Comprehensive quantitative modeling of translation efficiency in a genome-reduced bacterium.

Translation efficiency has been mainly studied by ribosome profiling, which only provides an incomplete picture of translation kinetics. Here, we integrated the absolute quantifications of tRNAs, mRNAs, RNA half-lives, proteins, and protein half-lives with ribosome densities and derived the initiation and elongation rates for 475 genes (67% of all genes), 73 with high precision, in the bacterium Mycoplasma pneumoniae (Mpn). We found that, although the initiation rate varied over 160-fold among genes, most of the known factors had little impact on translation efficiency. Local codon elongation rates could not be fully explained by the adaptation to tRNA abundances, which varied over 100-fold among tRNA isoacceptors. We provide a comprehensive quantitative view of translation efficiency, which suggests the existence of unidentified mechanisms of translational regulation in Mpn.

On Primary Adrenal Insufficiency with Normal Concentrations of Cortisol - Early Manifestation of Addison's Disease.

Primary adrenal insufficiency (AI) is an endocrine disorder in which hormones of the adrenal cortex are produced to an insufficient extent. Since receptors for adrenal steroids have a wide distribution, initial symptoms may be nonspecific. In particular, the lack of glucocorticoids can quickly lead to a life-threatening adrenal crisis. Therefore, current guidelines suggest applying a low threshold for testing and to rule out AI not before serum cortisol concentrations are higher than 500 nmol/l (18 µg/dl). To ease the diagnostic, determination of morning cortisol concentrations is increasingly used for making a diagnosis whereby values of>350 nmol/l are considered to safely rule out Addison's disease. Also, elevated corticotropin concentrations (>300 pg/ml) are indicative of primary AI when cortisol levels are below 140 nmol/l (5 µg/dl). However, approximately 10 percent of our patients with the final diagnosis of primary adrenal insufficiency would clearly have been missed for they presented with normal cortisol concentrations. Here, we present five such cases to support the view that normal to high basal concentrations of cortisol in the presence of clearly elevated corticotropin are indicative of primary adrenal insufficiency when the case history is suggestive of Addison's disease. In all cases, treatment with hydrocortisone had been started, after which the symptoms improved. Moreover, autoantibodies to the adrenal cortex had been present and all patients underwent a structured national education program to ensure that self-monitored dose adjustments could be made as needed.

Soft tissue tumor imaging in adults: whole-body staging in sarcoma, non-malignant entities requiring special algorithms, pitfalls and special imaging aspects. Guidelines 2024 from the European Society of Musculoskeletal Radiology (ESSR).

OBJECTIVES: The revised European Society of Musculoskeletal Radiology (ESSR) consensus guidelines on soft tissue tumor imaging represent an update of 2015 after technical advancements, further insights into specific entities, and revised World Health Organization (2020) and AJCC (2017) classifications. This second of three papers covers algorithms once histology is confirmed: (1) standardized whole-body staging, (2) special algorithms for non-malignant entities, and (3) multiplicity, genetic tumor syndromes, and pitfalls. MATERIALS AND METHODS: A validated Delphi method based on peer-reviewed literature was used to derive consensus among a panel of 46 specialized musculoskeletal radiologists from 12 European countries. Statements that had undergone interdisciplinary revision were scored online by the level of agreement (0 to 10) during two iterative rounds, that could result in 'group consensus', 'group agreement', or 'lack of agreement'. RESULTS: The three sections contain 24 statements with comments. Group consensus was reached in 95.8% and group agreement in 4.2%. For whole-body staging, pulmonary MDCT should be performed in all high-grade sarcomas. Whole-body MRI is preferred for staging bone metastasis, with [18F]FDG-PET/CT as an alternative modality in PET-avid tumors. Patients with alveolar soft part sarcoma, clear cell sarcoma, and angiosarcoma should be screened for brain metastases. Special algorithms are recommended for entities such as rhabdomyosarcoma, extraskeletal Ewing sarcoma, myxoid liposarcoma, and neurofibromatosis type 1 associated malignant peripheral nerve sheath tumors. Satisfaction of search should be avoided in potential multiplicity. CONCLUSION: Standardized whole-body staging includes pulmonary MDCT in all high-grade sarcomas; entity-dependent modifications and specific algorithms are recommended for sarcomas and non-malignant soft tissue tumors. CLINICAL RELEVANCE STATEMENT: These updated ESSR soft tissue tumor imaging guidelines aim to provide support in decision-making, helping to avoid common pitfalls, by providing general and entity-specific algorithms, techniques, and reporting recommendations for whole-body staging in sarcoma and non-malignant soft tissue tumors. KEY POINTS: An early, accurate, diagnosis is crucial for the prognosis of patients with soft tissue tumors. These updated guidelines provide best practice expert consensus for standardized imaging algorithms, techniques, and reporting. Standardization can improve the comparability examinations and provide databases for large data analysis.

