bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic social defeat stress caused region-specific oligodendrogenesis impairment in adolescent mice
Authors: Chen Huan , Kang Zhewei , Liu Xueqing , Zhao Yinglin , Fang Zeman , Zhang Jinling , Zhang Handi
Published: January 2023

Introduction

Social stress in adolescents precipitates stress-related emotional disorders. In this study we aimed to investigate oligodendrogenesis in three stress-associated brain regions, medial prefrontal cortex (mPFC), habenula, and amygdala in adolescent mice exposed to social defeat stress.

Methods

Four-week-old adolescent mice were subjected to social defeat for 10 days, followed by behavioral tests and evaluations of oligodendroglial proliferation and differentiation.

Results

Stressed mice showed reduced social interaction, more stretched approach posture, lower sucrose preference, but no changes in the forced swimming test. EdU labeled proliferative cells, newly formed NG2+EdU + oligodendrocyte precursor cells (OPCs), and Olig2+EdU+ oligodendrocyte lineage cells (OLLs) were significantly decreased in the mPFC and the lateral habenula, but not in the amygdala and the medial habenula in socially defeated mice. APC+Edu+ newly-generated mature oligodendrocytes (OLs) were decreased in the mPFC in stressed mice. However, the total number of NG2+ OPCs, APC+ mature OLs, and Olig2+ OLLs were comparable in all the brain regions examined between stressed and control mice except for a decrease of APC+ mature OLs in the prelimbic cortex of stressed mice.

Conclusion

Our findings indicate that adolescent social stress causes emotion-related behavioral changes and region-specific impairment of oligodendrogenesis.
The Temporal Voice Areas are not “just” Speech Areas
Authors: Trapeau Régis , Thoret Etienne , Belin Pascal
Published: January 2023

The Temporal Voice Areas (TVAs) respond more strongly to speech sounds than to non-speech vocal sounds, but does this make them Temporal “Speech” Areas? We provide a perspective on this issue by combining univariate, multivariate, and representational similarity analyses of fMRI activations to a balanced set of speech and non-speech vocal sounds. We find that while speech sounds activate the TVAs more than non-speech vocal sounds, which is likely related to their larger temporal modulations in syllabic rate, they do not appear to activate additional areas nor are they segregated from the non-speech vocal sounds when their higher activation is controlled. It seems safe, then, to continue calling these regions the Temporal Voice Areas.
Saliva based diagnostic methodologies for a fast track detection of autism spectrum disorder: A mini-review
Authors: Sharma Vaibhav , Choudhury Saptamita Paul , Kumar Saroj , Nikolajeff Fredrik
Published: January 2023

Autism spectrum disorder (ASD) is considered a complicated neurodevelopment disorder with rising prevalence globally. ASD is characterized by a series of events including varying degrees of defects in communication, learning, and social interaction which is accompanied by stereotypical behavioral patterns. Despite extensive research, the current diagnosis for ASD is complex and almost solely based on the behavioral assessments of the suspected individuals. The multifactorial etiopathology of this disease along with the diversity of symptoms among different individuals adds to the current intricacies for accurate prognosis of ASD. Hence, there exists a dire need for biologically relevant biomarkers for an early diagnosis and for tracking the efficacy of therapeutic interventions. Until recently, among various biofluids, saliva has gained increasing interest for biomarker identification, the advantages include the non-invasive nature and ease of sample handling. This mini-review aims to provide a succinct summary of recent literature on saliva-based diagnostic modalities for ASD, examine various studies that highlight the potential use of proteomic and/or RNA-based biomarkers. Finally, some conclusive perspectives of using the salivary system for ASD mechanistic details and diagnosis are also discussed.
Probabilities of evoked and spontaneous synaptic transmission at individual active zones: Lessons from Drosophila
Authors: Bykhovskaia Maria
Published: January 2023

Nerve terminals release neuronal transmitters at morphological specializations known as active zones (AZs). Synaptic vesicle fusion at individual AZs is probabilistic, and this property is fundamental for the neuronal information transfer. Until recently, a lack of appropriate tools limited the studies of stochastic properties of neuronal secretion at individual AZs. However, Drosophila transgenic lines that express postsynaptically tethered Ca2+ sensor GCaMP enabled the visualization of single exocytic event at individual AZs. The present mini-review discusses how this powerful approach enables the investigation of the evoked and spontaneous transmission at single AZs and promotes the understanding of the properties of both release components.
Analytical approaches to examine gamma-aminobutyric acid and glutamate vesicular co-packaging
Authors: Kim SeulAh , Sabatini Bernardo L.
Published: January 2023

Multi-transmitter neurons, i.e., those that release more than one type of neurotransmitter, have been found in many organisms and brain areas. Given the peculiar biology of these cells, as well as the potential for diverse effects of each of the transmitters released, new tools, and approaches are necessary to parse the mechanisms and functions of synaptic co-transmission. Recently, we and others have studied neurons that project to the lateral habenula and release both gamma-aminobutyric acid (GABA) and glutamate, in some cases by packaging both transmitters in the same synaptic vesicles. Here, we discuss the main challenges with current electrophysiological approaches to studying the mechanisms of glutamate/GABA co-release, a novel statistical analysis that can identify co-packaging of neurotransmitters versus release from separate vesicle, and the implications of glutamate/GABA co-release for synapse function and plasticity.
Hybrid parallel reduction algorithms for the multi-level CMFD acceleration in the neutron transport code PANDAS-MOC
Authors: Tao Shunjiang , Xu Yunlin
Published: January 2023

