bluuebunny/crossref_metadata_2025 huggingface dataset:
The relationship between obstructive sleep apnea and visual hallucinations in PD patients: a polysomnography study
Authors: Zhu Jun , Zhao Yang , Jiang Yinyin , Pan Yang , Jiang Xu , Wang Yaxi , Li Dongfong , Zhang Li
Published: January 2024

Purpose

Parkinson's disease (PD) patients frequently experience visual hallucinations (VHs) and obstructive sleep apnea (OSA). The aim of this study was to describe the prevalence and clinical correlates of VHs and OSA in the Chinese population with PD.

Materials and methods

A sample of 489 PD patients was recruited for the present study. Patients were categorized as having formed VHs (FVHs) or minor VHs (MVHs) or as non-hallucinators (NVHs) according to the Unified Parkinson's Disease Rating Scale (UPDRS) and an initial questionnaire. Polysomnography (PSG) was used for objective assessment of sleep.

Results

VHs were observed in 143 (29.2%) patients. Among them, 75 of the hallucinators experienced MVHs, and 68 experienced FVHs. The disease duration, UPDRS Part III score, Hoehn and Yahr (H–Y) stage, Pittsburgh Sleep Quality Index (PSQI) score and rapid eye movement (REM) sleep behavior disorder (RBD) score of hallucinators were significantly greater than those of non-hallucinators (P < 0.05). We also observed OSA in 38.7, 54.7, and 63.3% of the NVH, MVH, and FVH groups, respectively. PSG showed that the VH groups had a lower total sleep time, lower sleep efficiency, higher arousal index, lower sleep latency, lower N1%, higher apnea-hypopnea index (AHI), higher average duration of apnea, higher respiratory-related arousal (RRA), and lower values of the lowest O2 and mean O2. The forward binary logistic regression model showed that AHI, N1%, RRA and lowest O2 were independently associated with VHs in PD patients.

Conclusions

Our results confirm the high prevalence of VHs and OSA as well as their relationship in patients with PD.
Metabolic alterations in the right anterior insula among patients with cirrhosis without overt hepatic encephalopathy: a magnetic resonance spectroscopy study
Authors: Huang Nao-Xin , Huang Hui-Wei , Dong Qiu-Yi , Wen Yu-Lin , Li Dan , Li Jian-Qi , Chen Hua-Jun
Published: January 2024

Purpose

We investigated metabolic alterations in the right anterior insula (rAI) in cirrhotic patients and determined its association with patients' cognitive dysfunction.

Methods

In this study, 31 healthy controls (HCs) and 32 cirrhotic patients without overt hepatic encephalopathy participated. Both blood ammonia level and Child-Pugh score were measured. The psychometric hepatic encephalopathy score (PHES) was used to evaluate cognitive function. 1H-magnetic resonance spectroscopy (MRS) data located in the rAI were recorded on a commercially available 3T magnetic resonance imaging scanner. The ratios of metabolites were measured, including N-acetylaspartate (NAA)/total creatine (tCr), glutamate plus glutamine (Glx)/tCr, myo-inositol (mI)/tCr, and total choline (tCho)/tCr. We adopted the non-parametric Mann–Whitney U-test for intergroup comparison of metabolic ratios. To determine the association between metabolite concentration and clinical parameters, we performed Spearman correlation analyses.

Results

Patients with cirrhosis performed worse on PHES in comparison with HCs (P < 0.001). Patients with cirrhosis had significantly decreased mI/tCr (0.87 ± 0.07 vs. 0.74 ± 0.19, P = 0.025) and increased Glx/tCr (1.79 ± 0.17 vs. 2.07 ± 0.29, P < 0.001) in the rAI. We did not observe any significant between-group differences in tCho/tCr and NAA/tCr. The blood ammonia level was correlated with Glx/tCr (r = 0.405, P = 0.022) and mI/tCr (r = −0.398, P = 0.024) of the rAI. In addition, PHES was negatively correlated with Glx/tCr of the rAI (r = −0.379, P = 0.033).

Conclusion

Metabolic disturbance of the rAI, which is associated with ammonia intoxication, might account for the neural substrate of cirrhosis-related cognitive dysfunction to some extent.
Optimizing the prediction of sepsis-associated encephalopathy with cerebral circulation time utilizing a nomogram: a pilot study in the intensive care unit
Authors: Mei Jiangjun , Zhang Xiajing , Sun Xuesong , Hu Lihua , Song Ye
Published: January 2024

Background

Sepsis-associated encephalopathy (SAE) is prevalent in intensive care unit (ICU) environments but lacks established treatment protocols, necessitating prompt diagnostic methods for early intervention. Traditional symptom-based diagnostics are non-specific and confounded by sedatives, while emerging biomarkers like neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100B) have limited specificity. Transcranial Doppler (TCD) indicators, although is particularly relevant for SAE, requires high operator expertise, limiting its clinical utility.

Objective

This pilot study aims to utilize cerebral circulation time (CCT) assessed via contrast-enhanced ultrasound (CEUS) as an innovative approach to investigate the accuracy of SAE prediction. Further, these CCT measurements are integrated into a nomogram to optimize the predictive performance.

