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[Display omitted] • Different concentration of Gd doped Fe-Co thin films were successively deposited on Cu using electrodeposition method. • Gd-concentration of 0.05 M showed excellent magnetic behaviour. • Electrode prepared by 0.05 M sample exhibited enhanced water splitting performance under external applied magnetic field. We investigated the magnetic characteristics of Gadolinium-doped Iron-Cobalt/Copper (Gd-Fe-Co/Cu) electrodeposited thin films at various Gd concentrations over 20 min at room temperature and pH 3. The structure and composition of metal ions are confirmed by X-ray diffraction and the EDAX spectrum. SEM examination of the microstructures revealed a variety of morphologies, including spherical ball-like crystallites and one-dimensional spike-like crystallites. The varied Gd ion concentrations had an effect on the Gd-Fe-Co/Cu thin films, which exhibited soft magnetic properties. The introduction of Gd3+ into the system has demonstrated ferromagnetic properties at room temperature, as verified through VSM analysis. Elevating the Gd concentration in the thin film led to an augmentation in saturation magnetization and a reduction in coercivity. Selected samples were subjected to BET and CV studies. CV studies confirmed the capacitive behaviours of the sample. The best magnetic behaviour was seen for the Gd concentration of 0.05 M, suggesting that these films might be suitable candidates for application in energy storage and conversion. Further, the best sample was taken for water splitting studies and showcased excellent HER performance under magnetic field. [ABSTRACT FROM AUTHOR]

Western blot is a popular biomolecular analysis method for measuring the relative quantities of independent proteins in complex biological samples. However, variability in quantitative western blot data analysis poses a challenge in designing reproducible experiments. The lack of rigorous quantitative approaches in current western blot statistical methodology may result in irreproducible inferences. Here we describe best practices for the design and analysis of western blot experiments, with examples and demonstrations of how different analytical approaches can lead to widely varying outcomes. To facilitate best practices, we have developed the blotRig tool for designing and analyzing western blot experiments to improve their rigor and reproducibility. The blotRig application includes functions for counterbalancing experimental design by lane position, batch management across gels, and analytics with covariates and random effects. [ABSTRACT FROM AUTHOR]

To develop transparent materials with superior mechanical properties, nanocrystalline magnesium aluminate (MgAl 2 O 4) spinel with grain sizes ranging from 3.7 to 80 nm has been synthesized by environmentally controlled pressure assisted sintering. In this study, we investigated the microstructure and grain size dependence of the mechanical properties of nanocrystalline MgAl 2 O 4 by performing transmission electron microscopy, nanoindentation, uniaxial micropillar compression, and micro-cantilever bending. Electron microscopy confirmed that the environmentally controlled pressure assisted sintering technique produces a nearly fully dense grain structure with a porosity of less than 1% in larger grain-sized ceramics and observably pore-free grain structures in the smaller grain-sized ceramics. Mechanical characterization revealed that nanoindentation hardness, compressive fracture strength, and fracture toughness each exhibit distinct grain size dependence. Our experimental results and numerical analyses point to a change in dominant strain accommodating mechanisms from dislocation-based plasticity to shear banding as the grain size is reduced, as previously suggested by the literature. Practical implications of the change in strain accommodation mechanisms manifest as the emergence of indentation size effect, weak grain size dependence of hardness and strength, and a ∼2-fold increase in apparent fracture toughness for the smaller grain-sized ceramics. [Display omitted] [ABSTRACT FROM AUTHOR]

• Two target validation approaches are emerging as useful in phase I (P1): P1-PIV and P1-FCTE. • P1-PIV uses primary endpoints in pivotal clinical studies (PIV). • P1-FCTE uses functional changes necessary for therapeutic effects (FCTE). • Their benefits and challenges are compared with those of the conventional P1 approach. This review discusses the growing importance of target validation within phase I (P1) trials as a new trend in drug development, especially in establishing proof of concept (POC) for first-in-class drugs. The paper describes two approaches: the P1-PIV approach, which directly evaluates the primary endpoint for a pivotal clinical study to confirm therapeutic effects during P1, and the newly introduced P1-FCTE, which assesses functional changes necessary for therapeutic effect as a novel target validation milestone in P1. By providing practical examples of first-in-class drugs, we compare the benefits, costs, hurdles and applicable therapeutic areas of these approaches. Finally, we discuss the potential of these novel approaches to facilitate POC success, shorten development timelines and ultimately increase drug discovery success rates. [ABSTRACT FROM AUTHOR]

