bluuebunny/crossref_metadata_2025 huggingface dataset:
Sum of boxes of the clinical dementia rating scale highly predicts conversion or reversion in predementia stages
Authors: Tzeng Ray-Chang , Yang Yu-Wan , Hsu Kai-Cheng , Chang Hsin-Te , Chiu Pai-Yi
Published: September 2022

Background

The clinical dementia rating (CDR) scale is commonly used to diagnose dementia due to Alzheimer’s disease (AD). The sum of boxes of the CDR (CDR-SB) has recently been emphasized and applied to interventional trials for tracing the progression of cognitive impairment (CI) in the early stages of AD. We aimed to study the influence of baseline CDR-SB on disease progression to dementia or reversion to normal cognition (NC).

Materials and methods

The baseline CDR < 1 cohort registered from September 2015 to August 2020 with longitudinal follow-up in the History-based Artificial Intelligence Clinical Dementia Diagnostic System (HAICDDS) database was retrospectively analyzed for the rates of conversion to CDR ≥ 1. A Cox regression model was applied to study the influence of CDR-SB levels on progression, adjusting for age, education, sex, neuropsychological tests, neuropsychiatric symptoms, parkinsonism, and multiple vascular risk factors.

Results

A total of 1,827 participants were analyzed, including 1,258 (68.9%) non-converters, and 569 (31.1%) converters with mean follow-up of 2.1 (range 0.4–5.5) and 1.8 (range 0.3–5.0) years, respectively. Conversion rates increased with increasing CDR-SB scores. Compared to a CDR-SB score of 0, the hazard ratios (HR) for conversion to dementia were 1.51, 1.91, 2.58, 2.13, 3.46, 3.85, 3.19, 5.12, and 5.22 for CDR-SB scores of 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, and ≥4.5, respectively (all p < 0.05 except for CDR-SB score = 0.5). In addition, older age, lower education, lower cognitive performance, and a history of diabetes also increased conversion rates. Furthermore, reversions to NC were 12.5, 5.6, 0.9, and 0% for CDR-SB scores of 0.5, 1.0–2.0, 2.5–3.5 and ≥4.0, respectively (p < 0.001).

Conclusion

CDR-SB in predementia or very mild dementia (VMD) stages highly predicts progression to dementia or reversion to NC. Therefore, CDR-SB could be a good candidate for tracing the effectiveness of pharmacological and non-pharmacological interventions in populations without dementia.
Hypoplasia of dopaminergic neurons by hypoxia-induced neurotoxicity is associated with disrupted swimming development of larval zebrafish
Authors: Son Jong-Hyun , Gerenza Amanda K. , Bingener Gabrielle M. , Bonkowsky Joshua L.
Published: September 2022

Hypoxic injury to the developing brain increases the risk of permanent behavioral deficits, but the precise mechanisms of hypoxic injury to the developing nervous system are poorly understood. In this study, we characterized the effects of developmental hypoxia (1% pO2 from 24 to 48 h post-fertilization, hpf) on diencephalic dopaminergic (DA) neurons in larval zebrafish and the consequences on the development of swimming behavior. Hypoxia reduced the number of diencephalic DA neurons at 48 hpf. Returning zebrafish larvae to normoxia after the hypoxia (i.e., hypoxia-recovery, HR) induced reactive oxygen species (ROS) accumulation. Real-time qPCR results showed that HR caused upregulation of proapoptotic genes, including p53 and caspase3, suggesting the potential for ROS-induced cell death. With HR, we also found an increase in TUNEL-positive DA neurons, a persistent reduction in the number of diencephalic DA neurons, and disrupted swimming development and behavior. Interestingly, post-hypoxia (HR) with the antioxidant N-acetylcysteine partially restored the number of DA neurons and spontaneous swimming behavior, demonstrating potential recovery from hypoxic injury. The present study provides new insights for understanding the mechanisms responsible for motor disability due to developmental hypoxic injury.
N6-methyladenosine modification: A potential regulatory mechanism in spinal cord injury
Authors: Liu Derong , Fan Baoyou , Li Jinze , Sun Tao , Ma Jun , Zhou Xianhu , Feng Shiqing
Published: September 2022

N6-methyladenosine (m6A), an essential post-transcriptional modification in eukaryotes, is closely related to the development of pathological processes in neurological diseases. Notably, spinal cord injury (SCI) is a serious traumatic disease of the central nervous system, with a complex pathological mechanism which is still not completely understood. Recent studies have found that m6A modification levels are changed after SCI, and m6A-related regulators are involved in the changes of the local spinal cord microenvironment after injury. However, research on the role of m6A modification in SCI is still in the early stages. This review discusses the latest progress in the dynamic regulation of m6A modification, including methyltransferases (“writers”), demethylases (“erasers”) and m6A -binding proteins (“readers”). And then analyses the pathological mechanism relationship between m6A and the microenvironment after SCI. The biological processes involved included cell death, axon regeneration, and scar formation, which provides new insight for future research on the role of m6A modification in SCI and the clinical transformation of strategies for promoting recovery of spinal cord function.
Hearing, touching, and multisensory integration during mate choice
Authors: Lenschow Constanze , Mendes Ana Rita P. , Lima Susana Q.
Published: September 2022