Methods

This study employed a prospective, observational design, enrolling 67 ICU patients diagnosed with sepsis within the initial 24 h. Receiver operating characteristic (ROC) curve analyses were conducted to assess the predictive accuracy of potential markers including NSE, S100B, TCD parameters, and CCT for SAE. A nomogram was constructed via multivariate Logistic Regression to further explore the combined predictive potential of these variables. The model's predictive performance was evaluated through discrimination, calibration, and decision curve analysis (DCA).

Results

SAE manifested at a median of 2 days post-admission in 32 of 67 patients (47.8%), with the remaining 35 sepsis patients constituting the non-SAE group. ROC curves revealed substantial predictive utility for CCT, pulsatility index (PI), and S100B, with CCT emerging as the most efficacious predictor, evidenced by an area under the curve (AUC) of 0.846. Multivariate Logistic Regression identified these markers as independent predictors for SAE, leading to the construction of a nomogram with excellent discrimination, substantiated by an AUC of 0.924 through bootstrap resampling. The model exhibited satisfactory concordance between observed and predicted probabilities, and DCA confirmed its clinical utility for the prompt identification of SAE.

Conclusion

This study highlighted the enhanced predictive value of CCT in SAE detection within ICU settings. A novel nomogram incorporating CCT, PI, and S100B demonstrated robust discrimination, calibration, and clinical utility, solidifying it as a valuable tool for early SAE intervention.
Different decision-making in spine metastasis management among radiation oncologists and orthopedic surgeons: a Korean online survey study
Authors: Byun Hwa Kyung , Koom Woong Sub , Park Se-Jun , Kim Sang-Il , Kim Jin Ho , Kim Young-Hoon , Chang Bong-Soon , Ahn Yong Chan
Published: January 2024

Purpose

To understand the current practice of radiation oncologists (ROs) and orthopedic surgeons (OSs) regarding spine metastasis.

Methods

In 2022, an internet-based survey was conducted for ROs and OSs who treat spinal metastasis in Korea. Respondents were asked to choose the treatment option for two clinical scenarios. Scenario 1 involved a case displaying symptoms of leg weakness due to spinal cord compression and Scenario 2 involved a case with back pain due to pathologic compression fracture. The survey also included a question that required respondents to rank the importance of 11 clinical factors that affect treatment decisions.

Results

Forty-nine ROs and 30 OSs responded to the survey. There were significant differences in treatment choices between two groups for both scenarios (P = 0.001). In Scenario 1, more OSs chose surgical resection than ROs (43.3% vs. 16.7%), while more ROs chose radiotherapy than OSs (83.3% vs. 53.3%). In Scenario 2, a similar proportion of OSs and ROs chose radiotherapy (OSs, 71.4% vs. ROs, 67.3%), while more OSs opted for prophylactic fixation after radiotherapy than ROs (95.0% vs. 42.4%). The top three factors influencing treatment decisions were general performance status, life expectancy, and spinal instability for both ROs and OSs. In both Scenarios 1 and 2, the treatment decisions of ROs changed significantly when clinical conditions related to these top three factors were altered.

Conclusion

Although ROs and OSs share the same factors influencing treatment decisions for spinal metastases, notable differences exist in their actual treatment preferences, with ROs preferring radiotherapy and OSs opting for surgical resection. Multidisciplinary discussions may be necessary to reduce the gap in decision-making.
Random forest algorithm for predicting postoperative delirium in older patients
Authors: Sheng Weixuan , Tang Xianshi , Hu Xiaoyun , Liu Pengfei , Liu Lei , Miao Huihui , Wang Dongxin , Li Tianzuo
Published: January 2024

Objective

In this study, we were aimed to identify important variables via machine learning algorithms and predict postoperative delirium (POD) occurrence in older patients.

Methods

This study was to make the secondary analysis of data from a randomized controlled trial. The Boruta function was used to screen relevant basic characteristic variables. Four models including Logistic Regression (LR), K-Nearest Neighbor (KNN), the Classification and Regression Tree (CART), and Random Forest (RF) were established from the data set using repeated cross validation, hyper-parameter optimization, and Smote technique (Synthetic minority over-sampling technique, Smote), with the calculation of confusion matrix parameters and the plotting of Receiver operating characteristic curve (ROC), Precision recall curve (PRC), and partial dependence graph for further analysis and evaluation.

Results

The basic characteristic variables resulting from Boruta screening included grouping, preoperative Mini-Mental State Examination(MMSE), CHARLSON score, preoperative HCT, preoperative serum creatinine, intraoperative bleeding volume, intraoperative urine volume, anesthesia duration, operation duration, postoperative morphine dosage, intensive care unit (ICU) duration, tracheal intubation duration, and 7-day postoperative rest and move pain score (median and max; VAS-Rest-M, VAS-Move-M, VAS-Rest-Max, and VAS-Move-Max). And Random Forest (RF) showed the best performance in the testing set among the 4 models with Accuracy: 0.9878; Matthews correlation coefficient (MCC): 0.8763; Area under ROC curve (AUC-ROC): 1.0; Area under the PRC Curve (AUC-PRC): 1.0.

