Subthalamic nucleus-language network connectivity predicts dopaminergic modulation of speech function in Parkinson's disease.

Speech impediments are a prominent yet understudied symptom of Parkinson's disease (PD). While the subthalamic nucleus (STN) is an established clinical target for treating motor symptoms, these interventions can lead to further worsening of speech. The interplay between dopaminergic medication, STN circuitry, and their downstream effects on speech in PD is not yet fully understood. Here, we investigate the effect of dopaminergic medication on STN circuitry and probe its association with speech and cognitive functions in PD patients. We found that changes in intrinsic functional connectivity of the STN were associated with alterations in speech functions in PD. Interestingly, this relationship was characterized by altered functional connectivity of the dorsolateral and ventromedial subdivisions of the STN with the language network. Crucially, medication-induced changes in functional connectivity between the STN's dorsolateral subdivision and key regions in the language network, including the left inferior frontal cortex and the left superior temporal gyrus, correlated with alterations on a standardized neuropsychological test requiring oral responses. This relation was not observed in the written version of the same test. Furthermore, changes in functional connectivity between STN and language regions predicted the medication's downstream effects on speech-related cognitive performance. These findings reveal a previously unidentified brain mechanism through which dopaminergic medication influences speech function in PD. Our study sheds light into the subcortical-cortical circuit mechanisms underlying impaired speech control in PD. The insights gained here could inform treatment strategies aimed at mitigating speech deficits in PD and enhancing the quality of life for affected individuals.

Genotypes and phenotypes of DNM1 encephalopathy.

BACKGROUND: Variants in the dynamin-1 (DNM1) gene typically cause synaptopathy, leading to developmental and epileptic encephalopathy (DEE). We aimed to determine the genotypic and phenotypic spectrum of DNM1 encephalopathy beyond DEE. METHODS: Electroclinical phenotyping and genotyping of patients with a DNM1 variant were conducted for patients undergoing next-generation sequencing at our centre, followed by a systematic review. RESULTS: Six patients with heterozygous DNM1 variants were identified in our cohort. Three had a typical DEE phenotype characterised by epileptic spasms, tonic seizures and severe-to-profound intellectual disability with pathogenic variants located in the GTPase or middle domain. The other three patients had atypical phenotypes of milder cognitive impairment and focal epilepsy. Genotypically, two patients with atypical phenotypes had variants located in the GTPase domain, while the third patient had a novel variant (p.M648R) in the linker region between pleckstrin homology and GTPase effector domains. The third patient with an atypical phenotype showed normal development until he developed febrile status epilepticus. Our systematic review on 55 reported cases revealed that those with GTPase or middle domain variants had more severe intellectual disability (p<0.001) and lower functional levels of ambulation (p=0.001) or speech and language (p<0.001) than the rest. CONCLUSION: DNM1-related phenotypes encompass a wide spectrum of epilepsy and neurodevelopmental disorders, with specific variants underlying different phenotypes.

Efficient Assessment of Tumor Vascular Shutdown by Photodynamic Therapy on Orthotopic Pancreatic Cancer Using High-Speed Wide-Field Waterproof Galvanometer Scanner Photoacoustic Microscopy.

To identify the vascular alteration by photodynamic therapy (PDT), the utilization of high-resolution, high-speed, and wide-field photoacoustic microscopy (PAM) has gained enormous interest. The rapid changes in vasculature during PDT treatment and monitoring of tumor tissue activation in the orthotopic pancreatic cancer model have received limited attention in previous studies. Here, a fully two-axes waterproof galvanometer scanner-based photoacoustic microscopy (WGS-PAM) system was developed for in vivo monitoring of dynamic variations in micro blood vessels due to PDT in an orthotopic pancreatic cancer mouse model. The photosensitizer (PS), Chlorin e6 (Ce6), was utilized to activate antitumor reactions in response to the irradiation of a 660 nm light source. Microvasculatures of angiogenesis tissue were visualized on a 40 mm2 area using the WGS-PAM system at 30 min intervals for 3 h after the PDT treatment. The decline in vascular intensity was observed at 24.5% along with a 32.4% reduction of the vascular density at 3 h post-PDT by the analysis of PAM images. The anti-vascularization effect was also identified with fluorescent imaging. Moreover, Ce6-PDT increased apoptotic and necrotic markers while decreasing vascular endothelial growth factor (VEGF) expression in MIA PaCa-2 and BxPC-3 pancreatic cancer cell lines. The approach of the WGS-PAM system shows the potential to investigate PDT effects on the mechanism of angiographic dynamics with high-resolution wide-field imaging modalities.

