Algorithmic Individual Fairness and Healthcare: A Scoping Review.

Objective: Statistical and artificial intelligence algorithms are increasingly being developed for use in healthcare. These algorithms may reflect biases that magnify disparities in clinical care, and there is a growing need for understanding how algorithmic biases can be mitigated in pursuit of algorithmic fairness. Individual fairness in algorithms constrains algorithms to the notion that "similar individuals should be treated similarly." We conducted a scoping review on algorithmic individual fairness to understand the current state of research in the metrics and methods developed to achieve individual fairness and its applications in healthcare. Methods: We searched three databases, PubMed, ACM Digital Library, and IEEE Xplore, for algorithmic individual fairness metrics, algorithmic bias mitigation, and healthcare applications. Our search was restricted to articles published between January 2013 and September 2023. We identified 1,886 articles through database searches and manually identified one article from which we included 30 articles in the review. Data from the selected articles were extracted, and the findings were synthesized. Results: Based on the 30 articles in the review, we identified several themes, including philosophical underpinnings of fairness, individual fairness metrics, mitigation methods for achieving individual fairness, implications of achieving individual fairness on group fairness and vice versa, fairness metrics that combined individual fairness and group fairness, software for measuring and optimizing individual fairness, and applications of individual fairness in healthcare. Conclusion: While there has been significant work on algorithmic individual fairness in recent years, the definition, use, and study of individual fairness remain in their infancy, especially in healthcare. Future research is needed to apply and evaluate individual fairness in healthcare comprehensively.

Analytical validation of NeXT Personal®, an ultra-sensitive personalized circulating tumor DNA assay.

We describe the analytical validation of NeXT Personal®, an ultra-sensitive, tumor-informed circulating tumor DNA (ctDNA) assay for detecting residual disease, monitoring therapy response, and detecting recurrence in patients diagnosed with solid tumor cancers. NeXT Personal uses whole genome sequencing of tumor and matched normal samples combined with advanced analytics to accurately identify up to ~1,800 somatic variants specific to the patient's tumor. A personalized panel is created, targeting these variants and then used to sequence cell-free DNA extracted from patient plasma samples for ultra-sensitive detection of ctDNA. The NeXT Personal analytical validation is based on panels designed from tumor and matched normal samples from two cell lines, and from 123 patients across nine cancer types. Analytical measurements demonstrated a detection threshold of 1.67 parts per million (PPM) with a limit of detection at 95% (LOD95) of 3.45 PPM. NeXT Personal showed linearity over a range of 0.8 to 300,000 PPM (Pearson correlation coefficient = 0.9998). Precision varied from a coefficient of variation of 12.8% to 3.6% over a range of 25 to 25,000 PPM. The assay targets 99.9% specificity, with this validation study measuring 100% specificity and in silico methods giving us a confidence interval of 99.92 to 100%. In summary, this study demonstrates NeXT Personal as an ultra-sensitive, highly quantitative and robust ctDNA assay that can be used to detect residual disease, monitor treatment response, and detect recurrence in patients.

Anaesthetic management of a patient with severe pulmonary hypertension, moderate tricuspid regurgitation and moderate right ventricular dysfunction presenting for a dilation and curettage.

A primigravida woman in her 30s with severe pulmonary hypertension, tricuspid regurgitation and depressed right ventricular function presented for therapeutic termination of pregnancy at 7 weeks gestation after referral and multidisciplinary recommendation. A slowly titrated lumbar epidural was chosen for the primary anaesthetic. Under standard American Society of Anesthesiologists (ASA) monitoring, invasive blood pressure monitoring and continuous transthoracic echocardiography, the patient's right ventricular systolic function was monitored throughout the case using qualitative and quantitative metrics and was notable for a right ventricular systolic pressure of 102.4 mm Hg. Milrinone, started prior to epidural titration, was used for inotropic support. Vasopressin was used in conjunction to sustain systemic vascular resistance while having little effect on the pulmonary vascular resistance. The patient experienced no complications or exacerbation of her pulmonary hypertension and was discharged home the following day.

Measuring and Reducing Racial Bias in a Pediatric Urinary Tract Infection Model.