Conclusion

A high-performance algorithm was established and verified in this study demonstrating the degree of POD risk changes in perioperative elderly patients. And the major risk factors for the development of POD were CREA and VAS-Move-Max.
The pathogenesis of blepharospasm
Authors: Zhu Lixia , Meng Hongmei , Zhang Wuqiong , Xie Wenjing , Sun Huaiyu , Hou Shuai
Published: January 2024

Blepharospasm is a focal dystonia characterized by involuntary tetanic contractions of the orbicularis oculi muscle, which can lead to functional blindness and loss of independent living ability in severe cases. It usually occurs in adults, with a higher incidence rate in women than in men. The etiology and pathogenesis of this disease have not been elucidated to date, but it is traditionally believed to be related to the basal ganglia. Studies have also shown that this is related to the decreased activity of inhibitory neurons in the cerebral cortex caused by environmental factors and genetic predisposition. Increasingly, studies have focused on the imbalance in the regulation of neurotransmitters, including dopamine, serotonin, and acetylcholine, in blepharospasm. The onset of the disease is insidious, and the misdiagnosis rate is high based on history and clinical manifestations. This article reviews the etiology, epidemiological features, and pathogenesis of blepharospasm, to improve understanding of the disease by neurologists and ophthalmologists.
Neurosyphilis: insights into its pathogenesis, susceptibility, diagnosis, treatment, and prevention
Authors: Wu Sirui , Ye Fei , Wang Yuanfang , Li Dongdong
Published: January 2024

Background and aim

Invasion of the central nervous system by Treponema pallidum can occur at any stage of syphilis. In the event that T. pallidum is not cleared promptly, certain individuals may experience progression to neurosyphilis, which manifests as cognitive and behavioral abnormalities, limb paralysis, and potentially fatal outcomes. Early identification or prevention of neurosyphilis is therefore crucial. The aim of this paper is to conduct a critical and narrative review of the latest information focusing exclusively to the pathogenesis and clinical management of neurosyphilis.

Methodology

To compile this review, we have conducted electronic literature searches from the PubMed database relating to neurosyphilis. Priority was given to studies published from the past 10 years (from 2013 to 2023) and other studies if they were of significant importance (from 1985 to 2012), including whole genome sequencing results, cell structure of T. pallidum, history of genotyping, and other related topics. These studies are classic or reflect a developmental process.

Results

Neurosyphilis has garnered global attention, yet susceptibility to and the pathogenesis of this condition remain under investigation. Cerebrospinal fluid examination plays an important role in the diagnosis of neurosyphilis, but lacks the gold standard. Intravenous aqueous crystalline penicillin G continues to be the recommended therapeutic approach for neurosyphilis. Considering its sustained prominence, it is imperative to develop novel public health tactics in order to manage the resurgence of neurosyphilis.

Conclusion

This review gives an updated narrative description of neurosyphilis with special emphasis on its pathogenesis, susceptibility, diagnosis, treatment, and prevention.
Written discourse in diagnosis for acquired neurogenic communication disorders: current evidence and future directions
Authors: Kim Hana , Obermeyer Jessica , Wiley Robert W.
Published: January 2024

Purpose

We aimed to perform the first review of research focusing on written discourse performance in people with acquired neurogenic communication disorders. In studies from 2000 onward, we specifically sought to determine: (1) the differences between patient populations and control groups, (2) the differences between different patient populations, (3) longitudinal differences between patient populations, and (4) modality differences between spoken and written discourse performance.

Methods

We completed a thorough search on MEDLINE, Embase, Cochrane, APAPsycinfo, Web of Science, and Scopus databases. We identified studies that focus on written discourse performance in people with aphasia, primary progressive aphasia, mild cognitive impairment, and Alzheimer’s disease.

Results

Nineteen studies were identified from the review of literature, some of which addressed more than one of our review questions. Fifteen studies included a comparison between clinical populations and controls. Six studies compared different characteristics of patient populations. Three studies reported changes over time in progressive disorders. Six studies targeted different modalities of discourse.

Conclusion

Differences in linguistic features by patient populations are not yet clear due to the limited number of studies and different measures and tasks used across the studies. Nevertheless, there is substantial evidence of numerous linguistic features in acquired neurogenic communication disorders that depart from those of healthy controls. Compared to the controls, people with aphasia tend to produce fewer words, and syntactically simpler utterances compared to the controls. People with Alzheimer’s disease produce less information content, and this feature increases over time, as reported in longitudinal studies. Our review imparts additional information that written and spoken discourse provide unique insights into the cognitive and linguistic deficits experienced by people with aphasia, Alzheimer’s disease, mild cognitive impairment and primary progressive aphasia and provide targets for treatment to improve written communication in these groups.
Online group therapies for anxiety, obsessive-compulsive, and trauma-related disorders: a systematic review
Authors: Laurito Luana D. , dos Santos-Ribeiro Samara , Moreira-de-Oliveira Maria E. , Loureiro Carla P. , Hühne Verônica , Torres Bianca , de Faro Livi Ferreira Testoni , de Menezes Gabriela B. , Fontenelle Leonardo F.
Published: January 2024

Background

This systematic review examined the existing literature to determine the evidence supporting the efficacy of online group treatments for anxiety-, obsessive-compulsive- and trauma-related disorders (AOTDs).

Methods

A systematic review using the PUBMED, PsycInfo, Web of Science, and ClinicalTrials databases with no language, date, or study design filters was performed. The inclusion criteria comprised studies that examined individuals who had received a formal diagnosis of AOTDs, were aged 18 years or older, and had baseline and endpoint assessments of symptom severity using formal tools.

