bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of Deep Learning-Based DFCNN in Extremely Large-Scale Virtual Screening and Application in Trypsin I Protease Inhibitor Discovery
Authors: Zhang Haiping , Lin Xiao , Wei Yanjie , Zhang Huiling , Liao Linbu , Wu Hao , Pan Yi , Wu Xuli 
Published: June 2022

Computational methods with affordable computational resources are highly desirable for identifying active drug leads from millions of compounds. This requires a model that is both highly efficient and relatively accurate, which cannot be achieved by most of the current methods. In real virtual screening (VS) application scenarios, the desired method should perform much better in selecting active compounds by prediction than by random chance. Here, we systematically evaluate the performance of our previously developed DFCNN model in large-scale virtual screening, and the results show our method has approximately 22 times the success rate compared to the random chance on average with a score cutoff of 0.99. Of the 102 test cases, 10 cases have more than 98 times the success rate of a random guess. Interestingly, in three cases, the prediction success rate is 99 times that of a random guess by a score cutoff of 0.99. This indicates that in most situations after our extremely large-scale VS, the dataset can be reduced 20 to 100 times for the next step of virtual screening based on docking or MD simulation. Furthermore, we have employed an experimental method to verify our computational method by finding several activity inhibitors for Trypsin I Protease. In addition, we also show its proof-of-concept application in de novo drug screening. The results indicate the massive potential of this method in the first step of the real drug development workflow. Moreover, DFCNN only takes about 0.0000225s for one protein–compound prediction on average with 80 Intel CPU cores (2.00 GHz) and 60 GB RAM, which is at least tens of thousands of times faster than AutoDock Vina or Schrödinger high-throughput virtual screening. Additionally, an online webserver based on DFCNN for large-scale screening is available at http://cbblab.siat.ac.cn/DFCNN/index.php for the convenience of the users.
Comparison of Clinical Symptoms and Neurophysiological Findings in Patients With Chemotherapy Induced Peripheral Neuropathy
Authors: Cho Kye Hee , Han Eun Young , Shin Ji Cheol , Ha Min Cheol , Ahn Kwang Ho , Cho Su Hyun , IM Sang Hee 
Published: June 2022

IntroductionTaxanes are associated with a distal sensory neuropathy, significantly affecting cancer survivor quality of life. However, chemotherapy-induced peripheral neuropathy (CIPN) assessments are primarily based on clinical symptoms rather than objective neurophysiologic findings. Therefore, we investigated neurophysiologic changes in symptomatic subjects, comparing them with symptom severity.Materials and MethodsMedical charts of 111 subjects who were referred for CIPN diagnosis after chemotherapy for breast or ovarian cancer between May 1, 2016, and December 31, 2019, were retrospectively reviewed. Demographics, anthropometric parameters, and Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale data were collected. The nerve conduction study (NCS) results, including sensory nerve action potentials recorded from sural nerves, were analyzed relative to clinical symptoms. To optimize follow-up (FU) NCS diagnostic sensitivity, relative references of FU sural amplitude reductions to &gt;30% and an absolute reference &lt;10 μV were used.ResultsEighty-eight female patients met the criteria, and 20 underwent FU NCS. Baseline and FU sural amplitudes showed significant positive correlation with respective LANSS scores (p &lt; 0.01). FU sural amplitude was significantly lower than the initial result (p &lt; 0.05). The FU LANSS score was not different from the initial score. Initial NCS sensitivity and specificity for clinically suspected CIPN diagnoses with LANSS were 69.7 and 47.3%, respectively. All 20 subjects with FU evaluation were clinically compatible with CIPN (LANSS &gt;12) at initial and FU assessments. Among them, only six (30.0%) had abnormal sural amplitudes (&lt;10μV for ≤50 s, &lt;3 μV for 60 s, &lt;1 μV for 70 s) in the initial NCS. In the FU NCS, sural amplitude became abnormal in five additional subjects. Between the initial and FU NCS, sural amplitude was reduced by &gt; 30% in eight subjects (40.0%). NCS sensitivity increased to 65.0% when including either abnormal sural amplitudes or a &gt; 30% reduction in sural amplitude in FU studies.ConclusionsAlthough clinical symptoms and NCS results were positively correlated, a single NCS point had limited value for suspected CIPN electrophysiological diagnoses. Serial NCS during chemotherapy might help assess the degree of chemotherapy-induced nerve damage, attain evidence of CIPN prior to symptom aggravation, and monitor the progression of CIPN. Further study is needed to find specific relative references for variable patient factors to increase the sensitivity of electrophysiological studies of clinically suspected CIPN.
Medical Cannabis for the Treatment of Migraine in Adults: A Review of the Evidence
Authors: Okusanya Babasola O. , Lott Breanne E. , Ehiri John , McClelland Jean , Rosales Cecilia 
Published: June 2022