Mate choice is a potent generator of diversity and a fundamental pillar for sexual selection and evolution. Mate choice is a multistage affair, where complex sensory information and elaborate actions are used to identify, scrutinize, and evaluate potential mating partners. While widely accepted that communication during mate assessment relies on multimodal cues, most studies investigating the mechanisms controlling this fundamental behavior have restricted their focus to the dominant sensory modality used by the species under examination, such as vision in humans and smell in rodents. However, despite their undeniable importance for the initial recognition, attraction, and approach towards a potential mate, other modalities gain relevance as the interaction progresses, amongst which are touch and audition. In this review, we will: (1) focus on recent findings of how touch and audition can contribute to the evaluation and choice of mating partners, and (2) outline our current knowledge regarding the neuronal circuits processing touch and audition (amongst others) in the context of mate choice and ask (3) how these neural circuits are connected to areas that have been studied in the light of multisensory integration.
Impact of Pre-operative Embolization With Onyx for Brain Arteriovenous Malformation Surgery
Authors: Izumo Tsuyoshi , Okamura Kazuaki , Takahira Ryotaro , Matsunaga Yuki , Sadakata Eisaku , Maeda Hajime , Yamaguchi Susumu , Baba Shiro , Morofuji Yoichi , Hiu Takeshi , Horie Nobutaka , Anda Takeo , Kitagawa Naoki , Tokunaga Yoshiharu , Hayashi Kentaro , Matsumoto Yasushi , Nagata Izumi , Matsuo Takayuki
Published: September 2022

Objective

To clarify the safety and efficacy of pre-operative embolization using Onyx liquid embolic agent (Onyx; ev3) compared with N-butyl cyanoacrylate (NBCA; Cordis Neurovascular, Inc.) or coils in cerebral arteriovenous malformation (AVM) surgery.

Methods

This was a retrospective review of a prospectively collected clinical database of brain AVMs treated at our institute from January 2005 to March 2021. A total of 38 consecutive patients who underwent AVM resection after pre-operative embolization were included. Based on pre-operative embolization materials, the patients were divided into the pre-Onyx group (n = 16), in which NBCA or coils were used for embolization, and the Onyx group (n = 22). Patient characteristics and treatment results were compared between the two groups.

Results

Patient characteristics were comparable between the two groups in terms of age, sex, and rupture status. While the Spetzler–Martin grade was also similar between the two groups, the location of the AVM nidus in the eloquent area was slightly higher in patients in the Onyx group (72.7%) than in patients in the pre-Onyx group (43.8%) (P = 0.09). The embolization rate was higher in the pre-Onyx group (mean: 63.0%; range: 12.7–100%) than in the Onyx group (mean: 50.0%; range: 15.8–100%), but the difference was not statistically significant (P = 0.06). The time needed for surgical removal was shorter in the Onyx group (mean: 354.8 min; range: 144–884 min) than in the pre-Onyx group (mean: 457.9 min; range: 240–1,294 min); however, this difference was not statistically significant (P = 0.13). The amount of intraoperative bleeding was significantly lower in the Onyx group (mean: 129.8 ml; range: 20–540 mL) than in the pre-Onyx group (mean: 448.8 mL; range: 120–1,550 ml) (P = 0.0008). The surgical complication rates were comparable between the two groups (pre-Onyx group, 18.8%; Onyx group, 4.5%; P = 0.29).

Conclusions

Pre-operative embolization with Onyx can significantly reduce the amount of intraoperative bleeding in AVM resection and may contribute to safe AVM surgery.
Intra- and post-operative acute hemorrhagic complications of Onyx embolization of brain arteriovenous malformations: A single-center experience
Authors: Chen Xuan , Wang Yiheng , Yu Jinlu
Published: September 2022

Background

The intra- and post-operative acute (within 72 h) hemorrhagic complications of endovascular treatment (EVT) for a brain arteriovenous malformation (BAVM) are disastrous. Thus, further experiential summaries are required to fully understand them.

Materials and methods

This was a retrospective study of 25 patients with consecutive BAVM who were treated via EVT with Onyx embolization and suffered intra- and post-operative acute hemorrhage. The clinical and imaging data of the patients were recorded, analyzed, and discussed.

Result

Twenty-five patients were aged 11–70 years (mean, 37.2 ± 16.1 years), of whom 12 were female (48%, 12/25). Of the 25 hemorrhagic complications, 17 (68%, 17/25) were intraoperative, and 8 (32%, 8/25) were post-operative and occurred between 1 and 12 h after EVT. Of 17 intraoperative hemorrhages, 13 (76.5%, 13/17) were due to high-pressure Onyx casting. Of eight post-operative hemorrhages, six (75%, 6/8) were attributed to normal perfusion pressure breakthrough. The degree of nidus Onyx embolization was more than 2/3 or complete in seven (87.5%, 7/8) BAVMs. Draining vein occlusion was observed in eight (32%, 8/25) of 25 BAVMs. After hemorrhage, conservative treatment was administered in 12 (48%, 12/25) cases, and surgical management was performed in other cases. There were eight cases of mortality; the remaining 17 patients had follow-up data. Among them, 15 patients had good outcomes, with Glasgow Outcome Scale scores of 5 and 4, accounting for 60% (15/25).

