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Abstract Purpose To report a case series of patients with uveitic glaucoma who were treated with micropulse transscleral cyclophotocoagulation (mpCPC). Methods This retrospective case series consists of patients from the University of Colorado Sue Anschutz-Rodgers Eye Center from 2015 to 2020 who were diagnosed with uveitic glaucoma. Information collected includes demographic data, type of uveitis, glaucoma severity, and prior glaucoma surgeries. Pre- and postoperative best corrected visual acuity, intraocular pressure (IOP), glaucoma medications, degree of inflammation, and uveitis therapies were included up to 36 months postoperatively. Surgical success was defined as an IOP reduction of 30% with achievement of IOP goal using the same number of glaucoma medications or less at 6 months or 1 year. Uveitis success was defined as the absence of persistent anterior uveitis at 3 months. Results Six patients and seven eyes with uveitic glaucoma underwent mpCPC. Types of uveitis included idiopathic anterior uveitis, HLA-B27-associated anterior uveitis, varicella zoster virus anterior uveitis, juvenile idiopathic arthritis-associated chronic anterior uveitis, lichen planus-associated intermediate uveitis, and sarcoidosis-associated panuveitis. Two of six eyes (33.3%) at 6 months and three of five eyes (60%) at 1 year achieved surgical success. Around 6 months postoperatively, two out of seven eyes (28.6%) required Ahmed glaucoma valve placement (n = 1) or repeat mpCPC (n = 1). One eye (14.3%) required phacoemulsification with goniotomy followed by an Ahmed glaucoma valve 18 months after mpCPC. There were no cases of persistent anterior uveitis, hypotony, or phthisis after mpCPC in this cohort. Conclusions Micropulse transscleral cyclophotocoagulation may safely reduce intraocular pressure in some patients with uveitic glaucoma without exacerbation of intraocular inflammation. Multiple treatments may be required to achieve longer-term success.

Abstract Background Regulations put in place to protect the privacy of individuals receiving substance use disorder (SUD) treatment have resulted in an unintended consequence of siloed SUD treatment and referral information outside of the integrated electronic health record (EHR). Recent revisions to these regulations have opened the door to data integration, which creates opportunities for enhanced patient care and more efficient workflows. We report on the experience of one safety-net hospital system integrating SUD treatment data into the EHR. Methods SUD treatment and referral information was integrated from siloed systems into the EHR through the implementation of a referral order, treatment episode definition, and referral and episode-related tools for addiction therapists and other clinicians. Integration was evaluated by monitoring SUD treatment episode characteristics, patient characteristics, referral linkage, and treatment episode retention before and after integration. Satisfaction of end-users with the new tools was evaluated through a survey of addiction therapists. Results After integration, three more SUD treatment programs were represented in the EHR. This increased the number of patients that could be tracked as initiating SUD treatment by 250%, from 562 before to 1,411 after integration. After integration, overall referral linkage declined (74% vs. 48%) and treatment episode retention at 90-days was higher (45% vs. 74%). Addiction therapists appreciated the efficiency of having all SUD treatment information in the EHR but did not find that the tools provided a large time savings shortly after integration. Conclusions Integration of SUD treatment program data into the EHR facilitated both care coordination in patient treatment and quality improvement initiatives for treatment programs. Referral linkage and retention rates were likely modified by a broader capture of patients and changed outcome definition criteria. Greater preparatory workflow analysis may decrease initial end-user burden. Integration of siloed data, made possible given revised regulations, is essential to an efficient hub-and-spoke model of care, which must standardize and coordinate patient care across multiple clinics and departments.

Background Excess nitrogen (N) loading to coastal ecosystems impairs estuarine water quality. Land management decisions made within estuarine watersheds have a direct impact on downstream N delivery. Natural features within watersheds can act as landscape sinks for N, such as wetlands, streams and ponds that transform dissolved N into gaseous N, effectively removing it from the aquatic system. Identifying and evaluating these landscape sinks and their spatial relationship to N sources can help managers understand the effects of alternative decisions on downstream resources. Methods The N-Sink approach uses widely available GIS data to identify landscape sinks within HUC-12 (or larger) catchments, estimate their N removal potential and map the effect of those sinks on N movement through the catchment. Static maps are produced to visualize N removal efficiency, transport and delivery, the latter in the form of an index. The R package nsink was developed to facilitate data acquisition, processing and visualization. Results nsink creates static maps for a specific HUC-12, or users can visit the University of Connecticut website to explore previously mapped areas. Users can investigate specific flowpaths interactively by clicking on any location within the catchment. A flowpath is generated with a table describing N removal along each segment. We describe the motivation behind developing nsink, discuss implementation in R, and present two use case examples. nsink is available from https://github.com/USEPA/nsink. Conclusions N-Sink is a decision support tool created for local decision-makers and NGOs to facilitate better understanding of the relationship between land use and downstream N delivery. Local decision-makers that have prioritized N mitigation in their long-term planning can use nsink to better understand the potential impact of proposed development projects, zoning variances, and land acquisition or restoration. nsink also allows resource economists to investigate the tradeoffs among different, often costly, N reduction strategies.

Abstract Introduction The annulus fibrosus (AF) of the Intervertebral disc (IVD) is composed of concentric lamellae of helically wound collagen fibers. Understanding the spatial variation of collagen fiber orientations in these lamellae, and the resulting material anisotropy, is crucial to predicting the mechanical behavior of the complete IVD. Methods This study builds on a prior model predicated on path‐independent displacement of fiber endpoints during vertebral body growth to predict a complete, three‐dimensional annulus fibrosus fiber network from a small number of subject‐independent input parameters and vertebral endplate topographies obtained from clinical imaging. To evaluate the model, it was first fit to mid‐plane fiber orientations obtained using polarized light microscopy in a population of bovine caudal discs for which computed tomography images vertebral endplates were also available. Additionally, the model was used to predict the trajectories based on human lumbar disc geometries and results were compared to previously reported data. Finally, the model was employed to investigate potential disc‐related variations in fiber angle distributions. Results The model was able to accurately predict experimentally measured fiber distributions in both bovine and human discs using only endplate topography and three input parameters. Critically, the model recapitulated previously observed asymmetry between the inclinations of right‐ and left‐handed fibers in the posterolateral aspect of the human AF. Level to level variation of disc height and aspect ratio in the human lumbar spine was predicted to affect absolute values of fiber inclination, but not this asymmetry. Conclusion Taken together these results suggest that patient‐specific distributions of AF fiber orientation may be readily incorporated into computational models of the spine using only disc geometry and a small number of subject‐independent parameters.

Abstract The abrupt cessation of ovarian hormone release is associated with declines in muscle contractile function, yet the impact of gradual ovarian failure on muscle contractility across peri‐, early‐ and late‐stage menopause remains unclear. In this study, a 4‐vinylcyclohexene diepoxide (VCD)‐induced ovarian failure mouse model was used to examine time course changes in muscle mechanical function. Plantar flexors of female mice (VCD: n = 10; CON: n = 8) were assessed at 40 (early perimenopause), 80 (late perimenopause), 120 (menopause onset) and 176 (late menopause) days post‐initial VCD injection. A torque–frequency relationship was established across a range of frequencies (10–200 Hz). Isotonic dynamic contractions were elicited against relative loads (10–80% maximal isometric torque) to determine the torque–velocity–power relationship. Mice then performed a fatigue task using intermittent 100 Hz isometric contractions until torque dropped by 60%. Recovery of twitch, 10 Hz and 100 Hz torque were tracked for 10 min post‐task failure. Additionally, intact muscle fibres from the flexor digitorum brevis underwent a fatigue task (50 repetitions at 70 Hz), and 10 and 100 Hz tetanic [Ca2+] were monitored for 10 min afterward. VCD mice exhibited 16% lower twitch torque than controls across all time points. Apart from twitch torque, 10 Hz torque and 10 Hz tetanic [Ca2+], where VCD showed greater values relative to pre‐fatigue during recovery, no significant differences were observed between control and VCD mice during recovery. These results indicate that gradual ovarian failure has minimal detriments to in vivo muscle mechanical function, with minor alterations observed primarily for low‐frequency stimulation during recovery from fatigue.

