The Proton Resonance Enhancement for CEST imaging and Shift Exchange (PRECISE) family of RF pulse shapes for Chemical Exchange Saturation Transfer MRI.

Purpose: To optimize a 100 msec pulse for producing CEST MRI contrast and evaluate in mice. Methods: A gradient ascent algorithm was employed to generate a family of 100 point, 100 msec pulses for use in CEST pulse trains ('PRECISE'). Gradient ascent optimizations were performed for exchange rates (k ca ) = 500 s -1 , 1,500 s -1 , 2,500 s -1 , 3,500 s -1 and 4,500 s -1 and offsets (Δω) = 9.6, 7.8, 4.2 and 2.0 ppm. 7 PRECISE pulse shapes were tested on an 11.7 T scanner using a phantom containing three representative CEST agents with peak saturation B 1 = 4 µT. The pulse producing the most contrast in phantoms was then evaluated for CEST MRI pH mapping of the kidneys in healthy mice after iopamidol administration. Results: The most promising pulse in terms of contrast performance across all three phantoms was the 9.6 ppm, 2500 s -1 optimized pulse with ∼2.7 x improvement over Gaussian and ∼1.3x's over Fermi pulses. This pulse also displayed a large improvement in contrast over the Gaussian pulse after administration of iopamidol in live mice. Conclusion: A new 100 msec pulse was developed based on gradient ascent optimizations which produced better contrast compared to standard Gaussian and Fermi pulses in phantoms. This shape also showed a substantial improvement for CEST MRI pH mapping in live mice over the Gaussian shape and appears promising for a wide range of CEST applications.

Advancing neoadjuvant therapies in resectable non-small cell lung cancer: implications for novel treatment strategies and biomarker discovery.

The delivery of neoadjuvant and perioperative therapies for non-small cell lung cancer has been radically altered by significant advances and by the incorporation of targeted therapies as well as immune checkpoint inhibitors alone or alongside conventional chemotherapy. This evolution has been particularly notable in the incorporation of immunotherapy and targeted therapy into the treatment of resectable NSCLC, where recent FDA approvals of drugs such as nivolumab and pembrolizumab, in combination with platinum doublet chemotherapy, have led to considerable improvements in pathological complete response rates and the potential for enhanced long-term survival outcomes. This review emphasizes the growing importance of biomarkers in optimizing treatment selection and explores the impact of emerging studies that challenge existing treatment paradigms and investigate novel therapeutic combinations poised to redefine standard of care practices. Furthermore, the discussion extends to the unmet needs within perioperative treatment assessment and prognostication, highlighting the prospective value of biomarkers in evaluating treatment responses and prognosis.

Microneedle-based sampling of dermal interstitial fluid using a vacuum-assisted skin patch.

Interstitial fluid (ISF) contains a wealth of biomolecules, yet it is underutilized for diagnostic testing due to a lack of rapid and simple techniques for collecting abundant amounts of fluid. Here, we report a simple and minimally invasive technique for rapidly sampling larger quantities of ISF from human skin. A microneedle array is used to generate micropores in skin from which ISF is extracted using a vacuum-assisted skin patch. Using this technique, an average of 20.8 µL of dermal ISF is collected in 25 min, which is an ∼6-fold improvement over existing sampling methods. Proteomic analysis of collected ISF reveals that it has nearly identical protein composition as blood, and >600 medically relevant biomarkers are identified. Toward this end, we demonstrate the detection of SARS-CoV-2 neutralizing antibodies in ISF collected from COVID-19 vaccinees using two commercial immunoassays, showcasing the utility of this technique for diagnostic testing.

Emergency Department Visits And Hospital Capacity In The US: Trends In The Medicare Population During The COVID-19 Pandemic.

Although emergency department (ED) and hospital overcrowding were reported during the later parts of the COVID-19 pandemic, the true extent and potential causes of this overcrowding remain unclear. Using data on the traditional fee-for-service Medicare population, we examined patterns in ED and hospital use during the period 2019-22. We evaluated trends in ED visits, rates of admission from the ED, and thirty-day mortality, as well as measures suggestive of hospital capacity, including hospital Medicare census, length-of-stay, and discharge destination. We found that ED visits remained below baseline throughout the study period, with the standardized number of visits at the end of the study period being approximately 25 percent lower than baseline. Longer length-of-stay persisted through 2022, whereas hospital census was considerably above baseline until stabilizing just above baseline in 2022. Rates of discharge to postacute facilities initially declined and then leveled off at 2 percent below baseline in 2022. These results suggest that widespread reports of overcrowding were not driven by a resurgence in ED visits. Nonetheless, length-of-stay remains higher, presumably related to increased acuity and reduced available bed capacity in the postacute care system.

