bluuebunny/crossref_metadata_2025 huggingface dataset:
Behavioral and Neuroanatomical Consequences of Cell-Type Specific Loss of Dopamine D2 Receptors in the Mouse Cerebral Cortex
Authors: Lee Gloria S. , Graham Devon L. , Noble Brenda L. , Trammell Taylor S. , McCarthy Deirdre M. , Anderson Lisa R. , Rubinstein Marcelo , Bhide Pradeep G. , Stanwood Gregg D.
Published: January 2022

Developmental dysregulation of dopamine D2 receptors (D2Rs) alters neuronal migration, differentiation, and behavior and contributes to the psychopathology of neurological and psychiatric disorders. The current study is aimed at identifying how cell-specific loss of D2Rs in the cerebral cortex may impact neurobehavioral and cellular development, in order to better understand the roles of this receptor in cortical circuit formation and brain disorders. We deleted D2R from developing cortical GABAergic interneurons (Nkx2.1-Cre) or from developing telencephalic glutamatergic neurons (Emx1-Cre). Conditional knockouts (cKO) from both lines, Drd2fl/fl, Nkx2.1-Cre+ (referred to as GABA-D2R-cKO mice) or Drd2fl/fl, Emx1-Cre+ (referred to as Glu-D2R-cKO mice), exhibited no differences in simple tests of anxiety-related or depression-related behaviors, or spatial or nonspatial working memory. Both GABA-D2R-cKO and Glu-D2R-cKO mice also had normal basal locomotor activity, but GABA-D2R-cKO mice expressed blunted locomotor responses to the psychotomimetic drug MK-801. GABA-D2R-cKO mice exhibited improved motor coordination on a rotarod whereas Glu-D2R-cKO mice were normal. GABA-D2R-cKO mice also exhibited spatial learning deficits without changes in reversal learning on a Barnes maze. At the cellular level, we observed an increase in PV+ cells in the frontal cortex of GABA-D2R-cKO mice and no noticeable changes in Glu-D2R-cKO mice. These data point toward unique and distinct roles for D2Rs within excitatory and inhibitory neurons in the regulation of behavior and interneuron development, and suggest that location-biased D2R pharmacology may be clinically advantageous to achieve higher efficacy and help avoid unwanted effects.
Visual Saliency via Multiscale Analysis in Frequency Domain and Its Applications to Ship Detection in Optical Satellite Images
Authors: Yu Ying , Qian Jun , Wu Qinglong
Published: January 2022

This article proposes a bottom-up visual saliency model that uses the wavelet transform to conduct multiscale analysis and computation in the frequency domain. First, we compute the multiscale magnitude spectra by performing a wavelet transform to decompose the magnitude spectrum of the discrete cosine coefficients of an input image. Next, we obtain multiple saliency maps of different spatial scales through an inverse transformation from the frequency domain to the spatial domain, which utilizes the discrete cosine magnitude spectra after multiscale wavelet decomposition. Then, we employ an evaluation function to automatically select the two best multiscale saliency maps. A final saliency map is generated via an adaptive integration of the two selected multiscale saliency maps. The proposed model is fast, efficient, and can simultaneously detect salient regions or objects of different sizes. It outperforms state-of-the-art bottom-up saliency approaches in the experiments of psychophysical consistency, eye fixation prediction, and saliency detection for natural images. In addition, the proposed model is applied to automatic ship detection in optical satellite images. Ship detection tests on satellite data of visual optical spectrum not only demonstrate our saliency model's effectiveness in detecting small and large salient targets but also verify its robustness against various sea background disturbances.
Loss of α-9 Nicotinic Acetylcholine Receptor Subunit Predominantly Results in Impaired Postural Stability Rather Than Gaze Stability
Authors: Chang Hui Ho Vanessa , Morley Barbara J. , Cullen Kathleen E.
Published: January 2022

The functional role of the mammalian efferent vestibular system (EVS) is not fully understood. One proposal is that the mammalian EVS plays a role in the long-term calibration of central vestibular pathways, for example during development. Here to test this possibility, we studied vestibular function in mice lacking a functional α9 subunit of the nicotinic acetylcholine receptor (nAChR) gene family, which mediates efferent activation of the vestibular periphery. We focused on an α9 (−/−) model with a deletion in exons 1 and 2. First, we quantified gaze stability by testing vestibulo-ocular reflex (VOR, 0.2–3 Hz) responses of both α9 (−/−) mouse models in dark and light conditions. VOR gains and phases were comparable for both α9 (−/−) mutants and wild-type controls. Second, we confirmed the lack of an effect from the α9 (−/−) mutation on central visuo-motor pathways/eye movement pathways via analyses of the optokinetic reflex (OKR) and quick phases of the VOR. We found no differences between α9 (−/−) mutants and wild-type controls. Third and finally, we investigated postural abilities during instrumented rotarod and balance beam tasks. Head movements were quantified using a 6D microelectromechanical systems (MEMS) module fixed to the mouse’s head. Compared to wild-type controls, we found head movements were strikingly altered in α9 (−/−) mice, most notably in the pitch axis. We confirmed these later results in another α9 (−/−) model, with a deletion in the exon 4 region. Overall, we conclude that the absence of the α9 subunit of nAChRs predominately results in an impairment of posture rather than gaze.
Two Functional Classes of Rod Bipolar Cells in the Healthy and Degenerated Optogenetically Treated Murine Retina
Authors: Schilardi Giulia , Kleinlogel Sonja
Published: January 2022

