bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of nanomaterials against SARS-CoV-2: An emphasis on their usefulness against emerging variants of concern
Authors: Iqbal Reema , Khan Sadia , Ali Haroon Muhammad , Khan Maham , Wahab Shahid , Khan Tariq 
Published: December 2022

Researchers are now looking to nanomaterials to fight serious infectious diseases that cause outbreaks and even pandemics. SARS-CoV-2 brought chaos to almost every walk of life in the past 2 years and has challenged every available treatment method. Although vaccines were developed in no time against it, the most pressing issue was the emergence of variants of concern arising because of the rapidly evolving viral strains. The higher pathogenicity and, in turn, the higher mortality rate of infections caused by these variants renders the existing vaccines less effective and the effort to produce further vaccines a costly endeavor. While several techniques, such as immunotherapy and repurposed pharmaceutical research, are being studied to minimize viral infection, the fundamentals of nanotechnology must also be considered to enhance the anti-SARS-CoV-2 efforts. For instance, silver nanoparticles (AgNPs) have been applied against SARS-CoV-2 effectively. Similarly, nanomaterials have been tested in masks, gloves, and disinfectants to aid in controlling SARS-CoV-2. Nanotechnology has also contributed to diagnoses such as rapid and accurate detection and treatment such as the delivery of mRNA vaccines and other antiviral agents into the body. The development of polymeric nanoparticles has been dubbed a strategy of choice over traditional drugs because of their tunable release kinetics, specificity, and multimodal drug composition. Our article explores the potential of nanomaterials in managing the variants of concern. This will be achieved by highlighting the inherent ability of nanomaterials to act against the virus on fronts such as inhibition of SARS-CoV-2 entry, inhibition of RNA replication in SARS-CoV-2, and finally, inhibition of their release. In this review, a detailed discussion on the potential of nanomaterials in these areas will be tallied with their potential against the current and emerging future variants of concern.
Case Report: A case of PLA2G6 gene-related early-onset Parkinson's disease and review of literature
Authors: Gao Lili , Shi Chunlan , Lin Qing , Wu Yujing , Hu Liqi , Wang Mingwang , Guan Jianhua , Lin Sheng , Liao Yuansheng , Wu Chenghan 
Published: December 2022

BackgroundEarly onset Parkinson's disease (EOPD) is a neurodegenerative disease associated with the action ofto genetic factors. A mutated phospholipase A2 type VI gene (PLA2G6) is considered to be one of pathogenic genes involved in EOPD development. Although EOPD caused by a mutated PLA2G6 has been recorded in major databases, not all mutant genotypes have been reported. Here, we report a case of PLA2G6-related EOPD caused by a novel compound heterozygous mutation.Case presentationThe case was an of 26-year-old young male with a 2-year course of disease. The onset of the disease was insidious and developed gradually. The patient presented with unsteady walking, bradykinesia, unresponsiveness, and decreased facial expression. Auxiliary examination showed a compound heterozygous mutation of the PLA2G6gene with c.991G &gt; T and c.1427 + 1G &gt; A. Mild atrophy of the cerebrum and cerebellum was detected on brain MRI. The patient was diagnosed with EOPD. We administered treatment with Madopar, which was effective. After a two-year disease course, we observed progression to stage 5 according to the Hoehn-Yahr Scale (without medicine in the off-stage). An MDS-UPDRS III score of 62 was obtained, with characteristics of severe disease and rapid progress. The diagnosis was an EOPD phenotype caused by a combination of mutations at the c.991G &gt; T and c.1427 + 1G &gt; A sites of the PLA2G6gene.ConclusionAfter active treatment, the disease was set under control, with no significant progression during the three-month follow-up period. Dyskinesia did not recur after reducing the Madopar dose. The freezing sign was slightly decreased and the wearing-off was delayed to 2 h.
Anosmia in COVID-19 could be associated with long-term deficits in the consolidation of procedural and verbal declarative memories
Authors: Llana Tania , Mendez Marta , Zorzo Candela , Fidalgo Camino , Juan M.-Carmen , Mendez-Lopez Magdalena 
Published: December 2022

