Low-intensity focused ultrasound represents groundbreaking medical advancements, characterized by its noninvasive feature, safety, precision, and broad neuromodulatory capabilities. This technology operates through mechanisms, for example, acoustic radiation force, cavitation, and thermal effects. Notably, with the evolution of medical technology, ultrasound neuromodulation has been gradually applied in treating central nervous system diseases, especially stroke. Furthermore, burgeoning research areas such as sonogenetics and nanotechnology show promising potential. Despite the benefit of low-intensity focused ultrasound the precise biophysical mechanism of ultrasound neuromodulation still need further exploration. This review discusses the recent and ongoing developments of low-intensity focused ultrasound for neurological regulation, covering the underlying rationale to current utility and the challenges that impede its further development and broader adoption of this promising alternative to noninvasive therapy.

Background: Products of conception samples are often collected and analyzed to try to determine the cause of an early pregnancy loss. However, sample collection may not always be possible, and maternal cell contamination and culture failure can affect the analysis. Cell-free DNA-based analysis of a blood sample could be used as an alternative method in early pregnancy loss cases to detect if aneuploidies were present in the fetus. Methods: In this prospective study, blood samples from early pregnancy loss patients were analyzed for the presence of fetal aneuploidies using a modified version of a noninvasive prenatal testing assay for cell-free DNA analysis. Results from cell-free DNA analysis were compared against the gold standard, microarray analysis of products of conception samples. This study was registered with ClinicalTrials.gov, identifier: NCT04935138. Results: Of the 76 patient samples included in the final study cohort, 11 were excluded from performance calculations. The 65 patient samples included in the final analysis included 49 with an abnormal microarray result and 16 with a normal microarray result. Based on results from these 65 samples, the study found that genome-wide cell-free DNA analysis had a sensitivity of 73.5% with a specificity of 100% for the detection of fetal aneuploidies in early pregnancy loss cases. Conclusions: This prospective study provides further support for the utility of cell-free DNA analysis in detecting fetal aneuploidies in early pregnancy loss cases. This approach could allow for a noninvasive method of investigating the etiology of miscarriages to be made available clinically.

OBJECTIVE: Endometriosis diagnostic delays are still encountered due to the lack of a reliable, noninvasive diagnostic test. Besides, menstrual blood is a relatively untapped field for diagnostics, yet it provides a readily accessible source for investigating common gynecological conditions. In the present study, we aim to evaluate the expression levels of menstrual blood aromatase, SF-1, and HSD17B2 from women with and without endometriosis and their diagnostic performance.
METHODS: A total of 40 subjects participated in this study, including 20 patients from each endometriosis and non-endometriosis group. The endometriosis group comprised patients with proven endometriosis confirmed by pathological diagnosis and pelvic ultrasound examination, then requiring endometrial biopsy determined by the clinicians. The non-endometriosis group consisted of women who had primary and secondary infertility and underwent endometrial examination without any visible endometriosis lesion. The menstrual blood and eutopic endometrial tissue of enrolled subjects were collected, and the relative expression of the genes was performed by quantitative real-time polymerase chain reaction (qPCR). ROC curve was used to evaluate the diagnostic efficacy of aromatase, SF-1, and HSD17B2.
RESULTS: We found significantly higher expressions of aromatase, SF-1, and HSD17B2 in the menstrual blood of the endometriosis group compared to non-endometriosis (P < 0.05). In contrast, examination of eutopic endometrial tissue of both groups only found significant in HSD17B2 (P < 0.05), while aromatase and SF-1 showed no statistically significant variance. The Area Under Curve (AUC) of aromatase, SF-1, and HSD17B2 in the menstrual blood was 0.977, 0.862, and 0.807, respectively. The optimal cutoff value was determined to be >1.63 (sensitivity = 95 % and specificity = 90 %) for aromatase, >1.71 (sensitivity = 90 % and specificity = 80 %) for SF-1, and >1.83 (sensitivity = 80 % and specificity = 75 %) for HSD17B2.
CONCLUSIONS: Our study showed that aromatase, SF-1, and HSD17B2 in the menstrual blood solidly discriminate between endometriosis and non-endometriosis patients with high diagnostic accuracy. However, further confirmation in larger cohorts is required to validate the reliability of these biomarkers to endometriosis.