Clinical predictive models that include race as a predictor have the potential to exacerbate disparities in healthcare. Such models can be respecified to exclude race or optimized to reduce racial bias. We investigated the impact of such respecifications in a predictive model - UTICalc - which was designed to reduce catheterizations in young children with suspected urinary tract infections. To reduce racial bias, race was removed from the UTICalc logistic regression model and replaced with two new features. We compared the two versions of UTICalc using fairness and predictive performance metrics to understand the effects on racial bias. In addition, we derived three new models for UTICalc to specifically improve racial fairness. Our results show that, as predicted by previously described impossibility results, fairness cannot be simultaneously improved on all fairness metrics, and model respecification may improve racial fairness but decrease overall predictive performance.

Scaphoid fracture and nonunion: new directions.

The scaphoid is the largest of the carpal bones, articulating with both proximal and distal carpal rows. If scaphoid fractures are not appropriately diagnosed and treated, there is a risk of nonunion, osteonecrosis and degenerative arthritis. Operative management of the scaphoid fracture is primarily determined by the fracture location and amount of displacement. There is increased momentum for dual screw fixation constructs, intended to provide greater stability and reduce the risk of nonunion. Our current practice is to utilize two screws without graft as a first-line treatment for scaphoid nonunion with or without humpback deformity and cyst formation. This review will discuss the management of acute scaphoid fractures and the treatment of nonunion.

Tunable assembly of host-guest colloidal crystals.

Entropy compartmentalization provides new self-assembly routes to colloidal host-guest (HG) structures. Leveraging host particle shape to drive the assembly of HG structures has only recently been proposed and demonstrated. However, the extent to which the guest particles can dictate the structure of the porous network of host particles has not been explored. In this work, by modifying only the guest shape, we show athermal, binary mixtures of star-shaped host particles and convex polygon-shaped guest particles assemble as many as five distinct crystal structures, including rotator and discrete rotator guest crystals, two homoporous host crystals, and one heteroporous host crystal. Edge-to-edge alignment of neighboring stars results in the formation of three distinct pore motifs, whose preferential formation is controlled by the size and shape of the guest particles. Finally, we confirm, via free volume calculations, that assembly is driven by entropy compartmentalization, where the hosts and guests contribute differently to the free energy of the system; free volume calculations also explain differences in assembly based on guest shape. These results provide guest design rules for assembling colloidal HG structures, especially on surfaces and interfaces.

Tumor Treating Fields Alter the Kinomic Landscape in Glioblastoma Revealing Therapeutic Vulnerabilities.

Treatment for the deadly brain tumor glioblastoma (GBM) has been improved through the non-invasive addition of alternating electric fields, called tumor treating fields (TTFields). Improving both progression-free and overall survival, TTFields are currently approved for treatment of recurrent GBMs as a monotherapy and in the adjuvant setting alongside TMZ for newly diagnosed GBMs. These TTFields are known to inhibit mitosis, but the full molecular impact of TTFields remains undetermined. Therefore, we sought to understand the ability of TTFields to disrupt the growth patterns of and induce kinomic landscape shifts in TMZ-sensitive and -resistant GBM cells. We determined that TTFields significantly decreased the growth of TMZ-sensitive and -resistant cells. Kinomic profiling predicted kinases that were induced or repressed by TTFields, suggesting possible therapy-specific vulnerabilities. Serving as a potential pro-survival mechanism for TTFields, kinomics predicted the increased activity of platelet-derived growth-factor receptor alpha (PDGFRα). We demonstrated that the addition of the PDGFR inhibitor, crenolanib, to TTFields further reduced cell growth in comparison to either treatment alone. Collectively, our data suggest the efficacy of TTFields in vitro and identify common signaling responses to TTFields in TMZ-sensitive and -resistant populations, which may support more personalized medicine approaches.

Analytic validation of NeXT Dx™, a comprehensive genomic profiling assay.

