed interlimb intervention and assessed gait function of patients with stroke will be included. Clinical functions of gait, balance, lower limb functions, and neurophysiologic changes are the outcome measures of interest. Statistical analyses will be performed using the Comprehensive Meta-Analysis version 3.

Discussion

The findings of this study will provide insight into the clinical benefits and the neurophysiological adaptations of the nervous system induced by interlimb-coordinated intervention in patients with stroke. This would guide clinical decision-making and the future development of targeted neurorehabilitation protocol in stroke rehabilitation to improve gait and motor function in patients with stroke. Increasing neuroplasticity through four-limb intervention might complement therapeutic rehabilitation strategies in this patient group. The findings could also be insightful for other cerebral diseases.
RETRACTED: Adherence to lifelines diet score and risk factors of metabolic syndrome among overweight and obese adults: A cross-sectional study
Authors: Akhavanfar Roozbeh , Hojati Ali , Kahrizi Mohammad Saeed , Farhangi Mahdieh Abbasalizad , Ardekani Abnoos Mokhtari
Published: November 2022

Background

Metabolic syndrome (MetS) is one of the most significant public health issues worldwide, and diet quality is an important controllable environmental factor influencing the incidence of MetS. Numerous dietary scores have been established to assess compliance with dietary recommendations or eating patterns, many of which are not entirely food-based. Hence, Lifelines Diet Score (LLDS) was developed in response to the shortcomings of existing tools. This study aimed to assess any possible links between total food quality and cardiometabolic risk factors among overweight and obese adults.

Methods

This cross-sectional study included 338 overweight and obese individuals [body mass index (BMI) > 25 kg/m2] aged 20–50 years in Tabriz, Iran. To collect dietary data, we used a validated semi-quantitative Food Frequency Questionnaire (FFQ) for Iranian population. Enzymatic-colorimetric methods were used to assess serum glucose and lipids, and enzyme-linked immunosorbent assay (ELISA) kits were used to measure insulin levels. In addition, the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI) were calculated.

Results

BMI and hip circumference (HC) were significantly different (P < 0.05) amongst LLDS tertiles. Adherence to the highest tertile of LLDS was associated with lower SBP, and the subjects in higher LLDS tertiles significantly had lower systolic blood pressure (SBP) (P = 0.04). Triglyceride (TG) levels were also lower in the third tertile of LLDS with a near-significant P-value (P = 0.05).

Conclusion

According to our results, a higher diet quality score, determined by LLDS, can be associated with a lower risk of MetS. Further experimental and longitudinal studies are needed to better understand this relationship.
The prognostic significance of further axillary dissection for sentinel lymph node micrometastases in female breast cancer: A competing risk analysis using the SEER database
Authors: Zhou Yudong , Pu Shengyu , Jiang Siyuan , Li Danni , Li Shouyu , Liu Yang , Ren Yu , Hao Na
Published: November 2022

Background

Sentinel lymph node (SLN) biopsy has been widely recognized as an excellent surgical and staging procedure for early-stage breast cancer, and its development has greatly improved the detection of micrometastases. However, the axillary treatment of micrometastasis has been the subject of much debate.

Methods

We identified 427,131 women diagnosed with breast cancer from 2010 to 2018 in the Surveillance, Epidemiology, and End Results (SEER) database. Patients whose nodal status was micrometastases (pTxN1miM0) were classified into two groups: the SLNB only group and SLNB with complete ALND group, and we used these classifications to carry out propensity-score matching (PSM) analysis. The primary and secondary endpoints were OS and BCSS, respectively. We then implemented the Kaplan-Meier method and Cox proportional hazard model and used Fine and Gray competitive risk regression to identify factors associated with the risk of all-cause mortality.

