Modulated Expression of Specific tRNAs Drives Gene Expression and Cancer Progression.

Transfer RNAs (tRNAs) are primarily viewed as static contributors to gene expression. By developing a high-throughput tRNA profiling method, we find that specific tRNAs are upregulated in human breast cancer cells as they gain metastatic activity. Through loss-of-function, gain-of-function, and clinical-association studies, we implicate tRNAGluUUC and tRNAArgCCG as promoters of breast cancer metastasis. Upregulation of these tRNAs enhances stability and ribosome occupancy of transcripts enriched for their cognate codons. Specifically, tRNAGluUUC promotes metastatic progression by directly enhancing EXOSC2 expression and enhancing GRIPAP1-constituting an "inducible" pathway driven by a tRNA. The cellular proteomic shift toward a pro-metastatic state mirrors global tRNA shifts, allowing for cell-state and cell-type transgene expression optimization through codon content quantification. TRNA modulation represents a mechanism by which cells achieve altered expression of specific transcripts and proteins. TRNAs are thus dynamic regulators of gene expression and the tRNA codon landscape can causally and specifically impact disease progression.

Endogenous tRNA-Derived Fragments Suppress Breast Cancer Progression via YBX1 Displacement.

Upon exposure to stress, tRNAs are enzymatically cleaved, yielding distinct classes of tRNA-derived fragments (tRFs), yielding distinct classes of tRFs. We identify a novel class of tRFs derived from tRNA(Glu), tRNA(Asp), tRNA(Gly), and tRNA(Tyr) that, upon induction, suppress the stability of multiple oncogenic transcripts in breast cancer cells by displacing their 3' untranslated regions (UTRs) from the RNA-binding protein YBX1. This mode of post-transcriptional silencing is sequence specific, as these fragments all share a common motif that matches the YBX1 recognition sequence. Loss-of-function and gain-of-function studies, using anti-sense locked-nucleic acids (LNAs) and synthetic RNA mimetics, respectively, revealed that these fragments suppress growth under serum-starvation, cancer cell invasion, and metastasis by breast cancer cells. Highly metastatic cells evade this tumor-suppressive pathway by attenuating the induction of these tRFs. Our findings reveal a tumor-suppressive role for specific tRNA-derived fragments and describe a molecular mechanism for their action. This transcript displacement-based mechanism may generalize to other tRNA, ribosomal-RNA, and sno-RNA fragments.

Nuclear TARBP2 Drives Oncogenic Dysregulation of RNA Splicing and Decay.

Post-transcriptional regulation of RNA stability is a key step in gene expression control. We describe a regulatory program, mediated by the RNA binding protein TARBP2, that controls RNA stability in the nucleus. TARBP2 binding to pre-mRNAs results in increased intron retention, subsequently leading to targeted degradation of TARBP2-bound transcripts. This is mediated by TARBP2 recruitment of the m6A RNA methylation machinery to its target transcripts, where deposition of m6A marks influences the recruitment of splicing regulators, inhibiting efficient splicing. Interactions between TARBP2 and the nucleoprotein TPR then promote degradation of these TARBP2-bound transcripts by the nuclear exosome. Additionally, analysis of clinical gene expression datasets revealed a functional role for TARBP2 in lung cancer. Using xenograft mouse models, we find that TARBP2 affects tumor growth in the lung and that this is dependent on TARBP2-mediated destabilization of ABCA3 and FOXN3. Finally, we establish ZNF143 as an upstream regulator of TARBP2 expression.

A phase 1 study to assess the absolute bioavailability, mass balance, pharmacokinetics, metabolism, and excretion of [14C]-mobocertinib, an oral inhibitor of EGFR exon 20 insertion mutations, in healthy participants.

