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Objectives: To evaluate radiomics features' reproducibility using inter-package/inter-observer measurement analysis in renal masses (RMs) based on MRI and to employ machine learning (ML) models for RM characterization., Methods: 32 Patients (23M/9F; age 61.8 ± 10.6 years) with RMs (25 renal cell carcinomas (RCC)/7 benign masses; mean size, 3.43 ± 1.73 cm) undergoing resection were prospectively recruited. All patients underwent 1.5 T MRI with T2-weighted (T2-WI), diffusion-weighted (DWI)/apparent diffusion coefficient (ADC), and pre-/post-contrast-enhanced T1-weighted imaging (T1-WI). RMs were manually segmented using volume of interest (VOI) on T2-WI, DWI/ADC, and T1-WI pre-/post-contrast imaging (1-min, 3-min post-injection) by two independent observers using two radiomics software packages for inter-package and inter-observer assessments of shape/histogram/texture features common to both packages (104 features; n = 26 patients). Intra-class correlation coefficients (ICCs) were calculated to assess inter-observer and inter-package reproducibility of radiomics measurements [good (ICC ≥ 0.8)/moderate (ICC = 0.5-0.8)/poor (ICC < 0.5)]. ML models were employed using reproducible features (between observers and packages, ICC > 0.8) to distinguish RCC from benign RM., Results: Inter-package comparisons demonstrated that radiomics features from T1-WI-post-contrast had the highest proportion of good/moderate ICCs (54.8-58.6% for T1-WI-1 min), while most features extracted from T2-WI, T1-WI-pre-contrast, and ADC exhibited poor ICCs. Inter-observer comparisons found that radiomics measurements from T1-WI pre/post-contrast and T2-WI had the greatest proportion of features with good/moderate ICCs (95.3-99.1% T1-WI-post-contrast 1-min), while ADC measurements yielded mostly poor ICCs. ML models generated an AUC of 0.71 [95% confidence interval = 0.67-0.75] for diagnosis of RCC vs. benign RM., Conclusion: Radiomics features extracted from T1-WI-post-contrast demonstrated greater inter-package and inter-observer reproducibility compared to ADC, with fair accuracy for distinguishing RCC from benign RM., Clinical Relevance: Knowledge of reproducibility of MRI radiomics features obtained on renal masses will aid in future study design and may enhance the diagnostic utility of radiomics models for renal mass characterization., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

To investigate the cellular and molecular mechanisms associated with targeting CD30-expressing Hodgkin lymphoma (HL) and immune checkpoint modulation induced by combination therapies of CTLA4 and PD1, we leveraged Phase 1/2 multicenter open-label trial NCT01896999 that enrolled patients with refractory or relapsed HL (R/R HL). Using peripheral blood, we assessed soluble proteins, cell composition, T-cell clonality, and tumor antigen-specific antibodies in 54 patients enrolled in the phase 1 component of the trial. NCT01896999 reported high (>75%) overall objective response rates with brentuximab vedotin (BV) in combination with ipilimumab (I) and/or nivolumab (N) in patients with R/R HL. We observed a durable increase in soluble PD1 and plasmacytoid dendritic cells as well as decreases in plasma CCL17, ANGPT2, MMP12, IL13, and CXCL13 in N-containing regimens (BV + N and BV + I + N) compared with BV + I (P < 0.05). Nonresponders and patients with short progression-free survival showed elevated CXCL9, CXCL13, CD5, CCL17, adenosine-deaminase, and MUC16 at baseline or after one treatment cycle and a higher prevalence of NY-ESO-1-specific autoantibodies (P < 0.05). The results suggest a circulating tumor-immune-derived signature of BV ± I ± N treatment resistance that may be useful for patient stratification in combination checkpoint therapy., Significance: Identification of multi-omic immune markers from peripheral blood may help elucidate resistance mechanisms to checkpoint inhibitor and antibody-drug conjugate combinations with potential implications for treatment decisions in relapsed HL., (©2024 The Authors; Published by the American Association for Cancer Research.)

Background: Sex disparities have been noted across various aspects of total hip/knee arthroplasty (THA/TKA). Given incentives to standardize care, bundled payment initiatives including the Comprehensive Care for Joint Replacement (CJR) program may reduce disparities. This study aimed to assess the CJR program's impact on sex disparities in THA/TKA care and outcomes., Methods: This retrospective cohort study included 259,673 THAs (61.7% women) and 506,311 TKAs (64.0% women) from a large national database (2013 to 2017). Sex disparities were assessed for care and outcomes related to the period (1) before surgery, (2) during hospitalization for THA/TKA, and (3) after discharge. Disparities were reported as women:men ratios. Difference-in-differences analyses estimated the impact of the CJR program on pre-existing sex disparities., Results: For both THA and TKA, women were less likely than men to present with a Charlson-Deyo comorbidity index >0 (women:men ratio 0.88 to 0.92), but were more likely to require blood transfusions (women:men ratio 1.48 to 1.79) and be discharged to institutional postacute care (women:men ratio 1.50 to 1.66). Difference-in-differences models demonstrated that the CJR bundled payment program reduced sex disparities in institutional postacute care discharges (THA: -2.28%; 95% confidence interval [CI] -4.20 to -0.35%, P = .02; TKA: -2.07%; 95% CI -3.93 to -0.20%; P = .03) and THA 90-day readmissions (-1.00%, 95% CI -1.88 to -0.13%, P = .02), indicating a differential impact of CJR in women versus men for some outcomes., Conclusions: While sex disparities in THA/TKA persist, the CJR program demonstrates potential to impact such differences. Future research should focus on how potential mechanisms could be leveraged to reduce disparities., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Identifying molecular and immune features to guide immune checkpoint inhibitor (ICI)-based regimens remains an unmet clinical need., Experimental Design: Tissue and longitudinal blood specimens from phase III trial S1400I in patients with metastatic squamous non-small cell carcinoma (SqNSCLC) treated with nivolumab monotherapy (nivo) or nivolumab plus ipilimumab (nivo+ipi) were subjected to multi-omics analyses including multiplex immunofluorescence (mIF), nCounter PanCancer Immune Profiling Panel, whole-exome sequencing, and Olink., Results: Higher immune scores from immune gene expression profiling or immune cell infiltration by mIF were associated with response to ICIs and improved survival, except regulatory T cells, which were associated with worse overall survival (OS) for patients receiving nivo+ipi. Immune cell density and closer proximity of CD8+GZB+ T cells to malignant cells were associated with superior progression-free survival and OS. The cold immune landscape of NSCLC was associated with a higher level of chromosomal copy-number variation (CNV) burden. Patients with LRP1B-mutant tumors had a shorter survival than patients with LRP1B-wild-type tumors. Olink assays revealed soluble proteins such as LAMP3 increased in responders while IL6 and CXCL13 increased in nonresponders. Upregulation of serum CXCL13, MMP12, CSF-1, and IL8 were associated with worse survival before radiologic progression., Conclusions: The frequency, distribution, and clustering of immune cells relative to malignant ones can impact ICI efficacy in patients with SqNSCLC. High CNV burden may contribute to the cold immune microenvironment. Soluble inflammation/immune-related proteins in the blood have the potential to monitor therapeutic benefit from ICI treatment in patients with SqNSCLC., (©2024 The Authors; Published by the American Association for Cancer Research.)

The mechanisms underlying the influence of the surface chemistry of inorganic materials on polymer structures and fracture behaviours near adhesive interfaces are not fully understood. This study demonstrates the first clear and direct evidence that molecular surface segregation and cross-linking of epoxy resin are driven by intermolecular forces at the inorganic surfaces alone, which can be linked directly to adhesive failure mechanisms. We prepare adhesive interfaces between epoxy resin and silicon substrates with varying surface chemistries (OH and H terminations) with a smoothness below 1 nm, which have different adhesive strengths by ~13 %. The epoxy resins within sub-nanometre distance from the surfaces with different chemistries exhibit distinct amine-to-epoxy ratios, cross-linked network structures, and adhesion energies. The OH- and H-terminated interfaces exhibit cohesive failure and interfacial delamination, respectively. The substrate surface chemistry impacts the cross-linked structures of the epoxy resins within several nanometres of the interfaces and the adsorption structures of molecules at the interfaces, which result in different fracture behaviours and adhesive strengths., (© 2024. The Author(s).)

