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Background and study aims The aim of this study was to evaluate whether timed barium esophagram within 24 hours post-per-oral endoscopic myotomy (POEM) (TBE-PP) could predict clinical outcomes. Patients and methods This was a single-center retrospective study of prospectively collected data on consecutive patients with ≥ 6-month follow-up who underwent POEM followed by TBE-PP. Esophageal contrast retention 2 minutes after TBE-PP was assessed as Grade 1 ( 90 %). Eckardt score, esophagogastroduodenoscopy (EGD), high-resolution manometry (HRM) and function lumen imaging probe (FLIP) of the esophagogastric junction (EGJ) were obtained at baseline. These tests along with pH testing of antisecretory therapy were repeated 6 and 24 months after POEM. Clinical response by Eckardt score ≤ 3, EGJ-distensibility index (EGJ-DI) > 2.8 mm2/mm Hg, and integrated relaxation pressure (IRP)

Implication Statement The Education Innovation Institute (EII) of Medical College of Georgia, Augusta University, hosted a conference on Twitter about Professional Identity Formation (PIF), #MCGConf2021PIF, on February 25, 2021. The conference featured five presentations by 15 authors from Canada and the U.S. A Twitter conference is a versatile, affordable, and accessible digital option for medical education groups interested in diversifying conference offerings and reaching a broader audience. It was low-cost, organized in six months, and garnered over 9,000 Twitter impressions. Small networks and interest groups can organize Twitter conferences for their constituencies and larger conference organizations can host online mini-conferences to supplement in-person events.

Blastomycosis is a rare fungal infection that frequently involves the skin. Atypical presentations are important to identify, especially in pregnant patients, to initiate appropriate therapy and prevent complications. Uniquely, we describe a case of atypical blastomycosis that presented with painful cutaneous abscesses in a pregnant patient, with dissemination to the central nervous system. The case was successfully treated with liposomal amphotericin B transitioned to voriconazole after delivery without complications for the patient or fetus. Keywords: Blastomycosis, pregnancy, amphotericin B

Radiation-induced morphea (RIM) is a rare and underrecognized complication of radiation therapy that most commonly occurs in women after treatment for breast cancer. Although not fully understood, RIM is hypothesized to arise from an increase in cytokines that stimulate collagen production and extracellular matrix formation. Most documented cases of RIM occur 1 year after radiation therapy and are localized to areas that were treated for breast cancer. We report on a case of a female patient with stage IB endometrial adenocarcinoma who was treated with 24 Gray of adjuvant brachytherapy. The patient developed a diffuse morpheaform, pruritic eruption only at distant sites from the brachytherapy treatment field. Although treatment for RIM is generally unsatisfactory, our patient experienced improvement in the pruritus and a regression of the lesions while applying topical 0.1% tacrolimus ointment and 0.1% triamcinolone creme. An early diagnosis of RIM can prevent extensive workup, guide treatment, and improve quality of life for patients. Keywords: radiation-induced morphea, postirradiation morphea

Background and aims The impact of the advent of an institutional endoscopic eradication therapy (EET) program on surgical practice for Barrett’s esophagus (BE)-associated high grade dysplasia (HGD) or suspected T1a esophageal adenocarcinoma (EAC) is unknown. The aims of this study are to evaluate the different endoscopic modalities used during development of our EET program and factors associated with the use of EET or surgery for these patients after its development. Methods Patients who underwent primary endoscopic or surgical treatment for BE-HGD or early EAC at our hospital between January 1992 and December 2014 were retrospectively identified. They were categorized by their initial modality of treatment during the first year, and the impact over time for choice of therapy was assessed by multivariable logistic regression. Results We identified 386 patients and 80 patients who underwent EET and surgery, respectively. EET included single modality therapy in 254 (66 %) patients and multimodal therapy in 132 (34 %) patients. Multivariable logistic regression showed that, for each subsequent study year, EET was more likely to be performed in patients who were older (P = 0.0009), with shorter BE lengths (P

Background and study aims Data on clinical outcomes of endoscopic drainage of debris-free pseudocysts (PDF) versus pseudocysts containing solid debris (PSD) are very limited. The aims of this study were to compare treatment outcomes between patients with PDF vs. PSD undergoing endoscopic ultrasound (EUS)-guided drainage via transmural stents. Patients and methods Retrospective review of 142 consecutive patients with pseudocysts who underwent EUS-guided transmural drainage (TM) from 2008 to 2014 at 15 academic centers in the United States. Main outcome measures included TM technical success, treatment outcomes (symptomatic and radiologic resolution), need for endoscopic re-intervention at follow-up, and adverse events (AEs). Results TM was performed in 90 patients with PDF and 52 with PSD. Technical success: PDF 87 (96.7 %) vs. PSD 51 (98.1 %). There was no difference in the rates for endoscopic re-intervention (5.5 % in PDF vs. 11.5 % in PSD; P = 0.33) or AEs (12.2 % in PDF vs. 19.2 % in PSD; P = 0.33). Median long-term follow-up after stent removal was 297 days (interquartile range [IQR]: 59 – 424 days) for PDF and 326 days (IQR: 180 – 448 days) for PSD (P = 0.88). There was a higher rate of short-term radiologic resolution of PDF (45; 66.2 %) vs. PSD (21; 51.2 %) (OR = 0.30; 95 % CI: 0.13 – 0.72; P = 0.009). There was no difference in long-term symptomatic resolution (PDF: 70.4 % vs. PSD: 66.7 %; P = 0.72) or radiologic resolution (PDF: 68.9 % vs. PSD: 78.6 %; P = 0.72) Conclusions There was no difference in need for endoscopic re-intervention, AEs or long-term treatment outcomes in patients with PDF vs. PSD undergoing EUS-guided drainage with transmural stents. Based on these results, the presence of solid debris in pancreatic fluid collections does not appear to be associated with a poorer outcome.