Mobocertinib (TAK-788) is a first-in-class oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that received accelerated approval for the treatment of patients with non-small cell lung cancer with EGFR exon 20 insertion mutations previously treated with platinum-based chemotherapy. This phase 1, 2-period, study was conducted to assess the absolute bioavailability of mobocertinib (Period 1), as well as mass balance, pharmacokinetics, metabolism, and excretion of [14C]-mobocertinib (Period 2) in healthy adult males. In Period 1, participants received a single oral capsule dose of 160 mg mobocertinib, followed by a 15-minute intravenous infusion of 50 µg (~ 2 µCi) [14C]-mobocertinib administered from 3.75 to 4 h after the capsule dose. In Period 2, a single oral dose of 160 mg (~ 100 µCi) [14C]-mobocertinib was administered as an oral solution. The geometric mean absolute bioavailability of mobocertinib was determined to be 36.7%. After oral administration of [14C]-mobocertinib, mobocertinib and its active metabolites, AP32960 and AP32914, were minor components in plasma, accounting for only 0.275% of total plasma radioactivity as the majority of mobocertinib-related material was covalently bound to plasma proteins. The geometric mean percentage of the administered radioactive dose recovered in the urine and feces was 3.57% and 76.0%, respectively. Only 0.39% of the oral dose of [14C]-mobocertinib was recovered in the urine as mobocertinib; thus, indicating that renal excretion of unchanged drug was a very minor pathway of elimination. In both treatment periods, mobocertinib was generally safe and well-tolerated as all adverse events were Grade 1 in severity. (Trial registration number ClinicalTrials.gov NCT03811834. Registration date January 22, 2019).

Role of c-Myc haploinsufficiency in the maintenance of HSCs in mice.

This study was conducted to determine the dosage effect of c-Myc on hematopoiesis and its distinct role in mediating the Wnt/ß-catenin pathway in hematopoietic stem cell (HSC) and bone marrow niche cells. c-Myc haploinsufficiency led to ineffective hematopoiesis by inhibiting HSC self-renewal and quiescence and by promoting apoptosis. We have identified Nr4a1, Nr4a2, and Jmjd3, which are critical for the maintenance of HSC functions, as previously unrecognized downstream targets of c-Myc in HSCs. c-Myc directly binds to the promoter regions of Nr4a1, Nr4a2, and Jmjd3 and regulates their expression. Our results revealed that Nr4a1 and Nr4a2 mediates the function of c-Myc in regulating HSC quiescence, whereas all 3 genes contribute to the function of c-Myc in the maintenance of HSC survival. Adenomatous polyposis coli (Apc) is a negative regulator of the Wnt/ß-catenin pathway. We have provided the first evidence that Apc haploinsufficiency induces a blockage of erythroid lineage differentiation through promoting secretion of IL6 in bone marrow endothelial cells. We found that c-Myc haploinsufficiency failed to rescue defective function of Apc-deficient HSCs in vivo but it was sufficient to prevent the development of severe anemia in Apc-heterozygous mice and to significantly prolong the survival of those mice. Furthermore, we showed that c-Myc-mediated Apc loss induced IL6 secretion in endothelial cells, and c-Myc haploinsufficiency reversed the negative effect of Apc-deficient endothelial cells on erythroid cell differentiation. Our studies indicate that c-Myc has a context-dependent role in mediating the function of Apc in hematopoiesis.

Persistence and switching patterns of migraine prophylactic medications in Canada: A retrospective claims analysis comparing adherence and evaluating the economic burden of illness.

PURPOSE: To describe patient characteristics, treatment patterns, and the burden of illness among adult migraine patients in Canada prescribed migraine prophylactics. Little is known about the relative persistence of treatments in the real-world setting and the impact of migraine prophylactic therapy on patients. As a result, migraine care in Canada continues to inadequately serve patients suffering from frequent headache days, reflecting a large unmet need. METHODS: This retrospective study used Reformulary Group's longitudinal prescription claims database. Private payer data were analyzed to identify 2007 migraine prophylactic naïve patients, with a prior history of acute therapy, for tracking over 24 months to determine treatment patterns and costs. Patient flow is summarized in a Sankey diagram visualizing persistence and switching across different timepoints. RESULTS: Patient persistence to migraine prophylactic medications was low at 24.9% (n=500); Switching from index medications to another prophylactic medication was common (27%), however 50% of patients discontinued without switching. It was observed that acute treatment and opioid use were much lower when patients established and maintained therapy on migraine prophylactics. Overall, angiotensin receptor blockers and CGRP antagonists had high persistence but were underutilized therapies while the inverse was true for antidepressants and anticonvulsants. CONCLUSION: In a real-word setting, recognizing that many patients may discontinue preventative treatment completely after their first therapy, there is a need to employ migraine-specific prophylactics and/or tolerable medications early. Treatment guidelines aligned to costs savings and/or requiring step therapy may be inadvertently failing patients. Further, the impact of migraine on the day-to-day lives of patients and high societal costs such as its impact on productivity should be weighed in considering migraine's burden of illness and the benefits of treatment.