Results

Five studies on social anxiety disorder (SAD), four on post-traumatic stress disorder (PTSD) and one on tic disorders (TDs) were found. The studies were open-label (n = 2) and randomized controlled trials (RCTs) (n = 8), with five of the RCTs being non-inferiority trials. Most studies were conducted in the US and investigated psychological CBT based interventions via internet-based therapies (IBT: n = 4), video teleconferencing (VTC: n = 5) or a combination of both (n = 1). In SAD, IBT studies associated with a clinician assisted web-based forum (here termed “forum-enhanced” studies) were superior to waiting lists and not inferior to similar versions that were also “forum enhanced” but self-guided, “telephone enhanced” by a contact with a non-specialist, and “email enhanced” by a contact with a clinician individually. Studies involving VTC have shown comparable effectiveness to in-person interventions across some online group CBT based treatments for PTSD. Two open trials also demonstrated symptoms reductions of social anxiety and tics through VTC.

Conclusion

There is evidence supporting the effectiveness of online group treatments for SAD and PTSD. Further studies from different research groups may be needed to replicate the use of these and other forms of online treatments in individuals with SAD, PTSD, and other clinical populations, such as OCD, panic disorder, agoraphobia and specific phobias.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42023408491.
The California Cognitive Assessment Battery (CCAB)
Authors: Woods David , Pebler Peter , Johnson David K. , Herron Timothy , Hall Kat , Blank Mike , Geraci Kristi , Williams Garrett , Chok Jas , Lwi Sandy , Curran Brian , Schendel Krista , Spinelli Maria , Baldo Juliana
Published: January 2024

Introduction

We are developing the California Cognitive Assessment Battery (CCAB) to provide neuropsychological assessments to patients who lack test access due to cost, capacity, mobility, and transportation barriers.

Methods

The CCAB consists of 15 non-verbal and 17 verbal subtests normed for telemedical assessment. The CCAB runs on calibrated tablet computers over cellular or Wi-Fi connections either in a laboratory or in participants’ homes. Spoken instructions and verbal stimuli are delivered through headphones using naturalistic text-to-speech voices. Verbal responses are scored in real time and recorded and transcribed offline using consensus automatic speech recognition which combines the transcripts from seven commercial ASR engines to produce timestamped transcripts more accurate than those of any single ASR engine. The CCAB is designed for supervised self-administration using a web-browser application, the Examiner. The Examiner permits examiners to record observations, view subtest performance in real time, initiate video chats, and correct potential error conditions (e.g., training and performance failures, etc.,) for multiple participants concurrently.

Results

Here we describe (1) CCAB usability with older (ages 50 to 89) participants; (2) CCAB psychometric properties based on normative data from 415 older participants; (3) Comparisons of the results of at-home vs. in-lab CCAB testing; (4) We also present preliminary analyses of the effects of COVID-19 infection on performance. Mean z-scores averaged over CCAB subtests showed impaired performance of COVID+ compared to COVID- participants after factoring out the contributions of Age, Education, and Gender (AEG). However, inter-cohort differences were no longer significant when performance was analyzed with a comprehensive model that factored out the influences of additional pre-existing demographic factors that distinguished COVID+ and COVID- cohorts (e.g., vocabulary, depression, race, etc.,). In contrast, unlike AEG scores, comprehensive scores correlated significantly with the severity of COVID infection. (5) Finally, we found that scoring models influenced the classification of individual participants with Mild Cognitive Impairment (MCI, z-scores < –1.50) where the comprehensive model accounted for more than twice as much variance as the AEG model and reduced racial bias in MCI classification.

Discussion

The CCAB holds the promise of providing scalable laboratory-quality neurodiagnostic assessments to underserved urban, exurban, and rural populations.
Attentional bias to threat is modulated by stimulus content: an fNIRS study
Authors: Liu Hejun , Zhang Qihan , Elhai Jon D. , Montag Christian , Yang Haibo
Published: January 2024

People are evolutionarily predisposed to associate threat relevant stimuli with fear or aversiveness and show an attentional bias toward threat. Attentional bias modification (ABM) has been shown to reduce threat biases, while quantitative reviews assessing the effectiveness of bias modification yielded inconsistent results. The current study examined the relationship between the training effect of attentional bias to threat and the type of threatening stimuli. Twenty-two participants performed a modified dot-probe task while undergoing functional near-infrared spectroscopy (fNIRS) imaging. Results indicated that there was a strong pattern of attentional avoidance among individuals in an animal but not human threat condition. Furthermore, findings from fNIRS confirmed that the influence from type of threatening stimulus would be modulated by cortical activation patterns, especially in the ventrolateral prefrontal cortices (vlPFC) and angular gyrus. Overall, these results suggest that stimulus-specific may play a major role in personalization of specific psychological interventions.
Facing emotions: real-time fMRI-based neurofeedback using dynamic emotional faces to modulate amygdala activity
Authors: Watve Apurva , Haugg Amelie , Frei Nada , Koush Yury , Willinger David , Bruehl Annette Beatrix , Stämpfli Philipp , Scharnowski Frank , Sladky Ronald
Published: January 2024

Introduction

Maladaptive functioning of the amygdala has been associated with impaired emotion regulation in affective disorders. Recent advances in real-time fMRI neurofeedback have successfully demonstrated the modulation of amygdala activity in healthy and psychiatric populations. In contrast to an abstract feedback representation applied in standard neurofeedback designs, we proposed a novel neurofeedback paradigm using naturalistic stimuli like human emotional faces as the feedback display where change in the facial expression intensity (from neutral to happy or from fearful to neutral) was coupled with the participant’s ongoing bilateral amygdala activity.

