Disentangling Competitive and Synergistic Chemical Reactivities During the Seeded Growth of High-Entropy Alloys on High-Entropy Metal Sulfide Nanoparticles.

The seeded growth of one type of nanoparticle on the surface of another is foundational to synthesizing many multifunctional nanostructures. High-entropy nanoparticles that randomly incorporate five or more elements offer enhanced properties due to synergistic interactions. Incorporating high-entropy nanoparticles into seeded growth platforms is essential for merging their unique properties with the functional enhancements that arise from particle-particle interactions. However, the complex compositions of high-entropy materials complicate the seeded growth process due to competing particle growth and chemical reactivity pathways. Here, we design and synthesize a 36-member nanoparticle library to identify and disentangle these competitive interactions, ultimately defining chemical characteristics that underpin the seeded growth of high-entropy alloys on high-entropy metal sulfide nanoparticles. As a model system, we focus on (Cu,Zn,Co,In,Ga)S-SnPdPtRhIr, which combines a high-entropy metal sulfide semiconductor with a high-entropy alloy catalyst. We study the seeded growth of all possible pairwise combinations of Sn, Pd, Pt, Rh, Ir, and SnPdPtRhIr on the metal sulfides Cu1.8S, ZnS, Co9S8, CuInS2, CuGaS2, and (Cu,Zn,Co,In,Ga)S, which have comparable morphologies and sizes. Through these studies, we uncover unexpected chemical reactivities, including cation exchange, redox reactions, and diffusion. Reaction temperature, threshold reduction potentials, metal/sulfide chemical reactivity, and the relative strengths of the various bonds that could be formed during particle growth emerge as the primary factors that underpin seeded growth. Finally, we disentangle these competitive and synergistic chemical reactivities to generate a reactivity map that provides practical guidelines for achieving seeded growth in compositionally complex systems.

Simultaneous quantification of five antiretrovirals in human tissues using ultra-high performance liquid chromatography-tandem mass spectrometry methods for therapeutic drug monitoring at the sites of action.

Although antiretroviral therapy (ART) is highly effective for the treatment of HIV-1 infection to suppress virus in the blood, HIV persists in tissues. HIV persistence in the tissues is due to numerous factors, and one of those factors are antiretroviral (ARV) concentrations. ARV concentrations in tissues must be adequate to suppress HIV at the sites of action. While therapeutic drug monitoring in the plasma is well-known, drug monitoring in the tissues provides local assessments of adequate ARV exposure to prevent localized HIV resistance formation. Towards these efforts, we validated an ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS/MS) method in human tissues (cervical, rectal, and vaginal tissues) for the simultaneous quantification of five ARVs: bictegravir, cabotegravir, dolutegravir, doravirine, and raltegravir. For this assay, protein precipitation with acetonitrile with stable, isotopically-labeled internal standards followed by supernatant pre-concentration was performed. Analyte separation was accomplished using a multistep UPLC gradient mixture of 0.1 % formic acid in water (A) and acetonitrile (B) with a Waters Cortecs T3 (2.1x100 mm) column. The assay was extensively validated as per the United States Food and Drug Administration Bioanalytical Method Validation Guidance over a clinically observed range (0.05-50 ng/mL) with superb linearity (R2 > 0.99 across all ARVs). The assay run time was 8.5 min. This analytical method achieves appropriate performance of trueness (85.5-107.4 %), repeatability, and precision (CV < 15 %). Our method will be employed for the therapeutic monitoring of guideline-recommended ARVs in human tissues for monitoring therapeutic efficacy in HIV treatment and prevention research efforts.

Synthetic Roadmap to a Large Library of Colloidal High-Entropy Rare Earth Oxyhalide Nanoparticles Containing up to Thirteen Metals.