Aggressive Treatment Strategy at Index TEVAR Is Associated With Reduced Need For Short-Term Reintervention In Patients With Aortic Dissection.

INTRODUCTION: Thoracic endovascular aortic surgery (TEVAR) is the modern standard of treatment for patients with Type B aortic dissection, however it is unclear how the initial length of treated aorta affects long-term outcomes. This study aims to elucidate risk factors for secondary intervention after TEVAR for aortic dissection, focusing on length of aortic treatment at index operation. METHODS: A retrospective multihospital chart review was completed for patients treated between 2011 and 2022 who underwent TEVAR for aortic dissection with at least one year of post-TEVAR imaging and follow-up. Patient demographics and characteristics were analyzed. In this study, aortic zones treated only included those managed with a covered stent graft. The primary outcome measure was any need for secondary intervention. RESULTS: A total of 151 patients were identified. Demographics included a mean age of 57 years, with 31.8% of the patients being female. Forty-three patients (28.5%) underwent secondary intervention after TEVAR, with a mean follow-up of 1.6 years. The most common indication for secondary intervention was aneurysmal degeneration of the residual false lumen (76%). There was a significant difference in the number of aortic zones treated in patients who did and did not require secondary intervention (2.3 ± 1 vs. 2.7 ± 1, p = 0.04). Additionally, patients with three or more aortic zones of treatment had a significant difference in the need for reintervention (32% secondary intervention vs 52% no secondary intervention, p = 0.02). CONCLUSIONS: At least three zones of aortic treatment at index TEVAR is associated with a decreased need for overall reintervention. Modern treatment of acute and subacute type B dissection should stress an aggressive initial repair, balanced by the potential increased risk of spinal cord ischemia.

Thrombectomy in young adults with embolic stroke of undetermined source: Analysis of the Young ESUS study.

OBJECTIVES: Embolic Stroke of Undetermined Source (ESUS) is a distinct stroke entity that disproportionately affects young adults. We sought to describe characteristics, workup and outcomes of young adult ESUS patients who underwent thrombectomy, and compare outcomes to those reported in different age groups. MATERIALS AND METHODS: Young-ESUS is a multicenter longitudinal cohort study that enrolled consecutive patients aged 21-50 years at 41 stroke centers in 13 countries between 2017- 2019. Between-group comparisons were performed using Wilcoxon rank sum test for continuous variables or Fisher's exact test for binary variables. Distribution of functional outcomes after thrombectomy for our young adult cohort versus pediatric and older adult cohorts reported in the literature were described using the Kruskal-Wallis test. RESULTS: Of 535 patients enrolled in Young-ESUS, 65 (12.1%) were treated with endovascular thrombectomy. Patients who underwent thrombectomy were more likely to undergo in-depth cardiac testing than those who did not, but cardiac abnormalities were not detected more often in this group. Among thrombectomy patients, 35/63 (55.6%) had minimal to no functional disability at follow up. When adjusted for age, stroke severity and IV alteplase, the odds of achieving favorable outcome did not differ between treated versus untreated patients. CONCLUSIONS: Thrombectomy is not rare in young adults with ESUS. Despite extensive workup, cardiac abnormalities were not more prevalent in the thrombectomy group. More research to determine optimal workup, etiologic factors and favorable outcome of stroke across the lifespan is needed.

The mitochondrial calcium uniporter: Balancing tumourigenic and anti-tumourigenic responses.