Results

After the PSM, 1,833 pairs were included in total. The SLNB with complete ALND showed no significant difference in OS (HR=1.04, 95% CI: 0.84-1.28, P=0.73) or BCSS (HR= 1.03, 95% CI: 0.79-1.35, P=0.82) compared to the SLNB only group, and axillary treatment was not associated with breast cancer-specific death (BCSD) (HR=1.13, 95% CI: 0.86-1.48, P=0.400) or other cause-specific death (OCSD) (HR=0.98, 95% CI:0.70-1.38, P=0.920). There was no statistically significant difference in the cumulative incidence of BCSD (Grey’s test, P=0.819) or OCSD (Grey’s test, P=0.788) for between the two groups either. For different molecular subtypes, patients in the SLNB only group showed no statistically significant differences from those in the SLNB with complete ALND group with Luminal A (HR=1.00, 95% CI:0.76-1.32, P=0.98) or Luminal B (HR=0.82, 95% CI:0.42-1.62, P=0.55) but similar OS to HER2-enriched (HR=1.58, 95% CI:0.81-3.07, P=0.19) or triple negative breast cancers (HR=1.18, 95% CI:0.76-1.81, P=0.46).

Conclusions

Our results suggest that in early breast cancer patients with micrometastasis, complete ALND does not seem to be required and that SLNB suffices to control locoregional and distant disease, with no significant adverse effects on survival compared to complete ALND.
β-(4-fluorobenzyl) Arteannuin B induced interaction of ATF-4 and C/EBPβ mediates the transition of breast cancer cells from autophagy to senescence
Authors: Mir Khalid Bashir , Faheem Mir Mohd , Ahmad Syed Mudabir , Rasool Javeed Ur , Amin Tanzeeba , Chakraborty Souneek , Bhagat Madhulika , Ahmed Zabeer , Ali Asif , Goswami Anindya
Published: November 2022

ATF-4 is a master regulator of transcription of genes essential for cellular-adaptive function. In response to the quantum and duration of stress, ATF-4 diligently responds to both pro-apoptotic and pro-survival signals converging into either autophagy or apoptosis/senescence. Despite emerging cues implying a relationship between autophagy and senescence, how these two processes are controlled remains unknown. Herein, we demonstrate β-(4-fluorobenzyl) Arteannuin B (here after Arteannuin 09), a novel semisynthetic derivative of Arteannuin B, as a potent ER stress inducer leading to the consistent activation of ATF-4. Persistent ATF-4 expression at early time-points facilitates the autophagy program and consequently by upregulating p21 at later time-points, the signaling is shifted towards G2/M cell cycle arrest. As bZIP transcription factors including ATF-4 are obligate dimers, and because ATF-4 homodimers are not highly stable, we hypothesized that ATF-4 may induce p21 expression by physically interacting with another bZIP family member i.e., C/EBPβ. Our co-immunoprecipitation and co-localization studies demonstrated that ATF-4 is principally responsible for the autophagic potential of Arteannuin 09, while as, induction of both ATF-4 and C/EBPβ is indispensable for the p21 regulated-cell cycle arrest. Interestingly, inhibition of autophagy signaling switches the fate of Arteannuin 09 treated cells from senescence to apoptosis. Lastly, our data accomplished that Arteannuin 09 is a potent inhibitor of tumor growth and inducer of premature senescence in vivo.
Bruton’s tyrosine kinase inhibitors in the treatment of primary central nervous system lymphoma: A mini-review
Authors: Shen Jing , Liu Jinghua
Published: November 2022

Primary central nervous system lymphoma (PCNSL) is a highly aggressive brain tumor with poor prognosis if no treatment. The activation of the NF-κB (nuclear factor kappa-B) is the oncogenic hallmark of PCNSL, and it was driven by B cell receptor (BCR) and Toll-like receptor (TLR) signaling pathways. The emergence of Bruton’s tyrosine kinase inhibitors (BTKis) has brought the dawn of life to patients with PCNSL. This review summarizes the management of PCNSL with BTKis and potential molecular mechanisms of BTKi in the treatment of PCNSL. And the review will focus on the clinical applications of BTKi in the treatment of PCNSL including the efficacy and adverse events, the clinical trials currently being carried out, the underlying mechanisms of resistance to BTKi and possible solutions to drug resistance.
Effect of autologous hematopoietic stem cell transplantation for patients with peripheral T-cell lymphoma in China: A propensity score-matched analysis
Authors: Gao Hongye , Wu Meng , Hu Shaoxuan , Ding Ning , Ji Xinqiang , Mi Lan , Wang Xiaopei , Song Yuqin , Zhu Jun , Liu Weiping
Published: November 2022

Background

The role of consolidation therapy with autologous stem cell transplantation (ASCT) in patients with peripheral T-cell lymphoma (PTCL) in first complete remission (CR1) or partial remission (PR1) remains controversial. The existing data from China are limited. Therefore, we aimed to investigate the effect of ASCT on the survival of Chinese patients with PTCL showing response to induction chemotherapy at our hospital.