Nanoparticles of high-entropy materials that incorporate five or more elements randomized on a crystalline lattice often exhibit synergistic properties that can be influenced by both the identity and number of elements combined. These considerations are especially important for structurally and compositionally complex materials such as multimetal multianion compounds, where cation and anion mixing can influence properties in competitive and contradictory ways. Here, we demonstrate the synthesis of a large library of colloidal high-entropy rare earth oxyhalide (REOX) nanoparticles. We begin with the synthesis of (LaCePrNdSmEuGdDyHoErYbScY)OCl, which homogeneously incorporates 13 distinct rare earth elements. Through time point studies, we find that (LaNdSmGdDy)OCl, a 5-metal analogue, forms through in situ generation of compositionally segregated core@shell@shell intermediates that convert to homogeneously mixed products through apparent core-shell interdiffusion. Assuming that all possible combinations of 5 through 13 rare earth metals are synthetically accessible, we propose the existence of a 7099-member REOCl nanoparticle library, of which we synthesize and characterize 40 distinct members. We experimentally validate the incorporation of a large number of rare earth elements using energy dispersive X-ray spectra, despite closely spaced and overlapping X-ray energy lines, using several fingerprint matching strategies to uniquely correlate experimental and simulated spectra. We confirm homogeneous mixing by analyzing elemental distributions in high-entropy nanoparticles versus physical mixtures of their constituent compounds. Finally, we characterize the band gaps of the 5- and 13-metal REOCl nanoparticles and find a significantly narrowed band gap, relative to the constituent REOCl phases, in (LaCePrNdSmEuGdDyHoErYbScY)OCl but not in (LaNdSmGdDy)OCl.

Defining Patient Satisfaction after Reverse Total Shoulder Arthroplasty: A Systematic Review.

BACKGROUND: The prevalence of reverse total shoulder arthroplasty (rTSA) has grown rapidly. As indications for the procedure expand, the proportion of patients who have satisfactory outcomes after rTSA has not been well defined. This systematic literature review explores overall patient satisfaction after rTSA and defines patient satisfaction based on indication for surgery. METHODS: A literature search was performed for studies describing patient satisfaction after rTSA in accordance with Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Papers were included if they investigated patient satisfaction after rTSA at a minimum of 2-year follow-up. Data were collected on patient demographics, including age, gender, and body mass index (BMI). Follow-up duration, indication for surgery, and patient reported outcome measures (PROMs) relating to patient satisfaction were also recorded. RESULTS: There were a total of 5234 patients and 5288 shoulders from the 45 included studies. The overall study population was 61.2% female and the average age was 71.1 years (range 23-99). Satisfaction results were recorded at final follow-up, with average follow-up of 49.1 months (range 24-228). Overall patient satisfaction ranged from 77.7 to 87.8%, depending on patient satisfaction PROMs. When stratified by diagnosis, patients with a diagnosis of glenohumeral osteoarthritis (GHOA) rated better satisfaction on all metrics when compared to patients with a diagnosis of cuff tear arthropathy (CTA) or massive rotator cuff tear (MRCT). CONCLUSION: This systematic review demonstrated that patients who undergo rTSA for either GHOA, CTA, or MRCT are generally satisfied with their procedure, with the rate of satisfaction highest in GHOA. Focusing on patient satisfaction may provide the best overall assessment of health care quality in a very understandable and tangible form. Overall satisfaction rate is valuable information for patient education and can be utilized as part of effective surgical counseling.

How does pretreatment expectancy influence pain outcomes with electroacupuncture and battlefield acupuncture in cancer survivors?: Pretreatment expectancy and pain reduction by acupuncture.

Background: Outcome expectancy is an important component of non-specific effect that may play an important role in pain research and clinical care. We sought to evaluate whether pretreatment expectancy predicts pain reduction in cancer survivors receiving electroacupuncture (EA) or battlefield acupuncture (BFA). Methods: We analyzed data from a randomized clinical trial that compared EA and BFA versus wait list control (WLC) for chronic musculoskeletal pain in cancer survivors. Expectancy was measured by the Acupuncture Expectancy Scale (AES) at baseline. Pain severity was assessed using the Brief Pain Inventory (BPI) at baseline and week 12. For each treatment arm, multivariable regression models were used to evaluate the association between pretreatment expectancy and week 12 pain severity, controlling for baseline pain severity, age, sex, race, and education. Results: Among 360 participants enrolled, the mean age was 62.1 years (SD 12.7), with 251 (69.7 %) women and 88 (24.4 %) non-white survivors. Pretreatment expectancy was similar for all groups at baseline (EA: 13.9 ± 3.6; BFA: 13.2 ± 3.7, WLC:12.8 ± 3.3, p = 0.14). Greater pretreatment expectancy was not significantly associated with greater pain reduction in any group, after adjusting for co-variates (EA: Coef. = -0.05, 95 % CI = -0.14 - 0.04, p = 0.28; BFA: Coef. = -0.07, 95 % CI = -0.16 - 0.02, p = 0.15; WLC: Coef. = -0.09, 95 % CI = -0.25 - 0.06, p = 0.23). Conclusions: Pretreatment expectancy did not predict pain reduction for either EA or BFA in cancer survivors. Our study contributes to the interpretation of analgesic effects of EA or BFA, beyond the notion of a mere 'placebo effect'.