Nociceptive input diminishes recovery and increases lesion area after a spinal cord injury (SCI). Recent work has linked these effects to the expansion of hemorrhage at the site of injury. The current article examines whether these adverse effects are linked to a pain-induced rise in blood pressure (BP) and/or flow. Male rats with a low-thoracic SCI were treated with noxious input (electrical stimulation [shock] or capsaicin) soon after injury. Locomotor recovery and BP were assessed throughout. Tissues were collected 3 h, 24 h, or 21 days later. Both electrical stimulation and capsaicin undermined locomotor function and increased the area of hemorrhage. Changes in BP/flow varied depending on type of noxious input, with only shock producing changes in BP. Providing behavioral control over the termination of noxious stimulation attenuated the rise in BP and hemorrhage. Pretreatment with the α-1 adrenergic receptor inverse agonist, prazosin, reduced the stimulation-induced rise in BP and hemorrhage. Prazosin also attenuated the adverse effect that noxious stimulation has on long-term recovery. Administration of the adrenergic agonist, norepinephrine 1 day after injury induced an increase in BP and disrupted locomotor function, but had little effect on hemorrhage. Further, inducing a rise in BP/flow using norepinephrine undermined long-term recovery and increased tissue loss. Mediational analyses suggest that the pain-induced rise in blood flow may foster hemorrhage after SCI. Increased BP appears to act through an independent process to adversely affect locomotor performance, tissue sparing, and long-term recovery. [ABSTRACT FROM AUTHOR]

• Quantitative, high-resolution absorption spectra measured in the vacuum-ultraviolet for functionalized cyclic hydrocarbons, the majority of which for the first time. • Absorption cross-sections calculated for intermediates relevant to combustion chemistry and atmospheric chemistry. • Uncertainty analysis conducted. • Extensive comparison with literature, including 1-butene and acetic acid. Absorption cross-sections were measured in the vacuum ultraviolet (9.92–5.17 eV) using differential absorption spectroscopy for a series of six-membered hydrocarbon rings: cyclohexane, cyclohexene, 1,3-cyclohexadiene, 1,4-cyclohexadiene, benzene, tetrahydropyran, 3,4-dihydro-2 H -pyran, 1,4-dioxane, 1,4-dioxene, cyclohexanol, cyclohexen-4-ol, cyclohexen-3-ol, cyclohexanone, cyclohexen-4-one, cyclohexen-3-one, 3,4-epoxycyclohexene, and 4,5-epoxycyclohexene. In addition, cross-sections for 1-butene and acetic acid were measured for comparison with the literature. Uncertainties were quantified in all cases by accounting for errors in gas-phase concentration, experimental repeatability, and signal-to-noise ratio as a function of photon energy. Convolving the sources of error using the root-sum-square method led to an upper limit of 5% uncertainty above the detection limit, which is largely attributable to chemical purity. The primary objective of the present work is to provide absolute cross-sections along with quantified uncertainty limits. The majority of the absorption spectra, which reflect electronic transitions such as σ → σ * and n → σ *, are reported for the first time and provide insight into fundamental chemical physics, such as vibrational band structure and Rydberg transitions. In addition, the absorption cross-sections enable quantitative isomer-resolved speciation measurements in combustion chemistry, photolysis calculations for laser spectroscopy and atmospheric chemistry, and spectral assignments in astrochemistry. [ABSTRACT FROM AUTHOR]

Abstract The effect of Nitrogen - ion implantation and post annealing treatment on Metal Organic Chemical Vapor Deposited (MOCVD) InGaN/GaN heterostructured samples were studied using structural, optical, morphological and electrical characterizations. Three samples with various implantation dosage (1 × 1015, 3 × 1015 and 5 × 1015 ions/cm2) has been studied. A clear increase in crystallinity was observed for post annealed implanted samples from HRXRD. The roughness of the sample increases from 1.3 nm to 5.8 nm when fluency of N - ion increases but is reduced after annealing. The PL spectra for our ion implanted sample shows that there is a remarkable suppression of the YL bands (∼500 nm–650 nm) as the dosage of ions are increased due to the passivation of the YL centers. Hall Effect Measurement shows N+ implanted samples offers high resistance which is reduced on annealing. [ABSTRACT FROM AUTHOR]