Hormone monitoring of at-risk species can be valuable for evaluation of individual physiological status. Traditional non-invasive endocrine monitoring from urine and faeces typically captures only a short window in time, poorly reflecting long-term hormone fluctuations. We examined toenail trimmings collected from African (Loxodonta africana) and Asian (Elephas maximus) elephants during routine foot care, to determine if long-term hormone patterns are preserved in these slow-growing keratinized tissues. We first measured the growth rate of elephant toenails biweekly for one year, to establish the temporal delay between deposition of hormones into nail tissue (at the proximal nail bed) and collection of toenail trimmings months later (at the distal tip of the nail). In African elephants, toenails grew ~0.18 ± 0.015 mm/day (mean ± SEM) and in Asian elephants, toenails grew ~0.24 ± 0.034 mm/day. This slow growth rate, combined with the large toenail size of elephants, may mean that toenails could contain a \'hormone timeline\' of over a year between the nail bed and nail tip. Progesterone, testosterone and cortisol were readily detectable using commercial enzyme immunoassays, and all assays passed validations, indicating that these hormones can be accurately quantified in elephant toenail extract. In most cases, variations in hormone concentrations reflected expected physiological patterns for adult females and males (e.g. ovarian cycling and musth) and matched individual health records from participating zoos. Progesterone patterns aligned with our calculations of temporal delay, aligning with female ovarian cycling from over six months prior. Unexpectedly, male testosterone patterns aligned with current musth status at the time of sample collection (i.e. rather than prior musth status). Though this sample type will require further study, these results indicate that preserved hormone patterns in elephant toenails could give conservationists a new tool to aid management of elephant populations.

BACKGROUND: Early screening using low-dose computed tomography (LDCT) can reduce mortality caused by non-small-cell lung cancer. However, ∼25% of the \'suspicious\' pulmonary nodules identified by LDCT are later confirmed benign through resection surgery, adding to patients\' discomfort and the burden on the healthcare system. In this study, we aim to develop a noninvasive liquid biopsy assay for distinguishing pulmonary malignancy from benign yet \'suspicious\' lung nodules using cell-free DNA (cfDNA) fragmentomics profiling.
METHODS: An independent training cohort consisting of 193 patients with malignant nodules and 44 patients with benign nodules was used to construct a machine learning model. Base models using four different fragmentomics profiles were optimized using an automated machine learning approach before being stacked into the final predictive model. An independent validation cohort, including 96 malignant nodules and 22 benign nodules, and an external test cohort, including 58 malignant nodules and 41 benign nodules, were used to assess the performance of the stacked ensemble model.
RESULTS: Our machine learning models demonstrated excellent performance in detecting patients with malignant nodules. The area under the curves reached 0.857 and 0.860 in the independent validation cohort and the external test cohort, respectively. The validation cohort achieved an excellent specificity (68.2%) at the targeted 90% sensitivity (89.6%). An equivalently good performance was observed while applying the cut-off to the external cohort, which reached a specificity of 63.4% at 89.7% sensitivity. A subgroup analysis for the independent validation cohort showed that the sensitivities for detecting various subgroups of nodule size (<1 cm: 91.7%; 1-3 cm: 88.1%; >3 cm: 100%; unknown: 100%) and smoking history (yes: 88.2%; no: 89.9%) all remained high among the lung cancer group.
CONCLUSIONS: Our cfDNA fragmentomics assay can provide a noninvasive approach to distinguishing malignant nodules from radiographically suspicious but pathologically benign ones, amending LDCT false positives.