Development of a deviated focusing-based optical coherence microscope with a variable depth of focus for high-resolution imaging.

The aim of this study was to develop an optically deviated focusing-based variable depth-of-focus (DOF) oriented optical coherence microscopy (OCM) system to improve the DOF in high-resolution and precise focused imaging. In this study, an approach of varying beam diameter using deviated focusing was employed in the sample arm to enhance the DOF and to confirm precise focusing in OCM imaging. The optically deviated focusing technique was used to vary the focal point and DOF by altering the sample arm beam. The efficacy of the variable DOF imaging approach utilizing an optimized sample arm was confirmed by tissue-level imaging, where OCM images with varying DOF were obtained using deviated focusing. Experimentally confirmed lateral resolution of 2.19 µm was sufficient for the precise non-invasive visualization of abnormalities of fruit specimens. Thus, the proposed variable DOF-OCM system can be an alternative for precisely focused, high-resolution, and variable DOF imaging by improving the DOF in minimum lateral resolution variation.

Dopaminergic medication normalizes aberrant cognitive control circuit signalling in Parkinson's disease.

Dopaminergic medication is widely used to alleviate motor symptoms of Parkinson's disease, but these medications also impact cognition with significant variability across patients. It is hypothesized that dopaminergic medication impacts cognition and working memory in Parkinson's disease by modulating frontoparietal-basal ganglia cognitive control circuits, but little is known about the underlying causal signalling mechanisms and their relation to individual differences in response to dopaminergic medication. Here we use a novel state-space computational model with ultra-fast (490 ms resolution) functional MRI to investigate dynamic causal signalling in frontoparietal-basal ganglia circuits associated with working memory in 44 Parkinson's disease patients ON and OFF dopaminergic medication, as well as matched 36 healthy controls. Our analysis revealed aberrant causal signalling in frontoparietal-basal ganglia circuits in Parkinson's disease patients OFF medication. Importantly, aberrant signalling was normalized by dopaminergic medication and a novel quantitative distance measure predicted individual differences in cognitive change associated with medication in Parkinson's disease patients. These findings were specific to causal signalling measures, as no such effects were detected with conventional non-causal connectivity measures. Our analysis also identified a specific frontoparietal causal signalling pathway from right middle frontal gyrus to right posterior parietal cortex that is impaired in Parkinson's disease. Unlike in healthy controls, the strength of causal interactions in this pathway did not increase with working memory load and the strength of load-dependent causal weights was not related to individual differences in working memory task performance in Parkinson's disease patients OFF medication. However, dopaminergic medication in Parkinson's disease patients reinstated the relation with working memory performance. Our findings provide new insights into aberrant causal brain circuit dynamics during working memory and identify mechanisms by which dopaminergic medication normalizes cognitive control circuits.

Optical Coherence Tomography as a Non-Invasive Tool for Plant Material Characterization in Agriculture: A Review.

Characterizing plant material is crucial in terms of early disease detection, pest control, physiological assessments, and growth monitoring, which are essential parameters to increase production in agriculture and prevent unnecessary economic losses. The conventional methods employed to assess the aforementioned parameters have several limitations, such as invasive inspection, complexity, high time consumption, and costly features. In recent years, optical coherence tomography (OCT), which is an ultra-high resolution, non-invasive, and real-time unique image-based approach has been widely utilized as a significant and potential tool for assessing plant materials in numerous aspects. The obtained OCT cross-sections and volumetrics, as well as the amplitude signals of plant materials, have the capability to reveal vital information in both axial and lateral directions owing to the high resolution of the imaging system. This review discusses recent technological trends and advanced applications of OCT, which have been potentially adapted for numerous agricultural applications, such as non-invasive disease screening, optical signals-based growth speed detection, the structural analysis of plant materials, and microbiological discoveries. Therefore, this review offers a comprehensive exploration of recent advanced OCT technological approaches for agricultural applications, which provides insights into their potential to incorporate OCT technology into numerous industries.

