bluuebunny/crossref_metadata_2025 huggingface dataset:
MHC class II: a predictor of outcome in melanoma treated with immune checkpoint inhibitors
Authors: Amrane Karim , Le Noac'h Pierre , Hemon Patrice , Abgral Ronan , Le Meur Coline , Pradier Olivier , Misery Laurent , Legoupil Delphine , Berthou Christian , Uguen Arnaud
Published: February 2025

This study aimed to evaluate the predictive value of MHC class II (MHC-II) expression by melanoma cells in a large cohort of metastatic cutaneous melanoma patients treated with immune checkpoint inhibitors (ICIs). We conducted a single-center, retrospective study involving stage IV cutaneous melanoma patients who received ICI as first-line therapy. MHC-II expression in melanoma cells was quantified using dual-color anti-SOX10 and anti-MHC-II immunohistochemistry on tumor samples from 95 patients. The primary endpoint was event-free survival (EFS), with secondary endpoints including 1-year EFS, 1-year overall survival (OS), disease control rate (DCR), and the correlation between MHC-II expression and clinico-biological characteristics. The cohort had a median age of 67 years (range, 33–90), with a male-to-female ratio of 50 : 45. Thirty-three percent of patients received the ipilimumab-nivolumab combination. The median follow-up was 16.8 months. Disease progression occurred in 58 patients (61%), with a median time to progression of 4.8 months. Forty-six patients (48.4%) experienced an event within the first year, and 52 patients (54.7%) died during follow-up. MHC-II positivity was observed in ≥10% of melanoma cells in 6.3% of patients. MHC-II expression was significantly associated with 1-year EFS (P = 0.037) and DCR (P = 0.032), but not with EFS or 1-year OS. Age, phototype, and brain metastases were correlated with MHC-II expression status. Our findings suggest that MHC-II expression by melanoma cells may serve as a favorable predictive biomarker for survival in metastatic cutaneous melanoma patients treated with ICIs.
Mortality and Complications in Hybrid Extracorporeal Membrane Oxygenation: A Meta-Analysis of Initial Use Versus Transition
Authors: Shin Irin , Ryu Haein , Hou Yujeong , Kim Mi Sung , Rhie Sandy Jeong
Published: February 2025

Hybrid extracorporeal membrane oxygenation (ECMO), containing additional ECMO cannulations in addition to conventional ECMO, is increasingly used for the treatment of serious cardiopulmonary conditions. Patients initiating non-hybrid ECMO may transition to hybrid ECMO as their condition worsens. This study compared mortality rates between patients initially on hybrid ECMO and those who transitioned from non-hybrid to hybrid ECMO. We also examined complications related to hybrid ECMO, comparing them with those of non-hybrid ECMO. Data from PubMed, Embase, and Cochrane databases were analyzed using Peto odds ratios and 95% confidential intervals (CIs), with an additional safety comparison to the Extracorporeal Life Support Organization registry to overcome the small number of selected studies. A meta-analysis was performed using review manager. The mortality rate did not differ significantly between whether the hybrid ECMO was used initially or transitioned from non-hybrid ECMO during treatment. Renal-related complications were the most frequent in both hybrid and non-hybrid ECMO cases, with overall higher complication rates in hybrid ECMO. The study concludes that transitioning to hybrid ECMO during treatment does not increase mortality compared to starting with hybrid ECMO, but potential complications, especially with commodity conditions, should be considered. This study provides valuable guidance for clinicians choosing ECMO modalities in clinical practice.
Histologic Comparison of Ultra-fine Diced Cartilage and Conventionally Diced Cartilage Wrapped in Fascia in a Rabbit model
Authors: Lee Seok Joon , Kim Young Sam , Jeong Hyung Hwa , Kim Tae Hyung , Choi Jong Woo
Published: February 2025

Background:

Ultra-fine dicing, which reduces cartilage particles to less than 0.2 mm, has gained attention for producing dense implants with reduced distortion. However, concerns about long-term viability and cell damage due to extensive manipulation remain. We aimed to compare the histological outcomes of ultra-fine and conventionally diced cartilage wrapped in fascia in a rabbit model, providing insight into their potential use in rhinoplasty.

Methods:

Ten New Zealand White rabbits were divided into two groups. Cartilage was harvested from both ears, with one graft diced into 1–2 mm pieces and the other into pieces less than 0.2 mm. Both types were wrapped in fascia and implanted subcutaneously. Histological analyses using hematoxylin and eosin, Masson’s trichrome, and Safranin-O staining were performed at 8 weeks and 6 months postoperatively. The percentages of cartilage cells and dead space were compared between groups.

Results:

Results demonstrated significantly higher cartilage cell density in the ultra-fine diced group at both 8 weeks and 6 months than that in the conventionally diced group. The ultra-fine diced cartilage also exhibited less dead space and maintained a dense composition of type II collagen, suggesting a resilient and natural implant material.

Conclusions:

Ultra-fine dicing resulted in superior histological outcomes, with higher cartilage cell density and less fibrosis compared to those observed with conventional methods. These findings suggest that ultra-fine diced cartilage may be an effective method for achieving natural and stable results in rhinoplasty. However, further research involving human participants is needed to confirm these results.