Objective: To determine the appropriateness of ophthalmology recommendations from an online chat-based artificial intelligence model to ophthalmology questions. Patients and Methods: Cross-sectional qualitative study from April 1, 2023, to April 30, 2023. A total of 192 questions were generated spanning all ophthalmic subspecialties. Each question was posed to a large language model (LLM) 3 times. The responses were graded by appropriate subspecialists as appropriate, inappropriate, or unreliable in 2 grading contexts. The first grading context was if the information was presented on a patient information site. The second was an LLM-generated draft response to patient queries sent by the electronic medical record (EMR). Appropriate was defined as accurate and specific enough to serve as a surrogate for physician-approved information. Main outcome measure was percentage of appropriate responses per subspecialty. Results: For patient information site-related questions, the LLM provided an overall average of 79% appropriate responses. Variable rates of average appropriateness were observed across ophthalmic subspecialties for patient information site information ranging from 56% to 100%: cataract or refractive (92%), cornea (56%), glaucoma (72%), neuro-ophthalmology (67%), oculoplastic or orbital surgery (80%), ocular oncology (100%), pediatrics (89%), vitreoretinal diseases (86%), and uveitis (65%). For draft responses to patient questions via EMR, the LLM provided an overall average of 74% appropriate responses and varied by subspecialty: cataract or refractive (85%), cornea (54%), glaucoma (77%), neuro-ophthalmology (63%), oculoplastic or orbital surgery (62%), ocular oncology (90%), pediatrics (94%), vitreoretinal diseases (88%), and uveitis (55%). Stratifying grades across health information categories (disease and condition, risk and prevention, surgery-related, and treatment and management) showed notable but insignificant variations, with disease and condition often rated highest (72% and 69%) for appropriateness and surgery-related (55% and 51%) lowest, in both contexts. Conclusion: This LLM reported mostly appropriate responses across multiple ophthalmology subspecialties in the context of both patient information sites and EMR-related responses to patient questions. Current LLM offerings require optimization and improvement before widespread clinical use.

Abstract The precise temporal coordination of neural activity is crucial for brain function. In the hippocampus, this precision is reflected in the oscillatory rhythms observed in CA1. While it is known that a balance between excitatory and inhibitory activity is necessary to generate and maintain these oscillations, the differential contribution of feedforward and feedback inhibition remains ambiguous. Here we use conditional genetics to chronically silence CA1 pyramidal cell transmission, ablating the ability of these neurons to recruit feedback inhibition in the local circuit, while recording physiological activity in mice. We find that this intervention leads to local pathophysiological events, with ripple amplitude and intrinsic frequency becoming significantly larger and spatially triggered local population spikes locked to the trough of the theta oscillation appearing during movement. These phenotypes demonstrate that feedback inhibition is crucial in maintaining local sparsity of activation and reveal the key role of lateral inhibition in CA1 in shaping circuit function.

IntroductionAs an essential part of plant cell walls, lignin provides mechanical support for plant growth, enhances water transport, and helps to defend against pathogens. As the most abundant natural aromatic-based renewable resource on earth, its biosynthesis has always been a research focus, and it is still currently under study.MethodsIn this study, the p-coumaryl alcohol analog (HALK) and the coniferyl alcohol analog (GALK) containing an alkyne group at the ortho position were synthesized and applied to lignification in vivo and in vitro. The incorporation of these novel lignin monomers was observed via fluorescence imaging.Results and DiscussionIt was found that the two monolignol analogs could be incorporated in dehydrogenated polymers (DHPs) in vitro and in flax cell walls in vivo. The results showed that as the cultivation time and precursor concentration varied, the deposition of H and G-type lignin exhibited differences in deposition mode. At the subcellular scale, the deposited lignin first appears in the cell corner and the middle lamella, and then gradually appears on the cell walls. Furthermore, lignin was also found in bast fiber. It was demonstrated that these new molecules could provide high-resolution localization of lignin during polymerization.

The increased use of plastics and the associated environmental impact has catalyzed research on the development of bio-derived polymers. Bio-based polyesters have gained increased attention due to the abundance of their starting materials and ease of processing. Lignin is naturally occurring in biomass with rich carbon content, whose functionality and rigidity make it an ideal bio-derived candidate for bio-based polyesters. Herein, a lignin-based polyester with good thermal stability and self-repairability was synthesized from carboxylated lignin and epoxidized soybean oil. The synthesized lignin/epoxidized soybean oil (ESO) vitrimer was brittle such that its mechanical performance could not be recorded. However, when polyethylene glycol (PEG) was incorporated as a plasticizer, polymer samples exhibited acceptable ductility. From thermomechanical analysis of the synthesized polyesters, the plasticizer did not impair thermal stability of polymers, but greatly enhanced mechanical properties. Notably, all samples exhibited stability at high temperatures, and good glass transition temperatures (51.0 ± 0.9–78.0 ± 1.2 °C). The highest tensile strength (3.983 ± 0.1 MPa) and storage modulus (1463.67 ± 12.6 MPa) were recorded for the polyester containing 6 % w/w PEG. Moreover, the polymer samples exhibited self-healing capability at 180 °C. This work expands on valorization of lignin through the synthesis of bio-derived materials.

Background: Gestational diabetes mellitus (GDM) is associated with increased long-term risk of cardiovascular disease but the cardiovascular structural and functional changes that contribute to risk are not well understood. Objectives: The purpose of this study was to determine whether GDM is associated with adverse cardiac remodeling and endothelial dysfunction a decade after delivery, independent of type 2 diabetes. Methods: Women with deliveries between 2008 and 2009 were initially selected from a prospective clinical cohort. Pregnancy history was chart abstracted and a follow-up study visit was conducted at 8 to 10 years postpartum. Cardiac structure and function were assessed with echocardiography. Endothelial function was measured with peripheral arterial tonometry and glycocalyx analysis. Results: Among 254 women assessed at an average age of 38 years, 53 (21%) had prior GDM. At follow-up, women with GDM had more incident prediabetes or diabetes (58% vs 20% without GDM), more impairment in peripheral arterial tonometry (reactive hyperemia 1.58 vs 1.95; P = 0.01) and reduced perfusion, a marker of glycocalyx assessment (red blood cell filling 0.70 ± 0.04 vs 0.72 ± 0.05; P

Light‐emitting diodes (LEDs) are widely used in lighting and display applications. Carbon quantum dots (CQDs), which have high biocompatibility, high resistance to photobleaching, and full‐spectrum luminescence, have inherent advantages as fluorescent materials for LED devices. Herein, multicolor CQDs are prepared by a new reagent engineering strategy due to the difference of effective conjugate length and the surface electron‐withdrawing groups of CQDs. White CQDs are realized by mixing blue, green, and red CQDs proportionally. Then, the aggregation‐caused quenching phenomenon of CQDs is suppressed through the hydrogen‐bonding network of cellulose nanofibrils (CNFs). Multicolor fluorescent films are prepared from CQDs and CNFs by simple mixing and casting methods. Finally, thin‐film encapsulation based on the photosensitive resin ABPE‐10 coating can be realized and rapidly assembles into fluorescent films with different light‐emitting colors into LED devices, leading to have superior thermal performance compared with conventional LEDs. White LEDs have excellent white‐light illumination performance, with Commission Internationale de L’Eclairage color coordinates of (0.33, 0.37), a correlated color temperature of 5688 K, and a color rendering index of 86. This strategy provides a convenient and scalable pathway for low‐cost, environmentally friendly, and high‐performance CQDs‐based LEDs.

