bluuebunny/crossref_metadata_2025 huggingface dataset:
Coping Style in Glioma Patients and Their Caregiver: Evaluation During Disease Trajectory
Authors: Guariglia Lara , Ieraci Sonia , Villani Veronica , Tanzilli Antonio , Benincasa Dario , Sperati Francesca , Terrenato Irene , Pace Andrea
Published: September 2021

Background: Patients with glioma have a poor prognosis and, in a short period of time, have to deal with severe forms of disability, which compromise their psychological distress and quality of life. The caregivers of these patients consequently carry a heavy burden in terms of emotional and patient care. The study aims to evaluate the coping strategies of patients and their caregivers during the course of the disease in order to frame the adaptation process in a rapidly progressing pathology.

Methods: A prospective study on 24 dyads of patients affected by malignant glioma and their caregivers was conducted between May 2016 and July 2018. Questionnaires designed to identify the coping style (MINI-MaC Scale) and psychological distress (HADS scores) and assess QOL (EQ-5D) were administered at two time points: at first lines of treatment and at disease recurrence.

Results: Patients and their caregiver structure adaptive coping strategies during the disease: a coping style oriented toward a fighting spirit prevails at baseline (Mini-Mac Mean 3.23); fatalism prevails at recurrence (Mini-Mac Mean 3.03). Psychological distress affects the coping style expressed: high levels of anxiety symptoms were found to be significantly associated with a coping style oriented toward anxious preoccupation, helpless–hopeless, and fatalism; low depressive symptoms were inversely correlated with fighting spirit coping style. Patients' and caregivers' perceptions of quality of life were correlated between them and with performance status assessed by clinicians. In a dyadic perspective, the adaptation of a member of the couple varies as a function of the other partner's coping style.

Conclusions: Our data are in line with previous literature on cancer patients, demonstrating that coping style is not a persistent dimension of personality, but can change depending on the situation. Despite the disease rapid course, patients and their caregivers can structure adaptive and functional defenses to manage the disease.
A Prospective Stroke Register in Sierra Leone: Demographics, Stroke Type, Stroke Care and Hospital Outcomes
Authors: Youkee Daniel , Deen Gibrilla , Barrett Edward , Fox-Rushby Julia , Johnson Israel , Langhorne Peter , Leather Andrew , Marshall Iain J. , O'Hara Jessica , Rudd Anthony , Sama Albert , Scott Christella , Thompson Melvina , Wafa Hatem , Wall Jurate , Wang Yanzhong , Watkins Caroline , Wolfe Charles , Lisk Durodami Radcliffe , Sackley Catherine Mary
Published: September 2021

Introduction: Stroke is the second most common cause of adult death in Africa. This study reports the demographics, stroke types, stroke care and hospital outcomes for stroke in Freetown, Sierra Leone.

Methods: A prospective observational register recorded all patients 18 years and over with stroke between May 2019 and April 2020. Stroke was defined according to the WHO criteria. Pearson's chi-squared test was used to examine associations between categorical variables and unpaired t-tests for continuous variables. Multivariable logistic regression, to explain in-hospital death, was reported as odds ratios (ORs) and 95% confidence intervals.

Results: Three hundred eighty-five strokes were registered, and 315 (81.8%) were first-in-a-lifetime events. Mean age was 59.2 (SD 13.8), and 187 (48.6%) were male. Of the strokes, 327 (84.9%) were confirmed by CT scan. Two hundred thirty-one (60.0%) were ischaemic, 85 (22.1%) intracerebral haemorrhage, 11 (2.9%) subarachnoid haemorrhage and 58 (15.1%) undetermined stroke type. The median National Institutes of Health Stroke Scale on presentation was 17 [interquartile range (IQR) 9–25]. Haemorrhagic strokes compared with ischaemic strokes were more severe, 20 (IQR 12–26) vs. 13 (IQR 7–22) (p < 0.001), and occurred in a younger population, mean age 52.3 (SD 12.0) vs. 61.6 (SD 13.8) (p < 0.001), with a lower level of educational attainment of 28.2 vs. 40.7% (p = 0.04). The median time from stroke onset to arrival at the principal referral hospital was 25 hours (IQR 6–73). Half of the patients (50.4%) sought care at another health provider prior to arrival. One hundred fifty-one patients died in the hospital (39.5%). Forty-three deaths occurred within 48 hours of arriving at the hospital, with median time to death of 4 days (IQR 0–7 days). Of the patients, 49.6% had ≥1 complication, 98 (25.5%) pneumonia and 33 (8.6%) urinary tract infection. Male gender (OR 3.33, 1.65–6.75), pneumonia (OR 3.75, 1.82–7.76), subarachnoid haemorrhage (OR 43.1, 6.70–277.4) and undetermined stroke types (OR 6.35, 2.17–18.60) were associated with higher risk of in-hospital death.