Bladder cancer (BCa) is a significant health issue and poses a healthcare burden on patients, highlighting the importance of an effective detection method. Here, we developed a urine DNA methylation diagnostic panel for distinguishing between BCa and non-BCa. In the discovery stage, an analysis of the TCGA database was conducted to identify BCa-specific DNA hypermethylation markers. In the validation phase, DNA methylation levels of urine samples were measured with real-time quantitative methylation-specific PCR (qMSP). Comparative analysis of the methylation levels between BCa and non-BCa, along with the receiver operating characteristic (ROC) analyses with machine learning algorithms (logistic regression and decision tree methods) were conducted to develop practical diagnostic panels. The performance evaluation of the panel shows that the individual biomarkers of ZNF671, OTX1, and IRF8 achieved AUCs of 0.86, 0.82, and 0.81, respectively, while the combined yielded an AUC of 0.91. The diagnostic panel using the decision tree algorithm attained an accuracy, sensitivity, and specificity of 82.6%, 75.0%, and 90.9%, respectively. Our results show that the urine-based DNA methylation diagnostic panel provides a sensitive and specific method for detecting and stratifying BCa, showing promise as a standard test that could enhance the diagnosis and prognosis of BCa in clinical settings.

Background: Pediatric Hematology Oncology patients undergo frequent needlestick procedures, often leading to negative outcomes including pain and anxiety. Animal-assisted therapy has been shown to minimize pediatric patient distress; however, its utilization by a Certified Child Life Specialist (CCLS) to reduce patient distress has not been widely studied., Methods: Pediatric patients receiving needlesticks in the Hematology Oncology Clinic were enrolled between March 2018 and May 2021. Patients who had scheduled visits when the facility dog was present were assigned to the intervention group. Patients were assigned to the control group if the facility dog was not present. The primary objective was to use the Children's Anxiety and Pain Scale to determine whether the CCLS and facility dog dyad minimized patient pain and anxiety during procedures., Results: A total of 285 patients, 5 to 17 years of age, were enrolled. One hundred forty-three patients were assigned the intervention and received procedural support from the CCLS and facility dog; 142 patients were assigned the control group and received support from the CCLS only. Patient-reported pain scores were significantly lower among patients who received the intervention ( P =0.033)., Conclusions: Utilization of a CCLS and facility dog dyad during painful needlestick procedures decreases patient-reported pain compared with utilization of CCLS support alone., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Given the rapid deployment of telemedicine at the onset of the COVID - 19 pandemic, updated assessment methods are needed to study and characterize telemedicine programs. We developed a novel semi - structured survey instrument to systematically describe the characteristics and implementation processes of telemedicine programs in primary care., Methods: In the context of a larger study aiming to describe telemedicine programs in primary care, a survey was developed in 3 iterative steps: 1) literature review to obtain a list of telemedicine features, facilitators, and barriers; 2) application of three evaluation frameworks; and 3) stakeholder engagement through a 2-stage feedback process. During survey refinement, items were tested against the evaluation frameworks while ensuring it could be completed within 20-25 min. Data reduction techniques were applied to explore opportunity for condensed variables/items., Results: Sixty initially identified telemedicine features were reduced to 32 items / questions after stakeholder feedback. Per the life cycle framework, respondents are asked to report a month in which their telemedicine program reached a steady state, i.e., "maturation". Subsequent questions on telemedicine features are then stratified by telemedicine services offered at the pandemic onset and the reported point of maturation. Several open - ended questions allow for additional telemedicine experiences to be captured. Data reduction techniques revealed no indication for data reduction., Conclusion: This 32-item semi-structured survey standardizes the description of primary care telemedicine programs in terms of features as well as maturation process. This tool will facilitate evaluation of and comparisons between telemedicine programs across the United States, particularly those that were deployed at the pandemic onset., (© 2023. The Author(s).)

Background: Few studies have assessed the relationship between the quantity of preoperative corticosteroid injections (CSIs) or hyaluronic acid injections (HAIs) and postoperative infection risk after total knee or hip arthroplasty (TKA, THA). We aimed to (1) determine whether the number of injections administered before TKA/THA procedures is associated with postoperative infections and (2) establish whether infection risk varies by injection type., Methods: This retrospective cohort study included 230,487 THAs and 371,511 TKAs from the 2017 to 2018 Medicare Limited Data Set. The quantity of CSI or HAI, defined as receiving either CSI or HAI ≤2 years before TKA/THA, was identified and categorized as 0, 1, 2, or >2. The primary outcome was 90-day postoperative infection. Multivariable regression models measured the association between the number of injections and 90-day postoperative infection. Odds ratios and 95% confidence intervals were reported., Results: The percentage of THA patients receiving 1, 2, and >2 preoperative CSIs was 6.1%, 1.6%, and 0.8%, respectively. Receiving >2 CSIs within 2 years before THA was associated with higher odds of 90-day postoperative infection (odds ratios = 1.74, 95% CI = 1.11 to 2.74, P = 0.02). The percentage of TKA patients receiving 1, 2, and >2 CSIs was 3.0%, 1.2%, and 1.1%, respectively. For HAIs in TKA patients, percentage receiving injections was 98.3%, 0.6%, 0.2%, and 0.9%, respectively. Quantity of CSIs or HAIs administered was not associated with postoperative infection among TKA patients., Conclusion: Patients receiving >2 injections before THA had higher odds of 90-day postoperative infection. This finding was not observed in TKA patients. These results suggest that the use of >2 injections within 2 years of THA should be avoided., (Copyright © 2023 by the American Academy of Orthopaedic Surgeons.)

The interaction of two subsequent ultra-short sub-milli-Joule laser pulses with a thin water flow results in an emission of a strong single-cycle THz pulse associated with enhanced soft X-ray emission. In this paper, a chain of processes produced in this interaction is analyzed and compared with other THz generation studies. It is demonstrated that the enhanced THz and X-ray emissions are produced by an energetic electron beam accelerated in the interaction of a main laser pulse with liquid water ejected from the surface by the pre-pulse. This scheme thus provides an efficient laser energy conversion in a THz pulse, avoiding laser self-focusing and filamentation in air.

Bifunctional catalysts can facilitate two different electrochemical reactions with conflicting characteristics. Here, a highly reversible bifunctional electrocatalyst for rechargeable zinc-air batteries (ZABs) is reported featuring a "core-shell structure" in which N-doped graphene sheets wrap around vanadium molybdenum oxynitride nanoparticles. Single Mo atoms are released from the particle core during synthesis and anchored to electronegative N-dopant species in the graphitic shell. The resultant Mo single-atom catalysts excel as active oxygen evolution reaction (OER) sites in pyrrolic-N and as active oxygen reduction reaction (ORR) sites in pyridinic-N environments. ZABs with such bifunctional and multicomponent single-atom catalysts deliver high power density (≈376.4 mW cm -2 ) and long cycle life of over 630 h, outperforming noble-metal-based benchmarks. Flexible ZABs that can tolerate a wide range of temperatures (-20 to 80 °C) under severe mechanical deformation are also demonstrated., (© 2023 Wiley-VCH GmbH.)

Purpose: To evaluate the effectiveness and safety of intra-arterial imipenem/cilastatin sodium (IPM/CS) infusion for painful interphalangeal joint osteoarthritis (OA)., Materials and Methods: Fifty-eight patients with interphalangeal joint OA who underwent intra-arterial IPM/CS infusion were retrospectively evaluated. Intra-arterial infusions were performed via percutaneous wrist arterial access. The Numerical Rating Scale (NRS), Functional Index for Hand Osteoarthritis (FIHOA), and Patient Global Impression of Change (PGIC) scale scores were assessed at intervals of 1, 3, 6, 12, and 18 months. Clinical success was evaluated based on PGIC., Results: All patients were followed up for at least 6 months after treatment. Of them, 30 and 6 patients were followed up for 12 and 18 months, respectively. No severe or life-threatening adverse events were encountered. The mean NRS score was 6.0 ± 1.4 at baseline, which significantly decreased to 2.8 ± 1.4, 2.2 ± 1.9, and 2.4 ± 1.9 at 1, 3, and 6 months after treatment, respectively (all P < .001). The mean NRS scores were 2.8 ± 1.7 and 2.9 ± 1.9 at 12 and 18 months, respectively, in the remaining patients. The mean FIHOA score significantly decreased from 9.8 ± 5.0 at the baseline to 4.1 ± 3.5 at 3 months (P < .001). The mean FIHOA score was 4.5 ± 3.3 at 12 months in the remaining 30 patients. The clinical success rates based on PGIC at 1, 3, 6, 12, and 18 months were 62.1%, 77.6%, 70.7%, 63.4%, and 50.0%, respectively., Conclusions: Intra-arterial IPM/CS infusion is a potential treatment option for interphalangeal joint OA refractory to medical management., (Copyright © 2023. Published by Elsevier Inc.)