Increased malignancy and poor treatability associated with solid tumour cancers have commonly been attributed to mitochondrial calcium (Ca2+) dysregulation. The mitochondrial Ca2+ uniporter complex (mtCU) is the predominant mode of Ca2+ uptake into the mitochondrial matrix. The main components of mtCU are the pore-forming mitochondrial Ca2+ uniporter (MCU) subunit, MCU dominant-negative beta (MCUb) subunit, essential MCU regulator (EMRE) and the gatekeeping mitochondrial Ca2+ uptake 1 and 2 (MICU1 and MICU2) proteins. In this review, we describe mtCU-mediated mitochondrial Ca2+ dysregulation in solid tumour cancer types, finding enhanced mtCU activity observed in colorectal cancer, breast cancer, oral squamous cell carcinoma, pancreatic cancer, hepatocellular carcinoma and embryonal rhabdomyosarcoma. By contrast, decreased mtCU activity is associated with melanoma, whereas the nature of mtCU dysregulation remains unclear in glioblastoma. Furthermore, we show that numerous polymorphisms associated with cancer may alter phosphorylation sites on the pore forming MCU and MCUb subunits, which cluster at interfaces with EMRE. We highlight downstream/upstream biomolecular modulators of MCU and MCUb that alter mtCU-mediated mitochondrial Ca2+ uptake and may be used as biomarkers or to aid in the development of novel cancer therapeutics. Additionally, we provide an overview of the current small molecule inhibitors of mtCU that interact with the Asp residue of the critical Asp-Ile-Met-Glu motif or through other allosteric regulatory mechanisms to block Ca2+ permeation. Finally, we describe the relationship between MCU- and MCUb-mediating microRNAs and mitochondrial Ca2+ uptake that should be considered in the discovery of new treatment approaches for cancer.

Assessing the Stability of Photon-Counting CT: Insights from a Two-Year Longitudinal Study.

Background: Among the advancements in computed tomography (CT) technology, photon-counting computed tomography (PCCT) stands out as a significant innovation, providing superior spectral imaging capabilities while simultaneously reducing radiation exposure. Its long-term stability is important for clinical care, especially longitudinal studies, but is currently unknown. Purpose: This study sets out to comprehensively analyze the long-term stability of a first-generation clinical PCCT scanner. Materials and Methods: Over a two-year period, from November 2021 to November 2023, we conducted weekly identical experiments utilizing the same multi-energy CT protocol. These experiments included various tissue-mimicking inserts to rigorously assess the stability of Hounsfield Units (HU) and image noise in Virtual Monochromatic Images (VMIs) and iodine density maps. Throughout this period, notable software and hardware modifications were meticulously recorded. Each week, VMIs and iodine density maps were reconstructed and analyzed to evaluate quantitative stability over time. Results: Spectral results consistently demonstrated the quantitative stability of PCCT. VMIs exhibited stable HU values, such as variation in relative error for VMI 70 keV measuring 0.11% and 0.30% for single-source and dual-source modes, respectively. Similarly, noise levels remained stable with slight fluctuations linked to software changes for VMI 40 and 70 keV that corresponded to changes of 8 and 1 HU, respectively. Furthermore, iodine density quantification maintained stability and showed significant improvement with software and hardware changes, especially in dual-source mode with nominal errors decreasing from 1.44 to 0.03 mg/mL. Conclusion: This study provides the first long-term reproducibility assessment of quantitative PCCT imaging, highlighting its potential for the clinical arena. This study indicates its long-term utility in diagnostic radiology, especially for longitudinal studies.

Intraluminal oxygen can keep small bowel mucosa intact in a segmental ischemia model.

Intestinal preservation for transplantation is accompanied by hypoperfusion with long periods of ischemia with total blood cessation and absolute withdrawal of oxygen leading to structural damage. The application of intraluminal oxygen has been successfully tested in small-animal series during storage and transport of the organ but have been so far clinically unrelatable. In this study, we tested whether a simple and clinically approachable method of intraluminal oxygen application could prevent ischemic damage in a large animal model, during warm ischemia time. We utilised a local no-flow ischemia model of the small intestine in pigs. A low-flow and high-pressure intraluminal oxygen deliverance system was applied in 6 pigs and 6 pigs served as a control group. Mucosal histopathology, hypoxia and barrier markers were evaluated after two hours of no-flow conditions, in both treatment and sham groups, and in healthy tissue. Macro- and microscopically, the luminal oxygen delivered treatment group showed preserved small bowel's appearance, viability, and mucosal integrity. A gradual deterioration of histopathology and barrier markers and increase in hypoxia-inducible factor 1-α expression towards the sites most distant from the oxygen application was observed. Intraluminal low-flow, high oxygen delivery can preserve the intestinal mucosa during total ischemia of the small intestine. This finding can be incorporated in methods to overcome small bowel ischemia and improve intestinal preservation for transplantation.

SWIFT clustering analysis of intracellular cytokine staining flow cytometry data of the HVTN 105 vaccine trial reveals high frequencies of HIV-specific CD4+ T cell responses and associations with humoral responses.