The coarse mesh finite difference (CMFD) technique is considered efficiently in accelerating the convergence of the iterative solutions in the computational intensive 3D whole-core pin-resolved neutron transport simulations. However, its parallel performance in the hybrid MPI/OpenMP parallelism is inadequate, especially when running with larger number of threads. In the original Whole-code OpenMP threading hybrid model (WCP) model of the PANDAS-MOC neutron transport code, the hybrid MPI/OpenMP reduction has been determined as the principal issue that restraining the parallel speedup of the multi-level coarse mesh finite difference solver. In this paper, two advanced reduction algorithms are proposed: Count-Update-Wait reduction and Flag-Save-Update reduction, and their parallel performances are examined by the C5G7 3D core. Regarding the parallel speedup, the Flag-Save-Update reduction has attained better results than the conventional hybrid reduction and Count-Update-Wait reduction.
The temporal trend of disease burden attributable to metabolic risk factors in China, 1990–2019: An analysis of the Global Burden of Disease study
Authors: Jin Yingzhao , So Ho , Cerin Ester , Barnett Anthony , Mubarik Sumaira , Hezam Kamal , Feng Xiaoqi , Wang Ziyue , Huang Junjie , Zhong Chenwen , Hayat Khezar , Wang Fang , Wu Ai-Min , Xu Suowen , Zou Zhiyong , Lim Lee-Ling , Cai Jiao , Song Yimeng , Tam Lai-shan , Wu Dongze
Published: January 2023

Background and aims

The disease burden attributable to metabolic risk factors is rapidly increasing in China, especially in older people. The objective of this study was to (i) estimate the pattern and trend of six metabolic risk factors and attributable causes in China from 1990 to 2019, (ii) ascertain its association with societal development, and (iii) compare the disease burden among the Group of 20 (G20) countries.

Methods

The main outcome measures were disability-adjusted life-years (DALYs) and mortality (deaths) attributable to high fasting plasma glucose (HFPG), high systolic blood pressure (HSBP), high low-density lipoprotein (HLDL) cholesterol, high body-mass index (HBMI), kidney dysfunction (KDF), and low bone mineral density (LBMD). The average annual percent change (AAPC) between 1990 and 2019 was analyzed using Joinpoint regression.

Results

For all six metabolic risk factors, the rate of DALYs and death increased with age, accelerating for individuals older than 60 and 70 for DALYs and death, respectively. The AAPC value in rate of DALYs and death were higher in male patients than in female patients across 20 age groups. A double-peak pattern was observed for AAPC in the rate of DALYs and death, peaking at age 20–49 and at age 70–95 plus. The age-standardized rate of DALYs increased for HBMI and LBMD, decreased for HFPG, HSBP, KDF, and remained stable for HLDL from 1990 to 2019. In terms of age-standardized rate of DALYs, there was an increasing trend of neoplasms and neurological disorders attributable to HFPG; diabetes and kidney diseases, neurological disorders, sense organ diseases, musculoskeletal disorders, neoplasms, cardiovascular diseases, digestive diseases to HBMI; unintentional injuries to LBMD; and musculoskeletal disorders to KDF. Among 19 countries of Group 20, in 2019, the age-standardized rate of DALYs and death were ranked fourth to sixth for HFPG, HSBP, and HLDL, but ranked 10th to 15th for LBMD, KDF, and HBMI, despite the number of DALYs and death ranked first to second for six metabolic risk factors.

Conclusions

Population aging continuously accelerates the metabolic risk factor driven disease burden in China. Comprehensive and tight control of metabolic risk factors before 20 and 70 may help to mitigate the increasing disease burden and achieve healthy aging, respectively.
Spinal oncologic paraparesis: Analysis of neurological and surgical outcomes in patients with intramedullary, extramedullary, and extradural tumors
Authors: Alhalabi Obada T. , Heene Stefan , Landré Vincent , Neumann Jan-Oliver , Scherer Moritz , Ishak Basem , Kiening Karl , Zweckberger Klaus , Unterberg Andreas W. , Younsi Alexander
Published: January 2023

Objectives

Paraparesis due to oncologic lesions of the spine warrants swift neurosurgical intervention to prevent permanent disability and hence maintain independence of affected patients. Clinical parameters that predict a favorable outcome after surgical intervention could aid decision-making in emergency situations.

Methods

Patients who underwent surgical intervention for paraparesis (grade of muscle strength <5 according to the British Medical Research Council grading system) secondary to spinal neoplasms between 2006 and 2020 were included in a single-center retrospective analysis. Pre- and postoperative clinical data were collected. The neurological status was assessed using the modified McCormick Disability Scale (mMcC) Score. In a univariate analysis, patients with favorable (discharge mMcC improved or stable at <3) and non-favorable outcome (discharge mMcC deteriorated or stable at >2) and different tumor anatomical compartments were statistically compared.

Results

117 patients with oncologic paraparesis pertaining to intramedullary lesions (n=17, 15%), intradural extramedullary (n=24, 21%) and extradural lesions (n=76, 65%) with a mean age of 65.3 ± 14.6 years were included in the analysis. Thoracic tumors were the most common (77%), followed by lumbar and cervical tumors (13% and 12%, respectively). Surgery was performed within a mean of 36±60 hours of admission across all tumors and included decompression over a median of 2 segments (IQR:1-3) and mostly subtotal tumor resection (n=83, 71%). Surgical and medical complications were documented in 9% (n=11) and 7% (n=8) of cases, respectively. The median hospital length-of-stay was 9 (7-13) days. Upon discharge, the median mMcC score had improved from 3 to 2 (p<0.0001). At last follow-up (median 180; IQR 51-1080 days), patients showed an improvement in their mean Karnofsky Performance Score (KPS) from 51.7±18.8% to 65.3±20.4% (p<0.001). Localization in the intramedullary compartment, a high preoperative mMcC score, in addition to bladder and bowel dysfunction were associated with a non-favorable outcome (p<0.001).