Time trend analysis of Injury Severity score of adult trauma patients with emergent CT examination.

PURPOSE: Controversy exists about whole-body computed tomography (CT) as a primary screening modality for suspected multiple trauma patients. Therefore, the aim of this study was to analyze time trends of CT examinations for trauma patients in relation to the Injury Severity Score (ISS). METHODS: We retrospectively analyzed 561 adult trauma patients (mean age = 54 years) who were admitted to the trauma room of our hospital, immediately followed by a CT examination, in 2009, 2013 und 2017. Review of electronic patient charts was performed to determine the cause of injury. ISS was either calculated upon hospital charts and CT imaging reports or documented in the TraumaRegister DGU® for trauma patients with ICU treatment or ISS ≥ 16. RESULTS: An increasing number of CT examinations of acute trauma patients were performed at our hospital with 117 patients in 2009 compared to 192 in 2013 and 252 in 2017. Their mean age increased (50 years in 2009, 54 in 2013 and 55 in 2017;p = 0.046), whereas their mean ISS decreased over time (15.2 in 2009 compared to 12.1 in 2013 and 10.6 in 2017;p = 0.001), especially in women (15.1 in 2009, 11.8 in 2013 and 7.4 in 2017;p = 0.001 both), younger age groups (18 to 24 years:15.6 in 2009, 6.5 in 2013 and 8.9 in 2017; p = 0.033 and 25 to 49 years:15.0 in 2009, 11.2 in 2013 and 8.3 in 2017;p = 0.001) as well as motor vehicle collision (MVC) victims (16.2 in 2009, 11.8 in 2013 and 6.1 in 2017; p < 0.001). Trauma patients with a high ISS were especially more likely of older age (OR 1.02,p < 0.001) and with the type of incident being a fall (< 3 m: OR3.84,p < 0.001;>3 m: OR6.22,p < 0.001) compared to MVC. CONCLUSION: Previous studies suggesting a benefit of primary whole-body CT for trauma patients might not reflect the current patient population with decreasing ISS. Especially females, younger age groups and MVC patients might benefit from stricter selection criteria for receiving whole-body CT. Our results also emphasize the importance of prevention of fall or tumble for elderly people.

[Expert recommendations for magnetic resonance imaging of muscle disorders]. / Expertenempfehlung zur Magnetresonanztomographie bei Muskelerkrankungen.

BACKGROUND: Magnetic resonance (MRI) imaging of the skeletal muscles (muscle MRI for short) is increasingly being used in clinical routine for diagnosis and longitudinal assessment of muscle disorders. However, cross-centre standards for measurement protocol and radiological assessment are still lacking. OBJECTIVES: The aim of this expert recommendation is to present standards for the application and interpretation of muscle MRI in hereditary and inflammatory muscle disorders. METHODS: This work was developed in collaboration between neurologists, neuroradiologists, radiologists, neuropaediatricians, neuroscientists and MR physicists from different university hospitals in Germany. The recommendations are based on expert knowledge and a focused literature search. RESULTS: The indications for muscle MRI are explained, including the detection and monitoring of structural tissue changes and oedema in the muscle, as well as the identification of a suitable biopsy site. Recommendations for the examination procedure and selection of appropriate MRI sequences are given. Finally, steps for a structured radiological assessment are presented. CONCLUSIONS: The present work provides concrete recommendations for the indication, implementation and interpretation of muscle MRI in muscle disorders. Furthermore, it provides a possible basis for the standardisation of the measurement protocols at all clinical centres in Germany.

Varicose Veins as Model for Apportionment among Risk Factors for Compensation Purposes.