Methods

We retrospectively reviewed the data of patients with PTCL (excluding Natural killer/T cell lymphoma) in CR1 or PR1 treated at Peking University Hospital &Institute from 1996 to 2020. Propensity score matching (PSM) was used to balance clinical characteristics between the ASCT and non-ASCT groups. The primary endpoints were event-free survival (EFS) and overall survival (OS).

Results

Of the 414 selected patients, 73 received ASCT consolidation and 341 did not. Over a median follow-up of 5.7 years, survival was significantly better in the ASCT group than in the non-ASCT group (median EFS, 8.1 years vs. 2.8 years, P = 0.002; median OS, 14.9 years vs. 10.2 years, P = 0.007). The 5-year EFS and OS rates were 68.4% and 77.0% in ASCT group, and 43.2% and 57.6% in non-ASCT group, respectively. The survival benefit was confirmed in the propensity score matched cohort (46 patients who received ASCT and 84 patients who did not receive ASCT): P = 0.007 for median EFS and P = 0.022 for the median OS. Cox regression analysis showed that ASCT was independently associated with better survival: hazard ratio (HR) for EFS, 0.46 (95% CI: 0.28-0.76); HR for OS, 0.50 (95% CI: 0.31-0.84). Subgroup analysis showed that ASCT was more likely to benefit higher-risk patients and those with advanced disease. Among the subtypes of PTCL, the benefit was significant in angioimmunoblastic T-cell lymphoma (HR = 0.26 [95% CI: 0.10-0.66] for EFS and 0.29 [95% CI: 0.12-0.74] for OS), but not in the other subtypes.

Conclusion

ASCT may improve the long-term survival of patients with PTCL in first CR or PR, especially for patients with angioimmunoblastic T-cell lymphoma. The specific groups most likely to benefit from upfront ASCT need to be clearly identified.
Machine learning based prognostic model of Chinese medicine affecting the recurrence and metastasis of I-III stage colorectal cancer: A retrospective study in China
Authors: Tang Mo , Gao Lihao , He Bin , Yang Yufei
Published: November 2022

Background

To construct prognostic model of colorectal cancer (CRC) recurrence and metastasis (R&M) with traditional Chinese medicine (TCM) factors based on different machine learning (ML) methods. Aiming to offset the defects in the existing model lacking TCM factors.

Methods

Patients with stage I-III CRC after radical resection were included as the model data set. The training set and the internal verification set were randomly divided at a ratio of 7: 3 by the “set aside method”. The average performance index and 95% confidence interval of the model were calculated by repeating 100 tests. Eight factors were used as predictors of Western medicine. Two types of models were constructed by taking “whether to accept TCM intervention” and “different TCM syndrome types” as TCM predictors. The model was constructed by four ML methods: logistic regression, random forest, Extreme Gradient Boosting (XGBoost) and support vector machine (SVM). The predicted target was whether R&M would occur within 3 years and 5 years after radical surgery. The area under curve (AUC) value and decision curve analysis (DCA) curve were used to evaluate accuracy and utility of the model.

Results

The model data set consisted of 558 patients, of which 317 received TCM intervention after radical resection. The model based on the four ML methods with the TCM factor of “whether to accept TCM intervention” showed good ability in predicting R&M within 3 years and 5 years (AUC value > 0.75), and XGBoost was the best method. The DCA indicated that when the R&M probability in patients was at a certain threshold, the models provided additional clinical benefits. When predicting the R&M probability within 3 years and 5 years in the model with TCM factors of “different TCM syndrome types”, the four methods all showed certain predictive ability (AUC value > 0.70). With the exception of the model constructed by SVM, the other methods provided additional clinical benefits within a certain probability threshold.