The use of natural language processing in detecting and predicting falls within the healthcare setting: a systematic review.

Falls are a common problem associated with significant morbidity, mortality, and economic costs. Current fall prevention policies in local healthcare settings are often guided by information provided by fall risk assessment tools, incident reporting, and coding data. This review was conducted with the aim of identifying studies which utilized natural language processing (NLP) for the automated detection and prediction of falls in the healthcare setting. The databases Ovid Medline, Ovid Embase, Ovid Emcare, PubMed, CINAHL, IEEE Xplore, and Ei Compendex were searched from 2012 until April 2023. Retrospective derivation, validation, and implementation studies wherein patients experienced falls within a healthcare setting were identified for inclusion. The initial search yielded 2611 publications for title and abstract screening. Full-text screening was conducted on 105 publications, resulting in 26 unique studies that underwent qualitative analyses. Studies applied NLP towards falls risk factor identification, known falls detection, future falls prediction, and falls severity stratification with reasonable success. The NLP pipeline was reviewed in detail between studies and models utilizing rule-based, machine learning (ML), deep learning (DL), and hybrid approaches were examined. With a growing literature surrounding falls prediction in both inpatient and outpatient environments, the absence of studies examining the impact of these models on patient and system outcomes highlights the need for further implementation studies. Through an exploration of the application of NLP techniques, it may be possible to develop models with higher performance in automated falls prediction and detection.

Spine or Hip First? Outcomes in Patients Undergoing Sequential Lumbar Spine or Hip Surgery.

BACKGROUND: Lumbar spine pathology frequently coexists in patients who have hip arthrosis. There is controversy on whether lumbar or hip pathology should be first addressed. The purpose of this study was to evaluate the outcomes of sequential lumbar spine (LSP) or hip arthroplasty (THA). METHODS: Using a large national database from 2010 to 2020, we reviewed the records of 241,279 patients who had concurrent hip arthritis and lumbar spine disease defined as spinal stenosis, lumbar radiculopathy, or degenerative disc disease. During the study period, 6,458 (2.7%) patients with concurrent hip/spine disease underwent sequential operative treatment of either the hip joint or lumbar spine within 2 years. The rates of subsequent surgery in either the hip or the spine, opioid requirements, and rates of hip dislocation were determined and analyzed using compared Chi-squared analyses. RESULTS: Patients undergoing THA first had lower risk of subsequent spinal procedure compared to patients who had spinal procedures first (5.7 versus 23.7%, P < .001). This disparity was maintained up to 5 years (P < .001). Opioid requirements at 1 year were highest in patients who underwent spinal procedures only (836 pills/patient) compared to any other group THA only (566 pills/patient), LSP and then THA (564 pills/patient), THA and LSP (586 pills/patient). Also, THA following LSP was associated with significantly higher rates of dislocation compared to patients undergoing THA first (3.2 versus 1.9%, P < .001). CONCLUSION: Total hip arthroplasty first in patients who have concurrent spine disease was associated with lower risk of subsequent surgery, opioid requirement, and risk of postoperative instability compared to patients having lumbar procedure first.

Saving the Exposed Deep Brain Stimulation Implant: A Comprehensive Review of Implant Extrusion and Reconstructive Options.