Clinical relevance statement:

Ultra-fine dicing of cartilage provides superior histological outcomes, with higher cell density and less fibrosis compared to conventional methods. This technique may offer plastic surgeons a more effective option for achieving stable, natural results in rhinoplasty, pending further human studies.
First-in-Human Safety, Tolerability, Efficacy, and Pharmacokinetics of Pegfosimer Manganese (SN132D) for Contrast-Enhanced MRI of Breast Cancer
Authors: Wärnberg Fredrik , Axelsson Oskar , Curiac Dan , Hargreaves Paul , Karakatsanis Andreas , Lekmeechai Sujinna , Hansen Mats
Published: February 2025

Objectives

The primary objective of the first-in-human (FIH) study was to evaluate the safety and tolerability of the manganese (Mn)-based contrast agent pegfosimer manganese in participants with newly diagnosed breast cancer, and secondary objectives included preliminary efficacy, and pharmacokinetics (PK) of the agent.

Methods

A single intravenous 1-hour infusion of pegfosimer manganese was administered to 2 cohorts; 6 participants at the starting dose of 10 μmol Mn/kg, followed by 8 participants at the expansion dose of 20 μmol Mn/kg, cohorts 1 and 2, respectively. The safety was evaluated based on reported adverse events (AEs), including serious AEs, physical examination, vital signs, electrocardiogram, and safety laboratory parameters. Magnetic resonance imaging (MRI) acquisition was performed precontrast and postcontrast to assess the clinical relevance of images in primary breast tumors, liver, and pancreas relative to reference tissue. PK parameters were calculated from a noncompartmental analysis of the plasma Mn concentrations versus time.

Results

There was a total of 29 AEs reported to all participants of the 2 cohorts. The AEs were mostly of mild to moderate severity and possibly or probably related to the contrast agent. No clinically significant changes in the safety laboratory parameters were reported, except for transiently elevated transaminases observed at the end of the infusion. Clinically relevant low-background MRI scans for clinical visualization of primary breast tumor, liver, and pancreas were obtained at the expanded dose level. Pegfosimer manganese has an initial plasma half-life of approximately 7 minutes.

Conclusion

The FIH study of pegfosimer manganese demonstrated an acceptable safety profile and sufficient contrast enhancement for clinically relevant MRI sequences in participants with primary breast tumors.
Tamsulosin to Prevent Urinary Retention After Vaginal Urogynecologic Surgery
Authors: Song Jun , Carrillo Luis , Tibon Jasmine , Botros-Brey Sylvia , Evans Elizabeth , Alas Alexandriah
Published: February 2025

Importance

Postoperative urinary retention (POUR) affects up to 51% of women undergoing surgery for pelvic organ prolapse (POP). Effective prevention strategies remain elusive, although alpha receptor antagonists show promise in recent literature.

Objectives

This study sought to evaluate the effect of preoperative tamsulosin on POUR after vaginal surgery for POP.

Study Design

We conducted a retrospective cohort study of female patients undergoing vaginal surgery for POP, with or without concomitant midurethral sling. Patients who received preoperative tamsulosin were compared with controls. All patients were discharged on the day of surgery after undergoing a standardized voiding trial. The primary outcome was the rate of POUR, defined by a failed voiding trial. Secondary outcomes included complication rates and risk factors for POUR.

Results

A total of 195 patients were included for analysis, with 60 patients (30.8%) receiving tamsulosin and 135 (69.2%) not. Baseline demographics were similar between groups, except the tamsulosin group had lower parity and were less likely to splint to void. The tamsulosin group had similar rates of POUR compared with control (31.7% vs 34.8%, P = 0.67). Multivariate logistic regression controlling for confounders showed no significant effect of tamsulosin on POUR rates (odds ratio, 0.65; 95% confidence interval, 0.31–1.35; P = 0.24). Concomitant sling placement was identified as the only independent risk factor for POUR (odds ratio, 3.00; 95% confidence interval, 1.55–5.81; P = 0.001).

Conclusions

Preoperative tamsulosin does not appear to be effective in preventing postoperative urinary retention in women undergoing vaginal surgery for POP, whereas concomitant sling placement appears to increase its risk.
Comparative syncytia formation dynamics of coronavirus MHV-A59 and pneumovirus hRSV A2 and incorporation into improved kinetic virus replication models
Authors: Landwehr Emily H. , Vivian Lyla R. , Papadeas George G. , White Ethan J. , Doster Jayden M. , Brenner Nicholas R. , Selesky Kara M. , Zilinski Cora A. , Donovan Angelena M. , Farha Stefania M. , Lewellyn Lindsay , Beachboard Dia C. , Kaschner Scott , Stobart Christopher C.
Published: February 2025

Replication models have been developed to describe the replication dynamics of a variety of viruses to better understand the kinetics and key contributing factors affecting infectivity and spread. However, accurate representations of the dynamics of virus replication observed in vitro and in vivo are often limited due to the failure of these models to account for both environmental influences, such as temperature, and the variety of possible mechanisms employed by viruses to spread. Several major families of viruses including paramyxoviruses, pneumoviruses and coronaviruses, induce and use the formation of syncytia, large multinucleated cell masses formed through fusion of cells, to aid in spread to neighbouring susceptible cells. In this study, we evaluate and compare both the dynamics and roles of temperature and syncytia formation on the replication of two different fusogenic viruses in vitro: human respiratory syncytial virus (hRSV) and a murine coronavirus, mouse hepatitis virus (MHV). Thermal stability, replication kinetics and both the rates and dynamics of syncytia formation were evaluated for hRSV and MHV. These data were then incorporated into a novel and improved replication model for each of the two viruses, which provides new insights into the contributions of both temperature and syncytia formation in the replication of fusogenic viruses.
Persistent Haldane phase in carbon tetris chains
Authors: Abdelwahab Anas , Karrasch Christoph , Rausch Roman
Published: February 2025