We describe the analytic validation of NeXT Dx, a comprehensive genomic profiling assay to aid therapy and clinical trial selection for patients diagnosed with solid tumor cancers. Proprietary methods were utilized to perform whole exome and whole transcriptome sequencing for detection of single nucleotide variants (SNVs), insertions/deletions (indels), copy number alterations (CNAs), and gene fusions, and determination of tumor mutation burden and microsatellite instability. Variant calling is enhanced by sequencing a patient-specific normal sample from, for example, a blood specimen. This provides highly accurate somatic variant calls as well as the incidental reporting of pathogenic and likely pathogenic germline alterations. Fusion detection via RNA sequencing provides more extensive and accurate fusion calling compared to DNA-based tests. NeXT Dx features the proprietary Accuracy and Content Enhanced technology, developed to optimize sequencing and provide more uniform coverage across the exome. The exome was validated at a median sequencing depth of >500x. While variants from 401 cancer-associated genes are currently reported from the assay, the exome/transcriptome assay is broadly validated to enable reporting of additional variants as they become clinically relevant. NeXT Dx demonstrated analytic sensitivities as follows: SNVs (99.4%), indels (98.2%), CNAs (98.0%), and fusions (95.8%). The overall analytic specificity was >99.0%.

Inhibition of Erb-B2 Receptor Tyrosine Kinase 3 and Associated Regulatory Pathways Potently Impairs Malignant Peripheral Nerve Sheath Tumor Proliferation and Survival.

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive, currently untreatable Schwann cell-derived neoplasms with hyperactive mitogen-activated protein kinase and mammalian target of rapamycin signaling pathways. To identify potential therapeutic targets, previous studies used genome-scale shRNA screens that implicated the neuregulin-1 receptor erb-B2 receptor tyrosine kinase 3 (erbB3) in MPNST proliferation and/or survival. The current study shows that erbB3 is commonly expressed in MPNSTs and MPNST cell lines and that erbB3 knockdown inhibits MPNST proliferation and survival. Kinomic and microarray analyses of Schwann and MPNST cells implicate Src- and erbB3-mediated calmodulin-regulated signaling as key pathways. Consistent with this, inhibition of upstream (canertinib, sapitinib, saracatinib, and calmodulin) and parallel (AZD1208) signaling pathways involving mitogen-activated protein kinase and mammalian target of rapamycin reduced MPNST proliferation and survival. ErbB inhibitors (canertinib and sapitinib) or erbB3 knockdown in combination with Src (saracatinib), calmodulin [trifluoperazine (TFP)], or proviral integration site of Moloney murine leukemia kinase (AZD1208) inhibition even more effectively reduces proliferation and survival. Drug inhibition enhances an unstudied calmodulin-dependent protein kinase IIα phosphorylation site in an Src-dependent manner. The Src family kinase inhibitor saracatinib reduces both basal and TFP-induced erbB3 and calmodulin-dependent protein kinase IIα phosphorylation. Src inhibition (saracatinib), like erbB3 knockdown, prevents these phosphorylation events; and when combined with TFP, it even more effectively reduces proliferation and survival compared with monotherapy. These findings implicate erbB3, calmodulin, proviral integration site of Moloney murine leukemia kinases, and Src family members as important therapeutic targets in MPNSTs and demonstrate that combinatorial therapies targeting critical MPNST signaling pathways are more effective.

Inconsistency and Ambiguity Within the International Classification of Disease 10 Procedure Coding System for Hip Fractures.

BACKGROUND: The International Statistical Classification of Diseases (ICD), 10th Revision Procedure Coding System (PCS) was created to increase the granularity of procedural coding. These codes are entered by hospital coders from information derived from the medical record. Concern exists that this increase in complexity could lead to inaccurate data. METHODS: Medical records and ICD-10-PCS codes were reviewed for operatively treated geriatric hip fractures from January 2016 through February 2019 at a tertiary referral medical center. Definitions for each of the 7-unit figures from the 2022 American Medical Association's ICD-10-PCS official codebook were compared to the medical, operative, and implant records. RESULTS: There were 56% (135 of 241) of PCS codes that had ambiguous, partially incorrect, or frankly incorrect figures within the code. One or more inaccurate figures were noted in 72% (72 of 100) of fractures treated with arthroplasty compared to 44.7% (63 of 141) treated with fixation (P < .01). There was at least 1 frankly incorrect figure contained in 9.5% (23 of 241) of codes. Approach was coded ambiguously for 24.8% (29 of 117) of pertrochanteric fractures. Device/implant codes were partially incorrect in 34.9% (84 of 241) of all hip fracture PCS codes. Hemi and total hip arthroplasties were partially incorrect in 78.4% (58 of 74) and 30.8% (8/26) of device/implant codes, respectively. Significantly more femoral neck (69.4%, 86 of 124) than pertrochanteric fractures (41.9%, 49 of 117) had 1 or more incorrect or partially correct figures (P < .01). CONCLUSION: Despite the increased granularity of ICD-10-PCS codes, the application of this system is inconsistent and often incorrect when applied to hip fracture treatments. The definitions in the PCS system are difficult to be utilized by coders and do not reflect the operation performed.

