NRG Oncology-Radiation Therapy Oncology Group Study 1014: 1-Year Toxicity Report From a Phase 2 Study of Repeat Breast-Preserving Surgery and 3-Dimensional Conformal Partial-Breast Reirradiation for In-Breast Recurrence.

PURPOSE: To determine the associated toxicity, tolerance, and safety of partial-breast reirradiation. METHODS AND MATERIALS: Eligibility criteria included in-breast recurrence occurring \u3e1 year after whole-breast irradiation, \u3c3 \u3ecm, unifocal, and resected with negative margins. Partial-breast reirradiation was targeted to the surgical cavity plus 1.5 cm; a prescription dose of 45 Gy in 1.5 Gy twice daily for 30 treatments was used. The primary objective was to evaluate the rate of grade ≥3 treatment-related skin, fibrosis, and/or breast pain adverse events (AEs), occurring ≤1 year from re-treatment completion. A rate of ≥13% for these AEs in a cohort of 55 patients was determined to be unacceptable (86% power, 1-sided α = 0.07). RESULTS: Between 2010 and 2013, 65 patients were accrued, and the first 55 eligible and with 1 year follow-up were analyzed. Median age was 68 years. Twenty-two patients had ductal carcinoma in situ, and 33 had invasive disease: 19 ≤1 cm, 13 \u3e1 to ≤2 cm, and 1 \u3e2 cm. All patients were clinically node negative. Systemic therapy was delivered in 51%. All treatment plans underwent quality review for contouring accuracy and dosimetric compliance. All treatment plans scored acceptable for tumor volume contouring and tumor volume dose-volume analysis. Only 4 (7%) scored unacceptable for organs at risk contouring and organs at risk dose-volume analysis. Treatment-related skin, fibrosis, and/or breast pain AEs were recorded as grade 1 in 64% and grade 2 in 7%, with only 1 ( CONCLUSION: Partial-breast reirradiation with 3-dimensional conformal radiation therapy after second lumpectomy for patients experiencing in-breast failures after whole-breast irradiation is safe and feasible, with acceptable treatment quality achieved. Skin, fibrosis, and breast pain toxicity was acceptable, and grade 3 toxicity was rare

A New Adenovirus Based Vaccine Vector Expressing an Eimeria tenella Derived TLR Agonist Improves Cellular Immune Responses to an Antigenic Target

Adenoviral based vectors remain promising vaccine platforms for use against numerous pathogens, including HIV. Recent vaccine trials utilizing Adenovirus based vaccines expressing HIV antigens confirmed induction of cellular immune responses, but these responses failed to prevent HIV infections in vaccinees. This illustrates the need to develop vaccine formulations capable of generating more potent T-cell responses to HIV antigens, such as HIV-Gag, since robust immune responses to this antigen correlate with improved outcomes in long-term non-progressor HIV infected individuals.. Moreover, we show that these improved responses were dependent upon improved TLR pathway interactions.The data presented in this study illustrate the potential utility of Ad-based vectors expressing TLR agonists to improve clinical outcomes dependent upon induction of robust, antigen specific immune responses

Nonoperative management of tibial stress fractures result in higher return to sport rates despite increased failure versus operative management: A systematic review

PURPOSE: To compare return to sport (RTS) rates and complications after nonoperative versus operative management of tibial stress fractures. METHODS: A literature search was conducted per the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using EMBASE, PubMed, and Scopus computerized data from database inception to February 2023. Studies evaluating RTS sport rates and complications after nonoperative or operative management of tibial stress fractures were included. Failure was defined as defined by persistent stress fracture line seen on radiographic imaging. Study quality was assessed using the Modified Coleman Methodology Score. RESULTS: Twenty-two studies consisting of 341 patients were identified. The overall RTS rate ranged from 91.2% to 100% in the nonoperative group and 75.5% to 100% in the operative group. Failures rates ranged from 0% to 25% in the nonoperative groups and 0% to 6% in the operative group. Reoperations were reported in 0% to 6.1% of patients in the operative group, whereas 0% to 12.5% of patients initially managed nonoperatively eventually required operative treatment. CONCLUSIONS: Patients can expect high RTS rates after appropriate nonoperative and operative management of tibial stress fractures. Treatment failure rates were greater in patients undergoing nonoperative management, with up to 12.5% initially treated nonoperatively later undergoing operative treatment. LEVEL OF EVIDENCE: Level IV; Systematic Review of level I-IV studies

Adverse events and complications after primary ACL reconstruction with quadriceps tendon autograft: A systematic review