The mechanisms of electron irradiation damage to epoxy resin samples were evaluated using their electron diffraction patterns and electron energy-loss spectra. Their electron diffraction patterns consisted of three indistinct halo rings. The halo ring corresponding to an intermolecular distance of ∼6.4 Å degraded rapidly. Such molecular-scale collapse could have been caused by cross-linking between molecular chains. The degree of electron irradiation damage to the samples changed with the accelerating voltage. The tolerance dose limit of the epoxy resin estimated from the intensity of the halo ring was found to be improved at a higher accelerating voltage. Changes in low-loss electron energy-loss spectra indicated that the mass loss of the epoxy resin was remarkable in the early stage of electron irradiation., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Society of Microscopy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Knowledge of digestion mechanism of starch nanoparticles are crucial for their utilization and potential applications. In this study, molecular structural evolution and digestion kinetics of starch nanoparticles from green banana (GBSNPs) during digestion (0-180 min) was investigated. Distinctive topographic changes of the GBSNPs during digestion with decreased particle size and increased surface roughness were detected. The GBSNPs showed markedly decreased average molecular weight and polydispersity in the initial digestion phase (0-20 min), and these two structural characteristics remained nearly unchanged thereafter. The GBSNPs exhibited a B-type polymorph throughout digestion, while their crystallinity decreased with increasing digestion duration. The infrared spectra revealed that the initial digestion phase led to the increased absorbance ratios 1047/1022 and 1047/1035 cm -1 , reflecting the markedly increased short-range molecular order that was substantiated by the blue-shifting of COH-bending band. Logarithm of slope analysis of digestogram revealed that the GBSNPs were digested by a two-phase process that reflected the surface barrier effect exerted by the increased short-range order. The short-range molecular order strengthening induced from the initial digestion phase was responsible for the increased enzymatic resistance. The results can help to elucidate the gastrointestinal fate of starch nanoparticles for their potential applications as health-promoting ingredients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Poor preoperative mental health has been associated with worse outcomes after total hip (THA) and total knee arthroplasty (TKA). To fully understand these relationships, we assessed post-THA and post-TKA improvements in patient-reported mental and joint health by preoperative mental health groups., Methods: Elective cases (367 THA, 462 TKA) were subgrouped by low (<25th percentile), middle (25th-74th), and high (≥75th) preoperative mental health, using Veterans RAND 12-Item Health Survey Mental Component Summary (MCS) scores. In each subgroup, we assessed the relationship between preoperative MCS and 1-year postoperative change in mental and joint health. Pairwise comparisons and multivariable regression models were applied for THA and TKA separately., Results: Median postoperative mental health change was +14.0 points for the low-MCS THA group, +11.1 low-TKA, +2.0 middle-THA and TKA, -4.0 high-THA, and -4.9 high-TKA (between-group differences P < .001). All MCS groups had improved median joint health scores, without significant between-group differences. Preoperative mental health was negatively associated with mental health improvements in all groups (B = -0.94 - -0.68, P < .001-P = .01) but with improvements in joint health only in the low-THA group (B = -0.74, P = .02). Improvements in mental and joint health were positively associated for low and middle (B = 0.61-0.87, P < .001), but not for high-MCS groups, with this relationship differing for the low versus high group., Conclusion: Patients who have low preoperative mental health experienced greater postoperative mental health improvement and similar joint health improvement compared to patients who have high preoperative mental health. Findings can guide subgroup-targeted surgical decision-making and preoperative counseling., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Imaging and computational processing fusion technologies have expanded the wavelength range that can be visualized. However, it is still challenging to realize a system that can image a wide range of wavelengths, including non-visible regions, in a single system. Here, we propose a broadband imaging system based on femtosecond-laser-driven sequential light source arrays. The light source arrays allow us to form ultra-broadband illumination light depending on the excitation target and irradiated pulse energy. We demonstrated X-ray and visible imaging under atmospheric pressure by using a water film as an excitation target. Furthermore, by applying a compressive sensing algorithm, the imaging time was reduced while maintaining the number of pixels in the reconstructed image.

Purpose: Hand and wrist injuries are common among competitive athletes and can have a substantial impact on playing time and future participation. The purpose of this study was to provide epidemiological data from the National Collegiate Athletic Association Injury Surveillance Program to correlate injury diagnosis with the need for surgery and time loss., Methods: Using the National Collegiate Athletic Association Injury Surveillance Program, this retrospective study extracted data of hand and wrist injuries for all 25 National Collegiate Athletic Association sports from the academic years 2004-2005 to 2013-2014. The "severe" category was defined as injuries resulting in the following: (1) surgery, (2) season-ending status, or (3) more than 30 days of playing time loss. The epidemiologic data included injury rate per 100,000 athlete exposures (defined as 1 athlete participating in 1 practice or competition) based on diagnoses and demographic information such as sports and sex. We used a Poisson regression model to estimate the incidence rate and 95% confidence interval., Results: Overall, 4,851 hand injuries were identified, with an injury rate of 41.2 per 100,000 athlete exposures. The most common diagnoses were metacarpal or phalangeal fractures (19.9%), lacerations or contusions (15.4%), and wrist sprains (14.7%). The surgical rate was 9.6%, and the season-ending rate was 5.8%. Severe injuries occurred in 17.5% of the hand and wrist injuries; within this subset, the most common diagnoses included metacarpal or phalangeal fractures (43.8%), scaphoid fractures (12.8%), and thumb ulnar collateral ligament tears (8.7%). Scaphoid fractures and metacarpal or phalangeal fractures had the highest surgical rate and season-ending rate among all the injuries., Conclusions: The injury rate of hand and wrist injuries is comparable with those of other common sports injuries. Approximately one fifth of the injuries were considered severe, which led to a high surgical rate, and these had a considerable impact on the athletes' ability to finish the season., Type of Study/level of Evidence: Outcome research level II., (Copyright © 2023. Published by Elsevier Inc.)

THz emission in air under the irradiation of a pair of tightly-focused femtosecond laser pulses (800nm, 35fs) with nanosecond time delay and micro-meter spatial offsets is studied with polarization-sensitive THz time-domain spectroscopy and time-resolved imaging. The pre-pulse irradiation induces air-breakdown at its focus, which results in the expansion of shockwave front traveling outward. When the main pulse irradiates such shockwave front far from the pre-pulse focus with nanosecond delay, THz emission intensity was enhanced up to ∼13-times and its linear polarization was aligned along the line between the two focus positions of the pre- and the main pulses which is parallel to the expansion direction of the shockwave front. Asymmetric density profiles of the shockwave fronts prepared by the pre-pulse irradiation define the polarization of THz emission. Mechanisms are discussed from the viewpoint of electron diffusion in such asymmetric density profiles.

Purpose: To describe ultrasound (US) quality for hepatocellular carcinoma (HCC) screening/surveillance using the US LI-RADS scoring system, and to assess predictive factors of worse US quality scores., Methods: This retrospective study included adult patients (n = 470; M/F 264/206, median age 59y) at risk for HCC that underwent US for HCC screening/surveillance. US examinations were independently reviewed by 2 radiologists that assigned a visualization score (A: no/minimal, B: moderate, C: severe limitation) and US diagnostic category (US LI-RADS 1: negative, US LI-RADS 2: subthreshold, US LI-RADS 3: positive) to each study. A generalized linear mixed model was used to assess the predictive factors of worse visualization score using OR (odds ratio) statistics. Simple Kappa coefficient (K) assessed inter-reader agreement., Results: For readers 1 and 2, 295/320 (62.8%/68.1%) cases were scored A, 153/134 (32.6%/28.5%) were scored B, and 22/16 (4.6%/3.4%) were scored C, respectively. There was moderate inter-reader agreement for US LI-RADS visualization score (K = 0.478) and 100% concordance for US diagnostic category (K = 1), with 30 (6.4%) cases scored as positive (US LI-RADS 3). Cirrhosis and obesity were significant independent predictors of worse visualization scores (B/C) (cirrhosis: OR 10.4 confidence intervals: [4.25-25.48], p < 0.001; obesity: OR 3.61 [2.11-6.20], p < 0.001). Of the 30 lesions scored as US LI-RADS 3, 9 were characterized as probable or definite HCC on confirmatory CT/MRI, yielding a PPV of 30% (9/30) and a false-positive rate of 70% (21/30)., Conclusion: Moderate to severe limitations in quality of US performed for HCC screening/surveillance was observed in approximately one-third of patients. Patients with cirrhosis and/or elevated BMI have poorer quality US studies and may benefit from other screening modalities such as CT or MRI., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

