bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence of infections in clinical trials of treatments for relapsed/refractory multiple myeloma: Systematic review and meta-analysis.
Authors: Omofuma Omonefe O , Zhang Yue , Hampp Christian , Breskin Alexander , Makaratzi Martha , Parmar Saager , Kroog Glenn Scott , Rodriguez-Lorenc Karen
Published: June 2024

e19517

Background: Although immunotherapy shows favorable survival outcomes among heavily pretreated relapsed/refractory multiple myeloma (RRMM) patients, infections are a common cause of morbidity and mortality that are not well characterized in this patient population. The goal of this study was to estimate the incidence of infections from clinical trials of treatments for RRMM by grade, infection type, and treatment received. Methods: We conducted a literature search in EMBASE, PubMed, Cochrane, approval packages and labeling, and conference proceedings to identify phase 2-3 clinical trials of single drug interventions published prior to 18 June 2023 with data on infections. We included studies of patients aged ≥18 years who received prior MM treatment with an immunomodulatory agent, protease inhibitor, and anti-CD38 antibody. A Bayesian meta-analysis accounting for left-censored data was used to estimate the pooled incidence of infection from the studies by infection type (upper respiratory tract infection [uRTI], sepsis, bacteremia, pneumonia, SARS-COV-2, and bacterial and viral infections), grade (all, grades ≥3, and 5/fatal) and type of treatment received (antibody and CAR-T). Results: Nine studies (7 phase 2, 1 phase 3 and 1 product label) of seven compounds (1 selective inhibitor of nuclear export, 2 CAR-T, and 4 monoclonal and bispecific antibodies) were identified and are/were approved in the US for RRMM treatment. All included articles were published after July 2019 on treatments approved since 2020 for patients who had received ≥4 prior lines of therapy. They included a total of 1,141 patients (median follow-up 10.1 - 23 months). The pooled incidence of all infections was 61.6% (95% credible interval, 58.6%-64.6%), 28.7% (24.7%-32.2%) and 4.1% (2.9%-5.6%) for all-grades, grades ≥3, and 5 respectively. uRTI was the most common type of all-grade infection (22.8% [20.0%-25.6%]) while SARS-COV-2 (6.8% [4.9%-9.4%]) and pneumonia (6.8% [5.0%-9.1%]) were the most common grade ≥3 infections. Sepsis was the most common fatal infection (1.0% [0.4%-1.8%]). Patients treated with monoclonal/bispecific antibodies had a slightly higher incidence of all-grade infections (64.2% [60.4%-67.9%]) compared to CAR-T (58.6% [52.8%-64.2%]). The incidences for these treatments were similar for grades ≥3 (28.9% vs 28.2%) and 5 (3.5% vs 4.5%) infections. Conclusions: In clinical trials of treatment for triple class exposed RRMM, the incidence of infection was high, including grade 3 or higher infections. A large proportion of grade ≥3 infections were attributable to SARS-COV-2 and pneumonia, with sepsis as the most common fatal infection. The incidence of grade ≥3 infection was generally consistent for CAR-T and monoclonal/bispecific antibody therapy.
Real-world comparison of adherence to branded 20 mg dexamethasone tablets and generic 4 mg dexamethasone tablets among patients with multiple myeloma.
Authors: Worley Daniel G , Melnyk Iryna , Johannesen Dawn , Ellis Jennifer , Landsman-Blumberg Pamela
Published: June 2024

e19518

Background: Branded 20 mg dexamethasone tablets (BDex) is the first and only FDA-approved dexamethasone specifically indicated for the treatment of adult patients with multiple myeloma (MM) in combination with other anti-myeloma products. Generic oral dexamethasone is only available at lower dosages (e.g., 4 mg) despite the standard dexamethasone dosage for MM being 20 or 40 mg. The availability of 20 mg tablets would, therefore, reduce pill burden and assumably improve adherence in MM patients. The objective of this analysis was to quantify and compare adherence of BDex and generic 4 mg dexamethasone (GDex) among MM patients using real-world evidence. Methods: Using an open claims database, which included professional, hospital, and pharmacy claims for over 295 million individuals across the United States from 2015 to 2023, BDex and GDex users aged ≥18 years with MM were identified. Baseline summary statistics were generated and chi-squared and t-tests were performed comparing continuous and categorical variables respectively between the treatment cohorts. Treatment adherence was determined using a medication possession ratio for flexible time period (MPRF) given variable numbers of cycles across patients. MPRF was reported as both a continuous and binary measure (≥80%). Differences in MPRF were determined utilizing t-tests. Results: Between September 1, 2020 and June 30, 2023, 43 BDex and 3,775 GDex users meeting all study criteria, including ≥2 prescription claims, were identified. Overall, 30.8% were aged 18-64 years, 54.6% were male, 71.2% were insured through Medicare, and 20.3% were insured commercially. Bortezomib monotherapy, immunomodulatory agent monotherapy, and daratumumab and bortezomib were the most common treatment regimens (17.5%, 11.1%, 7.2%, respectively). Mean MPRF was significantly higher in BDex users compared to GDex overall (97.1% vs 89.5%, p <0.001), among those 18-64 (98.7% vs 89.1%, p <0.001), those with commercial insurance (99.9% vs 90.4%, p<0.001), and those with Medicare (96.1% vs 89.6%, p=0.048). A significantly greater proportion of BDex users were considered adherent compared to GDex patients (95.3% vs 78.4%, p=0.007). This trend was seen across age and payer sub-cohorts, with significant differences seen in those with Medicare (96.0% vs 78.7%, p= 0.035). Conclusions: Adherence to BDex was greater than to GDex in this MM study population overall, and for age group and payer sub-cohorts. Given these findings, physicians may want to consider overall pill burden and regimen complexity when prescribing MM treatment for their patients.
Quadruplet therapy for transplant-eligible newly diagnosed multiple myeloma (TENDMM): A systematic review and meta-analysis.
Authors: Channar Aneeta , Naqvi Syed Arsalan Ahmed , Khan Muhammad Ali , Bibi Arifa , Saxena Akshat , Tripathi Nikita , Iftikhar Ahmad , Raina Ammad , Khakwani Kaneez Zahra Rubab , Riaz Irbaz Bin , Husnain Muhammad
Published: June 2024