Background: Radiographic fracture classification helps with research on prognosis and treatment. AO/OTA classification into fracture type has shown to be reliable, but further classification of fractures into subgroups reduces the interobserver agreement and takes a considerable amount of practice and experience in order to master.Questions/purposes: We assessed: (1) differences between more and less experienced trauma surgeons based on hip fractures treated per year, years of experience, and the percentage of their time dedicated to trauma, (2) differences in the interobserver agreement between classification into fracture type, group, and subgroup, and (3) differences in the interobserver agreement when assessing fracture stability compared to classifying fractures into type, group and subgroup.Methods: This study used the Science of Variation Group to measure factors associated with variation in interobserver agreement on classification of proximal femur fractures according to the AO/OTA classification on radiographs. We selected 30 anteroposterior radiographs from 1061 patients aged 55 years or older with an isolated fracture of the proximal femur, with a spectrum of fracture types proportional to the full database. To measure the interobserver agreement the Fleiss' kappa was determined and bootstrapping (resamples = 1000) was used to calculate the standard error, z statistic, and 95% confidence intervals. We compared the Kappa values of surgeons with more experience to less experienced surgeons.Results: There were no statistically significant differences in the Kappa values on each classification level (type, group, subgroup) between more and less experienced surgeons. When all surgeons were combined into one group, the interobserver reliability was the greatest for classifying the fractures into type (kappa, 0.90; 95% CI, 0.83 to 0.97; p < 0.001), reflecting almost perfect agreement. When comparing the kappa values between classes (type, group, subgroup), we found statistically significant differences between each class. Substantial agreement was found in the clinically relevant groups stable/unstable trochanteric, displaced/non-displaced femoral neck, and femoral head fractures (kappa, 0.60; 95% CI, 0.53 to 0.67, p < 0.001).Conclusions: This study adds to a growing body of evidence that relatively simple distinctions are more reliable and that this is independent of surgeon experience. [ABSTRACT FROM AUTHOR]

Metal Semiconductor Metal (MSM) photodetector devices based on metal organic chemical vapour deposition grown InGaN/GaN heterostructures with Ni/Au contacts has been fabricated with activity under near ultraviolet/visible region of spectra. Composition controlled InGaN/GaN heterostructures has been utilized for device fabrication to realize its correlation with the electrical performance and responsivity of the device. The steady and transient performance of the as designed photodetectors were investigated and a photo response time <9 ms, responsivity of 0.920 A/W and high detectivity range of ∼3.46 × 1013 Jones has been achieved at a wavelength of 360 nm for an indium composition of 10%. We have observed that an increasing indium content in InGaN layers up to an optimum value resulted in an increase in device performance which has been explained with the help of various structural, morphological, optical and spectroscopic analysis. The obtained results were competing with the many previously reported photodetectors. [Display omitted] • Composition varied InGaN/GaN Thin film successfully deposited using MOCVD technique. • MSM photodetector successfully fabricated with single step lithography. • Photo response time (<9 ms), responsivity (0.920 A/W) and detectivity (∼1013 Jones) has been achieved. [ABSTRACT FROM AUTHOR]

InGaN layers were grown by metal organic chemical vapour deposition (MOCVD) technique on GaN/sapphire substrates by varying the growth time. The formation of spiral-like growth domains was observed using atomic force microscopy, revealed that the InGaN layer is atomically flat. In addition, the surface roughness was found to be dependent on the thickness of InGaN layer. The spiral-like islands was correlated with screw type threading dislocation density of InGaN. The thickness-dependent threading dislocation density was investigated using high-resolution x-ray diffraction. The Indium composition and thickness of InGaN were found to be 15–16% and 20–50 nm using the smooth fit software. The structural characteristics obtained using reciprocal space mapping indicate that the InGaN/GaN heterostructures are coherently strained. Photoluminescence (PL) spectra exhibit variations in the band-edge emissions between 437.0 and 443.5 nm peaks with varying temperature, showcasing a slight shift in all the InGaN samples. The low-temperature PL spectra revealed dominant emission mechanism. From the hall effect data it was observed that InGaN layer attained high mobility value close to that of the theoretical limit of GaN and/or InN at 300 K. It is worth to note that the compressive strain present in InGaN layer led to high sheet concentration when compared to that of the tensile strained InGaN layer. Hence, the spiral like islands entrenched InGaN layers which can be effectively utilized for optoelectronic applications. [Display omitted] • Strained InGaN/GaN heterostructures grown by MOCVD. • Analysis of Spiral-like islands through screw dislocation density estimated using HRXRD. • Shift in the NBE peaks of PL excited at different temperature ranges. • Achieving InGaN mobility close to that of GaN and/or InN. [ABSTRACT FROM AUTHOR]

