Implementation of an Institution-Wide Rules-Based Automated CT Protocoling System.

BACKGROUND. Examination protocoling is a noninterpretive task that increases radiologists' workload and can cause workflow inefficiencies. OBJECTIVE. The purpose of this study was to evaluate effects of an automated CT protocoling system on examination process times and protocol error rates. METHODS. This retrospective study included 317,597 CT examinations (mean age, 61.8 ± 18.1 [SD] years; male, 161,125; female, 156,447; unspecified sex, 25) from July 2020 to June 2022. A rules-based automated protocoling system was implemented institution-wide; the system evaluated all CT orders in the EHR and assigned a protocol or directed the order for manual radiologist protocoling. The study period comprised pilot (July 2020 to December 2020), implementation (January 2021 to December 2021), and postimplementation (January 2022 to June 2022) phases. Proportions of automatically protocoled examinations were summarized. Process times were recorded. Protocol error rates were assessed by counts of quality improvement (QI) reports and examination recalls and comparison with retrospectively assigned protocols in 450 randomly selected examinations. RESULTS. Frequency of automatic protocoling was 19,366/70,780 (27.4%), 68,875/163,068 (42.2%), and 54,045/83,749 (64.5%) in pilot, implementation, and postimplementation phases, respectively (p < .001). Mean (± SD) times from order entry to protocol assignment for automatically and manually protocoled examinations for emergency department examinations were 0.2 ± 18.2 and 2.1 ± 69.7 hours, respectively; mean inpatient examination times were 0.5 ± 50.0 and 3.5 ± 105.5 hours; and mean outpatient examination times were 361.7 ± 1165.5 and 1289.9 ± 2050.9 hours (all p < .001). Mean (± SD) times from order entry to examination completion for automatically and manually protocoled examinations for emergency department examinations were 2.6 ± 38.6 and 4.2 ± 73.0 hours, respectively (p < .001); for inpatient examinations were 6.3 ± 74.6 and 8.7 ± 109.3 hours (p = .001); and for outpatient examinations were 1367.2 ± 1795.8 and 1471.8 ± 2118.3 hours (p < .001). In the three phases, there were three, 19, and 25 QI reports and zero, one, and three recalls, respectively, for automatically protocoled examinations, versus nine, 19, and five QI reports and one, seven, and zero recalls for manually protocoled examinations. Retrospectively assigned protocols were concordant with 212/214 (99.1%) of automatically protocoled versus 233/236 (98.7%) of manually protocoled examinations. CONCLUSION. The automated protocoling system substantially reduced radiologists' protocoling workload and decreased times from order entry to protocol assignment and examination completion; protocol errors and recalls were infrequent. CLINICAL IMPACT. The system represents a solution for reducing radiologists' time spent performing noninterpretive tasks and improving care efficiency.

Society of Radiologists in Ultrasound Consensus Conference Recommendations for Incidental Gallbladder Polyp Management: Interreader Agreement Among 10 Radiologists.

