Acoustic Character Governing Variation in Normal, Benign, and Malignant Voices.

INTRODUCTION: Benign and malignant vocal fold lesions are growths that occur on the vocal folds. However, the treatments for these two types of lesions differ significantly. Therefore, it is imperative to use a multidisciplinary approach to properly recognize suspicious lesions. This study aims to determine the important acoustic characteristics specific to benign and malignant vocal fold lesions. METHODS: The acoustic model of voice quality was utilized to measure various acoustic parameters in 157 participants, including individuals with normal, benign, and malignant conditions. The study comprised 62 female and 95 male participants (43 ± 10 years). Voice samples were collected at the Shanghai Eye, Ear, Nose and Throat Hospital between May 2020 and July 2021.The acoustic variables of the participants were analyzed using Principal Component Analysis to present important acoustic characteristics that are specific to normal vocal folds, benign vocal fold lesions, and malignant vocal fold lesions. The similarities and differences in acoustic factors were also studied for benign conditions including Reinke's edema, polyps, cysts, and leukoplakia. RESULTS: Using the Principal Component Analysis method, the components that accounted for the variation in the data were identified, highlighting acoustic characteristics in the normal, benign, and malignant groups. The analysis indicated that coefficients of variation in root mean square energy were observed solely within the normal group. Coefficients of variation in pitch were found to be significant only in benign voices, while higher formant frequencies and their variability were identified as contributors to the acoustic variance within the malignant group. The presence of formant dispersion as a weighted factor in Principal Component Analysis was exclusively noted in individuals with Reinke's edema. The amplitude ratio between subharmonics and harmonics and its coefficients of variation were evident exclusively in the polyps group. In the case of voices with cysts, both pitch and coefficients of variation for formant dispersion were observed to contribute to variations. Additionally, higher formant frequencies and their coefficients of variation played a role in the acoustic variance among voices of patients with leukoplakia. CONCLUSION: Experimental evidence demonstrates the utility of the Principal Component Analysis method in the identification of vibrational alterations in the acoustic characteristics of voice affected by lesions. Furthermore, the Principal Component Analysis analysis has highlighted underlying acoustic differences between various conditions such as Reinke's edema, polyps, cysts, and leukoplakia. These findings can be used in the future to develop an automated malignant voice analysis algorithm, which will facilitate timely intervention and management of vocal fold conditions.

Utility of Diffusion Tensor Imaging (DTI) for Prognosis and Management of Cervical Spondylotic Myelopathy: a PRISMA Review.

OBJECTIVE: As advances are made in quantitative magnetic resonance imaging, specifically diffusion tensor imaging, researchers have investigated its potential to serve as a biomarker of disease or prognosticator for post-operative recovery in the management of cervical spondylotic myelopathy. Here, we narratively review the current state of the emerging literature, describing areas of consensus and disagreement. METHODS: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we queried two large databases for original manuscripts published in English and systematically produced a narrative review of the use of diffusion tensor imaging in the management of cervical spondylotic myelopathy. RESULTS: Of the 437 manuscripts initially returned in our query, 29 met the final inclusion criteria, and data were extracted regarding diffusion tensor imaging indices and their relationships with clinical outcomes following surgery. Preoperative fractional anisotropy was most commonly found to correlate closely with post-surgical clinical outcomes, though results were mixed. CONCLUSION: Preoperative fractional anisotropy most frequently and best correlates with functional outcomes following surgery for cervical spondylotic myelopathy, according to a review of the current literature. The findings were not universal and at times contradictory, highlighting the need for high-quality future investigations to better define the utility of diffusion tensor imaging in spinal disease.

4-hydroxy-2-oxoglutarate metabolism in a mouse model of Primary Hyperoxaluria Type 3.