Methods

The feasibility of this experimental approach was tested on 64 healthy participants who completed a single training session with four neurofeedback runs. Participants were assigned to one of the four experimental groups (n = 16 per group), i.e., happy-up, happy-down, fear-up, fear-down. Depending on the group assignment, they were either instructed to “try to make the face happier” by upregulating (happy-up) or downregulating (happy-down) the amygdala or to “try to make the face less fearful” by upregulating (fear-up) or downregulating (fear-down) the amygdala feedback signal.

Results

Linear mixed effect analyses revealed significant amygdala activity changes in the fear condition, specifically in the fear-down group with significant amygdala downregulation in the last two neurofeedback runs as compared to the first run. The happy-up and happy-down groups did not show significant amygdala activity changes over four runs. We did not observe significant improvement in the questionnaire scores and subsequent behavior. Furthermore, task-dependent effective connectivity changes between the amygdala, fusiform face area (FFA), and the medial orbitofrontal cortex (mOFC) were examined using dynamic causal modeling. The effective connectivity between FFA and the amygdala was significantly increased in the happy-up group (facilitatory effect) and decreased in the fear-down group. Notably, the amygdala was downregulated through an inhibitory mechanism mediated by mOFC during the first training run.

Discussion

In this feasibility study, we intended to address key neurofeedback processes like naturalistic facial stimuli, participant engagement in the task, bidirectional regulation, task congruence, and their influence on learning success. It demonstrated that such a versatile emotional face feedback paradigm can be tailored to target biased emotion processing in affective disorders.
Exploring retro-cue effects on visual working memory: insights from double-cue paradigm
Authors: Guo Ruiqiao , Wang Junbo , Fu Kai , Liu Qiang
Published: January 2024

In the realm of visual working memory research, the retro-cue paradigm helps us study retro-cue effects such as retro-cue benefit (RCB) and retro-cue cost (RCC). RCB reflects better performance with cued items, while RCC indicates poorer performance with uncued items. Despite consistent evidence for RCB, it’s still uncertain whether it remains when previously uncued items are cued afterward. Additionally, research findings have been inconsistent. This study combines prior experiments by controlling the proportion of cue types and the number of memory items. Besides, using a CDA index to assess the status of items after the cue appeared. Results showed better performance under the double-cue condition (involving two cues pointing inconsistently with only the second cue being valid) compared to the neutral-cue condition, and better performance under the single-cue condition compared to double-cue. EEG data revealed that after the appearance of the second cue in the double-cue condition, there was a significant increase in CDA wave amplitude compared to the single-cue condition. Behavior results suggests that RCB occurs under double-cue but to a lesser extent than the single-cue. And EEG outcomes indicates that individuals did not remove the uncued item from their visual working memory after the first cue. Instead, they kept it in a passive state and then shifted it to an active state after the appearance of the second cue.
Macrophage-related immune responses in inner ear: a potential therapeutic target for sensorineural hearing loss
Authors: Liu Yu-Chen , Xu Kai
Published: January 2024

Hearing loss is the most common sensory disorder in human beings. Cochlear sensory cells are the basis of hearing. Cochlear sensory cells suffer from various acute or chronic injuries, such as excessive sound stimulation, ototoxic drugs, and age-related degeneration. In response to these stresses, the cochlea develops an immune response. In recent years, studies have shown that the immune response of the inner ear has been regarded as one of the important pathological mechanisms of inner ear injury. Therapeutic interventions for inflammatory responses can effectively alleviate different types of inner ear injury. As the main immune cells in the inner ear, macrophages are involved in the process of inner ear injury caused by various exogenous factors. However, its specific role in the immune response of the inner ear is still unclear. This review focuses on discusses the dynamic changes of macrophages during different types of inner ear injury, and clarifies the potential role of macrophage-related immune response in inner ear injury.
Differential expression of slow and fast-repriming tetrodotoxin-sensitive sodium currents in dorsal root ganglion neurons
Authors: Tan Zhi-Yong , Wu Bin , Su Xiaolin , Zhou You , Ji Yong-Hua
Published: January 2024

Sodium channel Nav1.7 triggers the generation of nociceptive action potentials and is important in sending pain signals under physiological and pathological conditions. However, studying endogenous Nav1.7 currents has been confounded by co-expression of multiple sodium channel isoforms in dorsal root ganglion (DRG) neurons. In the current study, slow-repriming (SR) and fast-repriming (FR) tetrodotoxin-sensitive (TTX-S) currents were dissected electrophysiologically in small DRG neurons of both rats and mice. Three subgroups of small DRG neurons were identified based on the expression pattern of SR and FR TTX-S currents. A majority of rat neurons only expressed SR TTX-S currents, while a majority of mouse neurons expressed additional FR TTX-S currents. ProTx-II inhibited SR TTX-S currents with variable efficacy among DRG neurons. The expression of both types of TTX-S currents was higher in Isolectin B4-negative (IB4−) compared to Isolectin B4-positive (IB4+) neurons. Paclitaxel selectively increased SR TTX-S currents in IB4− neurons. In simulation experiments, the Nav1.7-expressing small DRG neuron displayed lower rheobase and higher frequency of action potentials upon threshold current injections compared to Nav1.6. The results suggested a successful dissection of endogenous Nav1.7 currents through electrophysiological manipulation that may provide a useful way to study the functional expression and pharmacology of endogenous Nav1.7 channels in DRG neurons.
The metabolic effect of Momordica charantia cannot be determined based on the available clinical evidence: a systematic review and meta-analysis of randomized clinical trials
Authors: Laczkó-Zöld Eszter , Csupor-Löffler Boglárka , Kolcsár Edina-Blanka , Ferenci Tamás , Nan Monica , Tóth Barbara , Csupor Dezső
Published: January 2024