BACKGROUND. The 2022 Society of Radiologists in Ultrasound (SRU) consensus conference recommendations for small gallbladder polyps support management that is less aggressive than earlier approaches and may help standardize evaluation of polyps by radiologists. OBJECTIVE. The purpose of the present study was to assess the interreader agreement of radiologists in applying SRU recommendations for management of incidental gallbladder polyps on ultrasound. METHODS. This retrospective study included 105 patients (75 women and 30 men; median age, 51 years) with a gallbladder polyp on ultrasound (without features highly suspicious for invasive or malignant tumor) who underwent cholecystectomy between January 1, 2003, and January 1, 2021. Ten abdominal radiologists independently reviewed ultrasound examinations and, using the SRU recommendations, assessed one polyp per patient to assign risk category (extremely low risk, low risk, or indeterminate risk) and make a possible recommendation for surgical consultation. Five radiologists were considered less experienced (< 5 years of experience), and five were considered more experienced (≥ 5 years of experience). Interreader agreement was evaluated. Polyps were classified pathologically as nonneoplastic or neoplastic. RESULTS. For risk category assignments, interreader agreement was substantial among all readers (k = 0.710), less-experienced readers (k = 0.705), and more-experienced readers (k = 0.692). For surgical consultation recommendations, inter-reader agreement was substantial among all readers (k = 0.795) and more-experienced readers (k = 0.740) and was almost perfect among less-experienced readers (k = 0.811). Of 10 readers, a median of 5.0 (IQR, 2.0-8.0), 4.0 (IQR, 2.0-7.0), and 0.0 (IQR, 0.0-0.0) readers classified polyps as extremely low risk, low risk, and indeterminate risk, respectively. Across readers, the percentage of polyps classified as extremely low risk ranged from 32% to 72%; as low risk, from 24% to 65%; and as indeterminate risk, from 0% to 8%. Of 10 readers, a median of zero change to 0 (IQR, 0.0-1.0) readers recommended surgical consultation; the percentage of polyps receiving a recommendation for surgical consultation ranged from 4% to 22%. Of a total of 105 polyps, 102 were nonneo-plastic and three were neoplastic (all benign). Based on readers' most common assessments for nonneoplastic polyps, the risk category was extremely low risk for 53 polyps, low risk for 48 polyps, and indeterminate risk for one polyp; surgical consultation was recommended for 16 polyps. CONCLUSION. Ten abdominal radiologists showed substantial agreement for polyp risk categorizations and surgical consultation recommendations, although areas of reader variability were identified. CLINICAL IMPACT. The findings support the overall reproducibility of the SRU recommendations, while indicating opportunity for improvement.

Clinical Intricacies and Advances in Neuroendocrine Tumors: An Organ-Based Multidisciplinary Approach.

ABSTRACT: Neuroendocrine neoplasms (NENs) are rare neoplasms originating from neuroendocrine cells, with increasing incidence due to enhanced detection methods. These tumors display considerable heterogeneity, necessitating diverse management strategies based on factors like organ of origin and tumor size. This article provides a comprehensive overview of therapeutic approaches for NENs, emphasizing the role of imaging in treatment decisions. It categorizes tumors based on their locations: gastric, duodenal, pancreatic, small bowel, colonic, rectal, appendiceal, gallbladder, prostate, lung, gynecological, and others. The piece also elucidates the challenges in managing metastatic disease and controversies surrounding MEN1-neuroendocrine tumor management. The article underscores the significance of individualized treatment plans, underscoring the need for a multidisciplinary approach to ensure optimal patient outcomes.

Prevalence of Malignancy in Adrenal Nodules With Heterogeneous Microscopic Fat on Chemical-Shift MRI: A Multiinstitutional Study.

BACKGROUND. Homogeneous microscopic fat within adrenal nodules on chemical-shift MRI (CS-MRI) is diagnostic of benign adrenal adenoma, but the clinical relevance of heterogeneous microscopic fat is not well established. OBJECTIVE. This study sought to determine the prevalence of malignancy in adrenal nodules with heterogeneous microscopic fat on dual-echo T1-weighted CS-MRI. METHODS. We performed a retrospective study of adult patients with adrenal nodules detected on MRI performed between August 2007 and November 2020 at seven institutions. Eligible nodules had a short-axis diameter of 10 mm or larger with heterogeneous microscopic fat (defined by an area of signal loss of < 80% on opposed-phase CS-MRI). Two radiologists from each center, blinded to reference standard results, determined the signal loss pattern (diffuse, two distinct parts, speckling pattern, central loss, or peripheral loss) within the nodules. The reference standard used was available for 283 nodules (pathology for 21 nodules, ≥ 1 year of imaging follow-up for 245, and ≥ 5 years of clinical follow-up for 17) in 282 patients (171 women and 111 men; mean age, 60 ± 12 [SD] years); 30% (86/282) patients had prior malignancy. RESULTS. The mean long-axis diameter was 18.7 ± 7.9 mm (range, 10-80 mm). No malignant nodules were found in patients without prior cancer (0/197; 95% CI, 0-1.5%). Four of the 86 patients with prior malignancy (hepatocellular carcinoma [HCC], renal cell carcinoma [RCC], lung cancer, or both colon cancer and RCC) (4.7%; 95% CI, 1.3-11.5%) had metastatic nodules. Detected patterns were diffuse heterogeneous signal loss (40% [114/283]), speckling (28% [80/283]), two distinct parts (18% [51/283]), central loss (9% [26/283]), and peripheral loss (4% [12/283]). Two metastases from HCC and RCC showed diffuse heterogeneous signal loss. Lung cancer metastasis manifested as two distinct parts, and the metastasis in the patient with both colon cancer and RCC showed peripheral signal loss. CONCLUSION. Presence of heterogeneous microscopic fat in adrenal nodules on CS-MRI indicates a high likelihood of benignancy, particularly in patients without prior cancer. This finding is also commonly benign in patients with cancer; however, caution is warranted when primary malignancies may contain fat or if the morphologic pattern of signal loss may indicate a collision tumor. CLINICAL IMPACT. In the absence of prior cancer, adrenal nodules with heterogeneous microscopic fat do not require additional imaging evaluation.