The shipping industry transports nearly 80% of the goods worldwide and requires large funding. The shipping industry shifted from debt to equity as the source of funding in the last decade. Because most shipping companies already had their initial public offering before 2013, these companies tend to engage in follow-on equity offerings (FPO). However, the challenge faced by the shipping companies is the lack of knowledge on successful FPO. The purpose of this study is to identify the most influential factors affecting shipping companies’ FPO from the investor perspective. This research applies a hybrid multiple-criteria decision-making model integrating the fuzzy-Delphi method and Decision-Making Trial and Evaluation Laboratory, processing survey responses covering four dimensions and 16 criteria from 33 investment experts. The results show that financial indicator is the primary cause affecting offering condition, technical indicators. An increase in earnings per share would help the financial performance of the shipping companies to appear most attractive to investors.

Background: Minimum clinically important difference (MCID) values are commonly used to measure treatment success for total knee arthroplasty (TKA). MCID values vary according to calculation methodology, and prior studies have shown that patient factors are associated with failure to achieve MCID thresholds. The purpose of this study was to determine if anchor-based 1-year Knee Injury and Osteoarthritis Outcome Score Joint Replacement (KOOS-JR) MCID values varied among patients undergoing TKA based on patient-specific factors. Methods: This was a retrospective review of patients undergoing TKA from 2017-2018. Patients without baseline or 1-year KOOS-JR or Patient-Reported Outcome Measurement Information System Global Health data or that underwent procedures other than primary TKA were excluded. MCIDs were calculated and compared between patient groups according to preoperative characteristics. Results: Among the included 976 patients, 1-year KOOS-JR MCIDs were 26.6 for men, 28.2 for women, 30.7 for patients with a diagnosis of anxiety and/or depression, and 26.7 for patients without a diagnosis. One-year MCID values did not differ significantly according to gender (P = .379) or mental health diagnosis (P = .066), nor did they correlate with body mass index (β = −0.034, P = .822). Preoperative KOOS-JR decile demonstrated an inverse relationship with 1-year MCID values and attainment of MCID. Conclusions: The proportion of patients attaining KOOS-JR MCID values demonstrated an inverse relationship with preoperative baseline function. Future investigation may identify patient factors that allow surgeons to better capture patient satisfaction with their procedure despite failure to attain a 1-year MCID.

Abstract Human genetic studies have revealed rare missense and protein-truncating variants in GRIN2A, encoding for the GluN2A subunit of the NMDA receptors, that confer significant risk for schizophrenia (SCZ). Mutations in GRIN2A are also associated with epilepsy and developmental delay/intellectual disability (DD/ID). However, it remains enigmatic how alterations to the same protein can result in diverse clinical phenotypes. Here, we performed functional characterization of human GluN1/GluN2A heteromeric NMDA receptors that contain SCZ-linked GluN2A variants, and compared them to NMDA receptors with GluN2A variants associated with epilepsy or DD/ID. Our findings demonstrate that SCZ-associated GRIN2A variants were predominantly loss-of-function (LoF), whereas epilepsy and DD/ID-associated variants resulted in both gain- and loss-of-function phenotypes. We additionally show that M653I and S809R, LoF GRIN2A variants associated with DD/ID, exert a dominant-negative effect when co-expressed with a wild-type GluN2A, whereas E58Ter and Y698C, SCZ-linked LoF variants, and A727T, an epilepsy-linked LoF variant, do not. These data offer a potential mechanism by which SCZ/epilepsy and DD/ID-linked variants can cause different effects on receptor function and therefore result in divergent pathological outcomes.

Abstract Introduction The use of serial coronary computed tomography angiography (CCTA) allows for the early assessment of coronary plaque progression, a crucial factor in averting major adverse cardiac events (MACEs). Traditionally, serial CCTA is assessed using anatomical landmarks to match baseline and follow-up scans. Recently, a tool has been developed that allows for the automatic quantification of local plaque thickness differences in serial CCTA utilizing plaque contour delineation. The aim of this study was to determine thresholds of plaque thickness differences that define whether there is plaque progression and/or regression. These thresholds depend on the contrast-to-noise ratio (CNR). Methods Plaque thickness differences between two scans acquired at the same moment in time should always be zero. The negative and positive differences in plaque contour delineation in these scans were used along with the CNR in order to create calibration graphs on which a linear regression analysis was performed. This analysis was conducted on a cohort of 50 patients referred for a CCTA due to chest complaints. A total of 300 coronary vessels were analyzed. First, plaque contours were semi-automatically determined for all major epicardial coronary vessels. Second, manual drawings of seven regions of interest (ROIs) per scan were used to quantify the scan quality based on the CNR for each vessel. Results A linear regression analysis was performed on the CNR and negative and positive plaque contour delineation differences. Accounting for the standard error of the estimate, the linear regression analysis revealed that above 1.009 − 0.002 × CNR there is an increase in plaque thickness (progression), and below − 1.638 + 0.012 × CNR there is a decrease in plaque thickness (regression). Conclusion This study demonstrates the feasibility of developing vessel-specific, quality-based thresholds for visualizing local plaque thickness differences evaluated by serial CCTA. These thresholds have the potential to facilitate the early detection of atherosclerosis progression.

Abstract In this paper, we introduce a new quantity called SVD entanglement entropy. This is a generalization of entanglement entropy in that it depends on two different states, as in pre- and post-selection processes. This SVD entanglement entropy takes non-negative real values and is bounded by the logarithm of the Hilbert space dimensions. The SVD entanglement entropy can be interpreted as the average number of Bell pairs distillable from intermediates states. We observe that the SVD entanglement entropy gets enhanced when the two states are in the different quantum phases in an explicit example of the transverse-field Ising model. Moreover, we calculate the Rényi SVD entropy in various field theories and examine holographic calculations using the AdS/CFT correspondence.

Background:. Social media use has grown across healthcare delivery and practice, with dramatic changes occurring in response to the coronavirus (COVID-19) pandemic. The purpose of this study was to conduct a comprehensive systematic review to determine the current landscape of social media use by (1) orthopaedic surgery residencies/fellowship training programs and (2) individual orthopaedic surgeons and the change in use over time. Methods:. We searched 3 electronic databases (PubMed, MEDLINE, and Embase) from their inception to April 2022 for all studies that analyzed the use of social media in orthopaedic surgery. Two reviewers independently determined study eligibility, rated study quality, and extracted data. Methodology was in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results:. Twenty-eight studies were included, of which 11 analyzed social media use by orthopaedic surgery residency and fellowship training programs and 17 examined its use by individual orthopaedic surgeons. Among residency and fellowship programs, Instagram was identified as the most common platform used, with 42% to 88% of programs reporting program-specific Instagram accounts, followed by Twitter/X (20%-52%) and Facebook (10%-38%). Social media was most commonly used by programs for recruitment and information dissemination to prospective residency applicants (82% and 73% of included studies, respectively). After the start of the COVID-19 pandemic, there was a 620% and 177% increase in the number of training programs with Instagram and Twitter/X accounts, respectively. Individual use of social media ranged from 1.7% to 76% (Twitter/X), 10% to 73% (Facebook), 0% to 61% (Instagram), 22% to 61% (LinkedIn), and 6.5% to 56% (YouTube). Conclusions:. Instagram, Twitter/X, and Facebook are the premier platforms that patients, residency applicants, and institutions frequent. With the continued growth of social media use anticipated, it will be critical for institutions and individuals to create and abide by guidelines outlining respectful and professional integration of social media into practice. Level of Evidence:. Level IV.