INTRODUCTION: Deep brain stimulation (DBS) for the treatment of Parkinson disease is susceptible to complications, such as hardware extrusion, most commonly at the scalp and chest. The authors describe their experience with the management of hardware extrusion and reconstruction with one of the largest single-institution experience and suggest an evidence-based treatment algorithm for the management of such cases. METHODS: A retrospective review of hospital records was performed to identify patients who underwent DBS-related surgery and reconstruction from January 2015 to April 2020. Management of these patients involved culture-directed antibiotics, local wound debridement, various forms of reconstruction, and hardware removal when indicated. RESULTS: Ninety-four patients with 131 DBS-related procedures were included. Twelve patients (12.8%) had hardware extrusion, of which 6 occurred primarily at the scalp and 6 occurred primarily at the chest. Primary closure of scalp wounds (odds ratio, 0.05 [0.004-0.71], P = 0.035) was negatively associated with treatment success. The type of reconstruction of chest wounds did not affect its success ( P = 0.58); however, none of them involved a new surgical bed, such as contralateral or hypochondrial placement. CONCLUSIONS: Hardware extrusion is a significant complication of DBS-related surgery. Management of extrusion at the scalp should involve the use of tension-free, well-vascularized locoregional flaps as opposed to primary closure. Implantable pulse generator extrusions at the chest can be managed with both primary closure and repositioning in a new surgical bed. Extruded DBS implants may be salvaged with appropriate reconstructive considerations, and the authors suggest an evidence-based treatment algorithm.

Topological Hall Effect in a Topological Insulator Interfaced with a Magnetic Insulator.

A topological insulator (TI) interfaced with a magnetic insulator (MI) may host an anomalous Hall effect (AHE), a quantum AHE, and a topological Hall effect (THE). Recent studies, however, suggest that coexisting magnetic phases in TI/MI heterostructures may result in an AHE-associated response that resembles a THE but in fact is not. This Letter reports a genuine THE in a TI/MI structure that has only one magnetic phase. The structure shows a THE in the temperature range of T = 2-3 K and an AHE at T = 80-300 K. Over T = 3-80 K, the two effects coexist but show opposite temperature dependencies. Control measurements, calculations, and simulations together suggest that the observed THE originates from skyrmions, rather than the coexistence of two AHE responses. The skyrmions are formed due to a Dzyaloshinskii-Moriya interaction (DMI) at the interface; the DMI strength estimated is substantially higher than that in heavy metal-based systems.

Valorisation of mine waste - Part I: Characteristics of, and sampling methodology for, consolidated mineralised tailings by using Witwatersrand gold mines (South Africa) as an example.

The quest for steady primary supplies of critical raw materials (CRMs) creates significant waste, which is inevitably generated at each phase of mining and mineral processing. Waste from extraction, separation and refinement of non-renewable natural resources is accumulated globally and creates not only environmental hazards but also economic possibilities. Mine waste management is an expensive and prolonged task but unavoidable. Mine tailings, especially historical ones, can contain economically feasible resources, and given the right condition, such tailings could be reutilised through a waste valorisation concept. A prominent example are the Witwatersrand gold mine tailings in South Africa, which have been reused in small-scale projects. Tailing reutilisation is only possible if a sound classification, sampling and resource modelling framework is established to thoroughly and accurately profile the economic, environmental, health and geometallurgical aspects. Our study on valorisation of mine waste is presented in two parts: Here, in Part I, we focus on the essential components of a mine waste valorisation framework that includes the characterization and development of a systematic sampling framework for consolidated mineralised tailings. The development of a mine waste valorisation framework will hopefully enable worldwide reduction and reutilisation of mine waste.

Valorisation of mine waste - Part II: Resource evaluation for consolidated and mineralised mine waste using the Central African Copperbelt as an example.

