First Results from a Broadband Search for Dark Photon Dark Matter in the 44 to 52 µeV Range with a Coaxial Dish Antenna.

We present first results from a dark photon dark matter search in the mass range from 44 to 52 µeV (10.7-12.5 GHz) using a room-temperature dish antenna setup called GigaBREAD. Dark photon dark matter converts to ordinary photons on a cylindrical metallic emission surface with area 0.5 m^{2} and is focused by a novel parabolic reflector onto a horn antenna. Signals are read out with a low-noise receiver system. A first data taking run with 24 days of data does not show evidence for dark photon dark matter in this mass range, excluding dark photon photon mixing parameters χ≳10^{-12} in this range at 90% confidence level. This surpasses existing constraints by about 2 orders of magnitude and is the most stringent bound on dark photons in this range below 49 µeV.

Spatial Multiplex In Situ Tagging (MIST) Technology for Rapid, Highly Multiplexed Detection of Protein Distribution on Brain Tissue.

Highly multiplexed analysis of biospecimens significantly advances the understanding of biological basics of diseases, but these techniques are limited by the number of multiplexity and the speed of processing. Here, we present a rapid multiplex method for quantitative detection of protein markers on brain sections with the cellular resolution. This spatial multiplex in situ tagging (MIST) technology is built upon a MIST microarray that contains millions of small microbeads carrying barcoded oligonucleotides. Using antibodies tagged with UV cleavable oligonucleotides, the distribution of protein markers on a tissue slice could be "printed" on the MIST microarray with high fidelity. The performance of this technology in detection sensitivity, resolution, and signal-to-noise level has been fully characterized by detecting brain cell markers. We showcase the codetection of 31 proteins simultaneously within 2 h, which is about 10 times faster than the other immunofluorescence-based approaches of similar multiplexity. A full set of computational toolkits was developed to segment the small regions and identify the regional differences across the entire mouse brain. This technique enables us to rapidly and conveniently detect dozens of biomarkers on a tissue specimen, and it can find broad applications in clinical pathology and disease mechanistic studies.

Broadband Solenoidal Haloscope for Terahertz Axion Detection.

We introduce the Broadband Reflector Experiment for Axion Detection (BREAD) conceptual design and science program. This haloscope plans to search for bosonic dark matter across the [10^{-3},1] eV ([0.24, 240] THz) mass range. BREAD proposes a cylindrical metal barrel to convert dark matter into photons, which a novel parabolic reflector design focuses onto a photosensor. This unique geometry enables enclosure in standard cryostats and high-field solenoids, overcoming limitations of current dish antennas. A pilot 0.7 m^{2} barrel experiment planned at Fermilab is projected to surpass existing dark photon coupling constraints by over a decade with one-day runtime. Axion sensitivity requires <10^{-20} W/sqrt[Hz] sensor noise equivalent power with a 10 T solenoid and 10 m^{2} barrel. We project BREAD sensitivity for various sensor technologies and discuss future prospects.

New Class of Radially Adjustable Stentrievers for Acute Ischemic Stroke: Primary Results of the Multicenter TIGER Trial.

[Figure: see text].

Telogen effluvium associated with COVID-19 infection.

Telogen effluvium (TE) is characterized by diffuse hair shedding 2-3 months after a stressor, and COVID-19 infection is potentially one such stressor. Those who were infected with the virus were under immense psychosocial and physiologic stress. We retrospectively reviewed electronic medical records of 552 patients who were evaluated by a Henry Ford Health System dermatologist between February 2020 and September 2020 and had a diagnosis of COVID-19 infection. Ten patients were identified with TE attributed to COVID-19 infection and described their presentations as a case series. For the ten patients selected, the mean age was 48.5 years old and 90% were female. Six of the patients were Black, one Middle Eastern, and three White. On average, the hair shedding began 50 days after the first symptom of COVID-19 infection. About 80% of these patients were treated with antibiotics, systemic corticosteroids, and/or hydroxychloroquine for their COVID-19 infection and 70% were hospitalized. The presentations of these patients suggest that COVID-19 infection may be a significant trigger of TE. TE caused by hydroxychloroquine, azithromycin or other medications cannot be ruled out, and the global pandemic itself is a source of psychosocial stress. Further studies will be needed to understand the long-term prevalence and prognosis of TE associated with COVID-19 infection.