Abstract Highly efficient isomerization of glucose to fructose is essential for valorizing cellulose fraction of biomass to value-added chemicals. This work provided an innovative method for preparing Mg-biochar and Mg–K-biochar catalysts by impregnating either MgCl2 alone or in combination with different K compounds (Ding et al. in Bioresour Technol 341:125835, 2021, https://doi.org/10.1016/j.biortech.2021.125835 and KHCO3) on cellulose-derived biochar, followed by hydrothermal carbonization and pyrolysis. Single active substance MgO existing in the 10Mg–C could give better catalytic effect on glucose isomerization than the synergy of MgO and KCl crystalline material present in 10Mg–KCl–C. But the catalytic effect of 10Mg–C was decreased when the basic site of MgO was overloaded. Compared to other carbon-based metal catalysts, 10Mg–KHCO3–C with 10 wt% MgCl2 loading had excellent catalytic performance, which gave a higher fructose yield (36.7%) and selectivity (74.54%), and catalyzed excellent glucose conversion (53.99%) at 100 °C in 30 min. Scanning electron microscope–energy dispersive spectrometer and X-Ray diffraction revealed that the distribution of Mg2+ and K+ in 10Mg–KHCO3–C was uniform and the catalytic active substances (MgO, KCl and K2CO3) were more than 10Mg–C (only MgO). The synergy effects of MgO and K2CO3 active sites enhanced the pH of reaction system and induced H2O ionization to form considerable OH− ions, thus easily realizing a deprotonation of glucose and effectively catalyzing the isomerization of glucose. In this study, we developed a highly efficient Mg–K-biochar bimetallic catalyst for glucose isomerization and provided an efficient method for cellulose valorization. Graphical Abstract

Abstract Background High dose unilobar radioembolization (also termed ‘radiation lobectomy’)—the transarterial unilobar infusion of radioactive microspheres as a means of controlling tumour growth while concomitantly inducing future liver remnant hypertrophy—has recently gained interest as induction strategy for surgical resection. Prospective studies on the safety and efficacy of the unilobar radioembolization-surgery treatment algorithm are lacking. The RALLY study aims to assess the safety and toxicity profile of holmium-166 unilobar radioembolization in patients with hepatocellular carcinoma ineligible for surgery due to insufficiency of the future liver remnant. Methods The RALLY study is a multicenter, interventional, non-randomized, open-label, non-comparative safety study. Patients with hepatocellular carcinoma who are considered ineligible for surgery due to insufficiency of the future liver remnant (

Abstract Background For safe and effective holmium-166 (166Ho) liver radioembolization, dosimetry is crucial and requires accurate healthy liver definition. The current clinical standard relies on manual segmentation and registration of a separately acquired contrast enhanced CT (CECT), a prone-to-error and time-consuming task. An alternative is offered by simultaneous imaging of 166Ho and technetium-99m stannous–phytate accumulating in healthy liver cells (166Ho–99mTc dual-isotope protocol). This study compares healthy liver segmentation performed with an automatic method using 99mTc images derived from a 166Ho–99mTc dual-isotope acquisition to the manual segmentation, focusing on healthy liver dosimetry and corresponding hepatotoxicity. Data from the prospective HEPAR PLuS study were used. Automatic healthy liver segmentation was obtained by thresholding the 99mTc image (no registration step required). Manual segmentation was performed on CECT and then manually registered to the SPECT/CT and subsequently to the corresponding 166Ho SPECT to compute absorbed dose in healthy liver. Results Thirty-one patients (66 procedures) were assessed. Manual segmentation and registration took a median of 30 min per patient, while automatic segmentation was instantaneous. Mean ± standard deviation of healthy liver absorbed dose was 18 ± 7 Gy and 20 ± 8 Gy for manual and automatic segmentations, respectively. Mean difference ± coefficient of reproducibility between healthy liver absorbed doses using the automatic versus manual segmentation was 2 ± 6 Gy. No correlation was found between mean absorbed dose in the healthy liver and hepatotoxicity. Conclusions 166Ho–99mTc dual-isotope protocol can automatically segment the healthy liver without hampering the 166Ho dosimetry assessment. Trial registration: ClinicalTrials.gov, NCT02067988. Registered 20 February 2014. https://clinicaltrials.gov/ct2/show/NCT02067988

Abstract Background C-lignin is a homopolymer of caffeyl alcohol present in the seed coats of a variety of plant species including vanilla orchid, various cacti, and the ornamental plant Cleome hassleriana. Because of its unique chemical and physical properties, there is considerable interest in engineering C-lignin into the cell walls of bioenergy crops as a high-value co-product of bioprocessing. We have used information from a transcriptomic analysis of developing C. hassleriana seed coats to suggest strategies for engineering C-lignin in a heterologous system, using hairy roots of the model legume Medicago truncatula. Results We systematically tested strategies for C-lignin engineering using a combination of gene overexpression and RNAi-mediated knockdown in the caffeic acid/5-hydroxy coniferaldehyde 3/5-O-methyltransferase (comt) mutant background, monitoring the outcomes by analysis of lignin composition and profiling of monolignol pathway metabolites. In all cases, C-lignin accumulation required strong down-regulation of caffeoyl CoA 3-O-methyltransferase (CCoAOMT) paired with loss of function of COMT. Overexpression of the Selaginella moellendorffii ferulate 5-hydroxylase (SmF5H) gene in comt mutant hairy roots resulted in lines that unexpectedly accumulated high levels of S-lignin. Conclusion C-Lignin accumulation of up to 15% of total lignin in lines with the greatest reduction in CCoAOMT expression required the strong down-regulation of both COMT and CCoAOMT, but did not require expression of a heterologous laccase, cinnamyl alcohol dehydrogenase (CAD) or cinnamoyl CoA reductase (CCR) with preference for 3,4-dihydroxy-substituted substrates in M. truncatula hairy roots. Cell wall fractionation studies suggested that the engineered C-units are not present in a heteropolymer with the bulk of the G-lignin.

Abstract Aerosol measurements during the DOE ARM Layered Atlantic Smoke Interactions with Clouds (LASIC) campaign were used to quantify the differences between clean and smoky cloud condensation nuclei (CCN) budgets. Accumulation‐mode particles accounted for ∼70% of CCN at supersaturations 0.3% Aitken particles contributions increased to 30%–40% of clean CCN. For clean conditions, the Hoppel minimum diameter was correlated to the accumulation‐mode number concentration, indicating aerosol‐correlated cloud activation was controlling the lower diameter cutoff for which particles serve as CCN. For smoky conditions, the contributions of Aitken particles increase and the correlation of cloud activation to accumulation‐mode particles is masked by the lower‐hygroscopicity smoke. These results provide the first multi‐month in situ quantitative constraints on the role of aerosol number size distributions in controlling cloud activation in the tropical Atlantic boundary layer.

Abstract During its first decade of life, Physiological Reports has become a home for well‐conceived and rigorously performed exercise physiology and metabolism studies. The breadth of research within this area is impressive, covering exercise‐induced increases in skeletal muscle gene expression to the effects of exercise on the gut microbiome. The purpose of the current review is to highlight some of the impactful exercise physiology and metabolism papers published in the journal and to look ahead to what areas exercise physiology publications might address in the next 10 years.