OmpA, the most abundant porin in Stenotrophomonas maltophilia KJ, exists as a two-domain structure with an N-terminal domain of β-barrel structure embedded in the outer membrane and a C-terminal domain collocated in the periplasm. KJΔOmpA 299-356 , an ompA mutant of S. maltophilia KJ with a truncated OmpA devoid of 299 to 356 amino acids (aa), was able to stably embed in the outer membrane. KJΔOmpA 299-356 was more susceptible to β-lactams than wild-type KJ. We aimed to elucidate the mechanism underlying the Δ ompA 299-356 -mediated increase in β-lactam susceptibility (abbreviated as "ΔOmpA 299-356 phenotype"). KJΔOmpA 299-356 displayed a lower ceftazidime (CAZ)-induced β-lactamase activity than KJ. Furthermore, KJ2, a L1/L2 β-lactamases-null mutant, and KJ2ΔOmpA 299-356 , a KJ2 mutant with truncated OmpA devoid of299 to 356 aa, had comparable β-lactam susceptibility. Both lines of evidence indicate that decreased β-lactamase activity contributes to the ΔOmpA 299-356 phenotype. We analyzed the transcriptome results of KJ and KJΔOmpA 299-356 , focusing on PG homeostasis-associated genes. Among the 36 genes analyzed, the nagA gene was upregulated 4.65-fold in KJΔOmpA 299-356 . Deletion of the nagA gene from the chromosome of KJΔOmpA 299-356 restored β-lactam susceptibility and CAZ-induced β-lactamase activity to wild-type levels, verifying that nagA -upregulation in KJΔOmpA 299-356 contributes to the ΔOmpA 299-356 phenotype. Furthermore, transcriptome analysis revealed that rpoE (Smlt3555) and rpoP (Smlt3514) were significantly upregulated in KJΔOmpA 299-356 . The deletion mutant construction, β-lactam susceptibility, and β-lactamase activity analysis demonstrated that σ P , but not σ E , was involved in the ΔOmpA 299-356 phenotype. A real-time quantitative (qRT-PCR) assay confirmed that nagA is a member of the σ P regulon. The involvement of the σ P -NagA-L1/L2 regulatory circuit in the ΔOmpA 299-356 phenotype was manifested. IMPORTANCE Porins of Gram-negative bacteria generally act as channels that allow the entry or extrusion of molecules. Moreover, the structural role of porins in stabilizing the outer membrane by interacting with peptidoglycan (PG) and the outer membrane has been proposed. The linkage between porin deficiency and antibiotic resistance increase has been reported widely, with a rationale for blocking antibiotic influx. In this study, a link between porin defects and β-lactam susceptibility increase was demonstrated. The underlying mechanism revealed that a novel σ P -NagA-L1/L2 regulatory circuit is triggered due to the loss of the OmpA-PG interaction. This study extends the understanding on the porin defect and antibiotic susceptibility. Porin defects may cause opposite impacts on antibiotic susceptibility, which is dependent on the involvement of the defect. Blocking the porin channel role can increase antibiotic resistance; in contrast, the loss of porin structure role may increase antibiotic susceptibility.

COVID-19 often manifests with different outcomes in different patients, highlighting the complexity of the host-pathogen interactions involved in manifestations of the disease at the molecular and cellular levels. In this paper, we propose a set of postulates and a framework for systematically understanding complex molecular host-pathogen interaction networks. Specifically, we first propose four host-pathogen interaction (HPI) postulates as the basis for understanding molecular and cellular host-pathogen interactions and their relations to disease outcomes. These four postulates cover the evolutionary dispositions involved in HPIs, the dynamic nature of HPI outcomes, roles that HPI components may occupy leading to such outcomes, and HPI checkpoints that are critical for specific disease outcomes. Based on these postulates, an HPI Postulate and Ontology (HPIPO) framework is proposed to apply interoperable ontologies to systematically model and represent various granular details and knowledge within the scope of the HPI postulates, in a way that will support AI-ready data standardization, sharing, integration, and analysis. As a demonstration, the HPI postulates and the HPIPO framework were applied to study COVID-19 with the Coronavirus Infectious Disease Ontology (CIDO), leading to a novel approach to rational design of drug/vaccine cocktails aimed at interrupting processes occurring at critical host-coronavirus interaction checkpoints. Furthermore, the host-coronavirus protein-protein interactions (PPIs) relevant to COVID-19 were predicted and evaluated based on prior knowledge of curated PPIs and domain-domain interactions, and how such studies can be further explored with the HPI postulates and the HPIPO framework is discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yu, Li, Huffman, Beverley, Hur, Merrell, Huang, Wang, Liu, Ong, Cheng, Zeng, Zhang, Li, Liu, Wang, Zhang, Ye, Handelman, Sexton, Eaton, Higgins, Omenn, Athey, Smith, Chen and He.)

Background: The current COVID-19 pandemic and the previous SARS/MERS outbreaks of 2003 and 2012 have resulted in a series of major global public health crises. We argue that in the interest of developing effective and safe vaccines and drugs and to better understand coronaviruses and associated disease mechenisms it is necessary to integrate the large and exponentially growing body of heterogeneous coronavirus data. Ontologies play an important role in standard-based knowledge and data representation, integration, sharing, and analysis. Accordingly, we initiated the development of the community-based Coronavirus Infectious Disease Ontology (CIDO) in early 2020., Results: As an Open Biomedical Ontology (OBO) library ontology, CIDO is open source and interoperable with other existing OBO ontologies. CIDO is aligned with the Basic Formal Ontology and Viral Infectious Disease Ontology. CIDO has imported terms from over 30 OBO ontologies. For example, CIDO imports all SARS-CoV-2 protein terms from the Protein Ontology, COVID-19-related phenotype terms from the Human Phenotype Ontology, and over 100 COVID-19 terms for vaccines (both authorized and in clinical trial) from the Vaccine Ontology. CIDO systematically represents variants of SARS-CoV-2 viruses and over 300 amino acid substitutions therein, along with over 300 diagnostic kits and methods. CIDO also describes hundreds of host-coronavirus protein-protein interactions (PPIs) and the drugs that target proteins in these PPIs. CIDO has been used to model COVID-19 related phenomena in areas such as epidemiology. The scope of CIDO was evaluated by visual analysis supported by a summarization network method. CIDO has been used in various applications such as term standardization, inference, natural language processing (NLP) and clinical data integration. We have applied the amino acid variant knowledge present in CIDO to analyze differences between SARS-CoV-2 Delta and Omicron variants. CIDO's integrative host-coronavirus PPIs and drug-target knowledge has also been used to support drug repurposing for COVID-19 treatment., Conclusion: CIDO represents entities and relations in the domain of coronavirus diseases with a special focus on COVID-19. It supports shared knowledge representation, data and metadata standardization and integration, and has been used in a range of applications., (© 2022. The Author(s).)