Primary Hyperoxaluria Type 3 (PH3) results from 4-hydroxy-2-oxoglutarate (HOG) aldolase (HOGA) deficiency, which causes an increase in endogenous oxalate synthesis leading to calcium oxalate kidney stone disease. The mechanisms underlying HOG metabolism and increased oxalate synthesis in PH3 are not well understood. We used a Hoga1 knock-out mouse model of PH3 to investigate two aspects of HOG metabolism: reduction to dihydroxyglutarate (DHG), a pathway that may limit oxalate synthesis in PH3, and metabolism to glyoxylate, which is a direct precursor to oxalate. The metabolism of HOG to DHG was highest in liver and kidney cortical tissue, enhanced in the cytosolic compartment of the liver, and preferred NADPH as a cofactor. In the absence of HOGA, HOG to glyoxylate aldolase activity was highest in liver mitoplasts, with no activity present in brain tissue lysates. These findings will assist in the identification of enzymes responsible for the metabolism of HOG to DHG and glyoxylate, which may lead to novel therapeutic approaches to limit oxalate synthesis in those afflicted with PH3.

MRI-Based Prediction of Clinical Improvement Following Ventricular Shunt Placement for Normal Pressure Hydrocephalus (NPH): Development and Evaluation of an Integrated Multi-Sequence Machine Learning Algorithm.

BACKGROUND AND PURPOSE: Symptoms of normal pressure hydrocephalus (NPH) are sometimes refractory to shunt placement, with limited ability to predict improvement for individual patients. We evaluated an MRI-based artificial intelligence method to predict post-shunt NPH symptom improvement. MATERIALS AND METHODS: NPH patients who underwent magnetic resonance imaging (MRI) prior to shunt placement at a single center (2014-2021) were identified. Twelve-month post-shunt improvement in modified Rankin Scale (mRS), incontinence, gait, and cognition were retrospectively abstracted from clinical documentation. 3D deep residual neural networks were built on skull stripped T2-weighted and fluid attenuated inversion recovery (FLAIR) images. Predictions based on both sequences were fused by additional network layers. Patients from 2014-2019 were used for parameter optimization, while those from 2020-2021 were used for testing. Models were validated on an external validation dataset from a second institution (n=33). RESULTS: Of 249 patients, n=201 and n=185 were included in the T2-based and FLAIR-based models according to imaging availability. The combination of T2-weighted and FLAIR sequences offered the best performance in mRS and gait improvement predictions relative to models trained on imaging acquired using only one sequence, with AUROC values of 0.7395 [0.5765-0.9024] for mRS and 0.8816 [0.8030-0.9602] for gait. For urinary incontinence and cognition, combined model performances on predicting outcomes were similar to FLAIR-only performance, with AUROC values of 0.7874 [0.6845-0.8903] and 0.7230 [0.5600-0.8859]. CONCLUSIONS: Application of a combined algorithm using both T2-weighted and FLAIR sequences offered the best image-based prediction of post-shunt symptom improvement, particularly for gait and overall function in terms of mRS. ABBREVIATIONS: NPH = normal pressure hydrocephalus; iNPH = idiopathic NPH; sNPH = secondary NPH; AI = artificial intelligence; ML = machine learning; CSF = cerebrospinal fluid; AUROC = area under the receiver operating characteristic; FLAIR = fluid attenuated inversion recovery; BMI = body mass index; CCI = Charlson Comorbidity Index; SD = standard deviation; IQR = interquartile range.

Microbubble Contrast-Enhanced Transcutaneous Ultrasound Enables Real-Time Spinal Cord Perfusion Monitoring Following Posterior Cervical Decompression.