Extensor Mechanism Disruption Remains a Challenging Problem.

BACKGROUND: Extensor mechanism disruption (EMD) following total knee arthroplasty (TKA) is a devastating problem commonly treated with allograft or synthetic reconstruction. Understanding of reconstruction success rates and patient recorded outcomes is lacking. METHODS: Patients who have an EMD after TKA undergoing mesh or whole-extensor allograft reconstruction between 2011 and 2019, with minimum 2-year follow-up were reviewed at two tertiary care centers. Functional failure was defined as extensor lag >30 degrees, amputation, or fusion, as well as revision extensor mechanism reconstruction (EMR). Survivorship was assessed using Kaplan-Meier curves, and factors for success were determined with logistic regressions. RESULTS: Of fifty-six EMRs (49 patients), 50.0% (28/56) were functionally successful at 3.2 years of mean follow-up (range, 0.2 to 7.4). In situ survivorship of the reconstructions at 36 months was 75.0% (42 of 58). There were 50.0% (14 of 28) of functionally failed EMRs that retained their reconstruction at last follow-up. Mean extensor lag among successes and failures was 5.4 and 71.0° (P = .01), respectively. Mean Knee Injury and Osteoarthritis Outcome Score, Joint Replacement scores were 67.1 and 48.8 among successes and failures (P = .01). There were 64.0% (16 of 25) of successes and 1 of 19 failures that obtained a Knee Injury and Osteoarthritis Outcome Score, Joint Replacement score above the minimum patient-acceptable symptom state for TKA. Survivorship and success rates were similar between reconstruction methods (P = .86; P = .76). All-cause mortality was 8.2% (4 of 49), each with EMR failure prior to death. All-cause reoperation rate was 42.9% (24 of 56), with a 14.3% (8 of 56) rate of revision EMR and 10.7% (6 of 56) rate of above-knee-amputation or modular fusion. CONCLUSIONS: This multicenter investigation of mesh or allograft EMR demonstrated modest functional success at 3.2 years. Complication and reoperation rates were high, regardless of EMR technique. Therefore, EMD after TKA remains problematic.

Text validation: Overlooking discrepancies in question constructions.

There is converging evidence that readers monitor text coherence and consistency by immediate, nonstrategic processes of validation. The literature also offers numerous instances of deficient validation. A prominent example of the latter is that understanders tend to overlook discourse anomalies that are embedded in given (presupposed) sentence information. However, we previously documented reading time "consistency effects" (O'Brien & Albrecht, 1992) that exposed readers' sensitivity to both given and new text discrepancies in numerous declarative syntactic constructions (Singer et al., 2017; Singer & Spear, 2020). Five new experiments addressed these phenomena with reference to constructions regularly shown to mask discourse inconsistencies: namely, interrogatives. In striking contrast with declaratives, five interrogative conditions in four experiments yielded no significant consistency effect. Experiments 2-4 documented coincident consistency effects with declarative but not interrogative constructions. A fifth experiment denied that the interrogative-construction findings resulted from readers' lack of knowledge about critical concepts. The cognitive-scientific linguistic construct of verb resolutivity offers a possible basis for these outcomes. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Diagnostic KASP markers differentiate Vanilla planifolia, V. odorata, V. pompona, and their hybrids using leaf or cured pod tissues.