Objectives: Baseball players are highly susceptible to shoulder injuries due to repetitive overhead throwing. The purpose of this study was to investigate men's collegiate baseball shoulder injury rates and associated risk factors., Methods: Using the NCAA Injury Surveillance Program (ISP) database, shoulder injury data for men's baseball players was analyzed from 2009-2010 through 2013-2014. Only the most common shoulder injuries were examined, including acromioclavicular (AC) sprain, anterior dislocation, biceps tear, biceps tendinitis, SLAP (superior labrum from anterior to posterior) tear, non-SLAP labral tear, rotator cuff tear, rotator cuff tendinitis, and shoulder impingement. Statistical analysis was performed using proportion ratios (PR). Statistical significance was initially defined as p < 0.05; a post-hoc Bonferroni adjustment was applied using a p < 0.005 threshold balancing the likelihood of false positive and false negative findings., Results: Overall, 138 shoulder injuries were identified of which 51.4% occurred during practice. Rotator cuff pathology represented 45.6% of all injuries, with rotator cuff tears significantly more likely to be season-ending injuries (PR 2.5, 95% CI 1.2-5.6, p = 0.019). Pitching or throwing was the mechanism of injury in 100% of players with rotator cuff tendonitis, 87.5% of SLAP tears, 70% of players with biceps tendinitis, and 67% of players with rotator cuff tears. Biceps tendinitis (PR 3.9, 95% CI 1.2-12.5, p = 0.024) and SLAP tears (PR 6.4, 95% CI 1.6-25.0, p = 0.008) were significantly more likely to be chronic. SLAP tears were significantly more likely to be recurrent (PR 5.5, 95% CI = 1.5-20.4, p = 0.010). Being a freshman or sophomore was significantly associated with a lower proportion of biceps tendinitis (PR = 0.2, 95% CI = 0.04-0.8, p = 0.028). All anterior shoulder dislocations occurred while running the bases or sliding, and AC sprains were significantly associated with contact (PR 20.6, 95% CI = 2.5-168.7, p = 0.0048)., Conclusions: Repetitive overhead throwing in college baseball is a common cause of overuse shoulder injuries. These athletes are especially susceptible to rotator cuff pathology, which is significantly more likely to cause season-ending injuries. While we have to interpret these results in light of both adjusted and unadjusted p-values, this information signifies the importance of shoulder injury prevention strategies by physicians and trainers taking care of collegiate baseball players.

Background & Aims: Anti-granulocyte macrophage-colony stimulating factor autoantibodies (aGMAbs) are detected in patients with ileal Crohn's disease (CD). Their induction and mode of action during or before disease are not well understood. We aimed to investigate the underlying mechanisms associated with aGMAb induction, from functional orientation to recognized epitopes, for their impact on intestinal immune homeostasis and use as a predictive biomarker for complicated CD., Methods: We characterized using enzyme-linked immunosorbent assay naturally occurring aGMAbs in longitudinal serum samples from patients archived before the diagnosis of CD (n = 220) as well as from 400 healthy individuals (matched controls) as part of the US Defense Medical Surveillance System. We used biochemical, cellular, and transcriptional analysis to uncover a mechanism that governs the impaired immune balance in CD mucosa after diagnosis., Results: Neutralizing aGMAbs were found to be specific for post-translational glycosylation on granulocyte macrophage-colony stimulating factor (GM-CSF), detectable years before diagnosis, and associated with complicated CD at presentation. Glycosylation of GM-CSF was altered in patients with CD, and aGMAb affected myeloid homeostasis and promoted group 1 innate lymphoid cells. Perturbations in immune homeostasis preceded the diagnosis in the serum of patients with CD presenting with aGMAb and were detectable in the noninflamed CD mucosa., Conclusions: Anti-GMAbs predict the diagnosis of complicated CD long before the diagnosis of disease, recognize uniquely glycosylated epitopes, and impair myeloid cell and innate lymphoid cell balance associated with altered intestinal immune homeostasis., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

We report the draft genome sequence of Stenotrophomonas maltophilia strain KJ, which was isolated from a sputum sample from a patient with a respiratory tract infection. Multilocus sequence typing analysis suggested that strain KJ belongs to a novel S. maltophilia sequence type.

Background: Surgical scheduling, specifically the day of the week on which surgery is performed, has been associated with various postoperative outcomes in patients undergoing lower extremity joint arthroplasty., Purpose: We sought to investigate surgical scheduling as a potential modifiable factor for patient quality metrics and related costs., Methods: In a retrospective prognostic study, all total knee and total hip arthroplasty (TKA/THA) cases that took place in 2017 to 2018 at a multihospital academic health system were queried. Patients were separated by the day of the week the surgery was performed, with Monday/Tuesday compared to Thursday/Friday. Outcomes included length of stay (LOS) (extended LOS defined as 3 days or longer), cost, and complications. Multivariable regression models measured associations between scheduling of surgery and outcomes; odds ratios (OR) and 95% confidence intervals (CIs) are reported., Results: Overall, 1,571 TKA and 992 THA patients were included (65% and 35%, respectively, performed on Monday/Tuesday and 70% and 30%, respectively, performed on Thursday/Friday). Patients undergoing TKA on Monday/Tuesday versus Thursday/Friday had higher American Society of Anesthesiologists scores (42% vs 33% with score of 3 or higher) but less often an extended LOS (31% vs 54%; adjusted OR: 2.76, 95% CI: 2.22-3.46), lower skilled nursing facility costs (unadjusted mean, $12,515 vs $14,154) and lower home health aide costs (unadjusted mean, $3,793 vs $4,192). Similar patterns were observed in THA patients., Conclusion: These results from institutional data suggest that surgical scheduling is a modifiable factor possibly associated with postoperative outcomes. Furthermore, more rigorous study is warranted., Competing Interests: Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Sofia Ahsanuddin, BA; Hsin-Hui Huang, MD, PhD; Aakash Keswani, MD; Jashvant Poeran, MD, PhD; and Daniel J. Snyder, BS, declare they have nothing to disclose. Calin S. Moucha, MD, reports relationships with 3M and Biocomposites., (© The Author(s) 2021.)

Background: Disparate COVID-19 outcomes have been observed between Hispanic, non-Hispanic Black, and White patients. The underlying causes for these disparities are not fully understood., Methods: This was a retrospective study utilizing electronic medical record data from five hospitals within a single academic health system based in New York City. Multivariable logistic regression models were used to identify demographic, clinical, and lab values associated with in-hospital mortality., Results: A total of 3,086 adult patients with self-reported race/ethnicity information presenting to the emergency department and hospitalized with COVID-19 up to April 13, 2020, were included in this study. While older age (multivariable odds ratio (OR) 1.06, 95% CI 1.05-1.07) and baseline hypoxia (multivariable OR 2.71, 95% CI 2.17-3.36) were associated with increased mortality overall and across all races/ethnicities, non-Hispanic Black (median age 67, interquartile range (IQR) 58-76) and Hispanic (median age 63, IQR 50-74) patients were younger and had different comorbidity profiles as compared to non-Hispanic White patients (median age 73, IQR 62-84; p < 0.05 for both comparisons). Among inflammatory markers associated with COVID-19 mortality, there was a significant interaction between the non-Hispanic Black population and interleukin-1-beta (interaction p-value 0.04)., Conclusions: This analysis of a multiethnic cohort highlights the need for inclusion and consideration of diverse populations in ongoing COVID-19 trials targeting inflammatory cytokines., Competing Interests: EW has consulting agreements with and/or is on the scientific advisory board for Merck, Elstar, Janssen, Jounce, Related Sciences, Synthekine, and Surface Oncology. EW is a founder of Surface Oncology and Arsenal Biosciences. EW has a patent licensing agreement on the PD-1 pathway with Roche/Genentech. TJ is employed by and owns stock in Sema4. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jun, Mathew, Sharma, Nirenberg, Huang, Kovatch, Wherry and Huang.)

Background: There is a paucity of literature on racial differences across a full total joint arthroplasty (TJA) "episode of care" and beyond. Given various incentives, the Comprehensive Care for Joint Replacement (CJR) program in the U.S. may have impacted preexisting racial differences across this care continuum. The purposes of the present study were (1) to assess trends in racial differences in care/outcome characteristics before, during, and after TJA surgery and (2) to assess if the CJR program coincided with reductions in these racial differences., Methods: This retrospective cohort study includes data on 1,483,221 TJAs (based on Medicare claims data, 2013 to 2018). Racial differences between Black and White patients were assessed for (1) preoperative characteristics (Deyo-Charlson comorbidity index, patient sex, and age), (2) characteristics during hospitalization (length of stay, blood transfusions, and combined complications), and (3) postoperative characteristics (90 and 180-day readmission rates and institutional post-acute care). Additionally, Medicare payments for each period were assessed. Racial differences (Black versus White patients) were expressed in terms of odds ratios (ORs) and 95% confidence intervals (CIs) per year. A "difference-in-differences" analysis (comparing before and after CJR implementation, with non-CJR hospitals being used as controls) estimated the association of the CJR program with changes in racial differences., Results: In both 2013 and 2018, Black patients (n = 74,390; 5.0%) were more likely than White patients to have a higher Deyo-Charlson comorbidity index (score of >0) (OR = 1.32 [95% CI = 1.28 to 1.36] and OR = 1.32 [95% CI = 1.28 to 1.37]), to require more transfusions (OR = 1.55 [95% CI = 1.49 to 1.62] and OR = 1.77 [95% CI = 1.56 to 2.01]), to be discharged to institutional post-acute care (OR = 1.40 [95% CI = 1.36 to 1.44] and OR = 1.49 [95% CI = 1.43 to 1.56]), and to be readmitted within 90 days (OR = 1.38 [95% CI = 1.32 to 1.44] and OR = 1.21 [95% CI = 1.13 to 1.29]) (p < 0.05 for all). Adjusted difference-in-differences analyses demonstrated that the CJR program coincided with reductions in racial differences in 90-day readmission (-1.24%; 95% CI, -2.46% to -0.03%) and 180-day readmission (-1.28%; 95% CI, -2.52% to -0.03%) (p = 0.044 for both)., Conclusions: Racial differences persist among patients managed with TJA. The CJR program coincided with reductions in some racial differences, thus identifying bundle design as a potential novel strategy to target racial disparities., Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/H3)., (Copyright © 2022 by The Journal of Bone and Joint Surgery, Incorporated.)