Conclusion

In EVT for BAVMs, intra- and post-operative acute hemorrhagic complications are disastrous; only 60% of patients have a good outcome. Therefore, high-pressure Onyx casting or casting too much Onyx at one time to pursue a high degree of nidus embolization should be performed cautiously, and primary draining vein occlusion should be avoided. In short, EVT needs to be performed carefully.
Reducing delay to endovascular reperfusion after relocating a thrombolysis unit
Authors: Laugesen Nicolaj Grønbæk , Hansen Klaus , Højgaard Joan , Iversen Helle Klingenberg , Truelsen Thomas
Published: September 2022

Background and aims

Functional outcome following mechanical thrombectomy (MT) in patients with acute ischemic stroke and large vessel occlusion is time-dependent and worsens with increasing delay. Time to endovascular reperfusion is potentially modifiable with changes in organizational structure. We investigated the changes in time to reperfusion of relocating the intravenous thrombolysis (IVT) services from a non-MT center to a MT-capable center.

Methods

We present an observational, consecutive, retrospective, single-center cohort study of 253 stroke patients treated with MT, 2017–2019. The observation period was divided into before and after the relocation of IVT services in 2018, period 1 and period 2, respectively. The two hospitals were located 13 km apart in an urban area, and following the relocation, IVT was administered at the MT-capable center. Time metrics were registered and divided into two main intervals, namely, ambulance departure from stroke onset location to imaging (ambulance-imaging) and imaging to reperfusion (imaging-reperfusion). The interval imaging-reperfusion included inter-hospital transfer to the MT-capable center in period 1. The association of the imaging-reperfusion duration and functional outcome at 90 days was analyzed using ordinal logistic regression.

Results

No significant change in ambulance-imaging was observed from a median of 27 min (interquartile range [IQR] 22–37) in period 1 to 30 min (IQR 23–40) in period 2, p = 0.19, while the median time of imaging-reperfusion decreased from 173 min (IQR 137–230) to 114 min (IQR 84–152), p < 0.001. The largest absolute time reduction from imaging to reperfusion was seen from imaging to arrival at the angio suite from 89 min (IQR 76–111) to 42 min (IQR 28–63), p < 0.001, which included inter-hospital transfer in period 1. In multivariate analysis, every 10 min of increased delay from imaging to reperfusion was associated with poorer functional outcome with an adjusted odds ratio of 0.95 (95% CI: 0.95–0.98), p < 0.001.

Conclusion

Relocation of IVT services to an MT-capable center was the main cause of reduced time to reperfusion for patients treated with MT and was implemented without affecting prehospital transportation time. These results suggest that patient outcome can be improved by optimizing the organization of IVT and MT services in urban areas.
A pediatric near-infrared spectroscopy brain-computer interface based on the detection of emotional valence
Authors: Floreani Erica D. , Orlandi Silvia , Chau Tom
Published: September 2022

Brain-computer interfaces (BCIs) are being investigated as an access pathway to communication for individuals with physical disabilities, as the technology obviates the need for voluntary motor control. However, to date, minimal research has investigated the use of BCIs for children. Traditional BCI communication paradigms may be suboptimal given that children with physical disabilities may face delays in cognitive development and acquisition of literacy skills. Instead, in this study we explored emotional state as an alternative access pathway to communication. We developed a pediatric BCI to identify positive and negative emotional states from changes in hemodynamic activity of the prefrontal cortex (PFC). To train and test the BCI, 10 neurotypical children aged 8–14 underwent a series of emotion-induction trials over four experimental sessions (one offline, three online) while their brain activity was measured with functional near-infrared spectroscopy (fNIRS). Visual neurofeedback was used to assist participants in regulating their emotional states and modulating their hemodynamic activity in response to the affective stimuli. Child-specific linear discriminant classifiers were trained on cumulatively available data from previous sessions and adaptively updated throughout each session. Average online valence classification exceeded chance across participants by the last two online sessions (with 7 and 8 of the 10 participants performing better than chance, respectively, in Sessions 3 and 4). There was a small significant positive correlation with online BCI performance and age, suggesting older participants were more successful at regulating their emotional state and/or brain activity. Variability was seen across participants in regards to BCI performance, hemodynamic response, and discriminatory features and channels. Retrospective offline analyses yielded accuracies comparable to those reported in adult affective BCI studies using fNIRS. Affective fNIRS-BCIs appear to be feasible for school-aged children, but to further gauge the practical potential of this type of BCI, replication with more training sessions, larger sample sizes, and end-users with disabilities is necessary.
Development and validation of mathematical nomogram for predicting the risk of poor sleep quality among medical students
Authors: Ding Jiahao , Guo Xin , Zhang Mengqi , Hao Mingxia , Zhang Shuang , Tian Rongshen , Long Liting , Chen Xiao , Dong Jihui , Song Haiying , Yuan Jie
Published: September 2022

Background

Despite the increasing prevalence of poor sleep quality among medical students, only few studies have identified the factors associated with it sing methods from epidemiological surveys. Predicting poor sleep quality is critical for ensuring medical Students’ good physical and mental health. The aim of this study was to develop a comprehensive visual predictive nomogram for predicting the risk of poor sleep quality in medical students.

Methods

We investigated medical Students’ association with poor sleep quality at JiTang College of North China University of Science and Technology through a cross-sectional study. A total of 5,140 medical students were randomized into a training cohort (75%) and a validation cohort (25%). Univariate and multivariate logistic regression models were used to explore the factors associated with poor sleep quality. A nomogram was constructed to predict the individual risk of poor sleep quality among the medical students studied.