Discussion: We observed severe strokes occurring in a young population with high in-hospital mortality. Further work to deliver evidence-based stroke care is essential to reduce stroke mortality in Sierra Leone.
Comparison of 2-Hydroxyglutarate Detection With sLASER and MEGA-sLASER at 7T
Authors: Shams Zahra , van der Kemp Wybe J. M. , Emir Uzay , Dankbaar Jan Willem , Snijders Tom J. , de Vos Filip Y. F. , Klomp Dennis W. J. , Wijnen Jannie P. , Wiegers Evita C.
Published: September 2021

The onco-metabolite 2-hydroxyglutarate (2HG), a biomarker of IDH-mutant gliomas, can be detected with1H MR spectroscopy (1H-MRS). Recent studies showed measurements of 2HG at 7T with substantial gain in signal to noise ratio (SNR) and spectral resolution, offering higher specificity and sensitivity for 2HG detection. In this study, we assessed the sensitivity of semi-localized by adiabatic selective refocusing (sLASER) and J-difference MEsher-GArwood-semi-LASER (MEGA-sLASER) for 2HG detection at 7T. We performed spectral editing at long TE using a TE-optimized sLASER sequence (110 ms) and J-difference spectroscopy using MEGA-sLASER (TE= 74ms) in phantoms with different 2HG concentrations to assess the sensitivity of 2HG detection. The robustness of the methods against B0inhomogeneity was investigated. Moreover, the performance of these two techniques was evaluated in four patients with IDH1-mutated glioma. In contrary to MEGA-sLASER, sLASER was able to detect 2HG concentration as low as 0.5 mM. In case of a composite phantom containing 2HG with overlapping metabolites, MEGA-sLASER provided a clean 2HG signal with higher fitting reliability (lower %CRLB). The results demonstrate that sLASER is more robust against field inhomogeneities and experimental or motion-related artifacts which promotes to adopt sLASER in clinical implementations.
The Effects of Intensive Neurorehabilitation on Sequence Effect in Parkinson's Disease Patients With and Without Freezing of Gait
Authors: Putortì Alessia , Corrado Michele , Avenali Micol , Martinelli Daniele , Allena Marta , Cristina Silvano , Grillo Valentina , Martinis Luca , Tamburin Stefano , Serrao Mariano , Pisani Antonio , Tassorelli Cristina , De Icco Roberto
Published: September 2021

Background: The sequence effect (SE), defined as a reduction in amplitude of repetitive movements, is a common clinical feature of Parkinson's disease (PD) and is supposed to be a major contributor to freezing of gait (FOG). During walking, SE manifests as a step-by-step reduction in step length when approaching a turning point or gait destination, resulting in the so-called destination sequence effect (dSE). Previous studies explored the therapeutic effects of several strategies on SE, but none of them evaluated the role of an intensive rehabilitative program.

Objectives: Here we aim to study the effects of a 4-week rehabilitative program on dSE in patients with PD with and without FOG.

Methods: Forty-three patients (30 males, 70.6 ± 7.5 years old) with idiopathic PD were enrolled. The subjects were divided into two groups: patients with (PD + FOG, n = 23) and without FOG (PD – FOG, n = 20). All patients underwent a standardized 4-week intensive rehabilitation in-hospital program. At hospital admission (T0) and discharge (T1), all subjects were evaluated with an inertial gait analysis for dSE recording.

Results: At T0, the dSE was more negative in the PD + FOG group (−0.80 ± 0.6) when compared to the PD – FOG group (−0.39 ± 0.3) (p = 0.007), even when controlling for several clinical and demographic features. At T1, the dSE was reduced in the overall study population (p = 0.001), with a more pronounced improvement in the PD + FOG group (T0: −0.80 ± 0.6; T1: −0.23 ± 0.4) when compared to the PD – FOG group (T0: −0.39 ± 0.3; T1: −0.22 ± 0.5) (p = 0.012). At T1, we described in the overall study population an improvement in speed, cadence, stride duration, and stride length (p = 0.001 for all variables).

Conclusions: dSE is a core feature of PD gait dysfunction, specifically in patients with FOG. A 4-week intensive rehabilitative program improved dSE in PD patients, exerting a more notable beneficial effect in the PD + FOG group.
Integrative Neuroinformatics for Precision Prognostication and Personalized Therapeutics in Moderate and Severe Traumatic Brain Injury
Authors: Zeiler Frederick A. , Iturria-Medina Yasser , Thelin Eric P. , Gomez Alwyn , Shankar Jai J. , Ko Ji Hyun , Figley Chase R. , Wright Galen E. B. , Anderson Chris M.
Published: September 2021

Despite changes in guideline-based management of moderate/severe traumatic brain injury (TBI) over the preceding decades, little impact on mortality and morbidity have been seen. This argues against the “one-treatment fits all” approach to such management strategies. With this, some preliminary advances in the area of personalized medicine in TBI care have displayed promising results. However, to continue transitioning toward individually-tailored care, we require integration of complex “-omics” data sets. The past few decades have seen dramatic increases in the volume of complex multi-modal data in moderate and severe TBI care. Such data includes serial high-fidelity multi-modal characterization of the cerebral physiome, serum/cerebrospinal fluid proteomics, admission genetic profiles, and serial advanced neuroimaging modalities. Integrating these complex and serially obtained data sets, with patient baseline demographics, treatment information and clinical outcomes over time, can be a daunting task for the treating clinician. Within this review, we highlight the current status of such multi-modal omics data sets in moderate/severe TBI, current limitations to the utilization of such data, and a potential path forward through employing integrative neuroinformatic approaches, which are applied in other neuropathologies. Such advances are positioned to facilitate the transition to precision prognostication and inform a top-down approach to the development of personalized therapeutics in moderate/severe TBI.
Sodium Levels Predict Disability at Discharge in Guillain-Barré Syndrome: A Retrospective Cohort Study
Authors: Gagliardi Delia , Faravelli Irene , Podestà Manuel Alfredo , Brusa Roberta , Mauri Eleonora , Saccomanno Domenica , Di Fonzo Alessio , Bonato Sara , Scarpini Elio , Bresolin Nereo , Comi Giacomo Pietro , Corti Stefania
Published: September 2021