The adjustment process to becoming a mother is affected by culture. However, earlier studies have not clarified the relationship between parenting stress, social support, and maternal confidence in non-Western women. This study examined the associations between different types and sources of social support, maternal confidence, and parenting stress experienced by first-time mothers. The sample consisted of first-time mothers with a child under one year of age in northern Taiwan, and a total of 205 valid questionnaires were collected. The results supported the stress-buffering hypothesis, which suggests that social support reduces the adverse effect of stress on maternal confidence. Although previous studies have suggested that spouses and maternal relatives are critical in supporting first-time mothers' transition into their new roles, each source did not show a mediator effect in our study. The beneficial effect of social support was found only when all social network members collectively participated. Regarding the types of social support, only appraisal support had a significant mediator effect; no effect was found for emotional, instrumental, or informational support. These findings add to our understanding of how different types and sources of social support play a role in helping first-time mothers adapt.

Background: Stenotrophomonas maltophilia, a member of γ-proteobacteria, is a ubiquitous environmental bacterium that is recognized as an opportunistic nosocomial pathogen. FecABCD system contributes to ferric citrate acquisition in Escherichia coli. FeoABC system, consisting of an inner membrane transporter (FeoB) and two cytoplasmic proteins (FeoA and FeoC), is a well-known ferrous iron transporter system in γ-proteobacteria. As revealed by the sequenced genome, S. maltophilia appears to be equipped with several iron acquisition systems; however, the understanding of these systems is limited. In this study, we aimed to elucidate the ferric citrate acquisition system of S. maltophilia., Methods: Candidate genes searching and function validation are the strategy for elucidating the genes involved in ferric citrate acquisition. The candidate genes responsible for ferric citrate acquisition were firstly selected using FecABCD of E. coli as a reference, and then revealed by transcriptome analysis of S. maltophilia KJ with and without 2,2'-dipyridyl (DIP) treatment. Function validation was carried out by deletion mutant construction and ferric citrate utilization assay. The bacterial adenylate cyclase two-hybrid system was used to verify intra-membrane protein-protein interaction., Results: Smlt2858 and Smlt2356, the homologues of FecA and FecC/D of E. coli, were first considered; however, deletion mutant construction and functional validation ruled out their involvement in ferric citrate acquisition. FciA (Smlt1148), revealed by its upregulation in DIP-treated KJ cells, was the outer membrane receptor for ferric citrate uptake. The fciA gene is a member of the fciTABC operon, in which fciT, fciA, and fciC participated in ferric citrate acquisition. Uniquely, the Feo system of S. maltophilia is composed of a cytoplasmic protein FeoA, an inner membrane transporter FeoB, and a predicted inner membrane protein FeoI. The intra-membrane protein-protein interaction between FeoB and FeoI may extend the substrate profile of FeoB to ferric citrate. FeoABI system functioned as an inner membrane transporter of ferric citrate., Conclusions: The FciTABC and FeoABI systems contribute to ferric citrate acquisition in S. maltophilia., (© 2022. The Author(s).)

Background: Stenotrophomonas maltophilia, a species of highly genetic diversity, has emerged as an important nosocomial pathogen. S. maltophilia and Pseudomonas aeruginosa are often co-isolated from pneumonia patients. In our previous study, we have demonstrated that the pacIRA cluster present in some but not all clinical S. maltophilia isolates. Proteins encoded by pacIRA operon are an extracytoplasmic function (ECF) sigma factor, a transmembrane anti-sigma regulator, and a TonB-dependent receptor. This study aimed to elucidate PacIRA system function and its significance to S. maltophilia., Methods: The pacI, pacR, and pacA genes were individually or totally deleted from the chromosome of KJΔEnt, a pacIRA-positive and siderophore-null strain. Growth promotion assay was performed to examine the implication of pacIRA system in iron utilization. Gene expression was quantified by quantitative real time PCR (qRT-PCR). Growth competition assay was executed to investigate the significance of pacIRA operon to S. maltophilia., Results: PacIRA system contributed to utilize ferri-pyochelin of P. aeruginosa as iron sources for growth in an iron-depleted condition, but hardly utilized ferric citrate, hemin, ferri-stenobactin, and ferri-pyoverdine. PacIRA was founded to belong to Fur regulon and upregulated in response to iron-depleted stress. Growth competition assay demonstrated that pacIRA-positive S. maltophilia had a superiority over pacIRA-negative S. maltophilia in iron acquisition when they were co-cultured in P. aeruginosa ferri-pyochelin-supplemented medium., Conclusions: PacIRA system of S. maltophilia is a xenosiderophore uptake implement, involving in the acquisition of pyochelin of P. aeruginosa., Competing Interests: Declaration of competing interest All authors declare that there are no conflicts of interest., (Copyright © 2021. Published by Elsevier B.V.)

Stenotrophomonas maltophilia is a motile, opportunistic pathogen. The flagellum, which is involved in swimming, swarming, adhesion, and biofilm formation, is considered a virulence factor for motile pathogens. Three flagellin genes, fliC1 , fliC2 , and fliC3 , were identified from the sequenced S. maltophilia genome. FliC1 , fliC2 , and fliC3 formed an operon, and their encoding proteins shared 67-82% identity. Members of the fliC1C2C3 operon were deleted individually or in combination to generate single mutants, double mutants, and a triple mutant. The contributions of the three flagellins to swimming, swarming, flagellum morphology, adhesion, and biofilm formation were assessed. The single mutants generally had a compromise in swimming and no significant defects in swarming, adhesion on biotic surfaces, and biofilm formation on abiotic surfaces. The double mutants displayed obvious defects in swimming and adhesion on abiotic and biotic surfaces. The flagellin-null mutant lost swimming ability and was compromised in adhesion and biofilm formation. All tested mutants demonstrated substantial but different flagellar morphologies, supporting that flagellin composition affects filament morphology. Bacterial swimming motility was significantly compromised under an oxidative stress condition, irrespective of flagellin composition. Collectively, the utilization of these three flagellins for filament assembly equips S. maltophilia with flagella adapted to provide better ability in swimming, adhesion, and biofilm formation for its pathogenesis.

Background: Extensor mechanism injuries involving the quadriceps tendon, patella, or patellar tendon can be a devastating setback for athletes. Despite the potential severity and relative frequency with which these injuries occur, large-scale epidemiological data on collegiate-level athletes are lacking., Study Design: Descriptive epidemiology study., Level of Evidence: Level 4., Methods: Knee extensor mechanism injuries across 16 sports among National Collegiate Athletic Association (NCAA) men and women during the 2004-2005 to 2013-2014 academic years were analyzed using the NCAA Injury Surveillance Program (NCAA-ISP). Extensor mechanism injuries per 100,000 athlete-exposures (AEs), operative rate, annual injury and reinjury rates, in-season status (pre-/regular/postseason), and time lost were compiled and calculated., Results: A total of 11,778,265 AEs were identified and included in the study. Overall, 1,748 extensor mechanism injuries were identified, with an injury rate (IR) of 14.84 (per 100,000 AEs). N = 114 (6.5%) injuries were classified as severe injuries with a relatively higher median time loss (44 days) and operative risk (18.42%). Male athletes had higher risk of season-ending injuries in both all (3.20% vs 0.89%, P < 0.01) and severe (41.54% vs 16.33%, P < 0.01) extensor mechanism injuries. Similarly, contact injuries were more frequently season-ending injuries (4.44% vs 1.69%, P = 0.01). Women's soccer (IR = 2.59), women's field hockey (IR = 2.15), and women's cross country (IR = 2.14) were the sports with the highest rate of severe extensor mechanism injuries., Conclusion: Extensor mechanism injuries in collegiate athletes represent a significant set of injuries both in terms of volume and potentially to their athletic careers. Male athletes and contact injuries appear to have a greater risk of severe injuries. Injuries defined as severe had a higher risk of operative intervention and greater amount of missed playing time., Clinical Relevance: Knowledge of the epidemiology of extensor mechanism injuries may help clinicians guide their athlete patients in sports-related injury prevention and management.