Bipolar cells have become successful targets for optogenetic gene therapies that restore vision after photoreceptor degeneration. However, degeneration was shown to cause changes in neuronal connectivity and protein expression, which may impact the quality of synthetically restored signaling. Further, the expression of an optogenetic protein may alter passive membrane properties of bipolar cells affecting signal propagation. We here investigated the passive membrane properties of rod bipolar cells in three different systems, the healthy retina, the degenerated retina, and the degenerated retina expressing the optogenetic actuator Opto-mGluR6. We found that, based on the shape of their current-voltage relations, rod bipolar cells in healthy and degenerated retinas form two clear functional groups (type 1 and type 2 cells). Depolarizing the membrane potential changed recorded current-voltage curves from type 1 to type 2, confirming a single cell identity with two functional states. Expression of Opto-mGluR6 did not alter the passive properties of the rod bipolar cell. With progressing degeneration, dominant outward rectifying currents recorded in type 2 rod bipolar cells decreased significantly. We demonstrate that this is caused by a downregulation of BK channel expression in the degenerated retina. Since this BK conductance will normally recover the membrane potential after RBCs are excited by open TRPM1 channels, a loss in BK will decrease high-pass filtering at the rod bipolar cell level. A better understanding of the changes of bipolar cell physiology during retinal degeneration may pave the way to optimize future treatment strategies of blindness.
Apathy, Executive Function, and Emotion Recognition Are the Main Drivers of Functional Impairment in Behavioral Variant of Frontotemporal Dementia
Authors: Musa Salech Gada , Lillo Patricia , van der Hiele Karin , Méndez-Orellana Carolina , Ibáñez Agustín , Slachevsky Andrea
Published: January 2022

Background: The cognitive and neuropsychiatric deficits present in patients with behavioral variant frontotemporal dementia (bvFTD) are associated with loss of functionality in the activities of daily living (ADLs). The main purpose of this study was to examine and explore the association between the cognitive and neuropsychiatric features that might prompt functional impairment of basic, instrumental, and advanced ADL domains in patients with bvFTD.

Methods: A retrospective cross-sectional study was conducted with 27 patients with bvFTD in its early stage (<2 years of evolution) and 32 healthy control subjects. A neuropsychological assessment was carried out wherein measures of cognitive function and neuropsychiatric symptoms were obtained. The informant-report Technology–Activities of Daily Living Questionnaire was used to assess the percentage of functional impairment in the different ADL domains. To identify the best determinants, three separate multiple regression analyses were performed, considering each functional impairment as the dependent variable and executive function, emotion recognition, disinhibition, and apathy as independent variables.

Results: For the basic ADLs, a model that explains 28.2% of the variability was found, in which the presence of apathy (β = 0.33, p = 0.02) and disinhibition (β = 0.29, p = 0.04) were significant factors. Concerning instrumental ADLs, the model produced accounted for 63.7% of the functional variability, with the presence of apathy (β = 0.71, p < 0.001), deficits in executive function (β = −0.36, p = 0.002), and lack of emotion recognition (β = 0.28, p = 0.017) as the main contributors. Finally, in terms of advanced ADLs, the model found explained 52.6% of the variance, wherein only the presence of apathy acted as a significant factor (β = 0.59, p < 0.001).

Conclusions: The results of this study show the prominent and transverse effect of apathy in the loss of functionality throughout all the ADL domains. Apart from that, this is the first study that shows that the factors associated with loss of functionality differ according to the functional domain in patients with bvFTD in its early stage. Finally, no other study has analyzed the impact of the lack of emotion recognition in the functionality of ADLs. These results could guide the planning of tailored interventions that might enhance everyday activities and the improvement of quality of life.
More Than Spikes: On the Added Value of Non-linear Intracranial EEG Analysis for Surgery Planning in Temporal Lobe Epilepsy
Authors: Müller Michael , Dekkers Martijn , Wiest Roland , Schindler Kaspar , Rummel Christian
Published: January 2022

Epilepsy surgery can be a very effective therapy in medication refractory patients. During patient evaluation intracranial EEG is analyzed by clinical experts to identify the brain tissue generating epileptiform events. Quantitative EEG analysis increasingly complements this approach in research settings, but not yet in clinical routine. We investigate the correspondence between epileptiform events and a specific quantitative EEG marker. We analyzed 99 preictal epochs of multichannel intracranial EEG of 40 patients with mixed etiologies. Time and channel of occurrence of epileptiform events (spikes, slow waves, sharp waves, fast oscillations) were annotated by a human expert and non-linear excess interrelations were calculated as a quantitative EEG marker. We assessed whether the visually identified preictal events predicted channels that belonged to the seizure onset zone, that were later resected or that showed strong non-linear interrelations. We also investigated whether the seizure onset zone or the resection were predicted by channels with strong non-linear interrelations. In patients with temporal lobe epilepsy (32 of 40), epileptic spikes and the seizure onset zone predicted the resected brain tissue much better in patients with favorable seizure control after surgery than in unfavorable outcomes. Beyond that, our analysis did not reveal any significant associations with epileptiform EEG events. Specifically, none of the epileptiform event types did predict non-linear interrelations. In contrast, channels with strong non-linear excess EEG interrelations predicted the resected channels better in patients with temporal lobe epilepsy and favorable outcome. Also in the small number of patients with seizure onset in the frontal and parietal lobes, no association between epileptiform events and channels with strong non-linear excess EEG interrelations was detectable. In contrast to patients with temporal seizure onset, EEG channels with strong non-linear excess interrelations did neither predict the seizure onset zone nor the resection of these patients or allow separation between patients with favorable and unfavorable seizure control. Our study indicates that non-linear excess EEG interrelations are not strictly associated with epileptiform events, which are one key concept of current clinical EEG assessment. Rather, they may provide information relevant for surgery planning in temporal lobe epilepsy. Our study suggests to incorporate quantitative EEG analysis in the workup of clinical cases. We make the EEG epochs and expert annotations publicly available in anonymized form to foster similar analyses for other quantitative EEG methods.
Efficacy of Neuroendoscopic Treatment for Septated Chronic Subdural Hematoma
Authors: Deng Jianhong , Wang Fangyu , Wang Haojie , Zhao Mingpei , Chen Guorong , Shangguan Huangcheng , Yu Lianghong , Jiang Changzhen , Fang Wenhua , Yao Peisen , Kang Dezhi , Zheng Shufa
Published: January 2022