Guillain-Barré syndrome (GBS) is an inflammatory polyradiculopathy with potentially severe complications. Clinical tools for risk stratification have been developed, but no definitive prognostic biomarker has been reported. Hyponatremia is frequent in GBS patients, but the impact of serum sodium levels on clinical outcomes is still ill-defined. In this retrospective cohort study, we included all adult patients diagnosed with GBS spectrum disorders at our center from January 2010 to July 2020. Disability at discharge was assessed with the GBS Disability Score (GDS), and all clinical and laboratory data was retrieved from medical charts. Thirty (58.8%) of the 51 subjects included in the study were discharged with severe residual disability (GDS ≥ 3). After accounting for relevant confounders, the odds of experiencing severe disability decreased by 27% (p = 0.027) for each unitary increase in serum sodium concentration. Thirteen (25.5%) patients were diagnosed with mild to moderate hyponatremia; the use of intravenous immune globulin (IVIG) independently increased the odds of developing hyponatremia. In conclusion, we found a significant, independent association between baseline serum sodium levels and severe disability at discharge in GBS patients. In our cohort, hyponatremia was more frequently observed after treatment with IVIG, suggesting dilutional pseudohyponatremia as a probable cause.
First Language Attrition: What It Is, What It Isn’t, and What It Can Be
Authors: Gallo Federico , Bermudez-Margaretto Beatriz , Shtyrov Yury , Abutalebi Jubin , Kreiner Hamutal , Chitaya Tamara , Petrova Anna , Myachykov Andriy
Published: September 2021

This review aims at clarifying the concept of first language attrition by tracing its limits, identifying its phenomenological and contextual constraints, discussing controversies associated with its definition, and suggesting potential directions for future research. We start by reviewing different definitions of attrition as well as associated inconsistencies. We then discuss the underlying mechanisms of first language attrition and review available evidence supporting different background hypotheses. Finally, we attempt to provide the groundwork to build a unified theoretical framework allowing for generalizable results. To this end, we suggest the deployment of a rigorous neuroscientific approach, in search of neural markers of first language attrition in different linguistic domains, putting forward hypothetical experimental ways to identify attrition’s neural traces and formulating predictions for each of the proposed experimental paradigms.
The Ecological Task Dynamics of Learning and Transfer in Coordinated Rhythmic Movement
Authors: Leach Daniel , Kolokotroni Zoe , Wilson Andrew D.
Published: September 2021

Research spanning 100 years has revealed that learning a novel perception-action task is remarkably task-specific. With only a few exceptions, transfer is typically very small, even with seemingly small changes to the task. This fact has remained surprising given previous attempts to formalise the notion of what a task is, which have been dominated by common-sense divisions of tasks into parts. This article lays out an ecologically grounded alternative, ecological task dynamics, which provides us with tools to formally define tasks as experience from the first-person perspective of the learner. We explain this approach using data from a learning and transfer experiment using bimanual coordinated rhythmic movement as the task, and acquiring a novel coordination as the goal of learning. 10 participants were extensively trained to perform 60° mean relative phase; this learning transferred to 30° and 90°, against predictions derived from our previous work. We use recent developments in the formal model of the task to guide interpretation of the learning and transfer results.
Morality of the Heart: Heart Rate Variability and Moral Rule Adherence in Men
Authors: Lischke Alexander , Weippert Matthias , Mau-Moeller Anett , Pahnke Rike
Published: September 2021

Moral rules are a cornerstone of many societies. Most moral rules are concerned with the welfare of other individuals, reflecting individuals’ innate aversion against harming other individuals. Harming others is associated with aversive experiences, implying that individuals who are sensitive to the aversiveness of these experiences are more likely to follow moral rules than individuals who are insensitive to the aversiveness of these experiences. Individuals’ sensitivity for aversive experiences depends on individuals’ ability to integrate the underlying neural and physiological processes: Individuals who are more efficient in integrating these processes are more sensitive to the aversiveness that is associated with moral rule violations than individuals who are less efficient in integrating these processes. Individuals who differ in their ability to integrate these processes may, thus, also differ in their inclination to follow moral rules. We tested this assumption in a sample of healthy individuals (67 males) who completed measures of moral rule adherence and integration abilities. Moral rule adherence was assessed with self-report measure and integration abilities were assessed with a resting state measure of heart rate variability (HRV), which reflects prefrontal–(para-)limbic engagement during the integration of physical and neural processes. We found a positive association between individuals’ HRV and individuals’ moral rule adherence, implying that individuals with efficient integration abilities were more inclined to follow moral rules than individuals with inefficient integration abilities. Our findings support the assumption that individuals with different integration abilities also differ in moral rule adherence, presumably because of differences in aversiveness sensitivity.
rTMS Induces Brain Functional and Structural Alternations in Schizophrenia Patient With Auditory Verbal Hallucination
Authors: Xie Yuanjun , Guan Muzhen , Wang Zhongheng , Ma Zhujing , Wang Huaning , Fang Peng , Yin Hong
Published: September 2021

Background

Low-frequency transcranial magnetic stimulation (rTMS) over the left temporoparietal cortex reduces the auditory verbal hallucination (AVH) in schizophrenia. However, the underlying neural basis of the rTMS treatment effect for schizophrenia remains not well understood. This study investigates the rTMS induced brain functional and structural alternations and their associations with clinical as well as neurocognitive profiles in schizophrenia patients with AVH.

Methods

Thirty schizophrenia patients with AVH and thirty-three matched healthy controls were enrolled. The patients were administered by 15 days of 1 Hz rTMS delivering to the left temporoparietal junction (TPJ) area. Clinical symptoms and neurocognitive measurements were assessed at pre- and post-rTMS treatment. The functional (amplitude of low-frequency fluctuation, ALFF) and structural (gray matter volume, GMV) alternations were compared, and they were then used to related to the clinical and neurocognitive measurements after rTMS treatment.