Introduction: The HVTN 105 vaccine clinical trial tested four combinations of two immunogens - the DNA vaccine DNA-HIV-PT123, and the protein vaccine AIDSVAX B/E. All combinations induced substantial antibody and CD4+ T cell responses in many participants. We have now re-examined the intracellular cytokine staining flow cytometry data using the high-resolution SWIFT clustering algorithm, which is very effective for enumerating rare populations such as antigen-responsive T cells, and also determined correlations between the antibody and T cell responses. Methods: Flow cytometry samples across all the analysis batches were registered using the swiftReg registration tool, which reduces batch variation without compromising biological variation. Registered data were clustered using the SWIFT algorithm, and cluster template competition was used to identify clusters of antigen-responsive T cells and to separate these from constitutive cytokine producing cell clusters. Results: Registration strongly reduced batch variation among batches analyzed across several months. This in-depth clustering analysis identified a greater proportion of responders than the original analysis. A subset of antigen-responsive clusters producing IL-21 was identified. The cytokine patterns in each vaccine group were related to the type of vaccine - protein antigens tended to induce more cells producing IL-2 but not IFN-γ, whereas DNA vaccines tended to induce more IL-2+ IFN-γ+ CD4 T cells. Several significant correlations were identified between specific antibody responses and antigen-responsive T cell clusters. The best correlations were not necessarily observed with the strongest antibody or T cell responses. Conclusion: In the complex HVTN105 dataset, alternative analysis methods increased sensitivity of the detection of antigen-specific T cells; increased the number of identified vaccine responders; identified a small IL-21-producing T cell population; and demonstrated significant correlations between specific T cell populations and serum antibody responses. Multiple analysis strategies may be valuable for extracting the most information from large, complex studies.

Immunogenicity, reactogenicity, and IgE-mediated immune responses of a mixed whole-cell and acellular pertussis vaccine schedule in Australian infants: A randomised, double-blind, noninferiority trial.

BACKGROUND: In many countries, infant vaccination with acellular pertussis (aP) vaccines has replaced use of more reactogenic whole-cell pertussis (wP) vaccines. Based on immunological and epidemiological evidence, we hypothesised that substituting the first aP dose in the routine vaccination schedule with wP vaccine might protect against IgE-mediated food allergy. We aimed to compare reactogenicity, immunogenicity, and IgE-mediated responses of a mixed wP/aP primary schedule versus the standard aP-only schedule. METHODS AND FINDINGS: OPTIMUM is a Bayesian, 2-stage, double-blind, randomised trial. In stage one, infants were assigned (1:1) to either a first dose of a pentavalent wP combination vaccine (DTwP-Hib-HepB, Pentabio PT Bio Farma, Indonesia) or a hexavalent aP vaccine (DTaP-Hib-HepB-IPV, Infanrix hexa, GlaxoSmithKline, Australia) at approximately 6 weeks old. Subsequently, all infants received the hexavalent aP vaccine at 4 and 6 months old as well as an aP vaccine at 18 months old (DTaP-IPV, Infanrix-IPV, GlaxoSmithKline, Australia). Stage two is ongoing and follows the above randomisation strategy and vaccination schedule. Ahead of ascertainment of the primary clinical outcome of allergist-confirmed IgE-mediated food allergy by 12 months old, here we present the results of secondary immunogenicity, reactogenicity, tetanus toxoid IgE-mediated immune responses, and parental acceptability endpoints. Serum IgG responses to diphtheria, tetanus, and pertussis antigens were measured using a multiplex fluorescent bead-based immunoassay; total and specific IgE were measured in plasma by means of the ImmunoCAP assay (Thermo Fisher Scientific). The immunogenicity of the mixed schedule was defined as being noninferior to that of the aP-only schedule using a noninferiority margin of 2/3 on the ratio of the geometric mean concentrations (GMR) of pertussis toxin (PT)-IgG 1 month after the 6-month aP. Solicited adverse reactions were summarised by study arm and included all children who received the first dose of either wP or aP. Parental acceptance was assessed using a 5-point Likert scale. The primary analyses were based on intention-to-treat (ITT); secondary per-protocol (PP) analyses were also performed. The trial is registered with ANZCTR (ACTRN12617000065392p). Between March 7, 2018 and January 13, 2020, 150 infants were randomised (75 per arm). PT-IgG responses of the mixed schedule were noninferior to the aP-only schedule at approximately 1 month after the 6-month aP dose [GMR = 0·98, 95% credible interval (0·77 to 1·26); probability (GMR > 2/3) > 0·99; ITT analysis]. At 7 months old, the posterior median probability of quantitation for tetanus toxoid IgE was 0·22 (95% credible interval 0·12 to 0·34) in both the mixed schedule group and in the aP-only group. Despite exclusions, the results were consistent in the PP analysis. At 6 weeks old, irritability was the most common systemic solicited reaction reported in wP (65 [88%] of 74) versus aP (59 [82%] of 72) vaccinees. At the same age, severe systemic reactions were reported among 14 (19%) of 74 infants after wP and 8 (11%) of 72 infants after aP. There were 7 SAEs among 5 participants within the first 6 months of follow-up; on blinded assessment, none were deemed to be related to the study vaccines. Parental acceptance of mixed and aP-only schedules was high (71 [97%] of 73 versus 69 [96%] of 72 would agree to have the same schedule again). CONCLUSIONS: Compared to the aP-only schedule, the mixed schedule evoked noninferior PT-IgG responses, was associated with more severe reactions, but was well accepted by parents. Tetanus toxoid IgE responses did not differ across the study groups. TRIAL REGISTRATION: Trial registered at the Australian and New Zealand Clinical 207 Trial Registry (ACTRN12617000065392p).