Conclusion

The data presented on patients with spinal oncologic paraparesis provide a risk-benefit narrative that favors surgical intervention across all etiologies. At the same time, they outline clinical factors that confer a less-favorable outcome like intramedullary tumor localization, a high McCormick score and/or bladder and bowel abnormalities at admission.
Look how far we have come: BREAST cancer detection education on the international stage
Authors: Trieu Phuong Dung (Yun) , Mello-Thoms Claudia R. , Barron Melissa L. , Lewis Sarah J.
Published: January 2023

The development of screening mammography over 30 years has remarkedly reduced breast cancer–associated mortality by 20%-30% through detection of small cancer lesions at early stages. Yet breast screening programmes may function differently in each nation depending on the incidence rate, national legislation, local health infrastructure and training opportunities including feedback on performance. Mammography has been the frontline breast cancer screening tool for several decades; however, it is estimated that there are 15% to 35% of cancers missed on screening which are owing to perceptual and decision-making errors by radiologists and other readers. Furthermore, mammography screening is not available in all countries and the increased speed in the number of new breast cancer cases among less developed countries exceeds that of the developed world in recent decades. Studies conducted through the BreastScreen Reader Assessment Strategy (BREAST) training tools for breast screening readers have documented benchmarking and significant variation in diagnostic performances in screening mammogram test sets in different countries. The performance of the radiologists from less well-established breast screening countries such as China, Mongolia and Vietnam were significant lower in detecting early-stage cancers than radiologists from developed countries such as Australia, USA, Singapore, Italy. Differences in breast features and cancer presentations, discrepancies in the level of experiences in reading screening mammograms, the availability of high-quality national breast screening program and breast image interpretation training courses between developed and less developed countries are likely to have impact on the variation of readers’ performances. Hence dedicated education training programs with the ability to tailor to different reader cohorts and different population presentations are suggested to ameliorate challenges in exposure to a range of cancer cases and improve the interpretation skills of local radiologists. Findings from this review provide a good understanding of the radiologist’ performances and their improvement using the education interventions, primarily the BREAST program, which has been deployed in a large range of developing and developed countries in the last decade. Self-testing and immediate feedback loops have been shown to have important implications for benchmarking and improving the diagnostic accuracy in radiology worldwide for better breast cancer control.
NcRNA-regulated CAPZA1 associated with prognostic and immunological effects across lung adenocarcinoma
Authors: Qin Tingting , Xiang Wanping , Mao Yiming , Zhai Hongyan , Yang Zhihao , Zhang Hongpan
Published: January 2023

Recent discoveries have suggested that the F-actin capping protein α1 subunit (CAPZA1) in various human tumors could play a significantly important role in regulating cell proliferation, metastasis, and epithelial–mesenchymal transition. However, the immune-regulating role of CAPZA1 in the initiation and development of lung adenocarcinoma (LUAD) remains unclear. In our research, we first found that CAPZA1 serves as an oncogene in pan-cancers from the TCGA data and higher CAPZA1 expression process unfavorably prognostic value in LUAD based on starBase database, PrognoScan, and LOGpc database. Then, in our analyses, lncRNAs AC026356.1 in LUAD acted as a competitive endogenous RNA (ceRNA) of miR-30d-5p, which might be the possible regulatory miRNA of CAPZA1 based on the starBase database. Finally, we confirmed that CAPZA1 expression had a tightly positive correlation with immune infiltration cells, immune infiltration markers, TMB, MSI, immune score, stromal score, and immune checkpoints, indicating that CAPZA1 was a markedly reliable therapeutic target for immunological antitumor strategies. In conclusion, our investigations revealed that CAPZA1 might function as an immune-associated biomarker in the development and treatment of LUAD, thereby acting as a promising prognostic and therapeutic target against LUAD.
ESR1 fusions and therapeutic resistance in metastatic breast cancer
Authors: Nagy Zsuzsanna , Jeselsohn Rinath
Published: January 2023

Breast cancer is the most frequent female malignant tumor, and the leading cause of cancer death in women worldwide. The most common subtype of breast cancer is hormone receptor positive that expresses the estrogen receptor (ER). Targeting ER with endocrine therapy (ET) is the current standard of care for ER positive (ER+) breast cancer, reducing mortality by up to 40% in early- stage disease. However, resistance to ET represents a major clinical challenge for ER+ breast cancer patients leading to disease recurrence or progression of metastatic disease. Salient drivers of ET resistance are missense mutations in the ER gene (ESR1) leading to constitutive transcriptional activity and reduced ET sensitivity. These mutations are particularly prominent and deleterious in metastatic breast cancer (MBC). In addition to activating ESR1 point mutations, emerging evidence imposes that chromosomal translocation involving the ESR1 gene can also drive ET resistance through the formation of chimeric transcription factors with constitutive transcriptional activity. Although these ESR1 gene fusions are relatively rare, they are enriched in ET resistant metastatic disease. This review discusses the characteristics of ER fusion proteins and their association with clinical outcomes in more aggressive and metastatic breast cancer. The structure and classification of ER fusion proteins based on function and clinical significance are also addressed. Finally, this review summarizes the metastatic phenotypes exhibited by the ER fusion proteins and their role in intrinsic ET resistance.
CAR-T therapy followed by allogeneic hematopoietic stem cell transplantation for refractory/relapsed acute B lymphocytic leukemia: Long-term follow-up results
Authors: Li Zhihui , Yang Keyan , Song Yanzhi , Zhao Yongqiang , Wu Fan , Wen Xiaopei , Li Jing , Wang Xianxuan , Xu Teng , Zheng Xiaoyu , Zheng Qinglong , Wu Tong
Published: January 2023