Adrenal Neoplasms: Lessons from Adrenal Multidisciplinary Tumor Boards.

The radiologic diagnosis of adrenal disease can be challenging in settings of atypical presentations, mimics of benign and malignant adrenal masses, and rare adrenal anomalies. Misdiagnosis may lead to suboptimal management and adverse outcomes. Adrenal adenoma is the most common benign adrenal tumor that arises from the cortex, whereas adrenocortical carcinoma (ACC) is a rare malignant tumor of the cortex. Adrenal cyst and myelolipoma are other benign adrenal lesions and are characterized by their fluid and fat content, respectively. Pheochromocytoma is a rare neuroendocrine tumor of the adrenal medulla. Metastases to the adrenal glands are the most common malignant adrenal tumors. While many of these masses have classic imaging appearances, considerable overlap exists between benign and malignant lesions and can pose a diagnostic challenge. Atypical adrenal adenomas include those that are lipid poor; contain macroscopic fat, hemorrhage, and/or iron; are heterogeneous and/or large; and demonstrate growth. Heterogeneous adrenal adenomas may mimic ACC, metastasis, or pheochromocytoma, particularly when they are 4 cm or larger, whereas smaller versions of ACC, metastasis, and pheochromocytoma and those with washout greater than 60% may mimic adenoma. Because of its nonenhanced CT attenuation of less than or equal to 10 HU, a lipid-rich adrenal adenoma may be mimicked by a benign adrenal cyst, or it may be mimicked by a tumor with central cystic and/or necrotic change such as ACC, pheochromocytoma, or metastasis. Rare adrenal tumors such as hemangioma, ganglioneuroma, and oncocytoma also may mimic adrenal adenoma, ACC, metastasis, and pheochromocytoma. The authors describe cases of adrenal neoplasms that they have encountered in clinical practice and presented to adrenal multidisciplinary tumor boards. Key lessons to aid in diagnosis and further guide appropriate management are provided. © RSNA, 2023 Online supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.

Hereditary and Sporadic Pheochromocytoma: Comparison of Imaging, Clinical, and Laboratory Features.