Results

31.9% of medical students in the study reported poor sleep quality. We performed multivariate logistic analysis and obtained the final model, which confirmed the risk and protective factors of poor sleep quality (p < 0.05). Protective factors included the absence of physical discomfort (OR = 0.638, 95% CI: 0.546–0.745). Risk factors included current drinking (OR = 0.638, 95% CI: 0.546∼0.745), heavy study stress (OR = 2.753, 95% CI: 1.456∼5.631), very heavy study stress (OR = 3.182, 95% CI: 1.606∼6.760), depressive symptoms (OR = 4.305, 95% CI: 3.581∼5.180), and anxiety symptoms (OR = 1.808, 95% CI: 1.497∼2.183). The area under the ROC curve for the training set is 0.776 and the area under the ROC curve for the validation set is 0.770, which indicates that our model has good stability and prediction accuracy. Decision curve analysis and calibration curves demonstrate the clinical usefulness of the predictive nomograms.

Conclusion

Our nomogram helps predict the risk of poor sleep quality among medical students. The nomogram used includes the five factors of drinking, study stress, recent physical discomfort, depressive symptoms, and anxiety symptoms. The model has good performance and can be used for further research on and the management of the sleep quality of medical students.
Applications and challenges of rhodopsin-based optogenetics in biomedicine
Authors: Zhang Hanci , Fang Hui , Liu Deqiang , Zhang Yiming , Adu-Amankwaah Joseph , Yuan Jinxiang , Tan Rubin , Zhu Jianping
Published: September 2022

Optogenetics is an emerging bioengineering technology that has been rapidly developed in recent years by cross-integrating optics, genetic engineering, electrophysiology, software control, and other disciplines. Since the first demonstration of the millisecond neuromodulation ability of the channelrhodopsin-2 (ChR2), the application of optogenetic technology in basic life science research has been rapidly progressed, especially in neurobiology, which has driven the development of the discipline. As the optogenetic tool protein, microbial rhodopsins have been continuously explored, modified, and optimized, with many variants becoming available, with structural characteristics and functions that are highly diversified. Their applicability has been broadened, encouraging more researchers and clinicians to utilize optogenetics technology in research. In this review, we summarize the species and variant types of the most important class of tool proteins in optogenetic techniques, the microbial rhodopsins, and review the current applications of optogenetics based on rhodopsin qualitative light in biology and other fields. We also review the challenges facing this technology, to ultimately provide an in-depth technical reference to support the application of optogenetics in translational and clinical research.
Flying under the radar: CDH2 (N-cadherin), an important hub molecule in neurodevelopmental and neurodegenerative diseases
Authors: László Zsófia I. , Lele Zsolt
Published: September 2022

CDH2 belongs to the classic cadherin family of Ca2+-dependent cell adhesion molecules with a meticulously described dual role in cell adhesion and β-catenin signaling. During CNS development, CDH2 is involved in a wide range of processes including maintenance of neuroepithelial integrity, neural tube closure (neurulation), confinement of radial glia progenitor cells (RGPCs) to the ventricular zone and maintaining their proliferation-differentiation balance, postmitotic neural precursor migration, axon guidance, synaptic development and maintenance. In the past few years, direct and indirect evidence linked CDH2 to various neurological diseases, and in this review, we summarize recent developments regarding CDH2 function and its involvement in pathological alterations of the CNS.
COVID-19 masks: A barrier to facial and vocal information
Authors: Aguillon-Hernandez Nadia , Jusiak Renaud , Latinus Marianne , Wardak Claire
Published: September 2022

With the COVID-19 pandemic, we have become used to wearing masks and have experienced how masks seem to impair emotion and speech recognition. While several studies have focused on facial emotion recognition by adding images of masks on photographs of emotional faces, we have created a video database with actors really wearing masks to test its effect in more ecological conditions. After validating the emotions displayed by the actors, we found that surgical mask impaired happiness and sadness recognition but not neutrality. Moreover, for happiness, this effect was specific to the mask and not to covering the lower part of the face, possibly due to a cognitive bias associated with the surgical mask. We also created videos with speech and tested the effect of mask on emotion and speech recognition when displayed in auditory, visual, or audiovisual modalities. In visual and audiovisual modalities, mask impaired happiness and sadness but improved neutrality recognition. Mask impaired the recognition of bilabial syllables regardless of modality. In addition, it altered speech recognition only in the audiovisual modality for participants above 70 years old. Overall, COVID-19 masks mainly impair emotion recognition, except for older participants for whom it also impacts speech recognition, probably because they rely more on visual information to compensate age-related hearing loss.
Amblyopia is associated with impaired balance in 3–6-year-old children in China
Authors: Brin Taylor A. , Xu Zixuan , Zhou Yusong , Feng Lei , Li Jinrong , Thompson Benjamin
Published: September 2022

Purpose

School-age children in China have more advanced motor development than their North American counterparts. This is likely due to cultural differences in children’s regular motor activities. It is unknown whether the motor function impairments associated with binocular visual disorders (BVDs) such as amblyopia in children raised in North America exist for children raised in China.

Design

Prospective case-control study.

Methods

A major tertiary eye hospital in China tested children aged 3 to <7 (n = 63) belonging to three groups: anisometropic or strabismic amblyopia (n = 22), anisometropia or strabismus without amblyopia (n = 20), or controls (n = 21). The main outcome measure was motor function scores (Movement Assessment Battery for Children 2nd edition).