Magnesium is widely regarded as an excellent structural material, primarily because it forms the basis for a range of light-weight high-strength alloys. Recently, high-strain rate deformation of magnesium has received a great deal of attention due to the complicated deformation modes that involve combinations of dislocation slip and deformation twinning. In this study, single crystal magnesium samples were shock-compressed along the c- and a-axis, then released back to ambient conditions. Post-mortem transmission electron microscopy revealed that extension twins developed for both c- and a-axis shock loading. Also, the nanoindentation hardness values for these shocked samples were compared to those for samples compressed under quasi-static conditions; it was found that the hardness decreased with increasing strain rate for both c- and a-axis loading. Molecular dynamics simulations were performed to elucidate the detailed mechanisms of deformation twinning in terms of inertial confinement of sample geometry and different stress relaxation speed between impact and lateral directions. The conversion from work-done to heat was discussed to explain the influence of shock-induced heating on the residual hardness. These results give new insights into the residual mechanical response in shock-compressed materials and may help to develop a more fundamental understanding of shock phenomena in metallic materials. Unlabelled Image • Samples of single crystal magnesium were shock-compressed and released along both the a- and c- axes. • Extension twinning was observed using transmission electron microscopy. • Shock-induced softening was observed using nano-indentation. • Analytical model and molecular dynamics simulations were used to examine the evolution of pressure profiles and extension twinning during the shock-recovery process. [ABSTRACT FROM AUTHOR]

The present review explores the concept of learning within the context of neurorehabilitation after spinal cord injury (SCI). The aim of physical therapy and neurorehabilitation is to bring about a lasting change in function—to encourage learning. Traditionally, it was assumed that the adult spinal cord is hardwired—immutable and incapable of learning. Research has shown that neurons within the lower (lumbosacral) spinal cord can support learning after communication with the brain has been disrupted by means of a thoracic transection. Noxious stimulation can sensitize nociceptive circuits within the spinal cord, engaging signal pathways analogous to those implicated in brain-dependent learning and memory. After a spinal contusion injury, pain input can fuel hemorrhage, increase the area of tissue loss (secondary injury), and undermine long-term recovery. Neurons within the spinal cord are sensitive to environmental relations. This learning has a metaplastic effect that counters neural over-excitation and promotes adaptive learning through an up-regulation of brain-derived neurotrophic factor (BDNF). Exposure to rhythmic stimulation, treadmill training, and cycling also enhances the expression of BDNF and counters the development of nociceptive sensitization. SCI appears to enable plastic potential within the spinal cord by down-regulating the Cl− co-transporter KCC2, which reduces GABAergic inhibition. This enables learning, but also fuels over-excitation and nociceptive sensitization. Pairing epidural stimulation with activation of motor pathways also promotes recovery after SCI. Stimulating motoneurons in response to activity within the motor cortex, or a targeted muscle, has a similar effect. It is suggested that a neurofunctionalist approach can foster the discovery of processes that impact spinal function and how they may be harnessed to foster recovery after SCI. • Spinal cord injury (SCI) enables plasticity by reducing GABA-dependent inhibition • Pain input after SCI induces sensitization, fosters hemorrhage and impairs recovery • Controllable/predictable stimulation increases BDNF and promotes adaptive plasticity • Neurorehabilitative strategies that involve relational learning have a lasting effect • Procedures that introduce periodic (regular) stimulation promote adaptive plasticity [ABSTRACT FROM AUTHOR]

Cyclic ethers are important intermediates involved in degenerate chain-branching reactions during hydrocarbon and biofuel oxidation at temperatures below 1000 K. Depending on the molecular structure of the parent species, e.g. 1-butanol, butanone, or diethyl ether, cyclic ethers can include additional functional groups, such as an alcohol, carbonyl, or a second ether group. Electron-impact mass spectrometry (EI-MS) is a commonly used diagnostic to infer the molecular structure of cyclic ethers, and while mass spectra of simple cyclic ethers using EI are abundant in literature, measurements and related fragmentation patterns of complex cyclic ethers containing multiple functional groups are not, yet are important for determining the presence of species and inferring reaction mechanisms in combustion. The measurements in the present work provide reference EI mass spectra, which enable direct identification of cyclic ether species that are relevant to experimental chemical kinetics measurements of hydrocarbon and biofuel combustion. EI-MS measurements were conducted for 29 cyclic ethers with diverse functional groups such as alcohols, carbonyls, and alkyl substituents of varying length, 10 of which are reported for the first time: 2,3-epoxypentane, 3,4-epoxybutanol, (2-methyloxiranyl)methanol, 2,3-epoxybutanol, 1-(oxiran-2-yl)ethan-1-one, 3,4-epoxycyclohexene, 4,5-epoxycyclohexene, 2-methyloxetane, tetrahydrofuran-3-one, and 2-hydroxytetrahydrofuran. The objective of the present work is two-fold: (i) to provide reference measurements of EI mass spectra for complex combustion intermediates and (ii) to analyze fragmentation patterns of each species to assess the applicability of conventional mechanisms that are commonly employed for discerning molecular structure. The impetus for the latter objective is that, in the majority speciation experiments, EI mass spectra and fragmentation mechanisms are not reported, which raises open questions concerning the reliability of conventional mechanisms to define structural isomers of multi-functional cyclic ethers. In the present work, four conventional mechanisms were employed to analyze fragmentation patterns in the mass spectra: α -cleavage, inductive effect, hydrogen rearrangement, and transannular cleavage. The most common mechanism for the cyclic ethers was inductive cleavage, followed by α -cleavage or hydrogen rearrangement. Multi-functional cyclic ethers were more likely to undergo transannular cleavage occurring across the ring in a single step. For several species, however, abundant ion peaks in the mass spectra are not explained using conventional mechanisms. The present results highlight the importance of reference measurements of EI mass spectra for identifying complex molecules in speciation experiments, which is relevant given that ion fragments of the same mass-to-charge ratio (m/z) are common for species of the same mass. Image 1 • Electron-impact mass spectra measured for complex cyclic ether combustion intermediates for the first time. • Conventional fragmentation mechanisms utilized to predict ion peaks in the mass spectra. • For multi-functional cyclic ethers, α -cleavage, inductive effects, hydrogen rearrangement, and transannular cleavage were unable to explain abundant fragment ion peaks. [ABSTRACT FROM AUTHOR]