Background and purposeLong-COVID describes the long-term effects of the coronavirus disease 2019 (COVID-19). In long-COVID patients, neuropsychological alterations are frequently reported symptoms. Research points to medial temporal lobe dysfunction and its association with anosmia in long-COVID patients. This study aims to investigate the acquisition and consolidation of declarative and procedural memory in long-COVID patients and to explore whether anosmia is related to these dissociated memory functions.MethodsForty-two long-COVID participants and 30 controls (C) were recruited. The sample of long-COVID patients was divided into two groups based on the presence or absence of anosmia, group A and group NA, respectively. Objective performance in verbal declarative memory (Paired-Associate Learning, PAL), procedural memory (Mirror Tracing Test, MTT), general cognitive function (Montreal Cognitive Assessment scale), psychomotor speed, and incidental learning (Digit Symbol Substitution Test) were assessed and compared among the A, NA, and C groups. Long-term retention of PAL and MTT were assessed 24 h after acquisition.ResultsLower scores in general cognition, psychomotor speed, and sustained attention were found in A and NA compared with C. However, incidental learning, both cue-guided and free-recalled, was diminished in group A compared with C, with no differences with group NA. General cognition and incidental learning were related to declarative memory function exclusively in long-COVID groups. Long-COVID groups presented lower long-term retention of verbal declarative memory than controls in recall tests but no differences in recognition tests. No group differences were found in the acquisition of procedural memory. However, long-term retention of this memory was worse in group A as compared to the NA and C groups, respectively, when errors and time of execution were considered.ConclusionFindings support that consolidation of both procedural and declarative memories is more affected than the acquisition of these memories in long-COVID patients, who are also more vulnerable to deficits in delayed recall than in recognition of declarative memories. Deficits in the consolidation of procedural memory and immediate recall of declarative information are especially relevant in long-COVID participants with anosmia. This indicates that anosmia in COVID-19 could be associated with a long-term dysfunction of the limbic system.
Tractography-based navigated TMS language mapping protocol
Authors: Reisch Klara , Böttcher Franziska , Tuncer Mehmet S. , Schneider Heike , Vajkoczy Peter , Picht Thomas , Fekonja Lucius S. 
Published: December 2022

IntroductionThis study explores the feasibility of implementing a tractography-based navigated transcranial magnetic stimulation (nTMS) language mapping protocol targeting cortical terminations of the arcuate fasciculus (AF). We compared the results and distribution of errors from the new protocol to an established perisylvian nTMS protocol that stimulated without any specific targeting over the entire perisylvian cortex.MethodsSixty right-handed patients with language-eloquent brain tumors were examined in this study with one half of the cohort receiving the tractographybased protocol and the other half receiving the perisylvian protocol. Probabilistic tractography using MRtrix3 was performed for patients in the tractography-based group to identify the AF’s cortical endpoints. nTMS mappings were performed and resulting language errors were classified into five psycholinguistic groups.ResultsTractography and nTMS were successfully performed in all patients. The tractogram-based group showed a significantly higher median overall ER than the perisylvian group (3.8% vs. 2.9% p &lt;.05). The median ER without hesitation errors in the tractogram-based group was also significantly higher than the perisylvian group (2.0% vs. 1.4%, p &lt;.05). The ERs by error type showed no significant differences between protocols except in the no response ER, with a higher median ER in the tractogram-based group (0.4% vs. 0%, p &lt;.05). Analysis of ERs based on the Corina cortical parcellation system showed especially high nTMS ERs over the posterior middle temporal gyrus (pMTG) in the perisylvian protocol and high ERs over the middle and ventral postcentral gyrus (vPoG), the opercular inferior frontal gyrus (opIFG) and the ventral precentral gyrus (vPrG) in the tractography-based protocol.DiscussionBy considering the white matter anatomy and performing nTMS on the cortical endpoints of the AF, the efficacy of nTMS in disrupting patients’ object naming abilities was increased. The newly introduced method showed proof of concept and resulted in AF-specific ERs and noninvasive cortical language maps, which could be applied to additional fiber bundles related to the language network in future nTMS studies.
Impact of tumour characteristics and cancer treatment on cerebrovascular mortality after glioma diagnosis: Evidence from a population-based cancer registry
Authors: Jin Kai , Brennan Paul M. , Poon Michael T. C. , Figueroa Jonnie D. , Sudlow Cathie L. M. 
Published: December 2022