Results

Balance scores varied significantly across groups (F2,61 = 4.2, p = 0.02) with the amblyopia group (mean ± SD: 12.5 ± 3.0) exhibiting significantly poorer scores than controls (14.8 ± 2.3). The no-amblyopia BVD group (12.8 ± 3.1) did not differ significantly from the other groups. Manual dexterity, catching and throwing and total scores did not vary significantly across the three groups. A separate pre-planned comparison of only the amblyopia and control groups revealed significantly poorer total motor scores in the amblyopia group (10.1 ± 3.2) vs. controls (12 ± 2.4). A linear regression model was unable to significantly predict associations between total motor score and binocular function score (standardized β = −0.09, 95%, p = 0.7), amblyopia etiology (standardized β = 0.14, 95%, p = 0.4), or inter-ocular acuity difference (standardized β = −0.18, 95%, p = 0.4), in the amblyopia group.

Conclusion

Amblyopia is associated with motor function impairment in children raised in China. Motor deficits that may impact everyday activities have been observed in patients with amblyopia across multiple cultures.
The degree of food processing is associated with anthropometric measures of obesity in Canadian families with preschool-aged children
Authors: Ashraf Rahbika , Duncan Alison M. , Darlington Gerarda , Buchholz Andrea C. , Haines Jess , Ma David W. L.
Published: September 2022

Adopting a healthy diet remains central for the prevention of obesity. In adults, higher intake of ultra-processed food is associated with a greater risk of overweight and obesity. However, little is known about the degree of food processing and its association with anthropometric measures in families with preschool-aged children, a critical period for the development of dietary patterns. This cross-sectional study included preschool-aged children (n = 267) between 1.5 and 5 years of age and their parents (n = 365) from 242 families enrolled in the Guelph Family Health Study. Dietary assessment was completed using ASA24-Canada-2016. Foods and beverages were classified based on their degree of food processing using the NOVA Classification (unprocessed or minimally processed foods, processed culinary ingredients, processed foods, and ultra-processed foods). Associations between the energy contribution (% kcal) of each NOVA category and anthropometric measures were examined using linear regression models with generalized estimating equations, adjusted for sociodemographic variables. The energy contribution of ultra-processed foods was the highest relative to the other NOVA categories among parents (44.3%) and children (41.3%). The energy contribution of unprocessed or minimally processed foods was 29.1% for parents and 35.3% for children, processed foods was 24.0% for parents and 21.3% for children, and processed culinary ingredients was 2.6% for parents and 2.1% for children. Ultra-processed foods (% kcal) were positively associated with BMI (β = 0.04, 95% CI: 0.01–0.07, P = 0.02), waist circumference (β = 0.11, 95% CI: 0.03–0.18, P = 0.008) and body weight (β = 0.13, 95% CI: 0.03–0.22, P = 0.01) in parents, but not children. Unprocessed foods (% kcal) were negatively associated with waist circumference in parents (β = −0.09, 95% CI: 0.18–0.01, P = 0.03) and children (β = −0.03, 95% CI: 0.05–0.01, P = 0.01), as well as body weight (β = −0.12, 95% CI: 0.23–0.00, P = 0.04) in parents. The degree of food processing primarily influenced anthropometric outcomes in parents. Nevertheless, diets of children were similar, suggesting that such exposure in families may eventually lead to outcomes observed in parents.
Prediction of postoperative cardiopulmonary complications after lung resection in a Chinese population: A machine learning-based study
Authors: Huang Guanghua , Liu Lei , Wang Luyi , Li Shanqing
Published: September 2022

Background

Approximately 20% of patients with lung cancer would experience postoperative cardiopulmonary complications after anatomic lung resection. Current prediction models for postoperative complications were not suitable for Chinese patients. This study aimed to develop and validate novel prediction models based on machine learning algorithms in a Chinese population.

Methods

Patients with lung cancer receiving anatomic lung resection and no neoadjuvant therapies from September 1, 2018 to August 31, 2019 were enrolled. The dataset was split into two cohorts at a 7:3 ratio. The logistic regression, random forest, and extreme gradient boosting were applied to construct models in the derivation cohort with 5-fold cross validation. The validation cohort accessed the model performance. The area under the curves measured the model discrimination, while the Spiegelhalter z test evaluated the model calibration.

Results

A total of 1085 patients were included, and 760 were assigned to the derivation cohort. 8.4% and 8.0% of patients experienced postoperative cardiopulmonary complications in the two cohorts. All baseline characteristics were balanced. The values of the area under the curve were 0.728, 0.721, and 0.767 for the logistic, random forest and extreme gradient boosting models, respectively. No significant differences existed among them. They all showed good calibration (p > 0.05). The logistic model consisted of male, arrhythmia, cerebrovascular disease, the percentage of predicted postoperative forced expiratory volume in one second, and the ratio of forced expiratory volume in one second to forced vital capacity. The last two variables, the percentage of forced vital capacity and age ranked in the top five important variables for novel machine learning models. A nomogram was plotted for the logistic model.