OBJECTIVE.­: To demonstrate a method which is being used to apportion between risk factors for occupationally related disease and compensate individuals with multiple risk factors. The application to individuals will be demonstrated for varicose veins. BACKGROUND.­: The National Insurance Institute (NII) is tasked with compensating work related injuries and illness in Israel. Population attributable fraction (PAF) has been utilized in order to estimate the amount of disease that can potentially be eliminated in a population through the elimination of individual risk factors. PAF is based on relative risks and the prevalence of these risks. METHODS.­: A review of the medical literature consisting of epidemiological studies of varicose veins and its multiple risk factors was conducted, with special attention to prolonged occupational standing. Summary, weighted, relative risks were calculated for eight different risk factors. The proposed formula then allowed for apportioning among those risk factors in the individual. RESULTS.­: The findings of the current study indicate that prolonged standing may be associated with the presence of varicose veins, however in light of the multiple other risk factors associated, its overall contribution is generally minor. CONCLUSION.­: Apportionment among multiple risk factors for varicose veins can be accomplished mathematically in individuals. This application is being applied successfully for other diseases as well.

Clinical Application of Ultrahigh-Field-Strength Wrist MRI: A Multireader 3-T and 7-T Comparison Study.

Background Ultrahigh-field-strength MRI at 7 T may permit superior visualization of noninflammatory wrist pathologic conditions, particularly due to its high signal-to-noise ratio compared with the clinical standard of 3 T, but direct comparison studies are lacking. Purpose To compare the subjective image quality of 3-T and 7-T ultrahigh-field-strength wrist MRI through semiquantitative scoring of multiple joint tissues in a multireader study. Materials and Methods In this prospective study, healthy controls and participants with chronic wrist pain underwent 3-T and 7-T MRI (coronal T1-weighted turbo spin-echo [TSE], coronal fat-suppressed proton-density [PD]-weighted TSE, transversal T2-weighted TSE) on the same day, from July 2018 to June 2019. Images were scored by seven musculoskeletal radiologists. The overall image quality, presence of artifacts, homogeneity of fat suppression, and visualization of cartilage, the triangular fibrocartilage complex (TFCC), and scapholunate and lunotriquetral ligaments were semiquantitatively assessed. Pairwise differences between 3 T and 7 T were assessed using the Wilcoxon signed-rank test. Interreader reliability was determined using the Fleiss kappa. Results In total, 25 healthy controls (mean age, 25 years ± 4 [SD]; 13 women) and 25 participants with chronic wrist pain (mean age, 39 years ± 16; 14 men) were included. Overall image quality (P = .002) and less presence of artifacts at PD-weighted fat-suppressed MRI were superior at 7 T. T1- and T2-weighted MRI were superior at 3 T (both P < .001), as was fat suppression (P < .001). Visualization of cartilage was superior at 7 T (P < .001), while visualization of the TFCC (P < .001) and scapholunate (P = .048) and lunotriquetral (P = .04) ligaments was superior at 3 T. Interreader reliability showed slight to substantial agreement for the detected pathologic conditions (κ = 0.20-0.64). Conclusion A 7-T MRI of the wrist had potential advantages over 3-T MRI, particularly in cartilage assessment. However, superiority was not shown for all parameters; for example, visualization of the triangular fibrocartilage complex and wrist ligaments was superior at 3 T. © RSNA, 2023 Supplemental material is available for this article.

Suppressing ion migration in metal halide perovskite via interstitial doping with a trace amount of multivalent cations.

Cations with suitable sizes to occupy an interstitial site of perovskite crystals have been widely used to inhibit ion migration and promote the performance and stability of perovskite optoelectronics. However, such interstitial doping inevitably leads to lattice microstrain that impairs the long-range ordering and stability of the crystals, causing a sacrificial trade-off. Here, we unravel the evident influence of the valence states of the interstitial cations on their efficacy to suppress the ion migration. Incorporation of a trivalent neodymium cation (Nd3+) effectively mitigates the ion migration in the perovskite lattice with a reduced dosage (0.08%) compared to a widely used monovalent cation dopant (Na+, 0.45%). The photovoltaic performances and operational stability of the prototypical perovskite solar cells are enhanced with a trace amount of Nd3+ doping while minimizing the sacrificial trade-off.