Background and study aims: Endoscopic ultrasound – guided celiac plexus block (EUS-CPB) is an established treatment for pain in patients with chronic pancreatitis (CP), but the effectiveness and safety of repeated procedures are unknown. Our objective is to report our experience of repeated EUS-CPB procedures within a single patient. Patients and methods: A prospectively maintained EUS database was retrospectively analyzed to identify patients who had undergone more than one EUS-CPB procedure over a 17-year period. The main outcome measures included number of EUS-CPB procedures for each patient, self-reported pain relief, duration of pain relief, and procedure-related adverse events. Results: A total of 248 patients underwent more than one EUS-CPB procedure and were included in our study. Patients with known or suspected CP (N = 248) underwent a mean (SD) of 3.1 (1.6) EUS-CPB procedures. In 76 % of the patients with CP, the median (range) duration of the response to the first EUS-CPB procedure was 10 (1 – 54) weeks. Lack of pain relief after the initial EUS-CPB was associated with failure of the next EUS-CPB (OR 0.17, 95 %CI 0.06 – 0.54). Older age at first EUS-CPB and pain relief after the first EUS-CPB were significantly associated with pain relief after subsequent blocks (P = 0.026 and P = 0.002, respectively). Adverse events included peri-procedural hypoxia (n = 2) and hypotension (n = 1) and post-procedural orthostasis (n = 2) and diarrhea (n = 4). No major adverse events occurred. Conclusions: Repeated EUS-CPB procedures in a single patient appear to be safe. Response to the first EUS-CPB is associated with response to subsequent blocks.

Breast tumors remain a complex and prevalent health burden impacting millions of individuals worldwide. Challenges in treatment arise from the invasive nature of traditional surgery and, in malignancies, the complexity of treating metastatic disease. The development of noninvasive treatment alternatives is critical for improving patient outcomes and quality of life. This review aims to explore the advancements and applications of focused ultrasound (FUS) technology over the past 2 decades. FUS offers a promising noninvasive, nonionizing intervention strategy in breast tumors including primary breast cancer, fibroadenomas, and metastatic breast cancer., Competing Interests: Disclosure The work of N.D. Sheybani was supported by funding from the National Institutes of Health Director’s Early Independence Award (DP5OD031846) and Wallace H. Coulter Center for Translational Research. The work of Z.E.F. Demir was supported by an NIH Cancer Training Grant (T32 CA009109)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Patient expectations and baseline health are important drivers of outcomes following major genitourinary reconstructive surgery for neurogenic bladder (NGB). Differences in expectations and quality of life (QoL) improvements among different populations with NGB remain insufficiently explored in the literature., Objective: To compare decisional regret (DR) and urinary-related QoL (UrQoL) in patients undergoing urinary diversion for NGB arising from spinal cord injury of acquired (A-SCI) and congenital (C-SCI) etiologies. We hypothesize that patients with A-SCI have higher expectations of improvement in QoL following surgery when compared with C-SCI, which may lead to higher DR and decreased UrQoL, postoperatively., Design: In this cross-sectional survey study, we compared A-SCI to C-SCI in terms of DR, UrQoL, and postoperative changes in self-reported physical health, mental health, and pain using validated patient-reported outcome measures., Setting: Participants were enrolled from a quaternary care institution via mail and MyChart., Participants: The A-SCI group consisted of 17 patients with traumatic spinal cord injury; the C-SCI group was composed of 20 patients with spina bifida., Interventions: Not applicable., Main Outcome Measures: The Decisional Regret Scale, Short form- Qualiveen (SF-Qualiveen), and Patient-reported outcomes measurement Information system-10 (PROMIS-10) Global Health surveys., Results: The A-SCI group displayed poorer preoperative physical health than the C-SCI cohort, but absolute postoperative changes in this score, along with mental health score and pain level, were not significant after adjusting for baseline scores and follow-up time. SF-Qualiveen scores revealed significantly worse impact of NGB in UrQoL for A-SCI than for C-SCI when adjusted for other factors. No differences in DR were seen between the groups., Conclusions: Patients with A-SCI demonstrate lower self-reported baseline physical health compared with patients with C-SCI, which may have implications in setting patient expectations when undergoing urinary diversion. In this small cohort, we found a milder self-reported postoperative impact of NGB in UrQoL in patients with C-SCI., (© 2024 American Academy of Physical Medicine and Rehabilitation.)

Cytokine release syndrome (CRS), commonly known as cytokine storm, is an acute systemic inflammatory response that is a significant global health threat. Interleukin-6 (IL-6) and interleukin-1 (IL-1) are key pro-inflammatory cytokines involved in CRS and are hence critical therapeutic targets. Current antagonists, such as tocilizumab and anakinra, target IL-6R/IL-1R but have limitations due to their long half-life and systemic anti-inflammatory effects, making them less suitable for acute or localized treatments. Here we present the de novo design of small protein antagonists that prevent IL-1 and IL-6 from interacting with their receptors to activate signaling. The designed proteins bind to the IL-6R, GP130 (an IL-6 co-receptor), and IL-1R1 receptor subunits with binding affinities in the picomolar to low-nanomolar range. X-ray crystallography studies reveal that the structures of these antagonists closely match their computational design models. In a human cardiac organoid disease model, the IL-1R antagonists demonstrated protective effects against inflammation and cardiac damage induced by IL-1β. These minibinders show promise for administration via subcutaneous injection or intranasal/inhaled routes to mitigate acute cytokine storm effects., (© 2024. The Author(s).)