Flattening the curve in oncologic surgery: Impact of Covid-19 on surgery at tertiary care cancer center.

INTRODUCTION: Covid-19 has ushered in drastic changes to the healthcare system in order to "flatten the curve"; in particular, surgical operations that can consume vital, limited resources, not to mention the risk to staff, anesthesiologists, and surgeons. However, under unique circumstances with diligent preparation, vital oncologic operations can be performed safely. METHODS: Prospective comparison of surgical cases during the pandemic from December 2019 to May 2020 to the correlating time frame from December 2018 to May 2019. RESULTS: A significant decline in case volume was not appreciated until the United States declared a national state of emergency, allowing patients with cancer to continue to undergo curative tumor resection until then (428.3 ± 51.5 vs 166.6 ± 59.8 cases/week; P < .001). The decrease was consistent with the mean case volume during the holidays (213.8 ± 76.8 vs 166.6 ± 59.8 case/week; P = .648). Evaluation of surgical subspecialties demonstrated a significant decrease for all subspecialties with the greatest decline in sarcoma (P = .002) and endocrine (P = .001) surgeries, while vascular (P = .004) and thoracic (P = .011) surgeries had the least. CONCLUSIONS: The novel coronavirus has drastically reduced oncologic operations, but with proper evaluation of patients and allocation of resources, surgery can be performed safely without compromising the aim to flatten the curve and control the coronavirus pandemic.

Subarachnoid Hemorrhage Pattern Predicts Acute Cerebral Blood Flow Response in the Rat.

There is considerable variability in the presentation of patients with acute subarachnoid hemorrhage (aSAH). Evidence suggests that a thick, diffuse clot better predicts the development of delayed cerebral ischemia and poor outcomes. In a rodent model of acute SAH, we directly measured the effects of the volume of blood injected versus the pattern of distribution of hemorrhage in the subarachnoid space on markers of early brain injury, namely, cerebral blood flow (CBF), cerebrospinal fluid (CSF) concentrations of P450 eicosanoids and catecholamines, and cortical spreading depolarizations (CSDs). There is a significant decrease in CBF, an increase in CSF biomarkers, and a trend toward increasing frequency and severity of CSDs when grouped by severity of hemorrhage but not by volume of blood injected. In severe hemorrhage grade animals, there was a progressive decrease in CBF after successive CSD events. These results suggest that the pattern of SAH (thick diffuse clots) correlates with the "clinical" severity of SAH.

Search Strategy for Sleptons and Dark Matter Using the LHC as a Photon Collider.

We propose a search strategy using the LHC as a photon collider to open sensitivity to scalar lepton (slepton ℓ[over ˜]) production with masses around 15 to 60 GeV above that of neutralino dark matter χ[over ˜]_{1}^{0}. This region is favored by relic abundance and muon (g-2)_{µ} arguments. However, conventional searches are hindered by the irreducible diboson background. We overcome this obstruction by measuring initial state kinematics and the missing momentum four-vector in proton-tagged ultraperipheral collisions using forward detectors. We demonstrate sensitivity beyond LEP for slepton masses of up to 200 GeV for 15≲Δm(ℓ[over ˜],χ[over ˜]_{1}^{0})≲60 GeV with 100 fb^{-1} of 13 TeV proton collisions. We encourage the LHC collaborations to open this forward frontier for discovering new physics.

Skin cancer in the military: A systematic review of melanoma and nonmelanoma skin cancer incidence, prevention, and screening among active duty and veteran personnel.

BACKGROUND: Occupational sun exposure is a well-studied risk factor for skin cancer development, but more work is needed to assess melanoma and nonmelanoma skin cancer risk among US military personnel to improve education and screening efforts in this population. OBJECTIVE: To conduct an extensive review of skin cancer risks for US military personnel to inform preventive education, diagnosis, and treatment efforts to better protect these individuals from future skin cancer development. METHODS: A systematic review of published studies on the subject of melanoma and nonmelanoma skin cancer in military personnel was conducted. RESULTS: A total of 9 studies describing skin cancer incidence in the US military were identified, with 4 studies specific to melanoma. The study findings reveal an increased risk for melanoma associated with service in the military or prisoner of war status. Service in tropical environments was associated with an increased incidence of both melanoma and nonmelanoma skin cancer among World War II soldiers. Two studies found that increased melanoma risk was also branch dependent, with the highest rates among the United States Air Force. Several of the reviewed studies implicated increased sun exposure during military service and lack of sufficient sun protection as the causes of higher rates of skin cancer among US military and veteran populations as compared with among the nonmilitary population in the United States. LIMITATIONS: The reviewed articles have variable results; a prospective randomized controlled trial would be helpful to develop interventions that mitigate skin cancer risk in the US military. CONCLUSION: This review identifies an abundance of evidence for an increased risk for skin cancer development among US active duty and veteran populations.

