Planovalgus Foot Deformity in Patients Undergoing Total Hip Arthroplasty Is Associated With Increased Risk of Falls, Implant-Related Complications, and Revisions: A Case-Control Analysis.

BACKGROUND: Pes planus occurs due to the loss of the longitudinal arch of the foot, resulting in altered gait mechanics. This may lead to increased complications following total hip arthroplasty (THA). Thus, the aim of this study was to assess the effects that pes planus has on rates of falls, implant complications, fall-related injuries, and times to revision among THA patients. METHODS: A retrospective review of a private insurance claims database was conducted from 2010 to 2021. Patients who had a diagnosis of congenital or acquired pes planus and cases of THA were identified. Patients undergoing THA with a diagnosis of pes planus were matched to control patients 1:5 based on age, sex, and comorbidity profiles. Logistic regression was utilized to assess for differences in complication rates. RESULTS: A total of 3,622 pes planus patients were matched to 18,094 control patients. The pes planus group had significantly higher rates of falls than the control group (6.93 versus 2.97%, OR [odds ratio]: 2.43; CI [confidence interval]: 2.09 to 2.84; P < .001). Pes planus patients also had significantly greater odds of dislocation (OR: 1.89; CI: 1.58 to 2.27; P < .001), mechanical loosening (OR: 2.43; CI: 2.09 to 2.84; P = .019), and periprosthetic fracture (OR: 2.43; CI: 2.09 to 2.84; P < .001). The pes planus group had significantly greater rates of proximal humerus fractures (P = .008), but no difference was seen in distal radius fractures (P = .102). The time to revision was significantly shorter in the pes planus group (190 versus 554 days, P < .001). CONCLUSIONS: Pes planus in patients undergoing THA is associated with increased risk of complications and faster time to revision. These findings may allow orthopaedic surgeons to identify those patients at risk and allow for more educated patient counseling and operative planning.

Genome-resolved metagenomics reveals the effect of nutrient availability on bacterial genomic properties across 44 European freshwater lakes.

Understanding intricate microbial interactions in the environment is crucial. This is especially true for the relationships between nutrients and bacteria, as phosphorus, nitrogen and organic carbon availability are known to influence bacterial population dynamics. It has been suggested that low nutrient conditions prompt the evolutionary process of genome streamlining. This process helps conserve scarce nutrients and allows for proliferation. Genome streamlining is associated with genomic properties such as %GC content, genes encoding sigma factors, percent coding regions, gene redundancy, and functional shifts in processes like cell motility and ATP binding cassette transporters, among others. The current study aims to unveil the impact of nutrition on the genome size, %GC content, and functional properties of pelagic freshwater bacteria. We do this at finer taxonomic resolutions for many metagenomically characterized communities. Our study confirms the interplay of trophic level and genomic properties. It also highlights that different nutrient types, particularly phosphorus and nitrogen, impact these properties differently. We observed a covariation of functional traits with genome size. Larger genomes exhibit enriched pathways for motility, environmental interaction, and regulatory genes. ABC transporter genes reflect the availability of nutrients in the environment, with small genomes presumably relying more on metabolites from other organisms. We also discuss the distinct strategies different phyla adopt to adapt to oligotrophic environments. The findings contribute to our understanding of genomic adaptations within complex microbial communities.

Demystifying the Technology Barriers of Nurse Educators.

BACKGROUND: Technology is pivotal in nursing education, with methods such as the flipped classroom, active learning, and patient simulation becoming integral. Despite this, persistent barriers hinder technology's full integration. METHODS: An online survey collected data from nursing faculty members (n = 1761) in prelicensure nursing programs. The survey assessed their views on technology, barriers, training needs, and importance in classroom and simulation settings. RESULTS: Participants highlighted financial support, commitment, and administrative support as critical for technology adoption. Statistical analysis of the results revealed differences in the rankings of the importance of technology, emphasizing the significance of these factors. Additionally, time in the classroom was noted as a significant barrier. CONCLUSIONS: Technology's role in nursing education continues to expand. Overcoming financial constraints and enhancing faculty buy-in are essential for successful technology integration, ultimately, improving informatics competencies and advancing technological nursing education.

Bridging the Gap: Comparison of Outpatient Clinic and Emergency Department Patients Undergoing Cholecystectomy.