Background

Patients with refractory/relapsed (r/r) acute B lymphocytic leukemia (B-ALL) can achieve complete response (CR) after chimeric antigen receptor T-cell (CAR-T) therapy, but recurrence occurs in the short term. To reduce recurrence and improve survival, CAR-T therapy followed by transplantation is a feasible option. We analyzed the long-term follow-up outcomes and the risk factors for allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CR by CAR-T therapy in this study.

Methods

A total of 144 patients who underwent allo-HSCT after CAR-T therapy in our hospital were enrolled in this study. Target gene analysis was performed in 137 r/r B-ALL patients receiving allo-HSCT after CR by CAR-T therapy. Among the 137 patients, 87 were evaluated for germline predisposition gene mutations, and 92 were evaluated for tumor somatic gene mutations using NGS. The clinical factors, germline predisposition gene and somatic gene mutations associated with the prognosis of patients receiving transplantation after CAR-T therapy were analyzed using univariate Cox regression. Factors related to disease-free survival (DFS) and overall survival (OS) were analyzed using multivariate Cox regression analysis.

Results

In 137 r/r B-ALL patients, the 2-year cumulative incidence of recurrence (CIR), OS and DFS in patients receiving allo-HSCT after CAR-T therapy was 31.5%, 71.4%, and 60.5%, respectively. The 2-year OS and DFS in MRD-negative patients were 80.9% and 69.3%, respectively. Univariate Cox analysis showed that pretransplant MRD positivity, fungal infection, germline EP300 mutation and somatic TP53 mutation were associated with a poor prognosis after transplantation; a TBI-based regimen was a protective factor for survival and recurrence after transplantation. Multivariate Cox regression analysis showed that the TBI-based regimen was an independent protective factor for DFS, fungal infection and MRD positivity were independent risk factors for DFS, and tumor somatic TP53 mutation and germline EP300 mutation were independent risk factors for DFS and OS.

Conclusion

Germline EP300 mutation and tumor somatic TP53 mutation are poor prognostic factors for posttransplant recurrence and survival in r/r B-ALL patients achieving CR after CAR-T therapy. The prognostic risk factors should be considered in adjusting treatment strategies to improve the efficacy of clinical diagnosis and treatment.
CT-based delta radiomics in predicting the prognosis of stage IV gastric cancer to immune checkpoint inhibitors
Authors: Li Jiazheng , Chen Zifan , Chen Yang , Zhao Jie , He Meng , Li Xiaoting , Zhang Li , Dong Bin , Zhang Xiaotian , Tang Lei , Shen Lin
Published: January 2023

Introduction

To explore the prognostic value of CT-based delta radiomics in predicting the prognosis of patients with stage IV gastric cancer treated with immune checkpoint inhibitors (ICI).

Materials and methods

Forty-two patients with stage IV gastric cancer, who had received ICI monotherapy, were enrolled in this retrospective study. Baseline and first follow-up CT scans were analyzed. Intratumoral and peritumoral regions of interest (ROI) were contoured, enabling the extraction of 192 features from each ROI. The intraclass correlation coefficients were used to select features with high stability. The least absolute shrinkage and selection operator was used to select features with high weights for predicting patient prognosis. Kaplan–Meier analysis and log-rank test were performed to explore the association between features and progression free survival (PFS). Cox regression analyses were used to identify predictors for PFS. The C-index was used to assess the prediction performance of features.

Results

Two radiomics features of ΔVintra_ZV and postVperi_Sphericity were identified from intratumoral and peritumoral regions, respectively. The Kaplan–Meier analysis revealed significant differences in PFS between patients with low and high feature value (ΔVintra_ZV: P=0.000; postVperi_Sphericity: P=0.012), and the multivariable cox analysis demonstrated that ΔVintra_ZV was independent predictor for PFS (HR, 1.911; 95% CI: 1.163–3.142; P=0.011), with C-index of 0.705.

Conclusions

Based on CT scans at baseline and first follow-up, the delta radiomics features could efficiently predict the PFS of gastric cancer patients treated with ICI therapy.
Implications of BRAF V600E mutation in gliomas: Molecular considerations, prognostic value and treatment evolution
Authors: Di Nunno Vincenzo , Gatto Lidia , Tosoni Alicia , Bartolini Stefania , Franceschi Enrico
Published: January 2023