Objective: Neuroendoscopic treatment is an alternative therapeutic strategy for the treatment of septate chronic subdural hematoma (sCSDH). However, the safety and efficacy of this strategy remain controversial. We compared the clinical outcomes of neuroendoscopic treatment with those of standard (large bone flap) craniotomy for sCSDH reported in our center. Furthermore, the safety and efficacy of the neuroendoscopic treatment procedure for sCSDH were evaluated.

Methods: We retrospectively collected the clinical data of 43 patients (37 men and six women) with sCSDH who underwent either neuroendoscopic treatment or standard (large bone flap) craniotomy, such as sex, age, smoking, drinking, medical history, use of antiplatelet drugs, postoperative complications, sCSDH recurrence, length of hospital stay, and postoperative hospital stay. We recorded the surgical procedures and the neurological function recovery prior to surgery and 6 months following the surgical treatment.

Results: The enrolled patients were categorized into neuroendoscopic treatment (n = 23) and standard (large bone flap) craniotomy (n = 20) groups. There were no differences in sex, age, smoking, drinking, medical history, antiplatelet drug use, postoperative complications, and sCSDH recurrence between the two groups (p > 0.05). However, the patients in neuroendoscopic treatment group had a shorter length of total hospital stay and postoperative hospital stay as compared with the standard craniotomy group (total hospital stay: 5.26 ± 1.89 vs. 8.15 ± 1.04 days, p < 0.001; postoperative hospital stay: 4.47 ± 1.95 vs. 7.96 ± 0.97 days, p < 0.001). The imaging and Modified Rankin Scale at the 6-month follow-up were satisfactory, and no sCSDH recurrence was reported in the two groups.

Conclusions: The findings of this study indicate that neuroendoscopic treatment is safe and effective for sCSDH; it is minimally invasive and could be clinically utilized.
Association of Stress Hyperglycemia Ratio With Acute Ischemic Stroke Outcomes Post-thrombolysis
Authors: Shen Chuan-Li , Xia Nian-Ge , Wang Hong , Zhang Wan-Li
Published: January 2022

Background and Purpose: The association between stress hyperglycemia and clinical outcomes in patients with acute ischemic stroke treated with intravenous thrombolysis (IVT) is uncertain. We sought to analyze the association between the stress hyperglycemia ratio (SHR) using different definitions and clinical outcomes in acute patients with ischemic stroke undergoing IVT.

Methods: A total of 341 patients with ischemic stroke receiving IVT were prospectively enrolled in this study. The SHR was evaluated using different equations: SHR1, fasting glucose (mmol/L)/glycated hemoglobin (HbA1c) (%); SHR2, fasting glucose (mmol/L)/[(1.59 × HbA1c)−2.59]; SHR3, admission blood glucose (mmol/L)/[(1.59 × HbA1c)−2.59]. A poor functional outcome was defined as a modified Rankin scale score of 3–6 at 3 months. Multivariate logistic regression analysis was used to identify the relationship between different SHRs and clinical outcomes after IVT.

Results: A total of 127 (37.2%) patients presented with poor functional outcomes at 3 months. The predictive value of SHR1 for poor functional outcomes was better than that of SHR2 and SHR3 in receiver operating characteristic analyses. On multivariate analysis, SHR1 [odds ratio (OR) 14.639, 95% CI, 4.075–52.589; P = 0.000] and SHR2 (OR, 19.700; 95% CI; 4.475–86.722; P = 0.000) were independently associated with an increased risk of poor functional outcome but not SHR3.

Conclusions: Our study confirmed that the SHR, as measured by SHR1 and SHR2, is independently associated with worse clinical outcomes in patients with ischemic stroke after intravenous thrombolysis. Furthermore, SHR1 has a better predictive performance for outcomes than other SHR definitions.
Startle Increases the Incidence of Anticipatory Muscle Activations but Does Not Change the Task-Specific Muscle Onset for Patients After Subacute Stroke
Authors: Xia Nan , He Chang , Li Yang-An , Gu Minghui , Chen Zejian , Wei Xiupan , Xu Jiang , Huang Xiaolin
Published: January 2022

Objectives: To demonstrate the task-specificities of anticipatory muscle activations (AMAs) among different forward-reaching tasks and to explore the StartleReact Effect (SE) on AMAs in occurrence proportions, AMA onset latency or amplitude within these tasks in both healthy and stroke population.