Safety and Efficacy of Epithelium-Off Corneal Collagen Cross-Linking for the Treatment of Corneal Ectasia: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the evidence on the safety and effectiveness of epithelium-off corneal collagen cross-linking (CXL) for the treatment of progressive corneal ectasia. METHODS: A literature search of the PubMed database was most recently conducted in March 2024 with no date restrictions and limited to studies published in English. The search identified 359 citations that were reviewed in abstract form, and 43 of these were reviewed in full text. High-quality randomized clinical trials comparing epithelium-off CXL with conservative treatment in patients who have keratoconus (KCN) and post-refractive surgery ectasia were included. The panel deemed 6 articles to be of sufficient relevance for inclusion, and these were assessed for quality by the panel methodologist; 5 were rated level I, and 1 was rated level II. There were no level III studies. RESULTS: This analysis includes 6 prospective, randomized controlled trials that evaluated the use of epithelium-off CXL to treat progressive KCN (5 studies) and post-laser refractive surgery ectasia (1 study), with a mean postoperative follow-up of 2.4 years (range, 1-5 years). All studies showed a decreased progression rate in treated patients compared with controls. Improvement in the maximum keratometry (Kmax) value, corrected distance visual acuity (CDVA), and uncorrected distance visual acuity (UDVA) was observed in the treatment groups compared with control groups. A decrease in corneal thickness was observed in both groups but was greater in the CXL group. Complications were rare. CONCLUSIONS: Epithelium-off CXL is effective in reducing the progression of KCN and post-laser refractive surgery ectasia in most treated patients with an acceptable safety profile. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

On the response of elongating ribosomes to forces opposing translocation.

The elongation phase of protein synthesis is a cyclic, steady-state process. It follows that its directionality is determined by the thermodynamics of the accompanying chemical reactions, which strongly favor elongation. Its irreversibility is guaranteed by its coupling to those reactions, rather being a consequence of any of the conformational changes that occur as it unfolds. It also follows that, in general, the rate of elongation is not proportional to the forward rate constants of any of its steps, including its final, mechano-chemical step, translocation. Instead, the reciprocal of the rate of elongation should be linearly related to the reciprocal of those rate constants. When the results of experiments done a decade ago to measure the effect that forces opposing translocation have on the rate of elongation are reinterpreted in light of these findings, it becomes clear that translocation was rate limiting under conditions in which those experiments were done, and that it is likely to be a Brownian ratchet process, as was concluded earlier.

Microbial competition for phosphorus limits the CO2 response of a mature forest.