OBJECTIVE: Evaluation of noninvasive left ventricular (LV) myocardial work (MW) enables insights into cardiac contractility and efficacy beyond conventional echocardiography. However, there is limited intraoperative data on patients undergoing surgical aortic valve replacement (AVR). The aim of this study was to describe the feasibility and the intraoperative course of this technique of ventricular function assessment in these patients and compare it to conventional two (2D)- and three-dimensional (3D) echocardiographic measurements and strain analysis.
METHODS: Prospective observational study.
METHODS: Single university hospital.
METHODS: Twenty-five patients scheduled for isolated AVR with preoperative preserved left and right ventricular function, sinus rhythm, without significant other heart valve disease or pulmonary hypertension, and an uneventful intraoperative course.
METHODS: Transesophageal echocardiography was performed after induction of anesthesia (T1), after termination of cardiopulmonary bypass (T2), and after sternal closure (T3). Evaluation was performed in stable hemodynamics, in sinus rhythm or atrial pacing and vasopressor support with norepinephrine ≤ 0.1 µg/kg/min.
RESULTS: EchoPAC v206 software (GE Vingmed Ultrasound AS, Norway) was used for analysis of 2D and 3D LV ejection fraction (EF), LV global longitudinal strain (GLS), LV global work index (GWI), LV global constructive work (GCW), LV global wasted work (GWW), and LV global work efficiency (GWE). Estimation of myocardial work was feasible in all patients. Although there was no significant difference in the values of 2D and 3D EF, GWI and GCW decreased significantly after AVR (T1 v T2, 1,647 ± 380 mmHg% v 1,021 ± 233 mmHg%, p < 0.001; T1 v T2, 2,095 ± 433 mmHg% v 1,402 ± 242 mmHg%, p < 0.001, respectively), while GWW remained unchanged (T1 v T2, 296 mmHg% [IQR 178-452) v 309 mmHg% [IQR 255-438), p = 0.97). This resulted in a decreased GWE directly after bypass (T1 v T2, 84% ± 6% v 78% ± 5%, p < 0.001), but GWE already improved at the end of surgery (T2 v T3, 78% ± 5% v 81% ± 5%, p = 0.003). There was no significant change in the values of GWI, GCW, or 2D and 3D LVEF before and after sternal closure (T2 v T3).
CONCLUSIONS: LV MW analysis showed a reduction of LV workload after bypass in our group of patients, which was not detected by conventional echocardiographic measures. This evolving technique provides deeper insights into cardiac energetics and efficiency in the perioperative course of aortic valve replacement surgery.

This study endeavored to design and develop an innovative closed-loop diagnostic and therapeutic system with the following objectives: (a) the noninvasive detection of glucose concentration in sweat utilizing nanonengineered screen-printed biosensors; (b) the management of measured data through a specialized computer system comprising both hardware and software components, thereby enabling the precise control of therapeutic responses via a patch-based nanomedicine delivery system. This initiative addresses the significant challenges inherent in the management of diabetes mellitus, including the imperative need for glucose-level monitoring to optimize glycemic control. Leveraging chronoamperometric results as a foundational dataset and the in vivo hypoglycemic activity of nanoemulsion formulations, this research underscores the efficacy and accuracy of glucose concentration estimation, decision-making mechanism responses, and transdermal hypoglycemic treatment effects, within the proposed system.