Methods: Ten healthy and ten stroke subjects were recruited. Participants were asked to complete the three forward-reaching tasks (reaching, reaching to grasp a ball or cup) on the left and right hand, respectively, with two different starting signals (warning-Go, 80 dB and warning-startle, 114 dB). The surface electromyography of anterior deltoid (AD), flexor carpi radialis (FCR), and extensor carpi radialis (ECR) on the moving side was recorded together with signals from bilateral sternocleidomastoid muscles (SCM), lower trapezius (LT), latissimus dorsi (LD), and tibialis anterior (TA). Proportions of valid trials, the incidence of SE, AMA incidence of each muscle, and their onset latency and amplitude were involved in analyses. The differences of these variables across different move sides (healthy, non-paretic, and paretic), normal or startle conditions, and the three tasks were explored. The ECR AMA onset was selected to further explore the SE on the incidence of AMAs.

Results: Comparisons between move sides revealed a widespread AMA dysfunction in subacute stroke survivors, which was manifested as lower AMA onset incidence, changed onset latency, and smaller amplitude of AMAs in bilateral muscles. However, a significant effect of different tasks was only observed in AMA onset latency of muscle ECR (F = 3.56, p = 0.03, η2p = 0.011), but the significance disappeared in the subsequent analysis of the stroke subjects only (p > 0.05). Moreover, the following post-hoc comparison indicated significant early AMA onsets of ECR in task cup when comparing with reach (p < 0.01). For different stimuli conditions, a significance was only revealed on shortened premotor reaction time under startle for all participants (F = 60.68, p < 0.001, ηp2 = 0.056). Furthermore, stroke survivors had a significantly lower incidence of SE than healthy subjects under startle (p < 0.01). But all performed a higher incidence of ECR AMA onset (p < 0.05) than with normal signal. In addition, the incidence of ECR AMAs of both non-paretic and paretic sides could be increased significantly via startle (p ≤ 0.02).

Conclusions: Healthy people have task-specific AMAs of muscle ECR when they perform forward-reaching tasks with different hand manipulations. However, this task-specific adjustment is lost in subacute stroke survivors. SE can improve the incidence of AMAs for all subjects in the forward-reaching tasks involving precision manipulations, but not change AMA onset latency and amplitude.
Ten Good Reasons to Practice Neuroultrasound in Critical Care Setting
Authors: Bittencourt Rynkowski Carla , Caldas Juliana
Published: January 2022

In the beginning, cerebral ultrasound (US) was not considered feasible because the intact skull was a seemingly impenetrable obstacle. For this reason, obtaining a clear image resolution had been a challenge since the first use of neuroultrasound (NUS) for the assessment of small deep brain structures. However, the improvements in transducer technologies and advances in signal processing have refined the image resolution, and the role of NUS has evolved as an imaging modality for the brain parenchyma within multiple pathologies. This article summarizes ten crucial applications of cerebral ultrasonography for the evaluation and management of neurocritical patients, whose transfer from and to intensive care units poses a real problem to medical care staff. This also encompasses ease of use, low cost, wide acceptance by patients, no radiation risk, and relative independence from movement artifacts. Bedsides, availability and reliability raised the interest of critical care intensivists in using it with increasing frequency. In this mini-review, the usefulness and the advantages of US in the neurocritical care setting are discussed regarding ten aspects to encourage the intensivist physician to practice this important tool.
Clinical Features and Early Recognition of 242 Cases of Autoimmune Encephalitis
Authors: Yang Mu , Lian Yajun
Published: January 2022

Objective: To analyze the clinical features of common autoimmune encephalitis and evaluate the sensitivity of antibodies contributing to focal epilepsy signs and symptoms (ACES) score.

Methods: Collecting and analyzing the data of 242 patients with autoimmune encephalitis (AE) diagnosed in the First Affiliated Hospital of Zhengzhou University from August 2015 to December 2020 in this retrospective study. The six items of the ACES score (cognitive symptoms, behavioral changes, autonomic symptoms, speech problems, autoimmune diseases, temporal MRI hyperintensities) were screened in patients with complete clinical data.

Results: (1) In total, 242 patients were included, with 147 cases of anti-N-methyl-D-aspartate receptor encephalitis, 47 cases of anti-γ-aminobutyric acid type B (GABA-B) receptor encephalitis, and 48 cases of anti-leucine-rich glioma inactivating protein 1 (LGI1) encephalitis. The most common clinical symptoms are cognitive impairment (77%), behavioral changes (79%), and seizures (71%). In total, 129 cases (54%) combined with autonomic dysfunction, such as gastrointestinal dysmotility, sinus tachycardia, and central hypoventilation. Twelve patients had autoimmune diseases, most of which were of thyroid diseases. (2) One hundred and twenty-seven patients with complete clinical data evaluated ACES score, 126 cases of whom (126/127, 99.2%) were equal to or >2 points, 1 case (1/127, 0.8%) was of <2 points.

Interpretation: (1) Cognitive impairment, abnormal behavior, and seizures are the most common manifestations of AE and autonomic symptoms. Thyroid disease is the most autoimmune disease in AE. Clinically, for patients of suspected AE, increasing the knowledge and testing of thyroid function and rheumatism is necessary. (2) ACES score is a simple, effective, and easy-to-operate score, with a certain screening value for most patients suspected of AE.
Perspectives on Primary Blast Injury of the Brain: Translational Insights Into Non-inertial Low-Intensity Blast Injury
Authors: Siedhoff Heather R. , Chen Shanyan , Song Hailong , Cui Jiankun , Cernak Ibolja , Cifu David X. , DePalma Ralph G. , Gu Zezong
Published: January 2022