e19534

Background: Immunomodulatory drugs, proteasome inhibitors plus dexamethasone are the standard triplet induction regimen for TENDMM. We analyzed the efficacy of adding either anti-CD38 monoclonal antibodies (mAbs) or anti-SLAMF7 antibody to the triplet therapy. Methods: Ovid MEDLINE, EMBASE and published abstracts were systematically searched from each database’s inception through 01-31-2024 to identify II/III trials assessing quadruplet therapy versus triplet therapy in TENDMM patients. Hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS), odds ratios (OR) for overall response rates (ORR), measurable residual disease (MRD) negativity rate (with sensitivity of 10 -5) and grade 3 or higher treatment-related adverse events (G≥3 TRAE) were summarized using random effects meta-analysis via inverse variance approach. Additional subgroup analyses based on the cytogenetic risk were performed. P-value of interaction (Pint ) < 0.1 was pre-specified as statistically significant for the difference between the two groups. Results: 3806 studies were screened and seven trials were included with a total of 3546 patients. Four trials (2303 patients) assessed the addition of anti-CD-38 mAbs and three (1243 patients) assessed anti-SLAMF7 mAb, elotuzumab to the triplet regimen. Quadruplet therapy significantly improved PFS as compared to triplet (HR: 0.63; 95% CI: 0.43-0.92), and the PFS benefit was also observed in standard risk group (HR 0.5; 95% CI 0.2-0.9); however, results were insignificant for high-risk group (HR 0.8; 95% CI 0.62-1.93). No significant OS benefit was observed (HR: 0.79; 95% CI 0.49–1.26); however, data for three trials (CASSIOPEIA, DSMM XVII, PERSEUS) is immature, with longer-term follow-up ongoing. Quadruplet therapy showed significant results for very good partial response or better (OR: 1.7; 95% CI 1.2-2.36), stringent complete response (OR: 1.74; 95% CI 1.27-2.07) and complete response or better (OR: 1.91; 95% CI 1.19-3.06). MRD rate shows benefit with quadruplet therapy (OR: 2.59; 95% CI 2.22-3.01). Improved MRD rate was also observed for high-risk (OR 2.13; 95% CI 1.4-3.2) and standard-risk group (OR 2.58; 95% CI 1.68-3.94). Secondary analysis for efficacy of anti-CD38 mAbs showed benefit for PFS (HR: 0.44; 95% CI: 0.35-0.56), ORR (OR: 1.77;95% CI: 1.02-3.06), and MRD (OR: 2.98; 95% CI 1.8-4.8). G ≥3 TRAE did not significantly differ between the groups (OR: 1.05; 95% CI 0.97-1.12). However, quadruplet therapy showed significant risk of infection (OR: 1.2; 95% 1.05-1.35) and thrombocytopenia (OR: 1.41; 95% CI 1.24-1.59). Conclusions: Quadruplet therapy improved PFS, ORR, and MRD rates compared to triplet regimen and has demonstrated promising benefits to be considered the new standard of care for TENDMM patients.
MagnetisMM-30: A phase 1b, open-label study of elranatamab in combination with iberdomide in patients with relapsed or refractory multiple myeloma (RRMM).
Authors: Lesokhin Alexander M. , Raza Muhammed Saleem , Acosta Jorge , Muller Patrick , O'Connell Ashleigh , Yver Anne , Lou Carolyn , Finn Gregory
Published: June 2024

TPS7577

Background: Elranatamab (ELRA) is a humanized B-cell maturation antigen (BCMA)–CD3 bispecific antibody (BsAb). Single-agent ELRA induced deep and durable responses with a manageable safety profile in patients (pts) with RRMM enrolled in the phase 2 registrational MagnetisMM-3 study (NCT04649359; Lesokhin et al, Nat Med 2023). Iberdomide (IBER) is a novel CELMoD[TM] agent that induces enhanced antimyeloma tumoricidal and immunomodulatory activity in pts with RRMM (Lonial et al, Lancet Haematol 2022). While IBER in combination with ELRA has not been evaluated clinically, it may provide additional benefit to pts with RRMM based on the mechanisms of action of this novel combination. Methods: MagnetisMM-30 is a phase 1b, open-label, prospective study evaluating the safety, efficacy, and pharmacokinetics of ELRA in combination with IBER in pts with RRMM. The study has 2 parts: Part 1 for dose-escalation and Part 2, randomized for dose optimization. After 2 step-up priming doses of ELRA, pts will receive subcutaneous ELRA weekly with IBER given daily for 21 days of each 28-day cycle. After ≥6 months (cycles) of treatment, pts with a partial response or better for ≥2 months are eligible for reduced dosing frequency of ELRA. Once the 2 combination dose levels (dose levels A and B) are selected from Part 1 as the recommended phase 2 doses for ELRA and IBER, pts in Part 2 will be randomized 1:1 (stratified by the number of prior lines of therapy [LOTs; 1 vs >1]) to dose levels A and B. Key inclusion criteria are pts aged ≥18 years with a MM diagnosis per IMWG criteria, Eastern Cooperative Oncology Group performance status of 0-1, adequate organ and bone marrow function, and disease relapsed or refractory to the last antimyeloma regimen per IMWG response criteria. Pts who received 2-4 or 1-3 prior LOTs, including ≥1 immunomodulatory drug (IMiD) and ≥1 proteasome inhibitor (PI), are eligible for Parts 1 and 2, respectively. All pts must have received ≥2 consecutive cycles of an IMiD-containing regimen and ≥2 consecutive cycles of a PI or PI-containing regimen. Key exclusion criteria are pts with stem cell transplant ≤12 weeks prior to enrollment; active, uncontrolled infection; prior treatment with BCMA-directed or CD3 redirecting therapy or prior CELMoD agents (ie, IBER or mezigdomide). This study is ongoing; Part 1 and Part 2 will enroll approximately 27 and 60 pts, respectively. Study endpoints are listed in the table. Clinical trial information: NCT06215118 . [Table: see text]
Reelin differentially shapes dendrite morphology of medial entorhinal cortical ocean and island cells
Authors: Hamad Mohammad I. K. , Daoud Solieman , Petrova Petya , Rabaya Obada , Jbara Abdalrahim , Al Houqani Shaikha , BaniYas Shamsa , Alblooshi Meera , Almheiri Ayesha , Nakhal Mohammed M. , Ali Bassam R. , Shehab Safa , Allouh Mohammed Z. , Emerald Bright Starling , Schneider-Lódi Mária , Bataineh Mo'ath F. , Herz Joachim , Förster Eckart
Published: June 2024