Mine waste can create long-term and occasionally catastrophic environmental degradation. Due diligence of mine waste in the form of monitoring and maintenance requires a constant supply of societal resources. Furthermore, mine waste is unlikely to disappear with current mining methods and instead, it is more likely to accumulate at a faster rate due to decreasing primary ore grades and increasing societal demands. However, mine waste can be a societal asset, as it can offer an alternative source of partly critical raw materials (CRMs) that can augment primary sources and provide an opportunity to mitigate supply-risk while ensuring sustainability and easing geopolitical tensions. Cobalt is a critical raw material that is largely a by-product of mining of copper, nickel and platinum-group element ores. It is an element that the renewable energy and high-tech sectors critically depend on and for which no reasonable substitutes currently exist. The majority of the global cobalt production stems from the Central African Copperbelt. Published cobalt production figures for the Central African Copperbelt were used to evaluate cobalt tailings from the Central African Copperbelt. As part of a waste valorisation framework that focuses on primarily on the technical aspects of mine waste valorisation, this study assesses the application of key geostatistical methods, such as kriging and conditional simulation, followed by uniform conditioning, to evaluate the resource potential in a hypothetical copper-cobalt tailing deposit from the Central African Copperbelt. The results indicate that methods such as traditional algorithmic kriging, sequential Gaussian simulation and uniform conditioning are highly effective tools in resource modelling of mine waste. The resource assessment framework component developed in this study makes it possible to systematically characterise, profile and model any mine waste storage facility and thus supplements other framework components discussed in an accompanying paper to maximise mine waste utilization.

Cellulose II Aerogel-Based Triboelectric Nanogenerator.

Cellulose-based triboelectric nanogenerators (TENGs) have gained increasing attention. In this study, a novel method is demonstrated to synthesize cellulose-based aerogels and such aerogels are used to fabricate TENGs that can serve as mechanical energy harvesters and self-powered sensors. The cellulose II aerogel is fabricated via a dissolution-regeneration process in a green inorganic molten salt hydrate solvent (lithium bromide trihydrate), where. The as-fabricated cellulose II aerogel exhibits an interconnected open-pore 3D network structure, higher degree of flexibility, high porosity, and a high surface area of 221.3 m2 g-1. Given its architectural merits, the cellulose II aerogel-based TENG presents an excellent mechanical response sensitivity and high electrical output performance. By blending with other natural polysaccharides, i.e., chitosan and alginic acid, electron-donating and electron-withdrawing groups are introduced into the composite cellulose II aerogels, which significantly improves the triboelectric performance of the TENG. The cellulose II aerogel-based TENG is demonstrated to light up light-emitting diodes, charge commercial capacitors, power a calculator, and monitor human motions. This study demonstrates the facile fabrication of cellulose II aerogel and its application in TENG, which leads to a high-performance and eco-friendly energy harvesting and self-powered system.

Dynamic 1 H-MRS for detection of 13 C-labeled glucose metabolism in the human brain at 3T.

PURPOSE: In 2004, Boumezbeur et al proposed a simple yet powerful approach to detect the metabolism of 13 C-enriched substrates in the brain. Their approach consisted of dynamic 1 H-MRS, without a 13 C radiofrequency (RF) channel, and its successful application was demonstrated in monkeys. Since then, this promising method has yet to be applied rigorously in humans. In this study, we revisit the use of dynamic 1 H-MRS to measure the metabolism of 13 C-enriched substrates and demonstrate its application in the human brain. METHODS: In healthy participants, 1 H-MRS data were acquired dynamically before and following a bolus infusion of [1-13 C] glucose. Data were acquired on a 3T clinical MRI scanner using a short-TE SPECIAL sequence, with regions of interest in both anterior and posterior cingulate cortex. Using simulated basis spectra to model signal changes in both 12 C-bonded and 13 C-coupled resonances, the acquired spectra were fit in LCModel to obtain labeling time courses for glutmate and glutamine at both C4 and C3 positions. RESULTS: Presence of the 13 C label was clearly detectable, owing to the pronounced effect of heteronuclear (13 C-1 H) scalar coupling on the observed 1 H spectra. A decrease in signal from 12 C-bonded protons and an increase in signal from 13 C-coupled protons were observed. The fractional enrichment of Glu-C4, (Glu+Gln)-C4, and (Glu+Gln)-C3 at 30 minutes following infusion of [1-13 C] glucose was similar in both regions: 11% to 13%, 9% to 12% and 3% to 5%, respectively. CONCLUSION: These preliminary results confirm the feasibility of the use of dynamic 1 H-MRS to monitor 13 C labeling in the human brain, without a 13 C RF channel.