BACKGROUND. A considerable fraction of pheochromocytomas initially suspected to be sporadic, whether or not symptomatic, are a result of germline mutations. OBJECTIVE. The purpose of this article is to compare imaging features between hereditary and sporadic pheochromocytomas. METHODS. This retrospective study included 71 patients (39 women, 32 men; median age, 48 years) who underwent adrenal pheochromocytoma resection from January 2002 to October 2021 after preoperative CT or MRI. Two radiologists independently reviewed examinations to assess features of the largest resected pheochromocytoma. Interreader agreement was assessed by prevalence-adjusted bias-adjusted kappa coefficients; a third radiologist resolved discrepancies for further analysis. Genetic testing was used to classify pheochromocytomas as hereditary or sporadic and to classify hereditary pheochromocytomas by germline mutation clusters. Symptoms associated with pheochromocytomas and preoperative biochemical laboratory values were recorded. Groups were compared using Kruskal-Wallis, Fisher exact, and chi-square tests, and false-discovery rate-adjusted p values were computed to account for multiple comparisons. RESULTS. Hereditary pheochromocytoma (n = 32), compared with sporadic pheochromocytoma (n = 39), was associated with younger median age (38 vs 52 years, p = .001) and smaller median size (24 vs 40 mm, p < .001). Interreader agreement for CT and MRI features, expressed as kappa, ranged from 0.44 to 1.00. Hereditary and sporadic pheochromocytoma showed no difference in frequency of calcifications, hemorrhage, cystic change/necrosis, or macroscopic fat on CT, or in frequency of hemorrhage, cystic change/necrosis, macroscopic fat, or microscopic fat on MRI (p > .05). When combining CT and MRI, cystic change/necrosis was observed in 35% of hereditary versus 67% of sporadic pheochromocytomas (p = .10). Hereditary pheochromocytoma, compared with sporadic, had lower frequency of symptoms (31% vs 74%; p = .004) and lower 24-hour urinary normetanephrines (1.1 vs 5.1 times upper limits of normal, p = .006). Among hereditary pheochromocytomas, cystic change/necrosis (when assessable on imaging) was present in 18% and 45% of those with cluster 1 (n = 11) and cluster 2 (n = 21) germ-line mutations, respectively. CONCLUSION. Hereditary pheochromocytomas, compared with sporadic, are detected at a younger age and smaller size, produce lower 24-hour urinary normetanephrines, are less often symptomatic, and may less frequently show cystic change/necrosis. CLINICAL IMPACT. Imaging findings may complement clinical and biochemical features in raising suspicion for a previously unsuspected germline mutation in patients with pheochromocytoma.

Comparison of four methods to measure haemoglobin concentrations in whole blood donors (COMPARE): A diagnostic accuracy study.

OBJECTIVE: To compare four haemoglobin measurement methods in whole blood donors. BACKGROUND: To safeguard donors, blood services measure haemoglobin concentration in advance of each donation. NHS Blood and Transplant's (NHSBT) customary method have been capillary gravimetry (copper sulphate), followed by venous spectrophotometry (HemoCue) for donors failing gravimetry. However, NHSBT's customary method results in 10% of donors being inappropriately bled (ie, with haemoglobin values below the regulatory threshold). METHODS: We compared the following four methods in 21 840 blood donors (aged ≥18 years) recruited from 10 NHSBT centres in England, with the Sysmex XN-2000 haematology analyser, the reference standard: (1) NHSBT's customary method; (2) "post donation" approach, that is, estimating current haemoglobin concentration from that measured by a haematology analyser at a donor's most recent prior donation; (3) "portable haemoglobinometry" (using capillary HemoCue); (4) non-invasive spectrometry (using MBR Haemospect or Orsense NMB200). We assessed sensitivity; specificity; proportion who would have been inappropriately bled, or rejected from donation ("deferred") incorrectly; and test preference. RESULTS: Compared with the reference standard, the methods ranged in test sensitivity from 17.0% (MBR Haemospect) to 79.0% (portable haemoglobinometry) in men, and from 19.0% (MBR Haemospect) to 82.8% (portable haemoglobinometry) in women. For specificity, the methods ranged from 87.2% (MBR Haemospect) to 99.9% (NHSBT's customary method) in men, and from 74.1% (Orsense NMB200) to 99.8% (NHSBT's customary method) in women. The proportion of donors who would have been inappropriately bled ranged from 2.2% in men for portable haemoglobinometry to 18.9% in women for MBR Haemospect. The proportion of donors who would have been deferred incorrectly with haemoglobin concentration above the minimum threshold ranged from 0.1% in men for NHSBT's customary method to 20.3% in women for OrSense. Most donors preferred non-invasive spectrometry. CONCLUSION: In the largest study reporting head-to-head comparisons of four methods to measure haemoglobin prior to blood donation, our results support replacement of NHSBT's customary method with portable haemoglobinometry.

Interreader Concordance of the TI-RADS: Impact of Radiologist Experience.

