Nevin Manimala

JACC Adv. 2025 Dec 4;5(1):102385. doi: 10.1016/j.jacadv.2025.102385. Online ahead of print.

ABSTRACT

BACKGROUND: Current guidelines recommend screening for elevated aldosterone-renin ratio (ARR) in high-risk hypertensive patients. However, the definition, occurrence, and population-level characteristics of aldosterone dysregulation (AD) remain unclear.

OBJECTIVES: The purpose of this study was to examine the occurrence of AD and associated clinical characteristics.

METHODS: We conducted a population-based cohort study using health registries with complete laboratory test results for all Danish residents. We examined the annual proportion of ARR testing and AD occurrence, defined as ARR ≥27.7 pmol/mIU (1 ng/dL per mIU/L), in the general and hypertensive population. Clinical characteristics associated with testing and AD were described, and analyses were repeated using different ARR thresholds (138.7 pmol/mIU and 225.8 pmol/mIU).

RESULTS: Among 5.42 million Danish adults, 18,650 underwent ARR testing during 2017-2024. Testing was four-fold higher in hypertensive adults than in the general population. In 2023, AD prevalence per 100,000 was 39.1 in hypertensive adults compared to 10.0 in the general population. Among tested hypertensive adults, 25.0% met the AD threshold ARR ≥27.7 pmol/mIU, while 4.5% and 1.8% met stricter AD thresholds (138.7 and 225.8 pmol/mIU). Hypertensive adults with AD had longer hypertension duration (7.1 vs 5.2 years) and used more concurrent antihypertensive drugs.

CONCLUSIONS: In this first nationwide study of AD, detected AD was 4 times more prevalent in adults with hypertension compared to the general population. One in 4 hypertensive adults tested met the AD threshold of ARR ≥27.7 pmol/mIU and they had higher intensity of antihypertensive therapy.

PMID:41349148 | DOI:10.1016/j.jacadv.2025.102385

Cancer Genet. 2025 Nov 28;300-301:28-35. doi: 10.1016/j.cancergen.2025.11.013. Online ahead of print.

ABSTRACT

BACKGROUND: Double mutations (DMs) in cis within the same BRCA gene are extremely rare, and their clinical significance remains uncertain, as it is unclear whether they confer an additive risk compared with single pathogenic variants (PVs).

MATERIALS AND METHODS: We retrospectively analyzed a cohort of 1722 patients referred for suspected Hereditary Breast and Ovarian Cancer (HBOC). Among them, 9 unrelated probands were found to carry the same BRCA2 DM: c.631G>A (p.Val211Ile) in exon 7 and c.7008-2A>T (IVS13-2A>T) at the acceptor splice site of intron 13. Both variants were confirmed to co-segregate in cis. A control group of 19 probands with a single BRCA2 PV located between exons 7 and 14 was selected for comparison.

RESULTS: All DM families originated from the same geographic area in Southern Italy, suggesting a founder effect. The mean age at breast cancer onset was 50.7 years in the DM group and 51.4 years in the control group. Tumor spectrum and distribution among probands and relatives were comparable between groups, and BRCA2-related breast cancers were predominantly hormone receptor-positive in both cohorts. No statistically significant differences were observed regarding cancer types, stage, or receptor profile.

CONCLUSIONS: These findings suggest that the BRCA2 double mutation c.631G>A/c.7008-2A>T may have a founder effect, and the coexistence of the two variants does not appear to confer an additive cancer risk or a more severe clinical phenotype compared with carriers of a single BRCA2 pathogenic mutation.

PMID:41349144 | DOI:10.1016/j.cancergen.2025.11.013

Phys Rev Lett. 2025 Nov 21;135(21):210402. doi: 10.1103/gqjz-tyqg.

ABSTRACT

We explore the dynamics of two-dimensional Rydberg atom arrays coupled to a single-mode optical cavity, employing nonequilibrium diagrammatic techniques to capture nonlinearities and fluctuations beyond mean-field theory. We discover a novel prethermalization regime driven by the interplay between short-range Rydberg interactions and long-range photon-mediated interactions. In this regime, matter and light equilibrate at distinct-and in some cases opposite-effective temperatures, resembling the original concept of prethermalization from particle physics. Our results establish strongly correlated AMO platforms as tools to investigate fundamental questions in statistical mechanics, including quantum thermalization in higher-dimensional systems.