Several studies have shown that Momordica charantia L. (Cucurbitaceae, bitter melon) has beneficial effects on metabolic syndrome (MetS) parameters and exerts antidiabetic, anti-hyperlipidemic, and anti-obesity activities. Since the findings of these studies are contradictory, the goal of this systematic review and meta-analysis was to assess the efficacy of bitter melon in the treatment of metabolic syndrome, with special emphasis on the anti-diabetic effect. Embase, Cochrane, PubMed, and Web of Science databases were searched for randomized controlled human trials (RCTs). The meta-analysis was reported according to the PRISMA statement. The primary outcomes of the review are body weight, BMI, fasting blood glucose, glycated hemoglobin A1c, systolic blood pressure, diastolic blood pressure, serum triglyceride, HDL, LDL, and total cholesterol levels. Nine studies were included in the meta-analysis with 414 patients in total and 4–16 weeks of follow-up. In case of the meta-analysis of change scores, no significant effect could be observed for bitter melon treatment over placebo on fasting blood glucose level (MD = −0.03; 95% CI: −0.38 to 0.31; I2 = 34%), HbA1c level (MD = −0.12; 95% CI: −0.35 to 0.11; I2 = 56%), HDL (MD = −0.04; 95% CI: −0.17 to 0.09; I2 = 66%), LDL (MD = −0.10; 95% CI: −0.28 to 0.08; I2 = 37%), total cholesterol (MD = −0.04; 95% CI: −0.17 to 0.09; I2 = 66%,), body weight (MD = −1.00; 95% CI: −2.59–0.59; I2 = 97%), BMI (MD = −0.42; 95% CI: −0.99–0.14; I2 = 95%), systolic blood pressure (MD = 1.01; 95% CI: −1.07–3.09; I2 = 0%) and diastolic blood pressure levels (MD = 0.24; 95% CI: −1.04–1.53; I2 = 0%). Momordica treatment was not associated with a notable change in ALT, AST, and creatinine levels compared to the placebo, which supports the safety of this plant. However, the power was overall low and the meta-analyzed studies were also too short to reliably detect long-term metabolic effects. This highlights the need for additional research into this plant in carefully planned clinical trials of longer duration.
Non-small cell lung cancer with MET amplification: review of epidemiology, associated disease characteristics, testing procedures, burden, and treatments
Authors: Yang Mo , Mandal Erin , Liu Frank X. , O’Hara Richard M. , Lesher Beth , Sanborn Rachel E.
Published: January 2024

Introduction

Mesenchymal-epidermal transition factor gene amplification (METamp) is being investigated as a therapeutic target in advanced non-small cell lung cancer (NSCLC). We reviewed the epidemiology and disease characteristics associated with primary and secondary METamp, as well as the testing procedures used to identify METamp, in advanced NSCLC. Economic and humanistic burdens, and the practice patterns and treatments under investigation for METamp were also examined.

Methods

Embase and Medline (via ProQuest), ClinicalTrials.gov, and Cochrane Controlled Register of Trials (2015–2022) were systematically searched. Conference abstracts were searched via Embase and conference proceedings websites (2020–2022). The review focused on evidence from the United States; global evidence was included for identified evidence gaps.

Results

The median rate of primary METamp in NSCLC across the references was 4.8% (n=4 studies) and of secondary METamp (epidermal growth factor receptor [EGFR]-mutant NSCLC) was 15% (n=10). Next-generation sequencing (NGS; n=12) and/or fluorescence in situ hybridization (FISH; n=11) were most frequently used in real-world studies and FISH testing most frequently used in clinical trials (n=9/10). METamp definitions varied among clinical trials using ISH/FISH testing (MET to chromosome 7 centromere ratio of ≥1.8 to ≥3.0; or gene copy number [GCN] ≥5 to ≥10) and among trials using NGS (tissue testing: GCN ≥6; liquid biopsy: MET copy number ≥2.1 to >5). Limited to no data were identified on the economic and humanistic burdens, and real-world treatment of METamp NSCLC. Promising preliminary results from trials enrolling patients with EGFR-mutated, METamp advanced NSCLC progressing on an EGFR-tyrosine kinase inhibitor (TKI) were observed with MET-TKIs (i.e., tepotinib, savolitinib, and capmatinib) in combination with EGFR-TKIs (i.e., gefitinib and osimertinib). For metastatic NSCLC and high-level METamp, monotherapy with capmatinib, crizotinib, and tepotinib are recommended in the 2022 published NSCLC NCCN Guidelines.

