bluuebunny/crossref_metadata_2025_split huggingface dataset:
An open, observational, three-arm clinical study of 2–3 cycles of treatment as neoadjuvant therapy in operable locally advanced non-small cell lung cancer: An interim analysis
Authors: Gu Linping , Wang Xue , Sun Yile , Xu Yunhua , Niu Xiaomin , Zhao Ruiying , Yao Yaxian , Jian Hong , Han Yuchen , Wei Jinwang , Chen Zhiwei , Lu Shun 
Published: August 2022

BackgroundAn open, observational, three-arm clinical study aimed at investigating the efficacy of different neoadjuvant therapies (neoadjuvant immunotherapy with(out) chemotherapy, neoadjuvant chemotherapy, and neoadjuvant targeted therapy) in operable locally advanced non-small cell lung cancer (NSCLC) was conducted (NCT04197076). We report an interim analysis of 49 of 53 evaluable patients.MethodsThis study was conducted at Shanghai Chest Hospital and included eligible NSCLC patients who were 18 years old and had clinical stage IIB–IIIB disease. All 49 patients had surgical resection within 4–6 weeks after 2–3 cycles of neoadjuvant treatment consisting of immunotherapy (24 patients), chemotherapy (16 patients), and a targeted therapy (9 patients) regimen starting on the first day of each 21-day cycle. Pathologic complete response (pCR) was evaluated as the primary endpoint. Major pathological response (MPR) and tumor regression rate (TRR) were also evaluated.ResultsAn improved pathologic complete response was achieved in the neoadjuvant immunotherapy arm compared with the neoadjuvant chemotherapy arm and neoadjuvant targeted therapy arm [20.8% (5/24) vs. 6.3% (1/16) vs. 0.0% (0/9); P = 0.089, 95% CI 0.138–0.151]. More importantly, we found that the curative effect of the neoadjuvant immunotherapy arm in pCR+MPR was better than that of the neoadjuvant chemotherapy arm and neoadjuvant targeted therapy arm [45.8% (11/24) vs. 18.8% (3/16) vs. 0.0% (0/9); P = 0.006, 95% confidence interval, 0.008–0.012]. Different neoadjuvant therapies had a statistically significant effect on postoperative pathological tumor downstaging (P = 0.017).ConclusionsNeoadjuvant immunotherapy was associated with a trend toward better pCR than the neoadjuvant chemotherapy arm and neoadjuvant targeted therapy. Curative effect (pCR + MPR) was significantly better with neoadjuvant immunotherapy (P = 0.006, 95% confidence interval, 0.008–0.012).Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT04197076?recrs=a&amp;cond=NCT04197076&amp;draw=2&amp;rank=1.
Identification of necroptosis-related subtypes and prognosis model in triple negative breast cancer
Authors: Pu Shengyu , Zhou Yudong , Xie Peiling , Gao Xiaoqian , Liu Yang , Ren Yu , He Jianjun , Hao Na 
Published: August 2022

BackgroundNecroptosis is considered to be a new form of programmed necrotic cell death, which is associated with metastasis, progression and prognosis of various types of tumors. However, the potential role of necroptosis-related genes (NRGs) in the triple negative breast cancer (TNBC) is unclear.MethodsWe extracted the gene expression and relevant clinicopathological data of TNBC from The Cancer Genome Atlas (TCGA) databases and the Gene Expression Omnibus (GEO) databases. We analyzed the expression, somatic mutation, and copy number variation (CNV) of 67 NRGs in TNBC, and then observed their interaction, biological functions, and prognosis value. By performing Lasso and COX regression analysis, a NRGs-related risk model for predicting overall survival (OS) was constructed and its predictive capabilities were verified. Finally, the relationship between risk_score and immune cell infiltration, tumor microenvironment (TME), immune checkpoint, and tumor mutation burden (TMB), cancer stem cell (CSC) index, and drug sensitivity were analyzed.ResultsA total 67 NRGs were identified in our analysis. A small number of genes (23.81%) detected somatic mutation, most genes appeared to have a high frequency of CNV, and there was a close interaction between them. These genes were remarkably enriched in immune-related process. A seven-gene risk_score was generated, containing TPSG1, KRT6A, GPR19, EIF4EBP1, TLE1, SLC4A7, ESPN. The low-risk group has a better OS, higher immune score, TMB and CSC index, and lower IC50 value of common therapeutic agents in TNBC. To improve clinical practicability, we added age, stage_T and stage_N to the risk_score and construct a more comprehensive nomogram for predicting OS. It was verified that nomogram had good predictive capability, the AUC values for 1-, 3-, and 5-year OS were 0.847, 0.908, and 0.942.ConclusionOur research identified the significant impact of NRGs on immunity and prognosis in TNBC. These findings were expected to provide a new strategy for personalize the treatment of TNBC and improve its clinical benefit.
Molecular subtypes of osteosarcoma classified by cancer stem cell related genes define immunological cell infiltration and patient survival
Authors: Guo Lei , Yan Taiqiang , Guo Wei , Niu Jianfang , Wang Wei , Ren Tingting , Huang Yi , Xu Jiuhui , Wang Boyang 
Published: August 2022