Results

The results showed that the positive symptoms, including AVH, were relieved, and certain neurocognitive measurements, including visual learning (VisLearn) and verbal learning (VerbLearn), were improved after the rTMS treatment in the patient group. Furthermore, the rTMS treatment induced brain functional and structural alternations in patients, such as enhanced ALFF in the left superior frontal gyrus and larger GMV in the right inferior temporal cortex. The baseline ALFF and GMV values in certain brain areas (e.g., the inferior parietal lobule and superior temporal gyrus) could be associated with the clinical symptoms (e.g., positive symptoms) and neurocognitive performances (e.g., VerbLearn and VisLearn) after rTMS treatment in patients.

Conclusion

The low-frequency rTMS over the left TPJ area is an efficacious treatment for schizophrenia patients with AVH and could selectively modulate the neural basis underlying psychiatric symptoms and neurocognitive domains in schizophrenia.
Contribution of RNA/DNA Binding Protein Dysfunction in Oligodendrocytes in the Pathogenesis of the Amyotrophic Lateral Sclerosis/Frontotemporal Lobar Degeneration Spectrum Diseases
Authors: Valori Chiara F. , Neumann Manuela
Published: September 2021

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are two incurable neurodegenerative disorders, often considered as the extreme manifestations of a disease spectrum, as they share similar pathomechanisms. In support of this, pathological aggregation of the RNA/DNA binding proteins trans-activation response element DNA-binding protein 43 (TDP-43) or fused in sarcoma (FUS) is the pathological hallmark found in neurons and glial cells of subsets of patients affected by either condition (i.e., ALS/FTLD—TDP-43 or ALS/FTLD—FUS, respectively). Among glia, oligodendrocytes are the most abundant population, designated to ensheath the axons with myelin and to provide them with metabolic and trophic support. In this minireview, we recapitulate the neuropathological evidence for oligodendroglia impairment in ALS/FTLD. We then debate how TDP-43 and FUS target oligodendrocyte transcripts, thereby controlling their homeostatic abilities toward the axons. Finally, we discuss cellular and animal models aimed at investigating the functional consequences of manipulating TDP-43 and FUS in oligodendrocytes in vivo. Taken together, current data provide increasing evidence for an important role of TDP-43 and FUS-mediated oligodendroglia dysfunction in the pathogenesis of ALS/FTLD. Thus, targeting disrupted oligodendroglial functions may represent a new treatment approach for these conditions.
Comparison of Sensory and Motor Innervation Between the Acupoints LR3 and LR8 in the Rat With Regional Anatomy and Neural Tract Tracing
Authors: Xu Dongsheng , Zou Ling , Zhang Wenjie , Liao Jieying , Wang Jia , Cui Jingjing , Su Yuxin , Wang Yuqing , Guo Yating , Shen Yi , Bai Wanzhu
Published: September 2021

Objective

This study aimed to investigate the sensory and motor innervation of “Taichong” (LR3) and “Ququan” (LR8) in the rat and provide an insight into the neural relationship between the different acupoints in the same meridian.

Methods

The LR3 and LR8 were selected as the representative acupoints from the Liver Meridian and examined by using the techniques of regional anatomy and neural tract tracing in this study. For both acupoints, their local nerves were observed with regional anatomy, and their sensory and motor pathways were traced using neural tract tracing with single cholera toxin subunit B (CTB) and dual Alexa Fluor 594/488 conjugates with CTB (AF594/488-CTB).

Results

Using the regional anatomy, the branches of the deep peroneal nerve and saphenous nerve were separately found under the LR3 and LR8. Using single CTB, the sensory neurons, transganglionic axon terminals, and motor neurons associated with both LR3 and LR8 were demonstrated on the dorsal root ganglia (DRG), spinal dorsal horn, Clarke’s nucleus, gracile nucleus, and spinal ventral horn corresponding to their own spinal segments and target regions, respectively. Using dual AF594/488-CTB tracing, it was shown that the sensory and motor neurons associated with LR3 were separated from that of LR8.

Conclusion

This study demonstrates that LR3 and LR8 are innervated by different peripheral nerves, which originated from or terminated in their corresponding spinal segments and target regions independently through the sensory and motor pathways. These results provide an example for understanding the differential innervation between the different acupoints in the same meridian.
Neural Correlates of Trust in Automation: Considerations and Generalizability Between Technology Domains
Authors: Hopko Sarah K. , Mehta Ranjana K.
Published: September 2021

Investigations into physiological or neurological correlates of trust has increased in popularity due to the need for a continuous measure of trust, including for trust-sensitive or adaptive systems, measurements of trustworthiness or pain points of technology, or for human-in-the-loop cyber intrusion detection. Understanding the limitations and generalizability of the physiological responses between technology domains is important as the usefulness and relevance of results is impacted by fundamental characteristics of the technology domains, corresponding use cases, and socially acceptable behaviors of the technologies. While investigations into the neural correlates of trust in automation has grown in popularity, there is limited understanding of the neural correlates of trust, where the vast majority of current investigations are in cyber or decision aid technologies. Thus, the relevance of these correlates as a deployable measure for other domains and the robustness of the measures to varying use cases is unknown. As such, this manuscript discusses the current-state-of-knowledge in trust perceptions, factors that influence trust, and corresponding neural correlates of trust as generalizable between domains.
A Food System Approach for Sustainable Food-Based Dietary Guidelines: An Exploratory Scenario Study on Dutch Animal Food Products
Authors: van Dooren Corné , Man Laila , Seves Marije , Biesbroek Sander
Published: September 2021