The capacity for terrestrial ecosystems to sequester additional carbon (C) with rising CO2 concentrations depends on soil nutrient availability1,2. Previous evidence suggested that mature forests growing on phosphorus (P)-deprived soils had limited capacity to sequester extra biomass under elevated CO2 (refs. 3-6), but uncertainty about ecosystem P cycling and its CO2 response represents a crucial bottleneck for mechanistic prediction of the land C sink under climate change7. Here, by compiling the first comprehensive P budget for a P-limited mature forest exposed to elevated CO2, we show a high likelihood that P captured by soil microorganisms constrains ecosystem P recycling and availability for plant uptake. Trees used P efficiently, but microbial pre-emption of mineralized soil P seemed to limit the capacity of trees for increased P uptake and assimilation under elevated CO2 and, therefore, their capacity to sequester extra C. Plant strategies to stimulate microbial P cycling and plant P uptake, such as increasing rhizosphere C release to soil, will probably be necessary for P-limited forests to increase C capture into new biomass. Our results identify the key mechanisms by which P availability limits CO2 fertilization of tree growth and will guide the development of Earth system models to predict future long-term C storage.

Efficiency enhancement of ultrathin CIGS solar cells by optimal bandgap grading. Part III: piecewise-homogeneous grading.

In Parts I [Appl. Opt.58, 6067 (2019)APOPAI0003-693510.1364/AO.58.006067] and II [Appl. Opt.61, 10049 (2022)APOPAI0003-693510.1364/AO.474920], we used a coupled optoelectronic model to optimize a thin-film CIGS solar cell with a graded-bandgap photon-absorbing layer, periodically corrugated backreflector, and multilayered antireflection coatings. Bandgap grading of the CIGS photon-absorbing layer was continuous and either linear or nonlinear, in the thickness direction. Periodic corrugation and multilayered antireflection coatings were found to engender slight improvements in the efficiency. In contrast, bandgap grading of the CIGS photon-absorbing layer leads to significant enhancement of efficiency, especially when the grading is continuous and nonlinear. However, practical implementation of continuous nonlinear grading is challenging compared to piecewise-homogeneous grading. Hence, for this study, we investigated piecewise-homogeneous approximations of the optimal linear and nonlinear grading profiles, and found that an equivalent efficiency is achieved using piecewise-homogeneous grading. An efficiency of 30.15% is predicted with a three-layered piecewise-homogeneous CIGS photon-absorbing layer. The results will help experimentalists to implement optimal designs for highly efficient CIGS thin-film solar cells.

Barriers to Remote Burn Care Delivery: An Analysis of Burn Center Proximity and Access to Critical Telehealth Infrastructure.

ABSTRACT: Mounting evidence supports the use of telehealth to improve burn care access and efficiency. However, barriers to telehealth use remain throughout the United States and may disproportionately affect specific populations, such as rural and non-English-speaking patients. This study analyzes the association between physical proximity to burn care and determinants of telehealth access.The relationship between telehealth-associated measures and proximity to burn care was analyzed with linear regression analysis. County-level data was sourced from the Agency for Healthcare Research and Quality's Social Determinants of Health Database (2020) and the American Community Survey (2021). County-level distances to the nearest American Burn Association (ABA)-verified burn center were calculated based on verified centers listed in the ABA burn center directory (n = 59). A subsequent analysis was performed on income-stratified datasets available for subset counties.Distance was negatively correlated with access to a smartphone (P < 0.0001), broadband internet (P < 0.0001), and cellular data plan (P < 0.0001) and positively correlated with the percent of households with no computing device (P < 0.0001) and no internet access (P < 0.0001). Analysis of income-stratified data revealed similar results. The percent population not speaking English well (P < 0.0001) at all (P = 0.0009) and the proportion of limited English-speaking households (P = 0.0001) decreased as a function of distance.People living furthest from an ABA-verified burn center in the United States are less likely to have adequate access to critical telehealth infrastructure compared to their counterparts living closer to a burn center. However, income impacts overall access and the degree to which access changes with proximity. Conversely, language-associated barriers decrease as distance increases.

Cumulative loading increases and loading asymmetries persist during walking for people with a transfemoral bone-anchored limb.