We introduce the concept of “tetris chains,” which are linear arrays of four-site molecules that differ by their intermolecular hopping geometry. We investigate the fermionic symmetry-protected topological Haldane phase in these systems using Hubbard-type models. The topological phase diagrams can be understood via different competing limits and mechanisms: strong coupling U≫t, weak coupling U≪t, and the weak intermolecular hopping limit t′≪t. Our particular focus is on two tetris chains that are of experimental relevance. First, we show that a “Y-chain” of coarse-grained nanographene molecules (triangulenes) is robustly in the Haldane phase in the whole t′−U plane due to the cooperative nature of the three limits. Secondly, we study a near-homogeneous “Y′-chain” that is closely related to the electronic model for poly(p-phenylene vinylene). In the latter case, the above mechanisms compete, but the Haldane phase manifests robustly and is stable when long-ranged Pariser-Parr-Popple interactions are added. The site-edged Hubbard ladder can also be viewed as a tetris chain, which gives a very general perspective on the emergence of its fermionic Haldane phase. Our numerical results are obtained by large-scale, SU(2)-symmetric tensor network calculations. We employ the density-matrix-renormalization group as well as the variational uniform matrix-product state (VUMPS) algorithms for finite and infinite systems, respectively. The numerics are supplemented by analytical calculations of the band-structure winding number.

Published by the American Physical Society
2025
Strength measurements of the
ERlab=647
and 1842 keV resonances in the
Ca40(p,γ)Sc41
reaction and their relevance in novae nucleosynthesis
Authors: Sidhu R. S. , deBoer R. J. , Görres J. , Wiescher M. , Koros J. , Manukyan K. , Matney M. , McDonaugh J. , Picciotto V. , Sanchez A. T. , Stech E. , von Seeger W. W. , Zimmer L.
Published: February 2025

Here we report on the direct measurement of the resonance strengths of the ERlab=647keV and 1842 keV resonances in the Ca40(p,γ)Sc41 reaction. At novae temperatures, 0.2<T9<0.7, the Ca40(p,γ)Sc41 reaction is governed by the low energy resonance at ERlab=647keV, whereas the ERlab=1842keV resonance serves as a normalization standard for nuclear reaction experiments within the astrophysically relevant energy range. For the ERlab=647keV resonance, we obtain a resonance strength

ω

γ

=

(

2.51

±

0

.

09

stat

±

0

.

22

syst

)

meV

, with an uncertainty a factor of 2.5 smaller than the previous direct measurement value. For the ERlab=1842keV resonance, we obtain a resonance strength ωγ=(0.148±0.006stat±0.013syst)eV, which is consistent with previous studies but deviates by 2σ from the most recent measurement. Our results suggest Ca40 to be a strong waiting point in the nucleosynthesis path of oxygen-neon (ONe) novae.

Published by the American Physical Society
2025
Searching for stellar-origin binary black holes in LISA Data Challenge 1b: Yorsh
Authors: Bandopadhyay Diganta , Moore Christopher J.
Published: February 2025

This paper reports the first search for stellar-origin binary black holes within the LISA Data Challenges (LDC). The search algorithm and the LDC datasets, both previously described elsewhere, are only summarized briefly; the primary focus here is to present the results of applying the search to the challenge of data. The search employs a hierarchical approach, leveraging semicoherent matching of template waveforms to the data using a variable number of segments, combined with a particle swarm algorithm for parameter space exploration. The computational pipeline is accelerated using graphics processing unit (GPU) hardware. The results of two searches using different models of the LISA response are presented. The most effective search finds all five sources in the data challenge with injected signal-to-noise ratios ≳12. Rapid parameter estimation is performed for these sources.

Published by the American Physical Society
2025
Valley Polarization of Landau Levels in the ZrSiS Surface Band Driven by Residual Strain
Authors: Butler Christopher J. , Murase Masayuki , Sawada Shunki , Jiang Ming-Chun , Hashizume Daisuke , Guo Guang-Yu , Arita Ryotaro , Hanaguri Tetsuo , Sasagawa Takao
Published: February 2025

In a multivalley electronic band structure, lifting of the valley degeneracy is associated with rotational symmetry breaking in the electronic fluid and may emerge through spontaneous symmetry breaking order or through a large response to a small external perturbation such as strain. In this work, we use scanning tunneling microscopy to investigate an unexpected rotational symmetry breaking in Landau levels formed in the unusual floating surface band of ZrSiS. We visualize a ubiquitous splitting of Landau levels into valley-polarized sublevels. We demonstrate methods to measure valley-selective Landau level spectroscopy, to infer unknown Landau level indices, and to precisely measure each valley’s Berry phase in a way that is agnostic to the band structure and topology of the system. These techniques allow us to measure each valley’s low-energy dispersion and infer a rigid valley-dependent contribution to the band energies. Ruling out spontaneous symmetry breaking by establishing the sample dependence of this valley splitting, we explain the effect in terms of residual strain. A quantitative estimate indicates that uniaxial strain can be measured to a precision of <0.025%. The extreme valley polarization of the Landau levels results from as little as approximately 0.1% strain, and this suggests avenues for manipulation using deliberate strain engineering.