BackgroundMedical cannabis (MC) has been hypothesized as an alternative therapy for migraines, given the undesirable side effects of current migraine medications. The objective of this review was to assess the effectiveness and safety of MC in the treatment of migraine in adults.MethodsWe searched PubMed, EMBASE, PsycINFO, CINAHL, and Web of Science for eligible studies in adults aged 18 years and older. Two reviewers independently screened studies for eligibility. A narrative synthesis of the included studies was conducted.ResultsA total of 12 publications involving 1,980 participants in Italy and the United States of America were included.Medical cannabis significantly reduced nausea and vomiting associated with migraine attacks after 6 months of use. Also, MC reduced the number of days of migraine after 30 days, and the frequency of migraine headaches per month. MC was 51% more effective in reducing migraines than non-cannabis products. Compared to amitriptyline, MC aborted migraine headaches in some (11.6%) users and reduced migraine frequency. While the use of MC for migraines was associated with the occurrence of medication overuse headaches (MOH), and the adverse events were mostly mild and occurred in 43.75% of patients who used oral cannabinoid preparations.ConclusionsThere is promising evidence that MC may have a beneficial effect on the onset and duration of migraine headaches in adults. However, well-designed experimental studies that assess MC's effectiveness and safety for treating migraine in adults are needed to support this hypothesis.
Microscopic Transsphenoidal Resection of Giant Pituitary Adenomas: Analysis of the Factors Limiting the Degree of Resection in 73 Cases
Authors: Pei Zhijie , Wang Jiaxing , Mu Shuwen , Feng Tianshun , Wang Meina , Yu Shentong , Wei Liangfeng , Fang Yi , Wang Shousen 
Published: June 2022

PurposeTo analyze the risk factors affecting the gross-total resection of giant pituitary adenomas using a transsphenoidal approach under a microscope to provide a reference basis for formulating an appropriate surgical strategy.MethodsThe clinical data of patients who underwent microscopic transsphenoidal resection of giant pituitary adenomas in a single center from January 2011 to December 2020 were retrospectively analyzed. Based on magnetic resonance imaging and surgical records, the predictive factors affecting the gross-total resection of giant pituitary adenomas under microscopy were determined through univariate and multivariate analyses.ResultsA total of 73 patients with giant pituitary adenomas underwent transsphenoidal microsurgery. Gross-total resection was performed in 19 cases (26%), subtotal resection in 31 cases (42%), partial resection in 21 cases (29%), and the degree of resection was &lt;50% in only two cases (3%). After binary logistic analysis, it was found that it was more difficult to completely remove giant pituitary adenomas with a Knosp grade 3–4 [odds ratio (OR) = 0.214, 95% confidence interval (CI): 0.05–0.917; P = 0.038], greater proportion of tumor suprasellar volume (odds ratio = 0.937, 95% confidence interval: 0.898–0.978; P = 0.003), and intraoperative evidence of invasion of the cavernous sinus (odds ratio = 0.187, 95% CI: 0.039–0.898; P = 0.036).ConclusionIt is difficult to remove a giant pituitary adenoma invading the cavernous sinus completely with a higher degree of invasion of the suprasellar region using microscopic transsphenoidal surgery. The combined application of multiple surgical methods can help to improve the degree of resection during a single operation.
Dysautonomia in COVID-19 Patients: A Narrative Review on Clinical Course, Diagnostic and Therapeutic Strategies
Authors: Carmona-Torre Francisco , Mínguez-Olaondo Ane , López-Bravo Alba , Tijero Beatriz , Grozeva Vesselina , Walcker Michaela , Azkune-Galparsoro Harkaitz , López de Munain Adolfo , Alcaide Ana Belen , Quiroga Jorge , del Pozo Jose Luis , Gómez-Esteban Juan Carlos 
Published: June 2022