The function of medial entorhinal cortex layer II (MECII) excitatory neurons has been recently explored. MECII dysfunction underlies deficits in spatial navigation and working memory. MECII neurons comprise two major excitatory neuronal populations, pyramidal island and stellate ocean cells, in addition to the inhibitory interneurons. Ocean cells express reelin and surround clusters of island cells that lack reelin expression. The influence of reelin expression by ocean cells and interneurons on their own morphological differentiation and that of MECII island cells has remained unknown. To address this, we used a conditional reelin knockout (RelncKO) mouse to induce reelin deficiency postnatally in vitro and in vivo. Reelin deficiency caused dendritic hypertrophy of ocean cells, interneurons and only proximal dendritic compartments of island cells. Ca2+ recording showed that both cell types exhibited an elevation of calcium frequencies in RelncKO, indicating that the hypertrophic effect is related to excessive Ca2+ signalling. Moreover, pharmacological receptor blockade in RelncKO mouse revealed malfunctioning of GABAB, NMDA and AMPA receptors. Collectively, this study emphasizes the significance of reelin in neuronal growth, and its absence results in dendrite hypertrophy of MECII neurons.
Differential proliferation regulates multi-tissue morphogenesis during embryonic axial extension: integrating viscous modeling and experimental approaches
Authors: Romanos Michèle , Salisbury Tasha , Stephan Samuel , Lansford Rusty , Degond Pierre , Trescases Ariane , Bénazéraf Bertrand
Published: June 2024

A major challenge in biology is to understand how mechanical interactions and cellular behavior affect the shapes of tissues and embryo morphology. The extension of the neural tube and paraxial mesoderm, which form the spinal cord and musculoskeletal system, respectively, results in the elongated shape of the vertebrate embryonic body. Despite our understanding of how each of these tissues elongates independently of the others, the morphogenetic consequences of their simultaneous growth and mechanical interactions are still unclear. Our study investigates how differential growth, tissue biophysical properties and mechanical interactions affect embryonic morphogenesis during axial extension using a 2D multi-tissue continuum-based mathematical model. Our model captures the dynamics observed in vivo by time-lapse imaging of bird embryos, and reveals the underestimated influence of differential tissue proliferation rates. We confirmed this prediction in quail embryos by showing that decreasing the rate of cell proliferation in the paraxial mesoderm affects long-term tissue dynamics, and shaping of both the paraxial mesoderm and the neighboring neural tube. Overall, our work provides a new theoretical platform upon which to consider the long-term consequences of tissue differential growth and mechanical interactions on morphogenesis.
Charge block-driven liquid–liquid phase separation – mechanism and biological roles
Authors: Koyama Tetsu , Iso Naoki , Norizoe Yuki , Sakaue Takahiro , Yoshimura Shige H.
Published: June 2024

Liquid–liquid phase separation (LLPS) has increasingly been found to play pivotal roles in a number of intracellular events and reactions, and has introduced a new paradigm in cell biology to explain protein–protein and enzyme–ligand interactions beyond conventional molecular and biochemical theories. LLPS is driven by the cumulative effects of weak and promiscuous interactions, including electrostatic, hydrophobic and cation–π interactions, among polypeptides containing intrinsically disordered regions (IDRs) and describes the macroscopic behaviours of IDR-containing proteins in an intracellular milieu. Recent studies have revealed that interactions between ‘charge blocks’ – clusters of like charges along the polypeptide chain – strongly induce LLPS and play fundamental roles in its spatiotemporal regulation. Introducing a new parameter, termed ‘charge blockiness’, into physicochemical models of disordered polypeptides has yielded a better understanding of how the intrinsic amino acid sequence of a polypeptide determines the spatiotemporal occurrence of LLPS within a cell. Charge blockiness might also explain why some post-translational modifications segregate within IDRs and how they regulate LLPS. In this Review, we summarise recent progress towards understanding the mechanism and biological roles of charge block-driven LLPS and discuss how this new characteristic parameter of polypeptides offers new possibilities in the fields of structural biology and cell biology.
Understanding the influence of context on real-world walking energetics
Authors: Baroudi Loubna , Barton Kira , Cain Stephen M. , Shorter K. Alex
Published: June 2024

Speeds that minimize energetic cost during steady-state walking have been observed during lab-based investigations of walking biomechanics and energetics. However, in real-world scenarios, humans walk in a variety of contexts that can elicit different walking strategies, and may not always prioritize minimizing energetic cost. To investigate whether individuals tend to select energetically optimal speeds in real-world situations and how contextual factors influence gait, we conducted a study combining data from lab and real-world experiments. Walking kinematics and context were measured during daily life over a week (N=17) using wearable sensors and a mobile phone. To determine context, we utilized self-reported activity logs, GPS data and follow-up exit interviews. Additionally, we estimated energetic cost using respirometry over a range of gait speeds in the lab. Gross and net cost of transport were calculated for each participant, and were used to identify energetically optimal walking speed ranges for each participant. The proportion of real-world steady-state stride speeds within these ranges (gross and net) were identified for all data and for each context. We found that energetically optimal speeds predicted by gross cost of transport were more predictive of walking speeds used during daily life than speeds that would minimize net cost of transport. On average, 82.2% of all steady-state stride speeds were energetically optimal for gross cost of transport for all contexts and participants, while only 45.6% were energetically optimal for net cost of transport. These results suggest that while energetic cost is a factor considered by humans when selecting gait speed in daily life, it is not the sole determining factor. Context contributes to the observed variability in movement parameters both within and between individuals.
Effects of sublethal methylmercury and food stress on songbird energetic performance: metabolic rates, molt and feather quality
Authors: Bottini Claire L. J. , Whiley Rebecca E. , Branfireun Brian A. , MacDougall-Shackleton Scott A.
Published: June 2024

