Exploring the combinatorial explosion of amine-acid reaction space via graph editing.

Amines and carboxylic acids are abundant chemical feedstocks that are nearly exclusively united via the amide coupling reaction. The disproportionate use of the amide coupling leaves a large section of unexplored reaction space between amines and acids: two of the most common chemical building blocks. Herein we conduct a thorough exploration of amine-acid reaction space via systematic enumeration of reactions involving a simple amine-carboxylic acid pair. This approach to chemical space exploration investigates the coarse and fine modulation of physicochemical properties and molecular shapes. With the invention of reaction methods becoming increasingly automated and bringing conceptual reactions into reality, our map provides an entirely new axis of chemical space exploration for rational property design.

Diagnosis and management of indeterminate testicular lesions.

The sophistication and accessibility of modern-day imaging result in frequent detection of small or equivocal lesions of the testes. Traditionally, diagnosis of a testicular lesion with any possibility of malignancy would usually prompt radical orchidectomy. However, awareness is growing that a substantial proportion of these lesions might be benign and that universal application of radical orchidectomy risks frequent overtreatment. Given the potentially profound effects of radical orchidectomy on fertility, endocrine function and psychosexual well-being, particularly in scenarios of an abnormal contralateral testis or bilateral lesions, organ-preserving strategies for equivocal lesions should be considered. Image-based active surveillance can be applied for indeterminate lesions measuring ≤15 mm with a low conversion rate to surgical treatment. However, these outcomes are early and from relatively small, selected cohorts, and concerns prevail regarding the metastatic potential of even small undiagnosed germ cell tumours. No consensus exists on optimal surveillance (short interval (<3 months) ultrasonography is generally adopted); histological sampling is a widespread alternative, involving inguinal delivery of the testis and excisional biopsy of the lesion, with preoperative marking or intraoperative ultrasonographic localization when necessary. Frozen section analysis in this context demonstrates excellent diagnostic accuracy. Histological results support that approximately two-thirds of marker-negative indeterminate solitary testicular lesions measuring ≤25 mm overall are benign. In summary, modern imaging detects many small indeterminate testicular lesions, of which the majority are benign. Awareness is growing of surveillance and organ-sparing diagnostic and treatment strategies with the aim of minimizing rates of overtreatment with radical orchidectomy.

Dosimetric effects of rotational errors for single isocenter multiple targets in HyperArc plans: A phantom and retrospective imaging analysis study.

PURPOSE: This study uses a phantom to investigate the dosimetric impact of rotational setup errors for Single Isocenter Multiple Targets (SIMT) HyperArc plans. Additionally, it evaluates intra-fractional rotational setup errors in patients treated with Encompass immobilization system. METHODS: The Varian HyperArc system (Varian Medical systems) was used to create plans targeting spherical PTVs with diameters of 5, 10, and 15 mm and with offsets of 1.3-5.3 cm from the isocenter. Dosimetric parameters, including mean and maximum dose, D99% and D95% were evaluated for various rotational setup errors ranging from 0.5° to 2° for the PTVs and certain CTVs created within PTVs. These rotational errors were applied in an order and direction that resulted in the maximum displacement of targets. The rotation was applied both uniformly around all three axes and individually around each axis. Furthermore, to link the findings to actual treatment scenarios, the intra-fractional rotational setup errors were obtained for stereotactic cranial patients treated with the Encompass system using CBCT images acquired during treatments. RESULTS: The maximum displacement of 2.7 mm was observed for targets located at 4.4 and 4.5 cm from the isocenter with rotational setup errors of 2°. The dose reduction for D99% values corresponding to this displacement were about 50%, 40%, and 30% for PTVs with diameters of 5, 10, and 15 mm, respectively. Both D99% and D95% showed a consistent trend of dose reduction across various rotational errors and PTV volumes. While the maximum dose remained consistent for different targets with various rotational errors, the mean dose decreased by approximately 25%, 12%, and 6% for PTVs with diameters of 5, 10, and 15 cm, respectively, with rotational errors of 2°. In addition, by analyzing CBCT images, the absolute mean rotational setup errors obtained during treatment with Encompass for pitch, roll, and yaw were 0.17° ± 0.13°, 0.11° ± 0.10°, and 0.12° ± 0.10° respectively. This data, combined with existing studies, suggest that a 0.5° rotational setup error is a safe choice to consider for calculating additional PTV margin to ensure adequate CTV coverage. Therefore, the assessment of maximum displacement and dosimetric parameters in this study, for a 0.5° rotational error, highlights the need for an additional 0.7 mm PTV margin for targets positioned at distances of 4.4 cm or greater from the isocenter. CONCLUSIONS: For SIMT Plans, a 0.5° rotational setup error is recommended as a basis for calculating additional PTV margins to ensure adequate CTV coverage when using the Encompass system.