Objective: To evaluate urinary outcomes following cystoscopic external urinary sphincter onabotulinumtoxinA (BTX) injections in patients with cerebral palsy (CP). Adults with CP can suffer from bladder outlet obstruction and urinary retention due to a spastic external urethral sphincter ("pseudodysynergia"). We have used BTX injections into the sphincter to relieve the obstruction and allow patients to maintain spontaneous voiding rather than intermittent catheterization., Methods: Patients were included in this retrospective cohort study if they had a diagnosis of CP, were at least 18 years of age, and underwent a urethral external sphincter BTX injection between 2016-2023. The procedure included 100 u or 200 u of BTX mixed in 4cc of saline. Primary outcomes were subjective, patient or caregiver reported changes in retention, lower urinary tract symptoms (LUTS), frequency of recurrent urinary tract infections (UTIs), and hydronephrosis or bladder stones/debris on ultrasound., Results: Fifty patients were included; the majority were male (60%), lived at home with assistance (58%), and had a Gross Motor Function Classification System level of V (50%; ie, severe CP). The most common indications for BTX were retention (96%), LUTS (48%), hydronephrosis (18%), and recurrent UTIs (22%). Post-BTX improvement was seen in 67% of those with LUTS, 65% with retention, 67% with hydronephrosis, and 73% with recurrent UTIs. Most patients underwent repeat injections (60%). There were no significant complications associated with injections., Conclusion: External urethral sphincter BTX is a safe, effective option for treating pseudodysynergia in adults with CP., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2024. Published by Elsevier Inc.)

Vibrational wave-packet dynamics on the ground electronic state of the neutral silver pentamer (Ag 5 ) are studied by femtosecond (fs) pump-probe spectroscopy using the 'negative ion - to neutral - to positive ion' (NeNePo) excitation scheme. A vibrational wave packet is prepared on the 2 A 1 state of Ag 5 via photodetachment of mass-selected, cryogenically cooled Ag 5 - anions using a fs pump pulse. The temporal evolution of the vibrational wave packet is then probed by an ultrafast probe pulse via resonant multiphoton ionization to Ag 5 + . Frequency analysis of the fs NeNePo transients for pump-probe delay times from 0.2 to 8 ps reveals three primary beating frequencies at 157 cm -1 , 101 cm -1 and 56 cm -1 as well as four weaker features. A comparison of these experimentally obtained beating frequencies to harmonic normal mode frequencies calculated from electronic structure calculations confirms that Ag 5 in the gas phase adopts a planar trapezoidal geometry, similar to that previously observed in solid argon. The dependence of the ionization yield on the laser polarization indicates a s-d wave electron photodetachment from a 'p-type' occupied molecular orbital of Ag 5 . Franck-Condon analysis shows that both processes, photodetachment and subsequent photoionization determine the beating frequencies probed in the time-dependent cation yield. The present study extends the applicability of fs NeNePo spectroscopy to characterize the vibrational spectra in the far-IR frequency range in the absence of perturbations from a medium or a messenger atom to mass-selected neutral metal clusters with more than three atoms in the ground electronic states.

Objective: To evaluate outcomes of inflatable-penile-prosthesis (IPP) implantation after radical-cystectomy compared to other etiologies of erectile dysfunction., Materials and Methods: All IPPs within the past 20 years in a large regional health system were reviewed, and erectile dysfunction (ED) etiology was determined as radical-cystectomy, radical-prostatectomy, or organic/other ED. Cohorts were generated by 1:3 propensity score match using age, body mass index, and diabetes status. Baseline demographics and relevant comorbidities were evaluated. Clavien-Dindo complications, grade, and reoperation were assessed. Multivariable logarithmic regression was used to identify the predictors of 90-day complications following IPP implantation. Log-rank analysis was used to assess the time-to-reoperation after IPP implantation in patients with a history of cystectomy compared with noncystectomy etiologies., Results: Of 2600 patients, 231 subjects were included in the study. Comparing patients undergoing IPP for cystectomy vs pooled noncystectomy indications, those who underwent radical-cystectomy had a higher overall complication rate (24% vs 9%, p = 0.02). Clavien-Dindo complication grades did not differ across groups. Reoperation was significantly more common following cystectomy (cystectomy: 21% vs noncystectomy: 7%, p = 0.01), however time to reoperation did not differ significantly by indication (cystectomy: 8 years vs noncystectomy: 10 years,p = 0.09). Among cystectomy patients, 85% of reoperations were due to mechanical failure., Conclusion: Compared to other erectile dysfunction etiologies, patients undergoing IPP with a history of cystectomy have an increased risk of complications within 90-days of implantation and need for surgical device revision, but no greater risk for high-grade complications. Overall IPP remains a valid treatment option after cystectomy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