Objectives: While injuries among collegiate athletes are common and well-studied, there have been no studies comparing which sports and injury types have the highest operation rates. This information would be valuable for athlete governing bodies and providers to improve player safety. Our hypothesis was the surgery incidence rates vary substantially between sports and injury types, with football and knee injuries representing the sport and injury type with the highest respective surgery rates., Methods: This was a descriptive epidemiology study of all injuries requiring surgery as recorded in the National Collegiate Athletic Association (NCAA) Injury Surveillance Program (ISP) for academic years 2004-2005 to 2013-2014. Surgery incidence rates (and 95% confidence intervals, CI) were calculated for each sport (per 10,000 athletic exposures [AE]) and for the most common injury types, by academic year. In addition, absolute numbers of performed surgeries were calculated as well as rates of return to sport., Results: Sports with the highest surgery incidence rate (per 10,000 AEs) were women's gymnastics (8.9; 95% CI 7.2-10.9), men's football (6.1; 95% CI 5.8-6.4), and men's wrestling (5.3; 95% CI 4.5-6.3). Absolute numbers of injury-related surgeries performed were greatest for men's football (n = 31,043), women's basketball (6,625), and men's basketball (5,717). Anterior cruciate ligament tears had the greatest surgery incidence rate per 100,000 AEs for all sports combined (7.95; 95% CI = 7.5 to 8.5), and also represented the injuries with the lowest rate of return to sport., Conclusion: Women's gymnastics, men's football, and men's and women's basketball are NCAA sports with an elevated risk of injury requiring of surgery. The results from this study can guide the NCAA and providers regarding which sports should be the focus of future research, new injury prevention strategies, and healthcare personnel allocation during events.

Background: Gallstones are abnormal masses caused by impaired metabolism of cholesterol, bilirubin, or bile salts in the gallbladder or biliary tract. ATP-binding cassette subfamily G member 8 (ABCG8) is a protein that regulates cholesterol efflux from the liver. Genome-wide association studies (GWAS) and meta-analyses of GWAS revealed the ABCG8 rs11887534 variant as the most common genetic determinant of gallstones in humans. These findings have not been extensively replicated in Taiwanese. Therefore, we appraised the relationship between gallstones and rs11887534 in a relatively large Taiwanese sample., Methods: We retrieved data collected through questionnaires, physical and biochemical tests from the Taiwan Biobank Bank (TWB). The study participants comprised 7388 men and 13,880 women who voluntarily enrolled in the Taiwan Biobank project between 2008 and 2019. Gallstones were self-reported., Results: The overall sample size was 21,268 comprising 938 gallstone patients and 20,330 non-gallstone individuals. Among the participants, 20,640 had the GG and 628 had the GC + CC genotype. At p-value < 0.05, the baseline genotypes and gallstone status between men and women were not significantly different. The risk of gallstones was higher in participants having the GC + CC compared to the GG genotype: odds ratio (OR); 95% confidence interval (CI) = 1.698; 1.240-2.325), but was lower in men compared to women (OR = 0.763; 95% CI = 0.638-0.913). Compared to men with the rs11887534 GG genotype, women with the GG and GC + CC genotypes had a higher risk of gallstone (OR; 95% CI = 1.304; 1.087-1.565 for GG and 2.291; 1.514-3.467 for GC + CC). The positive association between GC + CC and gallstones was retained after we restricted the analysis to the female participants (OR; 95% CI = 1.789 = 1.208-2.648). Hormone use was associated with an elevated risk of gallstones (OR; 95% CI = 1.359; 1.107-1.668). Relative to GG and no hormone use, we found a significantly high risk among hormone users with the GC + CC genotype (OR; 95% CI = 3.596; 1.495-8.650)., Conclusions: The rs11887534 GC + CC genotype was independently associated with a higher risk of gallstones. This risk was much higher among women, especially those who used hormones for various gynecological purposes., (© 2021. The Author(s).)

Despite the growing recognition of gender equality worldwide, plausible strategies that reduce young children's gender stereotypes remain limited. Cognitive-based interventions have been widely used in school settings and have been suggested to play important roles in children's gender stereotyping and in their processing of counter-stereotypic information. We aimed to determine whether exposure to counter-stereotypical information could break gender stereotypes in kindergarten children. Fifty-four children (61-79 months old) from two public kindergarten classes in northern Taiwan participated in this study. One of the two classes was randomly selected as the experimental group ( n = 28), and the other was the control group ( n = 26). The experimental group consisted of a gender equality curriculum including script relationship training for two months, while the control group continued their regular curriculum. The picture classification task (PCT) was measured before and after the intervention to assess gender stereotypes. Before interventions, 87.50% of the children chose a gender stereotypic relationship, while 12.50% chose script/other relationships in PCT. After the interventions, the gender stereotypic relationship dropped to 73.22% in the experimental group. Children in the control group were more likely to maintain their gender stereotypic relationship choices in PCTs. Our findings suggest that cognitive-based interventions, such as a gender equality curriculum, have the potential to break gender stereotypes in kindergarten children.

A novel and simple flotation technique has been developed to prepare high-purity graphite from impure graphite. In this method, a suspension of pristine powdered graphite (PG) is dispersed and stirred in water without adding froth formers or supportive chemicals. This makes fine particles of graphite move upwards and float on water. X-ray diffraction (XRD) analysis reveals that the floated graphite (FG) has a lower c-axis parameter, indicating the removal of interlayer impurities. A notable increase in the intensity ratio of the D band to G band in the Raman spectra indicates that the FG has more edge defects due to their smaller crystallite sizes. Transmission electron microscopic (TEM) analysis shows the number of layers in FG has been reduced to 16 from 68 in PG. The absence of C=O vibration of Fourier Transformed Infrared (FT-IR) spectroscopy in treated and untreated samples suggests that their layers are not significantly oxidized. However, X-ray photoelectron spectroscopic (XPS) analysis shows the presence of C-O-C ether functionalities, possibly on edge planes. Further, the product has higher purity with increased carbon content. Therefore, the technique is helpful for the value enhancement of graphite, the reduction of the chemical cost of the conventional techniques, environmental friendliness, and improvement of its applications., (© 2021. The Author(s).)

Introduction: Patients with lung cancer (LC) are susceptible to severe outcomes from COVID-19. This study evaluated disruption to care of patients with LC during the COVID-19 pandemic., Methods: The COVID-19 and Cancer Outcomes Study (CCOS) is a prospective cohort study comprised of patients with a current or past history of hematological or solid malignancies with outpatient visits between March 2 and March 6, 2020, at two academic cancer centers in the Northeastern United States (US). Data was collected for the three months prior to the index week (baseline period) and the following three months (pandemic period)., Results: 313 of 2365 patients had LC, 1578 had other solid tumors, and 474 had hematological malignancies. Patients with LC were not at increased risk of COVID-19 diagnosis compared to patients with other solid or hematological malignancies. When comparing data from the pandemic period to the baseline period, patients with LC were more likely to have a decrease in in-person visits compared to patients with other solid tumors (aOR 1.94; 95% CI, 1.46-2.58), but without an increase in telehealth visits (aOR 1.13; 95% CI 0.85-1.50). Patients with LC were more likely to experience pandemic-related treatment delays than patients with other solid tumors (aOR 1.80; 95% CI 1.13-2.80) and were more likely to experience imaging/diagnostic procedure delays than patients with other solid tumors (aOR 2.59; 95% CI, 1.46-4.47) and hematological malignancies (aOR 2.01; 95% CI, 1.02-3.93). Among patients on systemic therapy, patients with LC were also at increased risk for decreased in-person visits and increased treatment delays compared to those with other solid tumors., Discussion: Patients with LC experienced increased cancer care disruption compared to patients with other malignancies during the early phase of the COVID-19 pandemic. Focused efforts to ensure continuity of care for this patient population are warranted., (Copyright © 2021. Published by Elsevier B.V.)