Objective: This review evaluates current literature on intensity selection, perceptual responses, activity enjoyment and adherence rates of exergaming., Methods: The literature search identified manuscripts that investigated exercise intensity, perceptual responses, or exercise adherence of exergaming in young adults., Results: Based on results of 29 studies, the current review suggest some exergaming activities have the potential to elicit moderate to vigorous exercise intensity and could potentially be substituted for traditional exercise. Additionally, exergame activities may aid in the start of exercise adherence by lowering the individual's perceived exertion when playing exergames. Exergaming not only has the potential to enhance enjoyment through an exercise objective but also through the distracting nature of video games., Conclusions: Exergaming shows potential to be substituted for traditional exercise and could offer a new, varied form of exercise for sedentary individuals. Future research should examine the influence of exergaming experience on intensity selection and adherence rates.

Aberrant endoplasmic reticulum (ER) and inner nuclear membrane (INM) proteins are destroyed through ER-associated degradation (ERAD) and INM-associated degradation (INMAD). We previously showed the Hrd1, Doa10, and Asi ERAD and INMAD ubiquitin ligases (E3s) in Saccharomyces cerevisiae confer resistance to hygromycin B, which distorts the ribosome decoding center. Here, we assessed the requirement of Ubc6 and Ubc7, the primary ERAD and INMAD ubiquitin-conjugating enzymes (E2s) for hygromycin B resistance. Loss of either E2 sensitized cells to hygromycin B, with UBC7 deletion having a greater impact, consistent with characterized roles for Ubc6 and Ubc7 in ER and INM protein quality control., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2024 by the authors.)

Cystic fibrosis (CF) has been traditionally viewed as a disease that affects White individuals. However, CF occurs among all races, ethnicities, and geographic ancestries. The disorder results from mutations in the CF transmembrane conductance regulator ( CFTR ). Varying incidence of CF is reported among Black, Indigenous, and People of Color (BIPOC), who typically exhibit worse clinical outcomes. These populations are more likely to carry rare CFTR variants omitted from newborn screening panels, leading to disparities in care such as delayed diagnosis and treatment. In this study, we present a case-in-point describing an individual of Gambian descent identified with CF. Patient genotype includes a premature termination codon (PTC) (c.2353C>T) and previously undescribed single nucleotide deletion (c.1970delG), arguing against effectiveness of currently available CFTR modulator-based interventions. Strategies for overcoming these two variants will likely include combinations of PTC suppressors, nonsense mediated decay inhibitors, and/or alternative approaches (e.g. gene therapy). Investigations such as the present study establish a foundation from which therapeutic treatments may be developed. Importantly, c.2353C>T and c.1970delG were not detected in the patient by traditional CFTR screening panels, which include an implicit racial and ethnic diagnostic bias as these tests are comprised of mutations largely observed in people of European ancestry. We suggest that next-generation sequencing of CFTR should be utilized to confirm or exclude a CF diagnosis, in order to equitably serve BIPOC individuals. Additional epidemiologic data, basic science investigations, and translational work are imperative for improving understanding of disease prevalence and progression, CFTR variant frequency, genotype-phenotype correlation, pharmacologic responsiveness, and personalized medicine approaches for patients with African ancestry and other historically understudied geographic lineages., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Research has shown that engaging pain (nociceptive) pathways after spinal cord injury (SCI) aggravates secondary injury and undermines locomotor recovery. This is significant because SCI is commonly accompanied by additional tissue damage (polytrauma) that drives nociceptive activity. Cutting communication with the brain by means of a surgical transection, or pharmacologically transecting the cord by slowly infusing a sodium channel blocker (lidocaine) rostral to a thoracic contusion, blocks pain-induced hemorrhage. These observations suggest that the adverse effect of pain after SCI depends on supraspinal (brain) systems. We hypothesize that inhibiting brain activity using a general anesthetic (e.g., pentobarbital, isoflurane) should have a protective effect. The present study shows that placing rats in an anesthetic state with pentobarbital or isoflurane 24 h after a lower thoracic contusion injury blocks pain-induced intraspinal inflammation and hemorrhage when administered before pain. Pentobarbital also extends protective effects against locomotor deficits produced by noxious stimulation. Inducing anesthesia after noxious stimulation, however, has no effect. Similarly, subanesthetic dosages of pentobarbital were also ineffective at blocking pain-induced hemorrhage. Also examined were the hemodynamic impacts of both pain and anesthetic delivery after SCI. Peripheral pain-input induced an acute increase in systolic blood pressure; isoflurane and pentobarbital prevent this increase, which may contribute to the protective effect of anesthesia. The results suggest that placing patients with SCI in a state akin to a medically induced coma can have a protective effect that blocks the adverse effects of pain.

Purpose of Review: The evaluation of a young athlete with an overuse injury to the knee involves a comprehensive approach. There are a number of elements to consider including assessments of skeletal maturity (biologic maturation), workload (training load + competition load), sport specialization status, and biomechanics. The type of injury and treatment, as well as future prognosis, may be influenced by these and other factors., Recent Findings: Calculating the percentage of predicted adult height (PPAH) is a valuable tool in assessing overuse injury patterns and diagnoses in youth athletes. Modifiable and non-modifiable overuse injury risk factors require monitoring from clinicians as young athletes mature and develop over time. Training and rehabilitation programs should be adapted to account for these. In this manuscript, we seek to introduce a novel, comprehensive approach: S.P.O.R.R.T. (Skeletal Maturity, Prior Injury Risk, One Sport Specialization, Rehabilitation, Return to Play, Training Recommendations) (Fig. 1). Overuse, non-traumatic injuries to the knee in youth athletes will be presented in a case-based and evidence-based model to provide a framework for a comprehensive approach to the assessment and treatment of youth athletes with overuse injuries., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cystic fibrosis (CF) is widely known as a disease of the lung, even though it is in truth a systemic disease, whose symptoms typically manifest in gastrointestinal dysfunction first. CF ultimately impairs not only the pancreas and intestine but also the lungs, gonads, liver, kidneys, bones, and the cardiovascular system. It is caused by one of several mutations in the gene of the epithelial ion channel protein CFTR. Intense research and improved antimicrobial treatments during the past eight decades have steadily increased the predicted life expectancy of a person with CF (pwCF) from a few weeks to over 50 years. Moreover, several drugs ameliorating the sequelae of the disease have become available in recent years, and notable treatments of the root cause of the disease have recently generated substantial improvements in health for some but not all pwCF. Yet, numerous fundamental questions remain unanswered. Complicating CF, for instance in the lung, is the fact that the associated insufficient chloride secretion typically perturbs the electrochemical balance across epithelia and, in the airways, leads to the accumulation of thick, viscous mucus and mucus plaques that cannot be cleared effectively and provide a rich breeding ground for a spectrum of bacterial and fungal communities. The subsequent infections often become chronic and respond poorly to antibiotic treatments, with outcomes sometimes only weakly correlated with the drug susceptibility of the target pathogen. Furthermore, in contrast to rapidly resolved acute infections with a single target pathogen, chronic infections commonly involve multi-species bacterial communities, called "infection microbiomes," that develop their own ecological and evolutionary dynamics. It is presently impossible to devise mathematical models of CF in its entirety, but it is feasible to design models for many of the distinct drivers of the disease. Building upon these growing yet isolated modeling efforts, we discuss in the following the feasibility of a multi-scale modeling framework, known as template-and-anchor modeling, that allows the gradual integration of refined sub-models with different granularity. The article first reviews the most important biomedical aspects of CF and subsequently describes mathematical modeling approaches that already exist or have the potential to deepen our understanding of the multitude aspects of the disease and their interrelationships. The conceptual ideas behind the approaches proposed here do not only pertain to CF but are translatable to other systemic diseases. This article is categorized under: Congenital Diseases > Computational Models., (© 2023 Wiley Periodicals LLC.)

Western blot is a popular biomolecular analysis method for measuring the relative quantities of independent proteins in complex biological samples. However, variability in quantitative western blot data analysis poses a challenge in designing reproducible experiments. The lack of rigorous quantitative approaches in current western blot statistical methodology may result in irreproducible inferences. Here we describe best practices for the design and analysis of western blot experiments, with examples and demonstrations of how different analytical approaches can lead to widely varying outcomes. To facilitate best practices, we have developed the blotRig tool for designing and analyzing western blot experiments to improve their rigor and reproducibility. The blotRig application includes functions for counterbalancing experimental design by lane position, batch management across gels, and analytics with covariates and random effects., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest.

Traumatic injury to the central nervous system (CNS) and stroke initiate a cascade of processes that expand the area of tissue loss. The current review considers recent studies demonstrating that the induction of an anesthetic state or cooling the affected tissue (hypothermia) soon after injury can have a therapeutic effect. We first provide an overview of the neurobiological processes that fuel tissue loss after traumatic brain injury (TBI), spinal cord injury (SCI) and stroke. We then examine the rehabilitative effectiveness of therapeutic anesthesia across a variety of drug categories through a systematic review of papers in the PubMed database. We also review the therapeutic benefits hypothermia, another treatment that quells neural activity. We conclude by considering factors related to the safety, efficacy and timing of treatment, as well as the mechanisms of action. Clinical implications are also discussed., (Copyright © 2023 Elsevier Inc. All rights reserved.)

While understanding hydrogen uptake by organic based getters such as 1,4-bis(phenylethynyl)benzene (DEB) combined with a palladium(0)bis(dibenzylideneacetone) (Pd(dba) 2 ) catalyst is essential, another crucial element to understand is the decomposition of the DEB, Pd(dba) 2 , and/or substrate material. The breakdown of these materials may create unwanted volatiles, which may interact with and lead to deterioration of sensitive materials. Moreover, it is critical to understand if different substrates cause the getter and/or catalyst to degrade in different manners. Utilizing comprehensive two-dimensional gas chromatography (GC×GC) with time-of-flight mass spectrometry (TOFMS), the presence of volatiles located in the headspace of various DEB/Pd(dba) 2 getter substrates is examined. These samples include a getter infused silicone foam, a hydrogenated getter infused silicone foam, an activated carbon getter pellet, and a hydrogenated activated carbon getter pellet. Application of Fisher ratio (F-ratio) analyses lead to the identification of several compounds that are generated or consumed through the hydrogenation process. These include benzene derivatives such as bibenzyl, benzaldehyde, and vinyl benzoate in the activated carbon pellets and 1,5-diphenyl-3-pentanone, toluene, styrene, and 1-1'(2-pentene 1,5-diyl)bis benzene in the silicone foams, and alkane/alkene derivatives such undecane, 4-tridecene, and decane in the activated carbon pellets and 2,6-dimethyl undecane in the silicone foams. Further comparison of the different hydrogenated getter substrates (e.g. activated carbon pellet and silicone foam) indicates that the different substrates alter the decomposition products created from the degradation of the DEB and Pd(dba) 2 ., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Networks are ubiquitous throughout biology, spanning the entire range from molecules to food webs and global environmental systems. Yet, despite substantial efforts by the scientific community, the inference of these networks from data still presents a problem that is unsolved in general. One frequent strategy of addressing the structure of networks is the assumption that the interactions among molecular or organismal populations are static and correlative. While often successful, these static methods are no panacea. They usually ignore the asymmetry of relationships between two species and inferences become more challenging if the network nodes represent dynamically changing quantities. Overcoming these challenges, two very different network inference approaches have been proposed in the literature: Lotka-Volterra (LV) models and Multivariate Autoregressive (MAR) models. These models are computational frameworks with different mathematical structures which, nevertheless, have both been proposed for the same purpose of inferring the interactions within coexisting population networks from observed time-series data. Here, we assess these dynamic network inference methods for the first time in a side-by-side comparison, using both synthetically generated and ecological datasets. Multivariate Autoregressive and Lotka-Volterra models are mathematically equivalent at the steady state, but the results of our comparison suggest that Lotka-Volterra models are generally superior in capturing the dynamics of networks with non-linear dynamics, whereas Multivariate Autoregressive models are better suited for analyses of networks of populations with process noise and close-to linear behavior. To the best of our knowledge, this is the first study comparing LV and MAR approaches. Both frameworks are valuable tools that address slightly different aspects of dynamic networks., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Olivença, Davis and Voit.)