INTRODUCTION: Literature shows failure of the outpatient clinic (OC) pathway after emergency department (ED) ultrasound diagnosis of symptomatic cholelithiasis (SC). We hypothesized SC to be more prevalent on final surgical pathology (FSP) in patients who successfully completed OC pathway. METHODS: This retrospective single-institution chart review compared OC and ED patients with right upper quadrant (RUQ) pain and cholelithiasis whom underwent cholecystectomy. Clinical evaluation was considered positive if RUQ pain >4 h, or + Murphy's sign. Ultrasound was positive if two of these three were present: sonographic Murphy's, wall thickness > 4 mm, or pericholecystic fluid. Results were compared with FSP. RESULTS: Six hundred-seven patients underwent cholecystectomy, 299 OC and 308 ED. OC was more likely to SC (23% versus 4.6%) (P < 0.0001) and ED acute cholecystitis (39.3% versus 4.7%). Chronic cholecystitis was the most common FSP in both OC (72%) and ED (56%) populations, of these, 73% of OC denied pain >4 h versus only 10% of ED (P < 0.001). Median time from evaluation to cholecystectomy was 14 d versus 14 h in the OC and ED respectively (P < 0.0001). CONCLUSIONS: While chronic cholecystitis was the most common FSP in both OC and ED, the majority of OC reported RUQ pain <4 h delineating these presentations. Duration of pain should be utilized as algorithm triage. We recommend patients with pain episode <4 h should complete OC algorithm with expedited cholecystectomy within 14 d.

Inhibition of PDIs Downregulates Core LINC Complex Proteins, Promoting the Invasiveness of MDA-MB-231 Breast Cancer Cells in Confined Spaces In Vitro.

Eukaryotic cells tether the nucleoskeleton to the cytoskeleton via a conserved molecular bridge, called the LINC complex. The core of the LINC complex comprises SUN-domain and KASH-domain proteins that directly associate within the nuclear envelope lumen. Intra- and inter-chain disulphide bonds, along with KASH-domain protein interactions, both contribute to the tertiary and quaternary structure of vertebrate SUN-domain proteins. The significance of these bonds and the role of PDIs (protein disulphide isomerases) in LINC complex biology remains unclear. Reducing and non-reducing SDS-PAGE analyses revealed a prevalence of SUN2 homodimers in non-tumorigenic breast epithelia MCF10A cells, but not in the invasive triple-negative breast cancer MDA-MB-231 cell line. Furthermore, super-resolution microscopy revealed SUN2 staining alterations in MCF10A, but not in MDA-MB-231 nuclei, upon reducing agent exposure. While PDIA1 levels were similar in both cell lines, pharmacological inhibition of PDI activity in MDA-MB-231 cells led to SUN-domain protein down-regulation, as well as Nesprin-2 displacement from the nucleus. This inhibition also caused changes in perinuclear cytoskeletal architecture and lamin downregulation, and increased the invasiveness of PDI-inhibited MDA-MB-231 cells in space-restrictive in vitro environments, compared to untreated cells. These results emphasise the key roles of PDIs in regulating LINC complex biology, cellular architecture, biomechanics, and invasion.

Emergency critical care: closing the gap between onset of critical illness and intensive care unit admission.

Critical illness is an exquisitely time-sensitive condition and follows a disease continuum, which always starts before admission to the intensive care unit (ICU), in the majority of cases even before hospital admission. Reflecting the common practice in many healthcare systems that critical care is mainly provided in the confined areas of an ICU, any delay in ICU admission of critically ill patients is associated with increased morbidity and mortality. However, if appropriate critical care interventions are provided before ICU admission, this association is not observed. Emergency critical care refers to critical care provided outside of the ICU. It encompasses the delivery of critical care interventions to and monitoring of patients at the place and time closest to the onset of critical illness as well as during transfer to the ICU. Thus, emergency critical care covers the most time-sensitive phase of critical illness and constitutes one missing link in the chain of survival of the critically ill patient. Emergency critical care is delivered whenever and wherever critical illness occurs such as in the pre-hospital setting, before and during inter-hospital transfers of critically ill patients, in the emergency department, in the operating theatres, and on hospital wards. By closing the management gap between onset of critical illness and ICU admission, emergency critical care improves patient safety and can avoid early deaths, reverse mild-to-moderate critical illness, avoid ICU admission, attenuate the severity of organ dysfunction, shorten ICU length of stay, and reduce short- and long-term mortality of critically ill patients. Future research is needed to identify effective models to implement emergency critical care systems in different healthcare systems.