BACKGROUND: Vanilla is a globally important spice crop used in a variety of food, cosmetic, and pharmaceutical products. V. planifolia is the primary commercial species with V. x tahitensis also permissible for food use. Other aromatic species, including V. pompona, are used for food throughout Central and South America. Supply chain complexity hinders the vanilla bean industry and can lead to false claims of genetic and geographical origins to obtain higher prices. Beans of some species can be differentiated by experienced buyers, but hybrids and morphological differences caused by environmental variability or disease would best be resolved by diagnostic tests. METHODS AND RESULTS: Kompetitive Allele Specific Polymerase Chain Reaction is a widely used molecular marker that can genotype single nucleotide polymorphisms efficiently and inexpensively. Assays were designed to differentiate V. planifolia, V. x tahitensis, and V. pompona using publicly available vanilla genomics data. Ten KASP assays on chromosomes 1 through 7, the ITS region, and plastid-encoded rbcL gene successfully differentiated V. planifolia, V. odorata, and V. x tahitensis. Additional KASP assays on chromosomes 1 through 4, the ITS region, and rbcL gene successfully differentiated V. planifolia and V. pompona. Further, a method for extracting KASP-quality DNA from cured vanilla bean seeds was developed and successfully differentiated V. planifolia, V. odorata, V. x tahitensis, V. pompona, and their hybrids. CONCLUSION: The methods and results from this study can be used to identify interspecific hybrids, ensure the authenticity of cured vanilla beans, and reduce abuse within the vanilla supply chain.

QTL mapping of yield components and kernel traits in wheat cultivars TAM 112 and Duster.

In the Southern Great Plains, wheat cultivars have been selected for a combination of outstanding yield and drought tolerance as a long-term breeding goal. To understand the underlying genetic mechanisms, this study aimed to dissect the quantitative trait loci (QTL) associated with yield components and kernel traits in two wheat cultivars `TAM 112' and `Duster' under both irrigated and dryland environments. A set of 182 recombined inbred lines (RIL) derived from the cross of TAM 112/Duster were planted in 13 diverse environments for evaluation of 18 yield and kernel related traits. High-density genetic linkage map was constructed using 5,081 single nucleotide polymorphisms (SNPs) from genotyping-by-sequencing (GBS). QTL mapping analysis detected 134 QTL regions on all 21 wheat chromosomes, including 30 pleiotropic QTL regions and 21 consistent QTL regions, with 10 QTL regions in common. Three major pleiotropic QTL on the short arms of chromosomes 2B (57.5 - 61.6 Mbps), 2D (37.1 - 38.7 Mbps), and 7D (66.0 - 69.2 Mbps) colocalized with genes Ppd-B1, Ppd-D1, and FT-D1, respectively. And four consistent QTL associated with kernel length (KLEN), thousand kernel weight (TKW), plot grain yield (YLD), and kernel spike-1 (KPS) (Qklen.tamu.1A.325, Qtkw.tamu.2B.137, Qyld.tamu.2D.3, and Qkps.tamu.6A.113) explained more than 5% of the phenotypic variation. QTL Qklen.tamu.1A.325 is a novel QTL with consistent effects under all tested environments. Marker haplotype analysis indicated the QTL combinations significantly increased yield and kernel traits. QTL and the linked markers identified in this study will facilitate future marker-assisted selection (MAS) for pyramiding the favorable alleles and QTL map-based cloning.

Molecular characterization of adenocarcinomas arising in the urinary bladder following augmentation cystoplasty: a multi-institutional study.

Development of malignancy is a rare complication following augmentation cystoplasty, and the majority of tumors observed in this setting are adenocarcinomas. Here, we sought to genetically profile these tumors by targeted DNA sequencing of a multi-institutional cohort of adenocarcinomas that developed in the urinary bladder following augmentation cystoplasty. Carcinomas arising in the urinary bladder of patients with history of augmentation cystoplasty were obtained from 4 major academic institutions, with cases diagnosed as urothelial carcinoma excluded from the study. The cases were analyzed using a DNA sequencing panel that includes 529 genes and genome-wide copy number assessment. The most frequently altered genes included TP53, KRAS, and MYC, and the vast majority of cases demonstrated mutational profiles consistent with gastrointestinal adenocarcinomas. One case demonstrated an EML4::ALK fusion together with an MSH3 frameshift mutation and hypermutated phenotype, characteristic of a rare but aggressive subtype of colorectal adenocarcinoma that may benefit from targeted ALK inhibition therapy. Importantly, six other tumors in the cohort also had potentially targetable molecular alterations, involving ATM (2 cases), BRCA1 (2 cases), EGFR (1 case), and ERBB2 (1 case). To our knowledge, this study represents the most comprehensive molecular characterization to date of adenocarcinomas arising in the urinary bladder following augmentation cystoplasty. Despite the unique environment of the augmented tissue, the resulting tumors demonstrate a spectrum of driver mutations similar to that of primary gastrointestinal adenocarcinomas. Importantly, molecular alterations potentially amenable to targeted therapy were identified in the majority of cases.