High-resolution photoelectron spectra of vibrationally pre-excited vinoxide anions (CH 2 CHO - ) are reported using the recently developed IR-cryo-SEVI technique. This method is combined with a newly developed implementation of vibrational perturbation theory that can readily identify relevant anharmonic couplings among nearly degenerate vibrational states. IR-cryo-SEVI spectra are obtained by resonant infrared excitation of vinoxide anions via the fundamental C-O (ν 4 , 1566 cm -1 ) or isolated C-H (ν 3 , 2540 cm -1 ) stretching vibrations prior to photodetachment. Excitation of the ν 4 mode leads to a well-resolved photoelectron spectrum that is in excellent agreement with a harmonic Franck-Condon simulation. Excitation of the higher-energy ν 3 mode results in a more complicated spectrum that requires consideration of the calculated anharmonic resonances in both the anion and the neutral. From this analysis, information about the zeroth-order states that contribute to the nominal ν 3 wave function in the anion is obtained. In the neutral, we observe anharmonic splitting of the ν 3 fundamental into a polyad feature with peaks at 2737(22), 2 835(18), and 2910(12) cm -1 , for which only the center frequency has been previously reported. Overall, 9 of the 12 fundamental frequencies of the vinoxy radical are extracted from the IR-cryo-SEVI and ground-state cryo-SEVI spectra, most of which are consistent with previous measurements. However, we provide a new estimate of the ν 5 (CH 2 scissoring) fundamental frequency at 1395(11) cm -1 and attribute the discrepancy with previously reported values to a Fermi resonance with the 2ν 11 overtone (CH 2 wagging).

General approaches for designing sequence-specific peptide-binding proteins would have wide utility in proteomics and synthetic biology. However, designing peptide-binding proteins is challenging, as most peptides do not have defined structures in isolation, and hydrogen bonds must be made to the buried polar groups in the peptide backbone 1-3 . Here, inspired by natural and re-engineered protein-peptide systems 4-11 , we set out to design proteins made out of repeating units that bind peptides with repeating sequences, with a one-to-one correspondence between the repeat units of the protein and those of the peptide. We use geometric hashing to identify protein backbones and peptide-docking arrangements that are compatible with bidentate hydrogen bonds between the side chains of the protein and the peptide backbone 12 . The remainder of the protein sequence is then optimized for folding and peptide binding. We design repeat proteins to bind to six different tripeptide-repeat sequences in polyproline II conformations. The proteins are hyperstable and bind to four to six tandem repeats of their tripeptide targets with nanomolar to picomolar affinities in vitro and in living cells. Crystal structures reveal repeating interactions between protein and peptide interactions as designed, including ladders of hydrogen bonds from protein side chains to peptide backbones. By redesigning the binding interfaces of individual repeat units, specificity can be achieved for non-repeating peptide sequences and for disordered regions of native proteins., (© 2023. The Author(s).)

Objective: Among patients with a history of ESBL infection, uncertainty remains regarding whether all of these patients require ESBL-targeted therapy when presenting with a subsequent infection. We sought to determine the risks associated with a subsequent ESBL infection to help inform empiric antibiotic decisions., Methods: A retrospective cohort study of adult patients with positive index culture for Escherichia coli or Klebsiella pneumoniae (EC/KP) receiving medical care during 2017 was conducted. Risk assessments were performed to identify factors associated with subsequent infection caused by ESBL-producing EC/KP., Results: In total, 200 patients were included in the cohort, 100 with ESBL-producing EC/KP and 100 with ESBL-negative EC/KP. Of 100 patients (50%) who developed a subsequent infection, 22 infections were ESBL-producing EC/KP, 43 were other bacteria, and 35 had no or negative cultures. Subsequent infection caused by ESBL-producing EC/KP only occurred when the index culture was also ESBL-producing (22 vs 0). Among those with ESBL-producing index culture, the incidences of subsequent infection caused by ESBL-producing EC/KP versus other bacterial subsequent infection were similar (22 vs 18; P = .428). Factors associated with subsequent infection caused by ESBL-producing EC/KP include history of ESBL-producing index culture, time ≤180 days between index culture and subsequent infection, male sex, and Charlson comorbidity index score >3., Conclusions: History of ESBL-producing EC/KP culture is associated with subsequent infection caused by ESBL-producing EC/KP, particularly within 180 days after the historical culture. Among patients presenting with infection and a history of ESBL-producing EC/KP, other factors should be considered in making empiric antibiotic decisions, and ESBL-targeted therapy may not always be warranted., Competing Interests: All authors report no conflicts of interest relevant to this article., (© The Author(s) 2023.)

The transition state of a chemical reaction is a dividing surface on the reaction potential energy surface (PES) between reactants and products and is thus of fundamental interest in understanding chemical reactivity. The transient nature of the transition state presents challenges to its experimental characterization. Transition-state spectroscopy experiments based on negative-ion photodetachment can provide a direct probe of this region of the PES, revealing the detailed vibrational structure associated with the transition state. Here we study the F + NH 3  → HF + NH 2 reaction using slow photoelectron velocity-map imaging spectroscopy of cryogenically cooled FNH 3 - anions. Reduced-dimensionality quantum dynamical simulations performed on a global PES show excellent agreement with the experimental results, enabling the assignment of spectral structure. Our combined experimental-theoretical study reveals a manifold of vibrational Feshbach resonances in the product well of the F + NH 3 PES. At higher energies, the spectra identify features attributed to resonances localized across the transition state and into the reactant complex that may impact the bimolecular reaction dynamics., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