OBJECTIVE. The objective of this article is to assess radiologist concordance in characterizing thyroid nodules using the American College of Radiology Thyroid Imaging Reporting and Data System (TI-RADS), focusing on the effect of radiologist experience on reader concordance. MATERIALS AND METHODS. Three experienced and three less experienced radiologists assessed 150 thyroid nodules using the TI-RADS lexicon. Percent concordance was determined for various endpoints. RESULTS. Interreader concordance for the five TI-RADS categories was 87.2% for shape, 81.2% for composition, 76.1% for echogenicity, 72.9% for margins, and 69.8% for echogenic foci. Concordance for individual features was 96.3% for rim calcifications, 90.8% for macrocalcifications, 90.1% for spongiform, 83.5% for comet tail artifact, and 77.7% for punctate echogenic foci. Concordance for the TI-RADS level and recommendation for fine-needle aspiration (FNA) were 50.4% and 78.9%, respectively. Concordance was significantly (p < 0.05) higher for less experienced readers in identifying margins (84.3% vs 67.4%), echogenic foci (76.9% vs 69.3%), comet tail artifact (89.6% vs 79.2%), and punctate echogenic foci (85.3% vs 75.5%), and lower for peripheral rim calcifications (95.0% vs 97.8 %), but was not different (p > 0.05) for the remaining categories and features. CONCLUSION. A range of TI-RADS categories, features, and recommendations for FNA had generally moderate interreader agreement among six radiologists. Our results show that concordance for numerous characteristics was significantly higher for the less experienced versus the more experienced readers. These results suggest that less experienced readers relied more on the explicit TI-RADS criteria, whereas the experienced radiologists partially relied on their accumulated experience when forming impressions. However, the overall TI-RADS level and recommendation for FNA were unaffected, supporting the robustness of the TI-RADS lexicon and its continued use in practice.

Biases incurred from nonrandom repeat testing of haemoglobin levels in blood donors: Selective testing and its implications.

To help prevent anaemia, it is a requisite for blood donors to undergo a haemoglobin test to ensure levels are not too low before donation. It is therefore important to have an accurate testing device and strategy to ensure donors are not being inappropriately bled. A recent study in blood donors used a selective testing strategy where if a donor's haemoglobin level is below the level required for donation, then another reading is taken and if this occurs again, a third and final reading is used. This strategy can reduce the average number of readings required per donor compared to taking three measurements for all donors. However, the final decision-making measurement will on average be higher than a single measurement. In this paper, a selective testing strategy is compared against other strategies. Individual-level biases are derived for the selective strategy and are shown to depend on how close a donor's true haemoglobin level is to the donation threshold and the magnitude of error in the testing device. A simulation study was conducted using the distribution of haemoglobin levels from a large donor population to investigate the effects different strategies have on population performance. We consider scenarios based on varying the measurement device bias and error, including differential biases that depend on the underlying haemoglobin level. Discriminatory performance is shown to be affected when using the selective testing strategies, especially when measurement error is large and when differential bias is present in the device. We recommend that the average of a number of readings should be used in preference to selective testing strategies if multiple measurements are available.

Synthesis of Benzodihydrofurans by Asymmetric C-H Insertion Reactions of Donor/Donor Rhodium Carbenes.

Metal carbenes appended with two electron-donating groups, known as "donor/donor" carbenes, undergo diastereo- and enantioselective rhodium-catalyzed C-H insertion reactions with ether substrates to form benzodihydrofurans. Unlike the reactions of metal carbenes with electron-withdrawing groups attached, the attenuated electrophilicity enables these reactions to be conducted in Lewis basic solvents (e.g., acetonitrile) and in the presence of water. The diazo precursors for these species are prepared in situ from hydrazone using a mild and chemoselective oxidant (MnO2 ). Although this sequence often can be performed in one-pot, control experiments have elucidated why a "two-pot" process is often more efficient. A thorough screening of achiral catalysts demonstrated that sterically encumbered catalysts are optimal for diastereoselective reactions. Although efficient insertion into allylic and propargylic C-H bonds is observed, competing dipolar cycloaddition processes are noted for some substrates. The full substrate scope of this useful method of benzodihydrofuran synthesis, mechanisms of side reactions, and computational support for the origins of stereoselectivity are described.

Synthesis of ß-Ketosulfonamides Derived from Amino Acids and Their Conversion to ß-Keto-α,α-difluorosulfonamides via Electrophilic Fluorination.