Noninvasive blood glucose detection using a quantum cascade laser.

A Quantum Cascade Laser (QCL) was invented in the late 90s as a promising mid-infrared light source and it has contributed to the fields of industry, military, medicine, and biology. The room temperature operation, watt-level output power, compact size, and wide tuning capability of this laser advanced the field of noninvasive blood glucose detection with the use of transmission, absorption, and photoacoustic spectroscopy. This review provides a complete overview of the recent progress and technical details of these spectroscopy techniques, using QCL as an infrared light source for detecting blood glucose concentrations in diabetic patients.

Metastasis-suppressor transcript destabilization through TARBP2 binding of mRNA hairpins.

Aberrant regulation of RNA stability has an important role in many disease states. Deregulated post-transcriptional modulation, such as that governed by microRNAs targeting linear sequence elements in messenger RNAs, has been implicated in the progression of many cancer types. A defining feature of RNA is its ability to fold into structures. However, the roles of structural mRNA elements in cancer progression remain unexplored. Here we performed an unbiased search for post-transcriptional modulators of mRNA stability in breast cancer by conducting whole-genome transcript stability measurements in poorly and highly metastatic isogenic human breast cancer lines. Using a computational framework that searches RNA sequence and structure space, we discovered a family of GC-rich structural cis-regulatory RNA elements, termed sRSEs for structural RNA stability elements, which are significantly overrepresented in transcripts displaying reduced stability in highly metastatic cells. By integrating computational and biochemical approaches, we identified TARBP2, a double-stranded RNA-binding protein implicated in microRNA processing, as the trans factor that binds the sRSE family and similar structural elements--collectively termed TARBP2-binding structural elements (TBSEs)--in transcripts. TARBP2 is overexpressed in metastatic cells and metastatic human breast tumours and destabilizes transcripts containing TBSEs. Endogenous TARBP2 promotes metastatic cell invasion and colonization by destabilizing amyloid precursor protein (APP) and ZNF395 transcripts, two genes previously associated with Alzheimer's and Huntington's disease, respectively. We reveal these genes to be novel metastasis suppressor genes in breast cancer. The cleavage product of APP, extracellular amyloid-α peptide, directly suppresses invasion while ZNF395 transcriptionally represses a pro-metastatic gene expression program. The expression levels of TARBP2, APP and ZNF395 in human breast carcinomas support their experimentally uncovered roles in metastasis. Our findings establish a non-canonical and direct role for TARBP2 in mammalian gene expression regulation and reveal that regulated RNA destabilization through protein-mediated binding of mRNA structural elements can govern cancer progression.

Cost-Minimization Analysis and Treatment Trends of Surgical and Nonsurgical Treatment of Proximal Humerus Fractures.

PURPOSE: Recent evidence demonstrated similar outcomes between nonsurgical and surgical management of displaced proximal humerus fractures. We analyzed treatment trends and performed a cost-minimization analysis comparing nonsurgical treatment, open reduction and internal fixation, reverse total shoulder arthroplasty, and hemiarthroplasty. We hypothesized that rates of surgical treatment have increased and that the costs associated with surgery are greater compared with nonsurgical management of proximal humerus fractures. METHODS: We used a US private-payer claims database of 22 million patient records from 2007 to 2016 to compare (1) cost for the episode of care from the payer perspective between each surgical group and nonsurgical treatment of proximal humerus fractures, and (2) annual trends and complication rates of each group. Cost data, including facility fees, physician fees, physical therapy, and clinic visits, were used to complete a cost-minimization analysis. RESULTS: Nonsurgical treatment was associated with lower average total costs compared with surgical intervention. Facility and physician fees accounted for most of this difference. Physical therapy costs and number of physical therapy visits were higher in each surgical group compared with nonsurgical treatment. Surgical treatment was associated with higher complications, revision rates, and length of stay. There was a small but statistically significant decrease in nonsurgical management of proximal humerus fractures between 2007 and 2016. No change was observed in rates of open reduction and internal fixation, whereas rates of reverse total shoulder arthroplasty increased and rates of hemiarthroplasty decreased. CONCLUSIONS: Nonsurgical management of proximal humerus fractures decreased during the study period. In the setting of treatment equipoise, cost-minimization analysis favors nonsurgical management of proximal humerus fractures. Surgical management is associated with higher complication rates, revision rates, and length of stay. TYPE OF STUDY/LEVEL OF EVIDENCE: Economic Decision Analysis IV.