Most traumatic brain injuries (TBIs) during military deployment or training are clinically “mild” and frequently caused by non-impact blast exposures. Experimental models were developed to reproduce the biological consequences of high-intensity blasts causing moderate to severe brain injuries. However, the pathophysiological mechanisms of low-intensity blast (LIB)-induced neurological deficits have been understudied. This review provides perspectives on primary blast-induced mild TBI models and discusses translational aspects of LIB exposures as defined by standardized physical parameters including overpressure, impulse, and shock wave velocity. Our mouse LIB-exposure model, which reproduces deployment-related scenarios of open-field blast (OFB), caused neurobehavioral changes, including reduced exploratory activities, elevated anxiety-like levels, impaired nesting behavior, and compromised spatial reference learning and memory. These functional impairments associate with subcellular and ultrastructural neuropathological changes, such as myelinated axonal damage, synaptic alterations, and mitochondrial abnormalities occurring in the absence of gross- or cellular damage. Biochemically, we observed dysfunctional mitochondrial pathways that led to elevated oxidative stress, impaired fission-fusion dynamics, diminished mitophagy, decreased oxidative phosphorylation, and compensated cell respiration-relevant enzyme activity. LIB also induced increased levels of total tau, phosphorylated tau, and amyloid β peptide, suggesting initiation of signaling cascades leading to neurodegeneration. We also compare translational aspects of OFB findings to alternative blast injury models. By scoping relevant recent research findings, we provide recommendations for future preclinical studies to better reflect military-operational and clinical realities. Overall, better alignment of preclinical models with clinical observations and experience related to military injuries will facilitate development of more precise diagnosis, clinical evaluation, treatment, and rehabilitation.
A Novel Motion Recognition Method Based on Force Myography of Dynamic Muscle Contractions
Authors: Li Xiangxin , Zheng Yue , Liu Yan , Tian Lan , Fang Peng , Cao Jianglang , Li Guanglin
Published: January 2022

Surface electromyogram-based pattern recognition (sEMG-PR) has been considered as the most promising method to control multifunctional prostheses for decades. However, the commercial applications of sEMG-PR in prosthetic control is still limited due to the ambient noise and impedance variation between electrodes and skin surface. In order to reduce these issues, a force-myography-based pattern recognition method was proposed. In this method, a type of polymer-based flexible film sensors, the piezoelectrets, were used to record the rate of stress change (RSC) signals on the muscle surface of eight able-bodied subjects for six hand motions. Thirteen time domain features and four classification algorithms of linear discriminant analysis (LDA), K-nearest neighbor (KNN), artificial neural network (ANN), and support vector machine (SVM) were adopted to decode the RSC signals of different motion classes. In addition, the optimal feature set, classifier, and analysis window length were investigated systematically. Results showed that the average classification accuracy was 95.5 ± 2.2% by using the feature combination of root mean square (RMS) and waveform length (WL) for the classifier of KNN, and the analysis window length of 300 ms was found to obtain the best classification performance. Moreover, the robustness of the proposed method was investigated, and the classification accuracies were observed above 90% even when the white noise ratio increased to 50%. The work of this study demonstrated the effectiveness of RSC-based pattern recognition method for motion classification, and it would provide an alternative approach for the control of multifunctional prostheses.
Task Difficulty Regulates How Conscious and Unconscious Monetary Rewards Boost the Performance of Working Memory: An Event-Related Potential Study
Authors: Xu Shiyang , Qi Senqing , Duan Haijun , Zhang Juan , Akioma Miriam , Gao Fei , Wu Anise M. S. , Yuan Zhen
Published: January 2022

The performance of working memory can be improved by the corresponding high-value vs. low-value rewards consciously or unconsciously. However, whether conscious and unconscious monetary rewards boosting the performance of working memory is regulated by the difficulty level of working memory task is unknown. In this study, a novel paradigm that consists of a reward-priming procedure and N-back task with differing levels of difficulty was designed to inspect this complex process. In particular, both high-value and low-value coins were presented consciously or unconsciously as the reward cues, followed by the N-back task, during which electroencephalogram signals were recorded. It was discovered that the high-value reward elicited larger event-related potential (ERP) component P3 along the parietal area (reflecting the working memory load) as compared to the low-value reward for the less difficult 1-back task, no matter whether the reward was unconsciously or consciously presented. In contrast, this is not the case for the more difficult 2-back task, in which the difference in P3 amplitude between the high-value and low-value rewards was not significant for the unconscious reward case, yet manifested significance for the conscious reward processing. Interestingly, the results of the behavioral analysis also exhibited very similar patterns as ERP patterns. Therefore, this study demonstrated that the difficulty level of a task can modulate the influence of unconscious reward on the performance of working memory.
Multifarious Indigenous Diazotrophic Rhizobacteria of Rice (Oryza sativa L.) Rhizosphere and Their Effect on Plant Growth Promotion
Authors: Mir Mohammad Imran , Hameeda Bee , Quadriya Humera , Kumar B. Kiran , Ilyas Noshin , Kee Zuan Ali Tan , El Enshasy Hesham Ali , Dailin Daniel Joe , Kassem Hazem S. , Gafur Abdul , Sayyed R. Z.
Published: January 2022

