University at Buffalo, State University of New York

Misinformation can be broadly defined as information that is inaccurate or false according to the best available evidence, or information whose validity cannot be verified. It is created and spread with or without clear intent to cause harm. There is well-documented evidence that misinformation persists despite fact-checking and the presentation of corrective information, often traveling faster and deeper than facts in the online environment. Drawing on the frameworks of social judgment theory, cognitive dissonance theory, and motivated information processing, the authors conceptualize corrective information as a generic type of counter-attitudinal message and misinformation as attitude-congruent messages. They then examine the persistence of misinformation through the lens of biased responses to attitude-inconsistent versus -consistent information. Psychological inoculation is proposed as a strategy to mitigate misinformation.

Magnetic materials are omnipresent in everyday life, with applications spanning a wide range of fields. This focus collection provides a comprehensive overview of recent developments in the synthesis and characterization of advanced magnetic materials, both in their bulk and low-dimensional forms. These studies aim to enhance our understanding of fundamental physical properties and identify suitable candidate materials for various device applications. We believe that this focus collection will serve not only as a valuable reference but also as a source of inspiration for further research on advanced magnetic materials.

Domain antibodies such as monobodies provide an attractive immunoglobin fold for evolving high‐affinity protein binders targeting the intracellular proteins implicated in cell signalling. However, it remains a challenge to endow cell permeability to these small and versatile protein binders. Here, we report a streamlined approach combining orthogonal crosslinking afforded by a genetically encoded β‐lactam‐lysine (BeLaK) and genetic supercharging to generate cell‐penetrating monobodies. When introduced to the N‐terminal β‐strand of a series of supercharged monobodies, BeLaK enabled efficient inter‐strand crosslinking with the neighbouring lysine. Compared to its non‐crosslinked counterpart, a BeLaK‐crosslinked, +18‐charged monobody exhibited enhanced thermostability and greater cellular uptake at 40 nM. Moreover, this structurally rigidified, supercharged monobody inhibited ERK1/2 phosphorylation in KYSE‐520 esophageal cancer cell line at sub‐micromolar concentration, indicating significant endosomal escape after endocytosis. Together, the discovery of this BeLaK‐encoded, rigidified immunoglobin fold should facilitate the design of cell‐penetrating monobodies targeting intracellular signalling proteins.

Pregnancy-induced changes to spinal anatomy and physiology can increase the complexity of neurosurgical intervention in this population. There are numerous reports focused on the neurosurgical management of intracranial pathology for pregnant patients. However, less is known about the neurosurgical management of acute spinal pathology. This study aims to discuss the management of emergent spinal pathology during late-term pregnancy. This is a case series of acute spinal pathologies in pregnancy. Epidural spinal needle fracture, epidural abscess, disc herniation causing an acute neurological deficit, and potential spine trauma. An extensive literature search relevant to the operative cases was performed to highlight the relevant themes to management. (1) The epidural spinal needle fracture was managed by surgical exploration under local anesthesia. (2) The epidural abscess was managed with laminectomy and surgical evacuation of the infective mass under general anesthesia. (3) The acute disc herniation was managed with laminectomy and discectomy under general anesthesia. All three examples were managed with emergent surgeries with improvement of symptoms. (4) The potential spine trauma was managed nonoperatively. Relevant similar cases from the literature review were summarized and strategies for management were outlined. Several factors such as anesthesia type, positioning, and operation sequencing must be considered when managing acute spinal pathology in late-term pregnant patients, necessitating multi-disciplinary input. However, effective management can result in successful surgical intervention and improvement of symptoms.

The objective of this review is to evaluate and summarize the evidence base for the effects of monetary intervention approaches (the use of positive monetary reinforcers and gains) on diabetes outcomes. A reproducible search using OVID Medline, PubMed, Scopus, and CINAHL was conducted. Articles published from database creation up to July 2024 were searched. Outcomes included hemoglobin A1c (HbA1c), LDL, BMI, blood pressure, quality of life (QOL), psychosocial factors, self-care behaviors, and diabetes complications. A total of 13 articles met inclusion criteria and were included for final synthesis. Looking at the monetary approach across each study, eight used financial incentives, three used a form of income supplementation, one used cash transfers, and one used a combination of income supplementation and financial incentives. Ten of the 13 studies found statistically significant and clinically meaningful changes in HbA1c. For participants receiving interventions, change in HbA1c ranged from 0.19% to 1.74% for interventions incorporating financial incentives, 0.7% to 1.3% for interventions incorporating income supplementation, and 0.2% to 0.7% for the study incorporating cash transfers. Overall, evidence supports the relationship between monetary approaches, diabetes-related outcomes, and self-care behaviors across monetary approaches. Future studies should consider comparison between different monetary approaches using designs that will allow identification of effective strategies. As these approaches are theoretically and structurally different, pathways identifying the underlying mechanisms of change are greatly needed to advance the field.