Gliomas are molecularly heterogeneous brain tumors responsible for the most years of life lost by any cancer. High-grade gliomas have a poor prognosis and despite multimodal treatment including surgery, radiotherapy, and chemotherapy, exhibit a high recurrence rate. There is a need for new therapeutic approaches based on precision medicine informed by biomarker assessment and BRAF, a key regulator of MAPK signaling pathway, influencing cell differentiation, proliferation, migration and pro-tumorigenic activity, is emerging as a promising molecular target. V600E, is the most frequent BRAF alteration in gliomas, especially in pediatric low-grade astrocytomas, pleomorphic xanthoastrocytoma, papillary craniopharyngioma, epithelioid glioblastoma and ganglioglioma. The possible application of BRAF-targeted therapy in gliomas is continuously growing and there is preliminary evidence of prolonged disease control obtained by BRAF inhibitors in tumors harboring BRAF V600E mutation. The possibility of introducing targeted therapies into the treatment algorithm represents a paradigm shift for patients with BRAF V600E mutant recurrent high-grade and low-grade glioma and BRAF routine testing should be considered in clinical practice. The focus of this review is to summarize the molecular landscape of BRAF across glioma subtypes and the novel therapeutic strategies for BRAF V600E mutated tumors.
Antibody-drug conjugates and predictive biomarkers in advanced urothelial carcinoma
Authors: Fenton Sarah E. , VanderWeele David J.
Published: January 2023

The use of antibody-drug conjugates (ADCs) is expanding in several malignancies, including urothelial carcinoma where two of these medications have been approved for use and several others remain under study. ADCs act by binding to specific cell surface proteins, delivering anticancer agents directly to the target cells. Preclinical studies suggest that loss of these surface proteins alters sensitivity to therapy and expression of target proteins vary significantly based on the tumor subtype, prior therapies and other characteristics. However, use of biomarkers to predict treatment response have not been regularly included in clinical trials and clinician practice. In this review we summarize what is known about potential predictive biomarkers for ADCs in UC and discuss potential areas where use of biomarkers may improve patient care.
Metabolic syndrome is a risk factor for breast cancer patients receiving neoadjuvant chemotherapy: A case-control study
Authors: Zhou Zhaoyue , Zhang Yue , Li Yue , Jiang Cong , Wu Yang , Shang Lingmin , Huang Yuanxi , Cheng Shaoqiang
Published: January 2023

Purpose

To investigate the impact of metabolic syndrome (MetS) on pathologic complete response (pCR) and clinical outcomes in breast cancer (BC) patients who received neoadjuvant chemotherapy (NAC).

Methods

We analyzed 221 female BC patients at Harbin Medical University Cancer Hospital who received NAC and divided them into MetS and non-MetS groups according to National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria to investigate the association between MetS and clinicopathological characteristics, pathologic response, and long-term survival and to observe the changes in metabolic parameters after NAC.

Results

A total of 53 (24.0%) BC patients achieved pCR after NAC in our study. MetS status was an independent predictor of pCR, and pCR was more difficult to obtain in the MetS group than the non-MetS group (P=0.028). All metabolic parameters deteriorated significantly after NAC, especially the blood lipid index (P<0.010). The median follow-up time was 6 years. After adjusting for other prognostic factors, MetS was found to be strongly associated with an increased risk of recurrence (P=0.007) and mortality (P=0.004) in BC patients receiving NAC. Compared to individuals without any MetS component, the risk of death and disease progression increased sharply as the number of MetS components increased.

Conclusions

In BC patients who received NAC, MetS was associated with poor outcomes, including a lower pCR rate and increased risks of recurrence and mortality.
Case report: The power of immunotherapy in advanced cutaneous squamous cell carcinoma
Authors: Brockwell Maximilian , Husain Marium , Verschraegen Claire , Wu Richard , Tinoco Gabriel
Published: January 2023

We describe the case of a neglected cutaneous squamous cell carcinoma with extensive facial involvement. The patient is a male in his late 70s who presented to dermatology with a large destructive facial mass that had increased in size gradually over 3 years and then rapidly proliferated, consuming a large portion of his left maxillofacial region. While the immediate reaction was referral to hospice care, medical oncology recommended treatment with cemiplimab, an immune checkpoint inhibitor. Collaboration with multiple providers facilitated the delivery of a multidisciplinary approach utilizing immunotherapy with QUAD shot radiotherapy. The immunotherapy treatment resulted in a dramatic disease regression, but the large facial anatomical defect caused by the carcinoma remained. The patient is undergoing reconstructive surgeries. This case illustrates the potential for significant response with immune checkpoint inhibitors delivered in combination with cyclical hypofractionated radiation therapy for patients with cutaneous squamous cell carcinoma, even in very advanced disease.
Case report: Rosai-Dorfman disease with rare extranodal lesions in the pelvis, heart, liver and skin
Authors: Yoshida Misaki , Zoshima Takeshi , Hara Satoshi , Takahashi Yoshinori , Nishioka Ryo , Ito Kiyoaki , Mizuhima Ichiro , Inoue Dai , Nakada Satoko , Kawano Mitsuhiro
Published: January 2023

Rosai-Dorfman disease (RDD), a rare form of non-Langerhans cell histiocytosis, can involve systemic extranodal lesions. Skin lesions are the most common, whereas intrapelvic, cardiac, and hepatic lesions are infrequent. The present study describes a 74-year-old woman with multiple extranodal lesions in the pelvis, heart, liver, and skin that were successfully treated with glucocorticoid therapy. She had experienced fever and persistent inflammation without cervical lymphadenopathy for several months and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) showed abnormal FDG uptake in the left cheek; cervical, axillary, inguinal lymph nodes; periatrium; and pelvis. She was diagnosed with RDD based on skin and pelvic biopsies. Although this was an atypical case without bilateral cervical lymphadenopathy, the FDG-PET detection of inflammatory lesions led to selection of suitable biopsy sites, and pathological examination led to a correct diagnosis. Findings in this patient indicate that RDD can present with an atypical distribution of infrequent extranodal lesions, with attention required to prevent a delayed diagnosis.
Correlation of ERCC5 polymorphisms and linkage disequilibrium associated with overall survival and clinical outcome to chemotherapy in breast cancer
Authors: Khan Iqra , Masood Nosheen , Yasmin Azra
Published: January 2023

Purpose

ERCC5 is a DNA endonuclease and nucleotide excision repair gene; its mutations lead to a lack of activity by this enzyme, causing oxidative DNA damage. This study aimed to assess the role of four selected single nucleotide polymorphisms (SNPs) in ERCC5 and their linkage disequilibrium associated with survival analysis and clinical outcomes in breast cancer.