Abstract Co‐administration of clesacostat (acetyl‐CoA carboxylase inhibitor, PF‐05221304) and ervogastat (diacylglycerol O‐acyltransferase inhibitor, PF‐06865571) in laboratory models improved non‐alcoholic fatty liver disease (NAFLD)/non‐alcoholic steatohepatitis (NASH) end points and mitigated clesacostat‐induced elevations in circulating triglycerides. Clesacostat is cleared via organic anion‐transporting polypeptide‐mediated hepatic uptake and cytochrome P450 family 3A (CYP3A); in vitro clesacostat is identified as a potential CYP3A time‐dependent inactivator. In vitro ervogastat is identified as a substrate and potential inducer of CYP3A. Prior to longer‐term efficacy trials in participants with NAFLD, safety and pharmacokinetics (PK) were evaluated in a phase I, non‐randomized, open‐label, fixed‐sequence trial in healthy participants. In Cohort 1, participants (n = 7) received clesacostat 15 mg twice daily (b.i.d.) alone (Days 1–7) and co‐administered with ervogastat 300 mg b.i.d. (Days 8–14). Mean systemic clesacostat exposures, when co‐administered with ervogastat, decreased by 12% and 19%, based on maximum plasma drug concentration and area under the plasma drug concentration–time curve during the dosing interval, respectively. In Cohort 2, participants (n = 9) received ervogastat 300 mg b.i.d. alone (Days 1–7) and co‐administered with clesacostat 15 mg b.i.d. (Days 8–14). There were no meaningful differences in systemic ervogastat exposures when administered alone or with clesacostat. Clesacostat 15 mg b.i.d. and ervogastat 300 mg b.i.d. co‐administration was overall safe and well tolerated in healthy participants. Cumulative safety and no clinically meaningful PK drug interactions observed in this study supported co‐administration of these two novel agents in additional studies exploring efficacy and safety in the management of NAFLD.

IntroductionThere is a lack of comprehensive and uniform data on head and neck paragangliomas (HNPGLs), and research is challenging due to its rarity and the involvement of multiple medical specialties. To improve current research data collection, we initiated the Head and Neck Paraganglioma Registry (HNPGL Registry). The aim of the HNPGL Registry is to a) collect extensive data on all HNPGL patients through a predefined protocol, b) give insight in the long term outcomes using patient reported outcome measures (PROMs), c) create uniformity in the diagnostic and clinical management of these conditions, and thereby d) help provide content for future (randomized) research.Methods and analysisThe HNPGL Registry is designed as a prospective longitudinal observational registry for data collection on HNPGL patients and carriers of (likely) pathogenic variants causative of HNPGLs. All patients, regardless of the received treatment modality, can be included in the registry after informed consent is obtained. All relevant data regarding the initial presentation, diagnostics, treatment, and follow-up will be collected prospectively in an electronic case report form. In addition a survey containing the EuroQol 5D-5L (EQ-5D-5L), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), Modified Fatigue Impact Scale (MFIS), Short QUestionnaire to Assess Health-enhancing physical activity (SQUASH), Cancer Worry Scale (CWS) and Hospital Anxiety and Depression Scale (HADS) will be sent periodically. The registry protocol was approved by the Medical Ethical Review Board of the University Medical Center Utrecht.ConclusionThe HNPGL Registry data will be used to further establish the optimal management for HNPGL patients and lay the foundation for guideline recommendations and the outline of future research.

BackgroundAcute rejection (AR) after kidney transplantation is an important allograft complication. To reduce the risk of post-transplant AR, determination of kidney transplant donor-recipient mismatching focuses on blood type and human leukocyte antigens (HLA), while it remains unclear whether non-HLA genetic mismatching is related to post-transplant complications.MethodsWe carried out a genome-wide scan (HLA and non-HLA regions) on AR with a large kidney transplant cohort of 784 living donor-recipient pairs of European ancestry. An AR polygenic risk score (PRS) was constructed with the non-HLA single nucleotide polymorphisms (SNPs) filtered by independence (r2 < 0.2) and P-value (< 1×10-3) criteria. The PRS was validated in an independent cohort of 352 living donor-recipient pairs.ResultsBy the genome-wide scan, we identified one significant SNP rs6749137 with HR = 2.49 and P-value = 2.15×10-8. 1,307 non-HLA PRS SNPs passed the clumping plus thresholding and the PRS exhibited significant association with the AR in the validation cohort (HR = 1.54, 95% CI = (1.07, 2.22), p = 0.019). Further pathway analysis attributed the PRS genes into 13 categories, and the over-representation test identified 42 significant biological processes, the most significant of which is the cell morphogenesis (GO:0000902), with 4.08 fold of the percentage from homo species reference and FDR-adjusted P-value = 8.6×10-4.ConclusionsOur results show the importance of donor-recipient mismatching in non-HLA regions. Additional work will be needed to understand the role of SNPs included in the PRS and to further improve donor-recipient genetic matching algorithms. Trial registry: Deterioration of Kidney Allograft Function Genomics (NCT00270712) and Genomics of Kidney Transplantation (NCT01714440) are registered on ClinicalTrials.gov.

Abstract Introduction From January 2021 to June 2022, the United States Centers for Disease Control and Prevention required predeparture SARS‐CoV‐2 testing for all air passengers arriving into the United States from a foreign country. Methods Using data collected during a surveillance project, we described predeparture testing behavior among a convenience sample of international air passengers entering the United States from July to September 2021 at six US ports of entry. We analyzed pairwise relationships between self‐reported test type, test timing, demographic and travel characteristics, and COVID‐19 vaccination status using chi‐square and Fisher's exact tests. Results Participants were more likely to get a NAAT versus antigen test if they identified as non‐Hispanic Asian or Pacific Islander (68.2%, n = 173), non‐Hispanic Black (62.6%, n = 147), or if they preferred not to report race and ethnicity (60.8%, n = 209) when compared to those who identified as non‐Hispanic White (47.1%, n = 1086, all p

Abstract Background There is uncertainty about the long-term risks of living kidney donation. Well-designed studies with controls well-matched on risk factors for kidney disease are needed to understand the attributable risks of kidney donation. Methods The goal of the Minnesota Attributable Risk of Kidney Donation (MARKD) study is to compare the long-term (> 50 years) outcomes of living donors (LDs) to contemporary and geographically similar controls that are well-matched on health status. University of Minnesota (n = 4022; 1st transplant: 1963) and Mayo Clinic LDs (n = 3035; 1st transplant: 1963) will be matched to Rochester Epidemiology Project (REP) controls (approximately 4 controls to 1 donor) on the basis of age, sex, and race/ethnicity. The REP controls are a well-defined population, with detailed medical record data linked between all providers in Olmsted and surrounding counties, that come from the same geographic region and era (early 1960s to present) as the donors. Controls will be carefully selected to have health status acceptable for donation on the index date (date their matched donor donated). Further refinement of the control group will include confirmed kidney health (e.g., normal serum creatinine and/or no proteinuria) and matching (on index date) of body mass index, smoking history, family history of chronic kidney disease, and blood pressure. Outcomes will be ascertained from national registries (National Death Index and United States Renal Data System) and a new survey administered to both donors and controls; the data will be supplemented by prior surveys and medical record review of donors and REP controls. The outcomes to be compared are all-cause mortality, end-stage kidney disease, cardiovascular disease and mortality, estimated glomerular filtration rate (eGFR) trajectory and chronic kidney disease, pregnancy risks, and development of diseases that frequently lead to chronic kidney disease (e.g. hypertension, diabetes, and obesity). We will additionally evaluate whether the risk of donation differs based on baseline characteristics. Discussion Our study will provide a comprehensive assessment of long-term living donor risk to inform candidate living donors, and to inform the follow-up and care of current living donors.