Life on the line - Incidence and management of central venous catheter complications in intestinal failure.

BACKGROUND & AIMS: Loss of venous access is threatening for patients with intestinal failure (IF) under long-term parenteral nutrition (PN). We aimed to identify the incidence of central venous catheter (CVC) complications, compare different devices, and analyze interventional recanalizing procedures to restore the patency of occluded CVCs. METHODS: For this retrospective cohort study, patient data from a prospective IF database spanning 16 years was analyzed at a tertiary referral center. Catheter dwell times (CDTs) were distinguished by Kaplan-Meier survival analysis and subgroup analyses were performed for different CVC types (tunneled/port catheters). Specific complications (occlusion, catheter-related infection (CRI), displacement, and material defect) were analyzed. Explantation rates and CDTs were compared. RESULTS: Overall, 193 CVCs in 77 patients with IF under PN could be enrolled (62.524 "CVC-days"). Broviac type "B" was found to be significantly superior to type "A" regarding occlusion, CRI, and material defects (log-rank test: p = 0.05; p = 0.026; p = 0.005 respectively). Port catheters were displaying the highest incidence of CRI (2.13 events/1000 catheter days). Interventional catheter recanalization was performed 91 times and significantly increased the CDT from a median of 131 days (IQR: 62; 258) to 389 days (IQR: 262; 731) (Mann-Whitney-U-test: p= <0.001) without increasing complications. CONCLUSIONS: Different complication rates and CDT were seen depending on CVC type. Tunneled catheters were significantly superior concerning CRI. Interventional catheter recanalization is a viable alternative to fibrinolytics to restore CVC patency, but long-term patency data is scarce.

Clinical predictors of negative/equivocal SPECT imaging outcomes in primary hyperparathyroidism: Factors calling for 18F-choline-PET.

PURPOSE: For minimally invasive surgery of parathyroid adenomas, exact localization diagnostics are essential. Main imaging modalities used for diagnostics are sonography, SPECT with/without CT (traditional imaging) and 18F-choline-PET. The aim of our study was to identify predictors for inconclusive SPECT imaging and subsequently determine in which cases 18F-choline-PET is needed. METHODS: Retrospective analysis of 138 patients with histologically confirmed primary hyperparathyroidism (pHPT). After sonography, patients underwent SPECT or SPECT/CT imaging, with subsequent 18F-choline-PET in cases of disconcordant results. Logistic regression analysis was used to identify clinical and laboratory factors predictive for negative SPECT results. RESULTS: Sensitivity rates for sonography, SPECT, SPECT/CT, and choline-PET were 47 %, 49 %, 71.7 %, and 97 %, respectively. Logistic regression revealed lower PTH levels (p < 0.001), presence of structural thyroid disease (p = 0.018), and negative sonography (p < 0.001) as predictive of negative/equivocal SPECT outcome. An additional traditional imaging CT scan to a SPECT enhanced detection odds, as did greater adenoma weight. Urolithiasis, osteoporosis, and calcium values as measurement of activity and duration of disease showed no significant association with the detection rate. Furthermore, our study demonstrated that 18F-choline-PET exhibited remarkable sensitivity in detecting adenomas among patients with negative/equivocal SPECT results. CONCLUSION: Our study reveals potential predictive factors for a negative/equivocal SPECT outcome in pHPT. Identifying these factors might allow minimizing futile SPECT examinations and perhaps encourage timely utilization of 18F-choline-PET imaging. Our study reinforces the clinical significance of 18F-choline-PET, especially in complex cases with disconcordant results by conventional parathyroid imaging methods.

Left Atrial Appendage Occlusion in Patients With Anticoagulation Failure vs Anticoagulation Contraindication.

