VSIG4 interaction with heparan sulfates inhibits VSIG4-complement binding.

V-set and immunoglobulin domain-containing 4 (VSIG4) is a complement receptor of the immunoglobulin superfamily that is specifically expressed on tissue resident macrophages, and its many reported functions and binding partners suggest a complex role in immune function. VSIG4 is reported to have a role in immune surveillance as well as in modulating diverse disease phenotypes such as infections, autoimmune conditions, and cancer. However, the mechanism(s) governing VSIG4's complex, context-dependent role in immune regulation remains elusive. Here, we identify cell surface and soluble glycosaminoglycans, specifically heparan sulfates, as novel binding partners of VSIG4. We demonstrate that genetic deletion of heparan sulfate synthesis enzymes or cleavage of cell-surface heparan sulfates reduced VSIG4 binding to the cell surface. Furthermore, binding studies demonstrate that VSIG4 interacts directly with heparan sulfates, with a preference for highly sulfated moieties and longer glycosaminoglycan chains. To assess the impact on VSIG4 biology, we show that heparan sulfates compete with known VSIG4 binding partners C3b and iC3b. Furthermore, mutagenesis studies indicate that this competition occurs through overlapping binding epitopes for heparan sulfates and complement on VSIG4. Together these data suggest a novel role for heparan sulfates in VSIG4-dependent immune modulation.

A Scoping Review of Kidney Transplantation in Africa: How Far have We Come?

INTRODUCTION: Kidney transplantation is a life-saving treatment for end-stage kidney disease (ESKD) patients. However, access to this treatment in Africa lags behind other regions, leading to significant disparities in care. We aimed to analyse the indications, demographics, and outcomes of kidney transplantation in Africa. METHOD: We conducted a systematic review of studies from PubMed, Google Scholar, and African Journal Online using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We pooled and analysed data on procedure type, graft outcomes, donor type, prophylaxis, post-operative complications, and survival from 33 eligible studies. RESULT: The most common causes of ESKD requiring transplantation were glomerulonephritis and nephroangiosclerosis. Open nephrectomy was the predominant surgical approach (95%). Living donors accounted for 56.3% (4221) of all donors, with 68.5% being related to the recipient. Cadaveric donors accounted for 43.7% (3280) of transplants. Graft rejection was the most common surgical complication (39.44%), and 60.49% of patients developed hypertension in the follow-up period. CONCLUSION: Our study highlights the potential of kidney transplantation to improve the lives of ESKD patients in Africa. However, further research and infrastructure development are necessary to make this treatment more widespread and successful.

Assessing invariance of cannabis use motives by veteran status and binary gender identity among college students.

Student service members/veterans (SSM/V) are distinct from non-veteran students in a variety of ways, including in their cannabis use patterns and potentially their motives for cannabis use. Additionally, previous research has shown that men and women endorse different motives for their cannabis use. The present study was designed to assess whether a popular measure of cannabis use motives is invariant across veteran status and gender identity. Based on previous research, we hypothesized that cannabis motives would show invariance across SSM/V men, SSM/V women, non-veteran men, and non-veteran women (n = 1,011, SSM/V = 553) among those who indicated using cannabis at least once in their lifetime. Results from the four-group invariance testing procedure revealed metric invariance. This suggests that while the factor structure and factor loadings are invariant, there are differences at the intercept level for cannabis motives across groups. The same items load onto the same latent constructs and the strength of the items loading onto the latent factors was also the same across groups. The demonstrated invariance has implications for use in SSM/V and non-veteran clients. As this scale is brief, it could easily be used as a screening tool or used to guide intervention content.

Decreased hospital admissions through emergency departments during the COVID-19 pandemic.

STUDY OBJECTIVE: Emergency Department (ED) visits decreased significantly in the United States during the COVID-19 pandemic. A troubling proportion of this decrease was among patients who typically would have been admitted to the hospital, suggesting substantial deferment of care. We sought to describe and characterize the impact of COVID-19 on hospital admissions through EDs, with a specific focus on diagnosis group, age, gender, and insurance coverage. METHODS: We conducted a retrospective, observational study of aggregated third-party, anonymized ED patient data. This data included 501,369 patient visits from twelve EDs in Massachusetts from 1/1/2019-9/9/2019, and 1/1/2020-9/8/2020. We analyzed the total arrivals and hospital admissions and calculated confidence intervals for the change in admissions for each characteristic. We then developed a Poisson regression model to estimate the relative contribution of each characteristic to the decrease in admissions after the statewide lockdown, corresponding to weeks 11 through 36 (3/11/2020-9/8/2020). RESULTS: We observed a 32% decrease in admissions during weeks 11 to 36 in 2020, with significant decreases in admissions for chronic respiratory conditions and non-orthopedic needs. Decreases were particularly acute among women and children, as well as patients with Medicare or without insurance. The most common diagnosis during this time was SARS-CoV-2. CONCLUSION: Our findings demonstrate decreased hospital admissions through EDs during the pandemic and suggest that several patient populations may have deferred necessary care. Further research is needed to determine the clinical and operational consequences of this delay.