Organisms regularly adjust their physiology and energy balance in response to predictable seasonal environmental changes. Stressors and contaminants have the potential to disrupt these critical seasonal transitions. No studies have investigated how simultaneous exposure to the ubiquitous toxin methylmercury (MeHg) and food stress affects birds' physiological performance across seasons. We quantified several aspects of energetic performance in song sparrows, Melospiza melodia, exposed or not to unpredictable food stress and MeHg in a 2×2 experimental design, over 3 months during the breeding season, followed by 3 months post-exposure. Birds exposed to food stress had reduced basal metabolic rate and non-significant higher factorial metabolic scope during the exposure period, and had a greater increase in lean mass throughout most of the experimental period. Birds exposed to MeHg had increased molt duration, and increased mass:length ratio of some of their primary feathers. Birds exposed to the combined food stress and MeHg treatment often had responses similar to the stress-only or MeHg-only exposure groups, suggesting these treatments affected physiological performance through different mechanisms and resulted in compensatory or independent effects. Because the MeHg and stress variables were selected in candidate models with a ΔAICc lower than 2 but the 95% confidence interval of these variables overlapped zero, we found weak support for MeHg effects on all measures except basal metabolic rate, and for food stress effects on maximum metabolic rate, factorial metabolic scope and feather mass:length ratio. This suggests that MeHg and food stress effects on these measures are statistically identified but not simple and/or were too weak to be detected via linear regression. Overall, combined exposure to ecologically relevant MeHg and unpredictable food stress during the breeding season does not appear to induce extra energetic costs for songbirds in the post-exposure period. However, MeHg effects on molt duration could carry over across multiple annual cycle stages.
The effects of humidity on thermoregulatory physiology of a small songbird
Authors: Porter Cody K. , Cortes Kevin M. , Levy Ofir , Riddell Eric A.
Published: June 2024

Scholander–Irving curves describe the relationship between ambient temperature and metabolic rate and are fundamental to understanding the energetic demands of homeothermy. However, Scholander–Irving curves are typically measured in dry air, which is not representative of the humidity many organisms experience in nature. Consequently, it is unclear (1) whether Scholander–Irving curves (especially below thermoneutrality) are altered by humidity, given the effects of humidity on thermal properties of air, and (2) whether physiological responses associated with Scholander–Irving curves in the lab reflect organismal performance in humid field conditions. We used laboratory experiments and biophysical models to test the effects of humidity on the thermoregulatory physiology of tree swallows (Tachycineta bicolor). We also tested whether physiological responses measured under lab conditions were correlated with field body temperatures and nestling provisioning rates. We found that humidity reduced rates of evaporative water loss but did not have large effects on body temperature or metabolic rate, suggesting that swallows can decouple evaporative cooling, body temperature and metabolic rate. Although the effect of humidity on metabolic rate in the lab was small, our biophysical models indicated that energetic costs of thermoregulation were ∼8% greater in simulations that used metabolic rates from birds in humid compared with dry conditions. Finally, we found mixed evidence that physiological responses measured in the lab under humid or dry conditions were associated with body temperature and nest provisioning rates in the field. Our results help clarify the effect of humidity on endotherm thermoregulation, which may help forecast organismal responses to environmental change.
Ο ρόλος των αντί-γδ TCR στην ενεργοποίηση των T-ρυθμιστικών κυττάρων και της Th17 οδού σε πειραματική ισχαιμία/επαναιμάτωση του ήπατος
Authors: Άλ-Μογράμπι Σάαντ
Published: June 2024