BACKGROUND: Left atrial appendage occlusion (LAAO) provides mechanical cardioembolic protection for atrial fibrillation (AF) patients who cannot use oral anticoagulation therapy (OAT). Patients with a thrombotic event despite OAT are at high risk for recurrence and may also benefit from LAAO. OBJECTIVES: This study sought to investigate the efficacy of LAAO in AF patients with a thrombotic event on OAT compared to: 1) LAAO in AF patients with a contraindication for OAT; and 2) historical data. METHODS: The international LAAO after stroke despite oral anticoagulation (STR-OAC LAAO) collaboration included patients who underwent LAAO because of thrombotic events on OAT. This cohort underwent propensity score matching and was compared to the EWOLUTION (Evaluating Real-Life Clinical Outcomes in Atrial Fibrillation Patients Receiving the WATCHMAN Left Atrial Appendage Closure Technology) registry, which represents patients who underwent LAAO because of OAT contraindications. The primary outcome was ischemic stroke. Event rates were compared between cohorts and with historical data without OAT, yielding relative risk reductions based on risk scores. RESULTS: Analysis of 438 matched pairs revealed no significant difference in the ischemic stroke rate between the STR-OAC LAAO and EWOLUTION cohorts (2.5% vs 1.9%; HR: 1.37; 95% CI: 0.72-2.61). STR-OAC LAAO patients exhibited a higher thromboembolic risk (HR: 1.71; 95% CI: 1.04-2.83) but lower bleeding risk (HR: 0.39; 95% CI: 0.18-0.88) compared to EWOLUTION patients. The mortality rate was slightly higher in EWOLUTION (4.3% vs 6.9%; log-rank P = 0.028). Relative risk reductions for ischemic stroke were 70% and 78% in STR-OAC LAAO and EWOLUTION, respectively, compared to historical data without OAT. CONCLUSIONS: LAAO in patients with a thrombotic event on OAT demonstrated comparable stroke rates to the OAT contraindicated population in EWOLUTION. The thromboembolic event rate was higher and the bleeding rate lower, reflecting the intrinsically different risk profile of both populations. Until randomized trials are available, LAAO may be considered in patients with an ischemic event on OAT.

Artificial intelligence in coronary artery calcium score: rationale, different approaches, and outcomes.

Almost 35 years after its introduction, coronary artery calcium score (CACS) not only survived technological advances but became one of the cornerstones of contemporary cardiovascular imaging. Its simplicity and quantitative nature established it as one of the most robust approaches for atherosclerotic cardiovascular disease risk stratification in primary prevention and a powerful tool to guide therapeutic choices. Groundbreaking advances in computational models and computer power translated into a surge of artificial intelligence (AI)-based approaches directly or indirectly linked to CACS analysis. This review aims to provide essential knowledge on the AI-based techniques currently applied to CACS, setting the stage for a holistic analysis of the use of these techniques in coronary artery calcium imaging. While the focus of the review will be detailing the evidence, strengths, and limitations of end-to-end CACS algorithms in electrocardiography-gated and non-gated scans, the current role of deep-learning image reconstructions, segmentation techniques, and combined applications such as simultaneous coronary artery calcium and pulmonary nodule segmentation, will also be discussed.

Evaluating the biodistribution for [68Ga]Ga-PSMA-11 and [18F]F-PSMA-1007 PET/CT with an inter- and intrapatient based analysis.

BACKGROUND: Liver uptake in [68Ga]Ga-PSMA-11 PET is used as an internal reference in addition to clinical parameters to select patients for [177Lu]Lu-PSMA-617 radioligand therapy (RLT). Due to increased demand, [68Ga]Ga-PSMA-11 was replaced by [18F]F-PSMA-1007, a more lipophilic tracer with different biodistribution and splenic uptake was suggested as a new internal reference. We compared the intra-patient tracer distribution between [68Ga]Ga-PSMA-11 and [18F]F-PSMA-1007. METHODS: Fifty patients who underwent PET examinations in two centers with both [18F]F-PSMA-1007 and [68Ga]Ga-PSMA-11 within one year were included. Mean standardized uptake values (SUVmean) were obtained for liver, spleen, salivary glands, blood pool, and bone. Primary tumor, local recurrence, lymph node, bone or visceral metastasis were also assessed for intra- and inter-individual comparison. RESULTS: Liver SUVmean was significantly higher with [18F]F-PSMA-1007 (11.7 ± 3.9) compared to [68Ga]Ga-PSMA-11 (5.4 ± 1.7, p < .05) as well as splenic SUVmean (11.2 ± 3.5 vs.8.1 ± 3.5, p < .05). The blood pool was comparable between the two scans. Malignant lesions did not show higher SUVmean on [18F]F-PSMA-1007. Intra-individual comparison of liver uptake between the two scans showed a linear association for liver uptake with SUVmean [68Ga]Ga-PSMA-11 = 0.33 x SUVmean [18F]F-PSMA-1007 + 1.52 (r = .78, p < .001). CONCLUSION: Comparing biodistribution of [68Ga]Ga and [18F]F tracers, liver uptake on [68Ga]Ga-PSMA-11 PET is the most robust internal reference value. Liver uptake of [18F]F-PSMA-1007 was significantly higher, but so was the splenic uptake. The strong intra-individual association of hepatic accumulation between the two scans may allow using of a conversion factor for [18F]F-PSMA-1007 as a basis for RLT selection.