ß-Ketosulfonamides derived from Boc or Cbz-protected amino acids bearing hydrophobic side chains were prepared in good to excellent yield by treating N-allyl, N-alkyl methanesulfonamides with n-BuLi, followed by reaction of the resulting carbanion with methyl esters of N-protected l-amino acids. The analogous reaction using the dianion derived from an N-alkyl methanesulfonamide proceeded in much lower yield. Electrophilic fluorination of the ß-ketosulfonamides using Selectfluor in the presence of CsF in DMF at room temperature for 15-60 min provided ß-keto-α,α-difluorosulfonamides in good to excellent yields. The allyl protecting group could be removed in good yield using cat. Pd(PPh)3)4 and dimethyl barbituric acid. When the fluorination reaction was performed with Cs2CO3 as base, ß-ketosulfonamides derived from Val, Leu or Ile gave the expected ß-keto-α,α-difluorosulfonamides, while ß-ketosulfonamides derived from Ala, Phe, or hPhe gave the hydrates of the imino ß-keto-α,α-difluorosulfonamides.

Endoscopic Endonasal Transsphenoidal Resection of Pituitary Adenomas in Patients Presenting With Monocular Blindness.

BACKGROUND AND OBJECTIVES: Suprasellar tumors, particularly pituitary adenomas (PAs), commonly present with visual decline, and the endoscopic endonasal transsphenoidal approach (EETA) is the primary management for optic apparatus decompression. Patients presenting with complete preoperative monocular blindness comprise a high-risk subgroup, given concern for complete blindness. This retrospective cohort study evaluates outcomes after EETA for patients with PA presenting with monocular blindness. METHODS: Retrospective analysis of all EETA cases at our institution from June 2012 to August 2023 was performed. Inclusion criteria included adults with confirmed PA and complete monocular blindness, defined as no light perception, and a relative afferent pupillary defect secondary to tumor mass effect. RESULTS: Our cohort includes 15 patients (9 males, 6 females), comprising 2.4% of the overall PA cohort screened. The mean tumor diameter was 3.8 cm, with 6 being giant PAs (>4 cm). The mean duration of preoperative monocular blindness was 568 days. Additional symptoms included contralateral visual field defects (n = 11) and headaches (n = 10). Two patients presented with subacute PA apoplexy. Gross total resection was achieved in 46% of patients, reflecting tumor size and invasiveness. Postoperatively, 2 patients experienced improvement in their effectively blind eye and 2 had improved visual fields of the contralateral eye. Those with improvements were operated within 10 days of presentation, and no patients experienced worsened vision. CONCLUSION: This is the first series of EETA outcomes in patients with higher-risk PA with monocular blindness on presentation. In these extensive lesions, vision remained stable for most without further decline and improvement from monocular blindness was observed in a small subset of patients with no light perception and relative afferent pupillary defect. Timing from vision loss to surgical intervention seemed to be associated with improvement. From a surgical perspective, caution is warranted to protect remaining vision and we conclude that EETA is safe in the management of these patients.

Beta-Band power modulation in the human amygdala differentiates between go/no-go responses in an arm reaching task.

Introduction Traditionally known for its involvement in emotional processing, the amygdala's involvement in motor control remains relatively unexplored, with sparse investigation into the neural mechanisms governing amygdaloid motor movement and inhibition. Objective This study aimed to characterize the amygdaloid beta-band (13-30 Hz) power between "Go" and "No-go" trials of an arm reaching task. Methods Ten participants with drug-resistant epilepsy implanted with stereoelectroencephalographic (SEEG) electrodes in the amygdala were enrolled in this study. SEEG data was recorded throughout discrete phases of a Direct Reach Go/No-go task, during which participants reached a touchscreen monitor or withheld movement based on a colored cue. Multitaper power analysis along with Wilcoxon signed-rank and Yates-corrected Z tests were used to assess significant modulations of beta power between the Response and Fixation (baseline) phases in the "Go" and "No-go" conditions. Results In the "Go" condition, nine out of the ten participants showed a significant decrease in relative beta-band power during the Response phase (p ≤ 0.0499). In the "No-go" condition, eight out of the ten participants presented a statistically significant increase in relative beta-band power during the Response phase (p ≤ 0.0494). Four out of the eight participants with electrodes in the contralateral hemisphere and seven out of the eight participants with electrodes in the ipsilateral hemisphere presented significant modulation in beta-band power in both the "Go" and "No-go" conditions. At the group level, no significant differences were found between the contralateral and ipsilateral sides or between genders. Conclusion This study reports beta-band power modulation in the human amygdala during voluntary movement in the setting of motor execution and inhibition. This finding supplements prior research in various brain regions associating beta-band power with motor control. The distinct beta-power modulation observed between these response conditions suggests involvement of amygdaloid oscillations in differentiating between motor inhibition and execution.