Nocebo expectations rather than placebo expectations affect topical pain relief: A randomized clinical trial.

Patients' expectations and beliefs regarding the potential benefits and harms of medical interventions may induce placebo and nocebo effects, and affect the response to pain therapies. In a randomized clinical trial, we examined the effect of placebo and nocebo expectations on pain relief and adverse events (AEs) in association with a topical treatment among 65 cancer survivors experiencing chronic musculoskeletal pain. Participants received either a 1% camphor-based topical pain patch or a placebo treatment for 14 days. We measured pain severity with the worst pain item of the Brief Pain Inventory (BPI) at baseline and 14 days and treatment expectations at baseline with validated expectation questionnaires. We found that high vs. low nocebo expectations decreased pain severity improvements by 2.5 points (95% confidence interval [CI] -3.8 to -1.2; p<0.001) on a 0-10 numeric rating scale of the BPI and pain response rate by 42.7% (95% CI 0.2-0.6; p<0.001) at day 14, irrespective of placebo expectation status or treatment arms. Patients with high vs. low nocebo expectations in the true arm reported 22.4% more unwanted AEs. High nocebo expectations were associated with increased AEs by 39.5% (odds ratio: 12.0, 95% CI 1.2, 145.5; p=0.029) and decreased pain response in the true arm vs. placebo. Our study demonstrated that nocebo expectations, rather than placebo expectations, elevate the risk of AEs and compromise the effect of topical pain interventions. The findings raise the possibility that nocebo expectations may worsen somatic symptoms through heightening central pain amplification and should be further investigated.

Development and validation of an UPLC-MS/MS method for the simultaneous determination of fexofenadine and olmesartan in human serum: Application to in vivo pharmacokinetic studies.

A sensitive, reproducible, robust, high-throughput ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous quantification of fexofenadine and olmesartan in human serum. Samples (50 µL) undergo protein precipitation prior to UPLC-MS/MS analysis. The analytes were separated using an Acquity BEH C18 column (2.1 mm × 50 mm, 1.7 µm) at a flow rate of 0.5 mL/min using a gradient elution with a total run time of 4 min. The analytes were detected in positive ion mode and selected reaction monitoring (SRM) was used for quantitation. The standard curve concentration range was 1.0-500.0 ng/mL for both analytes and each analyte showed excellent linearity with correlation coefficients (R2 > 0.99). The intra- and inter-day accuracy and precision were ±15% for each analyte, and excellent recovery was demonstrated (93-98%) for both analytes. The method is well suited for high-throughput quantitative determination of fexofenadine and olmesartan simultaneously and was successfully applied to an in vivo pharmacokinetic and transporter phenotyping study in humans.

Response of treatment-naive brain metastases to stereotactic radiosurgery.

With improvements in survival for patients with metastatic cancer, long-term local control of brain metastases has become an increasingly important clinical priority. While consensus guidelines recommend surgery followed by stereotactic radiosurgery (SRS) for lesions >3 cm, smaller lesions (≤3 cm) treated with SRS alone elicit variable responses. To determine factors influencing this variable response to SRS, we analyzed outcomes of brain metastases ≤3 cm diameter in patients with no prior systemic therapy treated with frame-based single-fraction SRS. Following SRS, 259 out of 1733 (15%) treated lesions demonstrated MRI findings concerning for local treatment failure (LTF), of which 202 /1733 (12%) demonstrated LTF and 54/1733 (3%) had an adverse radiation effect. Multivariate analysis demonstrated tumor size (>1.5 cm) and melanoma histology were associated with higher LTF rates. Our results demonstrate that brain metastases ≤3 cm are not uniformly responsive to SRS and suggest that prospective studies to evaluate the effect of SRS alone or in combination with surgery on brain metastases ≤3 cm matched by tumor size and histology are warranted. These studies will help establish multi-disciplinary treatment guidelines that improve local control while minimizing radiation necrosis during treatment of brain metastasis ≤3 cm.

Low acromial insufficiency fracture rate in reverse shoulder arthroplasty with distal clavicle excision.