Published by the American Physical Society
2025
Exciton-Condensate-Like Energy Transport in Light-Harvesting Complex 2
Authors: Schouten Anna O. , Mazziotti David A.
Published: February 2025

Bose-Einstein condensation of excitons, with its potential for frictionless energy transport, has recently been observed in materials at low temperatures. Here, we show that partial exciton condensation plays a significant role in the 18-chromophore B850 ring of the light-harvesting complex 2 (LH2) in purple bacteria. Even in the single-excitation regime, we observe that excitonic entanglement across multiple sites exhibits signatures of exciton condensation in the particle-hole reduced density matrix—a partial exciton condensate. Crucially, we find that, by distributing the exciton across multiple sites of the ring, the exciton-condensate-like state sets favorable conditions for enhanced energy transfer, both before and after decoherence. Surprisingly, this discovery reveals that excitonic condensation, previously thought to require extreme conditions, can occur in a partial form in biological systems under ambient conditions, providing new insight into energy transport. These results additionally bring new insight into the long-standing debate on quantum versus classical mechanisms in photosynthetic light harvesting by showing that quantum coherence, in the form of a partial exciton condensate, indirectly initializes subsequent classical transfer. Our findings not only deepen our understanding of quantum coherence in light harvesting but also suggest design principles for materials capable of leveraging excitonic entanglement for efficient energy transport.

Published by the American Physical Society
2025
Universal Niche Geometry Governs the Response of Ecosystems to Environmental Perturbations
Authors: Goyal Akshit , Rocks Jason W. , Mehta Pankaj
Published: February 2025

How ecosystems respond to environmental perturbations is a fundamental question in ecology, made especially challenging due to the strong coupling between species and their environment. Here, we introduce a theoretical framework for calculating the steady-state response of ecosystems to environmental perturbations in generalized consumer-resource models. Our construction is applicable to a wide class of systems, including models with nonreciprocal interactions, cross-feeding, and nonlinear growth/consumption rates. Within our framework, all ecological variables are embedded into four distinct vector spaces, and ecological interactions are represented by geometric transformations between these spaces. We show that, near a steady state, such geometric transformations directly map environmental perturbations—in resource availability and mortality rates—to shifts in niche structure. We illustrate these ideas in a variety of settings including a minimal model for pH-induced toxicity in bacterial denitrification. We end by discussing the biological implications of our framework. We show that it is extremely difficult to distinguish cooperative and competitive interactions by measuring the responses of species to external perturbations.

Published by the American Physical Society
2025
Dynamic capabilities, intellectual capital and organisational performance: mediation and moderation effects
Authors: Awwad Mohammad Suleiman
Published: February 2025

Purpose

This study explores the relationship between intellectual capital (IC), dynamic capabilities (DCs) and organisational performance (OP), addressing disagreements on whether IC is an antecedent or consequence of DCs and whether IC and DCs mediate or moderate the interactions between these constructs.

Design/methodology/approach

To address the study questions, four different models were developed that highlight the controversy among researchers regarding the nature of the interplay between IC, DCs, and OP. A cross-sectional survey of 394 managers working for government agencies and departments in Jordan’s capital city, Amman, was conducted to investigate different scholars’ perspectives on the nature of the interaction between these variables. The retrieved responses (166 with a 42.1% response rate) were analysed using SmartPLS.

Findings

Our results revealed that IC did not affect OP, whereas DCs did across the four models. IC affects DCs, and DCs also affect IC, highlighting the potential reciprocal relationship. The relationship between the variables is one of mediation and not moderation, which implies that DCs do not function as a moderator between IC and OP, and IC does not act as a moderator between DCs and OP. These results offer a complex picture of the connections between IC, DCs and OP, which has interesting implications for practice.

Research limitations/implications

Our study reveals the significant role of DCs in OP within government institutions by extending theories on DCs’ adaptability and competitiveness. It emphasises the need for active management of IC to yield performance benefits, aligning with resource-based theories. This study also clarifies the mediation and moderation effects, opens new research avenues and highlights the potential reciprocal interaction between IC and DCs.

Originality/value

This study is the first to explore the reciprocal interaction between IC and DCs and the mediating and/or moderating role of either IC or DCs in their relationship with OP within the public sector, which has not received sufficient attention from scholars, especially in developing countries such as Jordan.
Building competitive advantage: how organizational culture shapes absorptive capacity through knowledge sharing
Authors: Iqbal Salman , Ullah Sami , Rizwan Amina , Nazeer Naima , Rasheed Mamoona , Siddiqi Ahmad Faisal Imtiaz
Published: February 2025

Purpose

The strict regulations and reporting requirements in microfinance institutions require a high level of knowledge and expertise in finance, accounting and risk management. Therefore, microfinance institutions (MFIs) must possess a high absorptive capacity to understand their customers’ needs and develop appropriate products and services to meet them. This study explains how organizational culture influences absorptive capacity in MFIs, with a particular focus on the mediating role of knowledge sharing.