Patients and methods

Four SNPs (rs751402, rs17655, rs2094258, and rs873601) of the ERCC5 gene were analyzed using the PCR-RFLP technique, followed by sequencing in 430 breast cancer (BC) cases and 430 cancer-free individuals. Statistical analysis was performed using MedCalc 17 and SPSS version 24, while bioinformatic analysis of linkage disequilibrium was performed using Haploview software 4.2.

Results

Multivariate analysis showed that the rs751402 and rs2094258 polymorphisms were significantly associated with an elevated risk of BC (P < 0.001), while the other two SNPs, rs17655 and rs873601, did not show any association (P > 0.001). Survival analysis revealed that rs751402 and rs2094258 had longer overall survival periods (P <0.001) than rs17655 and rs873601. Moreover, rs751402 and rs2094258 also had significantly longer overall survival (log-rank test, P < 0.005) for all three survival functions (positive family history, ER+PR status, and use of contraceptives), while rs17655 and rs873601 did not show any significant association. Only rs873601 showed a strong negative correlation with all the chemotherapeutic groups.

Conclusion

The current results suggest that variations in ERCC5 may contribute to BC development and that their genetic anomalies may be associated with cancer risk and may be used as a biomarker of clinical outcome.
Redox integration of signaling and metabolism in a head and neck cancer model of radiation resistance using COSMRO
Authors: Ji Zhiwei , Moore Jade , Devarie-Baez Nelmi O. , Lewis Joshua , Wu Hanzhi , Shukla Kirtikar , Lopez Elsa I. Silva , Vitvitsky Victor , Key Chia-Chi Chuang , Porosnicu Mercedes , Kemp Melissa L. , Banerjee Ruma , Parks John S. , Tsang Allen W. , Zhou Xiaobo , Furdui Cristina M.
Published: January 2023

Redox metabolism is increasingly investigated in cancer as driving regulator of tumor progression, response to therapies and long-term patients’ quality of life. Well-established cancer therapies, such as radiotherapy, either directly impact redox metabolism or have redox-dependent mechanisms of action defining their clinical efficacy. However, the ability to integrate redox information across signaling and metabolic networks to facilitate discovery and broader investigation of redox-regulated pathways in cancer remains a key unmet need limiting the advancement of new cancer therapies. To overcome this challenge, we developed a new constraint-based computational method (COSMro) and applied it to a Head and Neck Squamous Cell Cancer (HNSCC) model of radiation resistance. This novel integrative approach identified enhanced capacity for H2S production in radiation resistant cells and extracted a key relationship between intracellular redox state and cholesterol metabolism; experimental validation of this relationship highlights the importance of redox state in cellular metabolism and response to radiation.
A nomogram model to individually predict prognosis for esophageal cancer with synchronous pulmonary metastasis
Authors: Zhang Xin-yao , Lv Qi-yuan , Zou Chang-lin
Published: January 2023

Background

Esophageal cancer (EC) is a life−threatening disease worldwide. The prognosis of EC patients with synchronous pulmonary metastasis (PM) is unfavorable, but few tools are available to predict the clinical outcomes and prognosis of these patients. This study aimed to construct a nomogram model for the prognosis of EC patients with synchronous PM.

Methods

From the Surveillance, Epidemiology, and End Results database, we selected 431 EC patients diagnosed with synchronous PM. These cases were randomized into a training cohort (303 patients) and a validation cohort (128 patients). Univariate and multivariate Cox regression analyses, along with the Kaplan-Meier method, were used to estimate the prognosis and cancer-specific survival (CSS) among two cohorts. Relative factors of prognosis in the training cohort were selected to develop a nomogram model which was verified on both cohorts by plotting the receiver operating characteristic (ROC) curves as well as the calibration curves. A risk classification assessment was completed to evaluate the CSS of different groups using the Kaplan-Meier method.

Results

The nomogram model contained four risk factors, including T stage, bone metastasis, liver metastasis, and chemotherapy. The 6-, 12- and 18-month CSS were 55.1%, 26.7%, and 5.9% and the areas under the ROC curve (AUC) were 0.818, 0.781, and 0.762 in the training cohort. Likewise, the AUC values were 0.731, 0.764, and 0.746 in the validation cohort. The calibration curves showed excellent agreement both in the training and validation cohorts. There was a substantial difference in the CSS between the high-risk and low-risk groups (P<0.01).

Conclusion

The nomogram model serves as a predictive tool for EC patients with synchronous PM, which would be utilized to estimate the individualized CSS and guide therapeutic decisions.
The predictive and prognostic role of metabolic and volume-based parameters of positron emission tomography/computed tomography as non-invasive dynamic biological markers in early breast cancer treated with preoperative systemic therapy
Authors: Inno Alessandro , Peri Marta , Turazza Monica , Bogina Giuseppe , Modena Alessandra , Massocco Alberto , Pezzella Modestino , Valerio Matteo , Mazzola Rosario , Olivari Laura , Severi Fabrizia , Foti Giovanni , Mazzi Cristina , Marchetti Fabiana , Lunardi Gianluigi , Salgarello Matteo , Russo Antonio , Gori Stefania
Published: January 2023

Introduction

The role of fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in early breast cancer treated with preoperative systemic therapy (PST) is not yet established in clinical practice. PET parameters have aroused great interest in the recent years, as non-invasive dynamic biological markers for predicting response to PST.