PMID:41349111 | DOI:10.1103/gqjz-tyqg

Phys Rev Lett. 2025 Nov 21;135(21):211801. doi: 10.1103/fzzl-2dyr.

ABSTRACT

We report on a search for axion dark matter in the frequency range near 5.9 GHz, conducted using the haloscope technique. The experiment employed an 8-cell microwave resonator designed to extend the accessible frequency range by a multifold factor relative to conventional single-cell configurations, while maintaining a large detection volume. To enhance sensitivity, a flux-driven Josephson parametric amplifier operating near the quantum noise limit was utilized, together with a sideband-summing method that coherently combines mirrored spectral components generated by the Josephson parametric amplifier. Data were acquired over the frequency range 5.83-5.94 GHz. With no statistically significant excess observed, we exclude axion-photon couplings g_{aγγ} down to 1.2×10^{-14} GeV^{-1} at a 90% confidence level. The achieved sensitivity approaches the Kim-Shifman-Vainshtein-Zakharov benchmark prediction, setting the most stringent limits to date in this range.

PMID:41349099 | DOI:10.1103/fzzl-2dyr

Phys Rev Lett. 2025 Nov 21;135(21):212701. doi: 10.1103/d7dr-h36j.

ABSTRACT

We provide the first experimental cross section of the ^{73}As(p,γ)^{74}Se reaction to constrain one of the main destruction mechanisms of the p nucleus ^{74}Se in explosive stellar environments. The measurement was done using a radioactive ^{73}As beam at effective center-of-mass energies of 2.9 and 2.3 MeV/nucleon. Along with the total cross-section measurement, statistical properties of the ^{74}Se compound nucleus were extracted, constraining the reaction cross section in the upper Gamow window of the γ process. The impact of the experimentally constrained reaction rate on ^{74}Se production in Type II supernovae was investigated through Monte Carlo one-zone network simulations. The results indicate that the overproduction of ^{74}Se by Type II supernova models cannot be resolved by nuclear physics alone and point toward the need for a more detailed understanding of the astrophysical conditions of relevance for the γ process.

PMID:41349071 | DOI:10.1103/d7dr-h36j

Phys Rev Lett. 2025 Nov 21;135(21):216902. doi: 10.1103/mvdf-bdrx.

ABSTRACT

We investigated ultrafast defect-lattice dynamics in diamond using the N_{s}:H-C^{0} defect, an analog of bond-centered hydrogen in semiconductors. Combining synthesis, ultrafast vibrational spectroscopy, and ab initio calculations, we show that excitation of the defect’s stretch mode leads to the generation of localized phonons and the formation of a hot ground state, where the interatomic potential is transiently modified. Our results reveal unexpected nonequilibrium phonon effects despite diamond’s exceptionally high thermal conductivity, with implications for quantum defect engineering.

PMID:41349066 | DOI:10.1103/mvdf-bdrx

J Neurosurg. 2025 Dec 5:1-9. doi: 10.3171/2025.7.JNS25718. Online ahead of print.

ABSTRACT

OBJECTIVE: The US neurosurgical workforce faces growing demand driven by an aging population and rising prevalence of neurological conditions. This study projects workforce supply and demand from 2022 to 2037, highlighting potential shortages and geographic disparities.

METHODS: Workforce projections (2022-2037) were obtained from the Health Resources & Services Administration’s National Center for Health Workforce Analysis Dashboard, using the Health Workforce Simulation Model to estimate supply and demand by specialty, year, and location. Supply, measured in full-time equivalents (FTEs), accounted for new entrants, retirements, and attrition. Demand was projected under two scenarios: 1) status quo and 2) reduced barriers, reflecting improved access for underserved populations. Workforce adequacy (supply-to-demand ratio) was assessed, with descriptive statistics and state-level heat maps generated using Excel and Python in Google Colab.