Comparison between dedicated MRI and symphyseal fluoroscopic guided contrast agent injection in the diagnosis of cleft sign in athletic groin pain and association with pelvic ring instability.

OBJECTIVE: To compare dedicated MRI with targeted fluoroscopic guided symphyseal contrast agent injection regarding the assessment of symphyseal cleft signs in men with athletic groin pain and assessment of radiographic pelvic ring instability. METHODS: Sixty-six athletic men were prospectively included after an initial clinical examination by an experienced surgeon using a standardized procedure. Diagnostic fluoroscopic symphyseal injection of a contrast agent was performed. Additionally, standing single-leg stance radiography and dedicated 3-Tesla MRI protocol were employed. The presence of cleft injuries (superior, secondary, combined, atypical) and osteitis pubis was recorded. RESULTS: Symphyseal bone marrow edema (BME) was present in 50 patients, bilaterally in 41 patients and in 28 with an asymmetrical distribution. Comparison of MRI and symphysography was as followed: no clefts: 14 cases (MRI) vs. 24 cases (symphysography), isolated superior cleft sign: 13 vs. 10, isolated secondary cleft sign: 15 vs. 21 cases and combined injuries: 18 vs. 11 cases. In 7 cases a combined cleft sign was observed in MRI but only an isolated secondary cleft sign was visible in symphysography. Anterior pelvic ring instability was observed in 25 patients and was linked to a cleft sign in 23 cases (7 superior cleft sign, 8 secondary cleft signs, 6 combined clefts, 2 atypical cleft injuries). Additional BME could be diagnosed in 18 of those 23. CONCLUSION: Dedicated 3-Tesla MRI outmatches symphysography for purely diagnostic purposes of cleft injuries. Microtearing at the prepubic aponeurotic complex and the presence of BME is a prerequisite for the development of anterior pelvic ring instability. CLINICAL RELEVANCE STATEMENT: For diagnostic of symphyseal cleft injuries dedicated 3-T MRI protocols outmatch fluoroscopic symphysography. Prior specific clinical examination is highly beneficial and additional flamingo view x-rays are recommended for assessment of pelvic ring instability in these patients. KEY POINTS: • Assessment of symphyseal cleft injuries is more accurate by use of dedicated MRI as compared to fluoroscopic symphysography. • Additional fluoroscopy may be important for therapeutic injections. • The presence of cleft injury might be a prerequisite for the development of pelvic ring instability.

Soft tissue tumor imaging in adults: European Society of Musculoskeletal Radiology-Guidelines 2023-overview, and primary local imaging: how and where?

OBJECTIVES: Early, accurate diagnosis is crucial for the prognosis of patients with soft tissue sarcomas. To this end, standardization of imaging algorithms, technical requirements, and reporting is therefore a prerequisite. Since the first European Society of Musculoskeletal Radiology (ESSR) consensus in 2015, technical achievements, further insights into specific entities, and the revised WHO-classification (2020) and AJCC staging system (2017) made an update necessary. The guidelines are intended to support radiologists in their decision-making and contribute to interdisciplinary tumor board discussions. MATERIALS AND METHODS: A validated Delphi method based on peer-reviewed literature was used to derive consensus among a panel of 46 specialized musculoskeletal radiologists from 12 European countries. Statements were scored online by level of agreement (0 to 10) during two iterative rounds. Either "group consensus," "group agreement," or "lack of agreement" was achieved. RESULTS: Eight sections were defined that finally contained 145 statements with comments. Overall, group consensus was reached in 95.9%, and group agreement in 4.1%. This communication contains the first part consisting of the imaging algorithm for suspected soft tissue tumors, methods for local imaging, and the role of tumor centers. CONCLUSION: Ultrasound represents the initial triage imaging modality for accessible and small tumors. MRI is the modality of choice for the characterization and local staging of most soft tissue tumors. CT is indicated in special situations. In suspicious or likely malignant tumors, a specialist tumor center should be contacted for referral or teleradiologic second opinion. This should be done before performing a biopsy, without exception. CLINICAL RELEVANCE: The updated ESSR soft tissue tumor imaging guidelines aim to provide best practice expert consensus for standardized imaging, to support radiologists in their decision-making, and to improve examination comparability both in individual patients and in future studies on individualized strategies. KEY POINTS: • Ultrasound remains the best initial triage imaging modality for accessible and small suspected soft tissue tumors. • MRI is the modality of choice for the characterization and local staging of soft tissue tumors in most cases; CT is indicated in special situations. Suspicious or likely malignant tumors should undergo biopsy. • In patients with large, indeterminate or suspicious tumors, a tumor reference center should be contacted for referral or teleradiologic second opinion; this must be done before a biopsy.