De novo enzyme design has sought to introduce active sites and substrate-binding pockets that are predicted to catalyse a reaction of interest into geometrically compatible native scaffolds 1,2 , but has been limited by a lack of suitable protein structures and the complexity of native protein sequence-structure relationships. Here we describe a deep-learning-based 'family-wide hallucination' approach that generates large numbers of idealized protein structures containing diverse pocket shapes and designed sequences that encode them. We use these scaffolds to design artificial luciferases that selectively catalyse the oxidative chemiluminescence of the synthetic luciferin substrates diphenylterazine 3 and 2-deoxycoelenterazine. The designed active sites position an arginine guanidinium group adjacent to an anion that develops during the reaction in a binding pocket with high shape complementarity. For both luciferin substrates, we obtain designed luciferases with high selectivity; the most active of these is a small (13.9 kDa) and thermostable (with a melting temperature higher than 95 °C) enzyme that has a catalytic efficiency on diphenylterazine (k cat /K m  = 10 6  M -1  s -1 ) comparable to that of native luciferases, but a much higher substrate specificity. The creation of highly active and specific biocatalysts from scratch with broad applications in biomedicine is a key milestone for computational enzyme design, and our approach should enable generation of a wide range of luciferases and other enzymes., (© 2023. The Author(s).)

Objective: To document the incidence, risk factors, and prevalence of sacral insufficiency fractures (SIF) among patients who have undergone total pubectomy for osteomyelitis., Methods: A retrospective chart review was performed of patients undergoing total pubectomy for osteomyelitis at a single institution from 2016 to 2021. Descriptive statistics and univariate analysis were performed using the Wilcoxon rank-sum test and Fisher exact test as appropriate., Results: Sixteen patients underwent total pubectomy for osteomyelitis. The median age was 68 years. 12 of 16 (75%) had previously received pelvic radiotherapy. The median BMI was 27.8 kg/m2. Eleven (68.75%) had postoperative pelvic imaging, of which 3 (27.3%) had a new SIF. One other patient had a SIF 3 days before pubectomy. Three SIFs were detected via MRI and 1 by CT scan. The median BMI of patients with SIF was significantly lower than those without SIF (22.4 vs 30.5, P = .004). All patients with SIF presented with new pelvic or perineal pain without radiculopathy. Symptoms resolved for three patients with non-opioid analgesics, physical therapy, and/or a brief trial of opioids., Conclusion: Sacral insufficiency fracture is a rare sequela of total pubectomy for osteomyelitis. Lower BMI is significantly associated with SIF perhaps due to reduced muscle mass or poor bone condition and, as a result, baseline pelvic instability. Medical management should be first-line therapy., (Copyright © 2022. Published by Elsevier Inc.)

High-resolution photoelectron spectra of cryogenically cooled acetyl anions (CH 3 CO - ) obtained using slow photoelectron velocity-map imaging are reported. The high resolution of the photoelectron spectrum yields a refined electron affinity of 0.4352 ± 0.0012 eV for the acetyl radical as well as the observation of a new vibronic structure that is assigned based on ab initio calculations. Three vibrational frequencies of the neutral radical are measured to be 1047 ± 3 cm -1 (ν 6 ), 834 ± 2 cm -1 (ν 7 ), and 471 ± 1 cm -1 (ν 8 ). This work represents the first experimental measurement of the ν 6 frequency of the neutral. The measured electron affinity is used to calculate a refined value of 1641.35 ± 0.42 kJ mol -1 for the gas-phase acidity of acetaldehyde. Analysis of the photoelectron angular distributions provides insight into the character of the highest occupied molecular orbital of the anion, revealing a molecular orbital with strong d-character. Additionally, details of a new centroiding algorithm based on finite differences, which has the potential to decrease data acquisition times by an order of magnitude at no cost to accuracy, are provided.

Assessments of the status of tidal flats, one of the most extensive coastal ecosystems, have been hampered by a lack of data on their global distribution and change. Here we present globally consistent, spatially-explicit data of the occurrence of tidal flats, defined as sand, rock or mud flats that undergo regular tidal inundation. More than 1.3 million Landsat images were processed to 54 composite metrics for twelve 3-year periods, spanning four decades (1984-1986 to 2017-2019). The composite metrics were used as predictor variables in a machine-learning classification trained with more than 10,000 globally distributed training samples. We assessed accuracy of the classification with 1,348 stratified random samples across the mapped area, which indicated overall map accuracies of 82.2% (80.0-84.3%, 95% confidence interval) and 86.1% (84.2-86.8%, 95% CI) for version 1.1 and 1.2 of the data, respectively. We expect these maps will provide a means to measure and monitor a range of processes that are affecting coastal ecosystems, including the impacts of human population growth and sea level rise., (© 2022. The Author(s).)

We designed a protein biosensor that uses thermodynamic coupling for sensitive and rapid detection of neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in serum. The biosensor is a switchable, caged luciferase-receptor-binding domain (RBD) construct that detects serum-antibody interference with the binding of virus RBD to angiotensin-converting enzyme 2 (ACE-2) as a proxy for neutralization. Our coupling approach does not require target modification and can better distinguish sample-to-sample differences in analyte binding affinity and abundance than traditional competition-based assays., (© 2022. The Author(s).)