Τα ουδετερόφιλα και τα Τ-λεμφοκύτταρα μεταναστεύουν στο ήπαρ στα αρχικά στάδια της επαναιμάτωσης και συνεισφέρουν στην ηπατική βλάβη από ισχαιμία-επαναιμάτωση. Η αρχική ανοσολογική απάντηση ενορχηστρώνεται από τα κύτταρα Kupffer και τα ενδοθηλιακά κύτταρα των κολποειδών του ήπατος. Ωστόσο, σε αυτήν την απάντηση συμμετέχουν και άλλοι κυτταρικοί τύποι, μεταξύ των οποίων τα γδ Τ-λεμφοκύτταρα, τα οποία φαίνεται να είναι διαμεσολαβητές κλειδί όσον αφορά την στρατολόγηση των ουδετεροφίλων και την παραγωγή προφλεγμονωδών κυτταροκινών. Στη μελέτη που πραγματοποιήσαμε, χρησιμοποιήσαμε ένα invivo μοντέλο μερικής ηπατικής ισχαιμίας-επαναιμάτωσης (I-E) με σκοπό να μελετήσουμε τον ρόλο του υποδοχέα γδ T-cellreceptor (γδ TCR) στην παθογένεση της ηπατικής βλάβης. Τριάντα μύες τύπου C57BL6 υποβλήθηκαν σε 60 min ισχαιμίας ακολουθούμενα από 6h επαναιμάτωσης. Η πειραματική ομάδα έλαβε με ενδοπεριτοναϊκή έγχυση αντισώματα έναντι του γδ ΤCR (αντι-γδ TCR) 72 ώρες προτού υποβληθούν στο πρωτόκολλο της μερικής ηπατικής ισχαιμίας-επαναιμάτωσης. Η μελέτη εγκρίθηκε από την σχετική επιτροπή βιοηθικής με αριθμό πρωτοκόλλου RN 6339/2/2016.Η χορήγηση των αντι-γδ TCR αντισωμάτων οδήγησε σε μείωση των ιστολογικών και βιοχημικών παραμέτρων ηπατικής βλάβης, αλλά και σε μείωση της διήθησης του ηπατικού παρεγχύματος από λεμφοκύτταρα και λοιπά Τ-λεμφοκύτταρα. Η παραγωγή προφλεγμονωδών κυτταροκινών μειώθηκε και παρατηρήθηκε μειωμένη ενεργοποίηση μεταγραφικών παραγόντων, όπως ο NF-κB, που διαδραματίζει κεντρικό ρόλο στη φλεγμονώδη απάντηση μετά την Ι-Ε. Η αδρανοποίηση του υποδοχέα γδ TCR φαίνεται να παίζει προστατευτικό ρόλο στην ηπατική βλάβη από Ι-Ε κυρίως μειώνοντας την στρατολόγηση των ουδετεροφίλων και των Τ-λεμφοκυττάρων στο ήπαρ, αλλά και μειώνοντας τα επίπεδα διαφόρων προφλεγμονωδών κυτταροκινών. Το γεγονός αυτό αναδεικνύει τον γδ TCR ως φαρμακολογικό στόχο για μελλοντικές θεραπείες, που θα προσπαθήσουν να μειώσουν την ηπατική βλάβη σε πραγματικές συνθήκες.
Η υιοθέτηση της εταιρικής κοινωνικής ευθύνης στη στρατηγική μάρκετινγκ και η επίδραση στην αποτελεσματικότητα των επιχειρήσεων
Authors: Δραγώτης Ευθυμίος
Published: June 2024

Ο σύγχρονος ορισμός και οι σύγχρονες θεωρήσεις του Μάρκετινγκ έχουν ως αναπόσπαστο κομμάτι τους την κοινωνική διάσταση, γεγονός που υπογραμμίζει τη σημαντικότητα της Εταιρικής Κοινωνικής Ευθύνης (ΕΚΕ) στο σύγχρονο περιβάλλον. Η ΕΚΕ έχει αποτελέσει σημαντικό αντικείμενο έρευνας σε διεθνές επίπεδο τα τελευταία χρόνια υπό το πρίσμα της επίδρασής της σε διάφορες όψεις της επιχειρηματικής λειτουργίας και επί του αντικτύπου της στην καταναλωτική συμπεριφορά. Παρά το μεγάλο ερευνητικό ενδιαφέρον, λίγες έρευνες χρησιμοποιούν μια Ολιστική Προσέγγιση για την ΕΚΕ, εκτιμώντας την υιοθέτησή της σε όλα τα πιθανά επίπεδα. Η διατριβή χρησιμοποιεί μια τέτοια προσέγγιση εκτιμώντας την επίδραση που έχει η υιοθέτηση πολιτικών και πρακτικών ΕΚΕ στην αποτελεσματικότητα της επιχείρησης. Ως προς την αποτελεσματικότητα, η διατριβή ανοίγει μια μεγάλη βεντάλια ερωτημάτων σε σχέση με τους τομείς που πιθανώς ωφελείται η επιχείρηση, εξετάζοντας την οικονομική αποδοτικότητα, τις σχέσεις με τους πελάτες, την εταιρική εικόνα, την ανάπτυξη καινοτομιών, τις συνεργασίες και την απόδοση των εργαζομένων. Βασικό στοιχείο της διατριβής, διαδραματίζουν οι στρατηγικές επικοινωνίας μάρκετινγκ, οι οποίες αναδεικνύονται ιδιαίτερα σημαντικές στο σύγχρονο επιχειρηματικό περιβάλλον. Οι στρατηγικές επικοινωνίας διαδραματίζουν διαμεσολαβητικό ρόλο ανάμεσα στην υιοθέτηση της ΕΚΕ και τις πλευρές της αποτελεσματικότητας. Συνεπώς, η διατριβή χρησιμοποιεί ένα δομικό μοντέλο για να εξετάσει την υιοθέτηση της Εταιρικής Κοινωνικής Ευθύνης στη στρατηγική μάρκετινγκ και την επίδραση στην αποτελεσματικότητα των επιχειρήσεων. Το δείγμα της μελέτης αποτελείται από εργαζόμενους σε επιχειρήσεις που έχουν υιοθετήσει την ΕΚΕ. Τα βασικά ευρήματα της διατριβής δείχνουν ότι όλα τα πεδία υιοθέτησης της ΕΚΕ είναι ιδιαίτερα σημαντικά για την αποτελεσματικότητά της σε όψεις της λειτουργίας των επιχειρήσεων. Παρά την απευθείας στατιστικά σημαντική σχέση, η σχέση διαμεσολάβησης των στρατηγικών επικοινωνίας δεν επιβεβαιώνεται για όλες τις όψεις αποτελεσματικότητας. Οι στρατηγικές επικοινωνίας μάρκετινγκ επιβεβαιώνονται ως διαμεσολαβητική μεταβλητή μονάχα για την οικονομική αποδοτικότητα, τις σχέσεις με τους πελάτες και την ικανότητα ανάπτυξης καινοτομιών. Τα γενικά συμπεράσματα της διατριβής δείχνουν ότι η ΕΚΕ δεν μπορεί να εκλαμβάνεται ως διάσπαρτες δράσεις αλλά ως μια συνολική θεώρηση η οποία είναι συνυφασμένη με το σύνολο της δραστηριότητας των επιχειρήσεων, ριζωμένη στην εταιρική κουλτούρα. Συνεπώς, η ΕΚΕ αποδεικνύεται σημαντική για κάθε όψη της επιχειρηματικής λειτουργίας. Τέλος τα ευρήματα της διατριβής υπογραμμίζουν τη σημαντικότητα των στρατηγικών επικοινωνίας μάρκετινγκ ως παράγοντας που ενισχύει την επίδραση της υιοθέτησης σε όψεις της αποτελεσματικότητας. Αυτή η επίδραση θα πρέπει να μελετηθεί διεξοδικά από τα στελέχη των τμημάτων μάρκετινγκ και επιχειρηματικού σχεδιασμού των επιχειρήσεων, για την βελτιστοποίηση της δράσης τους και την ανάπτυξη πιο επικερδών στρατηγικών.
Short-term Persistence Performance of Equity Mutual Fund Returns: Evidence from India
Authors: Veeravel V.
Published: June 2024