BACKGROUND: Ultrasound imaging is inexpensive, portable, and widely available. The development of a real-time transcutaneous spinal cord perfusion monitoring system would allow more precise targeting of mean arterial pressure goals following acute spinal cord injury (SCI). There has been no prior demonstration of successful real-time cord perfusion monitoring in humans. METHODS: Four adult patients who had undergone posterior cervical decompression and instrumentation at a single center were enrolled into this prospective feasibility study. All participants had undergone cervical laminectomies spanning ≥2 contiguous levels ≥2 months prior to inclusion with no history of SCI. The first 2 underwent transcutaneous ultrasound without contrast and the second 2 underwent contrast-enhanced ultrasound (CEUS) with intravenously injected microbubble contrast. RESULTS: Using noncontrast ultrasound with or without Doppler (n = 2), the dura, spinal cord, and vertebral bodies were apparent however ultrasonography was insufficient to discern intramedullary perfusion or clear white-gray matter differentiation. With application of microbubble contrast (n = 2), it was possible to quantify differential spinal cord perfusion within and between cross-sectional regions of the cord. Further, it was possible to quantify spinal cord hemodynamic perfusion using CEUS by measuring peak signal intensity and the time to peak signal intensity after microbubble contrast injection. Time-intensity curves were generated and area under the curves were calculated as a marker of tissue perfusion. CONCLUSIONS: CEUS is a viable platform for monitoring real-time cord perfusion in patients who have undergone prior cervical laminectomies. Further development has the potential to change clinical management acute SCI by tailoring treatments to measured tissue perfusion parameters.

Multidisciplinary surgical considerations for en bloc resection of sacral chordoma: review of recent advances and a contemporary single-center series.

OBJECTIVE: Contemporary management of sacral chordomas requires maximizing the potential for recurrence-free and overall survival while minimizing treatment morbidity. En bloc resection can be performed at various levels of the sacrum, with tumor location and volume ultimately dictating the necessary extent of resection and subsequent tissue reconstruction. Because tumor resection involving the upper sacrum may be quite destabilizing, other pertinent considerations relate to instrumentation and subsequent tissue reconstruction. The primary aim of this study was to survey the surgical approaches used for managing primary sacral chordoma according to location of lumbosacral spine involvement, including a narrative review of the literature and examination of the authors' institutional case series. METHODS: The authors performed a narrative review of pertinent literature regarding reconstruction and complication avoidance techniques following en bloc resection of primary sacral tumors, supplemented by a contemporary series of 11 cases from their cohort. Relevant surgical anatomy, advances in instrumentation and reconstruction techniques, intraoperative imaging and navigation, soft-tissue reconstruction, and wound complication avoidance are also discussed. RESULTS: The review of the literature identified several surgical approaches used for management of primary sacral chordoma localized to low sacral levels (mid-S2 and below), high sacral levels (involving upper S2 and above), and high sacral levels with lumbar involvement. In the contemporary case series, the majority of cases (8/11) presented as low sacral tumors that did not require instrumentation. A minority required more extensive instrumentation and reconstruction, with 2 tumors involving upper S2 and/or S1 levels and 1 tumor extending into the lower lumbar spine. En bloc resection was successfully achieved in 10 of 11 cases, with a colostomy required in 2 cases due to rectal involvement. All 11 cases underwent musculocutaneous flap wound closure by plastic surgery, with none experiencing wound complications requiring revision. CONCLUSIONS: The modern management of sacral chordoma involves a multidisciplinary team of surgeons and intraoperative technologies to minimize surgical morbidity while optimizing oncological outcomes through en bloc resection. Most cases present with lower sacral tumors not requiring instrumentation, but stabilizing instrumentation and lumbosacral reconstruction are often required in upper sacral and lumbosacral cases. Among efforts to minimize wound-related complications, musculocutaneous flap closure stands out as an evidence-based measure that may mitigate risk.

Leveraging digital assets: lessons from a 14-year-old isotope tracer course for professional scientists.

The COVID-19 pandemic and subsequent policies (e.g., social distancing, travel restrictions) challenged both organizers for and attendees of programs typically held in-person. Many scientific training programs quickly adapted to virtual formats by incorporating digital assets developed for virtual learning and remote social engagement. At the outset, the value of continuing digital elements with future in-person events was unclear. To examine how virtual resources supported heterogeneous professional training programs, we reviewed survey data for a 14-year-old training program for scientific professionals titled Isotope Tracers in Metabolic Research: Principles and Practice of Kinetic Analysis. We found a positive relationship between survey satisfaction and the post-pandemic, in-person program that included digital assets held in 2022 when compared to pre-pandemic in-person programs. To better understand the post-pandemic program satisfaction, we assessed the 2021 virtual course format and survey data. We found that although there was a desire to return to in-person programs, the digital assets and approaches were valued. In examining the individual programmatic elements in the 2022 in-person course, there was better "value and understandability" of lectures over previous in-person years. These findings highlight how incorporating new digital engagement strategies for professional development benefit even the most established programs in supporting heterogeneous learners.