IntroductionOn March 11, 2020, the World Health Organization sounded the COVID-19 pandemic alarm. While efforts in the first few months focused on reducing the mortality of infected patients, there is increasing data on the effects of long-term infection (Post-COVID-19 condition). Among the different symptoms described after acute infection, those derived from autonomic dysfunction are especially frequent and limiting.ObjectiveTo conduct a narrative review synthesizing current evidence of the signs and symptoms of dysautonomia in patients diagnosed with COVID-19, together with a compilation of available treatment guidelines.ResultsAutonomic dysfunction associated with SARS-CoV-2 infection occurs at different temporal stages. Some of the proposed pathophysiological mechanisms include direct tissue damage, immune dysregulation, hormonal disturbances, elevated cytokine levels, and persistent low-grade infection. Acute autonomic dysfunction has a direct impact on the mortality risk, given its repercussions on the respiratory, cardiovascular, and neurological systems. Iatrogenic autonomic dysfunction is a side effect caused by the drugs used and/or admission to the intensive care unit. Finally, late dysautonomia occurs in 2.5% of patients with Post-COVID-19 condition. While orthostatic hypotension and neurally-mediated syncope should be considered, postural orthostatic tachycardia syndrome (POTS) appears to be the most common autonomic phenotype among these patients. A review of diagnostic and treatment guidelines focused on each type of dysautonomic condition was done.ConclusionSymptoms deriving from autonomic dysfunction involvement are common in those affected by COVID-19. These symptoms have a great impact on the quality of life both in the short and medium to long term. A better understanding of the pathophysiological mechanisms of Post-COVID manifestations that affect the autonomic nervous system, and targeted therapeutic management could help reduce the sequelae of COVID-19, especially if we act in the earliest phases of the disease.
Safety and Clinical Efficacy of Mesenchymal Stem Cell Treatment in Traumatic Spinal Cord Injury, Multiple Sclerosis and Ischemic Stroke – A Systematic Review and Meta-Analysis
Authors: Kvistad Christopher Elnan , Kråkenes Torbjørn , Gjerde Cecilie , Mustafa Kamal , Rekand Tiina , Bø Lars 
Published: June 2022

BackgroundMesenchymal stem cells (MSCs) is an attractive candidate in regenerative research and clinical trials have assessed their therapeutic potential in different neurological conditions with disparate etiologies. In this systematic review, we aimed to assess safety and clinical effect of MSC treatment in traumatic spinal cord injury (TSCI), multiple sclerosis (MS) and ischemic stroke (IS).MethodsA systematic search was performed 2021-12-10 in MEDLINE, EMBASE, Web of Science and Cochrane where clinical studies assessing MSC treatment in TSCI, MS or IS were included. Studies without control group were excluded for efficacy analysis, but included in the safety analysis. For efficacy, AIS score, EDSS score and mRS were used as clinical endpoints and assessed in a meta-analysis using the random effects model.FindingsOf 5,548 identified records, 54 studies were included. Twenty-six studies assessed MSC treatment in TSCI, 14 in MS and nine in IS, of which seven, seven and five studies were controlled, respectively. There were seven serious adverse events (SAEs), of which four were related to the surgical procedure and included one death due to complications following the implantation of MSCs. Three SAEs were considered directly related to the MSC treatment and all these had a transient course. In TSCI, a meta-analysis showed no difference in conversion from AIS A to C and a trend toward more patients treated with MSCs improving from AIS A to B as compared to controls (p = 0.05). A subgroup analysis performed per protocol, showed more MSC treated patients improving from AIS A to C in studies including patients within 8 weeks after injury (p = 0.04). In MS and IS, there were no significant differences in clinical outcomes between MSC treated patients and controls as measured by EDSS and mRS, respectively.InterpretationMSC-treatment is safe in patients with TSCI, MS and IS, although surgical implantation of MSC led to one fatal outcome in TSCI. There was no clear clinical benefit of MSC treatment, but this is not necessarily a proof of inefficacy due to the low number of controlled studies. Future studies assessing efficacy of MSC treatment should aim to do this in randomized, controlled studies.
High-Definition Transcranial Direct Current Stimulation of the Dorsolateral Prefrontal Cortex Modulates the Electroencephalography Rhythmic Activity of Parietal Occipital Lobe in Patients With Chronic Disorders of Consciousness
Authors: Han Jinying , Chen Chen , Zheng Shuang , Yan Xiaoxiang , Wang Changqing , Wang Kai , Hu Yajuan 
Published: June 2022