Machine Learning Models for Prediction of Posttreatment Recurrence in Early-Stage Hepatocellular Carcinoma Using Pretreatment Clinical and MRI Features: A Proof-of-Concept Study.

BACKGROUND. Posttreatment recurrence is an unpredictable complication after liver transplant for hepatocellular carcinoma (HCC) that is associated with poor survival. Biomarkers are needed to estimate recurrence risk before organ allocation. OBJECTIVE. This proof-of-concept study evaluated the use of machine learning (ML) to predict recurrence from pretreatment laboratory, clinical, and MRI data in patients with early-stage HCC initially eligible for liver transplant. METHODS. This retrospective study included 120 patients (88 men, 32 women; median age, 60.0 years) with early-stage HCC diagnosed who were initially eligible for liver transplant and underwent treatment by transplant, resection, or thermal ablation between June 2005 and March 2018. Patients underwent pretreatment MRI and posttreatment imaging surveillance. Imaging features were extracted from postcontrast phases of pretreatment MRI examinations using a pretrained convolutional neural network. Pretreatment clinical characteristics (including laboratory data) and extracted imaging features were integrated to develop three ML models (clinical model, imaging model, combined model) for predicting recurrence within six time frames ranging from 1 through 6 years after treatment. Kaplan-Meier analysis with time to recurrence as the endpoint was used to assess the clinical relevance of model predictions. RESULTS. Tumor recurred in 44 of 120 (36.7%) patients during follow-up. The three models predicted recurrence with AUCs across the six time frames of 0.60-0.78 (clinical model), 0.71-0.85 (imaging model), and 0.62-0.86 (combined model). The mean AUC was higher for the imaging model than the clinical model (0.76 vs 0.68, respectively; p = .03), but the mean AUC was not significantly different between the clinical and combined models or between the imaging and combined models (p > .05). Kaplan-Meier curves were significantly different between patients predicted to be at low risk and those predicted to be at high risk by all three models for the 2-, 3-, 4-, 5-, and 6-year time frames (p < .05). CONCLUSION. The findings suggest that ML-based models can predict recurrence before therapy allocation in patients with early-stage HCC initially eligible for liver transplant. Adding MRI data as model input improved predictive performance over clinical parameters alone. The combined model did not surpass the imaging model's performance. CLINICAL IMPACT. ML-based models applied to currently underutilized imaging features may help design more reliable criteria for organ allocation and liver transplant eligibility.

Mutation bias within oncogene families is related to proliferation-specific codon usage.

It is well known that in cancer gene families some members are more frequently mutated in tumor samples than their family counterparts. A paradigmatic case of this phenomenon is KRAS from the RAS family. Different explanations have been proposed ranging from differential interaction with other proteins to preferential expression or localization. Interestingly, it has been described that despite the high amino acid identity between RAS family members, KRAS employs an intriguing differential codon usage. Here, we found that this phenomenon is not exclusive to the RAS family. Indeed, in the RAS family and other oncogene families with two or three members, the most prevalently mutated gene in tumor samples employs a differential codon usage that is characteristic of genes involved in proliferation. Prompted by these observations, we chose the RAS family to experimentally demonstrate that the translation efficiency of oncogenes that are preferentially mutated in tumor samples is increased in proliferative cells compared to quiescent cells. These results were further validated by assessing the translation efficiency of KRAS in cell lines that differ in their tRNA expression profile. These differences are related to the cell division rate of the studied cells and thus suggest an important role in context-specific oncogene expression regulation. Altogether, our study demonstrates that dynamic translation programs contribute to shaping the expression profiles of oncogenes. Therefore, we propose this codon bias as a regulatory layer to control cell context-specific expression and explain the differential prevalence of mutations in certain members of oncogene families.