Efficacy and safety of azacitidine in pediatric patients with newly diagnosed advanced myelodysplastic syndromes before hematopoietic stem cell transplantation in the AZA-JMML-001 trial.

Here we report efficacy, pharmacokinetics, and safety data obtained in treatment-naive, pediatric patients with newly diagnosed advanced MDS receiving azacitidine in the AZA-JMML-001 study. The primary endpoint was response rate (proportion of patients with complete response [CR], partial response [PR], or marrow CR, sustained for ≥4 weeks). Of the 10 patients enrolled, one had an unconfirmed marrow CR and none had confirmed responses after three cycles; the study was therefore closed after stage 1. Azacitidine was well tolerated. The lack of efficacy of azacitidine in pediatric patients with newly diagnosed advanced MDS highlights the need for effective new treatments in these patients.

Animal model considerations for chordoma research: reproducing the tumor microenvironment in vivo with humanized mice.

Animal models have been commonly used in immunotherapy research to study the cell response to external agents and to assess the effectiveness and safety of new therapies. Over the past few decades, immunocompromised (also called immunodeficient) mice allowed researchers to grow human tumor cells without the impact of the host's immune system. However, while this model is very valuable to understand the tumor biology and to understand the underlying mechanism of immunotherapy, the results may not always directly translate to humans. The tumor microenvironment has significant implications for tumor engraftment, growth, invasion, etc., and the immune system plays a critical role in shaping the tumor microenvironment. Human immunocompetent mice, also named humanized mice, are engineered mice that possess functional human immune cells. This in vivo model can be used to effectively study the effect of the human immune system to a human implanted tumor. Moreover, this can effectively mimic the response to treatment. This section is an overview of the current understanding of the different humanized mice that could be utilized to mimic the tumor microenvironment in chordoma.

Clinical criteria for filum terminale resection in occult tethered cord syndrome.

OBJECTIVE: Tethered cord syndrome (TCS) comprises three symptom categories: back/leg pain, bowel/bladder, and neurological complaints. MRI typically reveals a low-lying conus medullaris, filum terminale (FT) pathology, or lumbosacral abnormalities. FT resection is established in TCS but not in radiologically occult TCS (OTCS). This study aims to identify patients with OTCS who are likely to benefit from FT resection. METHODS: The authors recruited 149 patients with OTCS (31 pediatric, 118 adult) treated with FT resection-including only cases with progressive TCS, negative spine MRI, and no concurrent neurological/urological conditions. A comprehensive questionnaire collected patient self-reported symptoms and clinical findings at the preoperative and at 3- and 12-month follow-up examinations. Based on questionnaire data, the authors extracted a 15-item symptoms and findings scale to represent the three TCS symptom categories, assigning 1 point for each item present. RESULTS: OTCS presents without radicular/segmental sensorimotor findings, but with leg/back pain and conus dysfunction, in addition to leg fatigue and spasticity; the latter indicating an upper motoneuron pathology. The 15-item scale showed clinical improvement in 89% of patients at the 3-month follow-up and 68% at the 12-month follow-up. Multivariate analysis of the scale revealed that it accurately predicts outcome of FT resection in 82% of cases. Patients with a preoperative score exceeding 6 points are most likely to benefit from surgery. CONCLUSIONS: By applying the study's inclusion criteria and incorporating the novel 15-item scale, surgeons can effectively select candidates for FT resection in patients with OTCS. The observed outcomes in these selected patients are comparable to those achieved in degenerative spine surgery.

Environmental stability of a uranium-plutonium-carbide phase.