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide in 2020. Colonoscopy and the fecal immunochemical test (FIT) are commonly used as CRC screening tests, but both types of tests possess different limitations. Recently, liquid biopsy-based DNA methylation test has become a powerful tool for cancer screening, and the detection of abnormal DNA methylation in stool specimens is considered as an effective approach for CRC screening. The aim of this study was to develop a novel approach in biomarker selection based on integrating primary biomarkers from genome-wide methylation profiles and secondary biomarkers from CRC comorbidity analytics. A total of 125 differential methylated probes (DMPs) were identified as primary biomarkers from 352 genome-wide methylation profiles. Among them, 51 biomarkers, including 48 hypermethylated DMPs and 3 hypomethylated DMPs, were considered as suitable DMP candidates for CRC screening tests. After comparing with commercial kits, three genes ( ADHFE1 , SDC2 , and PPP2R5C ) were selected as candidate epigenetic biomarkers for CRC screening tests. Methylation levels of these three biomarkers were significantly higher for patients with CRC than normal subjects. The sensitivity and specificity of integrating methylated ADHFE1 , SDC2 , and PPP2R5C for CRC detection achieved 84.6% and 92.3%, respectively. Through an integrated approach using genome-wide DNA methylation profiles and electronic medical records, we could design a biomarker panel that allows for early and accurate noninvasive detection of CRC using stool samples.

Background: Perianchor cyst formation (PCF) can occur after arthroscopic rotator cuff repair with poly-L-lactic acid (PLLA) anchors; however, little is known about PCF after all-suture anchor (ASA) use., Methods: We reviewed patients who underwent double-row arthroscopic rotator cuff repair from 2012 to 2017 with ASAs implanted in the medial row and PLLA anchors in the lateral row. We evaluated PCF (graded on magnetic resonance imaging) and compared physical examination and functional surveys between patients with PCF (WC) and without PCF (WoC) at long-term follow-up., Results: Among twenty-two patients (23 shoulders), 93% of PLLA anchors (vs. 79% ASA) displayed a grade 0 PCF, P  = .100. No PLLA anchors had a grade 3 or 4 PCF, compared to 11% of ASAs, P  = .158. At a mean postoperative follow-up time of 113 weeks, there was no significant difference between WC and WoC cohorts with regard to range of motion, rotator cuff strength, American Shoulder and Elbow Surgeons survey scores, or retear rates. However, the WoC cohort had a significantly higher University of California at Los Angeles shoulder survey score at final follow-up (34.3 WoC vs. 30.9 WC, P  = .024)., Conclusion: No difference was found in PCF between ASAs and PLLA anchors. At long-term follow-up, WoC patients had significantly improved functional outcome scores, based on the University of California at Los Angeles survey, but equivalent range of motion and rotator cuff strength examinations compared with WC patients., (© 2021 The Authors.)

OmpA , which encodes outer membrane protein A (OmpA), is the most abundant transcript in Stenotrophomonas maltophilia based on transcriptome analyses. The functions of OmpA, including adhesion, biofilm formation, drug resistance, and immune response targets, have been reported in some microorganisms, but few functions are known in S. maltophilia . This study aimed to elucidate the relationship between OmpA and swimming motility in S. maltophilia . KJΔOmpA, an ompA mutant, displayed compromised swimming and failure of conjugation-mediated plasmid transportation. The hierarchical organization of flagella synthesis genes in S. maltophilia was established by referencing the Pseudomonas aeruginosa model and was confirmed using mutant construction, qRT-PCR, and functional assays. Distinct from the P. aeruginosa model, rpoN , rather than fleQ and fliA , was at the top of the flagellar regulatory cascade in S. maltophilia . To elucidate the underlying mechanism responsible for ΔompA -mediated swimming compromise, transcriptome analysis of KJ and KJΔOmpA was performed and revealed rpoN downregulation in KJΔOmpA as the key element. The involvement of rpoN in ΔompA -mediated swimming compromise was verified using rpoN complementation, qRT-PCR, and function assays. Collectively, OmpA, which contributes to bacterial conjugation and swimming, is a promising target for adjuvant design in S. maltophilia .

Background: Stenotrophomonas maltophilia, an opportunistic pathogen, is intrinsically resistant to most β-lactams except ceftazidime and ticarcillin/clavulanate, due to the inducibly expressed L1 and L2 β-lactamases. A two-component regulatory system (TCS) allows organisms to sense and respond to changes in different environmental conditions. The PhoPQ TCS of S. maltophilia plays regulatory roles in antibiotic susceptibility, physiology, stress adaption and virulence. Inactivation of S. maltophilia phoPQ increases β-lactam susceptibility., Objectives: To elucidate the PhoPQ-regulating mechanism for β-lactam resistance., Methods: The candidate genes responsible for the ΔphoPQ-mediated β-lactam resistance compromise were identified by transcriptome analysis and verified by quantitative RT-PCR and complementation assay. Etest was used to assess β-lactam susceptibility. The phosphorylation level of the PhoP protein was determined by Phos-tag SDS-PAGE and western blotting. A β-lactam influx assay was used to investigate the influx efficiency of a β-lactam., Results: PhoPQ deletion down-regulated the expression of mltD1 and slt, attenuated the induced β-lactamase activity and then compromised the β-lactam resistance. Complementation of mutant phoPQ with mltD1 or slt genes partially reverted the induced β-lactamase activity and β-lactam resistance. The PhoPQ TCS was activated in logarithmically grown KJ cells and was further activated by low magnesium, but not by a β-lactam. However, low-magnesium-mediated PhoPQ activation hardly made an impact on β-lactam resistance enhancement. Furthermore, PhoPQ inactivation altered the outer membrane permeability and increased the influx of a β-lactam., Conclusions: The PhoPQ TCS is activated to some extent in physiologically grown S. maltophilia. Inactivation of phoPQ attenuates the expression of mltD1 and slt, and increases β-lactam influx, both synergically contributing to β-lactam resistance compromise., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The effects of foot injuries on collegiate athletes in the United States are of interest because of the short 5-year eligibility period in the National Collegiate Athletic Association (NCAA)., Purpose: To discuss the epidemiology of severe NCAA foot injuries sustained over 10 years in 25 sports., Study Design: Descriptive epidemiology study., Methods: We utilized the NCAA Injury Surveillance System, which prospectively collects deidentified injury data for collegiate athletes. Severe injuries were classified as season- or career-ending injuries, injuries with >30-day time loss, or injuries requiring operative treatment. Injury rates (IRs) were analyzed per 100,000 athlete-exposures., Results: Of 3607 total foot injuries, 18.71% (n = 675) were classified as severe, with an IR of 5.73 per 100,000 athletic-exposures. For all severe injuries, the operative rate was 24.3%, the season-ending rate 37.0%, and the career-ending rate 4.4%. The proportion of recurrent injuries was 13.9%. Men's sports with the highest severe foot IRs were basketball (IR = 10.71), indoor track (IR = 7.16), and football (IR = 7.08). Women's sports with the highest severe foot IRs were cross-country (IR = 17.15), gymnastics (IR = 14.76), and outdoor track (IR = 14.65). Among all severe foot injuries, the most common was a fifth metatarsal fracture. The highest contact/noncontact injury ratios were phalangeal fracture, turf toe, and Lisfranc injury. The severe injuries with the highest operative rates were Lisfranc injuries, fifth metatarsal fractures, and midfoot fractures. The severe injuries associated with the highest season-ending IRs were Lisfranc injury, midfoot fracture, and general metatarsal fractures. Severe flexor/extensor injuries had the highest career-ending IRs, followed by turf toe. Severe injuries with the highest median time loss were sesamoidal fractures, calcaneal fractures, and plantar fascial injuries., Conclusion: Of all collegiate foot injuries sustained over a 10-year period, 18.7% were characterized as severe, and 24.3% of severe injuries required surgery. Basketball was the men's sport with the highest severe IR, and cross-country was the women's sport with the highest severe IR. Overall, female athletes experienced slightly higher severe foot IRs as compared with male athletes., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: E.V. has received consulting fees from Wright Medical and education payments from Arthrex and Gotham Surgical. A.A. has received education payments from Arthrex; consulting fees from Arthrex, Medshape, and Medline Industries; nonconsulting fees from Arthrex and Medline Industries; honoraria from Paragon 28; and royalties from Elsevier. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2021.)