Conclusion

The prognostic model based on ML methods shows good accuracy and clinical utility. It can quantify the influence degree of TCM factors on R&M, and provide certain values for clinical decision-making.
Establishment of a risk model correlated with metabolism based on RNA-binding proteins associated with cell pyroptosis in acute myeloid leukemia
Authors: Bin Ting , Lin Chao , Liu Fang-Jie , Wang Ying , Xu Xiao-Jun , Lin Dong-Jun , Tang Jing , Lu Bo
Published: November 2022

Background

RNA-binding protein (RBP) regulates acute myeloid leukemia (AML) by participating in mRNA editing and modification. Pyroptosis also plays an immunomodulatory function in AML. Therefore, this study aimed to identify pyroptosis-related RBP genes that could predict the prognosis of AML patients.

Methods

AML related expression data were downloaded from the UCSC website and Gene Expression Omnibus (GEO) database. Pyroptosis-RPB-related differentially expressed genes (PRBP-DEGs) were conducted with a protein-protein interactions (PPI) network to screen out the key PRBP-DEGs, based on which a risk model was constructed by Cox analysis, and evaluated by plotting Receiver operating characteristic (ROC) curves and survival curves. Independent prognostic analysis was performed and a nomogram was constructed. Finally, enrichment analysis was performed for high and low risk groups.

Reuslts

A total of 71 PRBP-DEGs were obtained and a pyroptosis-RPB-related risk model was constructed based on IFIT5, MRPL14, MRPL21, MRPL39, MVP, and PUSL1 acquired from Cox analysis. RiskScore, age, and cytogenetics risk category were identified as independent prognostic factors, and the nomogram based on these independent prognostic factors could accurately predict 1-, 3- and 5-year survival of AML patients. Gene set enrichment analysis (GSEA) showed that the high-risk and low-risk groups were mainly enriched in metabolic- and immune-related processes and pathways.

Conclusion

In this study, a risk score model correlated with metabolism based on RNA-binding proteins associated with cell pyroptosis in acute myeloid leukemia was established, which provided a theoretical basis and reference value for therapeutic studies and prognosis of AML.
Development and validation of nomogram prognostic model for early-stage T1-2N0M0 small cell lung cancer: A population-based analysis
Authors: Ge Tao , Zhu Shuncang , Sun Liangdong , Yin Laibo , Dai Jie , Qian Jiayi , Chen Xiangru , Zhang Peng , Zhu Jialong , Jiang Gening
Published: November 2022

Background

Survival outcomes of early-stage T1-2N0M0 small cell lung cancer (SCLC) patients differ widely, and the existing Veterans Administration Lung Study Group (VALSG) or TNM staging system is inefficient at predicting individual prognoses. In our study, we developed and validated nomograms for individually predicting overall survival (OS) and lung cancer-specific survival (LCSS) in this special subset of patients.

Methods

Data on patients diagnosed with T1-2N0M0 SCLC between 2000 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. All enrolled patients were split into a training cohort and a validation cohort according to the year of diagnosis. Using multivariable Cox regression, significant prognostic factors were identified and integrated to develop nomograms for 1-, 3-, and 5-year OS and LCSS prediction. The prognostic performance of our new model was measured by the concordance index (C-index) and calibration curve. We compared our latest model and the 8th AJCC staging system using decision curve analyses (DCA). Kaplan–Meier survival analyses were applied to test the application of the risk stratification system.

Results

A total of 1,147 patients diagnosed from 2000 to 2011 were assigned to the training cohort, and 498 cases that were diagnosed from 2012 to 2015 comprised the validation cohort. Age, surgery, lymph node removal (LNR), and chemotherapy were independent predictors of LCSS. The variables of sex, age, surgery, LNR, and chemotherapy were identified as independent predictors of OS. The above-mentioned prognostic factors were entered into the nomogram construction of OS and LCSS. The C-index of this model in the training cohort was 0.663, 0.702, 0.733, and 0.658, 0.702, 0.733 for predicting 1-, 3-, and 5-year OS and LCSS, respectively. Additionally, in the validation cohort, there were 0.706, 0.707, 0.718 and 0.712, 0.691, 0.692. The calibration curve showed accepted prediction accuracy between nomogram-predicted survival and actual observed survival, regardless of OS or LCSS. In addition, there were significant distinctions in the survival curves of OS and LCSS between different risk groups stratified by prognostic scores. Compared with the 8th AJCC staging system, our new model also improved net benefits.