Rapid planning and analysis of high-throughput experiment arrays for reaction discovery.

High-throughput experimentation (HTE) is an increasingly important tool in reaction discovery. While the hardware for running HTE in the chemical laboratory has evolved significantly in recent years, there remains a need for software solutions to navigate data-rich experiments. Here we have developed phactor™, a software that facilitates the performance and analysis of HTE in a chemical laboratory. phactor™ allows experimentalists to rapidly design arrays of chemical reactions or direct-to-biology experiments in 24, 96, 384, or 1,536 wellplates. Users can access online reagent data, such as a chemical inventory, to virtually populate wells with experiments and produce instructions to perform the reaction array manually, or with the assistance of a liquid handling robot. After completion of the reaction array, analytical results can be uploaded for facile evaluation, and to guide the next series of experiments. All chemical data, metadata, and results are stored in machine-readable formats that are readily translatable to various software. We also demonstrate the use of phactor™ in the discovery of several chemistries, including the identification of a low micromolar inhibitor of the SARS-CoV-2 main protease. Furthermore, phactor™ has been made available for free academic use in 24- and 96-well formats via an online interface.

The structure of the Hospital Anxiety and Depression Scale: Theoretical and methodological considerations.

The Hospital Anxiety and Depression Scale (HADS; Zigmond - Snaith, 1983) is widely used; however, its factor structure is unclear, with studies reporting differing unidimensional, two-factor and three-factor models. We aimed to address some key theoretical and methodological issues contributing to inconsistencies in HADS structures across samples. We reviewed existing HADS models and compared their fit using confirmatory factor analysis (CFA). We also investigated methodological effects by comparing factor structures derived from Rasch and Principal Components Analysis (PCA) methods, as well as effects of a negative wording factor. An Australian community-dwelling sample consisting of 189 females and 158 males aged 17-86 (M = 35.73, SD = 17.41) completed the 14-item HADS. The Rasch Analysis, PCA and CFA all supported the original two-factor structure. Although some three-factor models had good fit, they had unacceptable reliability. In the CFA, a hierarchical bifactor model with a general distress factor and uncorrelated depression and anxiety subscales produced the best fit, but the general factor was not unidimensional. The addition of a negative wording factor improved model fit. These findings highlight the effects of differing methodologies in producing inconsistent HADS factor structures across studies. Further replication of model fit across samples and refinement of the HADS items is warranted.

Repurposing amine and carboxylic acid building blocks with an automatable esterification reaction.

New methodologies to unite amines and carboxylic acids that complement the popular amide coupling can significantly expand accessible chemical space if they yield products distinct from the classic R-NHC(O)-R' amide arrangement. Here we have developed an amine-acid esterification reaction based on pyridinium salt activation of amine C-N bonds to create products of type R-OC(O)-R' upon reaction with alkyl and aryl carboxylic acids. The protocol is robust and facile as demonstrated by automation on open-source robotics.

Examination of college student health behaviors and self-reported executive functions.