BACKGROUND: A bone-anchored limb (BAL) is an alternative to a traditional socket-type prosthesis for people with transfemoral amputation. Early laboratory-based evidence suggests improvement in joint and limb loading mechanics during walking with a BAL compared to socket prosthesis use. However, changes in cumulative joint and limb loading measures, which may be predictive of degenerative joint disease progression, remain unknown. RESEARCH QUESTION: Do cumulative total limb and hip joint loading during walking change using a BAL for people with unilateral transfemoral amputation, compared to prior socket prosthesis use? METHODS: A case-series cohort of eight participants with prior unilateral transfemoral amputation who underwent BAL hardware implantation surgery were retrospectively analyzed (4 M/4 F; BMI: 27.7 ± 3.1 kg/m2; age: 50.4 ± 10.2 years). Daily step count and whole-body motion capture data were collected before (using socket prosthesis) and one-year after BAL hardware implantation. Cumulative total limb and hip joint loading and between-limb loading symmetry metrics were calculated during overground walking at both time points and compared using Cohen's d effect sizes. RESULTS: One year after BAL hardware implantation, participants demonstrated bilateral increases in cumulative total limb loading (amputated: d = -0.65; intact: d = -0.72) and frontal-plane hip moment (amputated: d = -1.29; intact: d = -1.68). Total limb loading and hip joint loading in all planes remained asymmetric over time, with relative overloading of the intact limb in all variables of interest at the one-year point. SIGNIFICANCE: Despite increases in cumulative total limb and hip joint loading, between-limb loading asymmetries persist. Habitual loading asymmetry has been implicated in contributing to negative long-term joint health and onset or progression of degenerative joint diseases. Improved understanding of methods to address habitual loading asymmetries is needed to optimize rehabilitation and long-term joint health as people with transfemoral amputation increase physical activity when using a BAL.

Post-stroke hand gesture recognition via one-shot transfer learning using prototypical networks.

BACKGROUND: In-home rehabilitation systems are a promising, potential alternative to conventional therapy for stroke survivors. Unfortunately, physiological differences between participants and sensor displacement in wearable sensors pose a significant challenge to classifier performance, particularly for people with stroke who may encounter difficulties repeatedly performing trials. This makes it challenging to create reliable in-home rehabilitation systems that can accurately classify gestures. METHODS: Twenty individuals who suffered a stroke performed seven different gestures (mass flexion, mass extension, wrist volar flexion, wrist dorsiflexion, forearm pronation, forearm supination, and rest) related to activities of daily living. They performed these gestures while wearing EMG sensors on the forearm, as well as FMG sensors and an IMU on the wrist. We developed a model based on prototypical networks for one-shot transfer learning, K-Best feature selection, and increased window size to improve model accuracy. Our model was evaluated against conventional transfer learning with neural networks, as well as subject-dependent and subject-independent classifiers: neural networks, LGBM, LDA, and SVM. RESULTS: Our proposed model achieved 82.2% hand-gesture classification accuracy, which was better (P<0.05) than one-shot transfer learning with neural networks (63.17%), neural networks (59.72%), LGBM (65.09%), LDA (63.35%), and SVM (54.5%). In addition, our model performed similarly to subject-dependent classifiers, slightly lower than SVM (83.84%) but higher than neural networks (81.62%), LGBM (80.79%), and LDA (74.89%). Using K-Best features improved the accuracy in 3 of the 6 classifiers used for evaluation, while not affecting the accuracy in the other classifiers. Increasing the window size improved the accuracy of all the classifiers by an average of 4.28%. CONCLUSION: Our proposed model showed significant improvements in hand-gesture recognition accuracy in individuals who have had a stroke as compared with conventional transfer learning, neural networks and traditional machine learning approaches. In addition, K-Best feature selection and increased window size can further improve the accuracy. This approach could help to alleviate the impact of physiological differences and create a subject-independent model for stroke survivors that improves the classification accuracy of wearable sensors. TRIAL REGISTRATION NUMBER: The study was registered in Chinese Clinical Trial Registry with registration number CHiCTR1800017568 in 2018/08/04.

Trends in financial payments from industry to US cancer centers, 2014-2021.

BACKGROUND: Industry payments to US cancer centers are poorly understood. METHODS: US National Cancer Institute (NCI)-designated comprehensive cancer centers were identified (n = 51). Industry payments to NCI-designated comprehensive cancer centers from 2014 to 2021 were obtained from Open Payments and National Institutes of Health (NIH) grant funding from NIH Research Portfolio Online Reporting Tools (RePORT). Given our focus on cancer centers, we measured the subset of industry payments related to cancer drugs specifically and the subset of NIH funding from the NCI. RESULTS: Despite a pandemic-related decline in 2020-2021, cancer-related industry payments to NCI-designated comprehensive cancer centers increased from $482 million in 2014 to $972 million in 2021. Over the same period, NCI research grant funding increased from $2 481  million to $2 724  million. The large majority of nonresearch payments were royalties and licensing payments. CONCLUSION: Industry payments to NCI-designated comprehensive cancer centers increased substantially more than NCI funding in recent years but were also more variable. These trends raise concerns regarding the influence and instability of industry payments.