Protective role of p450 epoxyeicosanoids in subarachnoid hemorrhage.

BACKGROUND: Patients recovering from aneurysmal subarachnoid hemorrhage (SAH) are at risk for developing delayed cerebral ischemia (DCI). Experimental and human studies implicate the vasoconstrictor P450 eicosanoid 20-hydroxyeicosatetraenoic acid (20-HETE) in the pathogenesis of DCI. To date, no studies have evaluated the role of vasodilator epoxyeicosatrienoic acids (EETs) in DCI. METHODS: Using mass spectrometry, we measured P450 eicosanoids in cerebrospinal fluid (CSF) from 34 SAH patients from 1 to 14 days after admission. CSF eicosanoid levels were compared in patients who experienced DCI versus those who did not. We then studied the effect of EETs in a model of SAH using mice lacking the enzyme soluble epoxide hydrolase (sEH), which catabolizes EETs into their inactive diol. To assess changes in vessel morphology and cortical perfusion in the mouse brain, we used optical microangiography, a non-invasive coherence-based imaging technique. RESULTS: Along with increases in 20-HETE, we found that CSF levels of 14,15-EET were elevated in SAH patients compared to control CSF, and levels were significantly higher in patients who experienced DCI compared to those who did not. Mice lacking sEH had elevated 14,15-EET and were protected from the delayed decrease in microvascular cortical perfusion after SAH, compared to wild type mice. CONCLUSIONS: Our findings suggest that P450 eicosanoids play an important role in the pathogenesis of DCI. While 20-HETE may contribute to the development of DCI, 14,15-EET may afford protection against DCI. Strategies to enhance 14,15-EET, including sEH inhibition, should be considered as part of a comprehensive approach to prevent DCI.

The synergistic role of virtual coaching with simulation-based mastery learning for upper endoscopy.

Introduction: Our simulation-based mastery learning (SBML) curriculum, delivered in person, has been shown to successfully train novices in structured esophagogastroduodenoscopy (EGD). SBML with virtual coaching (VC) has the potential to improve the effectiveness and efficiency of endoscopy training and expand access to trainees from around the world. We share our observations conducting an EGD training course using SBML with VC. Methods: We conducted a 1-week virtual SBML course for novice trainees across seven academic centers in the USA and Asia. The cognitive component was delivered using an online learning platform. For technical skills, a virtual coach supervised hands-on training and local coaches provided assistance when needed. At the end of training, an independent rater assessed simulation-based performance using a validated assessment tool. We assessed the clinical performance of 30 EGDs using the ASGE Assessment of Competency in Endoscopy tool. We compared the trainees' scores to our cohort trained using in-person SBML training using non-inferiority t-tests. Results: We enrolled 21 novice trainees (mean age: 30.8 ± 3.6 years; female: 52%). For tip deflection, the trainees reached the minimum passing standard after 31 ± 29 runs and mastery after 52 ± 37 runs. For structured EGD, the average score for the overall exam was 4.6 ± 0.6, similar to the in-person cohort (4.7 ± 0.5, p = 0.49). The knowledge-based assessment was also comparable (virtual coaching: 81.9 ± 0.1; direct coaching: 78.3 ± 0.1; p = 0.385). Over time, our novice trainees reached clinical competence at a similar rate to our historical in-person control. Conclusions: VC appears feasible and effective for training novice gastroenterology trainees. VC allowed us to scale our SBML course, expand access to experts, and administer SBML simultaneously across different sites at the highest standards.

Fanconi anemia complementation group A (FANCA) protein has intrinsic affinity for nucleic acids with preference for single-stranded forms.