Conclusion

Three models were developed and validated for predicting postoperative cardiopulmonary complications among Chinese patients with lung cancer. They all exerted good discrimination and calibration. The percentage of predicted postoperative forced expiratory volume in one second and the ratio of forced expiratory volume in one second to forced vital capacity might be the most important variables. Further validation in different scenarios is still warranted.
Case Report: Successful therapy with all-trans retinoic acid combined with chemotherapy followed by hematopoietic stem cell transplantation for acute promyelocytic leukemia carrying the BCOR-RARA fusion gene
Authors: Chen Li , Zhu Hongming , Zhu Yongmei , Jin Wen , Dong Fangyi , Li Jianfeng , Hu Jiong , Chen Qiusheng , Wang Kankan , Li Junmin
Published: September 2022

Acute promyelocytic leukemia (APL) is characterized by the balanced translocation of chromosomes 15 and 17, resulting in the formation of PML-RARA fusion gene. More than 98% of APL have PML-RARA fusion, and less than 2% have other types of RARA gene partners, which named variant APL (vAPL). In the present study, we reported a vAPL with BCOR-RARA, which was the third case of BCOR-RARA APL published. The patient achieved complete remission (CR) with all-trans retinoic acid (ATRA) monotherapy, and molecular CR with ATRA plus standard chemotherapy. After that, he underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) and ATRA maintenance and maintained a molecular CR status. This case provided valuable insights into the accurate identification of vAPL. Moreover, ATRA combined with chemotherapy followed by allo-HSCT was suggested as an optimal choice for those vAPL patients who had a high risk of relapse.
Diagnosis of rapidly progressed primary cardiac lymphoma in liver transplant recipient: A case report
Authors: Li Jianghua , Liu Qiyun , Peng Quanzhou , Dong Shaohong
Published: September 2022

Primary cardiac lymphomas (PCLs) are extremely rare and affect the heart. Patients with PCLs usually have delayed diagnosis and treatment. As a consequence, their prognosis is quite unfavorable, and their median survival is approximately 7 months. Herein, we report a 64-year-old man who underwent liver transplantation, presented with chest pain and exertional dyspnea, developed a huge cardiac mass within 2 months and passed away on day 3 of hospitalization. Histological examination revealed diffuse large B-cell lymphoma (DLBCL), which is a rare cardiac tumor with a poor prognosis. In this case, DLBCL was only detected postmortem. The extension of the mass and its relationship with the heart were explored with non-invasive cardiac imaging. Despite the rarity of DLBCL, it should be considered in the differential diagnosis of cardiac tumors.
LncRNA PELATON, a Ferroptosis Suppressor and Prognositic Signature for GBM
Authors: Fu Haijuan , Zhang Zhaoyu , Li Danyang , Lv Qingqing , Chen Simin , Zhang Zuping , Wu Minghua
Published: September 2022

PELATON is a long noncoding RNA also known as long intergenic nonprotein coding RNA 1272 (LINC01272). The known reports showed that PELATON functions as an onco-lncRNA or a suppressor lncRNA by suppressing miRNA in colorectal cancer, gastric cancer and lung cancer. In this study, we first found that PELATON, as an onco-lncRNA, alleviates the ferroptosis driven by mutant p53 and promotes mutant p53-mediated GBM proliferation. We also first confirmed that PELATON is a new ferroptosis suppressor lncRNA that functions as a ferroptosis inhibitor mainly by mutant P53 mediating the ROS ferroptosis pathway, which inhibits the production of ROS, reduces the levels of divalent iron ions, promotes the expression of SLC7A11, and inhibits the expression of ACSL4 and COX2.PELATON can inhibit the expression of p53 in p53 wild-type GBM cells and regulate the expression of BACH1 and CD44, but it has no effect on p53, BACH1 and CD44 in p53 mutant GBM cells. PELATON and p53 can form a complex through the RNA binding protein EIF4A3. Knockdown of PELATON resulted in smaller mitochondria, increased mitochondrial membrane density, and enhanced sensitivity to ferroptosis inducers to inhibit GBM cell proliferation and invasion. In addition, we established a favourite prognostic model with NCOA4 and PELATON. PELATON is a promising target for the prognosis and treatment of GBM.
Treatment related toxicities with combination BRAF and MEK inhibitor therapy in resected stage III melanoma
Authors: Homan Morgan , Warrier Govind , Lao Christopher D. , Yentz Sarah , Kraft Shawna , Fecher Leslie A.
Published: September 2022

Combination dabrafenib (D) and trametinib (T) is an FDA approved adjuvant therapy for patients with resected stage III BRAF-mutant melanoma. We describe treatment-related toxicities with adjuvant D+T in a real-world population through a retrospective case series. The primary endpoint was development of toxicities.

Results

Eighteen of the 20 patients (90%) required at least one treatment interruption due to adverse events (AEs), 11 patients (55%) required a dose reduction and 13 (65%) permanently discontinued therapy due to an AE. The nine patients who did not require dose reduction had been initiated on a lower starting dose of dabrafenib. The most common treatment-limiting AEs were recurrent pyrexia and chills (85%) and liver laboratory abnormalities (50%). The median total time on therapy was 148.5 days (range 19-383), 40.7% (range 5.2-100%) of the intended one-year duration.

Conclusion

Adjuvant treatment of melanoma with combination D+T is associated with treatment-limiting toxicities in the majority of this patient group. Patients should be carefully monitored throughout therapy.
A novel germline HAVCR2 (TIM-3) compound heterozygous mutation is related to hemophagocytic lymphohistiocytic syndrome in EBV-positive peripheral T-cell lymphoma (NOS) with down-regulated TIM-3 signaling
Authors: Zhang Yang , Wang Zhihua , Hu Guoyu , Li Jieping , Chen Yongheng , Jiang Yi , Zhong Haiying , Liu Xianling , Hu Chunhong , Peng Honglin , Xu Yunxiao , Cheng Zhao , Zhang Guangsen
Published: September 2022