Emergency physicians' active patient queues over the course of a shift.

OBJECTIVES: When emergency physicians see new patients in an ad libitum system, they see fewer patients as the shift progresses. However, it is unclear if this reflects a decreasing workload, as patient assessments often span many hours. We sought to investigate whether the size of a physician's queue of active patients similarly declines over a shift. METHODS: Retrospective cohort study, conducted over two years in three community hospitals in the Northeastern United States, with 8 and 9-h shifts. Timestamps of all encounters were recorded electronically. Generalized estimating equations were constructed to predict the number of active patients a physician concurrently managed per hour. RESULTS: We evaluated 64 physicians over a two-year period, with 9822 physician-shifts. Across all sites, physicians managed an increasing queue of active patients in the first several hours. This queue plateaued in the middle of the shift, declining in the final hours, independently of other factors. Physicians' queues of active patients increased slightly with greater volume and acuity, but did not affect the overall pattern of work. Similarly, working alone or with colleagues had little effect on the number of active patients managed. CONCLUSIONS: Emergency physicians in an ad libitum system tend to see new patients until reaching a stable roster of active patients. This pattern may help explain why physicians see fewer new patients over the course of a shift, should be factored into models of throughput, and suggests new avenues for evaluating relationships between physician workload, patient safety, physicians' well-being, and the quality of care.

The pore-forming subunit MCU of the mitochondrial Ca2+ uniporter is required for normal glucose-stimulated insulin secretion in vitro and in vivo in mice.

AIMS/HYPOTHESIS: Mitochondrial oxidative metabolism is central to glucose-stimulated insulin secretion (GSIS). Whether Ca2+ uptake into pancreatic beta cell mitochondria potentiates or antagonises this process is still a matter of debate. Although the mitochondrial Ca2+ importer (MCU) complex is thought to represent the main route for Ca2+ transport across the inner mitochondrial membrane, its role in beta cells has not previously been examined in vivo. METHODS: Here, we inactivated the pore-forming subunit of the MCU, encoded by Mcu, selectively in mouse beta cells using Ins1Cre-mediated recombination. Whole or dissociated pancreatic islets were isolated and used for live beta cell fluorescence imaging of cytosolic or mitochondrial Ca2+ concentration and ATP production in response to increasing glucose concentrations. Electrophysiological recordings were also performed on whole islets. Serum and blood samples were collected to examine oral and i.p. glucose tolerance. RESULTS: Glucose-stimulated mitochondrial Ca2+ accumulation (p< 0.05), ATP production (p< 0.05) and insulin secretion (p< 0.01) were strongly inhibited in beta cell-specific Mcu-null (ßMcu-KO) animals, in vitro, as compared with wild-type (WT) mice. Interestingly, cytosolic Ca2+ concentrations increased (p< 0.001), whereas mitochondrial membrane depolarisation improved in ßMcu-KO animals. ßMcu-KO mice displayed impaired in vivo insulin secretion at 5 min (p< 0.001) but not 15 min post-i.p. injection of glucose, whilst the opposite phenomenon was observed following an oral gavage at 5 min. Unexpectedly, glucose tolerance was improved (p< 0.05) in young ßMcu-KO (<12 weeks), but not in older animals vs WT mice. CONCLUSIONS/INTERPRETATION: MCU is crucial for mitochondrial Ca2+ uptake in pancreatic beta cells and is required for normal GSIS. The apparent compensatory mechanisms that maintain glucose tolerance in ßMcu-KO mice remain to be established.

Theoretical bounds and approximation of the probability mass function of future hospital bed demand.