Conclusion

Primary METamp occurs in approximately 5% of NSCLC cases, and secondary METamp in approximately 15% of cases previously treated with an EGFR inhibitor. Variability in testing methods (including ISH/FISH and NGS) and definitions were observed. Several treatments are promising in treating METamp NSCLC. Additional studies evaluating the clinical, economic, and humanistic burdens are needed.
Human papillomavirus-associated head and neck squamous cell carcinoma cells rely on glycolysis and display reduced oxidative phosphorylation
Authors: Li Nora , Chamkha Imen , Verma Gaurav , Swoboda Sabine , Lindstedt Malin , Greiff Lennart , Elmér Eskil , Ehinger Johannes
Published: January 2024

Introduction

Head and neck squamous cell carcinoma (HNSCC) constitutes a heterogeneous group of cancers. Human papilloma virus (HPV) is associated with a subtype of HNSCC with a better response to treatment and more favorable prognosis. Mitochondrial function and metabolism vary depending on cancer type and can be related to tumor aggressiveness. This study aims to characterize the metabolism of HPV-positive and HPV-negative HNSCC cell lines.

Methods

Oxidative phosphorylation (OXPHOS) and glycolysis were assessed in intact cells, in four HNSCC cell lines using Seahorse XF Analyzer. OXPHOS was further studied in permeabilized cells using high-resolution respirometry in an Oroboros O2K. Metabolomic analysis was performed using mass spectroscopy.

Results

The HPV-negative cell lines were found to display a higher OXPHOS capacity and were also able to upregulate glycolysis when needed. The HPV-positive cell line had a higher basal glycolytic rate but lower spare OXPHOS capacity. These cells were also unable to increase respiration in response to succinate, unlike the HPV-negative cells. In the metabolomic analysis, the HPV-positive cells showed a higher kynurenine/tryptophan ratio.

Discussion

HPV-positive HNSCC preferred glycolysis to compensate for lower OXPHOS reserves, while the HPV-negative HNSCC displayed a more versatile metabolism, which might be related to increased tumor aggressiveness. The higher kynurenine/tryptophan ratio of HPV-positive HNSCC might be related to increased indoleamine 2,3-dioxygenase activity due to the carcinoma’s viral origin. This study highlights important metabolic differences between HPV-positive and HPV-negative cancers and suggests that future metabolic targets for cancer treatment should be individualized based on specific tumor metabolism.
Initial experiences of switching to faricimab for neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in an Asian population
Authors: Ibrahim Farah N. I. , Teo Kelvin Y. C. , Tan Tien-En , Chan Hiok Hong , Chandrasekaran Priya R. , Lee Shu-Yen , Tan Anna C. S. , Mathur Ranjana , Chan Choi Mun , Sim Shaun S. , Tan Gavin Siew Wei , Yeo Ian Y. S. , Cheung Chui Ming Gemmy
Published: January 2024

Purpose

To describe the early experiences of patients with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) whose treatment was switched to faricimab from other anti-vascular endothelial growth factor (VEGF) agents.

Methods

This is a prospective cohort of eyes with nAMD and PCV that were previously treated with anti-VEGF agents other than faricimab. We evaluated visual acuity (VA), central subfield thickness (CST), macular volume (MV), pigment epithelial detachment (PED) height, and choroidal thickness (CT) after one administration of faricimab. Where present, fluid was further evaluated according to intraretinal fluid (IRF), subretinal fluid (SRF), or within PED.

Results

Seventy-one eyes from 71 patients were included (45.07% PCV and 54.93% typical nAMD). The mean [standard deviation (± SD)] VA, CST, and MV improved from 0.50 logMAR (± 0.27 logMAR) to 0.46 logMAR (± 0.27 logMAR) (p = 0.20), 383.35 µm (± 111.24 µm) to 322.46 µm (± 103.89 µm (p < 0.01), and 9.40 mm3 (± 1.52 mm3) to 8.75 mm3 (± 1.17 mm3) (p < 0.01) from switch to post switch visit, respectively. The CT reduced from 167 µm (± 151 µm) to 149 µm (± 113 µm) (p < 0.01). There was also a significant reduction in the maximum PED height between visits [302.66 µm (± 217.97 µm)] and the post switch visit [236.66 µm (± 189.05 µm); p < 0.01]. This difference was greater in PEDs that were predominantly serous in nature. In the eyes with typical nAMD (n = 39), improvements were significant for CST, MV, CT, and PED. In the eyes with PCV (n = 32), only reductions in CT were statistically significant, while VA, CST, MV, and PED only showed numerically smaller improvements. One patient developed mild vitritis without vasculitis, which resolved with topical steroids with no sequelae.

Conclusions

In our case series of Asian nAMD patients, switching to faricimab was associated with a stable VA and meaningful anatomical improvements, particularly with typical nAMD subtypes.
“Death as the One Great Certainty”: ethical implications of children with irreversible cardiorespiratory failure and dependence on extracorporeal membrane oxygenation
Authors: Moynihan Katie M. , Taylor Lisa S. , Siegel Bryan , Nassar Natasha , Lelkes Efrat , Morrison Wynne
Published: January 2024

Introduction

Advances in medical technology have led to both clinical and philosophical challenges in defining death. Highly publicized cases have occurred when families or communities challenge a determination of death by the irreversible cessation of neurologic function (brain death). Parallels can be drawn in cases where an irreversible cessation of cardiopulmonary function exists, in which cases patients are supported by extracorporeal cardiopulmonary support, such as extracorporeal membrane oxygenation (ECMO).

Analysis

Two cases and an ethical analysis are presented which compare and contrast contested neurologic determinations of death and refusal to accept the irreversibility of an imminent death by cardiopulmonary standards. Ambiguities in the Uniform Determination of Death Act are highlighted, as it can be clear, when supported by ECMO, that a patient could have suffered the irreversible cessation of cardiopulmonary function yet still be alive (e.g., responsive and interactive). Parallel challenges with communication with families around the limits of medical technology are discussed.