High-resolution anion photoelectron spectra of cryogenically cooled NiO 2 - anions, obtained using slow photoelectron velocity-map imaging (cryo-SEVI), are presented in tandem with coupled cluster electronic structure calculations including relativistic effects. The experimental spectra encompass the X̃ 1 Σ g + ← X̃ 2 Π g , ã 3 Π g ← X̃ 2 Π g , and à 1 Π g ← X̃ 2 Π g photodetachment transitions of linear ONiO 0/- , revealing previously unobserved vibrational structure in all three electronic bands. The high-resolution afforded by cryo-SEVI allows for the extraction of vibrational frequencies for each state, consistent with those previously measured in the ground state and in good agreement with scalar-relativistic coupled-cluster calculations. Previously unobserved vibrational structure is observed in the ã 3 Π g and à 1 Π g states and is tentatively assigned. Further, a refined electron affinity of 3.0464(7) eV for NiO 2 is obtained as well as precise term energies for the ã and à states of NiO 2 of 0.3982(7) and 0.7422(10) eV, respectively. Numerous Franck-Condon forbidden transitions involving the doubly degenerate ν 2 bending mode are observed and ascribed to Herzberg-Teller coupling to an excited electronic state.

Function follows form in biology, and the binding of small molecules requires proteins with pockets that match the shape of the ligand. For design of binding to symmetric ligands, protein homo-oligomers with matching symmetry are advantageous as each protein subunit can make identical interactions with the ligand. Here, we describe a general approach to designing hyperstable C2 symmetric proteins with pockets of diverse size and shape. We first designed repeat proteins that sample a continuum of curvatures but have low helical rise, then docked these into C2 symmetric homodimers to generate an extensive range of C2 symmetric cavities. We used this approach to design thousands of C2 symmetric homodimers, and characterized 101 of them experimentally. Of these, the geometry of 31 were confirmed by small angle X-ray scattering and 2 were shown by crystallographic analyses to be in close agreement with the computational design models. These scaffolds provide a rich set of starting points for binding a wide range of C2 symmetric compounds.

The design of proteins that bind to a specific site on the surface of a target protein using no information other than the three-dimensional structure of the target remains a challenge 1-5 . Here we describe a general solution to this problem that starts with a broad exploration of the vast space of possible binding modes to a selected region of a protein surface, and then intensifies the search in the vicinity of the most promising binding modes. We demonstrate the broad applicability of this approach through the de novo design of binding proteins to 12 diverse protein targets with different shapes and surface properties. Biophysical characterization shows that the binders, which are all smaller than 65 amino acids, are hyperstable and, following experimental optimization, bind their targets with nanomolar to picomolar affinities. We succeeded in solving crystal structures of five of the binder-target complexes, and all five closely match the corresponding computational design models. Experimental data on nearly half a million computational designs and hundreds of thousands of point mutants provide detailed feedback on the strengths and limitations of the method and of our current understanding of protein-protein interactions, and should guide improvements of both. Our approach enables the targeted design of binders to sites of interest on a wide variety of proteins for therapeutic and diagnostic applications., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Background: Penile prosthesis surgeons face an ethical dilemma when confronted with a sex offender who seeks surgical management of erectile dysfunction., Aim: To provide practice guidelines to screen and manage patients with a history of sexual violence prior to surgery., Methods: Three urologists with expertise in penile prosthesis surgery and 1 medical bioethicist were asked to contribute their opinions and provide recommendations to address this controversial topic., Outcomes: Expert opinion supported by analysis of available literature and institutional experience., Results: The authors review current United States legislation, published literature on sex offender registration, and institutional data on the prevalence of sex offenders among men seeking penile prosthesis placement. Within a context established by medical bioethical principles, the authors propose a practice guideline for screening sex offenders prior to penile implantation surgery and referral for trained psychological evaluation prior to surgical management., Strengths & Limitations: Strengths: multidisciplinary approach in data acquisition including bioethical and legal review., Limitations: Lack of available evidence regarding recidivism risk in sex offenders who undergo penile prosthesis placement., Conclusion: Sex offenders exist among the population of patients seeking surgical placement of a penile prosthesis. A standardized practice guideline for management of this population should be employed with the intention to reduce future harm. Zhang JH, DeWitt-Foy M, Jankowski J, et al. The Dilemma of Penile Prosthesis Implantation in Sex Offenders. J Sex Med 2021;18:1826-1829., (Copyright © 2021 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Eutrophication is an emerging global issue associated with increasing anthropogenic nutrient loading. The impacts and extent of eutrophication are often limited to regions with dedicated monitoring programmes. Here we introduce the first global and Google Earth Engine-based interactive assessment tool of coastal eutrophication potential (CEP). The tool evaluates trends in satellite-derived chlorophyll-a (CHL) to devise a global map of CEP. Our analyses suggest that, globally, coastal waters (depth ≤200 m) covering ∼1.15 million km 2 are eutrophic potential. Also, waters associated with CHL increasing trends-eutrophication potential-are twofold higher than those showing signs of recovery. The tool effectively identified areas of known eutrophication with severe symptoms, like dead zones, as well as those with limited to no information of the eutrophication. Our tool introduces the prospect for a consistent global assessment of eutrophication trends with major implications for monitoring Sustainable Development Goals (SDGs) and the application of Earth Observations in support of SDGs., (© 2021. The Author(s).)

Electronically excited NdO is a possible product of the chemistry associated with the release of Nd into the ionosphere, and emission from these states may contribute to the observations following such experiments. To better characterize the energetics and spectroscopy of NdO, we report a combined experimental and theoretical study using slow photoelectron velocity-map imaging spectroscopy of cryogenically cooled NdO - anions (cryo-SEVI) supplemented by wave function-based quantum-chemical calculations. Using cryo-SEVI, we measure the electron affinity of NdO to be 1.0091(7) eV and resolve numerous transitions to low-lying electronic and vibrational states of NdO that are assigned with the aid of the electronic structure calculations. Additionally, temperature-dependent data suggest contributions from the (2)4.5 state of NdO - residing 2350 cm -1 above the ground anion state. Photodetachment to higher-lying excited states of NdO is also reported, which may help to clarify observations from prior release experiments.