Background: Psoriasis is an immune-mediated chronic disorder associated with various comorbidities. Even though biologics and small-molecule inhibitors are the mainstay treatment for moderate-to-severe psoriasis, there is no current consensus regarding which agent should be used for a specific type of patient. This paper aims to test the reliability of blood-count-derived inflammatory markers in assessing treatment response to biologics and small-molecule inhibitors in psoriasis. Material and Methods: Bio-naïve adult patients diagnosed with chronic plaque psoriasis fulfilling the inclusion criteria were enrolled. They were divided into study subgroups based on treatment of choice, and blood-count-derived inflammatory markers were analyzed at baseline, three-month, six-month, and at twelve-month visits. Results: A total of 240 patients were included. The highest number of patients underwent treatment with ixekizumab. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), platelet-to-monocyte ratio (PMR), monocyte-to-lymphocyte ratio (MLR), derived neutrophil-to-lymphocyte ratio (d-NLR), systemic inflammation response index (SIRI), systemic immune inflammation index (SII), and aggregate index of systemic inflammation (AISI) all varied significantly (p < 0.005) between the four visits. The psoriasis area severity index (PASI) score correlated with PLR, d-NLR, and SII, while the psoriasis scalp severity index (PSSI) score correlated with AISI and SIRI. More than half of patients reached the target goal of PASI90 at the six-month visit. A total of 77 patients were super-responders, with the highest number undergoing treatment with ixekizumab. Higher baseline values of d-NLR and SIRI are independent predictors of the super-responder status. Conclusions: Blood-count-derived inflammatory markers can serve as indicators of treatment response to biologics in psoriasis, while d-NLR and SIRI were independent predictors of super-responders in our study.

BACKGROUND: There has been a proliferation of physicians of different levels of experience and training offering nonsurgical cosmetic procedures. Rising demand, compounded by increasing utilization of new and existing technologies by numerous physician specialties, compels discussion of adequate standardized training and patient safety.
METHODS: A retrospective chart review of patients who presented to our single site dermatology clinic for managment of complications following chemical peel, laser or energy-based device treatments performed by core cosmetic physicians between the years of 2013 and 2024 was conducted. Core cosmetic physicians included plastic surgery, facial surgery/otolaryngology, oculoplastic surgery, and dermatology. Charts were reviewed for documentation of the type of complication, procedure causing the complication, and physician credentials, and referral source.
RESULTS: Twenty-five patients were identified as having complications from chemical peeling, laser treatment or energy-based devices. Devices implicated included CO2 laser (fractional or fully ablative), chemical peels, 1064 nm long-pulsed Nd:YAG laser, 1320 nm Nd:YAG laser, intense pulsed light, 595 nm pulsed dye laser, Q-switched Nd:YAG laser, radiofrequency with and without microneedling, and 1550 nm erbium-doped fiber laser. Complications included hypertrophic scarring, atrophic scarring, post-inflammatory erythema, post-inflammatory hyperpigmentation, and post-inflammatory hypopigmentation.
CONCLUSIONS: Even in experienced hands, complications can arise. It is imperative that all physicians offering cosmetic treatments are equipped to recognize clinical endpoints, identify and manage complications, or make a timely referral to decrease the risk of a permanent and potentially devastating esthetic outcome for patients.

BACKGROUND: Effective management of patients with aneurysmal subarachnoid hemorrhage (aSAH) demands vigilant monitoring and treatment, given the risks of complications such as cerebral vasospasm and delayed ischemic neurological deficits (DINDs). Transcranial transmission ultrasound (TTUS) is a well-established technique for assessing brain pulsatility. This pilot study aims to explore the utility of TTUS in detecting impaired intracerebral blood flow associated with DINDs.
METHODS: The authors examined 2 male patients, ages 45 and 52 years, with aSAH Hunt and Hess grades 4 and 2, respectively, who developed DINDs during their clinical course. Simultaneous recordings of arterial blood pressure, heart rate, and TTUS measurements were obtained in the intensive care unit. TTUS analysis revealed abnormal arrhythmic wave patterns during DIND episodes, whereas baseline measurements on DIND-free days showed no abnormalities. Following endovascular spasmolysis, TTUS demonstrated a normalization of abnormal waves, returning to baseline levels, alongside the resolution of neurological symptoms.
CONCLUSIONS: TTUS, a noninvasive method for assessing brain pulsatility, shows promise as a novel tool for monitoring aSAH patients, potentially aiding in prompt diagnostics and additional therapeutic interventions. Its capacity to provide further insights for individuals at risk of delayed cerebral ischemia warrants further investigation in clinical studies. https://thejns.org/doi/10.3171/CASE24146.