A plutonium-rich carbide, (U,Pu)(Al,Fe)3C3, was discovered in a hot particle from the Maralinga nuclear testing site in South Australia. The particle was produced between 1960 and 1963 and has been exposed to ambient conditions since then. The new phase belongs to a group of ternary carbides known as 'derivative-MAX phases'. It formed at high temperature within an explosion cloud via rapid eutectic crystallisation from a complex Al-Fe-U-Pu-C-O melt, and is the major Pu host in this particle. Despite signs of volume expansion due to radiation damage, (U,Pu)(Al,Fe)3C3 remains highly X-ray crystalline 60 years after its formation, with no evidence of Pu leaching from the crystals. Our results highlight that the high-energy conditions of (sub-)critical explosions can create unexpected species. Even micro-particles of a derivative-MAX phase can effectively retain low-valence (metallic-like character) Pu under environmental conditions; the slow physical and chemical weathering of these particles may contribute to the slow release of radionuclides over decades, explaining constant low-levels of radionuclides observed in fauna. This study further suggests that rapidly quenched eutectic melts may be engineered to stabilise actinides in nuclear waste products, removing the need for hydrometallurgical processing.

Insulin at the intersection of thermoregulation and glucose homeostasis.

Mammals are protected from changes in environmental temperature by altering energetic processes that modify heat production. Insulin is the dominant stimulus of glucose uptake and metabolism, which are fundamental for thermogenic processes. The purpose of this work was to determine the interaction of ambient temperature induced changes in energy expenditure (EE) on the insulin sensitivity of glucose fluxes. Short-term and adaptive responses to thermoneutral temperature (TN, ∼28 °C) and room (laboratory) temperature (RT, ∼22 °C) were studied in mice. This range of temperature does not cause detectable changes in circulating catecholamines or shivering and postabsorptive glucose homeostasis is maintained. We tested the hypothesis that a decrease in EE that occurs with TN causes insulin resistance and that this reduction in insulin action and EE is reversed upon short term (<12h) transition to RT. Insulin-stimulated glucose disposal (Rd) and tissue-specific glucose metabolic index were assessed combining isotopic tracers with hyperinsulinemic-euglycemic clamps. EE and insulin-stimulated Rd are both decreased (∼50%) in TN-adapted vs RT-adapted mice. When RT-adapted mice are switched to TN, EE rapidly decreases and Rd is reduced by ∼50%. TN-adapted mice switched to RT exhibit a rapid increase in EE, but whole-body insulin-stimulated Rd remains at the low rates of TN-adapted mice. In contrast, whole body glycolytic flux rose with EE. This higher EE occurs without increasing glucose uptake from the blood, but rather by diverting glucose from glucose storage to glycolysis. In addition to adaptations in insulin action, 'insulin-independent' glucose uptake in brown fat is exquisitely sensitive to thermoregulation. These results show that insulin action adjusts to non-stressful changes in ambient temperature to contribute to the support of body temperature homeostasis without compromising glucose homeostasis.

Endoscopic Lateral Lumbar Interbody Fusion: Technical Note and Case Series.

BACKGROUND: Our objective is to describe a minimally invasive endoscopic surgical technique for performing lateral lumbar interbody fusion (LLIF). LLIF is a common approach to lumbar fusion in cases of degenerative lumbar disease; however, complications associated with psoas and lumbar plexus injury sometimes arise. The endoscopic modification presented here diminishes the requirement for sustained muscle retraction, minimizing complication risk while allowing for adequate decompression in select cases. METHODS: Endoscopic LLIF (ELLIF) was performed in 3 patients from 2019 to 2021. Surgeries were performed in the lateral position under general anesthesia with neurophysiological monitoring. Discectomy, endplate preparation, and harvesting of iliac crest bone were performed through a working channel endoscope. The introduction of an interbody cage (Joimax EndoLIF) was performed over a nitinol blunt-tip wire (Joimax). No expandable blade retractors were required. RESULTS: At 2-year follow-up of these 3 patients, the mean visual analog scale (VAS) score for leg pain improved from 9.3 to 1.7, and the mean Oswestry Disability Index (ODI) score improved from 40 to 8.3. There were no complications, readmissions, or recurrence of symptoms during the 2-year follow-up period. Patients spent an average of 36 hours in the hospital postoperatively and returned to normal daily activities after an average of 48 days. CONCLUSIONS: A minimally invasive modification to the LLIF procedure is presented that offers several potential advantages due to the application of endoscopic techniques: reduced muscle retraction, smaller incision, and the opportunity to perform both indirect decompression and endoscopically visualized discectomy in the same fusion procedure. CLINICAL RELEVANCE: The proposed endoscopic lateral lumbar interbody fusion and decompression is a minimally invasive technique that may provide patients with minimal complications, quick recovery, and good functional recovery.