The effect of vibrational pre-excitation of anions on their photoelectron spectra is explored, combining slow photoelectron velocity-map imaging of cryogenically cooled anions (cryo-SEVI) with tunable IR radiation to pre-excite the anions. This new IR cryo-SEVI method is applied to OH - as a test system, where the R(0) transition of the hydroxyl anion (3591.53 cm -1 ) is pumped. Vibrational excitation induces a 30% depletion in photodetachment signal from the v = 0, J = 0 ground state of the anion and the appearance of all five allowed, rotationally resolved photodetachment transitions from the OH - ( v = 1, J = 1) level, each with peak widths between 1 and 2 cm -1 . By scanning the IR laser, IR cryo-SEVI can also serve as a novel action technique to obtain the vibrational spectrum of OH - , giving an experimental value for the R(0) transition of 3591(1.2) cm -1 .

The Breast Cancer Gene (BRCA) confers an 8.6-fold higher risk of developing prostate cancer in men ≤ 65 years of age and portends a worse prognosis as compared to noncarriers even in patients with low volume, localized disease. The BRCA2 gene, in particular, imparts a more biologically aggressive form of prostate cancer and a higher prostate cancer specific mortality. From a treatment standpoint, this translates to worse overall clinical outcomes for such patients. The most appropriate screening and management strategy for germline BRCA mutation carriers with prostate cancer is not known. Herein, we present an incidentally discovered prostate cancer in a 61-year-old BRCA1 and BRCA2 germline mutation carrier who was screened and managed using an individualized treatment approach., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: To assess whether prior interventional treatment for benign prostatic hyperplasia (BPH) influences oncologic or functional outcomes following primary whole-gland prostate cryoablation., Methods: Among 3831 men with prostate cancer who underwent primary whole-gland prostate cryoablation, we identified 160 with a history of prior BPH interventional therapy including transurethral needle ablation (n = 6), transurethral microwave thermotherapy (n = 9), or transurethral resection of the prostate (n = 145). Patients with a history of medically treated or unspecified BPH therapy were excluded from the study. Oncological and functional outcomes were compared between men with and without prior BPH interventional therapy., Results: In unadjusted analyses, prior interventional BPH therapy was associated with higher risks of postoperative urinary retention (17.5% vs. 9.6%, p = 0.001) and new-onset urinary incontinence (39.9% vs. 19.4%, p > 0.001) compared with no prior therapy. Interventional BPH therapy was not correlated with the risk of developing a rectourethral fistula (p = 0.84) or new-onset erectile dysfunction (ED) at 12 months (p = 0.08) following surgery. On multivariable regression, prior interventional BPH therapy was associated with increased risk of urinary retention (OR 1.9, 95%, p = 0.015) and new-onset urinary incontinence (OR 2.13, p < 0.001). The estimated 5 years Kaplan-Meier survival analysis showed no statistically significant difference (p = 0.3) in biochemical progression free survival between those who underwent interventional BPH therapy compared with those who did not. Local disease recurrence assessed by post cryoablation positive for-cause prostate biopsy showed no significant difference between the two groups (25.4% vs. 28.7%, p = 0.59)., Conclusions: Prior interventional BPH therapy did not affect the oncologic outcomes nor did it increase the risk of rectourethral fistula or ED in sexually performing patients prior to cryosurgery. Prior interventional BPH therapy was associated with increased risk of urinary retention and incontinence after primary whole-gland prostate cryoablation for prostate cancer.

During the COVID-19 pandemic, the antimicrobial stewardship module in our electronic medical record was reconfigured for the management of COVID-19 patients. This change allowed our subspecialist providers to review charts quickly to optimize potential therapy and management during the patient surge.

Fecal microbiota transplantation (FMT) is an alternative treatment option with minimal risk for patients with Crohn disease. This article explains FMT and how it effectively targets the gut microbiota changes associated with the pathogenesis of Crohn disease.

The decoy exon model has been proposed to regulate a subset of intron retention (IR) events involving predominantly larger introns (>1 kb). Splicing reporter studies have shown that decoy splice sites are essential for activity, suggesting that decoys act by engaging intron-terminal splice sites and competing with cross-intron interactions required for intron excision. The decoy model predicts that antisense oligonucleotides may be able to block decoy splice sites in endogenous pre-mRNA, thereby reducing IR and increasing productive gene expression. Indeed, we now demonstrate that targeting a decoy 5' splice site in the O-GlcNAc transferase ( OGT ) gene reduced IR from ∼80% to ∼20% in primary human erythroblasts, accompanied by increases in spliced OGT RNA and OGT protein expression. The remaining OGT IR was refractory to antisense treatment and might be mediated by independent mechanism(s). In contrast, other retained introns were strongly dependent on decoy function, since antisense targeting of decoy 5' splice sites greatly reduced ( SNRNP70 ) or nearly eliminated ( SF3B1 ) IR in two widely expressed splicing factors, and also greatly reduced IR in transcripts encoding the erythroid-specific structural protein, α-spectrin ( SPTA1 ). These results show that modulating decoy exon function can dramatically alter IR and suggest that dynamic regulation of decoy exons could be a mechanism to fine-tune gene expression post-transcriptionally in many cell types., (© 2020 Parra et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.)