ObjectiveWe aimed to examine brain tumour grade, a marker of biological aggressiveness, tumour size and cancer treatment are associated with cerebrovascular mortality among patients with malignant glioma, the most common and aggressive type of brain tumour.MethodsWe conducted a retrospective, observational cohort study using the US National Cancer Institute’s state and regional population-based cancer registries. We identified adult patients with glioma in 2000 to 2018 (N=72,916). The primary outcome was death from cerebrovascular disease. Cox regression modelling was used to estimate the associations with cerebrovascular mortality of tumour grade, tumour size and treatment (surgery, radiotherapy, chemotherapy), calculating hazard ratios (HR) adjusted for these factors as well as for age, sex, race, marital status and calendar year.ResultsHigher grade (Grade IV vs Grade II: HR=2.47, 95% CI=1.69-3.61, p&lt;0.001) and larger brain tumours (size 3 to &lt;6 cm: HR=1.40, 95% CI=1.03 -1.89, p&lt;0.05; size ≥ 6 cm: HR=1.47, 95% CI=1.02-2.13, p&lt;0.05 compared to size &lt; 3cm) were associated with increased cerebrovascular mortality. Cancer treatment was associated with decreased risk (surgery: HR= 0.60, p&lt;0.001; chemotherapy: HR=0.42, p&lt;0.001; radiation: HR= 0.69, p&lt;0.05). However, among patents surviving five years or more from cancer diagnosis radiotherapy was associated with higher risk of cerebrovascular mortality (HR 2.73, 95% CI 1.49-4.99, p&lt;0.01).ConclusionMore aggressive tumour characteristics are associated with increased cerebrovascular mortality. Radiotherapy increased risk of cerebrovascular mortality five-year after cancer diagnosis. Further research is needed to better understand the long-term cardiovascular consequences of radiation therapy, and whether the consequent risk can be mitigated.
Efficacy and safety of anlotinib-based treatment in metastatic breast cancer patients
Authors: Qian Yu , Lou Kexin , Zhou Hao , Zhang Lili , Yuan Yuan 
Published: December 2022

ObjectiveTo evaluate the efficacy and safety of anlotinib-based treatment in metastatic breast cancer (MBC) patients with failure of standard treatment.MethodsWe collected the medical data of 56 female patients with the diagnosis of MBC and had failed the standard treatment before. These patients received at least two cycles of anlotinib-based treatment as the second-line or beyond treatment between October 2019 and April 2022 in Jiangsu Cancer Hospital. The primary endpoint of our study was progression-free survival (PFS), and it was estimated with Kaplan-Meier. The second end points were disease control rate (DCR), objective response rate (ORR), and side effects.ResultsThe median PFS time of a total of 56 patients was 5.7 months (95% CI, 3.17-8.23 months). The ORR and DCR was 28.6% and 71.4%, respectively. In second-line, third-line, and beyond treatment, the median PFS was 11.7 months, 8.7 months, and 4.7 months, respectively. In different subtype of breast cancer, the median PFS was 5.6 months, 5.7months, and 6.4 months in human epidermal growth factor receptor 2 positive (HER2+), hormone receptor positive and HER2 negative (HR+/HER2-), and triple negative breast cancer (TNBC) patients, respectively. Most adverse effects were clinically manageable, and the most common events were platelet count decrease (35.7%), hand-foot syndrome (19.6%), diarrhea (19.6%), and fatigue (17.9%). The most common grade 3 and 4 adverse events were platelet count decrease (10.7%), diarrhea (7.1%), and oral mucositis (5.4%).ConclusionAnlotinib-based treatment showed good efficacy and manageable toxicity in multi-line treatment of MBC patients who failed the standard treatment.
Psychometric properties of the EQ-5D-5L compared with EQ-5D-3L in cancer patients in Iran
Authors: Moradi Nasrin , Poder Thomas G. , Safari Hossein , Mojahedian Mohammad M. , Ameri Hosein 
Published: December 2022