A diverse group of rhizobacteria persists in the rhizospheric soil, on the surface of roots, or in association with rice plants. These bacteria colonize plant root systems, enhance plant growth and crop yield. Indigenous rhizobacteria are known to promote soil health, grain production quality and serve as sustainable bioinoculant. The present study was aimed to isolate, identify and characterize indigenous plant growth promoting (PGP) diazotrophic bacteria associated with the rhizosphere of rice fields from different areas of Jammu and Kashmir, India. A total of 15 bacteria were isolated and evaluated for various PGP traits, antagonistic activity against phytopathogens, production of hydrolytic enzymes and biofilm formation under in-vitro conditions. The majority of the isolated bacteria were Gram-negative. Out of 15 bacterial isolates, nine isolates produced IAA (12.24 ± 2.86 to 250.3 ± 1.15 μg/ml), 6 isolates exhibited phosphate solubilization activity (36.69 ± 1.63 to 312.4 ± 1.15 μg/ml), 7 isolates exhibited rock phosphate solubilization while 5 isolates solubilized zinc (10–18 mm), 7 isolates showed siderophore production, 8 isolates exhibited HCN production, 6 isolates exhibited aminocyclopropane-1-carboxylate (ACC) deaminase activity, 13 isolates exhibited cellulase activity, nine isolates exhibited amylase and lipase activity and six isolates exhibited chitinase activity. In addition, 5 isolates showed amplification with the nifH gene and showed a significant amount of nitrogenase activity in a range of 0.127–4.39 μmol C2H4/mg protein/h. Five isolates viz., IHK-1, IHK-3, IHK-13, IHK-15 and IHK-25 exhibited most PGP attributes and successfully limited the mycelial growth of Rhizoctonia solani and Fusarium oxysporum in-vitro. All the five bacterial isolates were identified based on morphological, biochemical and 16S rDNA gene sequencing study, as Stenotrophomonas maltophilia, Enterobacter sp., Bacillus sp., Ochrobactrum haematophilum and Pseudomonas aeruginosa. Rice plants developed from seeds inoculated with these PGP strains individually had considerably higher germination percentage, seed vigor index and total dry biomass when compared to control. These findings strongly imply that the PGP diazotrophic bacteria identified in this work could be employed as plant growth stimulators in rice.
Benefits and Safety of Astaxanthin in the Treatment of Mild-To-Moderate Dry Eye Disease
Authors: Tian Lei , Wen Ya , Li Siyuan , Zhang Peng , Wang Yinghui , Wang Jingyi , Cao Kai , Du Lihua , Wang Ningli , Jie Ying
Published: January 2022

Objectives: To evaluate the effect of astaxanthin in the treatment of mild-to-moderate dry eye disease (DED) in middle-aged and elderly patients.

Methods: 120 eyes of 60 middle-aged and elderly patients with mild-to-moderate DED were enrolled in this prospective, one-group, quasi-experimental study. Six milligram Astaxanthin tablets (Weihong Haematococcus Pluvialis Astaxanthin, Hangzhou Xinwei Low Carbon Technology R&D Co., Ltd., China) were administered orally, twice daily for 30 ± 2 days. History of eye diseases, treatment, systemic disease, and medication before the test were recorded. In addition, the ocular surface disease index (OSDI) questionnaire, non-invasive tear break-up time (NIBUT), fluorescein break-up time (FBUT), corneal fluorescein staining (CFS) score, eyelid margin signs, meibomian gland (MG) expressibility, meibum quality, meibomian gland dropout (MGDR), Schirmer I test (SIt), tear meniscus height (TMH), bulbar conjunctiva congestion degree, blink frequency, incomplete blink rate, and thickness of tear film lipid layer were collected before treatment, 2 weeks after the initiation of treatment, and at the end of treatment. Visual acuity (VA), intraocular pressure (IOP), anterior segment, fundus, discomfort symptoms and other adverse reactions were also monitored throughout the study to assess the safety.

Results: OSDI score, NIBUT, BUT, CFS score, eyelid margin signs, MG expressibility, meibum quality, and blink frequency improved significantly to varying degrees after treatment compared with those before the treatment (P < 0.05), while TMH, SIt, conjunctival congestion, the thickness of tear film lipid layer, MGDR, incomplete blink rate, VA and IOP did not differ (P > 0.05).

Conclusions: Oral administration of astaxanthin improves the symptoms and signs of middle-aged and elderly patients with mild-to-moderate DED.
Biocontrol Potential of Essential Oils in Organic Horticulture Systems: From Farm to Fork
Authors: Chang Yuru , Harmon Philip F. , Treadwell Danielle D. , Carrillo Daniel , Sarkhosh Ali , Brecht Jeffrey K.
Published: January 2022

In recent decades, increasing attention has been paid to food safety and organic horticulture. Thus, people are looking for natural products to manage plant diseases, pests, and weeds. Essential oils (EOs) or EO-based products are potentially promising candidates for biocontrol agents due to their safe, bioactive, biodegradable, ecologically, and economically viable properties. Born of necessity or commercial interest to satisfy market demand for natural products, this emerging technology is highly anticipated, but its application has been limited without the benefit of a thorough analysis of the scientific evidence on efficacy, scope, and mechanism of action. This review covers the uses of EOs as broad-spectrum biocontrol agents in both preharvest and postharvest systems. The known functions of EOs in suppressing fungi, bacteria, viruses, pests, and weeds are briefly summarized. Related results and possible modes of action from recent research are listed. The weaknesses of applying EOs are also discussed, such as high volatility and low stability, low water solubility, strong influence on organoleptic properties, and phytotoxic effects. Therefore, EO formulations and methods of incorporation to enhance the strengths and compensate for the shortages are outlined. This review also concludes with research directions needed to better understand and fully evaluate EOs and provides an outlook on the prospects for future applications of EOs in organic horticulture production.
Porphyra yezoensis Sauces Fermented With Lactic Acid Bacteria: Fermentation Properties, Flavor Profile, and Evaluation of Antioxidant Capacity in vitro
Authors: Yang Jie , Gao Tengqi , Ge Feng , Sun Hao , Cui Zihang , Wei Zhen , Wang Shujun , Show Pau Loke , Tao Yang , Wang Wenbin
Published: January 2022