Beta-band power classification of Go/No-go arm reaching responses in the human hippocampus.

Introduction Can we decode movement execution and inhibition from hippocampal oscillations during arm-reaching tasks? Traditionally associated with memory encoding, spatial navigation, and motor sequence consolidation, the hippocampus has come under scrutiny for its potential role in movement processing. Stereotactic electroencephalography (SEEG) has provided a unique opportunity to study the neurophysiology of the human hippocampus during motor tasks. Objective In this study, we assess the accuracy of discriminant functions, in combination with principal component analysis (PCA), in classifying between "Go" and "No-go" trials in a Go/No-go arm-reaching task. Our approach centers on capturing the modulation of beta-band (13-30 Hz) power from multiple SEEG contacts in the hippocampus and minimizing the dimensional complexity of channels and frequency bins. Methods This study utilizes SEEG data from the human hippocampus of 10 participants diagnosed with epilepsy. Spectral power was computed during a "center-out" Go/No-go arm-reaching task, where participants reached or withheld their hand based on a colored cue. PCA was used to reduce data dimension and isolate the highest-variance components within the beta band. The Silhouette score was employed to measure the quality of clustering between "Go" and "No-go" trials. The accuracy of five different discriminant functions was evaluated using cross-validation. Results The Diagonal-Quadratic model performed best of the 5 classification models, exhibiting the lowest error rate in all participants (median: 9.91%, average: 14.67%). PCA showed that the first two principal components collectively accounted for 54.83% of the total variance explained on average across all participants, ranging from 36.92% to 81.25% among participants. Conclusion This study shows that PCA paired with a Diagonal-Quadratic model can be an effective method for classifying between Go/No-go trials from beta-band power in the hippocampus during arm-reaching responses. This emphasizes the significance of hippocampal beta-power modulation in motor control, unveiling its potential implications for brain-computer interface (BCI) applications.

Stereotactic Frame-Based Electrode Insertion: The Accuracy of Increasingly Oblique Insertion Angles.

AIM: To investigate the relationship between planned drill approach angle and angular deviation of the stereotactically placed intracranial electrode tips. MATERIAL AND METHODS: Stereotactic electrode implantation was performed in 13 patients with drug resistant epilepsy. A total of 136 electrodes were included in our analysis. Stereotactic targets were planned on pre-operative magnetic resonance imaging (MRI) scans and implantation was carried out using a Cosman-Roberts-Wells stereotactic frame with the Ad-Tech drill guide and electrodes. Post implant electrode angles in the axial, coronal, and sagittal planes were determined from post-operative computerized tomography (CT) scans and compared with planned angles using Bland-Altman plots and linear regression. RESULTS: Qualitative assessment of correlation plots between planned and actual angles demonstrated a linear relationship for axial, coronal, and sagittal planes, with no overt angular deflection for any magnitude of the planned angle. CONCLUSION: The accuracy of CRW frame-based electrode placement using the Ad-Tech drill guide and electrodes is not significantly affected by the magnitude of the planning angle. Based on our results, oblique electrode insertion is a safe and accurate procedure.

Variants in tubule epithelial regulatory elements mediate most heritable differences in human kidney function.