Recent studies have shown that tumor stemness has biological significance in tumorigenicity and tumor progression. However, the characteristics of TME immune infiltration in osteosarcoma mediated by the combined effects of multiple cancer stem cell-related genes remain unknown.MethodsIn this study, we identified different cancer stem cell-associated subtypes in osteosarcoma based on 25 cancer stem cell-associated genes by consensus clustering analysis, and we comprehensively evaluated the association between these subtypes and immunocytes infiltration in the TME. The cancer stem cell (CSC) score was constructed to quantify the stemness of individual tumors.ResultsWe performed a comprehensive evaluation of 218 osteosarcoma patients based on 25 cancer stem cell-related genes. Three different cancer stem cells related subtypes were identified, which were related to different biological processes and clinical outcomes. The three subtypes have different TME cells infiltrating characteristics, and CSC Cluster A had a higher level of immunocyte infiltration compared to CSC Cluster B and C. We constructed a scoring system, called the CSC score, to assess the stemness of individual patients. Then we found that the prognosis of patients was predicted by CSC score, and patients with low CSC score had prolonged survival. Further analyses showed that low CSC score was correlated with enhanced immune infiltration. CSC score may predict the effect of immunotherapy, and patients with low CSC score may have better immune response and clinical prognosis.ConclusionsThis study demonstrates that there could be three cancer stem cell-associated subtypes in osteosarcoma and that they were associated with different patient prognosis and TME immune infiltration characteristics. CSC score could be used to assess the stemness of individual patients, improve our comprehension of TME characteristics, and direct more effective immune therapy.
A TMPS-designed personalized mandibular scaffolds with optimized SLA parameters and mechanical properties
Authors: Zheng Xiaoxiao , Duan Feng , Song Zhenyu , Mo Hongbing , Li Zhehao , Song Yihan , Su Yucheng , Wang Xinyu 
Published: August 2022

With the rapid development of 3D printing technology, porous titanium scaffolds have provided a new restoration method to repair bone defects. Compared with the traditional body-centered cubic (bcc) dot matrix structure with a simple arrangement and repetitive structure, the topology-driven properties of triply periodic minimal surfaces (TPMS) can offer a continuous surface and smooth curvature, an excellent platform for cell proliferation. In this study, we used reverse engineering techniques to model the mandible. Sheet and solid networks of gyroid structure, the most common type of TPMS, were selected for porous design and then molded using metal 3D printing technology. At the same time, the surface treatment parameters of sandblasted, large-grit, and acid-etched (SLA) were optimized by orthogonal experimental design. Then, the optimized SLA parameter was used to treat the gyroid with 70% porosity. The result showed that reverse engineering reconstructed the TPMS-based mandibular model had good formability. Furthermore, the best surface morphology, wettability, and roughness were obtained for 3D printed Ti6Al4V under the treatment of 80 mesh Al2O3, blasting distances of 4 cm, and a 1:1:2 acid ratio. Moreover, the mechanical properties of Sheet-Gyroid and Solid-Gyroid were significantly different at 70% porosity. The porosity of the scaffolds was close to the design porosity after SLA treatment. However, no significant changes were found in its mechanical properties, all matching the mandible’s mechanical properties to meet the implantation conditions.
Subjective perception of activity level: A prognostic factor for developing chronic dizziness after vestibular schwannoma resection?
Authors: Van Laer Lien , Hallemans Ann , Van Rompaey Vincent , De Valck Claudia , Van de Heyning Paul , Vereeck Luc 
Published: August 2022