A concept to detect a subgingival finish line using an intraoral optical coherence tomography system: A clinical report.

This clinical report introduces an approach for detecting the supragingival finish line by penetrating the teeth and gingival tissue using optical coherence tomography (OCT) technology. This approach was used in 3 patients who underwent tooth preparation with a subgingival finish line. Consequently, the subgingival finish line, typically challenging to discern clearly in intraoral scans, was identifiable in the OCT image.

Trends in Viral Respiratory Infections During COVID-19 Pandemic, South Korea.

We compared weekly positivity rates of 8 respiratory viruses in South Korea during 2010-2019 and 2020. The overall mean positivity rate for these viruses decreased from 54.7% in 2010-2019 to 39.1% in 2020. Pandemic control measures might have reduced the incidence of many, but not all, viral respiratory infections.

Integrated Quad-Scanner Strategy-Based Optical Coherence Tomography for the Whole-Directional Volumetric Imaging of a Sample.

Whole-directional scanning methodology is required to observe distinctive features of an entire physical structure with a three dimensional (3D) visualization. However, the implementation of whole-directional scanning is challenging for conventional optical coherence tomography (OCT), which scans a limited portion of the sample by utilizing unidirectional and bidirectional scanning methods. Therefore, in this paper an integrated quad-scanner (QS) strategy-based OCT method was implemented to obtain the whole-directional volumetry of a sample by employing four scanning arms installed around the sample. The simultaneous and sequential image acquisition capabilities are the conceptual key points of the proposed QS-OCT method, and were implemented using four precisely aligned scanning arms and applied in a complementary way according to the experimental criteria. To assess the feasibility of obtaining whole-directional morphological structures, a roll of Scotch tape, an ex vivo mouse heart, and kidney specimens were imaged and independently obtained tissue images at different directions were delicately merged to compose the 3D volume data set. The results revealed the potential merits of QS-OCT-based whole-directional imaging, which can be a favorable inspection method for various discoveries that require the dynamic coordinates of the whole physical structure.

Non-Invasive Optical Coherence Tomography Data-Based Quantitative Algorithm for the Assessment of Residual Adhesive on Bracket-Removed Dental Surface.

The aim of this study was to quantitatively assess the residual adhesive on orthodontic ceramic bracket-removed dental surface. In orthodontic process, ceramic bracket was repeated debonding physically, then the adhesive remained on the dental surface. The residual adhesive caused a lack of adhesive strength between dental and ceramic bracket. Since commonly used adhesive in orthodontics is translucent, residual adhesive is hard to be detected with conventional microscopes. Therefore, 1310 nm center wavelength swept-source OCT system based on laboratory customized image processing algorithm was used for the precise detection of residual adhesive on tooth surface. The algorithm separates residual adhesive from dental surface by comparing the height of adjacent B-scan images, while providing color-scaled images emphasizing the thickness information of residual adhesive. Finally, the acquired results were compared with microscopic and adhesive remnant index scoring gold standards, while the comparison confirmed the potential merits and the improvements of the proposed method over gold standards.

Fully waterproof two-axis galvanometer scanner for enhanced wide-field optical-resolution photoacoustic microscopy.

A large field-of-view and fast scanning of photoacoustic microscopy (PAM) relatively have been difficult to obtain due to the water-drowned structure of the system for the transmission of ultrasonic signals. Researchers have widely studied the achievement of a waterproof scanner for dynamic biological applications with a high-resolution and high signal-to-noise ratio. This Letter reports a novel, to the best of our knowledge, waterproof galvanometer scanner-based PAM system with a successfully attainable ${9.0}\;{\rm mm} \times {14.5}\;{\rm mm}$9.0mm×14.5mm scan region, amplitude scan rate of 40 kHz, and spatial resolution of 4.9 µm. The in vivo characterization of a mouse brain in intact-skull microvascular visualization demonstrated its capability in biomedical imaging and is anticipated to be an effective technique for various preclinical and clinical studies.