The Fanconi anemia complementation group A (FANCA) gene is one of 15 disease-causing genes and has been found to be mutated in ∼60% of Fanconi anemia patients. Using purified protein, we report that human FANCA has intrinsic affinity for nucleic acids. FANCA binds to both single-stranded (ssDNA) and double-stranded (dsDNA) DNAs; however, its affinity for ssDNA is significantly higher than for dsDNA in an electrophoretic mobility shift assay. FANCA also binds to RNA with an intriguingly higher affinity than its DNA counterpart. FANCA requires a certain length of nucleic acids for optimal binding. Using DNA and RNA ladders, we determined that the minimum number of nucleotides required for FANCA recognition is ∼30 for both DNA and RNA. By testing the affinity between FANCA and a variety of DNA structures, we found that a 5'-flap or 5'-tail on DNA facilitates its interaction with FANCA. A patient-derived FANCA truncation mutant (Q772X) has diminished affinity for both DNA and RNA. In contrast, the complementing C-terminal fragment of Q772X, C772-1455, retains the differentiated nucleic acid-binding activity (RNA > ssDNA > dsDNA), indicating that the nucleic acid-binding domain of FANCA is located primarily at its C terminus, where most disease-causing mutations are found.

Quantitative surface-enhanced resonant Raman scattering multiplexing of biocompatible gold nanostars for in vitro and ex vivo detection.

Surface-enhanced Raman scattering (SERS)-active plasmonic nanomaterials have become a promising agent for molecular imaging and multiplex detection. To produce strong SERS intensity while retaining the nonaggregated state and biocompatibility needed for bioapplications, we integrated near-infrared (NIR) responsive plasmonic gold nanostars with resonant dyes for resonant SERS (SERRS). The SERRS on nanostars was several orders of magnitude greater than signals from SERRS on nanospheres and nonresonant SERS on nanostars. For the first time, we demonstrated quantitative multiplex detection using four unique nanostar SERRS probes in both in vitro solutions and ex vivo tissue samples under NIR excitation. With further optimization, in vivo tracking of multiple SERRS probes is possible.

Venous Sinus Stenting: Safety and Health Care Resource Evaluation for Optimal Recovery in an Evolving Health Care Environment.

BACKGROUND: Increasing evidence supports the effectiveness of venous sinus stenting (VSS) with favorable outcomes, safety, and expenses compared with shunting for idiopathic intracranial hypertension. Yet, no evidence is available regarding optimal postoperative recovery, which has increasing importance with the burdens on health care imposed by the coronavirus disease 2019 pandemic. We examined adverse events and costs after VSS and propose an optimal recovery pathway to maximize patient safety and reduce stress on health care resources. METHODS: A retrospective review was undertaken of elective VSS operations performed from May 2008 to August 2021 at a single institution. Primary data included hospital length of stay, intensive care unit (ICU) length of stay, adverse events, need for ICU interventions, and hospital costs. RESULTS: Fifty-three patients (98.1% female) met the inclusion criteria. Of these patients, 51 (96.2%) were discharged on postoperative day (POD) 1 and 2 patients were discharged on POD 2. Both patients discharged on POD 2 remained because of groin hematomas from femoral artery access. There were no major complications or care that required an ICU. Eight patients (15.1%) were lateralized to other ICUs or remained in a postanesthesia care unit because the neurosciences ICU was above capacity. Total estimated cost for initial recovery day in a neurosciences ICU room was $2361 versus $882 for a neurosurgery/neurology ward room. In our cohort, ward convalescence would save an estimated $79,866 for bed placement alone and increase ICU bed availability. CONCLUSIONS: Our findings reaffirm the safety of VSS. These patients should recover on a neurosurgery/neurology ward, which would save health care costs and increase ICU bed availability.

Low body mass index patients have worse outcomes after mechanical thrombectomy.