Objective: Emerging adulthood is characterized by maturation of executive functions (EF) and changes in health behaviors (HB). Interestingly, EF are bi-directionally related to many specific HB; yet how EF performs in relation to overall patterns of HB engagement is unclear. Groupings of HB and the relationship between these HB groupings and EF were examined. PARTICIPANTS: Full-time college students were recruited from three large Mid- and Southwest universities (N = 1,387). METHODS: Online self-report questionnaires assessing demographics, HB, and EF were completed. RESULTS: Latent class analysis of HB revealed three classes: (1) High Substance Use, (2) Moderately Healthy, (3) Healthy. In general, the Healthy class had significantly greater EF compared to no significant differences between the other two classes. CONCLUSIONS: Collective engagement in HB is associated with EF. Interventions targeting both HB and EF simultaneously may be most efficacious.

An 8-year, single-centre experience of primary image-guided insertion of 'button' gastrostomy catheters: Technical and clinical results.

INTRODUCTION: 'Button' gastrostomy insertion is traditionally a two-step procedure with an initial longer gastrostomy tube inserted followed by placement of the shorter 'button' gastrostomy in 6 weeks when the track is mature. The aim of this study is to assess whether the placement of a Button gastrostomy de novo is a safe and effective method of radiologically inserted gastrostomy (RIG) insertion. METHODS: Using our Picture Archive and Communication System (PACS) and electronic patient charts we identified all patients who underwent primary 'button' gastrostomy over an 8-year period with at least a 1-year follow-up period. We evaluated technical success rate, indications for insertion, major and minor complications, 30-day mortality and the number of exchanges performed. RESULTS: Overall, 482 patients underwent a primary button RIG insertion during this period with an overall success rate of 97.1%. Indications for RIG insertion included neurological and neurosurgical disorders 236 (48.9%), head and neck malignancy 182 (37.8%), oesophageal malignancy 27 (5.6%) and other indications in 37 (7.7%). The mean age was 59.55 years (range 18-88 years) with 290 men (60.2%) and 192 women (39.8%). Major complications were recorded in 0.8% and minor complications in 1.7%. A 30-day mortality of 1% was identified (five patients), mortality was directly related to the RIG insertion in one patient (0.2%). A total of 65 exchanges/replacements took place over this period of time, with 33 (50.1%) due to 'inadvertent removal'. CONCLUSION: Primary button RIG insertion is a procedure that has a high success rate and low morbidity and mortality. We believe it is a safe and effective alternative to deliver enteral nutrition.

Determination of correction factors in small MLC-defined fields for the Razor and microSilicon diode detectors and evaluation of the suitability of the IAEA TRS-483 protocol for multiple detectors.

Small field output factors for Multileaf collimator (MLC)-defined field sizes between 0.5 × 0.5 cm2 and 3 × 3 cm2 were measured with six different detectors for a Varian TrueBeam in 6-MV, 6-FFF, 10-MV, and 10-FFF photon beams. Correction factors k Q clin , Q ref f clin , f ref $k_{{Q_{{\rm{clin}}}},{Q_{{\rm{ref}}}}}^{{f_{{\rm{clin}}}},{f_{{\rm{ref}}}}}$ from the IAEA publication TRS-483 were used to correct the measured output factors. The corrected output factors from the six detectors were used to calculate correction factors for the PTW microSilicon T60023 (PTW, Freiburg, Germany) and IBA Razor (IBA Dosimetry, Schwarzenbruck, Germany) detectors. The uncertainty of the output and correction factors in this study was calculated and the calculations presented in detail. The application of the TRS-483 correction factors significantly reduced the variation in output factors between the various detectors, with the exception of the PTW 60016 diode in 6-MV and 6-FFF beams, and the IBA PFD in 10-MV and 10-FFF beams. Correction factors calculated for the Razor agreed within 2.9% of existing literature for all energies, while the microSilicon correction factors agreed within 1.6% to the literature for 6-MV beams. The uncertainty in the microSilicon and Razor correction factors was calculated to be less than 0.9% (k = 1). This study shows that TRS-483 correction factors reduce the variation in output factors between the detectors used in this study and presents a suitable method for determining correction factors for detectors with unpublished values.