Number-recognition tasks, such as the how-many task, involve set-to-word mapping, and number-creation tasks, such as the give-n task, entail word-to-set mapping. The present study involved comparing sixty 3-year-olds’ performance on the two tasks with collections of one to three items over three time points about 3 weeks apart. Inconsistent with the sparse evidence indicating equivalent task performance, an omnibus test indicated that success differed significantly by task (and set size but not by time). A follow-up analysis indicated that the hypothesis that success emerges first on the how-many task was, in general, significantly superior to the hypothesis of simultaneous development. It further indicated the how-many-first hypothesis was superior to a give-n-first hypothesis for sets of three. A theoretical implication is that set-to-word mapping appears to develop before word-to-set mapping, especially in the case of three. A methodological implication is that the give-n task may underestimate a key aspect of children’s cardinal understanding of small numbers. Another is that the traditional give-n task, which requires checking an initial response by one-to-one counting, confounds pre-counting and counting competencies.

Abstract Background Prostate cancer patients with locoregional lymph node disease at diagnosis (N1M0) still have a limited prognosis despite the improvements provided by aggressive curative intent multimodal locoregional external beam radiation therapy (EBRT) with systemic androgen deprivation therapy (ADT). Although some patients can be cured and the majority of patients have a long survival, the 5-year biochemical failure rate is currently 29–47%. [177Lu]Lu-PSMA-617 has shown impressive clinical and biochemical responses with low toxicity in salvage setting in metastatic castration-resistant prostate cancer. This study aims to explore the combination of standard EBRT and ADT complemented with a single administration of [177Lu]Lu-PSMA-617 in curative intent treatment for N1M0 prostate cancer. Hypothetically, this combined approach will enhance EBRT to better control macroscopic tumour localizations, and treat undetected microscopic disease locations inside and outside EBRT fields. Methods The PROQURE-I study is a multicenter prospective phase I study investigating standard of care treatment (7 weeks EBRT and 3 years ADT) complemented with one concurrent cycle (three, six, or nine GBq) of systemic [177Lu]Lu-PSMA-617 administered in week two of EBRT. A maximum of 18 patients with PSMA-positive N1M0 prostate cancer will be included. The tolerability of adding [177Lu]Lu-PSMA-617 will be evaluated using a Bayesian Optimal Interval (BOIN) dose-escalation design. The primary objective is to determine the maximum tolerated dose (MTD) of a single cycle [177Lu]Lu-PSMA-617 when given concurrent with EBRT + ADT, defined as the occurrence of Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 grade three or higher acute toxicity. Secondary objectives include: late toxicity at 6 months, dosimetric assessment, preliminary biochemical efficacy at 6 months, quality of life questionnaires, and pharmacokinetic modelling of [177Lu]Lu-PSMA-617. Discussion This is the first prospective study to combine EBRT and ADT with [177Lu]Lu-PSMA-617 in treatment naïve men with N1M0 prostate cancer, and thereby explores the novel application of [177Lu]Lu-PSMA-617 in curative intent treatment. It is considered likely that this study will confirm tolerability as the combined toxicity of these treatments is expected to be limited. Increased efficacy is considered likely since both individual treatments have proven high anti-tumour effect as mono-treatments. Trial registration ClinicalTrials, NCT05162573 . Registered 7 October 2021.

Therapeutic antibodies (Abs) which act on a broader range of epitopes may provide more durable protection against the genetic drift of a target, typical of viruses or tumors. When these Abs exist concurrently on the targeted antigen, several mechanisms of action (MoAs) can be engaged, boosting therapeutic potency. This study selected combinations of four and five Abs with non- or partially overlapping epitopes to the SARS-CoV-2 spike glycoprotein, on or outside the crucial receptor binding domain (RBD), to offer resilience to emerging variants and trigger multiple MoAs. The combinations were derived from a pool of unique-sequence scFv Ab fragments retrieved from two SARS-CoV-2-naïve human phage display libraries. Following recombinant expression to full-length human IgG1 candidates, a biolayer interferometric analysis mapped epitopes to bins and confirmed that up to four Abs from across the bins can exist simultaneously on the spike glycoprotein trimer. Not all the bins of Abs interfered with the spike protein binding to angiotensin converting enzyme 2 (ACE2) in competitive binding assays, nor neutralized the pseudovirus or authentic virus in vitro, but when combined in vivo, their inclusion resulted in a much stronger viral clearance in the lungs of intranasally challenged hamsters, compared to that of those treated with mono ACE2 blockers. In addition, the Ab mixtures activated in vitro reporter cells expressing Fc-gamma receptors (FcγRs) involved in antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP). The best four-Ab combination neutralized seventeen variants of concern from Wuhan-Hu1 to Omicron BA.4/BA.5 in vitro.

Summary: Background: New and emerging risks for invasive aspergillosis (IA) bring the need for contemporary analyses of the epidemiology and outcomes of IA, in order to improve clinical practice. Methods: The study was a retrospective, multicenter, cohort design of proven and probable IA in adults from 10 Australasian tertiary centres (January 2017–December 2020). Descriptive analyses were used to report patients’ demographics, predisposing factors, mycological characteristics, diagnosis and management. Accelerated failure-time model was employed to determine factor(s) associated with 90-day all-cause mortality (ACM). Findings: Of 382 IA episodes, 221 (in 221 patients) fulfilled inclusion criteria – 53 proven and 168 probable IA. Median patient age was 61 years (IQR 51–69). Patients with haematologic malignancies (HM) comprised 49.8% of cases. Fifteen patients (6.8%) had no pre-specified immunosuppression and eleven patients (5.0%) had no documented comorbidity. Only 30% of patients had neutropenia. Of 170 isolates identified, 40 (23.5%) were identified as non-Aspergillus fumigatus species complex. Azole-resistance was present in 3/46 (6.5%) of A. fumigatus sensu stricto isolates. Ninety-day ACM was 30.3%. HM (HR 1.90; 95% CI 1.04–3.46, p = 0.036) and ICU admission (HR 4.89; 95% CI 2.93–8.17, p

Summary: Even though the discovery of lytic polysaccharide monooxygenases (LPMOs) has fundamentally shifted our understanding of biomass degradation, most of the current studies focused on their roles in carbohydrate oxidation. However, no study demonstrated if LPMO could directly participate to the process of lignin degradation in lignin-degrading microbes. This study showed that LPMO could synergize with lignin-degrading enzymes for efficient lignin degradation in white-rot fungi. The transcriptomics analysis of fungi Irpex lacteus and Dichomitus squalens during their lignocellulosic biomass degradation processes surprisingly highlighted that LPMOs co-regulated with lignin-degrading enzymes, indicating their more versatile roles in the redox network. Biochemical analysis further confirmed that the purified LPMO from I. lacteus CD2 could use diverse electron donors to produce H2O2, drive Fenton reaction, and synergize with manganese peroxidase for lignin oxidation. The results thus indicated that LPMO might uniquely leverage the redox network toward dynamic and efficient degradation of different cell wall components.

Abstract The oceanic South Atlantic Convergence Zone (SACZ) has played a major role during South America’s 2021/2022 summer extreme rainy season, being responsible for more than 90% of the precipitation in some regions of Southeast Brazil and in some regions of the Southwestern Atlantic Ocean (SWA). The summer of 2021/2022 was unique and rare and considered an abnormally humid season as verified by official Brazilian Institutes. First, the unusual number of cases of SACZ episodes (seven), was the highest recorded in the last decade. Second, all the cases that occurred were oceanic SACZ that assumed characteristics of an Atmospheric River and produced an excessively anomalous amount of precipitation during this period. Excess precipitation along with the regions located in mountainous and very uneven relief, which by orographic effects favors high precipitation volumes, were responsible for amplifying the observed impacts, such as landslides and floods that caused several losses to society. We also showed the main effects of coupling and interaction between the waters of the surface layer of the SWA and the atmosphere. Our learning from this study ends with the unprecedented results of how the marine atmospheric boundary layer (MABL) is locally modulated by the sea surface temperature (SST) that lies just below it. Until the present moment, we emphasize that this important mechanism has not been widely highlighted in the literature, showing that even though the ocean is colder than before oceanic SACZ is established, it is still warmer than the overlying air, thus, the ocean continues to be an active source of heat and moisture for the atmosphere and enhances the MABL instability process.