IntroductionA vestibular schwannoma (VS) resection causes an acute unilateral vestibular deafferentation resulting in acute postoperative symptoms. Despite the expected resolution of most of the symptoms, due to central vestibular compensation, more than one out of four patients develop chronic dizziness. Several predictive factors, such as age and tumor size, have been suggested. Despite its potential effect on the process of central vestibular compensation, the level of physical activity after VS resection was not yet considered. Therefore, the association between the level of physical activity and chronic dizziness after VS resection will be investigated.MethodsThis retrospective cohort study included 66 patients who underwent a retro-sigmoid VS resection between October 2001 and February 2007. Patients were assessed before surgery and at 9 weeks and 6 months postoperatively. At 9 weeks, patients were asked to report their level of physical activity (PA) during the past week by using a visual analogue scale and their balance performance was assessed by four standing balance conditions with eyes closed and the Timed Up and Go test (TUG). Based on the Dizziness Handicap Inventory (DHI) score at 6 months, patients were divided in a chronic dizziness group (DHI &gt; 30) and non-chronic dizziness group (DHI-score ≤ 30). Age, sex, Koos classification, preoperative vestibular function, treatment group, balance performance, and level of PA were compared between both groups and used as independent variables in linear regression analyses with the DHI score at 6 months as dependent variable.ResultsThe chronic dizzy patients revealed to have significantly lower levels of PA (p &lt; 0.001) and worse static and dynamic balance performance (p = 0.023 and p = 0.041, respectively) 9 weeks after surgery. After elimination, the multiple regression analysis resulted in a model with two variables (PA level, TUG) which significantly predicted the DHI score (F2,42 = 6.581; R2 = 0.239; p = 0.003).ConclusionThis study revealed associations between (1) the level of PA and balance performance in the subacute phase and (2) chronic dizziness after VS resection. Assessment of the level of PA and balance performance during the subacute phase, which can be performed in a non-invasive and non-time-consuming way, might therefore provide prognostic information after VS resection.
Altered dynamic spontaneous neural activity in minimal hepatic encephalopathy
Authors: Guo Jie-Ru , Shi Jia-Yan , Dong Qiu-Yi , Cao Yun-Bin , Li Dan , Chen Hua-Jun 
Published: August 2022

Background and aims:Abnormal regional neural activity has been identified by the analysis of the static amplitude of low-frequency fluctuation (ALFF) in the setting of minimal hepatic encephalopathy (MHE). Brain activity is highly dynamic. This work sought to evaluate the temporal variability of ALFF to reveal MHE-related alterations in the dynamics of spontaneous neural activity.MethodsA total of 29 healthy controls and 49 patients with cirrhosis [including 20 patients with MHE and 29 patients without MHE (NHE)] who underwent resting-state functional magnetic resonance imaging and Psychometric Hepatic Encephalopathy Score (PHES) examination were enrolled in this investigation. Utilizing a sliding-window approach, we calculated the dynamic ALFF (dALFF) variability to reflect the temporal dynamics of regional neural activity. An analysis of the correlation between dALFF variability and PHES was performed, and receiver operating characteristic (ROC) curve analysis to determine the potential of the dALFF variability index in identifying MHE was completed.ResultsThe dALFF variability in the bilateral precuneus/posterior cingulate gyrus and left middle frontal gyrus progressively decreased from NHE to MHE group. In cirrhotic patients, the value of dALFF variability in the bilateral precuneus/posterior cingulate gyrus was positively correlated with their neurocognitive performance (r = 0.383 and P = 0.007). The index of dALFF variability in the bilateral precuneus/posterior cingulate gyrus could be used to distinguish NHE and MHE patients, with moderate power (area under the ROC curve = 0.712 and P = 0.012).ConclusionOur findings highlight the existence of aberrant dynamic brain function in MHE, which could underlie the neural basis of cognitive impairments and could be associated with the development of the disease. Analyzing dALFF could facilitate new biomarker identification for MHE.
The “hot cross bun sign” in patients with autoimmune cerebellar ataxia: A case report and literature review
Authors: Liu Mange , Ren Haitao , Lin Nan , Tan Ying , Fan Siyuan , Guan Hongzhi 
Published: August 2022