A single center 9-year experience in IVC filter retrieval - the importance of an IVC filter registry.

BACKGROUND: To evaluate Inferior vena cava (IVC) filter retrieval practices over a 9-year period at an academic hospital with a prospectively maintained IVC filter registry. METHOD: An IVC filter registry was maintained prospectively within our institution. We reviewed cases between August 2011 and June 2020, following filter status, retrieval plans, and eventual retrieval date. The validity of the database was cross referenced with a Picture Archiving and Communication System and patient records. RESULTS: Three hundred forty-three patients had IVC filters inserted. Three filter types were used, Celect (Cook Medical) in 189, Gunther Tulip (GT) (Cook Medical) in 65, ALN (ALN) in 89. 196 (57%) filters were retrieved, 108 (31.5%) were made permanent, 36 (10.5%) died before retrieval, and 3 (1%) were yet to be retrieved. Retrieval rates were 92.5% overall (86% for GT, 93% for Celect and 94.5% for ALN). The mean dwell time for successful retrieval was 59 days with the majority of insertions (85%) removed in under 100 days. Failed initial retrieval occurred in 23 patients, 10 (43%) were retrieved at second attempt, 13/23 filters remained in-situ and were deemed permanent. CONCLUSION: The removal of IVC filters, when indication for insertion has past, is no longer the sole responsibility of the referring physician but also the responsibility of the Interventionalist. Our retrieval rates of 92.5% of eligible IVC filters highlights the value of maintaining a prospective IVC filter registry.

Reinforcing the supply chain of umifenovir and other antiviral drugs with retrosynthetic software.

The global disruption caused by the 2020 coronavirus pandemic stressed the supply chain of many products, including pharmaceuticals. Multiple drug repurposing studies for COVID-19 are now underway. If a winning therapeutic emerges, it is unlikely that the existing inventory of the medicine, or even the chemical raw materials needed to synthesize it, will be available in the quantities required. Here, we utilize retrosynthetic software to arrive at alternate chemical supply chains for the antiviral drug umifenovir, as well as eleven other antiviral and anti-inflammatory drugs. We have experimentally validated four routes to umifenovir and one route to bromhexine. In one route to umifenovir the software invokes conversion of six C-H bonds into C-C bonds or functional groups. The strategy we apply of excluding known starting materials from search results can be used to identify distinct starting materials, for instance to relieve stress on existing supply chains.

MnSn2and MnSn2-TiO2nanostructured anode materials for lithium-ion batteries.

The high theoretical lithium storage capacity of Sn makes it an enticing anode material for Li-ion batteries (LIBs); however, its large volumetric expansion during Li-Sn alloying must be addressed. Combining Sn with metals that are electrochemically inactive to lithium leads to intermetallics that can alleviate volumetric expansion issues and still enable high capacity. Here, we present the cycling behavior of a nanostructured MnSn2intermetallic used in LIBs. Nanostructured MnSn2is synthesized by reducing Sn and Mn salts using a hot injection method. The resulting MnSn2is characterized by x-ray diffraction and transmission electron microscopy and then is investigated as an anode for LIBs. The MnSn2electrode delivers a stable capacity of 514 mAh g-1after 100 cycles at a C/10 current rate with a Coulombic efficiency >99%. Unlike other Sn-intermetallic anodes, an activation overpotential peak near 0.9 V versus Li is present from the second lithiation and in subsequent cycles. We hypothesize that this effect is likely due to electrolyte reactions with segregated Mn from MnSn2. To prevent these undesirable Mn reactions with the electrolyte, a 5 nm TiO2protection layer is applied onto the MnSn2electrode surface via atomic layer deposition. The TiO2-coated MnSn2electrodes do not exhibit the activation overpotential peak. The protection layer also increases the capacity to 612 mAh g-1after 100 cycles at a C/10 current rate with a Coulombic efficiency >99%. This higher capacity is achieved by suppressing the parasitic reaction of Mn with the electrolyte, as is supported by x-ray photoelectron spectroscopy analysis.