Kidney disease is highly heritable; however, the causal genetic variants, the cell types in which these variants function, and the molecular mechanisms underlying kidney disease remain largely unknown. To identify genetic loci affecting kidney function, we performed a GWAS using multiple kidney function biomarkers and identified 462 loci. To begin to investigate how these loci affect kidney function, we generated single-cell chromatin accessibility (scATAC-seq) maps of the human kidney and identified candidate cis -regulatory elements (cCREs) for kidney podocytes, tubule epithelial cells, and kidney endothelial, stromal, and immune cells. Kidney tubule epithelial cCREs explained 58% of kidney function SNP-heritability and kidney podocyte cCREs explained an additional 6.5% of SNP-heritability. In contrast, little kidney function heritability was explained by kidney endothelial, stromal, or immune cell-specific cCREs. Through functionally informed fine-mapping, we identified putative causal kidney function variants and their corresponding cCREs. Using kidney scATAC-seq data, we created a deep learning model (which we named ChromKid) to predict kidney cell type-specific chromatin accessibility from sequence. ChromKid and allele specific kidney scATAC-seq revealed that many fine-mapped kidney function variants locally change chromatin accessibility in tubule epithelial cells. Enhancer assays confirmed that fine-mapped kidney function variants alter tubule epithelial regulatory element function. To map the genes which these regulatory elements control, we used CRISPR interference (CRISPRi) to target these regulatory elements in tubule epithelial cells and assessed changes in gene expression. CRISPRi of enhancers harboring kidney function variants regulated NDRG1 and RBPMS expression. Thus, inherited differences in tubule epithelial NDRG1 and RBPMS expression may predispose to kidney disease in humans. We conclude that genetic variants affecting tubule epithelial regulatory element function account for most SNP-heritability of human kidney function. This work provides an experimental approach to identify the variants, regulatory elements, and genes involved in polygenic disease.

Understanding the human conflict processing network: A review of the literature on direct neural recordings during performance of a modified stroop task.

The Stroop Task is a well-known neuropsychological task developed to investigate conflict processing in the human brain. Our group has utilized direct intracranial neural recordings in various brain regions during performance of a modified color-word Stroop Task to gain a mechanistic understanding of non-emotional human conflict processing. The purpose of this review article is to: 1) synthesize our own studies into a model of human conflict processing, 2) review the current literature on the Stroop Task and other conflict tasks to put our research in context, and 3) describe how these studies define a network in conflict processing. The figures presented are reprinted from our prior publications and key publications referenced in the manuscript. We summarize all studies to date that employ invasive intracranial recordings in humans during performance of conflict-inducing tasks. For our own studies, we analyzed local field potentials (LFPs) from patients with implanted stereotactic electroencephalography (SEEG) electrodes, and we observed intracortical oscillation patterns as well as intercortical temporal relationships in the hippocampus, amygdala, and orbitofrontal cortex (OFC) during the cue-processing phase of a modified Stroop Task. Our findings suggest that non-emotional human conflict processing involves modulation across multiple frequency bands within and between brain structures.

Critical assessment of missense variant effect predictors on disease-relevant variant data.

Regular, systematic, and independent assessment of computational tools used to predict the pathogenicity of missense variants is necessary to evaluate their clinical and research utility and suggest directions for future improvement. Here, as part of the sixth edition of the Critical Assessment of Genome Interpretation (CAGI) challenge, we assess missense variant effect predictors (or variant impact predictors) on an evaluation dataset of rare missense variants from disease-relevant databases. Our assessment evaluates predictors submitted to the CAGI6 Annotate-All-Missense challenge, predictors commonly used by the clinical genetics community, and recently developed deep learning methods for variant effect prediction. To explore a variety of settings that are relevant for different clinical and research applications, we assess performance within different subsets of the evaluation data and within high-specificity and high-sensitivity regimes. We find strong performance of many predictors across multiple settings. Meta-predictors tend to outperform their constituent individual predictors; however, several individual predictors have performance similar to that of commonly used meta-predictors. The relative performance of predictors differs in high-specificity and high-sensitivity regimes, suggesting that different methods may be best suited to different use cases. We also characterize two potential sources of bias. Predictors that incorporate allele frequency as a predictive feature tend to have reduced performance when distinguishing pathogenic variants from very rare benign variants, and predictors supervised on pathogenicity labels from curated variant databases often learn label imbalances within genes. Overall, we find notable advances over the oldest and most cited missense variant effect predictors and continued improvements among the most recently developed tools, and the CAGI Annotate-All-Missense challenge (also termed the Missense Marathon) will continue to assess state-of-the-art methods as the field progresses. Together, our results help illuminate the current clinical and research utility of missense variant effect predictors and identify potential areas for future development.