BACKGROUND: Anterior cruciate ligament reconstruction (ACLR) surgery with quadriceps tendon (QT) grafts, both with and without a patellar bone plug, have gained popularity in recent years in the primary and revision settings. Postoperative complications occur with the use of QT autografts. PURPOSE: To systematically review the incidence of postoperative complications after primary ACLR QT autograft and compare complication rates in patients undergoing all-soft tissue QT grafts versus QT grafts with a patellar bone plug (QTPB). STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: A literature search using the 2020 PRISMA guidelines was performed by querying PubMed, Embase, and Scopus databases from database inception through August 2022. Included were evidence level 1 to 4 human clinical studies in English that reported complications after primary ACLR with QT autograft. The incidence of complications within the included studies was extracted. Differences in the incidence of postoperative complications between ACLR with QT with and without a patellar bone plug were calculated. RESULTS: A total of 20 studies from 2004 to 2022, comprised of 2381 patients (2389 knees; 68.3% male) with a mean age of 27 years (range, 12-58 years), were identified. The mean follow-up was 28.5 months (range, 6-47 months). The total incidence of complications was 10.3%, with persistent postoperative knee pain being the most common (10.8%). Patients who underwent ACLR with all-soft tissue QT grafts had a 2.7-times increased incidence of anterior knee pain (23.3% vs 8.6%) and reoperations (5.9% vs 3.2%) when compared with QTPB grafts ( CONCLUSION: Complications after primary ACLR using QT autograft were recorded in 10.5% of knees, with anterior knee pain being the most common. No difference was reported in the overall incidence of complications with the use of the QT versus QTPB grafts; however, anterior knee pain was 2.7 times greater with use of a soft tissue quadriceps graft

Functional divergence in the role of N-linked glycosylation in smoothened signaling

The G protein-coupled receptor (GPCR) Smoothened (Smo) is the requisite signal transducer of the evolutionarily conserved Hedgehog (Hh) pathway. Although aspects of Smo signaling are conserved from Drosophila to vertebrates, significant differences have evolved. These include changes in its active sub-cellular localization, and the ability of vertebrate Smo to induce distinct G protein-dependent and independent signals in response to ligand. Whereas the canonical Smo signal to Gli transcriptional effectors occurs in a G protein-independent manner, its non-canonical signal employs Gαi. Whether vertebrate Smo can selectively bias its signal between these routes is not yet known. N-linked glycosylation is a post-translational modification that can influence GPCR trafficking, ligand responsiveness and signal output. Smo proteins in Drosophila and vertebrate systems harbor N-linked glycans, but their role in Smo signaling has not been established. Herein, we present a comprehensive analysis of Drosophila and murine Smo glycosylation that supports a functional divergence in the contribution of N-linked glycans to signaling. Of the seven predicted glycan acceptor sites in Drosophila Smo, one is essential. Loss of N-glycosylation at this site disrupted Smo trafficking and attenuated its signaling capability. In stark contrast, we found that all four predicted N-glycosylation sites on murine Smo were dispensable for proper trafficking, agonist binding and canonical signal induction. However, the under-glycosylated protein was compromised in its ability to induce a non-canonical signal through Gαi, providing for the first time evidence that Smo can bias its signal and that a post-translational modification can impact this process. As such, we postulate a profound shift in N-glycan function from affecting Smo ER exit in flies to influencing its signal output in mice

Of less known literary work of Ivan Golub before the 1990s

Kronologija objavljivanja književnih djela svećenika, književnika i znanstvenika Ivana Goluba sugerira da se, osim rijetkih izuzetaka iz ranijeg razdoblja, književnim stvaralaštvom intenzivnije počeo baviti tek 1990-ih godina. No, kada u obzir uzmemo do danas uglavnom nepoznata njegova djela koja su nastala znatno prije, ali su objavljena tek 1990-ih godina, i to vjerojatno prije svega zahvaljujući slomu komunističkog društveno-političkog poretka koji je do tada proskribirao književnost kršćanskog nadahnuća, postaje jasno da se Golub književnim stvaralaštvom u kontinuitetu i otprilike jednakim intenzitetom ustvari bavio još od 1970-ih pa sve do danas.The order in which literary works by Ivan Golub, a Croatian priest, author and scientist, were published suggests, with some rare exceptions early on, that he started writing intensely only after the 1990s. However, we should take into consideration his works that are mostly unknown today and were created well before, but published only in the 1990s. That is probably because of the collapse of the communist socio-political order, which had prohibited literature of Christian inspiration up until then. It then becomes clear that Golub has been writing with the same intensity ever since the 1970s and to this day

Development and Initial Validation of the Endurance Sport Self-efficacy Scale (ESSES)

Self-efficacy is likely to be an important psychological construct for endurance sport performance. Research into the role of self-efficacy, however, is limited as there is currently no validated measure of endurance sport self-efficacy. Consequently, the purpose of the present research was to develop and validate the Endurance Sport Self-Efficacy Scale (ESSES). In Study 1, an initial item pool was developed following a review of the literature. These items were then examined for content validity by an expert panel. In Study 2, the resultant 18 items were subjected to exploratory factor analyses. These analyses provided support for a unidimensional scale comprised of 11 items. Study 2 also provided evidence for the ESSES’s convergent validity. In Study 3, using confirmatory factor analyses, further support was found for the 11-item unidimensional structure. Study 3 also provided evidence for the ESSES’s convergent and concurrent validity. The present findings provide initial evidence that the ESSES is a valid and reliable measure of self-efficacy beliefs in endurance sports