BackgroundDisorders of consciousness (DOC) are a spectrum of pathologies affecting one’s ability to interact with the external world. At present, High-Definition Transcranial Direct Current Stimulation (HD-tDCS) is used in many patients with DOC as a non-invasive treatment, but electrophysiological research on the effect of HD-tDCS on patients with DOC is limited.ObjectivesTo explore how HD-tDCS affects the cerebral cortex and examine the possible electrophysiological mechanisms underlying the effects of HD-tDCS on the cerebral cortex.MethodsA total of 19 DOC patients were assigned to HD-tDCS stimulation. Each of them underwent 10 anodal HD-tDCS sessions of the left dorsolateral prefrontal cortex (DLPFC) over 5 consecutive days. Coma Recovery Scale-Revision (CRS-R) scores were recorded to evaluate the consciousness level before and after HD-tDCS, while resting-state electroencephalography (EEG) recordings were obtained immediately before and after single and multiple HD-tDCS stimuli. Depending on whether the CRS-R score increased after stimulation, we classified the subjects into responsive (RE) and non-responsive (N-RE) groups and compared the differences in power spectral density (PSD) between the groups in different frequency bands and brain regions, and also examined the relationship between PSD values and CRS-R scores.ResultsFor the RE group, the PSD value of the parieto-occipital region increased significantly in the 6–8 Hz frequency band after multiple stimulations by HD-tDCS. After a single stimulation, an increase in PSD was observed at 10–13 and 13–30 Hz. In addition, for all subjects, a positive correlation was observed between the change in PSD value in the parieto-occipital region at 10–13 and 6–8 Hz frequency band and the change in CRS-R score after a single stimulation.ConclusionRepeated anodal HD-tDCS of the left DLPFC can improve clinical outcomes in patients with DOC, and HD-tDCS-related increased levels of consciousness were associated with increased parieto-occipital PSD.
On the Interplay Between the Medicine of Hildegard of Bingen and Modern Medicine: The Role of Estrogen Receptor as an Example of Biodynamic Interface for Studying the Chronic Disease's Complexity
Authors: Melino Sabrina , Mormone Elisabetta 
Published: June 2022

IntroductionHildegard of Bingen (1098-1179) interpreted the origins of chronic disease highlighting and anticipating, although only in a limited fashion, the importance that complex interactions among numerous genetic, internal milieu and external environmental factors have in determining the disease phenotype. Today, we recognize those factors, capable of mediating the transmission of messages between human body and environment and vice versa, as biodynamic interfaces.AimWe analyzed, in the light of modern scientific evidence, Hildegard of Bingen's medical approach and her original humoral theory in order to identify possible insights included in her medicine that could be referred to in the context of modern evidence-based medicine. In particular, the abbess's humoral theory suggests the identification of biodynamic interfaces with sex hormones and their receptors.FindingsWe found that the Hildegardian holistic vision of the organism-environment relationship can actually represent a visionary approach to modern endocrinology and that sex hormones, in particular estrogens, could represent an example of a biodynamic interface. Estrogen receptors are found in regions of the brain involved in emotional and cognitive regulation, controlling the molecular mechanism of brain function. Estrogen receptors are involved in the regulation of the hypothalamic-pituitary-adrenal axis and in the epigenetic regulation of responses to physiological, social, and hormonal stimuli. Furthermore, estrogen affects gene methylation on its own and related receptor promoters in discrete regions of the developing brain. This scenario was strikingly perceived by the abbess in the XIIth century, and depicted as a complex interplay among different humors and flegmata that she recognized to be sex specific and environmentally regulated.ViewpointConsidering the function played by hormones, analyzed through the last scientific evidence, and scientific literature on biodynamic interfaces, we could suggest Hildegardian insights and theories as the first attempt to describe the modern holistic, sex-based medicine.ConclusionHildegard anticipated a concept of pathogenesis that sees a central role for endocrinology in sex-specific disease. Furthermore, estrogens and estrogen receptors could represent a good example of molecular interfaces capable of modulating the interaction between the organism internal milieu and the environmental factors.
Prediction of Speech Intelligibility by Means of EEG Responses to Sentences in Noise
Authors: Muncke Jan , Kuruvila Ivine , Hoppe Ulrich 
Published: June 2022