Failing to match the supply of resources to the demand for resources in a hospital can cause non-clinical transfers, diversions, safety risks, and expensive under-utilized resource capacity. Forecasting bed demand helps achieve appropriate safety standards and cost management by proactively adjusting staffing levels and patient flow protocols. This paper defines the theoretical bounds on optimal bed demand prediction accuracy and develops a flexible statistical model to approximate the probability mass function of future bed demand. A case study validates the model using blinded data from a mid-sized Massachusetts community hospital. This approach expands upon similar work by forecasting multiple days in advance instead of a single day, providing a probability mass function of demand instead of a point estimate, using the exact surgery schedule instead of assuming a cyclic schedule, and using patient-level duration-varying length-of-stay distributions instead of assuming patient homogeneity and exponential length of stay distributions. The primary results of this work are an accurate and lengthy forecast, which provides managers better information and more time to optimize short-term staffing adaptations to stochastic bed demand, and a derivation of the minimum mean absolute error of an ideal forecast.

Slice-illuminated optical projection tomography.

To improve the imaging performance of optical projection tomography (OPT) in live samples, we have explored a parallelized implementation of semi-confocal line illumination and detection to discriminate against scattered photons. Slice-illuminated OPT (sl-OPT) improves reconstruction quality in scattering samples by reducing interpixel crosstalk at the cost of increased acquisition time. For in vivo imaging, this can be ameliorated through the use of compressed sensing on angularly undersampled OPT data sets. Here, we demonstrate sl-OPT applied to 3D imaging of bead phantoms and live adult zebrafish.

Acanthodes and shark-like conditions in the last common ancestor of modern gnathostomes.

Acanthodians, an exclusively Palaeozoic group of fish, are central to a renewed debate on the origin of modern gnathostomes: jawed vertebrates comprising Chondrichthyes (sharks, rays and ratfish) and Osteichthyes (bony fishes and tetrapods). Acanthodian internal anatomy is primarily understood from Acanthodes bronni because it remains the only example preserved in substantial detail, central to which is an ostensibly osteichthyan braincase. For this reason, Acanthodes has become an indispensible component in early gnathostome phylogenies. Here we present a new description of the Acanthodes braincase, yielding new details of external and internal morphology, notably the regions surrounding and within the ear capsule and neurocranial roof. These data contribute to a new reconstruction that, unexpectedly, resembles early chondrichthyan crania. Principal coordinates analysis of a character-taxon matrix including these new data confirms this impression: Acanthodes is quantifiably closer to chondrichthyans than to osteichthyans. However, phylogenetic analysis places Acanthodes on the osteichthyan stem, as part of a well-resolved tree that also recovers acanthodians as stem chondrichthyans and stem gnathostomes. As such, perceived chondrichthyan features of the Acanthodes cranium represent shared primitive conditions for crown group gnathostomes. Moreover, this increasingly detailed picture of early gnathostome evolution highlights ongoing and profound anatomical reorganization of vertebrate crania after the origin of jaws but before the divergence of living clades.

The Impact of Hospital and Patient Factors on the Emergency Department Decision to Admit.

BACKGROUND: Substantial variation exists in rates of emergency department (ED) admission. We examine this variation after accounting for local and community characteristics. OBJECTIVES: Elucidate the factors that contribute to admission variation that are amenable to intervention with the goal of reducing variation and health care costs. METHODS: We conducted a retrospective cross-sectional study of 1,412,340 patient encounters across 18 sites from 2012-2013. We calculated the adjusted hospital-level admission rates using multivariate logistic regression. We adjusted for patient, provider, hospital, and community factors to compare admission rate variation and determine the influence of these characteristics on admission rates. RESULTS: The average adjusted admission rate was 22.9%, ranging from 16.1% (95% confidence interval [CI] 11.5-22%) to 32% (95% CI 26.0-38.8). There were higher odds of hospital admission with advancing age, male sex (odds ratio [OR] 1.20, 95% CI 1.91-1.21), and patients seen by a physician vs. mid-level provider (OR 2.26, 95% CI 2.23-2.30). There were increased odds of admission with rising ED volume, at academic institutions (OR 2.23, 95% CI 2.20-2.26) and at for-profit hospitals (OR 1.15, 95% CI 1.12-1.18). Admission rates were lower in communities with a higher per capita income, a higher rate of uninsured patients, and in more urban hospitals. In communities with the most primary providers, there were lower odds of admission (OR 0.60, 95% CI 0.57-0.68). CONCLUSION: Variation in hospital-level admission rates is associated with a number of local and community characteristics. However, the presence of persistent variation after adjustment suggests there are other unmeasured variables that also affect admission rates that deserve further study, particularly in an era of cost containment.