Design/methodology/approach

Data were collected from 450 randomly selected employees of microfinance banking institutions in Pakistan. The data were tested for reliability and validity, and hypotheses were tested through structural equation modeling in WarpPLS 8.0.

Findings

The findings show that knowledge! sharing mediates the relationship between organizational culture and absorptive capacity. Thus, MFIs should promote knowledge sharing as a cultural value to improve their ability to acquire and utilize new knowledge, enhance absorptive capacity to drive innovation and facilitate the development of new products and services.

Practical implications

MFIs with higher absorptive capacity are more likely to be able to respond to changes in the market, such as new technologies or shifting customer demands. Therefore, managers should promote a culture of sharing knowledge and expertise to ensure adaptability in dynamic market conditions.

Originality/value

This research provides a framework for organizations to better understand the role of knowledge sharing in their success and how to leverage it to enhance their absorptive capacity. It is valuable for academics and practitioners seeking to improve organizational performance and competitiveness.
Becoming Bedridden and Being Bedridden: Implications for Nursing and Care for Older People in Long‐Term Care: A Scoping Review
Authors: Berger Bianca , Graeb Fabian , Baumann Manfred , Wolke Reinhold
Published: February 2025

Background

An increasing number of individuals aged 60 and older will rely on healthcare services, particularly due to increased physical limitations and mobility restrictions. This implies an increase in permanently immobile, often bedridden people who require targeted care. Mobility impairments progress gradually, leading to loss of autonomy and self‐care skills, physical decline, functional deterioration, disability, etc. This review synthesises research findings on the implications of becoming and being bedridden for nursing care of older people in long‐term care.

Objectives

The aim of this scoping review was to explore the current state of research on the topic of bedriddenness in older people in the context of long‐term care and to identify research gaps.

Methods

We analysed English and German language peer‐reviewed publications from the electronic databases MEDLINE (PubMed), CINAHL, LIVIO and Scopus. Publications from 1998 to 2023 were included if they addressed ‘bedriddenness’, the ‘process of becoming bedridden’, ‘prevention’ and the ‘consequences of bedriddenness’, and the ‘care of bedridden people’. The PRISMA‐ScR guidelines were used.

Results

We identified 250 publications based on the defined inclusion criteria. We included 47 in detail condensing their content and organising them according to developed categories, bedriddenness and its prevention, development, consequences and care, which were the subject of intensive research. Although researchers have focused on risk factors for the development of immobility and its negative consequences for those affected, they paid little attention to self‐determination and the organisation of life in bed, which enables those affected to participate. Different ideas regarding the term ‘bedriddenness’ indicate the need for a consensus definition.

Conclusion

Our review shows that articles strongly focus on the process of becoming bedridden. Many publications examine bedridden people's care by emphasising the perspective of (informal) caregivers and the challenges they face. The perspective of bedridden people, together with the consideration of psychosocial dimensions of bedriddenness and the promotion of opportunities for participation, should be focused on in further research. Appropriate concepts for training and nursing practice would be helpful.

Implications for Practice

Bedriddenness is a phenomenon that mainly affects older people, particularly those living in nursing homes. Concepts should be developed that reflect the reality of bedridden people's lives. Targeted interventions to improve the mobility of people with severe mobility impairments are important. Therefore, it is essential to establish educational modules for (informal) caregivers that consider mobility and rehabilitative practices as an integral part of care.
Significance of nonlinearity consideration in finite element analysis for preclinical strength assessment of extramedullary femur plates
Authors: Kumar Neeraj , Nag Pratik , Chanda Souptick
Published: February 2025

Accurate finite element (FE)-based evaluations demand realistic modeling of the bone-implant construct. For this, considering nonlinearity in the FE model sometimes becomes essential. Human femora exhibit nonlinear mechanical behavior, which could be attributed to material, large deformation, and boundary conditions. The nonlinearity due to material is specified as material nonlinearity, while due to large deformation or boundary conditions is specified as geometric nonlinearity. The objective of the present study is to comprehend the importance of incorporating nonlinearity into FE analyses of extramedullary plates used to treat proximal femoral fractures. Two extramedullary implants – one proximal femoral locking plate (PFLP) and another variable angle-dynamic hip screw (VA-DHS) - were fixated with a femur analog having a simulated intertrochanteric fracture. The constructs were analyzed dynamically for normal walking gait activity and sideways fall scenarios. The analyses were carried out by considering both geometric as well as total (geometric & material) nonlinearity, and the same were compared with the results from linear models. The results obtained from FE analyses of intact and implanted constructs were validated from in-vitro experimental data and FE analysis data reported in previous studies. The investigation revealed that a comprehensive nonlinear analysis, considering both geometric and material factors, can minimize the error percentage to less than 5% while comparing with the data obtained from the experimental approach. The PFLP implant was found to impart higher stiffness (~30%) as compared to the VA-DHS implant under both load cases of walking and sideways fall.
Understanding end corrections and flow near the open end of a flue instrument
Authors: Giordano N.
Published: February 2025