Background: This study investigated the rate of acromial insufficiency fractures (AIF) in patients undergoing reverse shoulder arthroplasty (RSA) with concomitant distal clavicle excision (DCE). Methods: Patients who underwent primary RSA with DCE by a single surgeon from 2010 to 2021 were identified. Exclusion criteria included revision RSA, RSA for fracture, or cases utilizing an augmented baseplate or bone graft. AIF was defined as a radiographically proven acromion or scapular spine fracture. Pain without an identifiable fracture on imaging was defined as an acromial insufficiency reaction. Patient demographics, implant information, and radiograph measurements were compared between patients with and without acromial pathology. Results: One hundred and seventy-five patients were included. Mean age was 72.8 years, and 67% of patients were female. There were 3/174 acromial insufficiency fractures (1.7%). AIF occurred at a mean of 9.3 months after surgery. Twelve patients had insufficiency reactions (6.9%). Patients with acromial pathology were more likely to be female (p = .003) and have a diagnosis of osteoporosis (p = .047) and inflammatory arthritis (p = .049). There was no significant difference between groups in terms of other factors. Conclusion: The AIF rate in patients who underwent RSA with DCE was 1.7%. These findings suggest that DCE in the setting of RSA may have a protective role against AIF.

Patient-Reported Outcomes as a Recruitment Strategy for Clinical Trial Enrollment.

Importance: Clinical trials are critical for progress in oncology; however, only 5% of the adult cancer population participates. Harnessing data that are routinely collected (ie, electronic patient-reported outcomes [ePROs]) may serve as a method to promote trial enrollment. Objective: To evaluate if an ePRO-prompted recruitment strategy is associated with increased clinical trial enrollment. Design, Setting, and Participants: A randomized substudy was conducted from September 2022 to March 2023 at a multisite tertiary cancer center as part of an ongoing clinical trial that was testing a symptom-intervention for cancer-related fatigue. Patients with breast cancer who were undergoing radiotherapy who completed at least 1 ePRO questionnaire during the study period were included. Physician-level cluster randomization assigned fatigue-eligible patients to either receive a portal message invitation to a symptom-intervention trial or standard of care (SOC; physician-based referral). Exposure: ePRO questionnaires distributed in routine practice were queried weekly and screened for moderate or greater fatigue, the principle inclusion criterion for the primary trial. To assess the association of the portal message source with response and enrollment, every other patient received a message from the primary radiation oncology team or the referral service. Main Outcomes and Measures: Clinical trial response/referral and enrollment. Results: A total of 1041 patients completed ePRO questionnaires, of whom 394 (38%; 53 Asian [13.6%], 43 Black [11.0%], 29 Hispanic [7.4%], and 262 White individuals [66.5%]; median [IQR] age, 55 [47-65] years) endorsed moderate or greater fatigue while receiving treatment. A total of 210 patients (53.3%) were assigned to receive a portal message and 184 (46.7%) patients, SOC. In the portal message group, 73 patients (35%) responded and 41 (20%) enrolled compared with 1 patient (0.5%) referred and 0 enrolled in the SOC group (P < .001). The response rate to portal messages favored the referral service vs the primary radiation oncology service (44% vs 26%; P = .01), but there was no significant difference in enrollments. Conclusions and Relevance: The study results suggest that use of routine care ePROs was associated with greater enrollment in a symptom-intervention trial compared with physician-based referral. Messaging directly from the referral service may support enrollment and help reduce oncology physician-level barriers to trial enrollment for studies testing symptom interventions.

Clinical and radiographic outcomes of shoulder hemiarthroplasty for patients with glenoid medialization.