Modelling attending physician productivity in the emergency department: a multicentre study.

OBJECTIVES: Emergency physician productivity, often defined as new patients evaluated per hour, is essential to planning clinical operations. Prior research in this area considered this a static quantity; however, our group's study of resident physicians demonstrated significant decreases in hourly productivity throughout shifts. We now examine attending physicians' productivity to determine if it is also dynamic. METHODS: This is a retrospective cohort study, conducted from 2014 to 2016 across three community hospitals in the north-eastern USA, with different schedules and coverage. Timestamps of all patient encounters were automatically logged by the sites' electronic health record. Generalised estimating equations were constructed to predict productivity in terms of new patients per shift hour. RESULTS: 207 169 patients were seen by 64 physicians over 2 years, comprising 9822 physician shifts. Physicians saw an average of 15.0 (SD 4.7), 20.9 (SD 6.4) and 13.2 (SD 3.8) patients per shift at the three sites, with 2.97 (SD 0.22), 2.95 (SD 0.24) and 2.17 (SD 0.09) in the first hour. Across all sites, physicians saw significantly fewer new patients after the first hour, with more gradual decreases subsequently. Additional patient arrivals were associated with greater productivity; however, this attenuates substantially late in the shift. The presence of other physicians was also associated with slightly decreased productivity. CONCLUSIONS: Physician productivity over a single shift follows a predictable pattern that decreases significantly on an hourly basis, even if there are new patients to be seen. Estimating productivity as a simple average substantially underestimates physicians' capacity early in a shift and overestimates it later. This pattern of productivity should be factored into hospitals' staffing plans, with shifts aligned to start with the greatest volumes of patient arrivals.

How (ED) admission decisions differ when the same physician works in two different emergency department.

STUDY OBJECTIVE: Emergency physicians often work in multiple hospital emergency departments (EDs). We study how emergency physician admission decisions vary in different settings. METHODS: We conducted a retrospective, cross-sectional study over two years (2012-3) in six EDs in three states. Included physicians had ≥200 encounters per site in two different EDs. "Admissions" were ED encounters resulting in admission to the hospital or transfer to another hospital. The primary outcome was the adjusted admission rate difference between the two sites. Hierarchical logistic regression analysis was used to calculate adjusted admission rates for each physician, which were then tabulated for each physician and compared across sites. RESULTS: In 51,807 ED encounters seen by 16 physicians the average admission rate was 20.0%, and unadjusted admission rates differed between sites by 2.9% (range 0-8.4%) for the same physician. The adjusted admission rate was 19.3% and differed between sites by 2.1% (range 0.4%-6.2%). CONCLUSION: In this sample, some ED physicians made similar admission decisions in different settings while others increased or decreased their admission rates up to 25% when practicing in a different ED.

The relative contribution of provider and ED-level factors to variation among the top 15 reasons for ED admission.

STUDY OBJECTIVE: We examine adult emergency department (ED) admission rates for the top 15 most frequently admitted conditions, and assess the relative contribution in admission rate variation attributable to the provider and hospital. METHODS: This was a retrospective, cross-sectional study of ED encounters (≥18years) from 19 EDs and 603 providers (January 2012-December 2013), linked to the Area Health Resources File for county-level information on healthcare resources. "Hospital admission" was the outcome, a composite of inpatient, observation, or intra-hospital transfer. We studied the 15 most commonly admitted conditions, and calculated condition-specific risk-standardized hospital admission rates (RSARs) using multi-level hierarchical generalized linear models. We then decomposed the relative contribution of provider-level and hospital-level variation for each condition. RESULTS: The top 15 conditions made up 34% of encounters and 49% of admissions. After adjustment, the eight conditions with the highest hospital-level variation were: 1) injuries, 2) extremity fracture (except hip fracture), 3) skin infection, 4) lower respiratory disease, 5) asthma/chronic obstructive pulmonary disease (A&C), 6) abdominal pain, 7) fluid/electrolyte disorders, and 8) chest pain. Hospital-level intra-class correlation coefficients (ICC) ranged from 0.042 for A&C to 0.167 for extremity fractures. Provider-level ICCs ranged from 0.026 for abdominal pain to 0.104 for chest pain. Several patient, hospital, and community factors were associated with admission rates, but these varied across conditions. CONCLUSION: For different conditions, there were different contributions to variation at the hospital- and provider-level. These findings deserve consideration when designing interventions to optimize admission decisions and in value-based payment programs.