Wind instruments containing a resonator (i.e., pipe) with an open end are expected to exhibit an acoustic standing wave characterized by a density oscillation whose amplitude falls to zero a short distance beyond the end of the resonator. An extrapolation of this amplitude based on the behavior inside the resonator yields an “effective” node of the standing wave (i.e., a point at which the extrapolated amplitude vanishes), and the distance from the end of the resonator to the location of this effective node (which is commonly referred to as simply a “node”) is known as the “end correction.” Recent work using a novel optical technique involving optical speckle patterns surprisingly suggested instead that a node is located inside the resonator with unexpected structure in the standing wave amplitude just beyond the end of the resonator. We have studied this problem by numerically solving the Navier-Stokes equations and find that the effective node of the density oscillation is located at the expected position outside the resonator with no unexpected structure in the functional form of the standing wave. We also show how pressure gradients and the flow pattern found near the end of the resonator can account for the unexpected behavior observed in the experiments. This sensitivity of optical interference effects to flow structure may give a new experimental way to investigate vorticity and other complex flows found in the mouthpiece of a musical instrument and in other situations.
Herpes simplex virus assembly and spread in murine skin after infection from the outside
Authors: Richardo Timmy , Liu Xiaokun , Döhner Katinka , Chao Tsung-Yu , Buch Anna , Binz Anne , Pohlmann Anja , de le Roi Madeleine , Baumgärtner Wolfgang , Brand Korbinian , Bauerfeind Rudolf , Förster Reinhold , Sodeik Beate , Halle Stephan
Published: February 2025

Herpes simplex viruses (HSV) cause many skin diseases, particularly in immunocompromised patients. HSV-1 infection of murine skin recapitulates many aspects of human pathology. However, many protocols rely on mechanical or enzymatic skin disruption to induce lesions, although this can alter skin homeostasis and prime antiviral inflammation before inoculation. To investigate the initial events following HSV-1 primary skin infection before the onset of symptoms, we developed a novel murine
ex vivo
explant model using gentle depilation without further scarification and infected keratinocytes from the outside with minimal tissue damage. Two-photon microscopy showed that HSV-1 spread exclusively in the epidermis. The infection centers increased in number and size over time and contained hundreds of infected keratinocytes. We investigated the HSV-1 spread at the cellular level, using reporter strains with fluorescently tagged capsid protein VP26, and observed the formation of nuclear capsid assembly sites and nuclear capsid egress and the recruitment of the inner tegument protein pUL37GFP, the outer tegument protein VP11/12GFP, and the envelope protein gDGFP to cytoplasmic capsids. By using electron microscopy, the skin appeared intact, and keratinocytes contained many nuclear capsids, primary virions in the nuclear envelope, cytosolic membrane-associated capsids, and enveloped virions. Our protocol provides a robust and reproducible approach to investigate the very early events of HSV-1 spread in the skin, to characterize the phenotypes of HSV-1 mutants in terminally differentiated skin tissues, and to evaluate potentially antiviral small molecules in a preclinical
ex vivo
infection model.

IMPORTANCE

This study describes a novel murine
ex vivo
skin explant model to investigate early events in HSV-1 infection without causing significant tissue damage. To infect from the outside, via the apical keratinocytes, this method relies on gentle depilation, which maintains skin integrity. HSV-1 spread exclusively within the epidermis, with infection centers increasing over time and involving hundreds of keratinocytes. Using advanced microscopy techniques, we tracked HSV-1 spread at the cellular level and intracellular assembly of all intermediate virus structures. This model offers a valuable tool for studying the initial stages of HSV-1 infection, assessing viral mutant phenotypes, and testing antiviral compounds in a more physiological context to provide critical insights into HSV-1 pathogenesis and therapeutic strategies.
Prophages are infrequently associated with antibiotic resistance in
Pseudomonas aeruginosa
clinical isolates
Authors: Chang Tony H. , Pourtois Julie D. , Haddock Naomi L. , Furukawa Daisuke , Kelly Kate E. , Amanatullah Derek F. , Burgener Elizabeth , Milla Carlos , Banaei Niaz , Bollyky Paul L.
Published: February 2025

Lysogenic bacteriophages can integrate their genome into the bacterial chromosome in the form of a prophage and can promote genetic transfer between bacterial strains
in vitro
. However, the contribution of lysogenic bacteriophages to the incidence of antimicrobial resistance (AMR) in clinical settings is poorly understood. Here, in a set of 186 clinical isolates of
Pseudomonas aeruginosa
collected from respiratory cultures from 82 patients with cystic fibrosis, we evaluate the links between prophage counts and both genomic and phenotypic resistance to six anti-pseudomonal antibiotics: tobramycin, colistin, ciprofloxacin, meropenem, aztreonam, and piperacillin–tazobactam. We identified 239 different prophages in total. We find that
P. aeruginosa
isolates contain on average 3.06 ± 1.84 (SD) predicted prophages. We find no significant association between the number of prophages per isolate and the minimum inhibitory concentration for any of these antibiotics. We then investigate the relationship between particular prophages and AMR. We identify a single lysogenic phage associated with phenotypic resistance to the antibiotic tobramycin and, consistent with this association, we observe that AMR genes associated with resistance to tobramycin are more likely to be found when this prophage is present. However, we find that they are not encoded directly on prophage sequences. Additionally, we identify a single prophage statistically associated with ciprofloxacin resistance but do not identify any genes associated with ciprofloxacin phenotypic resistance. These findings suggest that prophages are only infrequently associated with the AMR genes in clinical isolates of
P. aeruginosa
.