BACKGROUND: There is evidence that frailty is an independent predictor of worse outcomes after stroke. Similarly, although obesity is associated with a higher risk for stroke, there are multiple reports describing improved mortality and functional outcomes in higher body mass index (BMI) patients in a phenomenon known as the obesity paradox. We investigated the effect of low BMI on outcomes after mechanical thrombectomy (MT). METHODS: We conducted a retrospective analysis of 231 stroke patients who underwent MT at an academic medical center between 2020-2022. The patients' BMI data were collected from admission records and coded based on the Centers for Disease Control and Prevention (CDC) obesity guidelines. Recursive partitioning analysis (RPA) in R software was employed to automatically detect a BMI threshold associated with a significant survival benefit. Frailty was quantified using the Modified Frailty Index 5 and 11. RESULTS: In our dataset, by CDC classification, 2.6% of patients were underweight, 27.3% were normal BMI, 30.7% were overweight, 19.9% were class I obese, 9.5% were class II obese, and 10% were class III obese. There were no significant differences between these groups. RPA identified a clinically significant BMI threshold of 23.62 kg/m2. Independent of frailty, patients with a BMI ≤23.62 kg/m2 had significantly worse overall survival (P<0.001) and 90-day modified Rankin Scale (P=0.027) than patients above the threshold. CONCLUSIONS: Underweight patients had worse survival and functional outcomes after MT. Further research should focus on the pathophysiology underlying poor prognosis in underweight MT patients, and whether optimizing nutritional status confers any neuroprotective benefit.

Utilization of Vertebroplasty/Kyphoplasty in the Management of Compression Fractures: National Trends and Predictors of Vertebroplasty/Kyphoplasty.

OBJECTIVE: The purpose of this study is to examine the utilization of kyphoplasty/vertebroplasty procedures in the management of compression fractures. With the growing elderly population and the associated increase in rates of osteoporosis, vertebral compression fractures have become a daily encounter for spine surgeons. However, there remains a lack of consensus on the optimal management of this patient population. METHODS: A retrospective analysis of 91 million longitudinally followed patients from 2016 to 2019 was performed using the PearlDiver Patient Claims Database. Patients with compression fractures were identified using International Classification of Disease, 10th Revision codes, and a subset of patients who received kyphoplasty/vertebroplasty were identified using Common Procedural Terminology codes. Baseline demographic and clinical data between groups were acquired. Multivariable regression analysis was performed to determine predictors of receiving kyphoplasty/vertebroplasty. RESULTS: A total of 348,457 patients with compression fractures were identified with 9.2% of patients receiving kyphoplasty/vertebroplasty as their initial treatment. Of these patients, 43.5% underwent additional kyphoplasty/vertebroplasty 30 days after initial intervention. Patients receiving kyphoplasty/vertebroplasty were significantly older (72.2 vs. 67.9, p < 0.05), female, obese, had active smoking status and had higher Elixhauser Comorbidity Index scores. Multivariable analysis demonstrated that female sex, smoking status, and obesity were the 3 strongest predictors of receiving kyphoplasty/vertebroplasty (odds ratio, 1.27, 1.24, and 1.14, respectively). The annual rate of kyphoplasty/vertebroplasty did not change significantly (range, 8%-11%). CONCLUSION: The majority of vertebral compression fractures are managed nonoperatively. However, certain patient factors such as smoking status, obesity, female sex, older age, osteoporosis, and greater comorbidities are predictors of undergoing kyphoplasty/vertebroplasty.

Cdx2 levels modulate intestinal epithelium maturity and Paneth cell development.

BACKGROUND & AIMS: Caudal-related homeobox protein 2 (Cdx2) is an intestine-specific transcription factor that is important for intestinal development and intestine-specific gene expression. Cdx2 regulates intestinal cell-cell adhesion, proliferation, and the transcriptional activities of Wnt and ß-catenin in cell culture systems. We generated transgenic mice that overexpress Cdx2 in the small intestinal and colonic epithelium to investigate the role of Cdx2 in differentiation and function of the intestinal epithelium. METHODS: We established 4 different lines of villin-Cdx2 transgenic mice. Intestines were collected from infant, 3-month old, and wild-type mice. Genes of interest and cell lineage markers were examined by polymerase chain reaction and immunohistochemistry. RESULTS: Villin-Cdx2 transgenic mice had complex phenotypes that were associated with transgene expression levels. The 2 lines that had the greatest levels of transgene expression had significant, preweaning failure to grow and death; these were the result of early epithelial maturation and alterations in nutrient digestion and absorption. Fat malabsorption was a prominent feature. Other effects associated with the transgene expression included loss of Paneth cell markers, increases in goblet cells, and migration of proliferating, EphB2-expressing cells to the crypt base. Loss of Paneth cell markers was associated with reduced nuclear localization of ß-catenin but not homeotic posteriorization of the epithelium by Cdx2. CONCLUSIONS: Overexpression of Cdx2 in the small intestine is associated with reduced post-natal growth, early epithelial maturation, alterations in crypt base organization, and changes in Paneth and goblet cell lineages. Cdx2 is a critical regulator not only of intestine-specific genes, but also processes that determine epithelial maturity and function.