Conditionals by inversion provide a universal method for the generation of conditional alleles.

Conditional mutagenesis is becoming a method of choice for studying gene function, but constructing conditional alleles is often laborious, limited by target gene structure, and at times, prone to incomplete conditional ablation. To address these issues, we developed a technology termed conditionals by inversion (COIN). Before activation, COINs contain an inverted module (COIN module) that lies inertly within the antisense strand of a resident gene. When inverted into the sense strand by a site-specific recombinase, the COIN module causes termination of the target gene's transcription and simultaneously provides a reporter for tracking this event. COIN modules can be inserted into natural introns (intronic COINs) or directly into coding exons as part of an artificial intron (exonic COINs), greatly simplifying allele design and increasing flexibility over previous conditional KO approaches. Detailed analysis of over 20 COIN alleles establishes the reliability of the method and its broad applicability to any gene, regardless of exon-intron structure. Our extensive testing provides rules that help ensure success of this approach and also explains why other currently available conditional approaches often fail to function optimally. Finally, the ability to split exons using the COIN's artificial intron opens up engineering modalities for the generation of multifunctional alleles.

Paediatric Renal Stone Management in Africa: A Scoping Review and Analysis of Current Practices.

Renal stones are solid deposits formed from minerals and salts that develop within the kidneys and urinary tract. While the condition is more common among adults, children and even infants can also be affected. There is an increasing incidence of paediatric renal stones in Africa alongside multiple challenges faced in managing the condition. This scoping review aimed to provide an overview of the management modalities of paediatric renal stones in Africa. This study utilised Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. A systematic search was conducted in three electronic databases: PubMed, African Journal Online (AJOL), and Google Scholar, with 1,180 articles curated. After extensive examination, 10 articles satisfied the inclusion criteria. The review found that calcium oxalate stones were the most prevalent type, accounting for 34.03% of cases, followed by whewellite stones and ammonium urate stones. The most frequent location for stones was the kidney, and the most common symptom was pain. Abdominopelvic ultrasound was the most frequently utilised investigation. Of the 886 patients managed for renal stones, 75.4% were managed surgically, 2.9% medically, and 21.7% spontaneously resolved without intervention. This review identifies opportunities for improving the management of paediatric renal stones in Africa, including the need for standardised diagnostic and treatment protocols and the development of evidence-based guidelines tailored to the African context. Overall, this scoping review provides valuable insights into the patterns and management of paediatric renal stones in Africa and highlights the need for further research to improve the management of this condition in the region.

Prevention of bone loss and vertebral fractures in patients with chronic epilepsy--antiepileptic drug and osteoporosis prevention trial.

PURPOSE: To evaluate whether use of a bisphosphonate (risedronate) in addition to calcium and vitamin D in male veterans with epilepsy who were taking antiepileptic drugs (AEDs) long term can prevent the loss of bone mass (BMD, bone mineral density) associated with AED use compared to patients who were treated with a placebo plus calcium and vitamin D. As a secondary end point we studied the incidence of new morphometric vertebral and nonvertebral fractures. METHODS: Antiepileptic drug and osteoporosis prevention trial (ADOPT) was designed as a prospective 2-year double-blind, randomized placebo controlled study involving 80 male veterans with epilepsy who were being treated with AEDs such as phenytoin, phenobarbital, sodium valproate, or carbamazepine for a minimum of 2 years. All enrolled participants received calcium and vitamin D supplementation, and were randomized to risedronate or matching placebo. Total body, bilateral proximal femora, and anteroposterior (AP) lumbar spine BMDs in addition to morphometric lateral vertebral assessments (LVAs) were evaluated by a dual energy x-ray absorptiometry (DXA) instrument. Comparisons of BMDs were made between baseline, 1 year, and after 2 years of enrollment in the study. The incidence of new vertebral and nonvertebral fractures was secondary end point. KEY FINDINGS: Of the 80 patients initially enrolled in the study, 53 patients completed the study. Baseline characteristics of the two groups were similar. At the end of the study, in the placebo plus calcium and vitamin D group, we observed a significant improvement in BMD at any of the evaluated sites when compared to their baseline scans in 69% (18/26) of the participants. In the risedronate plus calcium and vitamin D group, we observed significant improvement of BMDs in 70% (19/27) of the participants. At the end of the study, the risedronate group experienced a significant increase of BMD at the lumbar spine L1-4 (1.267-1.332 g/cm(2)), which was significantly larger than that seen in the placebo group) (1.229 g/cm(2) vs. 1.245 g/cm(2) ; p = 0.0066).There were nonsignificant differences between the two groups regarding changes of total body BMD or at the proximal bilateral femora. Five new vertebral fractures and one nonvertebral fracture were observed only in the placebo group. SIGNIFICANCE: Calcium and vitamin D supplementation or calcium and vitamin D supplementation in addition to risedronate improved BMD in more than 69% of male veterans with epilepsy who were taking AEDs. In the group receiving risedronate plus calcium and vitamin D there was a significant improvement of BMD at the lumbar spine as compared to the placebo group, which also received calcium and vitamin D. The use of risedronate plus calcium and vitamin D prevented the incidence of new vertebral fractures and one nonvertebral fracture in this cohort.