Methods

In this retrospective study, we included 141 patients with stage II-III breast cancer who underwent surgery after PST. Using ROC analysis, we set optimal cutoff of FDG-PET/CT parameters predictive for pathological complete response (pCR). We investigated the correlation between FDG-PET/CT parameters and pCR, median disease-free survival (DFS), and median overall survival (mOS).

Results

At multivariable analysis, baseline SUVmax (high vs low: OR 9.00, CI 1.85 – 61.9, p=0.012) and Delta SUVmax (high vs low: OR 9.64, CI 1.84, 69.2, p=0.012) were significantly associated with pCR rates. Interestingly, we found that a combined analysis of the metabolic parameter Delta SUVmax with the volume-based parameter Delta MTV, may help to identify patients with pCR, especially in the subgroup of hormone receptor positive breast cancer. Delta SUVmax was also an independent predictive marker for both mDFS (high vs low: HR 0.17, 95%CI 0.05-0.58, p=0.004) and mOS (high vs. low: HR 0.19, 95%CI 0.04-0.95, p=0.029).

Discussion

Our results suggest that Delta SUVmax may predict survival of early BC patients treated with PST.
Case report: A novel c.1842_1845dup mutation of ETFDH in two Chinese siblings with multiple acyl-CoA dehydrogenase deficiency
Authors: Yuan Gaopin , Zhang Xiaohong , Chen Tingli , Lin Jiansheng
Published: January 2023

This article reports the characterization of two siblings diagnosed with late-onset multiple Acyl-CoA dehydrogenase deficiency (MADD) caused by mutations in electron transfer flavoprotein(ETF)-ubiquinone oxidoreductase (ETF-QO) (ETFDH) gene. Whole exome sequencing (WES) was performed in the proband's pedigree. Clinical phenotypes of Proband 1 (acidosis, hypoglycemia, hypotonia, muscle weakness, vomiting, hypoglycemia, hepatomegaly, glutaric acidemia, and glutaric aciduria) were consistent with symptoms of MADD caused by the ETFDH mutation. However, Proband 2 presented with only a short stature. The patients (exhibiting Probands 1 and 2) showed identical elevations of C6, C8, C10, C12, and C14:1. c.1842_1845 (exon13)dup, and c.250 (exon3) G > A of the ETFDH gene were compound heterozygous variants in both patients. The novel variant c.1842_1845dup was rated as likely pathogenic according to the American College of Medical Genetics and Genomics guidelines (ACMG). This is the first report on the c.1842_1845dup mutation of the ETFDH gene in patients with late-onset MADD, and the data described herein may help expand the mutation spectrum of ETFDH.
Exploring the immunomodulatory effects and mechanisms of Xinjiang fermented camel milk-derived bioactive peptides based on network pharmacology and molecular docking
Authors: Wang Yuxing , Liang Zhuangzhuang , Shen Fang , Zhou Wenting , Manaer Tabusi , Jiaerken Didaier , Nabi Xinhua
Published: January 2023

Purpose: Fermented camel milk from Xinjiang is rich in probiotics and has immunomodulatory effects as an important source of bioactive peptides. However, it is not clear whether it is the probiotic or the bioactive peptide that acts. The present study aimed to extract and identify bioactive peptides from fermented camel milk in Xinjiang and investigate their immunomodulatory effects and mechanisms based on network pharmacology and molecular docking.

Methods: Four probiotic bacteria were used to ferment the fresh camel milk and the bioactive peptides were extracted and isolated by ultrafiltration and column chromatography. Network pharmacology predicts targets and pathways of action. GeneCards and OMIM-GENE-MAP database were used in order to search disease target genes and screen common target genes. Then we used STRING web to construct a protein-protein interaction (PPI) interaction network of the common target protein. The key targets were analyzed by GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis through the David database. The "drug (bioactive peptide)-disease-targets-pathway" network was established and molecular docking was used for prediction.

Results: Two fractions were obtained by UV spectrophotometer; whey acidic protein, α-lactalbumin, and peptidoglycan recognition protein 1 were the main protein-like components of Xinjiang fermented camel milk-derived bioactive peptides. The repeat sequence of peptidoglycan recognition protein 1 was selected and then seven bioactive peptides were obtained. Bioactive peptides had 222 gene targets, anti-inflammatory diseases had 2598 gene targets, and immune regulation had 866 gene targets, the intersection of which was 66 in common gene targets. Gene ontology and KEGG analysis reveals that bioactive peptides mainly play a vital role in the signaling pathways of lipid and atherosclerosis, pathways in cancer. The molecular docking results showed that the seven bioactive peptides bound well to the top four scoring proteins.

Conclusion: The immunomodulatory and anti-inflammatory effects and mechanisms of Xinjiang fermented camel milk-derived bioactive peptides were initially investigated by network pharmacology and molecular docking, providing a scientific basis for future studies.
Systems and in vitro pharmacology profiling of diosgenin against breast cancer
Authors: Khanal Pukar , Patil Vishal S. , Bhandare Vishwambhar V. , Patil Priyanka P. , Patil B. M. , Dwivedi Prarambh S. R. , Bhattacharya Kunal , Harish Darasaguppe R. , Roy Subarna
Published: January 2023

Aim: The purpose of this study was to establish a mode of action for diosgenin against breast cancer employing a range of system biology tools and to corroborate its results with experimental facts.