The demand for roasted seaweed sandwich (Porphyra yezoensis) product has risen in recent years. The product slicing process has created a huge number of scraps that are not utilized effectively. Three lactic acid bacteria (LAB) strains were used to ferment P. yezoensis sauces in this study, including Lactobacillus fermentum, Lactobacillus casei, Streptococcus thermophilus, and the mixed strains (1:1:1, v/v). The fermentation characteristics, antioxidant capacity in vitro, sensory properties, and flavoring substances of fermented P. yezoensis sauces were analyzed. After 21 days of fermentation, all LAB strains grew well in the P. yezoensis sauces, with protease activity increased to 6.6, 9.24, 5.06, and 5.5 U/mL, respectively. Also, the flavors of P. yezoensis sauces fermented with L. casei and L. fermentum were satisfactory. On this premise, gas chromatography-mass spectrometry (GC-MS) was used to investigate the changes in gustatory compounds in P. yezoensis sauces fermented with L. casei and L. fermentum. In general, 42 and 41 volatile flavor chemicals were identified after the fermentation of L. casei and L. fermentum. Furthermore, the fermented P. yezoensis sauce possessed greater DPPH scavenging activity and ferric-reducing ability power than the unfermented P. yezoensis. Overall, the flavor and taste of P. yezoensis sauce fermented by L. casei was superior.
Safety and Efficacy of Transarterial Chemoembolization Combined With Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors for Hepatocellular Carcinoma
Authors: Yang Fei , Yang Jun , Xiang Wei , Zhong Bin-Yan , Li Wan-Ci , Shen Jian , Zhang Shuai , Yin Yu , Sun Hong-Peng , Wang Wan-Sheng , Zhu Xiao-Li
Published: January 2022

Purpose

To explore the safety and efficacy of transarterial chemoembolization (TACE) in combination with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) for the treatment of unresectable hepatocellular carcinoma (uHCC).

Materials and Methods

From August 2019 to July 2020, patients who received TACE combined with ICIs and TKIs were retrospectively analyzed. Treatment-related adverse events (AEs) were recorded. The Kaplan–Meier method was used to estimate time to progression (TTP) and progression-free survival (PFS).

Results

In total, 31 patients with uHCC were included. Eleven patients were classified as BCLC-C. Nineteen patients had multiple lesions, and the cumulative targeted lesions were 69 mm (range, 21-170 mm) according to mRECIST. Twenty-nine (93%) patients experienced at least one AE during the treatment. Four (12.9%) patients developed AEs of higher grade (grade≥3). The objective response rate (ORR) and disease control rate (DCR) were 64.5% and 77.4%, respectively. The median time to response was 7 weeks (range, 4-30 w), and the duration of response was 17.5 weeks (range, 2-46 w). From the first ICIs, TTP and PFS were 6.5 months (95% CI, 3.5-11) and 8.5 months (95% CI, 3.5-NE), respectively.

Conclusions

TACE combined with ICIs and TKIs shows an acceptable safety profile and considerable efficacy in patients with HCC.
A Novel Machine Learning Algorithm Combined With Multivariate Analysis for the Prognosis of Renal Collecting Duct Carcinoma
Authors: Wei Liwei , Huang Yongdi , Chen Zheng , Li Jinhua , Huang Guangyi , Qin Xiaoping , Cui Lihong , Zhuo Yumin
Published: January 2022

Objectives

To investigate the clinical and non-clinical characteristics that may affect the prognosis of patients with renal collecting duct carcinoma (CDC) and to develop an accurate prognostic model for this disease.

Methods

The characteristics of 215 CDC patients were obtained from the U.S. National Cancer Institute’s surveillance, epidemiology and end results database from 2004 to 2016. Univariate Cox proportional hazard model and Kaplan-Meier analysis were used to compare the impact of different factors on overall survival (OS). 10 variables were included to establish a machine learning (ML) model. Model performance was evaluated by the receiver operating characteristic curves (ROC) and calibration plots for predictive accuracy and decision curve analysis (DCA) were obtained to estimate its clinical benefits.

Results

The median follow-up and survival time was 16 months during which 164 (76.3%) patients died. 4.2, 32.1, 50.7 and 13.0% of patients were histological grade I, II, III, and IV, respectively. At diagnosis up to 61.9% of patients presented with a pT3 stage or higher tumor, and 36.7% of CDC patients had metastatic disease. 10 most clinical and non-clinical factors including M stage, tumor size, T stage, histological grade, N stage, radiotherapy, chemotherapy, age at diagnosis, surgery and the geographical region where the care delivered was either purchased or referred and these were allocated 95, 82, 78, 72, 49, 38, 36, 35, 28 and 21 points, respectively. The points were calculated by the XGBoost according to their importance. The XGBoost models showed the best predictive performance compared with other algorithms. DCA showed our models could be used to support clinical decisions in 1-3-year OS models.