Conclusions

We developed and validated novel nomograms for individual prediction of OS and LCSS, integrating the characteristics of patients and tumors. The model showed superior reliability and may help clinicians make treatment strategies and survival predictions for early-stage T1-2N0M0 SCLC patients.
Real-world assessment of attenuated dosing anti-PD1 therapy as an alternative dosing strategy in a high-income country (as defined by World Bank)
Authors: Low Jia Li , Huang Yiqing , Sooi Kenneth , Chan Zhi Yao , Yong Wei Peng , Lee Soo Chin , Goh Boon Cher
Published: November 2022

The rising cost of oncological drugs poses a global challenge to patients, insurers, and policy makers, with the leading drugs worldwide by revenue from immune checkpoint inhibitors (ICIs). Despite its cost, ICI is marked as a paradigm shift, offering the potential of a long-term cure. To reduce cost, an attenuated dose of ICI based on pharmacological principles can be used while maintaining efficacy. This real-world study aims to examine the prescribing patterns, the effect of financial constraints, and the outcomes in non-small cell lung cancer (NSCLC). All patients receiving palliative intent ICI treatment for advanced NSCLC between January 2014 and April 2021 in National University Hospital, Singapore were recruited. Demographics, prescription trends, factors affecting the prescription of attenuated dose ICI (AD ICI) versus standard dose ICI (SD ICI), and the effect of dose on survival outcomes, toxicities, and costs were examined. Two hundred seventy-four received ICI. The majority of them were treated in first-line setting. One hundred sixty-two (59%) of patients received AD ICI, whereas 112 (41%) received SD ICI. Patients who did not have a supplemental private as-charged health insurance plan were more likely to have received AD ICI (OR: 4.53 [2.69–7.61] p < 0.001). There was no difference in progression-free survival (PFS) and overall survival (OS)—adjusted HR 1.07 CI [0.76, 1.50] p = 0.697 and HR 0.95 CI [0.67, 1.34] p = 0.773, respectively, between patients who received AD versus SD ICI. A cost minimization analysis evaluating the degree of cost savings related to drug costs estimated a within study cost saving of USD 7,939,059 over 7 years. Our study provides evidence for AD-ICI as a promising strategy to maximize the number of patients who can be treated with ICI. This has the potential to make significant economic impact and allow more patients to benefit from novel therapies.
Immune checkpoint inhibitors for unresectable or metastatic pleomorphic dermal sarcomas
Authors: Helbig Doris , Klein Sebastian
Published: November 2022

Pleomorphic dermal sarcomas (PDS) are rare neoplasms of the skin that occur in UV-exposed sites in the elderly, but represent the most common cutaneous sarcomas. Although the majority of PDS can be surgically removed, local recurrences occur in up to 28%, usually occurring within the first two years after primary excision. Metastases are diagnosed in up to 20% of cases, mainly observed in the skin, lymph nodes and lungs, preferentially affecting patients with underlying hemato-oncologic diseases. Similar to other UV-induced tumors, PDS are inflammatory and immunogenic tumors (with a high number of CD4+/CD8+ tumor-infiltrating lymphocytes (TILs) and checkpoint molecule expression such as PD-L1, LAG-3, TIGIT) with a very high mutational burden. The most common genetic alterations include UV-induced TP53 loss of function mutations, followed by alterations in the CDKN2A/B gene. Rarely, targetable genetic alterations can be detected. Compelling experimental data and clinical reports about PD-1/PD-L1-blocking antibodies in patients with PDS suggest its use as first line treatment in unresectable or metastatic tumor stages. However, individual („off-line”) patient management should be discussed in an interdisciplinary tumor board based on molecular genetic testing, mutational burden, PD-L1 expression, and evidence of tumor-infiltrating lymphocytes in addition to comorbities of the individual patient.
Case report: Real-world experience using a personalized cancer-specific circulating tumor DNA assay in different metastatic melanoma scenarios
Authors: Khaddour Karam , Zhou Alice , Butt Omar H. , Budde Griffin , Malashevich Allyson Koyen , Ansstas George
Published: November 2022