Objective: To examine whether men who were childless at the time of vasectomy sought consultation for fertility restoration., Methods: Retrospective chart review was performed to determine if patients without children at the time of vasectomy sought consultation for fertility restoration (defined as vasectomy reversal or sperm retrieval). If the patient had not been seen in our healthcare system within the previous 12 months, he was contacted by phone to determine whether he had sought consultation for fertility restoration., Results: Of 1656 men, 68 men (4.1%) were childless at the time of vasectomy. Fifteen patients were excluded as they were not followed in our hospital system and were unreachable by phone. Zero patients sought consultation for fertility restoration., Conclusion: Our single institution study demonstrated that no men who were childless at the time of vasectomy sought consultation for fertility restoration. Given that there are no other FDA approved methods for nonbarrier sterilization for males, men with no children at the time of vasectomy should receive the same AUA guideline-recommended counseling that men with children receive., (Copyright © 2019 Elsevier Inc. All rights reserved.)

High-resolution anion photoelectron spectra of cryogenically cooled NO 3 ̅ anions obtained using slow photoelectron velocity-map imaging are presented and provide new insight into the vibronic structure of the corresponding neutral radical. A combination of improved spectral resolution, measurement of energy-dependent intensity effects, temperature control, and comparison to theory allows for full assignment of the vibronic features observed in this spectrum. We obtain a refined electron affinity of 3.9289(14) eV for NO 3 . Further, the appearance of Franck-Condon forbidden transitions from vibrationally cold anions to neutral states with excitation along the NO 3 ν 4 mode confirms that these features arise from vibronic coupling with the B̃ 2 E' excited state of NO 3 and are not hot bands, as has been suggested. Together, the suite of experimental and simulated results provides clear evidence that the ν 3 fundamental of NO 3 resides near 1050 cm -1 , addressing a long-standing controversy surrounding this vibrational assignment.

Emission measurements of black carbon (BC) mass were conducted on a T63 turboshaft engine, operated at idle and cruise power with conventional and alternative fuels, using an Artium LII-300 laser-induced incandescence analyzer (LII) and AVL model 483 micro soot sensor (MSS) photoacoustic instrument using the manufacturer's calibration for both instruments. These measurements were compared with elemental carbon (EC) determined by manual and semicontinuous thermal-optical transmission analyses according to National Institute for Occupational Safety and Health (NIOSH) method 5040 as the reference method. The results indicate that both the LII and MSS instruments show good linear correlation with EC for the two fuels and two engine power conditions evaluated. The LII measurements were observed to be biased high (27-49%) and the MSS measurements were biased low (24-35%) relative to EC. The agreement between the instruments and the reference method was substantially improved by applying a calibration of the instruments against a common BC aerosol source. Test data also suggest that the two instruments show some sensitivity to particle size (or properties related to size), specifically for particles with a geometric mean diameter (GMD) <30 nm. This sensitivity is problematic, since new engines or certain combustion conditions in current engines will produce smaller particles compared with the T63 model tested in this study. Further assessments of instrument performance for particles within this size range are therefore warranted. Implications: Accurate black carbon emission measurements are needed to certify new and in-production commercial aircraft engines. Both the Artium LII-300 and AVL 483 micro soot sensor are currently approved by the International Civil Aviation Organization for this purpose. This study compares the two instruments against elemental carbon (EC) using NIOSH method 5040 as the reference using a T63 turboshaft engine. The results indicate that both instruments correlate reasonably well with EC, and the correlation substantially improved when applying a calibration against a common aerosol source. Sensitivity to particle size may be an issue for both instruments.

Objectives: To determine the total numbers of privileged and full-time equivalent intensivists in acute care hospitals with intensivists and compare the characteristics of hospitals with and without intensivists., Design: Retrospective analysis of the American Hospital Association Annual Survey Database (Fiscal Year 2015)., Setting: Two-thousand eight-hundred fourteen acute care hospitals with ICU beds., Patients: None., Interventions: None., Measurements and Main Results: Of the 2,814 acute care hospitals studied, 1,469 (52%) had intensivists and 1,345 (48%) had no intensivists. There were 28,808 privileged and 19,996 full-time equivalent intensivists in the 1,469 hospitals with intensivists. In these hospitals, the median (25-75th percentile) numbers of privileged and full-time equivalent intensivists were 11 (5-24) and 7 (2-17), respectively. Compared with hospitals without intensivists, hospitals with privileged intensivists were primarily located in metropolitan areas (91% vs 50%; p < 0.001) and at the aggregate level had nearly thrice the number of hospital beds (403,522 [75%] vs 137,146 [25%]), 3.6 times the number of ICU beds (74,222 [78%] vs 20,615 [22%]), and almost twice as many ICUs (3,383 [65%] vs 1,846 [35%]). At the hospital level, hospitals with privileged intensivists had significantly more hospital beds (median, 213 vs 68; p < 0.0001), ICU beds (median, 32 vs 8; p < 0.0001), a higher ratio of ICU to hospital beds (15.6% vs 12.6%; p < 0.0001), and a higher number of ICUs per hospital (2 vs 1; p < 0.0001) than hospitals without intensivists., Conclusions: Analyzing the intensivist section of the American Hospital Association Annual Survey database is a novel approach to estimating the numbers of privileged and full-time equivalent intensivists in acute care hospitals with ICU beds in the United States. This methodology opens the door to an enhanced understanding of the current supply and distribution of intensivists as well as future research into the intensivist workforce.