BACKGROUND: Glenoid bone loss in shoulder arthroplasty is a difficult problem that is prone to complications because of challenges with achieving glenoid component fixation and stability. The purpose of this study was to evaluate the outcomes of primary shoulder hemiarthroplasty for patients with severe glenoid medialization precluding placement of a glenoid component. METHODS: This was a retrospective case series evaluating patients who underwent shoulder hemiarthroplasty for severe glenoid erosion and medialization between 2010 and 2020. Patients were evaluated via chart review and phone survey to determine if there were any reoperations at final follow-up and to obtain Single Assessment Numeric Evaluation (SANE), American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), and Simple Shoulder Test (SST) scores. Preoperative and postoperative radiographs were evaluated and compared to determine glenoid morphology, version, medialization, acromiohumeral distance, and humeral offset. Final postoperative films were also evaluated for anterosuperior migration and signs of mechanical failure, including loosening or periprosthetic fracture. RESULTS: Overall, there were 28 patients during this period who underwent shoulder hemiarthroplasty for severe glenoid medialization. Eight patients were deceased at the time of the study, 2 were unable to complete surveys because of dementia, and 7 were lost to follow-up. The final cohort included 11 shoulders and 11 patients with a mean age of 71 ± 7.1 years and mean follow-up of 6.7 years (range 1.6-13.0 years). Mean postoperative SANE, ASES, and SST scores were 80.6 ± 17.6, 71.5 ± 29.3, and 7.6 ± 2.0, respectively. There were no reoperations or revision surgeries at final follow-up. Radiographic evaluation demonstrated severe glenoid medialization and decreased lateral humeral offset, which was unchanged postoperatively. There were 2 patients with signs of anterosuperior migration at final radiographic follow-up but no signs of implant failure. CONCLUSION: Shoulder hemiarthroplasty for severe medial glenoid bone loss provides modest clinical outcomes and low rates of reoperation at mid- to long-term follow-up and is an option worth considering in cases where placement of a glenoid component is challenging because of deficient bone stock and high risk for complications.

Same-day discharge vs. inpatient total shoulder arthroplasty: an age stratified comparison of postoperative outcomes and hospital charges.

BACKGROUND: As the number of total shoulder arthroplasty (TSA) procedures increases, there is a growing interest in improving patient outcomes, limiting costs, and optimizing efficiency. One approach has been to transition these surgeries to an outpatient setting. Therefore, the purpose of this study was to conduct an age-stratified analysis comparing the 90-day postoperative outcomes of primary TSA in the same-day discharge (SDD) and inpatient (IP) settings with a specific focus on the super-elderly. METHODS: This retrospective study included all patients who underwent primary anatomic or reverse TSA between January 2018 and December 2021 in ambulatory and IP settings. The outcome measures included length of stay (LOS), complications, hospital charges, emergency department (ED utilization), readmissions, and reoperations within 90 days following TSA. Patients with LOS ≤8 hours were considered as SDD, and those with LOS >8 hours were considered as IP. P < .05 was considered statistically significant. RESULTS: There were 121 and 174 procedures performed in SDD and IP settings, respectively. There were no differences in comorbidity indices between the SDD and IP groups (American Society of Anesthesiologists score P = .12, Elixhauser Comorbidity Index P = .067). The SDD cohort was younger than the IP group (SDD 67.0 years vs. 73.0 IP years, P < .001), and the SDD group higher rate of intraoperative tranexamic acid use (P = .015) and lower estimated blood loss (P = .009). There were no differences in 90-day overall minor (P = .20) and major complications (P = 1.00), ED utilization (P = .63), readmission (P = .25), or reoperation (P = .51) between the SDD and IP groups. When stratified by age, there were no differences in overall major (P = .80) and minor (P = .36) complications among the groups. However, the LOS was directly correlated with increasing age (LOS = 8.4 hours in ≥65 to <75-year cohort vs. LOS = 25.9 hours in ≥80-year cohort; P < .001). There were no differences in hospital charges between SDD and IP primary TSA in all 3 age groups (P = .82). CONCLUSION: SDD TSA has a shorter LOS without increasing postoperative major and minor complications, ED encounters, readmissions, or reoperations. Older age was not associated with an increase in the complication profile or hospital charges even in the SDD setting, although it was associated with increased LOS in the IP group. These results suggest that TSA can be safely performed expeditiously in an outpatient setting.

Determining Which Combinatorial Combat-Relevant Factors Contribute to Heterotopic Ossification Formation in an Ovine Model.

Traumatic heterotopic ossification (HO) is frequently observed in Service Members following combat-related trauma. Estimates suggest that ~65% of wounded warriors who suffer limb loss or major extremity trauma will experience some type of HO formation. The development of HO delays rehabilitation and can prevent the use of a prosthetic. To date there are limited data to suggest a standard mechanism for preventing HO. This may be due to inadequate animal models not producing a similar bone structure as human HO. We recently showed that traumatic HO growth is possible in an ovine model. Within that study, we demonstrated that 65% of sheep developed a human-relevant hybrid traumatic HO bone structure after being exposed to a combination of seven combat-relevant factors. Although HO formed, we did not determine which traumatic factor contributed most. Therefore, in this study, we performed individual and various combinations of surgical/traumatic factors to determine their individual contribution to HO growth. Outcomes showed that the presence of mature biofilm stimulated a large region of bone growth, while bone trauma resulted in a localized bone response as indicated by jagged bone at the linea aspera. However, it was not until the combinatory factors were included that an HO structure similar to that of humans formed more readily in 60% of the sheep. In conclusion, data suggested that traumatic HO growth can develop following various traumatic factors, but a combination of known instigators yields higher frequency size and consistency of ectopic bone.