The expanded endoscopic endonasal approach for suprasellar meningiomas: long-term outcomes in a single-center series of 27 patients.

BACKGROUND: The endoscopic endonasal approach (EEA) has become increasingly employed in the treatment of suprasellar meningiomas. These tumors often cause visual symptoms due to compression of the anterior visual pathway. We aimed to examine long-term visual outcomes after EEA for optic nerve decompression and resection of suprasellar meningioma at our center, and to identify preoperative factors predictive of postoperative visual improvement. METHODS: We performed a retrospective cohort study on 27 patients who underwent the EEA for resection of meningiomas extending into the suprasellar cistern and decompression of anterior visual pathway between January 1, 2005, and March 1, 2019. RESULTS: We treated 8 male and 19 female patients, with a mean follow-up of 7.6 years. The mean age of our patients at initial presentation was 60.1 years. Eighteen patients (66.7%) presented with visual acuity deficits, and 12 (44.4%) patients presented with visual field deficits. Postoperatively, 11 patients had improved visual acuity, 6 had stable visual acuity, and 1 patient had slow and progressive decline of visual acuity; 5 patients had improved visual field, 6 had stable visual field, and 1 patient had slow and progressive decline in visual field. Patients less likely to have postoperative improvement of visual acuity were those with longer than 6-month duration of visual symptoms (P = 0.024*) as well as patients with the presence of a relative afferent pupillary defect (RAPD) (P = 0.023*). CONCLUSION: The EEA can achieve good visual outcomes in patients harboring suprasellar meningiomas. Symptom duration of less than 6 months and lack of a RAPD were positive predictors of postoperative visual acuity.

The Serial Interval of COVID-19 in Korea: 1,567 Pairs of Symptomatic Cases from Contact Tracing.

Although coronavirus disease 2019 (COVID-19) is an ongoing pandemic, the mean serial interval was measured differently across nations. Through the Korean national COVID-19 contact tracing system, we were able to investigate personal contacts in all symptomatic cases in Korea from January 20 to August 3, 2020. The mean serial interval was calculated by the duration between the symptom onset of the infector and infectee, and became shorter after the case definition changed to include not-imported cases in Korea on February 20, 2020. The mean serial interval before and after this fifth case definition was 6.12 and 3.93 days based on the infectors' symptom onset date, respectively, and 4.02 days in total with the median of 3 days. Older age and women lead to longer serial intervals.

Optical Interferometric Fringe Pattern-Incorporated Spectrum Calibration Technique for Enhanced Sensitivity of Spectral Domain Optical Coherence Tomography.

Depth-visualizing sensitivity can be degraded due to imperfect optical alignment and non-equidistant distribution of optical signals in the pixel array, which requires a measurement of the re-sampling process. To enhance this depth-visualizing sensitivity, reference and sample arm-channeled spectra corresponding to different depths using mirrors were obtained to calibrate the spectrum sampling prior to Fourier transformation. During the process, eight interferogram patterns corresponding to point spread function (PSF) signals at eight optical path length differences were acquired. To calibrate the spectrum, generated intensity points of the original interferogram were re-indexed towards a maximum intensity range, and these interferogram re-indexing points were employed to generate a new lookup table. The entire software-based process consists of eight consecutive steps. Experimental results revealed that the proposed method can achieve images with a high depth-visualizing sensitivity. Furthermore, the results validate the proposed method as a rapidly performable spectral calibration technique, and the real-time images acquired using our technique confirm the simplicity and applicability of the method to existing optical coherence tomography (OCT) systems. The sensitivity roll-off prior to the spectral calibration was measured as 28 dB and it was halved after the calibration process.