ObjectivesThe “hot cross bun sign” (HCBs) on magnetic resonance imaging (MRI) has been initially considered specific for multiple system atrophy with cerebellar features. However, a number of other conditions have since been described, which may be associated with this imaging sign. We herein describe a patient with anti-Ri and paraneoplastic cerebellar ataxia, and review the association of the HCBs on imaging with various neurological autoimmune conditions.MethodsWe report a 40-year-old woman with anti-Ri-associated paraneoplastic neurological syndrome and breast carcinoma, in whom brain MRI revealed the HCBs late in the disease course. We also reviewed similar cases reported in the literature.ResultsThe patient presented with cerebellar ataxia, polyneuropathy, and pyramidal signs. Although brain MRI was initially unremarkable, the HCBs and T2-weighted hyperintensity of the bilateral middle cerebellar peduncles were observed at later follow-up. Anti-Ri was detected in the serum and cerebrospinal fluid. Breast adenocarcinoma was confirmed via an axillary lymph node biopsy. Her symptoms partially resolved after the first corticosteroid pulse. However, subsequent immunotherapy and tumor treatments were ineffective. Four autoimmune cerebellar ataxia cases with the HCBs (two paraneoplastic and two non-paraneoplastic) were identified in the literature.DiscussionThe HCBs can be associated with paraneoplastic and non-paraneoplastic cerebellar ataxia, which may reflect neurodegeneration secondary to autoimmune injury. Thus, the HCBs should not be considered a contraindication for autoimmune cerebellar syndrome.
Major dietary patterns in relation to disease severity, symptoms, and inflammatory markers in patients recovered from COVID-19
Authors: Ebrahimzadeh Armin , Taghizadeh Mohsen , Milajerdi Alireza 
Published: August 2022

BackgroundCOVID-19 is a highly transmissible viral infection with high morbidity. Few studies have been done about dietary intakes in patients with COVID-19. This study aimed to evaluate the association between major dietary patterns before COVID-19 diagnosis in recovered patients and the risk of disease severity and symptoms after the disease begins.MethodsOverall, 250 recovered cases with both genders completed study questionnaires providing data on demographic characteristics, self-reported web-based 168-item food frequency questionnaire (FFQ), and COVID-19 outcomes in Shahid Beheshti Hospital, Kashan. PCR was used to determine a positive diagnosis of COVID-19. We used multivariable logistic regression models to assess the association between major dietary patterns and study outcomes. All statistical analyses were done by SPSS version 16.ResultsWe identified three major dietary patterns—unhealthy, traditional, and healthy dietary patterns. Serum levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were significantly higher in patients with unhealthy and traditional dietary patterns and lower in those with healthy dietary patterns. There was a significant direct relationship between unhealthy and traditional patterns with risk of severe COVID-19 and hospitalization duration and a significant direct association between an unhealthy pattern and the odds ratio (OR) of convalescence duration. A significant inverse relationship was found between healthy pattern and risk of severe COVID-19 and OR of convalescence duration. We found a significant direct association between unhealthy pattern and OR of cough, fever, chilling, weakness, myalgia, nausea and vomiting, and sore throat and between traditional pattern and OR of cough, fever, and chilling. In contrast, a significant inverse association was seen between healthy pattern and OR of dyspnea, weakness, and sore throat.ConclusionThis study showed that high adherence to an healthy pattern was associated with lower CRP and ESR levels and lower risk of severe COVID-19, hospitalization, and convalescence duration in patients who recovered from COVID-19. More adherence to unhealthy or traditional dietary patterns was associated with higher CRP and ESR levels and a higher risk of severe COVID-19 and hospitalization duration. A direct association was found between unhealthy and traditional patterns and the risk of some COVID-19 symptoms, while an inverse association was found for a healthy dietary pattern.
Safety and immunogenicity of the COVID-19 vaccine BNT162b2 for patients with breast and gynecological cancer on active anticancer therapy: Results of a prospective observational study
Authors: De Placido Pietro , Pietroluongo Erica , De Angelis Carmine , Tafuro Margherita , Barraco Chiara , Giannatiempo Rosa , Buonaiuto Roberto , Schettini Francesco , Iervolino Anna , Vozzella Emilia Anna , Giuliano Mario , Bianco Roberto , Arpino Grazia 
Published: August 2022

BackgroundVaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are highly effective. Nevertheless, immunocompromised participants were excluded from randomized controlled clinical trials. This study evaluates the efficacy and safety of the Pfizer/BioNTech BNT162b2 (BNT162b2) vaccine in patients with breast and gynecological cancer treated with active anticancer therapy versus a control cohort of healthy participants.MethodsImmune responses to the BNT162b2 vaccine in patients with breast cancer (n = 44) or a gynecological malignancy (n = 6) on active anticancer therapy (28 on chemotherapy, mostly anthracycline- or taxane-based, and 22 on target therapy) and in a control cohort of participants without cancer (n = 67) were investigated by SARS-CoV-2 neutralizing antibody titers measured by S1-binding immunoglobulin G (IgG) concentrations assessed using the LIAISON XL tools (DiaSorin S.p.A.). Response was assessed after a second dose of the BNT162b2 vaccine administered before and at least 3 weeks after the vaccine dose.ResultsOverall, 43/50 (86%) patients of the cancer cohort (74% in the breast cancer group and 100% in the gynecological malignancy group) developed IgG antibodies after the second dose of the BNT162b2 vaccine. There were no statistically significant differences in responder rates between patients treated with chemotherapy and those on target therapy. The majority of patients who received chemotherapy with or without target therapy, 21/28 (75%), developed a reliable antibody titer after a vaccine. All seven non-responder patients were undergoing an anthracycline-based regimen. Based on IgG levels (0–400 AU/ml), patients were classified as negative (‘non-responders’), weakly positive, or strongly positive (‘responders’). No delay in cancer therapy schedule or reported side effects were recorded after BNT162b2 vaccine administration. All healthy participants were strongly positive. Responder rates differed significantly between the two study cohorts (p &lt; 0.001).ConclusionsMost patients develop antibody titers after the second immunization. However, given the persistence of non-responders or weak responders, additional immunization booster seems to be required, along with proactive planning in the vaccination schedule, with vaccine administration spaced out over time with respect to chemotherapy.
Modified blink dynamic index predicts activity and severity in patient with facial nerve palsy
Authors: Kim Yuri , Lew Helen 
Published: August 2022

PurposeWe analyzed the dynamics of blink and defined the blink index in facial nerve palsy (FNP) patients using an ocular surface interferometer associated with clinical characteristics and clinical progress.MethodsIn total, 49 patients were enrolled this study. All patients were tested using an ocular surface interferometer which is used to measure blink patterns (total blink (TB), partial blink rate (PBR)) and blink dynamics (blink time (BT), lid closing time (LCT), closure time (CT), lid opening time (LOT), interblink time (IBT), closing speed (CS), and opening speed (OS)) using 600 frames recorded over 20 s. The distance of lagophthalmos and modified interpalpebral fissure (IPF), which was defined as the actual moving distance of the upper eyelid, subtracting the distance of lagophthalmos from IPF, was measured using the ImageJ program. The types of FNP were “idiopathic” (Bell’s palsy) and “surgical” (following the neurosurgery). Patients were classified into “acute” and “chronic” based on the duration of 6 months from the onset time of FNP. The clinical characteristics were classified into mild or severe according to the severe degree of exposure keratopathy—as “severe” if treatment such as tarsorrhaphy and gold plate insertion was required.ResultsReduced MRD1, brow height, and modified IPF and increased lagophthalmos were noted in the palsy side. LCT was longer and CS, modified CS, and modified OS were shorter in the palsy side. The LCT was longer and the modified CS was shorter in idiopathic patients with acute onset and with clinically severe. IBT was increased in idiopathic patients with clinically severe.ConclusionAnalyzing the blink patterns and blink dynamics, this study suggests meaningful indicators among blink profiles and dynamics, LCT, and modified CS based on modified IPF. It was more associated in the idiopathic type than in the surgical type of FNP patients. The modified CS can be a useful tool for evaluating the activity and severity indicator of FNP.