IMPORTANCE

Antibiotic-resistant infections of
Pseudomonas aeruginosa
(
Pa
), a leading pathogen in patients with cystic fibrosis (CF), are a global health threat. While lysogenic bacteriophages are known to facilitate horizontal gene transfer, their role in promoting antibiotic resistance in clinical settings remains poorly understood. In our analysis of 186 clinical isolates of
P. aeruginosa
from CF patients, we find that prophage abundance does not predict phenotypic resistance to key antibiotics but that specific prophages are infrequently associated with tobramycin resistance genes. In addition, we do not find antimicrobial resistance (AMR) genes encoded directly on prophages. These results highlight that while phages can be associated with AMR, phage-mediated AMR transfer may be rare in clinical isolates and difficult to identify. This work is important for future efforts on mitigating AMR in CFCF and other vulnerable populations affected by
Pa
infections and advances our understanding of bacterial-phage dynamics in clinical infections.
Acute generalised exanthematous pustulosis in a child
Authors: Pande Vineeta , Thakur Mrinali , Pathak Nakul , Jadhav Renuka
Published: February 2025

Acute generalised exanthematous pustulosis (AGEP) is a rare cutaneous adverse reaction which is caused due to drugs or other triggers in children. We report a very rare case of AGEP after introduction of oral cefixime for a female child who presented with complaints of fever, cough and cold for 6 days. It was noted that she developed a rash over the face within 24 hours and within the following few hours, it spread over the neck, in the axilla and over the groin. The patient has no history of allergy and had no history of similar reaction in the past. On examination, the patient was vitally stable with no sign of shock or any other significant systemic findings. The rash was characterised by erythematous base with multiple pinpoint pustules and culture of those was sterile. Haemogram was suggestive of mild leucocytosis with normal liver and renal functions. Treatment included stopping the triggering medication, that is, syrup cefixime and starting the child on oral corticosteroids along with antihistamines. The child started improving within 48 hours of medication, and rashes recovered with desquamation. AGEP is an adverse reaction which is rarely noted in children. It is treated with oral corticosteroids and supportive care of the local lesions.
Desmoid fibromatosis arising from caecum: an overview of the challenges in diagnosis and treatment
Authors: Luca Micheal C , Damadi Amir Ali , Katuwal Binit
Published: February 2025

Desmoid fibromatosis is a rare subtype of soft tissue neoplasms known for its locally aggressive behaviour and fibrotic consistency. While these tumours can arise in various anatomical sites, their occurrence within the colon is exceptionally rare and poses diagnostic and therapeutic challenges. We present a case of a female patient in her 30s with no significant medical history who presented with vague gastrointestinal and urinary symptoms. Imaging studies revealed a sizeable abdominal mass, initially raising uncertainty regarding its origin. Subsequent exploratory laparotomy revealed a desmoid fibromatosis involving the muscularis propria of the caecum, prompting a right hemicolectomy. Histopathological analysis confirmed the diagnosis, and the patient underwent a successful resection with negative margins. This case underscores the importance of individualised treatment plans and long-term surveillance in managing colonic desmoid tumours for optimal outcomes and disease-free survival.
Acute dystonia following the two-injection start of aripiprazole once-monthly
Authors: Levit Alexander , Procyshyn Ric M , Keramatian Kamyar
Published: February 2025

We present a case of an acute dystonic reaction (ADR) following the two-injection start of aripiprazole once-monthly (AOM) in a patient who previously tolerated equivalent doses of oral aripiprazole (20 mg daily). The ADR occurred two times within 3 weeks of the two-injection start and was effectively treated with benztropine each time. The patient tolerated maintenance treatments of AOM 400 mg without recurrent ADR. A key risk factor in this patient was a prior ADR to a different antipsychotic. We also speculate on the potential roles of strenuous physical activity and infection in increasing the sensitivity to the two-injection initiation regimen compared with the conventional one-injection start. The two-injection start of AOM has been approved by regulatory bodies on the basis of population pharmacokinetic modelling. Our case may, therefore, identify a new safety concern with this alternative initiation option that was not captured in the modelling.
Arcuate line hernia repair: a laparoscopic technique with transfascial primary repair and mesh reinforcement
Authors: Varama Abhishet , Pungpapong Suppa-ut , Manasnayakorn Sopark , Vacharathit Voranaddha
Published: February 2025

Arcuate line hernias (ALHs) are rare intraparietal hernias, with a prevalence ranging from 1.62% to 2%. These hernias occur at the arcuate line (AL)—a significant anatomical transition zone where the posterior lamella of the internal oblique and transversus abdominis aponeurosis shift from contributing fibres to the posterior sheath to the anterior sheath. Uniquely, ALHs do not present with a palpable defect. Although typically asymptomatic, incarceration and strangulation have been reported. Presently, there is no consensus regarding the optimal repair technique for ALHs, which pose a specific challenge in surgical repair due to the absence of a fascial edge to suture to below the AL, as commonly performed in other abdominal hernia repairs. We report an ALH repaired laparoscopically with transfascial sutures and intraperitoneal onlay mesh. Preoperative findings, imaging, anatomical considerations, and tailored surgical approach are discussed, complemented by an extensive review of the literature.
Implementation outcomes of tuberculosis digital adherence technologies: a scoping review using the RE-AIM framework
Authors: Chilala Chimweta I , Foster Nicola , Bahukudumbi Shruti , Mohamed Mona Salaheldin , Zary Miranda , Kafie Cedric , Patel Barbie , Gore Genevieve , Schwartzman Kevin , Subbaraman Ramnath , Fielding Katherine L
Published: February 2025

Introduction

Globally, tuberculosis (TB) remains one of the leading infectious causes of death, with 1.3 million deaths. Digital adherence technologies (DATs) have the potential to provide person-centred care and improve outcomes. Using the reach, effectiveness, adoption, implementation and maintenance (RE-AIM) framework, we conducted a scoping review of DAT implementations for TB treatment.