Physical and Occupational Therapy Use and Cost After Common Hand Procedures.

PURPOSE: The use of routine physical therapy (PT) and occupational therapy (OT) after certain hand procedures, such as carpal tunnel release, remains controversial. The objective of this study was to evaluate baseline use, the change in use, variation in prescribing patterns by region, and costs for PT/OT after common hand procedures. METHODS: Outpatient administrative claims data from patients who underwent procedures for carpal tunnel syndrome, trigger finger, carpometacarpal arthritis, de Quervain tenosynovitis, wrist ganglion cyst, and distal radius fracture were abstracted from the Truven Health MarketScan database from 2007 to 2015. The incidence of therapy and total reimbursement of therapy per patient were collected for each procedure over a 90-day postoperative observational period. Trends in use of therapy over time were described with average compound annual growth rates (CAGRs), a way of quantifying average growth over a specified observation period. Variations in the incidence of PT/OT use across 4 census regions were assessed. RESULTS: The incidence of 90-day utilization of PT and OT after hand procedures was 14.0% and increased for all procedures during the observation period with an average CAGR of 8.3%. Cost per therapy visit was relatively stable when adjusted for inflation, with an average CAGR of 0.63%. Patients in the northeast had a significantly higher incidence of PT/OT use than those in the south and west for all procedures except carpometacarpal arthritis. CONCLUSIONS: Use of PT and OT has increased over time after common hand procedures. Geographical variation in the utilization rate of these services is substantial. Limiting unwarranted variation of care is a health policy strategy for increasing value of care. TYPE OF STUDY/LEVEL OF EVIDENCE: Outcomes Research II.

Spin-to-Charge Conversion in Magnetic Weyl Semimetals.

Weyl semimetals (WSM) are a newly discovered class of quantum materials which can host a number of exotic bulk transport properties, such as the chiral magnetic effect, negative magnetoresistance, and the anomalous Hall effect. In this work, we investigate theoretically the spin-to-charge conversion in a bilayer consisting of a magnetic WSM and a normal metal (NM), where a charge current can be induced in the WSM by a spin current injection at the interface. We show that the induced charge current exhibits a peculiar anisotropy: it vanishes along the magnetization orientation of the magnetic WSM, regardless of the direction of the injected spin. This anisotropy originates from the unique band structure of magnetic WSMs and distinguishes the spin-to-charge conversion effect in WSM-NM structures from that observed in other systems, such as heterostructures involving heavy metals or topological insulators. The induced charge current depends strongly on injected spin orientation, as well as on the position of the Fermi level relative to the Weyl nodes and the separation between them. These dependencies provide additional means to control and manipulate spin-charge conversion in these topological materials.

Nonlinear Planar Hall Effect.

An intriguing property of a three-dimensional (3D) topological insulator (TI) is the existence of surface states with spin-momentum locking, which offers a new frontier of exploration in spintronics. Here, we report the observation of a new type of Hall effect in a 3D TI Bi_{2}Se_{3} film. The Hall resistance scales linearly with both the applied electric and magnetic fields and exhibits a π/2 angle offset with respect to its longitudinal counterpart, in contrast to the usual angle offset of π/4 between the linear planar Hall effect and the anisotropic magnetoresistance. This novel nonlinear planar Hall effect originates from the conversion of a nonlinear transverse spin current to a charge current due to the concerted actions of spin-momentum locking and time-reversal symmetry breaking, which also exists in a wide class of noncentrosymmetric materials with a large span of magnitude. It provides a new way to characterize and utilize the nonlinear spin-to-charge conversion in a variety of topological quantum materials.