Methodology: The diosgenin-regulated domains implicated in breast cancer were enriched in the Kyoto Encyclopedia of Genes and Genomes database to establish diosgenin-protein(s)-pathway(s) associations. Later, molecular docking and the lead complexes were considered for molecular dynamics simulations, MMPBSA, principal component, and dynamics cross-correlation matrix analysis using GROMACS v2021. Furthermore, survival analysis was carried out for the diosgenin-regulated proteins that were anticipated to be involved in breast cancer. For gene expression analyses, the top three targets with the highest binding affinity for diosgenin and tumor expression were examined. Furthermore, the effect of diosgenin on cell proliferation, cytotoxicity, and the partial Warburg effect was tested to validate the computational findings using functional outputs of the lead targets.

Results: The protein-protein interaction had 57 edges, an average node degree of 5.43, and a p-value of 3.83e-14. Furthermore, enrichment analysis showed 36 KEGG pathways, 12 cellular components, 27 molecular functions, and 307 biological processes. In network analysis, three hub proteins were notably modulated: IGF1R, MDM2, and SRC, diosgenin with the highest binding affinity with IGF1R (binding energy −8.6 kcal/mol). Furthermore, during the 150 ns molecular dynamics (MD) projection run, diosgenin exhibited robust intermolecular interactions and had the least free binding energy with IGF1R (−35.143 kcal/mol) compared to MDM2 (−34.619 kcal/mol), and SRC (-17.944 kcal/mol). Diosgenin exhibited the highest cytotoxicity against MCF7 cell lines (IC50 12.05 ± 1.33) µg/ml. Furthermore, in H2O2-induced oxidative stress, the inhibitory constant (IC50 7.68 ± 0.51) µg/ml of diosgenin was lowest in MCF7 cell lines. However, the reversal of the Warburg effect by diosgenin seemed to be maximum in non-cancer Vero cell lines (EC50 15.27 ± 0.95) µg/ml compared to the rest. Furthermore, diosgenin inhibited cell proliferation in SKBR3 cell lines more though.

Conclusion: The current study demonstrated that diosgenin impacts a series of signaling pathways, involved in the advancement of breast cancer, including FoxO, PI3K-Akt, p53, Ras, and MAPK signaling. Additionally, diosgenin established a persistent diosgenin-protein complex and had a significant binding affinity towards IGF1R, MDM2, and SRC. It is possible that this slowed down cell growth, countered the Warburg phenomenon, and showed the cytotoxicity towards breast cancer cells.
Efficacy and safety of Keluoxin capsule in combination with Western medicine for diabetic kidney disease: A systematic review and meta-analysis
Authors: Zhang Wenhua , Zhou Jingxin , Wang Churan , Wang Xu , Zhang Shuwen , Jia Weiyu , Jiang Yijia , Lin Lan , Gong Yanbing
Published: January 2023

Objective: Keluoxin capsule (KLXC) has been widely used in diabetic kidney disease (DKD), but its efficacy and safety have not yet been clarified. A systematic review and meta-analysis were performed to assess the efficacy and safety of KLXC for DKD.

Methods: The randomized control trials (RCTs) included KLXC searched from seven major English and Chinese databases up until 3 June 2022. The methodological quality and risk of bias were assessed by version 2 of the Cochrane risk-of-bias tool (RoB 2) for the RCTs from the Cochrane Handbook. The analyses were conducted by RevMan 5.4 and Stata 17.0.

Results: A total of 20 trials with 1,500 participants were identified. The meta-analysis showed that KLXC combined with Western medicine was superior to the use of Western medicine alone for DKD which included improvements in the estimated glomerular filtration rate (eGFR) [MD = 3.04, 95% CI (0.30, 5.78), p = 0.03], reduction in microalbuminuria (mALB) [MD = −25.83, 95% CI (−41.20, −10.47), p = 0.001], urinary albumin excretion rate (UAER) [SMD = −0.97, 95% CI (−1.50, −0.44), p = 0.0003], 24-h urine protein (24hUpro) [SMD = −1.31, 95% CI (−1.82, −0.80), p < 0.00001], serum creatinine (Scr) [MD = −11.39, 95% CI (−18.76, −4.02), p = 0.002], blood urea nitrogen (BUN) [MD = −1.28, 95% CI (−1.67, −0.88), p < 0.00001], fasting blood glucose (FBG) [MD = −0.51, 95% CI (−0.90, −0.11), p = 0.01], total cholesterol (TC) [MD = −1.04, 95% CI (−1.40, −0.68), p < 0.00001], triglycerides (TG) [MD = −0.36, 95% CI (−0.50, −0.23), p < 0.00001], and low-density lipoprotein cholesterol (LDL) [MD = −0.39, 95% CI (−0.71, −0.07), p = 0.02]. Results showed no statistically significant difference in glycated hemoglobin (HbA1c) (p = 0.14) or adverse events (p = 0.81) between the two groups.

Conclusion: The combination of KLXC and Western medicine had a positive effect on DKD. However, due to the high clinical heterogeneity and low quality of included studies, further standardized, large-scale, rigorously designed RCTs for DKD in the definitive stage are still necessary to achieve more accurate results.

Systematic Review Registration:https://inplasy.com/inplasy-2021-11-0067/, identifier INPLASY 2021110067.