New window into hepatitis B in Africa: Liver sampling combined with single cell omics enables deep and longitudinal assessment of intrahepatic immunity in Zambia.

In Lusaka, Zambia, we introduced liver fine needle aspiration (FNA) into a research cohort of adults with treatment-naïve chronic hepatitis B virus (HBV) infection, with and without HIV coinfection, as well as with acute HBV infection. Over 117 enrollment and 47 longitudinal FNAs (at 1 year follow-up), we established participant acceptability and safety. We also demonstrated the quality of the material through single cell RNA sequencing of selected enrollment FNAs, which revealed a range of immune cells. This approach can drive new insights into HBV immunology, informing cure strategies, and can improve our understanding of HBV natural history in Africa.

Determining the Surface pKa of Perfluorooctanoic Acid.

Perfluorooctanoic acid (PFOA) is an environmentally prevalent and persistent organic pollutant with toxic and bioaccumulative properties. Despite the known importance of perfluorinated pollutants in the global environment, molecular-level details of the physicochemical behavior of PFOA on aqueous interfaces remain poorly understood. Here, we utilized two surface-specific techniques, vibrational sum frequency generation spectroscopy (SFG) and surface tensiometry, to investigate the pH-induced structural changes of PFOA and octanoic acid (OA) and determined the apparent pKa at the air-water surface. The SFG spectra and surface activity model were investigated over a wide range of pHs. With the surface tension measurements, the surface pKa values for OA and PFOA are determined to be 3.8 ± 0.1 and 2.2 ± 0.2, respectively. These results could provide insights into improved remediation of PFOAs and may impact climate modeling of perfluorinated alkyl chain molecules.

Arterial pulses link heart-brain oscillations.

A central baroreceptor monitors arterial pressure to modulate brain activity.

Systematic Review of Prophylactic Plastic Surgery Closure to Prevent Postoperative Wound Complications Following Spine Surgery.

Spinal surgeries are increasingly performed in the United States, but complication rates can be unacceptably high at up to 26%. Consequently, plastic surgeons (PS) are sometimes recruited by spine surgeons (SS) for intraoperative assistance with soft tissue closures. An electronic multidatabase literature search was systematically conducted to determine whether spinal wound closure performed by PS minimizes postoperative wound healing complications when compared to closure by SS (neurosurgical or orthopedic), with the hypothesis that closures by PS minimizes incidence of complications. All published studies involving patients who underwent posterior spinal surgery with closure by PS or SS at index spine surgery were identified. Filtering by exclusion criteria identified 10 studies, 4 of which were comparative in nature and included both closures by PS and SS. Of these 4, none reported significant differences in postoperative outcomes between the groups. Across all studies, PS were involved in cases with higher baseline risk for wound complications and greater comorbidity burden. Closures by PS were significantly more likely to have had prior chemotherapy in 2 of the 4 (50%) studies (P = 0.014, P < 0.001) and radiation in 3 of the 4 (75%) studies (P < 0.001, P < 0.01, P < 0.001). In conclusion, closures by PS are frequently performed in higher risk cases, and use of PS in these closures may normalize the risk of wound complications to that of the normal risk cohort, though the overall level of evidence of the published literature is low.