spsurvey: Spatial Sampling Design and Analysis in R.

spsurvey is an R package for design-based statistical inference, with a focus on spatial data. spsurvey provides the generalized random-tessellation stratified (GRTS) algorithm to select spatially balanced samples via the grts() function. The grts() function flexibly accommodates several sampling design features, including stratification, varying inclusion probabilities, legacy (or historical) sites, minimum distances between sites, and two options for replacement sites. spsurvey also provides a suite of data analysis options, including categorical variable analysis (cat_analysis()), continuous variable analysis cont_analysis()), relative risk analysis (relrisk_analysis()), attributable risk analysis (attrisk_analysis()), difference in risk analysis (diffrisk_analysis()), change analysis (change_analysis()), and trend analysis (trend_analysis()). In this manuscript, we first provide background for the GRTS algorithm and the analysis approaches and then show how to implement them in spsurvey. We find that the spatially balanced GRTS algorithm yields more precise parameter estimates than simple random sampling, which ignores spatial information.

Monteggia fractures and Monteggia-like-lesions: a systematic review.

Monteggia injuries are rare, but severe injuries of the elbow including various injury patterns. Treatment of these injuries is still topic of debate and strategies differ widely. In this systematic review on Monteggia injuries in adults, we aimed to clarify the incidence of different injury patterns within Monteggia injuries, investigate the main reasons leading to revision surgery and explore which surgical treatments should be favored to achieve satisfactory clinical results.We initially identified 182 publications and ultimately included 17 retrospective studies comprising 651 cases. All patients were classified using the Bado classification, leading to 30.5% Bado type I fractures, 60.4% type II fractures, 5.1% type III and 3.1% type IV fractures. Mean revision rate was 23%. Ulna non-union (28%) and limited range-of-motion (22%) are the main reasons for revision surgery. Meta-analysis shows a trend toward the use of locking plates for ulna fixation which may lead to less revision surgery and fewer ulna non-unions. Further biomechanical and clinical research is necessary to clarify the role of radial head surgery.

Subacromial impingement syndrome: association of multiple magnetic resonance imaging parameters with shoulder function and pain.

INTRODUCTION: Shoulder pain is one of the most common complaints in orthopaedics. This study focusses on the relationship between shoulder function in subacromial impingement syndrome and imaging criteria in magnetic resonance imaging (MRI). MATERIALS AND METHODS: This prospective clinical trial included 69 patients treated for subacromial impingement syndrome. Shoulder function (Constant Score, range of abduction, abduction force) and pain were correlated with the following MRI parameters: tendinosis of the rotator cuff, "halo-sign" around the biceps tendon, subacromial distance, critical shoulder angle, size of subacromial osteophytic spurs and maximum width of subacromial and subdeltoid bursa. Statistical analyses included Pearson's and Spearman's coefficients of correlation, multiple regression analysis and Student's t-test. RESULTS: The Constant Score was correlated positively with the critical shoulder angle (r = 0.313; p = 0.009) and inversely with a "halo-sign" around the biceps tendon (rho = -0.384; p = 0.001). There was no significant correlation between spur size and shoulder function, but the size of the subacromial and subdeltoid bursae was positively correlated with the subacromial spur's size (subacromial bursa: coronal plane: r = 0.327; p = 0.006; sagittal view: r = 0.305; p = 0.011; subdeltoid bursa coronal view: r = 0.333 p = 0.005). The width of the subdeltoid bursa in coronal plane was positively correlated with shoulder pain (r = 0.248; p = 0.004) and negatively with the range of abduction (r = -0.270; p = 0.025), as well as the mean (r = -0.332; p = 0.005) and maximum (r = -0.334; p = 0.005) abduction force. CONCLUSIONS: Shoulder function and pain in subacromial impingement are best predicted by the width of the subdeltoid bursa measured in the coronal MRI plane as an indicator of bursitis as well as the presence of a "halo-sign" around the biceps tendon indicating glenohumeral joint effusion. Presence of a subacromial spur could lead to subacromial and subdeltoid bursitis, which impairs shoulder function. Shoulder function seems not to be compromised by the presence of a subacromial spur in absence of bursitis. This study was registered at the German Clinical Trials Register on 08 February 2013 (ID: DRKS00011548).