This study explores interconnections between food consumption and production of animal (by-)products in different food system scenarios within the scope of Dutch Food-Based Dietary Guidelines (FBDG). For this scenario study, a Microsoft Excel model was created that include seven scenarios with different quantities of eggs, milk, cheese, beef cattle, broilers, and pigs as input. Number of animals, intake of energy, animal protein, saturated fatty acids (SFAs), trans-fatty acids (TFAs), salt, greenhouse gas emissions (GHGEs), and land use (LU) were calculated and compared with current consumption and reference values. Based on the concept of eating the whole animal, every recommended lean, unprocessed portion of beef comes along with a non-recommended portion of beef (two portions for pork, 0.5 portion for broilers). The reference values for SFAs, TFAs, and salt were not exceeded if the intake of meat is limited to 410 g/week. The scenarios with recommended 450 mL semi-skimmed milk and 40 g/day low-fat cheese results in 36 g/day of butter as by-product, exceeding its acceptable intake three times. The near-vegetarian scenario with recommended amounts of eggs, milk, and cheese, includes only a portion of beef/calf per 6 days and a portion of chicken per 9 weeks as by-products. This scenario more than halves the GHGE and LU. Finally, the scenario that included the maximum recommended amounts of animal products is reachable with half the current size of Dutch livestock. This conceptual framework may be useful in the discussion on how future sustainable FBDG can incorporate a more food system-based approach.
A Four−Gene-Based Risk Score With High Prognostic Value in Gastric Cancer
Authors: Zhang Bingdong , Li Yuerui , Yang Liu , Chen Yongbing
Published: September 2021

Background

Gastric adenocarcinoma is an important contributor to cancer mortality and morbidity. This study aimed to explore the prognostic value of mutation patterns in gastric adenocarcinoma.

Materials and Methods

We extracted somatic mutation data for 437 gastric adenocarcinoma samples from The Cancer Genome Atlas (TCGA) Stomach Adenocarcinoma (STAD) cohort. Kaplan–Meier survival in the R package maftools was used to analyze associations between mutations and survival. Multivariate Cox proportional model was used to establish risk formula. A four-gene-based risk score was developed to predict the overall survival of patients with gastric adenocarcinoma. We used the Tianjin cohort dataset with survival information to further evaluate the clinical value of this mutation signature.

Results

Forty-five survival-related mutated genes were identified and verified, most of which were co-occurring in their mutation pattern and co-occurring with MLH3 and polymerase ϵ (POLE) mutations. Gastric adenocarcinoma samples with the 45 mutated genes had a significantly higher mutation count. Four-gene [UTRN, MUC16, coiled-coil domain-containing protein 178 (CCDC178), and HYDIN] mutation status was used to build a prognostic risk score that could be translated into the clinical setting. The association between the four-gene-based signature and overall survival remained statistically significant after controlling for age, sex, TNM stage, and POLE mutation status in the multivariate model [hazard ratio (HR), 1.88; 95% CI, 1.33–2.7; p < 0.001]. The prognostic significance of the four-gene-based risk score identified in TCGA cohort was validated in the Tianjin cohort.

Conclusion

A four-mutated gene risk formula was developed that correlated with the overall survival of patients with gastric adenocarcinoma using a multivariable Cox regression model. In two independent genomic datasets from TCGA and Tianjin cohorts, low risk scores were associated with higher tumor mutation loads and improved outcome in patients with gastric adenocarcinoma. This finding may have implications for prognostic prediction and therapeutic guidance for gastric adenocarcinoma.
Computed Tomography-Based Radiomics Nomogram: Potential to Predict Local Recurrence of Gastric Cancer After Radical Resection
Authors: Huang Liebin , Feng Bao , Li Yueyue , Liu Yu , Chen Yehang , Chen Qinxian , Li Changlin , Huang Wensi , Xue Huimin , Li Xuehua , Zhou Tao , Li Ronggang , Long Wansheng , Feng Shi-Ting
Published: September 2021

Objective

Accurate prediction of postoperative recurrence risk of gastric cancer (GC) is critical for individualized precision therapy. We aimed to investigate whether a computed tomography (CT)-based radiomics nomogram can be used as a tool for predicting the local recurrence (LR) of GC after radical resection.

Materials and Methods

342 patients (194 in the training cohort, 78 in the internal validation cohort, and 70 in the external validation cohort) with pathologically proven GC from two centers were included. Radiomics features were extracted from the preoperative CT imaging. The clinical model, radiomics signature, and radiomics nomogram, which incorporated the radiomics signature and independent clinical risk factors, were developed and verified. Furthermore, the performance of these three models was assessed by using the area under the curve (AUC) of receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA).

Results

The radiomics signature, which was comprised of two selected radiomics features, namely, contrast_GLCM and dissimilarity_GLCM, showed better performance than the clinical model in predicting the LR of GC, with AUC values of 0.83 in the training cohort, 0.84 in the internal validation cohort, and 0.73 in the external cohort, respectively. By integrating the independent clinical risk factors (N stage, bile acid duodenogastric reflux and nodular or irregular outer layer of the gastric wall) into the radiomics signature, the radiomics nomogram achieved the highest accuracy in predicting LR, with AUC values of 0.89, 0.89 and 0.80 in the three cohorts, respectively. DCA in the validation cohort showed that radiomics nomogram added more net benefit than the clinical model within the range of 0.01-0.98.