The present study verifies the short-term persistence performance of equity mutual fund returns. The study considers 47 equity funds' monthly excess returns spanning from January 2000 to December 2019. The study employs prominent asset pricing models such as Jensen (1968) one-factor model, Fama-French (1993) three-factor model, and Carhart (1997) four-factor model to capture the short-term persistence of equity mutual fund returns. The results show that Jensen’s one-factor and Fama-French three-factor models are explaining a better persistence performance in the Indian context.
Sustainability Committee, Audit Firm Type and Corporate Sustainability Reporting of Non-Financial Firms in Nigeria
Authors: Muhammed Kamaldeen Usman
Published: June 2024

In spite of the detrimental consequences, such as pollution and other environmental risks arising from corporate activities, there has been a noticeable lack of transparency in disclosing social, environmental, and economic information. In light of this, the research aims to present empirical evidence regarding the impact of sustainability committees and the type of audit firm on the reporting of corporate sustainability information by companies. The study utilized an Ex-post facto research design, considering a population of one hundred and fifteen (115) listed non-financial firms. Ninety-two (92) companies were selected as the sample. Both descriptive and inferential (Panel Corrected Standard Error) estimation techniques were employed to analyze data collected from the annual reports and accounts of the sampled listed manufacturing companies over a seven-year period (2016-2022). The findings revealed that the presence of a sustainability committee and audit type significantly predict corporate sustainability reporting among listed non-financial firms at a 5% level of significance. In conclusion, the study determined that sustainability committees and audit types play a crucial and meaningful role in shaping corporate sustainability reporting practices among listed non-financial firms in Nigeria. As a result, the study recommends that listed companies should establish sustainability committees to proactively address sustainability issues and enhance disclosure. Additionally, non-Big Four audit firms are encouraged to enhance their services by providing their staff with up-to-date audit skills.
Comparison Between Cardio-Electrophysiological Balance Index and Corrected Values in Different Age Groups Among School-Age Children
Authors: Güneş Ömer , Güney Ahmet Yasin , Halil Halit , Kayalı Akyol Aylin , Akyol Özhan , Üçkardeş Fatih , Öztelcan Gündüz Bahar , Aydoğmuş Yüksel Hakan , Pamuk Utku , Kılıç Ayhan , Ünay Bülent
Published: June 2024

Objective: The index of cardio-electrophysiological balance (iCEB) is a new non-invasive marker that can be used to predict malignant ventricular arrhythmias. Pediatric studies on iCEB are limited in number. Our study aimed to determine the range of its values in different age groups among school-age children.

Material and Methods: The study included patients aged 5-17 admitted to Gülhane Training and Research Hospital Pediatric Cardiology Outpatient Clinic between March 2020 and March 2022 without a history of chronic disease, cardiac disease, arrhythmia, or cardiac surgery. Participants were categorised into ages 5-8, 9-12, and 13-17. The iCEB and iCEBc values were calculated and compared between groups.

Results: The total number of 1303 cases were categorised into the 5-8 (n=270), 9-12 (n=389), and 13-17 (n=644) age groups. The mean iCEB and iCEBc values for all age groups were 4.39±0.53 and 5.16±0.53, respectively. Any difference was not detected among age groups of 5-8, 9-12, and 13-17 years in terms of iCEB and iCEBc values (4.42±0.56, 4.39±0.53 and 4.39±0.52 vs. 5.19±0.56, 5.15±0.55 and 5.16±0.52, respectively). However, a significant difference was found between male (n=699) and female (n=604) patients in terms of mean iCEB (4.23±0.52 vs. 4.59±0.47) and iCEBc (4.98±0.53 vs. 5.38±0.46) values (p <0.001).

Conclusion: iCEB and iCEBc values in school-age children did not differ according to age groups. However, these values differed between boys and girls. This study is the first to reveal normal ranges of iCEB and iCEBc values in school-age children.
PATH-2 TRIAL: PLATELET-RICH PLASMA FOR ACUTE ACHILLES TENDON RUPTURE. TWO-YEAR FOLLOW-UP OF THE RANDOMIZED, PLACEBO-CONTROLLED, SUPERIORITY TRIAL
Authors: Alsousou J. , Keene D. , Harrison P. , O'Connor H. , Wagland S. , Dutton S. , Hulley P. , Lamb S. , Willett K.
Published: June 2024

Background

The PATH-2 trial found no evidence of a benefit of Platelet Rich Plasma (PRP) injection versus a placebo after Achilles tendon rupture (ATR) at six-months. ATR often leave longer-term functional deficiencies beyond six-months. This study aim is to determine if PRP affect tendon functional outcomes at two-years after rupture.

Study design

Randomised multi-centre two-arm parallel-group, participant- and assessor-blinded, superiority trial.

Methods

Adults with acute ATR managed non-surgically were recruited in 19 UK hospitals from 2015 to 2019. Exclusions were insertion or musculotendinous injuries, leg injury or deformity, diabetes, haematological disorder, corticosteroids and anticoagulation therapy. Participants were randomised via an online system 1:1 to PRP or placebo. Primary outcome was Achilles Tendon Rupture Score (ATRS) at two-years. Secondary outcomes were pain, Patient-Specific Functional Scale (PSFS), SF-12 and re-rupture. Assessors were blinded. Intention-to-treat and Compliance Average Causal effects (CACE) analyses were carried out. Consistency of effects across subgroups age, BMI, smoking and gender were assessed using Forest plots. Pearson's correlation was used to explore ATRS correlation with blood and growth factors.