RESULTS: The neurosurgery workforce is projected to grow slightly from 7060 FTEs in 2022 to 7230 FTEs by 2037 (+2.4%). Under the status quo scenario, demand rises from 7060 to 8310 FTEs (+18%), while the reduced barriers scenario shows an increase from 9280 to 11,830 FTEs (+27%). Workforce adequacy decreases across both scenarios, with national adequacy dropping from 100% to 87% under the status quo and from 72% to 61% under reduced barriers. Metropolitan areas maintain higher adequacy compared with nonmetropolitan areas but still face shortages over time. State-level disparities persist through 2037, with adequacy ranging from 400% in the District of Columbia to 33% in Delaware. By then, neurosurgery ranks 18th under the status quo and 33rd under reduced barriers among 37 specialties.

CONCLUSIONS: Significant neurosurgical workforce shortages are projected through 2037, with growing demand outpacing modest supply increases, particularly under the reduced barriers scenario. Targeted strategies are needed to address geographic disparities and ensure adequate neurosurgical care nationwide.

PMID:41349031 | DOI:10.3171/2025.7.JNS25718

J Med Internet Res. 2025 Dec 5;27:e75313. doi: 10.2196/75313.

ABSTRACT

BACKGROUND: Accurate assessment of voiding patterns before and after surgery for lower urinary tract symptoms is critical in patient care, but it places heavy burdens on both the patient and the clinic. While methods for telemedicine have been devised, no technology for acoustic assessment of urinary patterns has been prospectively evaluated for clinical use.

OBJECTIVE: This study aims to assess the precision of a mobile app-based uroflowmetry and compare it with in-office uroflowmetry measurements for the management of patients undergoing surgical treatment for benign prostatic hyperplasia (BPH).

METHODS: This study was designed as a prospective, multicenter, observational pilot validation study conducted at 3 tertiary centers. A total of 46 patients with BPH who had not received any previous treatment within 4 weeks of their initial outpatient clinic visit were prospectively enrolled. After diagnosis, participants with BPH conducted subsequent uroflowmetry measurements by using a sound-based mobile app, proudP, for at least 4 days during the pretreatment period, followed by transurethral resection of prostate (TURP). Additional measurements were taken at the preoperative visit and 4-day periods after 2, 6, and 12 weeks of treatment initiation, with concurrent in-office measurements. Uroflowmetry parameters, including maximum flow rate (Q_max) and voided volume, were compared. Patient satisfaction was evaluated using a scale ranging from 0 to 10 at the end of the 12-week study.

RESULTS: TURP resulted in a mean Q_max improvement of 7.2 mL/s at conventional uroflowmetry, which correlated with a mean improvement of 5.1 mL/s when measured by the app. A statistically significant correlation (P<.05) was observed between the 2 methods. The app-based uroflowmetry effectively reflected the improvement in voiding symptoms over time after the initiation of medical treatment, with statistically significant improvement in total International Prostate Symptom Scores (IPSS; -4.7), IPSS obstructive (-5.7), IPSS irritative (-2.6), and quality of life (-5.9; all P<.05). Overall, the participants reported a high level of satisfaction, with a mean score of 9.5 (SD 0.8) points at the conclusion of the study.

CONCLUSIONS: The findings of this study demonstrate that app-based uroflowmetry (proudP) measurements serve as an accurate and reliable indicator of perioperative surveillance in patients undergoing TURP for BPH. By enabling personalized and portable uroflowmetry, clinicians can easily monitor treatment response as well as observe the risk of postoperative acute urinary retention.

PMID:41349029 | DOI:10.2196/75313

J Neurosurg Spine. 2025 Dec 5:1-10. doi: 10.3171/2025.7.SPINE24939. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective of this study was to investigate the incidence and postoperative clinical outcomes of lateral interbody cage migration (LCM) in patients undergoing multilevel stand-alone lateral lumbar interbody fusion (LLIF) compared with an aged-matched cohort undergoing LLIF with posterior pedicle screw instrumentation.