Fibroblast GSK-3α Promotes Fibrosis via RAF-MEK-ERK Pathway in the Injured Heart.

BACKGROUND: Heart failure is the leading cause of mortality, morbidity, and health care expenditures worldwide. Numerous studies have implicated GSK-3 (glycogen synthase kinase-3) as a promising therapeutic target for cardiovascular diseases. GSK-3 isoforms seem to play overlapping, unique and even opposing functions in the heart. Previously, we have shown that of the 2 isoforms of GSK-3, cardiac fibroblast GSK-3ß acts as a negative regulator of myocardial fibrosis in the ischemic heart. However, the role of cardiac fibroblast-GSK-3α in the pathogenesis of cardiac diseases is completely unknown. METHODS: To define the role of cardiac fibroblast-GSK-3α in myocardial fibrosis and heart failure, GSK-3α was deleted from fibroblasts or myofibroblasts with tamoxifen-inducible Tcf21- or Postn-promoter-driven Cre recombinase. Control and GSK-3α KO mice were subjected to cardiac injury and heart parameters were evaluated. The fibroblast kinome mapping was carried out to delineate molecular mechanism followed by in vivo and in vitro analysis. RESULTS: Fibroblast-specific GSK-3α deletion restricted fibrotic remodeling and preserved function of the injured heart. We observed reductions in cell migration, collagen gel contraction, α-SMA protein levels, and expression of ECM genes in TGFß1-treated KO fibroblasts, indicating that GSK-3α is required for myofibroblast transformation. Surprisingly, GSK-3α deletion did not affect SMAD3 activation, suggesting the profibrotic role of GSK-3α is SMAD3 independent. The molecular studies confirmed decreased ERK signaling in GSK-3α-KO CFs. Conversely, adenovirus-mediated expression of a constitutively active form of GSK-3α (Ad-GSK-3αS21A) in fibroblasts increased ERK activation and expression of fibrogenic proteins. Importantly, this effect was abolished by ERK inhibition. CONCLUSIONS: GSK-3α-mediated MEK-ERK activation is a critical profibrotic signaling circuit in the injured heart, which operates independently of the canonical TGF-ß1-SMAD3 pathway. Therefore, strategies to inhibit the GSK-3α-MEK-ERK signaling circuit could prevent adverse fibrosis in diseased hearts.

Selective suppression of melanoma lacking IFN-γ pathway by JAK inhibition depends on T cells and host TNF signaling.

Therapeutic resistance to immune checkpoint blockers (ICBs) in melanoma patients is a pressing issue, of which tumor loss of IFN-γ signaling genes is a major underlying mechanism. However, strategies of overcoming this resistance mechanism have been largely elusive. Moreover, given the indispensable role of tumor-infiltrating T cells (TILs) in ICBs, little is known about how tumor-intrinsic loss of IFN-γ signaling (IFNγR1KO) impacts TILs. Here, we report that IFNγR1KO melanomas have reduced infiltration and function of TILs. IFNγR1KO melanomas harbor a network of constitutively active protein tyrosine kinases centered on activated JAK1/2. Mechanistically, JAK1/2 activation is mediated by augmented mTOR. Importantly, JAK1/2 inhibition with Ruxolitinib selectively suppresses the growth of IFNγR1KO but not scrambled control melanomas, depending on T cells and host TNF. Together, our results reveal an important role of tumor-intrinsic IFN-γ signaling in shaping TILs and manifest a targeted therapy to bypass ICB resistance of melanomas defective of IFN-γ signaling.

An in vivo model of glioblastoma radiation resistance identifies long noncoding RNAs and targetable kinases.