The Monocle Sign on 18F-FDG PET Indicates Contralateral Peripheral Facial Nerve Palsy.

BACKGROUND: The aim of our study was to retrospectively analyze FDG PET/CT data in patients with facial nerve palsy (FNP) for the presence of the monocle sign. PATIENTS AND METHODS: A total of 85 patients with unilateral FNP were included into our study, thereof 73 with peripheral FNP and 12 with central FNP. FDG uptake (SUVmax, SUVmean, total lesion glycolysis) was measured in both orbicularis oculi muscles (OOMs). FDG uptake of paretic and nonparetic muscles was compared in patients with FNP (Wilcoxon test and Mann-Whitney U test) and was also compared with FDG uptake in 33 patients without FNP (Mann-Whitney U test). SUVmax ratios of OOM were compared. A receiver operating characteristic curve and Youden Index were used to determine the optimal cutoff SUVmax ratio for the prevalence of contralateral peripheral FNP. RESULTS: The SUVmax ratio of OOM was significantly higher in patients with peripheral FNP compared with patients with central FNP and those without FNP (1.70 ± 0.94 vs 1.16 ± 0.09 vs 1.18 ± 0.21, respectively; P < 0.001). The SUVmax ratio of OOM yielded an area under the curve (AUC) of 0.719 (95% confidence interval, 0.630-0.809), with an optimal cutoff of 1.41, yielding a specificity of 94.4% and a sensitivity of 44.1% for identifying contralateral peripheral FNP. One hundred percent specificity is achieved using a cutoff of 1.91 (sensitivity, 29.4%). CONCLUSIONS: Asymmetrically increased FDG uptake of the OOM (the "monocle sign") indicates contralateral peripheral FNP. A nearly 2-fold higher SUVmax represents a practically useful cutoff.

Asian elephant calf physiology and mahout perspectives during taming in Myanmar.

A quarter of Asian elephants are captive, with greater than 90% of these tamed and cared for by handlers (mahouts) in Asia. Although taming is a much-discussed welfare issue, no studies to our knowledge have empirically assessed its impact on calves, and dialogue surrounding taming often lacks perspectives of those involved. Here, we interviewed mahouts involved in taming and monitored five physiological measures (faecal glucocorticoid metabolites (FGMs), serum cortisol, glucose, creatine kinase (CK) and heterophil:lymphocyte (H:L)) over the first 10 days of taming and following six months in 41 calves undergoing taming and 16 control individuals. These measures assess the duration and intensity of stress during taming. Interviews suggested mahouts had major concerns for their safety when discussing changing taming practices, an important consideration for future management. Calf physiological measures were elevated by 50-70% (FGMs/cortisol/glucose), 135% (H:L) and greater than 500% (CK) over the first few days of taming, indicative of elevated stress, not seen to the same extent in control adults. Some measures stabilized sooner (glucose/cortisol/CK/FGM: 7-10 days) than others (H:L: one-two months), indicating mostly acute stress. Our findings inform the welfare of approximately 15 000 captive elephants around the world. Future studies should compare taming in different populations and consider calf and mahout welfare.

Lifelong persistence of nuclear RNAs in the mouse brain.

Genomic DNA that resides in the nuclei of mammalian neurons can be as old as the organism itself. The life span of nuclear RNAs, which are critical for proper chromatin architecture and transcription regulation, has not been determined in adult tissues. In this work, we identified and characterized nuclear RNAs that do not turn over for at least 2 years in a subset of postnatally born cells in the mouse brain. These long-lived RNAs were stably retained in nuclei in a neural cell type-specific manner and were required for the maintenance of heterochromatin. Thus, the life span of neural cells may depend on both the molecular longevity of DNA for the storage of genetic information and also the extreme stability of RNA for the functional organization of chromatin.

Determination of ileal endogenous nitrogen losses and true ileal nitrogen digestibility during non-steady-state conditions of the 15N-isotope dilution technique.