Recently, it have been reported that Hepatitis A Virus-Cellular Receptor 2(HAVCR2,encoding T-cell immunoglobulin and Mucin-Containing Protein 3[TIM3]) mutations are associated with severe hemophagocytic syndrome(HLH) in subcutaneous panniculitis-like T-cell lymphoma(SPTCL),and there are also frequent mutations in sporadic SPTCL, suggesting the individuals harboring HAVCR2(TIM-3) germline mutations are highly susceptible to familial or sporadic SPTCL. Here, we identify a novel germline compound heterozygous mutation of TIM-3 gene,c.245A>G (p.Tyr82Cys) and c.265C>T(p.Arg89Cys) variations in a single familial case with EBV-positive peripheral T-cell lymphoma(NOS),accompanied HLH;we also detected Tyr82Cys germline mutation in TIM-3 gene in one sporadic patient with cutaneous T cell lymphoma. We screened the distributive frequencies for TIM-3 mutations in healthy controls(n=87), B-(n=79) or T-cell lymphoma(n=25) not SPTCL, and the results showed that the mutation was found in two out of 25 patients with T-cell lymphoma but was not detected in 79 patients with B-cell lymphoma nor in a group of 87 controls. The mRNA expression of TIM-3 on primary cells and transfected HEK293 cells reduced significantly, indicating Tyr82Cys and Arg89Cys mutations is a loss-of function mutations on TIM-3,resulting in a weakened TIM-3 signaling. Our results suggest Tyr82Cys TIM-3 germline mutations are not only limited in SPTCL, and also occurred in other types of T-cell lymphoma, especially complicated HLH. TIM-3 mutations may be an predisposing factor for T-cell lymphoma and molecular marker for auxiliary diagnosis in T cell lymphoma,especially complicated with HLH.
Nomograms for prediction of breast cancer in breast imaging reporting and data system (BI-RADS) ultrasound category 4 or 5 lesions: A single-center retrospective study based on radiomics features
Authors: Hong Zhi-Liang , Chen Sheng , Peng Xiao-Rui , Li Jian-Wei , Yang Jian-Chuan , Wu Song-Song
Published: September 2022

Purpose

To develop nomograms for predicting breast malignancy in BI-RADS ultrasound (US) category 4 or 5 lesions based on radiomics features.

Methods

Between January 2020 and January 2022, we prospectively collected and retrospectively analyzed the medical records of 496 patients pathologically proven breast lesions in our hospital. The data set was divided into model training group and validation testing group with a 75/25 split. Radiomics features were obtained using the PyRadiomics package, and the radiomics score was established by least absolute shrinkage and selection operator regression. A nomogram was developed for BI-RADS US category 4 or 5 lesions according to the results of multivariate regression analysis from the training group.

Result

The AUCs of radiomics score consisting of 31 US features was 0.886. The AUC of the model constructed with radiomics score, patient age, lesion diameter identified by US and BI-RADS category involved was 0.956 (95% CI, 0.910–0.972) for the training group and 0.937 (95% CI, 0.893–0.965) for the validation cohort. The calibration curves showed good agreement between the predictions and observations.

Conclusions

Both nomogram and radiomics score can be used as methods to assist radiologists and clinicians in predicting breast malignancy in BI-RADS US category 4 or 5 lesions.
Functional lung imaging in thoracic tumor radiotherapy: Application and progress
Authors: Zhou Pi-Xiao , Zhang Shu-Xu
Published: September 2022

Radiotherapy plays an irreplaceable and unique role in treating thoracic tumors, but the occurrence of radiation-induced lung injury has limited the increase in tumor target doses and has influenced patients’ quality of life. However, the introduction of functional lung imaging has been incorporating functional lungs into radiotherapy planning. The design of the functional lung protection plan, while meeting the target dose requirements and dose limitations of the organs at risk (OARs), minimizes the radiation dose to the functional lung, thus reducing the occurrence of radiation-induced lung injury. In this manuscript, we mainly reviewed the lung ventilation or/and perfusion functional imaging modalities, application, and progress, as well as the results based on the functional lung protection planning in thoracic tumors. In addition, we also discussed the problems that should be explored and further studied in the practical application based on functional lung radiotherapy planning.
5-ALA-guided tumor resection during awake speech mapping in gliomas located in eloquent speech areas: Single-center experience
Authors: Goryaynov Sergey A. , Buklina Svetlana B. , Khapov Ivan V. , Batalov Artyom I. , Potapov Alexander A. , Pronin Igor N. , Belyaev Artem U. , Aristov Andrey A. , Zhukov Vadim U. , Pavlova Galina V. , Belykh Evgenii
Published: September 2022

Background

Achieving maximal functionally safe resection of gliomas located within the eloquent speech areas is challenging, and there is a lack of literature on the combined use of 5-aminolevulinic acid (5-ALA) guidance and awake craniotomy.

Objective

The aim of this study was to describe our experience with the simultaneous use of 5-ALA fluorescence and awake speech mapping in patients with left frontal gliomas located within the vicinity of eloquent speech areas.

Materials and methods

A prospectively collected database of patients was reviewed. 5-ALA was administered at a dose of 20 mg/kg 2 h prior to operation, and an operating microscope in BLUE400 mode was used to visualize fluorescence. All patients underwent surgery using the “asleep–awake–asleep” protocol with monopolar and bipolar electrical stimulation to identify the proximity of eloquent cortex and white matter tracts and to guide safe limits of resection along with fluorescence guidance. Speech function was assessed by a trained neuropsychologist before, during, and after surgery.