Abstract Social animals become stressed upon social isolation, proactively engaging in affiliative contacts among conspecifics after resocialization. We have previously reported that calcitonin receptor (Calcr) expressing neurons in the central part of the medial preoptic area (cMPOA) mediate contact-seeking behaviors in female mice. Calcr neurons in the posterodorsal part of the medial amygdala (MeApd) are also activated by resocialization, however their role in social affiliation is still unclear. Here we first investigated the functional characteristics of MeApd Calcr + cells; these neurons are GABAergic and show female-biased Calcr expression. Next, using an adeno-associated virus vector expressing a short hairpin RNA targeting Calcr we aimed to identify its molecular role in the MeApd. Inhibiting Calcr expression in the MeApd increased social contacts during resocialization without affecting locomotor activity, suggesting that the endogenous Calcr signaling in the MeApd suppresses social contacts. These results demonstrate the distinct roles of Calcr in the cMPOA and MeApd for regulating social affiliation.

Abstract Background Bacterial lignin degradation is believed to be primarily achieved by a secreted enzyme system. Effects of such extracellular enzyme systems on lignin structural changes and degradation pathways are still not clearly understood, which remains as a bottleneck in the bacterial lignin bioconversion process. Results This study investigated lignin degradation using an isolated secretome secreted by Pseudomonas putida KT2440 that grew on glucose as the only carbon source. Enzyme assays revealed that the secretome harbored oxidase and peroxidase/Mn2+-peroxidase capacity and reached the highest activity at 120 h of the fermentation time. The degradation rate of alkali lignin was found to be only 8.1% by oxidases, but increased to 14.5% with the activation of peroxidase/Mn2+-peroxidase. Gas chromatography–mass spectrometry (GC–MS) and two-dimensional 1H–13C heteronuclear single-quantum coherence (HSQC) NMR analysis revealed that the oxidases exhibited strong C–C bond (β-β, β-5, and β-1) cleavage. The activation of peroxidases enhanced lignin degradation by stimulating C–O bond (β-O-4) cleavage, resulting in increased yields of aromatic monomers and dimers. Further mass spectrometry-based quantitative proteomics measurements comprehensively identified different groups of enzymes particularly oxidoreductases in P. putida secretome, including reductases, peroxidases, monooxygenases, dioxygenases, oxidases, and dehydrogenases, potentially contributed to the lignin degradation process. Conclusions Overall, we discovered that bacterial extracellular degradation of alkali lignin to vanillin, vanillic acid, and other lignin-derived aromatics involved a series of oxidative cleavage, catalyzed by active DyP-type peroxidase, multicopper oxidase, and other accessory enzymes. These results will guide further metabolic engineering design to improve the efficiency of lignin bioconversion. Graphical Abstract

Abstract Background Activation of sphingomyelinase (SMase) as a result of a general inflammatory response has been implicated as a mechanism underlying disease‐related loss of skeletal muscle mass and function in several clinical conditions including heart failure. Here, for the first time, we characterize the effects of SMase activity on human muscle fibre contractile function and assess skeletal muscle SMase activity in heart failure patients. Methods The effects of SMase on force production and intracellular Ca2+ handling were investigated in single intact human muscle fibres. Additional mechanistic studies were performed in single mouse toe muscle fibres. RNA sequencing was performed in human muscle bundles exposed to SMase. Intramuscular SMase activity was measured from heart failure patients (n = 61, age 69 ± 0.8 years, NYHA III‐IV, ejection fraction 25 ± 1.0%, peak VO2 14.4 ± 0.6 mL × kg × min) and healthy age‐matched control subjects (n = 10, age 71 ± 2.2 years, ejection fraction 60 ± 1.2%, peak VO2 25.8 ± 1.1 mL × kg × min). SMase activity was related to circulatory factors known to be associated with progression and disease severity in heart failure. Results Sphingomyelinase reduced muscle fibre force production (−30%, P

Objective: To report a case of severe ovarian hyperstimulation syndrome (OHSS) persisting into the late second trimester of a singleton pregnancy. Design: Case report. Setting: Academic tertiary care center. Patient(s): A 29-year-old woman with severe OHSS after fresh embryo transfer after controlled ovarian hyperstimulation requiring intervention until 21 weeks’ gestation in a singleton pregnancy. Intervention(s): Thorough evaluation of an unusual case of severe OHSS and medical/procedural management of its sequelae in the setting of ongoing pregnancy. Main Outcome Measures(s): The clinical development of severe OHSS during pregnancy and its effect on pregnancy outcomes. Result(s): Severe OHSS persisted until 21 weeks’ gestation with reaccumulating ascitic fluid, which impacted pregnancy outcomes. Conclusion(s): Clinicians should be aware of the risk of severe OHSS and its possible effect on pregnancy outcomes beyond the first trimester.

There are challenges in monitoring and managing water quality due to spatial and temporal heterogeneity in contaminant sources, transport, and transformations. We demonstrate the importance of longitudinal stream synoptic (LSS) monitoring, which can track combinations of water quality parameters along flowpaths across space and time. Specifically, we analyze longitudinal patterns of chemical mixtures of carbon, nutrients, greenhouse gasses, salts, and metals concentrations along 10 flowpaths draining 1,765 km2 of the Chesapeake Bay region. These 10 longitudinal stream flowpaths are drained by watersheds experiencing either urban degradation, forest and wetland conservation, or stream and floodplain restoration. Along the 10 longitudinal stream flowpaths, we monitored over 300 total sampling sites along a combined stream length of 337 km. Synoptic monitoring along longitudinal flowpaths revealed: (1) increasing, decreasing, piecewise, or no trends and transitions in water quality with increasing distance downstream, which provide insights into water quality processes along flowpaths; (2) longitudinal trends and transitions in water quality along flowpaths can be quantified and compared using simple linear and non-linear statistical relationships with distance downstream and/or land use/land cover attributes, (3) attenuation and transformation of chemical cocktails along flowpaths depend on: spatial scales, pollution sources, and transitions in land use and management, hydrology, and restoration. We compared our LSS patterns with others from the global literature to synthesize a typology of longitudinal water quality trends and transitions in streams and rivers based on hydrological, biological, and geochemical processes. Applications of LSS monitoring along flowpaths from our results and the literature reveal: (1) if there are shifts in pollution sources, trends, and transitions along flowpaths, (2) which pollution sources can spread further downstream to sensitive receiving waters such as drinking water supplies and coastal zones, and (3) if transitions in land use, conservation, management, or restoration can attenuate downstream transport of pollution sources. Our typology of longitudinal water quality responses along flowpaths combines many observations across suites of chemicals that can follow predictable patterns based on watershed characteristics. Our typology of longitudinal water quality responses also provides a foundation for future studies, watershed assessments, evaluating watershed management and stream restoration, and comparing watershed responses to non-point and point pollution sources along streams and rivers. LSS monitoring, which integrates both spatial and temporal dimensions and considers multiple contaminants together (a chemical cocktail approach), can be a comprehensive strategy for tracking sources, fate, and transport of pollutants along stream flowpaths and making comparisons of water quality patterns across different watersheds and regions.