Wetland Flowpaths Mediate Nitrogen and Phosphorus Concentrations across the Upper Mississippi River Basin.

Eutrophication, harmful algal blooms, and human health impacts are critical environmental challenges resulting from excess nitrogen and phosphorus in surface waters. Yet we have limited information regarding how wetland characteristics mediate water quality across watershed scales. We developed a large, novel set of spatial variables characterizing hydrological flowpaths from wetlands to streams, that is, "wetland hydrological transport variables," to explore how wetlands statistically explain the variability in total nitrogen (TN) and total phosphorus (TP) concentrations across the Upper Mississippi River Basin (UMRB) in the United States. We found that wetland flowpath variables improved landscape-to-aquatic nutrient multilinear regression models (from R2 = 0.89 to 0.91 for TN; R2 = 0.53 to 0.84 for TP) and provided insights into potential processes governing how wetlands influence watershed-scale TN and TP concentrations. Specifically, flowpath variables describing flow-attenuating environments, for example, subsurface transport compared to overland flowpaths, were related to lower TN and TP concentrations. Frequent hydrological connections from wetlands to streams were also linked to low TP concentrations, which likely suggests a nutrient source limitation in some areas of the UMRB. Consideration of wetland flowpaths could inform management and conservation activities designed to reduce nutrient export to downstream waters.

Wide-Gap Perovskite via Synergetic Surface Passivation and Its Application toward Efficient Stacked Tandem Photovoltaics.

Superior bandgap tunability enables solution-processed halide perovskite a promising candidate for multi-junction photovoltaics (PVs). Particularly, optically coupling wide-gap perovskite by stacking with commercially available PVs such as silicon and CIGS (also known as 4-terminal tandem) simplifies the technology transfer process, and further advances the commercialization potential of perovskite technology. However, compared with matured PV materials and the phase-pure FAPbI3 , wide-gap perovskite still suffers from huge voltage deficits. Here, the authors take advantage of the synergetic effect behind a sequential fluoride and organic ammonium salt surface passivation strategy to control non-radiative energy losses, and obtained a 17.7% efficiency in infrared-transparent wide-gap perovskite solar cells (21.1% for opaque device), and achieved efficiencies of over 25% when stacked with commercial Si and CIGS products with original PCEs of 18-20% under a 4-terminal working condition.

Engineering a genome-reduced bacterium to eliminate Staphylococcus aureus biofilms in vivo.

Bacteria present a promising delivery system for treating human diseases. Here, we engineered the genome-reduced human lung pathogen Mycoplasma pneumoniae as a live biotherapeutic to treat biofilm-associated bacterial infections. This strain has a unique genetic code, which hinders gene transfer to most other bacterial genera, and it lacks a cell wall, which allows it to express proteins that target peptidoglycans of pathogenic bacteria. We first determined that removal of the pathogenic factors fully attenuated the chassis strain in vivo. We then designed synthetic promoters and identified an endogenous peptide signal sequence that, when fused to heterologous proteins, promotes efficient secretion. Based on this, we equipped the chassis strain with a genetic platform designed to secrete antibiofilm and bactericidal enzymes, resulting in a strain capable of dissolving Staphylococcus aureus biofilms preformed on catheters in vitro, ex vivo, and in vivo. To our knowledge, this is the first engineered genome-reduced bacterium that can fight against clinically relevant biofilm-associated bacterial infections.

CT imaging-based approaches to cochlear duct length estimation-a human temporal bone study.