As hydrogel research progresses, hydrogels are becoming essential tools in bioelectronics and biotechnology. This review explores the diverse range of natural and synthetic gel materials tailored for specific bioelectronic applications, with a focus on their integration with electronic components to create responsive, multifunctional systems. The role of Artificial Intelligence (AI) in advancing gel design and functionality from optimizing material properties to enabling precise, predictive modeling is investigated. Furthermore, recent innovations that harness the synergy between hydrogels, electronics, and AI are discussed, emphasizing the potential of these materials to drive future advances in biomedical technologies. AI‐driven approaches are transforming the development of hydrogels for applications in wound healing, biosensing, drug delivery, and tissue engineering.

Combined medicine-pediatrics training was formally established in 1967 by the American Board of Pediatrics and the American Board of Internal Medicine. More than 8000 physicians have completed dual training. Their career choices are not well-described. To describe career choices among graduates of combined medicine-pediatrics training programs. Nationally representative research surveys conducted each winter from 2017 to 2023 of combined medicine-pediatrics (Med-Peds) residency program directors (PDs), whose programs were (1) of continued accreditation status with the Accreditation Council for Graduate Medical Education (N = 77 to 80) and (2) members of the Medicine Pediatrics Program Directors Association. One of the recurring sections collected data on medicine-pediatrics residency program graduates from the previous academic year (AY), including career choices. From 2020 to 2023, the survey also collected data on the percentage of programs with fifth-year post-graduate year (PGY) chief medical residents who graduated during the previous AY, and PD-reported career choices for those chief residents. The survey response rates ranged from 70.9% (56/79) to 85.7% (66/77; mean response rate: 81.3%). Over the seven survey years, there was little variability in the mean percentage of medicine-pediatrics graduates (n = 2191) by PD-reported career field (p > 0.001 for all multi-year comparisons). Aggregated over all years, the top four reported career fields were internal medicine fellowship (16.9%), private ambulatory/outpatient practice (16.2%), medicine-pediatrics hospitalist (14.6%), and academic practice (10.2%). Medicine-pediatrics physicians pursue diverse career paths and make important contributions to the healthcare workforce.

In actinide chemistry, the formal number of open‐shell 5f electrons, n(open), is a well‐defined quantity with an integer value. The effective 5f occupation, n(f), additionally takes donation and back‐donation into account, generally has a non‐integer value, and varying numerical definitions. The present study explores the important distinction between n(f) and n(open) in actinide chemistry with the example of PuO2, by using electronic structure methods with a relativistic Hamiltonian in combination with experimental Pu M5‐edge high energy resolution X‐ray absorption and emission spectroscopic data. The total donation to the metal in PuO2 is between 3.1 and 2.4 electrons, depending on the type of calculation, most of which is to the Pu 6d and 5f shells. The donation into 5f is sensitive to the approximations in the electronic structure model but likely amounts to 1.6/0.8 electrons when the diffuse regions of the 5f shell are included/excluded. Valence band resonant inelastic X‐ray scattering (VB‐RIXS) experiments demonstrate that Pu 5f electron density is present in the valence band; thus, there is a clear experimental signature of covalent bonding in PuO2. Pu M5‐edge and M3‐edge high energy resolution X‐ray absorption near edge structure (HR‐XANES) for Pu3+ and Pu4+ in aqueous solution are compared to PuO2 showing that Pu in PuO2 has n(f) closer to Pu4+(aq).

Conventionally, the size, shape, and biomechanics of cartilages are determined by their voluminous extracellular matrix. By contrast, we found that multiple murine cartilages consist of lipid-filled cells called lipochondrocytes. Despite resembling adipocytes, lipochondrocytes were molecularly distinct and produced lipids exclusively through de novo lipogenesis. Consequently, lipochondrocytes grew uniform lipid droplets that resisted systemic lipid surges and did not enlarge upon obesity. Lipochondrocytes also lacked lipid mobilization factors, which enabled exceptional vacuole stability and protected cartilage from shrinking upon starvation. Lipid droplets modulated lipocartilage biomechanics by decreasing the tissue’s stiffness, strength, and resilience. Lipochondrocytes were found in multiple mammals, including humans, but not in nonmammalian tetrapods. Thus, analogous to bubble wrap, superstable lipid vacuoles confer skeletal tissue with cartilage-like properties without “packing foam–like” extracellular matrix.

International courts are increasingly serving as bulwarks of democracy. These courts, however, often depend on the cooperation of the very governments they seek to hold accountable, exposing them to potential retaliation for attempting to constrain their behavior. As governments’ response to adverse decision-making is often conditional on public support, we explore whether citizens actually support international courts’ judicial power over questions of democracy. We argue that citizens’ support for this form of judicial power depends on their democratic values and their desire for institutional checks and balances against the executive. