bluuebunny/crossref_metadata_2025_split huggingface dataset:
No Vaccine, No Organ? Ethics of Vaccine Mandates for Pediatric Transplant
Authors: Navin Mark Christopher , Wightman Aaron G. , Ross Lainie Friedman 
Published: January 2025

ABSTRACTMany transplant programs worldwide are likely to impose vaccine mandates for pediatric solid organ transplant candidates; some already do. Three potential benefits that advocates invoke to justify mandates are improved patient outcomes, efficient organ allocation, and contributions to community protection. We show that none of these benefits can justify mandates. The medical benefits of mandates are unlikely to outweigh the risks of denying life‐saving care, mandates threaten trust and equity in organ allocation, and the impact on community protection is likely negligible, while the burden on unvaccinated children would be disproportionate. We also reject the claim that clinician burdens in dealing with vaccine refusers are good reasons for mandates, and point out, to the contrary, that the potential political backlash to mandates is a good reason for restraint. Rather, we argue that vaccine mandates for pediatric transplant candidates should be a last resort; they should only be considered after all evidence‐based noncoercive measures have been exhausted, and after mandates for transplant professionals and staff are in place. Since there is little evidence that all such measures have been attempted, it is premature to consider vaccine mandates.
A Patient With NEMO Deficiency, Disseminated M. szulgai, and Post‐HSCT Inflammatory Disease
Authors: Rosenthal Ayelet , Goyal Alka , Chen Sharon F. , Lewis David B. , Shah Ami 
Published: January 2025

ABSTRACTBackgroundDisseminated mycobacterium poses a significant risk for patients with NEMO deficiency. Hematopoietic stem cell transplant (HSCT) corrects the NEMO defect in hematopoietic cells thus treating the immunodeficiency.MethodsWe present a patient with NEMO deficiency who successfully underwent HSCT despite a disseminated Mycobacterium szulgai infection.ResultsDespite successful engraftment and resolution of the mycobacterium infection, he developed inflammatory disease leading to his death.ConclusionHSCT does not cure all aspects of the NEMO protein defect and posttransplant inflammatory diseases involving nonhematopoietic cell types may manifest clinically.
Fate of Semilunar Valves From Discarded Hearts at the Time of Pediatric Heart Retransplantation
Authors: Arcadi Landon , Faateh Muhammad , Raees Muhammad Aanish , Morales David L. S. , Mantell Benjamin S. , Ashfaq Awais 
Published: January 2025

ABSTRACTBackgroundPartial heart transplantation (PHT) is a novel procedure for children in need of a growing valve replacement option. One challenge is identifying suitable donor valves. Semilunar heart valves from patients receiving a retransplant may be a source, however their functionality and growth potential especially at the time of retransplant are unknown. We aimed to assess growth and function of these valves.MethodsData from patients undergoing a retransplant at a single institution were analyzed. Echocardiograms were compared following the primary transplant and immediately before retransplant to assess growth and valve function.ResultsThirteen patients were included. Recipient and donor ages at the primary transplant were median (range): 2 years (0–13) and 3 years (0–40), respectively. The median time to retransplant was 11 years (2–21). There was an overall growth across all semilunar valve measurements; aortic valve annulus diameter (mean increase ± standard deviation): 0.2 ± 0.12 cm, aortic root: 0.29 ± 0.16 cm, and pulmonary valve annulus: 0.5 ± 0.34 cm; all p < 0.05. The growth rate of valves was higher in younger patients and showed a better correlation with graft age relative to recipient age: aortic valve annulus growth R2: 0.61 (graft age) versus 0.54 (recipient age); aortic root R2: 0.73 versus 0.57; pulmonary valve annulus R2: 0.94 versus 0.86. No patients had clinically significant regurgitation or stenosis on the latest echocardiogram. All except one patient's measurement had valve Z‐scores within ±2 at retransplant.ConclusionExplanted hearts from patients undergoing retransplantation could be considered an additional source of semilunar valves for PHT. Valves from these hearts were found to function normally and grew in proportion with the recipient's body. Valves from younger donors/recipients demonstrated a more rapid growth rate.
Investigating the impact of mitochondrial DNA: Insights into blood transfusion reactions and mitigation strategies
Authors: Bagheri Saeede , Hajiabadi Fatemeh , Vahabzadeh Reihaneh , Ahmadi Mohammad Hossein 
Published: January 2025

AbstractBackground and ObjectivesAlthough transfusion reactions occur in less than 2% of recipients, they are currently one of the most serious concerns in blood transfusion. Damage‐associated molecular patterns (DAMPs) are released from injured, stressed or dead cells, leading to inflammation and immune system activation. One of the recognized DAMPs is mitochondrial DNA (mtDNA). It is found in various blood products, including fresh frozen plasma (FFP), red blood cell units (RBCUs) and platelet concentrates (PCs), and can induce adverse reactions in recipients by stimulating the innate immune system and inflammatory cellular pathways. The aim of this study was to investigate the factors influencing the release of mtDNA in various blood products and its subsequent impact on transfusion reactions.Materials and MethodsIn this study, mtDNA, mitochondrial DNA, mtDNA DAMPs, extracellular mtDNA, blood products, blood components and transfusion reactions between 2009 and 2023 were searched in Google Scholar, PubMed and Scopus databases.ResultsThis study has demonstrated the presence of mtDNA in the extracellular milieu of various blood products, including PCs, FFP and RBCUs. Understanding the determinants of mtDNA release and its implications for transfusion safety is critical. Strategies aimed at reducing mtDNA release, such as optimizing preparation techniques and donor selection criteria, hold promise for reducing transfusion‐related complications.ConclusionBy addressing these factors, healthcare providers can enhance the safety and efficacy of blood transfusion practices, ultimately improving patient outcomes.
Evolution of rod bipolar cells and rod vision
Authors: Frederiksen Rikard , Peng Yi‐Rong , Sampath Alapakkam P. , Fain Gordon L. 
Published: January 2025

AbstractBipolar cells are vertebrate retinal interneurons conveying signals from rod and cone photoreceptors to amacrine and ganglion cells. Bipolar cells are found in all vertebrates and have many structural and molecular affinities with photoreceptors; they probably appeared very early during vertebrate evolution in conjunction with rod and cone progenitors. There are two types of bipolar cells, responding to central illumination with depolarization (ON) or hyperpolarization (OFF). In most vertebrate species, rod signals are conveyed to specialized rod bipolar cells, which sum signals from many rods and facilitate detection at the visual threshold. Lamprey, which diverged from all other vertebrates in the late Cambrian, have both rod ON and rod OFF bipolar cells, but mammals have only rod ON cells. Rod signals in mammals are conveyed to output neurons indirectly via AII (or A2) amacrine cells, which synapse onto cone ON and cone OFF bipolar‐cells and then to ganglion cells. These findings raise the question of when during retinal evolution rod OFF bipolar cells were lost. Because physiological recordings have been made from rod OFF bipolar cells in both cartilaginous fishes (dogfish) and urodeles (salamanders), rod OFF bipolar cells and their circuits must have been retained in vertebrate progenitors at least until the Devonian. Recent evidence showing that zebrafish retina processes rod signals similar to those in mammals indicates that rod OFF bipolar cells were lost at least twice. The sole utilization of rod ON bipolar cells may have provided a selective advantage from increased signal‐to‐noise discrimination near the visual threshold.
imageKey points
Rods and cones have many structural and molecular similarities to bipolar cells, which are retinal interneurons conveying signals from photoreceptors to the retinal output.
Bipolar cells can be either ON (centre depolarizing) or OFF (centre hyperpolarizing) and either rod or cone dominant.
Lamprey, which diverged from all other vertebrates 500 million years ago, have both ON and OFF bipolar cells, which can each be either rod or cone dominant. We argue that this configuration of separate rod/cone bipolar‐cell pathways is representative of early vertebrates.
Rod ON and rod OFF bipolars persisted at least until the progenitors of amphibians in the Devonian, but mammals and teleost fishes have only rod ON bipolar cells and convey rod OFF signals via a specialized amacrine cell.
We argue that rod OFF bipolar cells were lost in at least two different lineages during vertebrate evolution, probably to increase the signal‐to‐noise of rod vision.
Microplane Constitutive Model for Tension–Compression Asymmetry and Pressure-Sensitive Damage in Polymers
Authors: Wardhekar Sanket , Kirane Kedar 
Published: January 2025

Abstract
The multiaxial damage behavior of brittle polymers is highly complex, involving a stark tension–compression asymmetry and strong pressure sensitivity. These aspects are challenging to predict via phenomenological tensor-based damage models. Recognizing that these behaviors stem from various microscale damage mechanisms, this work presents a novel adaptation of the microplane constitutive model for these materials. The salient feature of the model is the semi-multiscale architecture consisting of “microplanes,” which are imagined planes of various orientations within the material microstructure. Various tensile and compressive damage mechanisms are formulated in terms of stress–strain vectors acting on these microplanes. The homogenized macroscale stress tensor is obtained via the principle of the virtual work. This multiscale arrangement allows simple, intuitive, and physically based formulations of microscale damage mechanisms as well as easy distinction of tension and compression. The mechanisms considered here include tensile microcracking, shear-driven plastic-frictional damage, and far postpeak compression hardening. The formulation involves splitting the volumetric and deviatoric components of stresses, which enables properly capturing Poisson ratios greater than 0.25. It also includes a normal strain dependence of the microplane strain limits governing frictional damage evolution. The model is calibrated and successfully validated against experimental data on several polymers under uniaxial tension, compression, and triaxial compression. The model is demonstrated to capture the tension–compression asymmetry of the inelastic behavior, as well as the pressure-sensitive nonlinear behavior under triaxial compression, in excellent agreement with experiments. Notably, the predictions under triaxial compression are found to outperform the Drucker Prager model, thus highlighting the superior potential of the microplane modeling approach for multiaxial damage in polymers.
Coefficient of Restitution in a Low-Velocity Normal Impact Using Elastoplastic Contact Stiffness
Authors: Iqbal Uzair , Revankar A. Gautam , Kasula Vineethkumar , Bobji M. S. 
Published: January 2025

Abstract
Elastoplastic deformation during particle impact occurs widely in many engineering applications. The material properties characterizing both the elastic and plastic behavior play an important role in particle impact. A non-linear contact stiffness-based model representing the elastic and plastic deformation of the material is used to obtain the coefficient of restitution during the impact of a sphere on a deformable substrate. The model consists of the Maxwell combination of perfectly plastic component and a non-linear elastic component. The proposed model is used to estimate the plastic energy dissipation during the impact. An analytical solution is obtained for residual contact radius and coefficient of restitution expressed in terms of experimentally determinable parameters. Our approach yields a single dimensionless parameter referred to as the “indentation parameter,” Λ, and it is shown that the impact response and coefficient of restitution for various impact situations can be determined based on this indentation parameter. The proposed model accurately predicts the residual contact radius and coefficient of restitution, validated through experimental results of low-velocity impacts (1–4 m/s) over a flat sample of aluminum alloy (Al6061) impacted by steel and zirconia balls. The present model is further compared with other existing theoretical contact models for the elastoplastic impact and the extension of the present model for other dissipative systems is also discussed.
The Effects of Surface Tension on Spherical Oscillatory Indentation of Viscoelastic Materials
Authors: Ding Yue , Yuan Wei-Ke , Chen Shi-Wen , Niu Xinrui , Wang Gang-Feng 
Published: January 2025

Abstract
The oscillatory indentation has become an attractive approach to characterizing the viscoelastic properties of soft biological solids. However, the influences of surface tension on oscillatory responses are ignored, which might lead to an inaccurate measurement of mechanical properties. In this work, the influences of surface tension on spherical oscillatory indentation for viscoelastic materials are investigated through the finite element method. The viscoelasticity of solids is characterized by the standard linear solid model and a sinusoidal displacement is applied as the excitation signal. During an entire cycle at the steady-state of oscillation, both the average value of contact radius and the dissipated energy decrease due to the presence of surface tension. For the oscillatory responses at various frequencies, the existence of surface tension results in an increase in average force but a decrease in phase angle. The force amplitude at low frequencies becomes higher when surface tension is considered. For the evaluation of the complex modulus, neglecting the surface tension would lead to a significant overestimation of storage modulus at low frequencies and an obvious underestimation of loss modulus when the normalized frequency approaches one. Our results provide a comprehensive understanding of the effects of surface tension on the mechanical responses of oscillation and the determination of viscoelastic properties through oscillatory indentation.
Transforming the chemotherapy of human African trypanosomiasis
Authors: Barrett Michael P. 
Published: January 2025

SUMMARY

Prior to 2019, when the orally available drug fexinidazole began its clinical use, the treatment of human African trypanosomiasis (HAT) was complex and unsatisfactory for many reasons. Two sub-species of the
Trypanosoma brucei
parasite are responsible for HAT, namely the rhodesiense form found in East and Southern Africa and the gambiense form found in Central and West Africa. Diseases caused by both forms manifest in two stages: stage 1 before and stage 2 after central nervous system involvement. Prior to 2019, different drugs were required for each of the two parasite sub-species at each stage. Gambiense disease required pentamidine or nifurtimox-eflornithine combination therapy, while for rhodesiense disease, suramin or melarsoprol was given for stages 1 and 2, respectively. These drugs all suffered complications including protracted administration regimens involving multiple injections with drug-induced adverse effects common. Today, a single drug, fexinidazole, can be given orally in most cases for both diseases at either stage. Another compound, acoziborole, effective in both stages 1 and 2 gambiense disease with a single dosing is anticipated to become available within a few years. Moreover, the recent engagement of multilateral organizations in seeking other compounds that could be used in HAT therapy has also been successful, and a rich vein of new trypanocides has been discovered. Here, the clinical use, modes of action, and resistance risks for drugs used against HAT are discussed.
Platelet factor 4-derived C15 peptide broadly inhibits enteroviruses by disrupting viral attachment
Authors: Lv Shuai , Li Congyi , Pei Zhichao , Hu Ziwei , Du Yining , Zheng Baisong , Zhang Wenyan 
Published: January 2025

ABSTRACT

Platelet factor 4 (PF4) has been shown to regulate several viral infections. Our previous study demonstrated that PF4 inhibits the entry of enterovirus A 71 (EV71) and coxsackievirus A16 (CA16), which cause hand, foot, and mouth disease (HFMD). In this study, we report that PF4 also inhibits the circulating HFMD pathogen coxsackievirus A6 (CA6) and the re-emerging enterovirus D68 (EVD68). A 15-amino acid peptide, C15, at the C-terminus of PF4 confers anti-viral activity against multiple enteroviruses (EVs) besides CA6 and EVD68, including EV71 and CA16. Mechanistic studies revealed that wild-type C15 with a net-positive charge (+3), but not its mutants C15M and C15A (both −1), specifically binds to the VP3 capsid protein of CA6 and EVD68, thereby disrupting their attachment to the host cell surface. In addition, VP3 of EVs contains a conserved domain (residues 155–170) crucial for binding to C15. An aspartic acid residue at position 156 imparts a net-negative charge to this domain, which, when substituted with a neutrally charged amino acid, reduces the binding affinity of VP3 for C15. Additionally, C15 protects neonatal mice from lethal challenge upon a CA6 infection. These results suggest that C15 is a promising broad-spectrum anti-viral candidate against multiple EVs.

IMPORTANCE
EVs, which pose a significant public health threat, can be classified into 15 species, with EV-A, -B, -C, and -D infecting humans and causing a wide range of diseases, from mild illnesses, such as HFMD, to more severe conditions, such as acute flaccid paralysis. The emergence of new and alternative strains highlights the urgent need for broad-spectrum anti-viral agents. In this study, we identified that the C15 of PF4 exhibits potent anti-viral activity against multiple EVs by binding to their surface and blocking their entry into host cells. Furthermore, C15 provides significant protection in vivo. These findings highlight the potential of C15 as a broad-spectrum anti-viral candidate. Our study opens a new avenue for developing treatments to combat the diverse and evolving threats posed by EVs.
Genetic and biochemical characterization of a radical SAM enzyme required for post-translational glutamine methylation of methyl-coenzyme M reductase
Authors: Rodriguez Carrero Roy J. , Lloyd Cody T. , Borkar Janhavi , Nath Shounak , Mirica Liviu M. , Nair Satish , Booker Squire J. , Metcalf William 
Published: January 2025

ABSTRACT

Methyl-coenzyme M reductase (MCR), the key catalyst in the anoxic production and consumption of methane, contains an unusual 2-methylglutamine residue within its active site.
In vitro
data show that a B12-dependent radical SAM (rSAM) enzyme, designated MgmA, is responsible for this post-translational modification (PTM). Here, we show that two different MgmA homologs are able to methylate MCR
in vivo
when expressed in
Methanosarcina acetivorans
, an organism that does not normally possess this PTM.
M. acetivorans
strains expressing MgmA showed small, but significant, reductions in growth rates and yields on methylotrophic substrates. Structural characterization of the Ni(II) form of Gln-methylated
M. acetivorans
MCR revealed no significant differences in the protein fold between the modified and unmodified enzyme; however, the purified enzyme contained the heterodisulfide reaction product, as opposed to the free cofactors found in eight prior
M. acetivorans
MCR structures, suggesting that substrate/product binding is altered in the modified enzyme. Structural characterization of MgmA revealed a fold similar to other B12-dependent rSAMs, with a wide active site cleft capable of binding an McrA peptide in an extended, linear conformation.

IMPORTANCE
Methane plays a key role in the global carbon cycle and is an important driver of climate change. Because MCR is responsible for nearly all biological methane production and most anoxic methane consumption, it plays a major role in setting the atmospheric levels of this important greenhouse gas. Thus, a detailed understanding of this enzyme is critical for the development of methane mitigation strategies.
Limnospira
(Cyanobacteria) chemical fingerprint reveals local molecular adaptation
Authors: Roussel Théotime , Hubas Cédric , Halary Sébastien , Chynel Mathias , Duval Charlotte , Cadoret Jean-Paul , Meziane Tarik , Vernès Léa , Yéprémian Claude , Bernard Cécile , Marie Benjamin 
Published: January 2025

ABSTRACT

Limnospira
can colonize a wide variety of environments (e.g., freshwater, brackish, alkaline, or alkaline-saline water) and develop dominant and even permanent blooms that overshadow and limit the diversity of adjacent phototrophs, especially in alkaline and saline environments. Previous phylogenomic analysis of
Limnospira
allowed us to distinguish two major phylogenetic clades (I and II) but failed to clearly segregate strains according to their respective habitats in terms of salinity or biogeography. In the present work, we attempted to determine whether
Limnospira
displays metabolic signatures specific to its different habitats, particularly brackish and alkaline-saline ecosystems. The impact of accessory gene repertoires on respective chemical adaptations was also determined. In complement of our previous phylogenomic investigation of
Limnospira
(Roussel et al., 2023), we develop a specific analysis of the metabolomic diversity of 93 strains of
Limnospira
, grown under standardized lab culture conditions. Overall, this original work showed distinct chemical fingerprints that were correlated with the respective biogeographic origins of the strains. The molecules that most distinguished the different
Limnospira
geographic groups were sugars, lipids, peptides, photosynthetic pigments, and antioxidants. Interestingly, these molecular enrichments might represent consequent adaptations to conditions of salinity, light, and oxidative stress in their respective sampling environments. Although the genes specifically involved in the production of these components remain unknown, we hypothesized that within extreme environments, such as those colonized by
Limnospira
, a large set of flexible genes could support the production of peculiar metabolite sets providing remarkable adaptations to specific local environmental conditions.

IMPORTANCE

Limnospira
are ubiquitous cyanobacteria with remarkable adaptive strategies allowing them to colonize and dominate a wide range of alkaline-saline environments worldwide. Phylogenomic analysis of
Limnospira
revealed two distinct major phylogenetic clades but failed to clearly segregate strains according to their habitats in terms of salinity or biogeography. We hypothesized that the genes found within this variable portion of the genome of these clades could be involved in the adaptation of
Limnospira
to local environmental conditions. In the present paper, we attempted to determine whether
Limnospira
displayed metabolic signatures specific to its different habitats. We also sought to understand the impact of the accessory gene repertoire on respective chemical adaptations.