Circulating-tumor DNA (ctDNA) has emerged as an important biomarker for monitoring disease status in cancer patients. Different ctDNA testing platforms have shown promising results in the early detection of disease, monitoring response to treatment, and prognostication in metastatic melanoma. However, several challenges exist, including the reduced shedding of ctDNA into the bloodstream in the metastatic setting, differences in sensitivity among various ctDNA assays, and the inherent inability to distinguish tumor-specific mutations from other mutations that are not related to the cancer of interest. Using a ctDNA assay that is designed to detect multiple single-nucleotide variants (SNVs) that are specific to the tumor itself may allow for more accurate monitoring of disease status in metastatic melanoma. In this case series, we describe a real-world experience using a personalized, tumor-informed ctDNA assay to monitor the clinical trajectories of four patients with metastatic melanoma. Our report highlights potential benefits and limitations using ctDNA in this setting to inform clinical decision-making. This report provides a proof of concept of the technique using an mPCR-NGS-based ctDNA assay (Signatera TM) in the clinical context and in adjunct with other radiological information. Large cohort prospective trials would be needed to validate the utility and validity of this approach.
Research trends on anti-PD-1/PD-L1 immunotherapy for esophageal cancer: A bibliometric analysis
Authors: Yang Yuanyuan , Wang Feng
Published: November 2022

Objectives

The study aims to summarize publication characteristics of anti-programmed cell death protein 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) immunotherapy for esophageal cancer and create scientific maps to explore hotspots and emerging trends with bibliometric methods.

Methods

The publications between 2012 and 2021 were retrieved from the Web of Science Core Collection (WoSCC) on June 20, 2022. Bibliometric tools including HistCite, VOSviewer, and CiteSpace were used for statistical analysis. Data on the trend of the annual output, countries/regions, institutions, journals, authors, subject categories, keywords, and co-cited references were presented in this study.

Results

A total of 552 publications written by 3,623 authors of 872 institutions, 44 countries/regions in 250 journals were included in the bibliometric study. China, USA and Japan were the key countries in this field. Kato Ken, Bang Yung-Jue, Frontiers in Oncology, Journal of Clinical Oncology and Natl Canc Ctr were the top 1 productive author, co-cited author, productive journal, co-cited journal and prolific institution, respectively. The top 4 most present keywords were esophageal cancer, immunotherapy, esophageal squamous cell carcinoma and PD-L1. Neoadjuvant chemotherapy, response, PD-1 blockade and CD8+ T cell were four latest research frontiers. The keywords reflected the progress from PD-1/PD-L1 expression to the clinical application of PD-1/PD-L1 inhibitors. The current researches mainly focus on neoadjuvant immunotherapy for esophageal cancer and development of biomarkers. Further research is warranted to determine effective predictive biomarkers or models, illustrate the molecular mechanism of combined treatment, and construct the optimal therapeutic strategy.

Conclusions

This study visually analyzed the global trend and hotspots of anti-PD-1/PD-L1 immunotherapy for esophageal cancer over the past decade. The results could guide scientists to comprehensively understand the global frontiers and determine future directions.
Impact of interaction networks of B cells with other cells on tumorigenesis, progression and response to immunotherapy of renal cell carcinoma: A review
Authors: Wang Yu-qi , Chen Wen-jin , Li Wen-yan , Pan Xiu-wu , Cui Xin−gang
Published: November 2022