Results

216/230 (94%) participants completed the 6-months follow-up were contacted. 182/216 (84%) completed the two-year follow-up. Participants were aged mean 46 (SD 13.0), 57 female/159 male. 96% received the allocated intervention. Two-years ATRS scores were 82.2 (SD 18.3) in the PRP group (n=85) and 83.8 (SD 16.0) in the placebo group (n=92). There was no evidence of a difference in the two-years ATRS (adjusted-mean difference −0.752 95%CI −5.523 to 4.020, p=0.757), or in any secondary outcome, and no re-rupture between at two-years. Neither PRP cellular or growth factors correlated with the two-year ATRS.

Conclusion

PRP did not improve patient-reported function or quality of life two-years after acute Achilles tendon rupture, compared with placebo, indicating that PRP offers no patient benefit in the longer term.
LONG-TERM FOLLOW-UP OF COMPLEX CALCANEAL OSTEOMYELITIS TREATED WITH MODIFIED GAENSLEN APPROACH
Authors: Kendal A. , Down B. , Loizou C. , McNally M.
Published: June 2024

Background

The treatment of chronic calcaneal osteomyelitis is a challenging and increasing problem because of the high prevalence of diabetes mellitus and operative fixation of heel fractures. In 1931, Gaenslen reported treatment of hematogenous calcaneal osteomyelitis by surgical excision through a midline, sagittal plantar incision. We have refined this approach to allow successful healing and early mobilization in a modern series of complex patients with hematogenous, diabetic, and postsurgical osteomyelitis.

Methods

Twenty-eight patients (mean age 54.6 years, range 20–94) with Cierny-Mader stage IIIB chronic osteomyelitis were treated with sagittal incision and calcaneal osteotomy, excision of infected bone, and wound closure. All patients received antibiotics for at least 6 weeks, and bone defects were filled with an antibiotic carrier in 20 patients. Patients were followed for a mean of 31 months (SD 25.4). Primary outcome measures were recurrence of calcaneal osteomyelitis and below-knee amputation. Secondary outcome measures included 30-day postoperative mortality and complications, duration of postoperative inpatient stay, footwear adaptions, mobility, and use of walking aids.

Results

All 28 patients had failed previous medical and surgical treatment. Eighteen patients (64%) had significant comorbidities. The commonest causes of infection were diabetes ± ulceration (11 patients), fracture-related infection (4 patients), pressure ulceration, hematogenous spread, and penetrating soft tissue trauma. The overall recurrence rate of calcaneal osteomyelitis was 18% (5 patients) over the follow-up period, of which 2 patients (7%) required a below-knee amputation. Eighteen patients (64%) had a foot that comfortably fitted into a normal shoe with a custom insole. A further 6 patients (21%) required a custom-made shoe, and only 3 patients required a custom-made boot.

Conclusion

Our results show that a repurposed Gaenslen calcanectomy is simple, safe, and effective in treating this difficult condition in a patient group with significant local and systemic comorbidities.
STRUCTURAL VALIDATION OF THE MANCHESTER-OXFORD FOOT QUESTIONNAIRE (MOXFQ) FOR USE IN FOOT AND ANKLE SURGERY
Authors: Goodall R. , Borsky K. , Harrison C. , Welck M. , Malhotra K. , Rodrigues J.
Published: June 2024

Background

The Manchester-Oxford Foot Questionnaire (MOxFQ) is a condition specific patient reported outcome measure (PROM) for foot and ankle surgery. It consists of 16 items across three subscales measuring distinct, but related traits: walking/standing ability, pain, and social interaction. Although it is the most used foot and ankle PROM in the UK, initial MOxFQ validation involved analysis of only 100 individuals undergoing hallux valgus surgery. This project aimed to establish whether an individual's response to the MOxFQ varies with anatomical region of disease (measurement invariance), and to explore structural validity of the factor structure (subscale items) of the MOxFQ.

Methods

This was a single-centre, prospective cohort study involving 6640 patients (mean age 52, range 10–90 years) presenting with a wide range of foot and ankle pathologies between 2013 and 2021. Firstly, to assess whether the MOxFQ responses vary by anatomical region of foot and ankle disease, we performed multi-group confirmatory factor analysis. Secondly, to assess the structural validity of the subscale items, exploratory and confirmatory factor analyses were performed.

Results

Measurement invariance by pathology was confirmed suggesting the same model can be used across all foot and ankle anatomical regions. Exploratory factor analysis demonstrated a 2–3 factor model, and suggested that item 13 (inability to carry out my work/everyday activities) and item 14 (inability to undertake social/recreational activities) loaded more positively onto the walking/standing subscale than their original social interaction subscale.

Conclusions

This large-cohort study supports the current widespread use of the MOxFQ across a broad range of foot and ankle pathologies. Items 13 and 14 might be better moved from the “social interaction” to the “walking/standing” subscale and this may have future implications for deriving/analysing subscale scores.
METAL DEBRIS RELEASE MAY BE UNDER-RECOGNIZED IN TOTAL ANKLE ARTHROPLASTY
Authors: Haston S. , Langton D. , Townshend D. , Bhalekar R. , Joyce T.
Published: June 2024