Background and ObjectivePsychometric evidence to support the validity and reliability of the EuroQol-5 Dimensions (EQ-5D) in cancer patients is limited. This study aimed to test the validity and reliability of the EQ-5D-5L (5L) in comparison with EQ-5D-3L (3L) in cancer patients.MethodsData of 650 cancer patients were collected through consecutive sampling method from three largest governmental cancer centers in Iran between June 2021 and January 2022. The data were gathered using the 3L, 5L, and the European Organization for Research and Treatment of Cancer quality of life questionnaire (QLQ-C30) instruments. The 3L and 5L were compared in terms of ceiling effect, discriminatory power, convergent and known-groups validity, relative efficiency, inconsistency, agreement, and reliability.ResultsCompared with the 3L, ceiling effect decreased by 27.86%. Absolute and relative informativity of discriminatory power improved by 45.93% and 22.92% in the 5L, respectively. All convergent validity coefficients with 5L were stronger than with 3L. Both 3L and 5L demonstrated good known-groups validity, and the relative efficiency was higher for 5L in 4 out of 7 patients’ characteristics. The two instruments showed low overall inconsistency (1.45%) and 92.57% of the differences of observations between the 3L and 5L were within the 95% limit of agreement. The interclass correlation coefficient (ICC) for 3L and 5L indexes were 0.88 and 0.85, respectively, and kappa coefficients in the 3L dimensions (range=0.66-0.92) were higher than the 5L(range=0.64-0.79).ConclusionsThe 5L demonstrated to be better than the 3L in terms of ceiling effect, inconsistency, discriminatory power, convergent validity, relative efficiency.
Development and validation of a machine learning model for survival risk stratification after esophageal cancer surgery
Authors: Xu Jinye , Zhou Jianghui , Hu Junxi , Ren Qinglin , Wang Xiaolin , Shu Yusheng 
Published: December 2022

BackgroundPrediction of prognosis for patients with esophageal cancer(EC) is beneficial for their postoperative clinical decision-making. This study’s goal was to create a dependable machine learning (ML) model for predicting the prognosis of patients with EC after surgery.MethodsThe files of patients with esophageal squamous cell carcinoma (ESCC) of the thoracic segment from China who received radical surgery for EC were analyzed. The data were separated into training and test sets, and prognostic risk variables were identified in the training set using univariate and multifactor COX regression. Based on the screened features, training and validation of five ML models were carried out through nested cross-validation (nCV). The performance of each model was evaluated using Area under the curve (AUC), accuracy(ACC), and F1-Score, and the optimum model was chosen as the final model for risk stratification and survival analysis in order to build a valid model for predicting the prognosis of patients with EC after surgery.ResultsThis study enrolled 810 patients with thoracic ESCC. 6 variables were ultimately included for modeling. Five ML models were trained and validated. The XGBoost model was selected as the optimum for final modeling. The XGBoost model was trained, optimized, and tested (AUC = 0.855; 95% CI, 0.808-0.902). Patients were separated into three risk groups. Statistically significant differences (p &lt; 0.001) were found among all three groups for both the training and test sets.ConclusionsA ML model that was highly practical and reliable for predicting the prognosis of patients with EC after surgery was established, and an application to facilitate clinical utility was developed.
Exosomes from cisplatin-induced dormant cancer cells facilitate the formation of premetastatic niche in bone marrow through activating glycolysis of BMSCs
Authors: Xu Jiaqi , Feng Xiang , Yin Na , Wang Lujuan , Xie Yaohuan , Gao Yawen , Xiang Juanjuan 
Published: December 2022

IntroductionLung cancer is the leading cause of cancer-related deaths worldwide. Chemotherapy kills most cancer cells; however, residual cells enter a dormant state. The dormant cancer cells can be reactivated under specific circumstances. The “premetastatic niche” that is suitable for colonization of cancer cells is formed before the arrival of cancer cells. Tumor-derived exosomes are the main mediators of tumorigenesis. We are aiming to elucidate the roles of exosomes from cisplatin-induced dormant lung cancer cells in the formation of premetastatic niches in bone marrow.MethodsWe performed differential proteomics in dormant A549 cell- and A549 cell-derived exosomes. Non-targeted metabolomics and RNA sequencing were performed to explore the molecular and metabolic reprogramming of bone marrow stromal cells (BMSCs). The growth and metastasis of A549 cells in vivo were monitored by bioluminescence imaging.ResultsWe found that Insulin-like growth factor 2 (IGF-2) and Insulin-like growth factor binding protein 2 (IGFBP2) were upregulated in dormant A549 cell-derived exosomes. BMSCs that took up exosomes from dormant A549 cells showed enhanced glycolysis and promoted the growth and metastasis of A549 cells possibly through Insulin-like growth factor 1 receptor (IGF-1R)-induced metabolic reprogramming. Inhibition of the production of lactate and IGF-1R signaling can suppress the growth and metastasis of A549 cells from bone marrow.DiscussionOverall, we demonstrated that BMSCs formed a premetastatic niche upon taking up exosomes from cisplatin-induced dormant lung cancer cells. BMSCs promoted lung cancer cell growth and metastasis through the reverse Warburg effect.
Synergic effects of some plant-derived essential oils and Iranian isolates of entomopathogenic fungus Metarhizium anisopliae Sorokin to control Acanthoscelides obtectus (Say) (Coleoptera: Chrysomelidae)
Authors: Lak Fatemeh , Zandi-Sohani Nooshin , Ghodoum Parizipour Mohammad Hamed , Ebadollahi Asgar 
Published: December 2022