Engineering Small HOMO-LUMO Gaps in Polycyclic Aromatic Hydrocarbons with Topologically Protected States.

Topological phases in laterally confined low-dimensional nanographenes have emerged as versatile design tools that can imbue otherwise unremarkable materials with exotic band structures ranging from topological semiconductors and quantum dots to intrinsically metallic bands. The periodic boundary conditions that define the topology of a given lattice have thus far prevented the translation of this technology to the quasi-zero-dimensional (0D) domain of small molecular structures. Here, we describe the synthesis of a polycyclic aromatic hydrocarbon (PAH) featuring two localized zero modes (ZMs) formed by the topological junction interface between a trivial and nontrivial phase within a single molecule. First-principles density functional theory calculations predict a strong hybridization between adjacent ZMs that gives rise to an exceptionally small HOMO-LUMO gap. Scanning tunneling microscopy and spectroscopy corroborate the molecular structure of 9/7/9-double quantum dots and reveal an experimental quasiparticle gap of 0.16 eV, corresponding to a carbon-based small molecule long-wavelength infrared (LWIR) absorber.

In Situ Formation of Fibronectin-Enriched Protein Corona on Epigenetic Nanocarrier for Enhanced Synthetic Lethal Therapy.

PARP inhibitors (PARPi)-based synthetic lethal therapy demonstrates limited efficacy for most cancer types that are homologous recombination (HR) proficient. To potentiate the PARPi application, a nanocarrier based on 5-azacytidine (AZA)-conjugated polymer (PAZA) for the codelivery of AZA and a PARP inhibitor, BMN673 (BMN) is developed. AZA conjugation significantly decreased the nanoparticle (NP) size and increased BMN loading. Molecular dynamics simulation and experimental validations shed mechanistic insights into the self-assembly of effective NPs. The small PAZA NPs demonstrated higher efficiency of tumor targeting and penetration than larger NPs, which is mediated by a new mechanism of active targeting that involves the recruitment of fibronectin from serum proteins following systemic administration of PAZA NPs. Furthermore, it is found that PAZA carrier sensitize the HR-proficient nonsmall cell lung cancer (NSCLC) to BMN, a combination therapy that is more effective at a lower AZA/BMN dosage. To investigate the underlying mechanism, the tumor immune microenvironment and various gene expressions by RNAseq are explored. Moreover, the BMN/PAZA combination increased the immunogenicity and synergized with PD-1 antibody in improving the overall therapeutic effect in an orthotopic model of lung cancer (LLC).

An evolutionary mechanism to assimilate new nutrient sensors into the mTORC1 pathway.

Animals sense and respond to nutrient availability in their environments, a task coordinated in part by the mTOR complex 1 (mTORC1) pathway. mTORC1 regulates growth in response to nutrients and, in mammals, senses specific amino acids through specialized sensors that bind the GATOR1/2 signaling hub. Given that animals can occupy diverse niches, we hypothesized that the pathway might evolve distinct sensors in different metazoan phyla. Whether such customization occurs, and how the mTORC1 pathway might capture new inputs, is unknown. Here, we identify the Drosophila melanogaster protein Unmet expectations (CG11596) as a species-restricted methionine sensor that directly binds the fly GATOR2 complex in a fashion antagonized by S-adenosylmethionine (SAM). We find that in Dipterans GATOR2 rapidly evolved the capacity to bind Unmet and to thereby repurpose a previously independent methyltransferase as a SAM sensor. Thus, the modular architecture of the mTORC1 pathway allows it to co-opt preexisting enzymes to expand its nutrient sensing capabilities, revealing a mechanism for conferring evolvability on an otherwise conserved system.

Participation in Virtual Prehabilitation and Outcomes Following Thoracic Cancer Surgery.