ObjectiveUnderstanding speech in noisy conditions is challenging even for people with mild hearing loss, and intelligibility for an individual person is usually evaluated by using several subjective test methods. In the last few years, a method has been developed to determine a temporal response function (TRF) between speech envelope and simultaneous electroencephalographic (EEG) measurements. By using this TRF it is possible to predict the EEG signal for any speech signal. Recent studies have suggested that the accuracy of this prediction varies with the level of noise added to the speech signal and can predict objectively the individual speech intelligibility. Here we assess the variations of the TRF itself when it is calculated for measurements with different signal-to-noise ratios and apply these variations to predict speech intelligibility.MethodsFor 18 normal hearing subjects the individual threshold of 50% speech intelligibility was determined by using a speech in noise test. Additionally, subjects listened passively to speech material of the speech in noise test at different signal-to-noise ratios close to individual threshold of 50% speech intelligibility while an EEG was recorded. Afterwards the shape of TRFs for each signal-to-noise ratio and subject were compared with the derived intelligibility.ResultsThe strongest effect of variations in stimulus signal-to-noise ratio on the TRF shape occurred close to 100 ms after the stimulus presentation, and was located in the left central scalp region. The investigated variations in TRF morphology showed a strong correlation with speech intelligibility, and we were able to predict the individual threshold of 50% speech intelligibility with a mean deviation of less then 1.5 dB.ConclusionThe intelligibility of speech in noise can be predicted by analyzing the shape of the TRF derived from different stimulus signal-to-noise ratios. Because TRFs are interpretable, in a manner similar to auditory evoked potentials, this method offers new options for clinical diagnostics.
Two, Six, and Twelve-Month Dropout Rate and Predictor Factors After a Multidisciplinary Residential Program for Obesity Treatment. A Prospective Cohort Study
Authors: Perna Simone , Salman Majeda , Gasparri Clara , Cavioni Alessandro , Faliva Milena Anna , Mansueto Francesca , Naso Maurizio , Patelli Zaira , Peroni Gabriella , Tartara Alice , Riva Antonella , Petrangolini Giovanna , Rondanelli Mariangela 
Published: June 2022

IntroductionThe aim of the present study was to assess the dropout rate at 2, 6, and 12 months after an inpatient multidisciplinary residential program (MRP) for the treatment of obesity. Furthermore, this study assessed anthropometric and biochemical predictors associated with the dropout.MethodsAdult and elderly patients (age 59 ± 14 years) with obesity had undergone an MRP, were followed up from 2 to 12 months. Biochemical and anthropometric markers have been assessed at the beginning of the follow-up period after the MRP.ResultsThe study enrolled 178 subjects, 117 women and 61 men. The overall dropout rate at 2 months was 21.3%, after 6 months was 44.4%, and after 1 year was 68.5%. There was no difference by gender recorded. Furthermore, patients under medical treatment with psychiatric disorders did not show an association with the dropout rate. Patients with a higher level of body mass index (BMI) at the discharge of MRP showed +48% of dropout at 6 months. After the MRP, the baseline values of uricemia and white blood cells (WBCs) resulted as predictors of dropout at 2 months (p &gt; 0.05). Furthermore, the excess percentage of fat mass lost during the MRP was associated with the risk of dropout at 2, 6, and 12 months (p &gt; 0.05).ConclusionThe MRP for obesity is an opportunity for losing weight for patients with established criteria. The future challenge will be addressing the best strategic plans in order to reduce the dropout rate after this intervention. Investigating deeply the main predictors could be an opportunity to improve the long-term efficacy of MRP.