METHODS: A retrospective review was conducted of the medical records of patients who underwent multilevel LLIF between 2017 and 2024 at a single institution and had ≥ 1 year of follow-up and postoperative radiographic follow-up. Demographic, operative, and postoperative data were collected and analyzed. Statistical analyses were performed using the chi-square test and independent-sample t-tests to assess the differences between continuous and categorical variables comparing both cohorts (stand-alone vs posterior instrumentation). Age-matched cohort analysis was performed, evaluating the distribution of both cohorts using a frequency matching analysis with the posterior instrumentation cohort as the control group and confirming equal distribution with the chi-square statistical test. Confounding factors were evaluated using logistic regression analyses.

RESULTS: Eighty-seven patients met the inclusion criteria (43 in the stand-alone cohort, 44 in the posterior instrumentation cohort). For the stand-alone cohort, the mean (SD) age was 70.2 (8.2) years (30 [70%] males, 13 [30%] females). For the posterior instrumentation cohort, the mean (SD) age was 69.6 (7.1) years (28 [64%] females, 16 [36%] males). In the stand-alone cohort, 43 surgeries were performed involving the following 110 levels: L1-2 (n = 9), L2-3 (n = 36), L3-4 (n = 42), L4-5 (n = 23), and L5-S1 (n = 0). In the posterior instrumentation cohort, 44 surgeries were performed involving the following 112 levels: L1-2 (n = 6), L2-3 (n = 21), L3-4 (n = 44), L4-5 (n = 41), and L5-S1 (n = 0). The incidence of LCM was 7% in the stand-alone cohort and 5% in the posterior instrumentation cohort, with no statistically significant differences observed between the 2 cohorts. There were no statistically significant confounding factors. Patient-related outcomes, including Oswestry Disability Index and visual analog scale scores, showed postoperative improvement in both cohorts.

CONCLUSIONS: The difference in the incidence of LCM between the stand-alone cohort and the posterior instrumentation cohort was not statistically significant. Although posterior instrumentation has traditionally been used to enhance construct stability, multilevel stand-alone LLIF can be a safe procedure. Prospective study designs are warranted to validate these findings and elucidate factors contributing to cage migration in multilevel stand-alone LLIF versus LLIF with posterior pedicle screw instrumentation procedures.

PMID:41349028 | DOI:10.3171/2025.7.SPINE24939

J Neurosurg. 2025 Dec 5:1-13. doi: 10.3171/2025.7.JNS242821. Online ahead of print.

ABSTRACT

OBJECTIVE: Although dopamine agonist (DA) therapy still represents the standard of care for prolactinomas, a reconsideration of the role of transsphenoidal surgery has been promoted in recent years. The aim of this multicenter retrospective study was to assess the short- and long-term results of the endoscopic endonasal approach (EEA) for prolactinomas, analyzing which factors have a favorable prognostic role.

METHODS: All consecutive prolactinomas operated on in 12 Italian neurosurgical centers between 2013 and 2023 were included. For each case, preoperative clinical and neuroradiological features were considered, as well as surgical complications and short- and long-term results.

RESULTS: The series included 215 patients (44.2% males, mean age 39.7 [SD 16.6] years), accounting for 4.5% of all pituitary surgeries in these centers. The majority of prolactinomas (67.9%) were macroprolactinomas. Radical tumor resection was achieved in 171 patients (79.5%), and 3-month biochemical remission in 154 patients (71.6%). The most common surgical complication was postoperative CSF leak (2.8%). Endocrinological sequelae consisted of new onset of anterior hypopituitarism in 10.7% of cases, transient diabetes insipidus (DI) in 3.3%, and permanent DI in 2.3%. Long-term remission (mean follow-up 33.5 [SD 25.0] months) was achieved in 75.4% of patients, 14 patients (6.5%) presented with tumor recurrence/progression, and 1 (0.5%) demonstrated tumor evolution to carcinoma.

CONCLUSIONS: The EEA is a valid option for the treatment of prolactinomas, with better results for micro tumors and regular macro tumors. This study found that preoperative prolactin values < 184 ng/ml were associated with higher chances of biochemical remission, as was larger pituitary surgery center volume. Currently, the most common surgical indications for prolactinomas are represented by cases that are not responsive or intolerant to DAs. However, interesting future perspectives considering EEA as a possible co-first-line therapy in selected patients have been recently proposed.

PMID:41349017 | DOI:10.3171/2025.7.JNS242821