Evaluation of Gastrointestinal Stromal Tumors (GIST) during initial clinical staging, surgical intervention, and postoperative management can be challenging. Current imaging modalities ( e.g. , PET and CT scans) lack sensitivity and specificity. Therefore, advanced clinical imaging modalities that can provide clinically relevant images with high resolution would improve diagnosis. KIT is a tyrosine kinase receptor overexpressed on GIST. Here, the application of a specific DNA aptamer targeting KIT, decorated onto a fluorescently labeled porous silicon nanoparticle (pSiNP), is used for the in vitro & in vivo imaging of GIST. This nanoparticle platform provides high-fidelity GIST imaging with minimal cellular toxicity. An in vitro analysis shows greater than 15-fold specific KIT protein targeting compared to the free KIT aptamer, while in vivo analyses of GIST-burdened mice that had been injected intravenously (IV) with aptamer-conjugated pSiNPs show extensive nanoparticle-to-tumor signal co-localization (>90% co-localization) compared to control particles. This provides an effective platform for which aptamer-conjugated pSiNP constructs can be used for the imaging of KIT-expressing cancers or for the targeted delivery of therapeutics.

Chronic (long-lasting) infections are globally a major and rising cause of morbidity and mortality. Unlike typical acute infections, chronic infections are ecologically diverse, characterized by the presence of a polymicrobial mix of opportunistic pathogens and human-associated commensals. To address the challenge of chronic infection microbiomes, we focus on a particularly well-characterized disease, cystic fibrosis (CF), where polymicrobial lung infections persist for decades despite frequent exposure to antibiotics. Epidemiological analyses point to conflicting results on the benefits of antibiotic treatment yet are confounded by the dependency of antibiotic exposures on prior pathogen presence, limiting their ability to draw causal inferences on the relationships between antibiotic exposure and pathogen dynamics. To address this limitation, we develop a synthetic infection microbiome model representing CF metacommunity diversity and benchmark on clinical data. We show that in the absence of antibiotics, replicate microbiome structures in a synthetic sputum medium are highly repeatable and dominated by oral commensals. In contrast, challenge with physiologically relevant antibiotic doses leads to substantial community perturbation characterized by multiple alternate pathogen-dominant states and enrichment of drug-resistant species. These results provide evidence that antibiotics can drive the expansion (via competitive release) of previously rare opportunistic pathogens and offer a path toward microbiome-informed conditional treatment strategies. IMPORTANCE We develop and clinically benchmark an experimental model of the cystic fibrosis (CF) lung infection microbiome to investigate the impacts of antibiotic exposures on chronic, polymicrobial infections. We show that a single experimental model defined by metacommunity data can partially recapitulate the diversity of individual microbiome states observed across a population of people with CF. In the absence of antibiotics, we see highly repeatable community structures, dominated by oral microbes. Under clinically relevant antibiotic exposures, we see diverse and frequently pathogen-dominated communities, and a nonevolutionary enrichment of antimicrobial resistance on the community scale, mediated by competitive release. The results highlight the potential importance of nonevolutionary (community-ecological) processes in driving the growing global crisis of increasing antibiotic resistance.

Single-cell proteomics (SCP) has great potential to advance biomedical research and personalized medicine. The sensitivity of such measurements increases with low-flow separations (<100 nL/min) due to improved ionization efficiency, but the time required for sample loading, column washing, and regeneration in these systems can lead to low measurement throughput and inefficient utilization of the mass spectrometer. Herein, we developed a two-column liquid chromatography (LC) system that dramatically increases the throughput of label-free SCP using two parallel subsystems to multiplex sample loading, online desalting, analysis, and column regeneration. The integration of MS1-based feature matching increased proteome coverage when short LC gradients were used. The high-throughput LC system was reproducible between the columns, with a 4% difference in median peptide abundance and a median CV of 18% across 100 replicate analyses of a single-cell-sized peptide standard. An average of 621, 774, 952, and 1622 protein groups were identified with total analysis times of 7, 10, 15, and 30 min, corresponding to a measurement throughput of 206, 144, 96, and 48 samples per day, respectively. When applied to single HeLa cells, we identified nearly 1000 protein groups per cell using 30 min cycles and 660 protein groups per cell for 15 min cycles. We explored the possibility of measuring cancer therapeutic targets with a pilot study comparing the K562 and Jurkat leukemia cell lines. This work demonstrates the feasibility of high-throughput label-free single-cell proteomics.