Due to its ability to spread quickly and result in tree mortality, Sphaerulina musiva (Septoria) is one of the most severe diseases impacting Populus. Previous studies have identified that Septoria infection induces differential expression of phenylpropanoid biosynthesis genes. However, more extensive characterization of changes to lignin in response to Septoria infection is lacking. To study the changes of lignin due to Septoria infection, four field grown, naturally variant Populus trichocarpa exhibiting visible signs of Septoria infection were sampled at health, infected, and reaction zone regions for cell wall characterization. Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and acid hydrolysis were applied to identify changes to the cell wall, and especially lignin. FTIR and subsequent principal component analysis revealed that infected and reaction zone regions were similar and could be distinguished from the non-infected (healthy) region. NMR results indicated the general trend that infected region had a higher syringyl:guaiacyl ratio and lower p-hydroxybenzoate content than the healthy regions from the same genotype. Finally, Klason lignin content in the infected and/or reaction zone regions was shown to be higher than healthy region, which is consistent with previous observations of periderm development and metabolite profiling. These results provide insights on the response of Populus wood characteristics to Septoria infection, especially between healthy and infected region within the same genotype.

Abstract. Objectives:. The purpose of this study was to obtain information on Canadian orthopaedic trauma surgeon practices and salary demographics. It was hypothesized that most of the practicing surgeons recognize specific practice aspects (compensation, call schedule, operating room availability, and provided support staff) as key factors in employment opportunity evaluation. Design:. Cross-sectional survey study. Setting:. Orthopaedic Trauma Association (OTA) practice surveys. Participants:. All active Canadian members of the OTA were eligible to participate. Main Outcome Measurement:. A 50-question survey was sent through email to OTA members assessing physician, practice, and compensation metrics of Canadian orthopaedic traumatologists. Results:. Fifty-two of 113 Canadian OTA members participated giving a response rate of 46%. All surgeons worked in an academic practice, either for a university (83%) or community hospital (17%). Only 2% of surgeons have changed jobs in the last 5 years, and over 73% of surgeons maintain the same place of employment during their careers. Most had an available dedicated orthopaedic trauma operating room (73%). The majority indicated having residents (71%) and fellows (63%) as support staff. Many reported completing 300–500 cases per year (42%), which decreased during COVID-19 for 50% of surgeons. The most common reported compensation was between $400,000 and $600,000 US dollars (25%) with many working 4–6 call shifts a month (48%) and 51–70 hours a week (48%). Conclusion:. This study demonstrated the varying practice and physician economic variables currently in Canada. The identification and continued surveillance of these employment variables will allow for transparency in job market evaluation by applicants. Level of Evidence:. Level V.

Coxsackieviruses (CVs) are common causes of infections and can be life-threatening. Unfortunately, rigorous studies guiding the clinician in interpreting CV serum antibody titer testing is lacking. To explore the epidemiology of circulating CVs and the serological test utility in aiding diagnosis of CV infections in our community, we obtained results of CV immunologic diagnostic tests between 2018 and 2022 from a regional healthcare database. For CV type A, rare individuals had positive CF (complement fixation) tests whereas all 16 individuals with IFA testing showed at least one positive serotype. For CV type B CF testing, 52.2% of 222 patients had at least one serotype positive, with B5 being most common and also the most common with higher titers (14.8% with ≥1:32). We found a significant reduction in seropositivity rate during the pandemic in 2020 compared to 2018, which continued through 2022 (OR: 0.2, 95% CI: 0.08–0.49, p-value < 0.001). During the pandemic, the seasonal pattern of positive tests varied from the pre-pandemic pattern. Testing for CVs was increased after the first year of the pandemic. Overall, the variability by month and seasonal change in our data support that CF testing can be used to identify recent CVB infection.

Biotic and abiotic stresses significantly affect plant fitness, resulting in a serious loss in food production. Biotic and abiotic stresses predominantly affect metabolite biosynthesis, gene and protein expression, and genome variations. However, light doses of stress result in the production of positive attributes in crops, like tolerance to stress and biosynthesis of metabolites, called hormesis. Advancement in artificial intelligence (AI) has enabled the development of high-throughput gadgets such as high-resolution imagery sensors and robotic aerial vehicles, i.e., satellites and unmanned aerial vehicles (UAV), to overcome biotic and abiotic stresses. These High throughput (HTP) gadgets produce accurate but big amounts of data. Significant datasets such as transportable array for remotely sensed agriculture and phenotyping reference platform (TERRA-REF) have been developed to forecast abiotic stresses and early detection of biotic stresses. For accurately measuring the model plant stress, tools like Deep Learning (DL) and Machine Learning (ML) have enabled early detection of desirable traits in a large population of breeding material and mitigate plant stresses. In this review, advanced applications of ML and DL in plant biotic and abiotic stress management have been summarized.

Purpose: Trans-arterial radioembolization is a well-studied tumoricidal treatment for liver malignancies; however, consensus and evidence regarding periprocedural prophylactic medication (PPM) are lacking. Methods: A single-center retrospective analysis from 2014 to 2020 was performed in patients treated with 90Y-glass microspheres for neuroendocrine or colorectal liver metastases. Inclusion criteria were the availability of at least 3 months of clinical, biochemical, and imaging follow-up and post-treatment 90Y-PET/CT imaging for the determination of the whole non-tumorous liver absorbed dose (Dh). Logistic regression models were used to investigate if variables (among which are P/UDCA and Dh) were associated with either clinical toxicity, biochemical toxicity, or hepatotoxicity. Additionally, a structured literature search was performed in November 2022 to identify all publications related to PPM use in radioembolization treatments. Results: Fifty-one patients received P/UDCA as post-treatment medication, while 19 did not. No correlation was found between toxicity and P/UDCA use. Dh was associated with biochemical toxicity (p = 0.05). A literature review resulted in eight relevant articles, including a total of 534 patients, in which no consistent advice regarding PPM was provided. Conclusion: In this single-center, retrospective review, P/UDCA use did not reduce liver toxicity in patients with metastatic liver disease. The whole non-tumorous liver-absorbed dose was the only significant factor for hepatotoxicity. No standardized international guidelines or supporting evidence exist for PPM in radioembolization.

The chemical, physical and optical properties of biomass burning aerosols are substantially altered during plume transport from Southern Africa over the southeast Atlantic, which leads to fewer but more absorptive aerosols in the marine boundary layer, according to airborne observations.

Abstract Background Despite its high specificity, PSMA PET/CT has a moderate to low sensitivity of 40–50% for pelvic lymph node detection, implicating that a negative PSMA PET/CT cannot rule out lymph node metastases. This study investigates a strategy of implementing PSMA PET/CT for initial prostate cancer staging and treatment planning compared to conventional diagnostics. In this PSMA PET/CT strategy, a bilateral extended pelvic lymph node dissection (ePLND) is only performed in case of a negative PSMA PET/CT; in case of a positive scan treatment planning is solely based on PSMA PET/CT results. Method A decision table and lifetime state transition model were created. Quality-adjusted life years and health care costs were modelled over lifetime. Results The PSMA PET/CT strategy of treatment planning based on initial staging with [68Ga]Ga-PSMA-11 PET/CT results in cost-savings of €674 and a small loss in quality of life (QoL), 0.011 QALY per patient. The positive effect of [68Ga]Ga-PSMA-11 PET/CT was caused by abandoning both an ePLND and unnecessary treatment in iM1 patients, saving costs and resulting in higher QoL. The negative effect was caused by lower QoL and high costs in the false palliative state, due to pN1lim patients (≤ 4 pelvic lymph node metastases) being falsely diagnosed as iN1ext (> 4 pelvic lymph node metastases). These patients received subsequently palliative treatment instead of potentially curative therapy. Conclusion Initial staging and treatment planning based on [68Ga]Ga-PSMA-11 PET/CT saves cost but results in small QALY loss due to the rate of false positive findings.