Cyclic microchip assay for measurement of hundreds of functional proteins in single neurons.

Despite the fact that proteins carry out nearly all cellular functions and mark the differences of cells, the existing single-cell tools can only analyze dozens of proteins, a scale far from full characterization of cells and tissue yet. Herein, we present a single-cell cyclic multiplex in situ tagging (CycMIST) technology that affords the comprehensive functional proteome profiling of single cells. We demonstrate the technology by detecting 182 proteins that include surface markers, neuron function proteins, neurodegeneration markers, signaling pathway proteins, and transcription factors. Further studies on cells derived from the 5XFAD mice, an Alzheimer's Disease (AD) model, validate the utility of our technology and reveal the deep heterogeneity of brain cells. Through comparison with control mouse cells, we have identified differentially expressed proteins in AD pathology. Our technology could offer new insights into cell machinery and thus may advance many fields including drug discovery, molecular diagnostics, and clinical studies.

A technical note on anterolateral mobilization in vertebrobasilar dolichoectasia for relief of brainstem compression.

Vascular compression of neural tissue causing neurological symptoms is a wellknown phenomenon. This is commonly seen in trigeminal neuralgia and, less commonly, in hemifacial spasm by small arteries, which can be treated by microvascular decompression. Rarely, larger arteries, such as the vertebral arteries, may compress the brainstem. This can lead to symptoms of pontine or medullary distress like hemiparesis, dysphagia, or respiratory distress. This is treated by macrovascular decompression. Due to the rare and heterogenous nature of this disease, there is no standardized approach. We describe a novel technique whereby the vertebrobasilar system is mobilized anterolaterally towards the occipital condyle with a sling to decompress the brainstem.
We report two cases of vertebrobasilar dolichoectasia causing brainstem compression. A carotid patch graft sling with anterolateral mobilization to the occipital condyle is described as a surgical nuance to macrovascular decompressive surgery. Briefly, the vertebral artery was identified and dissected away from the brainstem and the bulbar cranial nerves. Bovine pericardium graft was used to create a sling around the artery by suturing the two ends together. The sling was then fixed either to the occipital condyle using cranial plating screws or suturing to the dura of the occipital condyle.
A novel surgical technique for management of vertebrobasilar dolichoectasia causing brainstem compression with progressive neurological deterioration is reported. Anatomical location and the offending vessel should guide neurosurgeons to select the best surgical option to achieve complete decompression of the involved neural structures.

Operative Technique: Angiomatoid Fibrous Histiocytoma-Unique Case and Management.

Objective We describe the first jugular foramen angiomatoid fibrous histiocytoma (AFH) case and the first treatment with preoperative endovascular embolization. AFH is a rare intracranial neoplasm, primarily found in pediatric patient extremities. With an increase in AFH awareness and a well-described genetic profile, intracranial prevalence has also subsequently increased. Study Design We compare this case to previously reported cases using PubMed/Medline literature search, which was performed using the algorithm ["intracranial" AND "angiomatoid fibrous histiocytoma"] through December 2020 (23 manuscripts with 46 unique cases). Patient An 8-year-old female presented with failure to thrive and right-sided hearing loss. Work-up revealed an absence of right-sided serviceable hearing and a large jugular foramen mass. Angiogram revealed primary arterial supply from the posterior branch of the ascending pharyngeal artery, which was preoperatively embolized. Intervention Gross total resection was performed via a translabyrinthine approach. Conclusion The case presented is unique; the first reported AFH at the jugular foramen and the first reported case utilizing preoperative embolization. Preoperative embolization is a relatively safe technique that can improve the surgeon's ability to perform a maximally safe resection, which may decrease the need for adjuvant radiation in rare skull base tumors in young patients.