Using hyperspectral imagery to investigate large-scale seagrass cover and genus distribution in a temperate coast.

Seagrasses are regarded as indicators and first line of impact for anthropogenic activities affecting the coasts. The underlying mechanisms driving seagrass cover however have been mostly studied on small scales, making it difficult to establish the connection to seagrass dynamics in an impacted seascape. In this study, hyperspectral airborne imagery, trained from field surveys, was used to investigate broadscale seagrass cover and genus distribution along the coast of Adelaide, South Australia. Overall mapping accuracy was high for both seagrass cover (98%, Kappa = 0.93), and genus level classification (85%, Kappa = 0.76). Spectral separability allowed confident genus mapping in waters up to 10 m depth, revealing a 3.5 ratio between the cover of the dominant Posidonia and Amphibolis. The work identified the absence of Amphibolis in areas historically affected by anthropogenic discharges, which occasionally contained Posidonia and might be recovering. The results suggest hyperspectral imagery as a useful tool to investigate the interplay between seagrass cover and genus distribution at large spatial scales.

Furthering the Understanding of Wechsler Adult Intelligence Scale-Fourth Edition Factor Structure in a Clinical Sample.

The Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV) is a commonly administered battery for assessing intellectual and cognitive abilities. Despite its popularity, construct validation studies primarily utilize the WAIS-IV normative sample rather than ecologically-valid clinical samples. The current study expands the literature on the validity of WAIS-IV by testing a bifactor model in such a sample. We examined archival data from 300 concurrent psychological evaluations performed at a university-based community clinic. Participants received the full WAIS-IV standard battery. Consistent with recent literature, confirmatory factor analyses (CFAs) favored a direct hierarchical model, where the g factor has a direct influence on WAIS-IV subtest performance and index scores explain only modest degrees of residual variance. Results challenge traditional intelligence nosologies and suggest consideration of a two-step method of WAIS-IV interpretation in clinical samples, whereby the Full Scale IQ score (FSIQ) score is examined first and individual subtest scores are analyzed second.

Transcatheter Embolization of the Inferior Epigastric Artery: Technique and Clinical Outcomes.

PURPOSE: Symptomatic rectus muscle sheath hematoma may be the result of bleeding originating from the inferior epigastric artery. We report the technique and the results from a series of consecutive patients treated by transcatheter embolization, evaluating both ipsilateral and contralateral retrograde approaches. METHODS: This was a retrospective study including patients with verified rectus muscle sheath hematoma as a result of active extravasation from the inferior epigastric artery referred for transcatheter embolization. Technical success, clinical success and major complications were calculated. In addition, minor complications, blood transfusions required after a technically successful embolization, length of stay, peri-procedural and 30-day mortality and overall survival at 6 months were obtained. All statistical analysis was performed using SPSS. RESULTS: Twenty-one patients (mean age = 59.67 ± 19.51 years old) were included. The cause of the bleeding in the vast majority was iatrogenic trauma (n = 12/21, 57.14%). Both contralateral (n = 12/21, 57.14%%) and ipsilateral (n = 9/21, 42.86%) retrograde approaches were used. Embolic materials included micro-coils (n = 13/20, 65%), microspheres (PVA) (n = 1/20, 5%), a combination of PVA and micro-coils (n = 5/20, 25%) and gel-foam (n = 1/20, 5%). Overall technical success was 95.2% (n = 20/21) while clinical success was achieved in all but one of the technically successful cases 95% (n = 19/20). One patient died peri-procedurally due to profound hemodynamic shock. There were no other major complications. Additional transfusion was necessary in 7 patients (n = 7/21, 33.33%). There was a significant increase in the hemoglobin levels after the embolization (7.03 ± 1.78 g/dL pre-procedure Vs 10.91 ± 1.7 g/dL post-procedure, p = 0.048). The median hospital stay was 8 days. The peri-procedure and 30-day mortality was 4.8% (n = 1/21) and 28.6% (n = 6/21) respectively. The 6-month survival was 61.9% (13/21). CONCLUSION: Percutaneous embolization of the inferior epigastric artery is a minimally invasive method with satisfactory results. Both ipsilateral and contralateral retrograde approaches are feasible.