An increased rate of longitudinal cognitive decline is observed in Parkinson's disease patients with low CSF Aß42 and an APOE ε4 allele.

OBJECTIVE: Low concentrations of cerebrospinal fluid (CSF) amyloid-beta (Aß-42) are associated with increased risk of cognitive decline in Parkinson's disease (PD). We sought to determine whether APOE genotype modifies the rate of cognitive decline in PD patients with low CSF Aß-42 compared to patients with normal levels. METHODS: The Parkinson's Progression Markers Initiative is a longitudinal, ongoing study of de novo PD participants, which includes APOE genotyping, CSF Aß-42 determinations, and neuropsychological assessments. We used linear mixed effects models in three PD groups (PD participants with low CSF Aß at baseline, PD participants with normal CSF Aß, and both groups combined). Having at least one copy of the APOE ɛ4 allele, time, and the interaction of APOE ɛ4 and time were predictor variables for cognitive change, adjusting for age, gender and education. RESULTS: 423 de novo PD participants were followed up to 5 years with annual cognitive assessments. 103 participants had low baseline CSF Aß-42 (39 APOE ε4+, 64 APOE ε4-). Compared to participants with normal CSF Aß-42, those with low CSF Aß-42 declined faster on most cognitive tests. Within the low CSF Aß-42 group, APOE ε4+ participants had faster rates of decline on the Montreal Cognitive Assessment (primary outcome; 0.57 points annual decline, p = .005; 5-year standardized change of 1.2) and the Symbol Digit Modalities Test (1.4 points annual decline, p = .002; 5-year standardized change of 0.72). DISCUSSION: PD patients with low CSF Aß-42 and APOE ε4+ showed a higher rate of cognitive decline early in the disease. Tests of global cognition (Montreal Cognitive Assessment) and processing speed (Symbol Digit Modalities Test) were the most sensitive to early cognitive decline. Results suggest that CSF Aß-42 and APOE ε4 might interact to promote early cognitive changes in PD patients.

In Situ Characterization of Micro-Vibration in Natural Latex Membrane Resembling Tympanic Membrane Functionally Using Optical Doppler Tomography.

Non-invasive characterization of micro-vibrations in the tympanic membrane (TM) excited by external sound waves is considered as a promising and essential diagnosis in modern otolaryngology. To verify the possibility of measuring and discriminating the vibrating pattern of TM, here we describe a micro-vibration measurement method of latex membrane resembling the TM. The measurements are obtained with an externally generated audio stimuli of 2.0, 2.2, 2.8, 3.1 and 3.2 kHz, and their respective vibrations based tomographic, volumetric and quantitative evaluations were acquired using optical Doppler tomography (ODT). The micro oscillations and structural changes which occurred due to diverse frequencies are measured with sufficient accuracy using a highly sensitive ODT system implied phase subtraction method. The obtained results demonstrated the capability of measuring and analyzing the complex varying micro-vibration of the membrane according to implied sound frequency.

A phase II trial of the pan-HER inhibitor poziotinib, in patients with HER2-positive metastatic breast cancer who had received at least two prior HER2-directed regimens: results of the NOV120101-203 trial.

Although the introduction of human epidermal growth factor receptor (HER)2-directed therapy including trastuzumab, pertuzumab, lapatinib and trastuzumab emtansine (T-DM1) in the treatment of HER2-positive metastatic breast cancers (mBCs) favorably changed the natural history of this disease, most cases of HER2-positive mBC will eventually progress. Poziotinib is an oral pan-HER kinase inhibitor showing potent activity through irreversible inhibition of these kinases. This open-label, multicenter phase II study was designed to evaluate the efficacy and safety of poziotinib monotherapy in patients with HER2-positive mBC who had progressed from more than two HER2-directed therapies. Patients received 12 mg poziotinib once daily on a 14-day on/7-day off schedule. Progression-free survival (PFS) as the primary endpoint, the objective response rate (ORR), overall survival (OS) and safety were evaluated. From April 2015 to February 2016, 106 patients were enrolled in the trial from seven institutes in South Korea. They had a median age of 51 years (range 30-76) and had received a median of four prior therapies including two HER2-directed therapies for advanced or metastatic cancers. The median follow-up duration was 12 months. The median PFS was 4.04 months (95% confidence interval [CI], 2.94-4.40 months), and median overall survival has not been reached. The most common treatment-related adverse events were (total/grade ≥3) diarrhea (96.23%/14.15%), stomatitis (92.45%/12.26%) and rashes (63.21%/3.77%). Poziotinib showed meaningful activity in these heavily treated HER2-positive mBCs. Diarrhea and stomatitis were the major toxicities. Biomarker studies analyzed are warranted to support further evaluation of this treatment in such cases.