Single-shot optical projection tomography for high-speed volumetric imaging of dynamic biological samples.

A single-shot adaptation of Optical Projection Tomography (OPT) for high-speed volumetric snapshot imaging of dynamic mesoscopic biological samples is presented. Conventional OPT has been applied to in vivo imaging of animal models such as D. rerio, but the sequential acquisition of projection images typically requires samples to be immobilized during the acquisition. A proof-of-principle system capable of single-shot tomography of a ~1 mm3 volume is presented, demonstrating camera-limited rates of up to 62.5 volumes/s, which has been applied to 3D imaging of a freely swimming zebrafish embryo. This is achieved by recording eight projection views simultaneously on four low-cost CMOS cameras. With no stage required to rotate the sample, this single-shot OPT system can be implemented with a component cost of under £5000. The system design can be adapted to different sized fields of view and may be applied to a broad range of dynamic samples, including high throughput flow cytometry applied to model organisms and fluid dynamics studies.

Label-free intraoperative histology of bone tissue via deep-learning-assisted ultraviolet photoacoustic microscopy.

Obtaining frozen sections of bone tissue for intraoperative examination is challenging. To identify the bony edge of resection, orthopaedic oncologists therefore rely on pre-operative X-ray computed tomography or magnetic resonance imaging. However, these techniques do not allow for accurate diagnosis or for intraoperative confirmation of the tumour margins, and in bony sarcomas, they can lead to bone margins up to 10-fold wider (1,000-fold volumetrically) than necessary. Here, we show that real-time three-dimensional contour-scanning of tissue via ultraviolet photoacoustic microscopy in reflection mode can be used to intraoperatively evaluate undecalcified and decalcified thick bone specimens, without the need for tissue sectioning. We validate the technique with gold-standard haematoxylin-and-eosin histology images acquired via a traditional optical microscope, and also show that an unsupervised generative adversarial network can virtually stain the ultraviolet-photoacoustic-microscopy images, allowing pathologists to readily identify cancerous features. Label-free and slide-free histology via ultraviolet photoacoustic microscopy may allow for rapid diagnoses of bone-tissue pathologies and aid the intraoperative determination of tumour margins.

Single-shot 3D photoacoustic computed tomography with a densely packed array for transcranial functional imaging.

Photoacoustic computed tomography (PACT) is emerging as a new technique for functional brain imaging, primarily due to its capabilities in label-free hemodynamic imaging. Despite its potential, the transcranial application of PACT has encountered hurdles, such as acoustic attenuations and distortions by the skull and limited light penetration through the skull. To overcome these challenges, we have engineered a PACT system that features a densely packed hemispherical ultrasonic transducer array with 3072 channels, operating at a central frequency of 1 MHz. This system allows for single-shot 3D imaging at a rate equal to the laser repetition rate, such as 20 Hz. We have achieved a single-shot light penetration depth of approximately 9 cm in chicken breast tissue utilizing a 750 nm laser (withstanding 3295-fold light attenuation and still retaining an SNR of 74) and successfully performed transcranial imaging through an ex vivo human skull using a 1064 nm laser. Moreover, we have proven the capacity of our system to perform single-shot 3D PACT imaging in both tissue phantoms and human subjects. These results suggest that our PACT system is poised to unlock potential for real-time, in vivo transcranial functional imaging in humans.