Results

In 28 patients operated with cortical mapping and 5-ALA guidance (12 Grade 4, 6 Grade 3, and 10 Grade 2 gliomas), Broca’s area was identified in 23 cases and Wernicke’s area was identified in 5 cases. Fluorescence was present in 14 cases. Six tumors had residual fluorescence due to the positive speech mapping in the tumor bed. Transient aphasia developed in 14 patients, and permanent aphasia developed in 4 patients. In 6 patients operated with cortical and subcortical speech mapping and 5-ALA guidance (4 Grade 4, 1 Grade 3, and 1 Grade 2 gliomas), cortical speech areas were mapped in 5 patients and subcortical tracts were encountered in all cases. In all cases, resection was stopped despite the presence of residual fluorescence due to speech mapping findings. Transient aphasia developed in 6 patients and permanent aphasia developed in 4 patients. In patients with Grade 2–3 gliomas, targeted biopsy of focal fluorescence areas led to upgrading the grade and thus more accurate diagnosis.

Conclusion

5-ALA guidance during awake speech mapping is useful in augmenting the extent of resection for infiltrative high-grade gliomas and identifying foci of anaplasia in non-enhancing gliomas, while maintaining safe limits of functional resection based on speech mapping. Positive 5-ALA fluorescence in diffuse Grade 2 gliomas may be predictive of a more aggressive disease course.
The predictive value of total-body PET/CT in non-small cell lung cancer for the PD-L1 high expression
Authors: Hu Bingxin , Jin Huibin , Li Xiali , Wu Xinyu , Xu Junling , Gao Yongju
Published: September 2022

Purpose

Total-body positron emission tomography/computed tomography (PET/CT) provides faster scanning speed, higher image quality, and lower injected dose. To compensate for the shortcomings of the maximum standard uptake value (SUVmax), we aimed to normalize the values of PET parameters using liver and blood pool SUV (SUR-L and SUR-BP) to predict programmed cell death-ligand 1 (PD-L1) expression in non-small cell lung cancer (NSCLC) patients.

Materials and methods

A total of 138 (104 adenocarcinoma and 34 squamous cell carcinoma) primary diagnosed NSCLC patients who underwent 18F-FDG-PET/CT imaging were analyzed retrospectively. Immunohistochemistry (IHC) analysis was performed for PD-L1 expression on tumor cells and tumor-infiltrating immune cells with 22C3 antibody. Positive PD-L1 expression was defined as tumor cells no less than 50% or tumor-infiltrating immune cells no less than 10%. The relationships between PD-L1 expression and PET parameters (SUVmax, SUR-L, and SUR-BP) and clinical variables were analyzed. Statistical analysis included χ2 test, receiver operating characteristic (ROC), and binary logistic regression.

Results

There were 36 patients (26%) expressing PD-L1 positively. Gender, smoking history, Ki-67, and histologic subtype were related factors. SUVmax, SUR-L, and SUR-BP were significantly higher in the positive subset than those in the negative subset. Among them, the area under the curve (AUC) of SUR-L on the ROC curve was the biggest one. In NSCLC patients, the best cutoff value of SUR-L for PD-L1-positive expression was 4.84 (AUC = 0.702, P = 0.000, sensitivity = 83.3%, specificity = 54.9%). Multivariate analysis confirmed that age and SUR-L were correlated factors in adenocarcinoma (ADC) patients.

Conclusion

SUVmax, SUR-L, and SUR-BP had utility in predicting PD-L1 high expression, and SUR-L was the most reliable parameter. PET/CT can offer reference to screen patients for first-line atezolizumab therapy.
Radical surgery for stage IB2/IIA2 cervical cancer: A large retrospective study
Authors: Zhou Fang , Tang Xuedong , Shao Zhuyan , Chen Xi , Gao Wen , Fang Chenyan , Wang Zejia , Zhang Ping , Zhu Tao , Tang Huarong
Published: September 2022

Background

We aimed to evaluate survival, complications, and prognostic factors in patients with IB2/IIA2 (FIGO 2009, bulky early-stage) cervical cancer (CC) who were primarily treated with radical surgery (RS).

Methods

From January 2011 to January 2018, patients with stage IB2/IIA2 CC who underwent RS ± adjuvant therapy were enrolled and retrospectively evaluated. Survival was estimated using the Kaplan–Meier method. Significance was determined using the log-rank test. Multivariate regression analyses were performed to determine prognostic factors.

Results

Of the 975 enrolled patients, 877 (89.9%) received adjuvant therapy. The median follow-up was 48 months, the 5-year overall survival (OS) was 85.9%, and the 5-year progression-free survival (PFS) rate was 80.8%. Multivariate analysis showed that histological type, pelvic lymph nodes, and para-aortic lymph nodes were independent prognostic factors for PFS and OS. Tumor diameter was also an independent prognostic factor with OS. Recurrent disease developed in 14.3% (140) of patients., including local, distant, and both recurrences in 55 (5.6%), 71 (7.3%), and 14 (1.4%) patients, respectively. Grade 3–4 short-term complications occurred in 196 (20.1%) patients, and long-term complications occurred in 86 (8.8%) patients. Short-term hematological complications occurred in 99 cases (10.2%). No significant differences in non-hematological complications were detected between the RS and RS + adjuvant therapy groups.

Conclusions

RS followed by adjuvant therapy is a feasible and effective treatment for IB2/IIA2 CC, with a high 5-year survival rate and an acceptable incidence of complications. Positive pelvic lymph nodes and para-aortic abdominal lymph nodes significantly impact PFS and OS. Evaluation of lymph node status before surgery is important. RS is recommended for patients with negative lymph node metastasis.