Non-Destructive Classification of Diversely Stained Capsicum annuum Seed Specimens of Different Cultivars Using Near-Infrared Imaging Based Optical Intensity Detection.

The non-destructive classification of plant materials using optical inspection techniques has been gaining much recent attention in the field of agriculture research. Among them, a near-infrared (NIR) imaging method called optical coherence tomography (OCT) has become a well-known agricultural inspection tool since the last decade. Here we investigated the non-destructive identification capability of OCT to classify diversely stained (with various staining agents) Capsicum annuum seed specimens of different cultivars. A swept source (SS-OCT) system with a spectral band of 1310 nm was used to image unstained control C. annuum seeds along with diversely stained Capsicum seeds, belonging to different cultivar varieties, such as C. annuum cv. PR Ppareum, C. annuum cv. PR Yeol, and C. annuum cv. Asia Jeombo. The obtained cross-sectional images were further analyzed for the changes in the intensity of back-scattered light (resulting due to dye pigment material and internal morphological variations) using a depth scan profiling technique to identify the difference among each seed category. The graphically acquired depth scan profiling results revealed that the control specimens exhibit less back-scattered light intensity in depth scan profiles when compared to the stained seed specimens. Furthermore, a significant back-scattered light intensity difference among each different cultivar group can be identified as well. Thus, the potential capability of OCT based depth scan profiling technique for non-destructive classification of diversely stained C. annum seed specimens of different cultivars can be sufficiently confirmed through the proposed scheme. Hence, when compared to conventional seed sorting techniques, OCT can offer multipurpose advantages by performing sorting of seeds in respective to the dye staining and provides internal structural images non-destructively.

The learning curve in diagnosing acute appendicitis with emergency sonography among novice emergency medicine residents.

PURPOSE: Ultrasonography (US) has good accuracy for diagnosing appendicitis when it is performed by emergency physicians. This study aimed to determine the amount of experience that is required to achieve competency in this field. METHODS: Three novice emergency medicine residents completed a 1-day training course regarding the US diagnosis of appendicitis. Then, they performed appendix US in the emergency department on patients complaining of right lower quadrant pain. All included patients also underwent computed tomography or US performed by a board-certified radiologist, to confirm the emergency US diagnosis. The agreement between the diagnoses of novices and experts was evaluated. RESULTS: A total of 266 patients were included, and the overall Cohen's kappa coefficient was 0.77 (95% confidence interval [CI]: 0.69-0.84). The kappa value of first 20 cases was 0.49 (95% CI: 0.27-0.71). It increased rapidly during evaluation of the first 20 cases. After the first 20 cases, the kappa coefficient was 0.84 (95% CI: 0.77-0.92). The sensitivity and specificity values for the first 20 cases were 64.3% (95% CI: 77.6%-90.7%) and 84.4% (95% CI: 85.4%-95.4%), respectively. After the first 20 cases, the sensitivity and specificity values increased to 90.9% (95% CI: 83.4%-95.8%) and 93.5% (95% CI: 87.0%-97.3%), respectively. CONCLUSIONS: A minimum of 20 cases are needed to achieve competency in emergency US diagnosis of acute appendicitis.

Optical coherence tomography-integrated, wearable (backpack-type), compact diagnostic imaging modality for in situ leaf quality assessment: publisher's note.

This note points out additional funding that was not added to Appl. Opt.56, D108 (2017)APOPAI0003-693510.1364/AO.56.00D108.