Methods

We searched seven databases for papers published between January 2000 and April 2023, using keywords for ‘tuberculosis’ and ‘digital adherence technology’. Articles meeting prespecified inclusion criteria and containing data on RE-AIM domains were included. We defined ‘reach’ as comprising cellphone ownership and engagement by people with TB (PWTB) with DATs, ‘adoption’ as engagement by healthcare providers with DAT programmes, ‘implementation’ as the fidelity of the DAT programme implemented and ‘maintenance’ as longer-term uptake of DATs.

Results

Of 10 313 records, 102 contributed to the synthesis. DATs included short message service (SMS), phone, 99DOTS, video-supported therapy (VST) and pillboxes. For ‘reach’, across various settings, cellphone access varied from 50%–100% and 2%–31% of PWTB was excluded from accessing DATs due to technology challenges. 36%–100% of PWTB agreed to use a DAT. The weighted mean of DAT engagement over dose-days was 81% for SMS, 85% for phone, 61% for 99DOTS, 87% for pillbox and 82% for VST. Concerning ‘implementation’, the fidelity of DAT implementations was affected by technological issues such as cellphone coverage, DAT malfunction and provider-facing issues, including failure to initiate intensified patient management following low DAT engagement. Findings related to RE-AIM dimensions of ‘adoption’ and ‘maintenance’ were limited.

Conclusion

Our findings suggest that the ‘reach’ of DATs may be limited by a cascade of barriers, including limitations in cellphone accessibility and suboptimal sustained DAT engagement by PWTB. Video and pillbox DATs have higher levels of engagement. Implementation challenges included technological and provider-facing issues. Improving implementation outcomes may be important for TB DATs to achieve a broader public health impact.

PROSPERO registration number

CRD42022326968
Real-world efficacy and safety of 8 mg aflibercept in neovascular AMD: a case series
Authors: Sambhara Deepak , Vakharia Priya , Eichenbaum David A
Published: February 2025

Objective

This real-world retrospective case series evaluates the safety and efficacy of aflibercept 8 mg in patients diagnosed with neovascular age-related macular degeneration (nAMD).

Methods and analyses

Treatment-naïve or treatment-experienced patients with nAMD receiving aflibercept 8 mg with at least 6 months of follow-up were assessed.

Results

40 eyes from 33 patients were included, of which 36/40 eyes were previously treated. The mean age of subjects is 79.84 years. At baseline, 29/36 eyes had intraretinal fluid (IRF)/subretinal fluid (SRF) at an average interval of 40.97 days, logMAR VA of 0.346, and average central subfield thickness (CST) of 341.53 µm. At final follow-up, average logMAR VA was 0.315 and average CST decreased by 39.39 µm, with an average number of days since last treatment of 52.9. Of the 32 eyes with IRF, SRF, or both at the time of switch, 12 eyes achieved anatomical quiescence without IRF/SRF after the first injection of aflibercept 8 mg, including three of four treatment-naive patients.

Conclusions

This early case series suggests that patients treated with aflibercept 8 mg may achieve greater duration between treatments while preserving and, in some cases, improving visual acuity and anatomical outcomes in a real-world clinic setting. In this retrospective study, the patient population primarily consisted of treatment-experienced cases with recalcitrant disease or high treatment burdens, potentially using aflibercept 8 mg as salvage therapy. This selection bias limits generalisability to broader real-world populations. The small sample size precludes formal statistical conclusions. Multiple investigators made unstandardised treatment decisions based on individual clinical judgement, including whether to continue aflibercept 8 mg or revert to prior therapy, sometimes after just one injection.
Regression Modeling Using Generalized Pareto‐IV Distribution With Application to Household Budget Survey
Authors: Ponera January , Gadde Srinivasa Rao , Abbas Ismail
Published: February 2025

The study introduced the new regression model by the T‐X family technique of Type I half‐logistic and Pareto IV distribution (TIHLPIV) that had to solve the weaknesses of mixed methods, which are limited to applicability, data requirements, and computational complexity. Data transformation was needed for generalization (G‐family) of combined distributions, and the T‐X technique allowed flexibility, risk assessment, environmental studies, quality control, and scientific research in modeling different kinds of data and covering a wider range of real‐life applications such as survival and lifetime data, hydrology, economics (income inequality), and engineering. The general objective of the study was to introduce new regression modeling using generalized Pareto IV distribution (TIHLPIV) with application to the Household Budget Survey (HBS) for the years 2017‐18 on the Tanzania Mainland. According to empirical results, it is revealed that the proposed model gives better results than other existing models.