Ample evidence indicates that the development and progression of renal cell carcinoma (RCC) are complex pathological processes involving interactions between tumor cells, immune cells and stromal components. Tumor infiltrated immune cells determine whether tumor advancement is promoted or inhibited. Among them, infiltrated B lymphocytes are present in all stages of RCC, playing a major role in determining tumor formation and advancement, as an essential part in the tumor microenvironment (TME). Although the advent of targeted and immune therapies has remarkably improved the survival of patients with advanced RCC, few cases can achieve complete response due to drug resistance. In this review article, we intend to summary the recent studies that outline the interaction networks of B cells with other cells, discuss the role of B cells in RCC development and progression, and assess their impact on RCC immunotherapy.
Case report: Histological findings of peri-appendicitis in three children with SARS-CoV-2 – related multisystem inflammatory syndrome: A mark for systemic inflammation?
Authors: Fabi Marianna , Vasuri Francesco , Guida Fiorentina , Rocca Alessandro , Lima Mario , D’Errico Antonietta , Lanari Marcello
Published: November 2022

Background

Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious condition that can potentially develop after SARS-CoV-2 infection in children. Gastrointestinal manifestation in MIS-C can mimic acute abdomen, potentially leading to unnecessary surgical treatment. Immune-mediated mechanisms seem to be a determining factor in its pathogenesis, and histological studies can help to shed light on this aspect. We describe three cases of children diagnosed with MIS-C that underwent appendectomy.

Methods

We retrospectively collected the clinical features and histological findings of three previously healthy children who underwent appendectomy for clinical suspicion of acute appendicitis but were later diagnosed with MIS-C.

Findings

The three children presented with prominent abdominal manifestations and fever leading to the suspicion of acute abdomen. Histological findings showed transmural and perivascular inflammation. Notably, CD68+ macrophages were predominant in the child with milder abdominal symptoms without cardiac injury, while CD3+ lymphocytes in the patient presented with more severe abdominal pain and cardiovascular involvement at admission.

Interpretation

Gastrointestinal symptoms of children with MIS-C improve after proper immunomodulatory therapy, conversely showing inadequate response to surgical appendectomy. Histological findings revealed different inflammatory cell infiltration that primarily involved perivisceral fat and vessels, and subsequently mucosal tissue, in contrast to other forms of acute appendicitis. Our findings suggest that this kind of peri-appendicitis in MIS-C could represent a focal sign of systemic inflammation, with different histological patterns compared to other forms of acute appendicitis.
Clinical characteristics and genetics of ten Chinese children with PRRT2-associated neurological diseases
Authors: Liu Meiyan , Sun Xiaoang , Lin Longlong , Luo Xiaona , Wang Simei , Wang Chunmei , Zhang Yuanfeng , Xu Quanmei , Xu Wuhen , Wu Shengnan , Lan Xiaoping , Chen Yucai
Published: November 2022

Background

Proline-rich transmembrane protein 2 (PRRT2) plays an important role in the central nervous system and mutations in the gene are implicated in a variety of neurological disorders. This study aimed to summarize the clinical characteristics and gene expression analysis of neurological diseases related to the PRRT2 gene and explore the clinical characteristics, therapeutic effects, and possible pathogenic mechanisms of related diseases.

Methods

We enrolled 10 children with PRRT2 mutation-related neurological diseases who visited the Children's Hospital affiliated with the Shanghai Jiaotong University School of Medicine/Shanghai Children's Hospital between May 2017 and February 2022. Video electroencephalography (VEEG), cranial imaging, treatment regimens, gene results, and gene expression were analyzed. Genetic testing involved targeted sequencing or whole-exome genome sequencing (WES). We further analyzed the expression and mutation conservation of PRRT2 and synaptosome-associated protein 25 (SNAP25) in blood samples using quantitative polymerase chain reaction (qPCR) and predicted the protein structure. Summary analysis of the reported gene maps and domains was also performed.