Conclusions

Our ML models had the highest predictive accuracy and net benefits, which may potentially help clinicians to make clinical decisions and follow-up strategies for patients with CDC. Larger studies are needed to better understand this aggressive tumor.
Progress in the Treatment of HIV-Associated Lymphoma When Combined With the Antiretroviral Therapies
Authors: Wang Chaoyu , Liu Jun , Liu Yao
Published: January 2022

With the wide use of combination antiretroviral therapy (cART), the life expectancy of HIV-infected individuals drastically improved. However, HIV infection and HIV-associated cancers were the most common causes of death in the HIV-infected populations. The HIV-associated cancers are divided into acquired immune deficiency syndrome (AIDS)-defining and non-AIDS-defining cancers based on the incidence among the HIV-infected patients. Among HIV-associated cancers, acquired immune deficiency syndrome-related lymphoma (ARL) is still the most common condition and the leading cause of HIV/AIDS-related deaths. Diffuse large B-cell lymphoma (DLBCL) and Burkitt’s lymphoma (BL) are the most common subtypes of the ARL. Although Hodgkin’s lymphoma (HL) is not considered as an AIDS-defining cancer, incidence of HL in HIV-infected individuals is higher than the general population. The review summarizes the new progress in the treatment of HIV-associated lymphoma.
Comparison of Ultrasound-Guided Core Needle Biopsy Under the Assistance of Hydrodissection With Fine Needle Aspiration in the Diagnosis of High-Risk Cervical Lymph Nodes: A Randomized Controlled Trial
Authors: Teng Dengke , Dong Chunhui , Sun Daju , Liu Zhuo , Wang Hui
Published: January 2022

A randomized comparison of ultrasound (US)-guided core needle biopsy (CNB) under the assistance of hydrodissection with fine needle aspiration (FNA) was performed to evaluate the feasibility, safety and effectiveness for the diagnosis of high-risk cervical lymph nodes. Patients from December 2018 to May 2020 were randomly assigned to the CNB group and the FNA group at a ratio of 1:1. This study protocol was approved by the Ethics Committee of our hospital and registered in the Chinese Clinical Trial Registry (ChiCTR1800019370). The feasibility of CNB for high-risk cervical lymph nodes was evaluated by observing and recording the separation success rate (SSR) and technical success rate (TSR) of the CNB group. Safety was evaluated by comparing the incidence of major complications in the two groups. The diagnostic efficacy was evaluated by comparing the diagnostic accuracy, sensitivity, and specificity of the two groups. A total of 84 patients (84 lymph nodes) were randomized into the CNB (n = 42) and FNA (n = 42) groups. All patients in the CNB group achieved successful hydrodissection and biopsy. The SSR and TSR were both 100% in the CNB group. There were no major complications during or after the process in the two groups. Compared with the FNA group, the CNB group was significantly superior in terms of diagnostic accuracy and sensitivity (100% vs. 81.0%, P = 0.009; 100% vs. 79.2%, P = 0.035, respectively). The specificity of the two groups was 100%, and there was no significant difference. Compared with FNA, CNB under the assistance of hydrodissection is a feasible and safe method but is more effective for the diagnosis of high-risk cervical lymph nodes.

Clinical Trial Registration

http://www.medresman.org, ChiCTR1800019370.
Path to Clonal Theranostics in Luminal Breast Cancers
Authors: Hajjaji Nawale , Aboulouard Soulaimane , Cardon Tristan , Bertin Delphine , Robin Yves-Marie , Fournier Isabelle , Salzet Michel
Published: January 2022

Integrating tumor heterogeneity in the drug discovery process is a key challenge to tackle breast cancer resistance. Identifying protein targets for functionally distinct tumor clones is particularly important to tailor therapy to the heterogeneous tumor subpopulations and achieve clonal theranostics. For this purpose, we performed an unsupervised, label-free, spatially resolved shotgun proteomics guided by MALDI mass spectrometry imaging (MSI) on 124 selected tumor clonal areas from early luminal breast cancers, tumor stroma, and breast cancer metastases. 2868 proteins were identified. The main protein classes found in the clonal proteome dataset were enzymes, cytoskeletal proteins, membrane-traffic, translational or scaffold proteins, or transporters. As a comparison, gene-specific transcriptional regulators, chromatin related proteins or transmembrane signal receptor were more abundant in the TCGA dataset. Moreover, 26 mutated proteins have been identified. Similarly, expanding the search to alternative proteins databases retrieved 126 alternative proteins in the clonal proteome dataset. Most of these alternative proteins were coded mainly from non-coding RNA. To fully understand the molecular information brought by our approach and its relevance to drug target discovery, the clonal proteomic dataset was further compared to the TCGA breast cancer database and two transcriptomic panels, BC360 (nanoString®) and CDx (Foundation One®). We retrieved 139 pathways in the clonal proteome dataset. Only 55% of these pathways were also present in the TCGA dataset, 68% in BC360 and 50% in CDx. Seven of these pathways have been suggested as candidate for drug targeting, 22 have been associated with breast cancer in experimental or clinical reports, the remaining 19 pathways have been understudied in breast cancer. Among the anticancer drugs, 35 drugs matched uniquely with the clonal proteome dataset, with only 7 of them already approved in breast cancer. The number of target and drug interactions with non-anticancer drugs (such as agents targeting the cardiovascular system, metabolism, the musculoskeletal or the nervous systems) was higher in the clonal proteome dataset (540 interactions) compared to TCGA (83 interactions), BC360 (419 interactions), or CDx (172 interactions). Many of the protein targets identified and drugs screened were clinically relevant to breast cancer and are in clinical trials. Thus, we described the non-redundant knowledge brought by this clone-tailored approach compared to TCGA or transcriptomic panels, the targetable proteins identified in the clonal proteome dataset, and the potential of this approach for drug discovery and repurposing through drug interactions with antineoplastic agents and non-anticancer drugs.