Discussion

Cases that lead to conflict around the removal of technology considered not clinically beneficial are likely to increase. Reframing our goals when death is inevitable is important for both families and the medical team. Building relationships and trust between all parties will help families and teams navigate these situations. All parties may require support for moral distress. Suggested approaches are discussed.
Effects of a valved infant-bottle with ergonomic teat on the coordination of sucking, swallowing, and respiration in late-preterm infants. The Safe Oral Feeding randomized Trial
Authors: Cresi Francesco , Maggiora Elena , Capitanio Martina , Bovio Cecilia , Borla Federica , Cosimi Sara , Enrietti Desirèe , Faggiano Francesca , Loro Sara , Rovei Serena Maria , Runfola Federica , Scrufari Mariangela , Taglianti Michela Vigna , Vignali Federica , Peila Chiara , Coscia Alessandra
Published: January 2024

Introduction

Breastfeeding naturally enables the coordination of sucking, swallowing, and respiration patterns for safe feeding. When breastfeeding is not possible a feeding device that releases milk in response to intra-oral vacuum could potentially offer improved coordination of sucking, swallowing, and breathing patterns compared to conventional devices. The aim of the study is to evaluate the effect of a valved infant-bottle with an ergonomic teat compared to a standard infant-bottle.

Methods

This unblinded randomized controlled trial focused on late preterm infants fed by bottle for at least three meals over the day, admitted to the Neonatal Unit of Sant’Anna Hospital (Turin, Italy). Infants were randomized to be fed with a valved infant-bottle with an ergonomic teat (B-EXP arm) or with a standard infant-bottle (B-STD arm). Monitoring included a simultaneous synchronized recording of sucking, swallowing and respiration. The main outcome was the swallowing/breathing ratio.

Results

Forty infants (20 B-EXP arm; 20 B-STD arm) with a median gestational age of 35.0 weeks (IQR 35.0–36.0 weeks) completed the study. Four infants were censored for the presence of artifacts in the polygraphic traces. The median swallowing/breathing ratio was 1.11 (1.03–1.23) in the B-EXP arm and 1.75 (1.21–2.06) in the B-STD (p = .003). A lower frequency of swallowing events during the inspiratory phase of breathing was observed in B-EXP arm compared with B-STD arm (p = 0.013).

Discussion

The valved infant-bottle with an ergonomic teat improves the coordination of sucking-swallowing-respiration and limits the risk of inhalation reducing the frequency of swallowing during the inspiratory phase.
Characteristics of elderly diabetes patients: focus on clinical manifestation, pathogenic mechanism, and the role of traditional Chinese medicine
Authors: Yang Xiaofei , Xue Chongxiang , Chen Keyu , Gao Dongyang , Wang Han , Tang Cheng
Published: January 2024

Diabetes mellitus has become a major public health issue globally, putting an enormous burden on global health systems and people. Among all diseased groups, a considerable part of patients are elderly, while their clinical features, pathogenic processes, and medication regimens are different from patients of other ages. Despite the availability of multiple therapies and techniques, there are still numerous elderly diabetes patients suffering from poor blood glucose control, severe complications, and drug adverse effects, which negatively affect the quality of life in their golden years. Traditional Chinese Medicine (TCM) has been widely used in the treatment of diabetes for several decades, and its relevant clinical practice has confirmed that it has a satisfactory effect on alleviating clinical symptoms and mitigating the progression of complications. Chinese herbal medicine and its active components were used widely with obvious clinical advantages by multiple targets and signaling pathways. However, due to the particular features of elderly diabetes, few studies were conducted to explore Traditional Chinese Medicine intervention on elderly diabetic patients. This study reviews the research on clinical features, pathogenic processes, treatment principles, and TCM treatments, hoping to provide fresh perspectives on the prevention and management strategies for elderly diabetes.
Absence of the impurity-resonance spot at a Bi defect located near the Zn impurity in Bi2Sr2Ca(Cu1-xZnx)2O8+δ
Authors: Wang Zhaohui , Fan Shengtai , Li Han , Li Huazhou , Yang Huan , Wen Hai-Hu
Published: January 2024

Zn dopants to Cu sites in high-Tc cuprates strongly suppress superconductivity and act as impurities with a strong quasiparticle scattering resonance. Using the scanning tunneling microscope, we investigate the electronic structure in the atomic scale around Zn impurities in Bi2Sr2Ca(Cu1-xZnx)2O8+δ. The intense scattering resonance of the Zn impurity in the CuO2 layer strongly affects the measured local density of states of the BiO layer on the surface. The pattern of the bound state induced by a Zn impurity consists of a central spot at the Bi atom just above the Zn impurity and eight symmetric spots at the next nearest neighboring (NNN) and the third nearest neighboring (3NN) sites of Bi atoms. When the Bi atom above the NNN Cu atom is missing, the corresponding scattering spot is absent simultaneously. Our results indicate that the measured impurity-induced bound state pattern is strongly influenced by Bi atoms on the surface and therefore supports the “filter” theoretical model of the nonlocal interlayer tunneling effect from the CuO2 layer to the BiO layer on the surface. Our research provides extra information about the impurity-induced bound state by Zn impurities.