Conclusion

The CT-based radiomics nomogram has the potential to predict the LR of GC after radical resection.
The 100 Most Cited Papers in Radiotherapy or Chemoradiotherapy for Cervical Cancer: 1990–2020
Authors: Wang Weiping , Liu Xiaoliang , Wang Dunhuang , Ren Kang , Zhou Yuncan , Zhou Ziqi , Qiu Jie , Zhang Fuquan , Hu Ke
Published: September 2021

Objective

This work aims to analyze the 100 most cited papers in radiotherapy or chemoradiotherapy for cervical cancer.

Methods

The 100 most cited papers in radiotherapy or chemoradiotherapy between 1990 and 2020 were identified with Thompson Reuters Web of Science citation indexing on August 24, 2020. The publication years, source titles, countries/regions, total citations, and average citations per year were extracted from the Web of Science. The research type and research domain were classified by the authors.

Results

These 100 papers were cited a total of 28,714 times, and the median number of citations was 169.5 (ranging from 116 to 1,700 times). The most cited paper was “Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer” by Rose et al., with a total citation of 1,700 times. The International Journal of Radiation Oncology Biology Physics (40 papers), Radiotherapy and Oncology (14 papers), and the Journal of Clinical Oncology (12 papers) published the largest number of papers. USA (47 papers), Austria (18 papers), Canada (13 papers), and England (13 papers) contributed the largest number of papers. Image-guided adaptive brachytherapy (IGABT) had the largest number of papers (25 papers). Concurrent chemotherapy was the most cited research domain, with 10,663 total citations and 592.4 citations per paper.

Conclusion

In the present study, we conducted a bibliometric analysis of the 100 most cited papers in radiotherapy or concurrent chemoradiotherapy for cervical cancer in the past 30 years. IGABT and concurrent chemotherapy were the most cited research domains.
Metabolic Switch and Cytotoxic Effect of Metformin on Burkitt Lymphoma
Authors: Bagaloni Irene , Visani Axel , Biagiotti Sara , Ruzzo Annamaria , Navari Mohsen , Etebari Maryam , Mundo Lucia , Granai Massimo , Lazzi Stefano , Isidori Alessandro , Loscocco Federica , Li Jiejin , Leoncini Lorenzo , Visani Giuseppe , Magnani Mauro , Piccaluga Pier Paolo
Published: September 2021

Altered cellular energetic metabolism has recently emerged as important feature of neoplastic cells. Indeed, interfering with cancer cell metabolism might represent a suitable therapeutic strategy. In this study, we aimed to assess glucose metabolism activation in human lymphomas and evaluate how metformin can exert its action on lymphoma cells. We studied a large series of human lymphomas (N = 252) and an in vitro model of Burkitt lymphoma (BL) cells. We combined molecular biology techniques, including global gene expression profiling (GEP) analysis, quantitative PCR (qPCR) and Western blotting, and biochemical assays, aimed to assess pentose phosphate pathway, tricarboxylic acid (TCA) cycle, and aerobic glycolysis rates. We found that glucose metabolism is overall enhanced in most lymphoma subtypes, based on gene expression profiling (GEP), with general shift to aerobic glycolysis. By contrast, normal B cells only showed an overall increase in glucose usage during germinal center transition. Interestingly, not only highly proliferating aggressive lymphomas but also indolent ones, like marginal zone lymphomas, showed the phenomenon. Consistently, genes involved in glycolysis were confirmed to be overexpressed in BL cells by qPCR. Biochemical assays showed that while aerobic glycolysis is increased, TCA cycle is reduced. Finally, we showed that metformin can induce cell death in BL cells by stressing cellular metabolism through the induction of GLUT1, PKM2, and LDHA. In conclusion, we unveiled glucose metabolism abnormalities in human lymphomas and characterized the mechanism of action of metformin in Burkitt lymphoma model.
Analysis of MicroRNA Expression Changes During the Course of Therapy In Rectal Cancer Patients
Authors: Cervena Klara , Novosadova Vendula , Pardini Barbara , Naccarati Alessio , Opattova Alena , Horak Josef , Vodenkova Sona , Buchler Tomas , Skrobanek Pavel , Levy Miroslav , Vodicka Pavel , Vymetalkova Veronika
Published: September 2021

MicroRNAs (miRNAs) regulate gene expression in a tissue-specific manner. However, little is known about the miRNA expression changes induced by the therapy in rectal cancer (RC) patients. We evaluated miRNA expression levels before and after therapy and identified specific miRNA signatures reflecting disease course and treatment responses of RC patients. First, miRNA expression levels were assessed by next-generation sequencing in two plasma samplings (at the time of diagnosis and a year after) from 20 RC patients. MiR-122-5p and miR-142-5p were classified for subsequent validation in plasma and plasma extracellular vesicles (EVs) on an independent group of RC patients (n=107). Due to the intrinsic high differences in miRNA expression levels between samplings, cancer-free individuals (n=51) were included in the validation phase to determine the baseline expression levels of the selected miRNAs. Expression levels of these miRNAs were significantly different between RC patients and controls (for all p <0.001). A year after diagnosis, miRNA expression profiles were significantly modified in patients responding to treatment and were no longer different from those measured in cancer-free individuals. On the other hand, patients not responding to therapy maintained low expression levels in their second sampling (miR-122-5p: plasma: p=0.05, EVs: p=0.007; miR-142-5p: plasma: p=0.008). Besides, overexpression of miR-122-5p and miR-142-5p in RC cell lines inhibited cell growth and survival. This study provides novel evidence that circulating miR-122-5p and miR-142-5p have a high potential for RC screening and early detection as well as for the assessment of patients’ outcomes and the effectiveness of treatment schedule.
EGFR Exon 18 Mutations in Advanced Non-Small Cell Lung Cancer: A Real-World Study on Diverse Treatment Patterns and Clinical Outcomes
Authors: Xu Haiyan , Yang Guangjian , Li Weihua , Li Junling , Hao Xuezhi , Xing Puyuan , Yang Yaning , Wang Yan
Published: September 2021

Background

Approximately 3–5% of patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) harbor exon 18 mutations. The appropriate treatment for such patients has not been clarified. The aim of this study was to investigate the response of patients with NSCLC harboring EGFR exon 18 mutations to different therapeutic options.