The aim was to determine ileal endogenous nitrogen losses (ENL) and true ileal N-digestibility (TD-N) under non-steady-state conditions of the 15N-isotope dilution technique (15N-IDT), using diets generating low and high ENL and compare results to those obtained under steady-state conditions. Twelve growing pigs (mean LW 22.4 kg) fitted with a post-valve T-caecum cannula were fed an enzyme-hydrolysed casein (EHC)-based diet or an EHC diet + 4% quebracho tannins (QT) and were labelled via continuous 15N-leucine i.v. infusion or twice daily oral 15N-leucine administration. Digesta were collected daily over three consecutive hours with blood plasma sampled on the four consecutive days after cessation of 15N-labelling. There was a significant effect of sampling day on the dilution factor. Endogenous N losses were significantly lower for the EHC than the EHC+QT diet (2.41 vs. 8.69 g/kg DMI), while no significant effect of sampling day was observed. The TD-N of the EHC+QT diet did not differ from the TD-N of the EHC diet (95.1 vs. 92.0%). A significant effect of sampling day was observed for TD-N with day 1 and 2, being higher than day 4. Non-steady-state conditions overestimated ENL by 25-28% as compared to 3 h collections in steady-state conditions, but the relative overestimation was similar for the EHC diet as for the EHC+QT diet. TD-N did not differ significantly compared to 12 h steady-state measurements, but comparison to 3 h steady-state measurements showed that non-steady-state conditions overestimated TD-N for the EHC+QT diet by 9%. However, on day 4 this overestimation disappeared. Using the 15N-IDT during non-steady-state conditions can provide valuable additional data on endogenous N losses and TD-N.

Learning Curve of a Laparoscopic Pancreaticoduodenectomy Program at a Second Institution.

BACKGROUND: Historically, pancreaticoduodenectomy (PD) has been performed via a laparotomy, but increasingly, laparoscopic and robotic platforms are being employed for PD. Laparoscopic PD has a steep surgeon specific learning curve and programmatic elements that must be optimized. These factors may limit a surgeon who is proficient at laparoscopic PD to develop a program at another institution. We hypothesize that the learning curve for a surgeon transferring a program to a second institution is shorter than the initial laparoscopic PD learning curve for the same surgeon. METHODS: A retrospective review of patients who underwent laparoscopic PD for any indication at the first institution (FI) from 2012 to 2017 and the second institution (SI) from 2018 to 2021 was conducted. Standard statistical analysis was performed. The learning curve was identified using one-sided CUSUM analysis of operative times. RESULT: We identified 110 participants, 90 from the FI and 20 from the SI. More patients at the FI were diagnosed with periampullary adenocarcinoma on final pathology compared to the SI (65.6% vs 40.0%, P = .0132). FI operative times stabilized after the 25th laparoscopic PD and SI operative times stabilized after the 5th operation. No statistically significant difference was identified in postoperative complications. CONCLUSIONS: The learning curve and average operative time of an SI laparoscopic PD program was shorter than the initial learning curve for a single surgeon with comparable outcomes. This suggests that complex minimally invasive surgical programs can be safely transferred to another high-volume institution without significant loss of progress.

Cell-type-resolved mosaicism reveals clonal dynamics of the human forebrain.

Debate remains around the anatomical origins of specific brain cell subtypes and lineage relationships within the human forebrain1-7. Thus, direct observation in the mature human brain is critical for a complete understanding of its structural organization and cellular origins. Here we utilize brain mosaic variation within specific cell types as distinct indicators for clonal dynamics, denoted as cell-type-specific mosaic variant barcode analysis. From four hemispheres and two different human neurotypical donors, we identified 287 and 780 mosaic variants, respectively, that were used to deconvolve clonal dynamics. Clonal spread and allele fractions within the brain reveal that local hippocampal excitatory neurons are more lineage-restricted than resident neocortical excitatory neurons or resident basal ganglia GABAergic inhibitory neurons. Furthermore, simultaneous genome transcriptome analysis at both a cell-type-specific and a single-cell level suggests a dorsal neocortical origin for a subgroup of DLX1+ inhibitory neurons that disperse radially from an origin shared with excitatory neurons. Finally, the distribution of mosaic variants across 17 locations within one parietal lobe reveals that restriction of clonal spread in the anterior-posterior axis precedes restriction in the dorsal-ventral axis for both excitatory and inhibitory neurons. Thus, cell-type-resolved somatic mosaicism can uncover lineage relationships governing the development of the human forebrain.