Despite advancements, revision rates following total ankle replacement (TAR) are high in comparison to other total joint replacements. This explant analysis study aimed to investigate whether there was appreciable metal particulate debris release from various contemporary TARs by describing patterns of material loss. Twenty-eight explanted TARs (9 designs: 3 fixed and 6 mobile bearing), revised for any reason, were studied. The articulating surfaces of the metal tibial and talar components as well as the polyethylene insert were assessed for damage features using light microscopy. Based on the results of the microscopic analysis, scanning electron microscopy with energy dispersive X-ray spectroscopy was performed to determine the composition of embedded debris identified, as well as non-contacting 3D profilometry. Pitting, indicative of material loss, was identified on the articulating surfaces of 54% of tibial components and 96% of talar components. Bearing constraint was not found to be a factor, with similar proportions of fixed and mobile bearing metal components showing pitting. More cobalt-chromium than titanium alloy tibial components exhibited pitting (63% versus 20%). Significantly higher average surface roughness (Sa) values were measured for pitted areas in comparison to unpitted areas of these metal components (p<0.05). Additionally, metallic embedded debris (cobalt-chromium likely due to pitting of the tibial and talar components or titanium likely from loss of their porous coatings) was identified in 18% of polyethylene inserts. The presence of hard 3rd body particles was also indicated by macroscopically visible sliding plane scratching, identified on 79% of talar components. This explant analysis study demonstrates that metal debris is released from the articulating surfaces and the coatings of various contemporary TARs, both fixed and mobile bearing. These findings suggest that metal debris release in TARs may be an under-recognised issue that should be considered in the study of painful or failed TAR moving forwards.
Development of Jets rig dedicated for an Active Launch Escape Abort System Wind Tunnel Model
Authors: STOICAN Mihaita Gilbert , ANDREI Marina , SALAORU Tiberiu , BUNESCU Ionut , HOTHAZIE Mihai-Vladut , PRICOP Mihai Victor
Published: June 2024

The development of space launch systems requires rigorous testing and validation of safety mechanisms to ensure the protection of human life and mission-critical assets. One such safety mechanism is the Active Launch Escape/Abort System (ALEAS), designed to swiftly extract crew and spacecraft from a malfunctioning launch vehicle. To evaluate the performance of ALEAS, wind tunnel testing is indispensable. This paper presents the development of a specialized Jets Rig tailored for wind tunnel testing of an ALEAS model. The primary objectives of this research activity include the design, construction, and validation of a Jets Rig that can accurately simulate the propulsion dynamics of an ALEAS system within a wind tunnel environment. The Jets Rig incorporates a special instrumentation and control systems to replicate the complex operational conditions experienced during a launch abort scenario. By achieving this, it enables a comprehensive assessment of ALEAS performance, including thrust duration and plume interaction effects, among others. Key aspects of this study encompass the aerodynamic and structural considerations involved in designing the Jets Rig, the integration of high-fidelity sensors and data acquisition systems, and the development of advanced computational models for predictive analysis. Additionally, the research explores the challenges and solutions associated with the scalability of the Jets Rig to accommodate varying scales of ALEAS models. The findings from this project hold significant implications for advancing the safety and reliability of crewed space missions. A comprehensive understanding of ALEAS performance in a wind tunnel setting allows for the refinement of design parameters, algorithms, and the enhancement of abort system efficiency. Ultimately, the successful development of this dedicated Jets Rig contributes to the broader mission of ensuring the safe exploration of space and the protection of human life in the challenging and dynamic environment of space launch.
Quadcopter-Rover System for Environmental Survey Applications
Authors: ABOUGABAL Mohamed H. , GAMAL Mohammad K. , MOHAMED AMIEN Mohamed T. , MOHAMED Shehab O. , KASSEM Ayman H.
Published: June 2024

This paper explores the development of a Quadcopter-Rover System specifically designed for environmental survey applications. The system combines the capabilities of a quadcopter and a rover to provide a comprehensive and versatile solution for data collection and analysis. The paper presents a detailed overview of the system's modelling, design, and manufacturing of the two main components: the quadcopter and the differential wheel robot (the rover). The quadcopter’s main task is to carry the rover to/from the ground destination and collect aerial data while the rover`s main task is ground exploration and data collection. The paper discusses the development of a robust and efficient control algorithm that enables autonomous and coordinated operation between the quadcopter and the rover. Experimental results demonstrate the system's effectiveness in conducting environmental surveys, showcasing its ability to accurately navigate challenging terrains, and collect valuable data for environmental analysis. The Quadcopter-Rover System offers significant potential in applications such as ecological monitoring, disaster management, and precision agriculture, where comprehensive and efficient data collection is crucial for informed decision-making.
La ligereza del Tribunal Supremo ante las víctimas de trata
Authors: Martínez Escamilla Margarita
Published: June 2024

La sentencia analizada va más allá del caso concreto enjuiciado, al realizar importantes pronunciamientos sobre el “principio de no punición” a las víctimas de trata recogido en el art. 177 bis 11 del Código penal, pronunciamientos que restringen la aplicación de este principio, que es un derecho de las víctimas. Lo hace, además, con una motivación descuidada que no se corresponde con la novedad y trascendencia de las cuestiones planteadas, ni con el enfoque de derechos humanos que ha presidir el acercamiento a las víctimas de trata y que exige un deber reforzado de atención y motivación. 
La sentencia del Supremo revoca una sentencia absolutoria y devuelve el caso al tribunal de instancia para que examine otras posibilidades de adecuar la responsabilidad penal a la situación de necesidad y extrema vulnerabilidad de Angelina y al abuso que se hizo de ella. Este trabajo finaliza apuntando algunas alternativas posibles.
La protección de las víctimas de trata a traves del art. 4 del Convenio Europeo de Derechos Humanos
Authors: Valle Mariscal de Gante Margarita
Published: June 2024

El presente trabajo tiene como objetivo analizar la Sentencia del Tribunal Europeo de Derechos Humanos Zoletic y otros c. Azerbaiyán, de 7 de octubre de 2021. En dicha Sentencia se ocupa el Tribunal de asentar su doctrina jurisprudencial en relación con la inclusión de la trata de seres humanos dentro del ámbito aplicativo del art. 4 del Convenio Europeo de Derechos Humanos, analizando también qué ha de entenderse por trabajo forzado en el contexto de la trata y del propio art. 4. Por último concreta el contenido de las obligaciones positivas de los Estados, haciendo especial hincapié en la obligación de cooperación internacional entre Estados.