Methods

Between May 2014 and September 2020, the clinical outcomes of 82 patients harboring EGFR exon 18 mutations who received first-generation (1G) EGFR-tyrosine kinase inhibitor (TKI), second-generation (2G) EGFR-TKI afatinib, chemotherapy, and 1G TKI in combination with chemotherapy as the initial therapy were retrospectively analyzed.

Results

A total of 82 NSCLC patients harboring EGFR 18 mutations with whose treatment and survival outcomes were available were analyzed. The median age was 59 years, and 47 (57.3%) were female. The most common kind of EGFR exon 18 mutation was G719X (75.6%), followed by E709X (15.9%), E709_T710delinsD (3.6%), and other subtypes (4.9%). There was a significant difference in median progression-free survival (mPFS) by therapeutic strategy (P = 0.017). The mPFS of 1G TKI, 2G TKI afatinib, chemotherapy, and 1G TKI in combination with chemotherapy were 7.7 (95% CI, 4.2–11.2), 11.3 (95% CI, 5.6–17.0), 5.0 (95% CI, 2.3–17.7), and 11.1 (95% CI, 5.9–16.4) months, respectively. No significant difference in PFS was observed between afatinib and 1G TKI in combination with chemotherapy (P = 0.709).

Conclusions

Like afatinib, 1G TKI in combination with chemotherapy might be an effective treatment option for patients harboring EGFR exon 18 mutations.
Brain Microenvironment Heterogeneity: Potential Value for Brain Tumors
Authors: Álvaro-Espinosa Laura , de Pablos-Aragoneses Ana , Valiente Manuel , Priego Neibla
Published: September 2021

Uncovering the complexity of the microenvironment that emerges in brain disorders is key to identify potential vulnerabilities that might help challenging diseases affecting this organ. Recently, genomic and proteomic analyses, especially at the single cell level, have reported previously unrecognized diversity within brain cell types. The complexity of the brain microenvironment increases during disease partly due to the immune infiltration from the periphery that contributes to redefine the brain connectome by establishing a new crosstalk with resident brain cell types. Within the rewired brain ecosystem, glial cell subpopulations are emerging hubs modulating the dialogue between the Immune System and the Central Nervous System with important consequences in the progression of brain tumors and other disorders. Single cell technologies are crucial not only to define and track the origin of disease-associated cell types, but also to identify their molecular similarities and differences that might be linked to specific brain injuries. These altered molecular patterns derived from reprogramming the healthy brain into an injured organ, might provide a new generation of therapeutic targets to challenge highly prevalent and lethal brain disorders that remain incurable with unprecedented specificity and limited toxicities. In this perspective, we present the most relevant clinical and pre-clinical work regarding the characterization of the heterogeneity within different components of the microenvironment in the healthy and injured brain with a special interest on single cell analysis. Finally, we discuss how understanding the diversity of the brain microenvironment could be exploited for translational purposes, particularly in primary and secondary tumors affecting the brain.
Long Noncoding RNA AC007639.1 Promotes the Pathogenesis and Progression of Hepatocellular Carcinoma Through Inhibiting Apoptosis and Stimulating Chemotherapeutic Resistance
Authors: Bai Yun , Ding Meijuan , Lu Dan , Li Yiwen , Yao Shuai , Wang Lei , Li Hui , Cui Guanghua , Li Xue , Sun Xiaoke , Yang Yu
Published: September 2021

Background

Hepatocellular carcinoma (HCC) is known for its poor prognosis. Long noncoding RNAs (lncRNAs) are critical in the pathogenesis of various types of cancers. We tried to explore the role of lncRNA in the development of HCC.

Methods

We identified the role of lncRNA AC007639.1 in the pathogenesis of HCC through bioinformatics and biological experiments in HepG2, Hep3B, and SMMC-7721 cells as well as the nude mice xenograft model.

Results

We found that lncRNA AC007639.1 was overexpressed in hepatocellular carcinoma. Knocking down of lncRNA AC007639.1 by specific siRNAs or shRNAs promoted cancer cell death. The growth of mouse xenograft tumor created using lncRNA AC007639.1 deficient HepG2 cells was significantly slowed down. Furthermore, the knockdown of lncRNA AC007639.1 in HCC cells led to the increased expression of p53 and decreased expression of angiopoietin-like 4.