IntroductionThe bean weevil, Acanthoscelides obtectus, is one of the most important pests of the common bean, Phaseolus vulgaris. The pest attacks P. vulgaris seeds while they are still in the field. However, the damage continues during storage, where it causes the most significant losses.MethodsThe present study was conducted to evaluate the insecticidal activity, and synergic effects of three essential oils (EOs) extracted from fennel (Foeniculum vulgare), tarragon (Artemisia dracunculus), and lavender (Lavandula angustifolia), and three isolates from an entomopathogenic fungus (EPF), Metarhizium anisopliae, including IRAN2273C, IRAN2252C, and IRAN1018C against the adults of A. obtectus. The effects of EOs were also evaluated on mycelial growth and conidiation of the fungal isolates.Results and DiscussionThe results showed that all the EOs and the EPF exhibited insecticidal activity against A. obtectus. According to calculated LC50, L. angustifolia (1.2526 µl/l) and F. vulgare (0.9247 µl/l) EOs caused significantly higher mortality than A. dracunculus (3.1980 µl/l) against A. obtectus. The results of the pathogenicity of M. anisopliae isolates revealed that all isolates had insecticidal activity against A. obtectus. The cumulative mortality of insects varied from 59.12% in IRAN1018C to 80.86% in IRAN2273C. According to the compatibility test results, all EOs were compatible with fungal isolates except for A. dracunculus, which was toxic to the IRAN2252C isolate and showed incompatibility. The mortality of A. obtectus adults differed significantly among combined treatments of EOs and M. anisopliae isolates. According to the calculated synergic ratio, combinations of essential oils and fungal isolates had additive or synergistic effects on the mortality of A. obtectus. Based on the present findings, A. obtectus adults were susceptible to fennel, and lavender EOs, and their mortality was amplified when the EOs were combined with M. anisopliae isolates. These results can be helpful for the integrated management of A. obtectus during storage.
The root transcriptome dynamics reveals new valuable insights in the salt-resilience mechanism of wild grapevine (Vitis vinifera subsp. sylvestris)
Authors: Daldoul Samia , Hanzouli Faouzia , Hamdi Zohra , Chenenaoui Synda , Wetzel Thierry , Nick Peter , Mliki Ahmed , Gargouri Mahmoud 
Published: December 2022

IntroductionMost of elite cultivated grapevine varieties (Vitis viniferaL.), conventionally grafted on rootstocks, are becoming more and more affected by climate changes, such as increase of salinity. Therefore, we revisited the valuable genetic resources of wild grapevines (V. sylvestris) to elaborate strategies for a sustainable viticulture.MethodsHere, we compared physiological and biochemical responses of two salt-tolerant species: a wild grapevine genotype “Tebaba” from our previous studies and the conventional rootstock “1103 Paulsen”. Interestingly, our physio-biochemical results showed that under 150mM NaCl, “Tebaba” maintains higher leaf osmotic potential, lower Na+/K+ ratio and a significant peaked increase of polyphenol content at the first 8h of salinity stress. This behavior allowed to hypothesis a drastic repatterning of metabolism in “Tebaba’s” roots following a biphasic response. In order to deepen our understanding on the “Tebaba” salt tolerance mechanism, we investigated a time-dependent transcriptomic analysis covering three sampling times, 8h, 24h and 48h.ResultsThe dynamic analysis indicated that “Tebaba” root cells detect and respond on a large scale within 8h to an accumulation of ROS by enhancing a translational reprogramming process and inducing the transcripts of glycolytic metabolism and flavonoids biosynthesis as a predominate non-enzymatic scavenging process. Afterwards, there is a transition to a largely gluconeogenic stage followed by a combined response mechanism based on cell wall remodeling and lignin biosynthesis with an efficient osmoregulation between 24 and 48 h.DiscussionThis investigation explored for the first time in depth the established cross-talk between the physiological, biochemical and transcriptional regulators contributing to propose a hypothetical model of the dynamic salt mechanism tolerance of wild grapevines. In summary, these findings allowed further understanding of the genetic regulation mechanism of salt-tolerance in V. sylvestris and identified specific candidate genes valuable for appropriate breeding strategies.