Key molecular regulators of acquired radiation resistance in recurrent glioblastoma (GBM) are largely unknown, with a dearth of accurate preclinical models. To address this, we generated 8 GBM patient-derived xenograft (PDX) models of acquired radiation therapy-selected (RTS) resistance compared with same-patient, treatment-naive (radiation-sensitive, unselected; RTU) PDXs. These likely unique models mimic the longitudinal evolution of patient recurrent tumors following serial radiation therapy. Indeed, while whole-exome sequencing showed retention of major genomic alterations in the RTS lines, we did detect a chromosome 12q14 amplification that was associated with clinical GBM recurrence in 2 RTS models. A potentially novel bioinformatics pipeline was applied to analyze phenotypic, transcriptomic, and kinomic alterations, which identified long noncoding RNAs (lncRNAs) and targetable, PDX-specific kinases. We observed differential transcriptional enrichment of DNA damage repair pathways in our RTS models, which correlated with several lncRNAs. Global kinomic profiling separated RTU and RTS models, but pairwise analyses indicated that there are multiple molecular routes to acquired radiation resistance. RTS model-specific kinases were identified and targeted with clinically relevant small molecule inhibitors. This cohort of in vivo RTS patient-derived models will enable future preclinical therapeutic testing to help overcome the treatment resistance seen in patients with GBM.

Evaluation of Factors Affecting Return to Work Following Carpal Tunnel Release: A Statewide Cohort Study of Workers' Compensation Subjects.

PURPOSE: Most randomized trials comparing open carpal tunnel release (OCTR) to endoscopic carpal tunnel release (ECTR) are not specific to a working population and focus mainly on how surgical technique has an impact on outcomes. This study's primary goal was to evaluate factors affecting days out of work (DOOW) following carpal tunnel release (CTR) in a working population and to evaluate for differences in medical costs, indemnity payments, disability ratings, and opioid use between OCTR and ECTR with the intent of determining whether one or the other surgical method was a determining factor. METHODS: Using the Ohio Bureau of Workers' Compensation claims database, individuals were identified who underwent unilateral isolated CTR between 1993 and 2018. We excluded those who were on total disability, who underwent additional surgery within 6 months of their index CTR, including contralateral or revision CTR, and those not working during the same month as their index CTR. Outcomes were evaluated at 6 months after surgery. Multivariable linear regression was performed to evaluate covariates associated with DOOW. RESULTS: Of the 4596 included participants, 569 (12.4%) and 4027 (87.6%) underwent ECTR and OCTR, respectively. Mean DOOW were 58.4 for participants undergoing OCTR and 56.6 for those undergoing ECTR. Carpal tunnel release technique was not predictive of DOOW. Net medical costs were 20.7% higher for those undergoing ECTR. Multivariable linear regression demonstrated the following significant predictors of higher DOOW: preoperative opioid use, legal representation, labor-intensive occupation, increasing lag time from injury to filing of a worker's compensation claim, and female sex. Being married, higher income community, and working in the public sector were associated with fewer DOOW. CONCLUSIONS: In a large statewide worker's compensation population, demographic, occupational, psychosocial, and litigatory factors have a significant impact on DOOW following CTR, whereas differences in surgical technique between ECTR and OCTR did not. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

Telehealth adoption during the COVID-19 pandemic: A social media textual and network analysis.

Objective: The telemedicine industry has rapidly grown during the COVID-19 pandemic, and telemedicine has become a common form of care. The present study looks at the online conversation regarding telemedicine at the beginning of the pandemic and one year later. The Technology Acceptance Model is utilized to explain the findings. Methods: Brandwatch and NUVI software captured social mentions on Twitter regarding telemedicine during the beginning of the pandemic (March 15, 2020-April 20, 2020) and one year later (March 12, 2021-April 19, 2021). SAS text-mining software analyzed the social mentions and organized them into ten unique topics for each time period. The research team analyzed the topics and organized them into themes. A network analysis was also performed to examine structure and influence within the network. Results: In March-April 2020, the themes focused on the use of telehealth in general, telehealth for mental health applications, and Medicare covering telehealth services. In March-April 2021, the themes focused on news events regarding telehealth and the rise in prominence of telehealth services. The network analysis shows a shift in the distribution of telehealth information among influential accounts and reveals that the network became more connected, with a change in the control of information spread. Conclusions: Technology Acceptance Model explains the social acceptance and spread of telemedicine. The transition in the conversation about telemedicine suggests a pattern of greater system use consistent with the Technology Acceptance Model. Telemedicine may have greatly increased in use because of the pandemic, but data suggests that its use may persist after the pandemic subsides.