The Clinical Significance of Food Addiction.

OBJECTIVES: The construct of food addiction has received increased attention and has been proposed as a mental disorder. There is some evidence that supports the inclusion of food addiction in the psychiatric nosology; however, the construct has not been sufficiently validated for inclusion. This study used the addiction syndrome model as a guiding theoretical framework to understand food addiction. The addiction syndrome model emphasizes the shared antecedents and consequences of addictions even though specific manifestations may differ. METHODS: Participants were adult community members with food addiction (n = 26) or healthy controls (n = 26) as classified by the Yale Food Addiction Scale. Participants completed a battery of self-report questionnaires assessing cognitive, emotional, and behavioral domains often associated with addiction. RESULTS: Results revealed that individuals with food addiction demonstrated significantly higher scores than healthy controls on depressive symptoms, emotion dysregulation, emotional eating, demand characteristics, motives, impulsivity, and family history of mental health problems and addiction, providing support for the clinical significance of food addiction. CONCLUSIONS: Overall, this study replicates and extends previous findings, particularly in regard to behavioral economics and demand for food, providing further support for the consideration of food addiction in the psychiatric nosology.

Antegrade and Retrograde Endoscopic Approaches for Managing Obstructing Ureteral Calculi in Renal Transplant Patients: An Illustrative Case Series.

Purpose: To demonstrate the various antegrade and retrograde endourologic approaches that may be required for effectively treating kidney transplant recipients presenting with ureteral obstruction caused by urolithiasis. Materials and Methods: We prospectively evaluated endoscopic management techniques of renal transplant recipients referred to a national kidney transplant center with obstructing transplant ureteral calculi for a 12-month period (April 2019-April 2020). Results: Four kidney transplant recipients presented with ureteral obstruction caused by urolithiasis and the mean age was 66.6 (range: 62-71) years. The mean duration from renal transplantation was 16 (range: 6-25) years. Three patients presented with acute urosepsis and one patient presented with malaise and recurrent urinary tract infections. Two patients were definitively treated with percutaneous antegrade flexible ureteroscopic lithotripsy through a 16F minipercutaneous nephrolithotomy sheath. Two patients were definitively treated with retrograde flexible ureteroscopy (7F single-use disposable ureteroscope) and laser lithotripsy. Full stone clearance was achieved in all four patients and no perioperative complications occurred. Conclusion: Management of ureteral calculi in renal transplant recipients is challenging. A multimodal approach involving antegrade and retrograde endoscopic techniques may be required to achieve full stone clearance.

Developmental and Sexual Offense Onset Characteristics of Australian Indigenous and Non-Indigenous Male Youth Who Sexually Offend.

The present study sought to address gaps in knowledge concerning Australian Indigenous and non-Indigenous youth who commit sexual offenses. Developmental histories and onset sexual offense characteristics of Indigenous (n = 81) and non-Indigenous (n = 130) adjudicated male youth were compared. Results indicate that, in addition to problems affecting both groups, Indigenous youth in this sample were disproportionately exposed to systemic vulnerabilities (e.g., familial antisocial attitudes and incarceration, engagement with antisocial peers, poor school engagement and voluntary school dropout, low socioeconomic status) associated with onset of sexual offending. Differences in the circumstances and context surrounding the onset sexual offense (e.g., use of drugs/alcohol, relationship to person harmed, co-offending, age of person harmed, location, threats/force) were also found. When these analyses were stratified by age of person harmed, these differences were retained only for offenses against children below 16 years. Together, these findings highlight the need for more contextualized primary-, secondary-, and tertiary-level prevention efforts to reduce youth sexual offending in Australia and elsewhere.