Conclusion

LncRNA AC007639.1 was involved in the pathogenesis and progression of hepatocellular carcinoma by inhibition of apoptosis and increasing HCC resistance to chemotherapy.
Anticancer Effects of I-BET151, an Inhibitor of Bromodomain and Extra-Terminal Domain Proteins
Authors: Lai Jiacheng , Liu Ziqiang , Zhao Yulei , Ma Chengyuan , Huang Haiyan
Published: September 2021

I-BET151 is an inhibitor of bromodomain and extra-terminal domain (BET) proteins that selectively inhibits BET family members (BRD2, BRD3, BRD4, and BRDT). Over the past ten years, many studies have demonstrated the potential of I-BET151 in cancer treatment. Specifically, I-BET151 causes cell cycle arrest and inhibits tumor cell proliferation in some hematological malignancies and solid tumors, such as breast cancer, glioma, melanoma, neuroblastoma, and ovarian cancer. The anticancer activity of I-BET151 is related to its effects on NF-κB, Notch, and Hedgehog signal transduction pathway, tumor microenvironment (TME) and telomere elongation. Remarkably, the combination of I-BET151 with select anticancer drugs can partially alleviate the occurrence of drug resistance in chemotherapy. Especially, the combination of forskolin, ISX9, CHIR99021, I-BET151 and DAPT allows GBM cells to be reprogrammed into neurons, and this process does not experience an intermediate pluripotent state. The research on the anticancer mechanism of I-BET151 will lead to new treatment strategies for clinical cancer.
Enrichment of Double RUNX1 Mutations in Acute Leukemias of Ambiguous Lineage
Authors: Merati Gabriele , Rossi Marianna , Gallì Anna , Roncoroni Elisa , Zibellini Silvia , Rizzo Ettore , Pietra Daniela , Picone Cristina , Rocca Barbara , Cabrera Claudia Patricia Tobar , Gelli Eleonora , Santacroce Eugenio , Arcaini Luca , Zappasodi Patrizia
Published: September 2021

Acute leukemia of ambiguous lineage (ALAL) is a rare type of leukemia and represents an unmet clinical need. In fact, due to heterogeneity, substantial rarity and absence of clinical trials, there are no therapeutic guidelines available. We investigated the genetic basis of 10 cases of ALAL diagnosed at our centre from 2008 and 2020, through a targeted myeloid and lymphoid sequencing approach. We show that this rare group of acute leukemias is enriched in myeloid-gene mutations. In particular we found that RUNX1 mutations, which have been found double mutated in 40% of patients and tend to involve both alleles, are associated with an undifferentiated phenotype and with lineage ambiguity. Furthermore, because this feature is typical of acute myeloid leukemia with minimal differentiation, we believe that our data strengthen the idea that acute leukemia with ambiguous lineage, especially those with an undifferentiated phenotype, might be genetically more closer to acute myeloid leukemia rather than acute lymphoblastic leukemia. These data enrich the knowledge on the genetic basis of ALAL and could have clinical implications as an acute myeloid leukemia (AML) – oriented chemotherapeutic approach might be more appropriate.
Efficacy of Osimertinib in NSCLC Harboring Uncommon EGFR L861Q and Concurrent Mutations: Case Report and Literature Review
Authors: Lin Ruiting , Chen Ruilian , Chen Zhiqiang , Hu Leihao , Guo Wei , Zhang Zexin , Lin Lizhu , Chen Hanrui
Published: September 2021

The efficacy of first-and second-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in NSCLC patients with the EGFR L861Q mutation has been studied previously. However, there is little evidence on the efficacy of osimertinib in NSCLC patients with uncommon mutations. Here, we report the case of a 68-year-old man with advanced NSCLC with concurrent EGFR L861Q mutation as well as TP53 and RB1 mutations. The patient was treated with osimertinib as first-line therapy and achieved a remarkable progression-free survival of 15 months. His symptoms were significantly alleviated and the dose was well tolerated. The findings of the present study indicate that osimertinib might be a good treatment option for NSCLC patients with the L861Q mutation.
A Pilot Study of Low-Dose Craniospinal Irradiation in Patients With Newly Diagnosed Average-Risk Medulloblastoma
Authors: Minturn Jane E. , Mochizuki Aaron Y. , Partap Sonia , Belasco Jean B. , Lange Beverly J. , Li Yimei , Phillips Peter C. , Gibbs Iris C. , Fisher Paul G. , Fisher Michael J. , Janss Anna J.
Published: September 2021

Purpose

Medulloblastoma is one of the most common malignant brain tumors in children. To date, the treatment of average-risk (non-metastatic, completely resected) medulloblastoma includes craniospinal radiation therapy and adjuvant chemotherapy. Modern treatment modalities and now risk stratification of subgroups have extended the survival of these patients, exposing the long-term morbidities associated with radiation therapy. Prior to advances in molecular subgrouping, we sought to reduce the late effects of radiation in patients with average-risk medulloblastoma.

Methods

We performed a single-arm, multi-institution study, reducing the dose of craniospinal irradiation by 25% to 18 Gray (Gy) with the goal of maintaining the therapeutic efficacy as described in CCG 9892 with maintenance chemotherapy.

Results

Twenty-eight (28) patients aged 3-30 years were enrolled across three institutions between April 2001 and December 2010. Median age at enrollment was 9 years with a median follow-up time of 11.7 years. The 3-year relapse-free (RFS) and overall survival (OS) were 79% (95% confidence interval [CI] 58% to 90%) and 93% (95% CI 74% to 98%), respectively. The 5-year RFS and OS were 71% (95% CI 50% to 85%) and 86% (95% CI 66% to 94%), respectively. Toxicities were similar to those seen in other studies; there were no grade 5 toxicities.

Conclusions

Given the known neurocognitive adverse effects associated with cranial radiation therapy, studies to evaluate the feasibility of dose reduction are needed. In this study, we demonstrate that select patients with average-risk medulloblastoma may benefit from a reduced craniospinal radiation dose of 18 Gy without impacting relapse-free or overall survival.

Clinical Trial Registration

ClinicalTrials.gov identifier: NCT00031590