OBJECTIVES: Knowledge about cochlear duct length (CDL) may assist electrode choice in cochlear implantation (CI). However, no gold standard for clinical applicable estimation of CDL exists. The aim of this study is (1) to determine the most reliable radiological imaging method and imaging processing software for measuring CDL from clinical routine imaging and (2) to accurately predict the insertion depth of the CI electrode. METHODS: Twenty human temporal bones were examined using different sectional imaging techniques (high-resolution computed tomography [HRCT] and cone beam computed tomography [CBCT]). CDL was measured using three methods: length estimation using (1) a dedicated preclinical 3D reconstruction software, (2) the established A-value method, and (3) a clinically approved otosurgical planning software. Temporal bones were implanted with a 31.5-mm CI electrode and measurements were compared to a reference based on the CI electrode insertion angle measured by radiographs in Stenvers projection (CDLreference). RESULTS: A mean cochlear coverage of 74% (SD 7.4%) was found. The CDLreference showed significant differences to each other method (p < 0.001). The strongest correlation to the CDLreference was found for the otosurgical planning software-based method obtained from HRCT (CDLSW-HRCT; r = 0.87, p < 0.001) and from CBCT (CDLSW-CBCT; r = 0.76, p < 0.001). Overall, CDL was underestimated by each applied method. The inter-rater reliability was fair for the CDL estimation based on 3D reconstruction from CBCT (CDL3D-CBCT; intra-class correlation coefficient [ICC] = 0.43), good for CDL estimation based on 3D reconstruction from HRCT (CDL3D-HRCT; ICC = 0.71), poor for CDL estimation based on the A-value method from HRCT (CDLA-HRCT; ICC = 0.29), and excellent for CDL estimation based on the A-value method from CBCT (CDLA-CBCT; ICC = 0.87) as well as for the CDLSW-HRCT (ICC = 0.94), CDLSW-CBCT (ICC = 0.94) and CDLreference (ICC = 0.87). CONCLUSIONS: All approaches would have led to an electrode choice of rather too short electrodes. Concerning treatment decisions based on CDL measurements, the otosurgical planning software-based method has to be recommended. The best inter-rater reliability was found for CDLA-CBCT, for CDLSW-HRCT, for CDLSW-CBCT, and for CDLreference. KEY POINTS: • Clinically applicable calculations using high-resolution CT and cone beam CT underestimate the cochlear size. • Ten percent of cochlear duct length need to be added to current calculations in order to predict the postoperative CI electrode position. • The clinically approved otosurgical planning software-based method software is the most suitable to estimate the cochlear duct length and shows an excellent inter-rater reliability.

Primary renal sarcomas: imaging features and discrimination from non-sarcoma renal tumors.

OBJECTIVES: To assess imaging features of primary renal sarcomas in order to better discriminate them from non-sarcoma renal tumors. METHODS: Adult patients diagnosed with renal sarcomas from 1995 to 2018 were included from 11 European tertiary referral centers (Germany, Belgium, Turkey). Renal sarcomas were 1:4 compared to patients with non-sarcoma renal tumors. CT/MRI findings were assessed using 21 predefined imaging features. A random forest model was trained to predict "renal sarcoma vs. non-sarcoma renal tumors" based on demographics and imaging features. RESULTS: n = 34 renal sarcomas were included and compared to n = 136 non-sarcoma renal tumors. Renal sarcomas manifested in younger patients (median 55 vs. 67 years, p < 0.01) and were more complex (high RENAL score complexity 79.4% vs. 25.7%, p < 0.01). Renal sarcomas were larger (median diameter 108 vs. 43 mm, p < 0.01) with irregular shape and ill-defined margins, and more frequently demonstrated invasion of the renal vein or inferior vena cava, tumor necrosis, direct invasion of adjacent organs, and contact to renal artery or vein, compared to non-sarcoma renal tumors (p < 0.05, each). The random forest algorithm yielded a median AUC = 93.8% to predict renal sarcoma histology, with sensitivity, specificity, and positive predictive value of 90.4%, 76.5%, and 93.9%, respectively. Tumor diameter and RENAL score were the most relevant imaging features for renal sarcoma identification. CONCLUSION: Renal sarcomas are rare tumors commonly manifesting as large masses in young patients. A random forest model using demographics and imaging features shows good diagnostic accuracy for discrimination of renal sarcomas from non-sarcoma renal tumors, which might aid in clinical decision-making. KEY POINTS: • Renal sarcomas commonly manifest in younger patients as large, complex renal masses. • Compared to non-sarcoma renal tumors, renal sarcomas more frequently demonstrated invasion of the renal vein or inferior vena cava, tumor necrosis, direct invasion of adjacent organs, and contact to renal artery or vein. • Using demographics and standardized imaging features, a random forest showed excellent diagnostic performance for discrimination of sarcoma vs. non-sarcoma renal tumors (AUC = 93.8%, sensitivity = 90.4%, specificity = 76.5%, and PPV = 93.9%).