Results

Ten children with PRRT2 gene mutations were analyzed, and 4 mutations were identified, consisting of 2 new (c.518A > C, p.Glu173 Ala; c.879 + 112G > A, p.?) and two known (c. 649 dup, p. Arg217Profs * 8; c. 649 del, p. Arg217Glufs * 12) mutations. Among these mutations, one was de novo(P6), and three could not be determined because one parent refused genetic testing. The clinical phenotypes were paroxysmal kinesigenic dyskinesia (PKD), benign familial infantile epilepsy (BFIE), epilepsy, infantile spasms, and intellectual disability. The qPCR results showed that PRRT2 gene expression levels were significantly lower in children and parent carriers than the control group. The SNAP25 gene expression level of affected children was significantly lower (P ≤ 0.001) than that of the control group. The mutation sites reported in this study are highly conserved in different species. Among the various drugs used, oxcarbazepine and sodium valproate were the most effective. All 10 children had a good disease prognosis, and 8 were completely controlled with no recurrence, whereas 2 had less severe and fewer seizures.

Conclusion

Mutation of PRRT2 led to a significant decrease in its protein expression level and that of SNAP25, suggesting that the mutant protein may lead to the loss of its function and that of related proteins. This mutation site is highly conserved in most species, and there was no significant correlation between specific PRRT2 genotypes and clinical phenotypes. Asymptomatic carriers also have decreased gene expression levels, suggesting that more factors are involved.
Zhizhu Kuanzhong, a traditional Chinese medicine, alleviates gastric hypersensitivity and motor dysfunction on a rat model of functional dyspepsia
Authors: Xiao Zhuanglong , Xu Jing , Tan Jun , Zhang Shengyan , Wang Nian , Wang Ruiyun , Yang Pengcheng , Bai Tao , Song Jun , Shi Zhaohong , Lyu Wenliang , Zhang Lei , Hou Xiaohua
Published: November 2022

Ethnopharmacological relevance: Zhizhu Kuanzhong (ZZKZ) is a traditional Chinese medicine modified from classic formula Zhizhu decoction in “Synopsis of Golden Chamber” (Han Dynasty in the 3rd century) and the Zhizhu pill in “Differentiation on Endogenous” in Jin Dynasty (1,115–1,234). ZZKZ contains four botanical drugs, including Citrus × Aurantium L [Rutaceae; Aurantii Fructus Immaturus], Atractylodes Macrocephala Koidz. [Compositae; Rhizoma Atractylodis Macrocephalae], Bupleurum Chinense DC [Apiaceae; Radix Bupleuri Chinensis], and Crataegus Pinnatifida Bunge [Rosaceae; Fructus Crataegi Pinnatifidae], which have been widely used in clinical therapy for functional dyspepsia (FD).

Aim of the study: This study aimed to evaluate the pharmacological effects and mechanisms of action of ZZKZ on gastric hypersensitivity and motor dysfunction in a rat model of FD.

Materials and methods: FD was induced in Sprague-Dawley rats by neonatal gastric irritation with 0.1% iodoacetamide. The FD rats were treated with ZZKZ (0.5 g/kg, 1.0 g/kg, or 1.5 g/kg respectively) by gavage for 7 days, while domperidone (3 mg/kg) acted as treatment control. Body weight gain, food intake, gastric emptying, and intestinal propulsion were also measured. Ex vivo gastric smooth muscle activity recordings and greater splanchnic afferent (GSN) firing recordings were employed to evaluate gastric motility and sensation. Particularly, the role of 5-HT in the action of ZZKZ in improving gastric dysmotility and hypersensitivity was explored.

Results: ZZKZ promoted weight gain, food intake, gastric emptying, and intestinal propulsion in FD rats. ZZKZ promoted spontaneous and ACh-induced contractions of gastric smooth muscle strips in FD rats, alleviated spontaneous activity, and chemical (acid perfusion) and mechanical (intragastric distension) stimulated GSN firing in FD rats. ZZKZ ameliorated gastric smooth muscle contraction and GSN firing induced by 5-HT in FD rats. ZZKZ stimulated the release of serum 5-HT, with reduced 5-HT3 receptor and increased 5-HT4 receptor mRNA expression in the guts of FD rats.

Conclusion: This study demonstrated that ZZKZ improves FD-related gastric hypersensitivity and motor dysfunction and should be an effective compound for relieving FD symptoms. The gastric 5-HT system with lower 5-HT3 activity and increased 5-HT4 distribution is involved in the mechanisms of ZZKZ underlying the treatment of FD.