This cohort study evaluates the association of a virtual synchronized prehabilitation program with perioperative outcomes among patients undergoing thoracic cancer surgery.

How do cicadas emerge together? Thermophysical aspects of their collective decision-making.

Periodical cicadas exhibit life cycles with durations of 13 or 17 years, and it is now accepted that large prime cycles arose to avoid synchrony with predators. Less well explored is how, in the face of intrinsic biological and environmental noise, insects within a brood emerge together in large successive swarms from underground during springtime warming. Here, we consider the decision-making process of underground cicadas experiencing random, spatially correlated thermal microclimates such as those in nature. Introducing short-range communication between insects leads to an Ising model of consensus building with a quenched, spatially correlated random magnetic field and annealed site dilution, which displays the kinds of collective swarms seen in nature. These results highlight the need for fieldwork to quantify the spatial fluctuations in thermal microclimates and their relationship to the spatiotemporal dynamics of swarm emergence.

A psychoeducational intervention to improve sexual functioning in male rectal and anal cancer patients: A pilot randomized controlled trial study.

OBJECTIVES: Male rectal and anal cancer patients demonstrate high rates of sexual dysfunction. This pilot randomized controlled trial tested a psychoeducational intervention designed to improve psychosexual adjustment. METHODS: Rectal or anal cancer patients were randomized to a Sexual Health Intervention for Men (intervention) or to a referral and information control (control). The intervention included control activities plus 4 sexual health intervention sessions every 4-6 weeks and 3 brief telephone calls timed between these sessions. Assessments were completed pre-intervention (baseline) and 3 months (follow-up 1) and 8 months (follow-up 2) post-intervention. Differences were assessed with statistical significance and Cohen's d effect sizes (d = 0.2, small effect; d = 0.5, moderate effect; d = 0.8, large effect). RESULTS: Ninety subjects enrolled. Forty-three participants completed at least 1 follow-up assessment (intervention, n = 14; control n = 29). At follow-up 1, men in intervention, compared to control, improved on all domains of the International Index of Erectile Function (IIEF) (p < 0.001 to p < 0.05) and demonstrated large effects (d = 0.8 to d = 1.5). Similarly, at follow-up 2, changes in all domains of the IIEF except the orgasm domain were either statistically significant or marginally statistically significant (p = 0.01 to p = 0.08) and demonstrated moderate to large treatment effects for intervention versus control (d = 0.5 to d = 0.8). Men in the intervention, compared to control, demonstrated decreased sexual bother at follow-up 1 (p = 0.009, d = 1.1), while Self-Esteem and Relationship (SEAR) total scores and the SEAR sexual relationship subscale demonstrated moderate increases for intervention versus control (d = 0.4 to d = 0.6). SIGNIFICANCE OF RESULTS: This study provides initial evidence for combining a psychoeducational intervention with medical interventions to address sexual dysfunction following rectal and anal cancer. Trials register number: NCT00712751 (date of registration: 7/10/2008).

Colloidal Nanoparticles of High Entropy Materials: Capabilities, Challenges, and Opportunities in Synthesis and Characterization.

Materials referred to as "high entropy" contain a large number of elements randomly distributed on the lattice sites of a crystalline solid, such that a high configurational entropy is presumed to contribute significantly to their formation and stability. High temperatures are typically required to achieve entropy stabilization, which can make it challenging to synthesize colloidal nanoparticles of high entropy materials. Nonetheless, strategies are emerging for the synthesis of colloidal high entropy nanoparticles, which are of interest for their synergistic properties and unique catalytic functions that arise from the large number of constituent elements and their interactions. In this Perspective, we highlight the classes of materials that have been made as colloidal high entropy nanoparticles as well as insights into the synthetic methods and the pathways by which they form. We then discuss the concept of "high entropy" within the context of colloidal materials synthesized at much lower temperatures than are typically required for entropy to drive their formation. Next, we identify and address challenges and opportunities in the field of high entropy nanoparticle synthesis. We emphasize aspects of materials characterization that are especially important to consider for nanoparticles of high entropy materials, including powder X-ray diffraction and elemental mapping with scanning transmission electron microscopy, which are among the most commonly used techniques in laboratory settings. Finally, we share perspectives on emerging opportunities and future directions involving colloidal nanoparticles of high entropy materials, with an emphasis on synthesis, characterization, and fundamental knowledge that is needed for anticipated advances in key application areas.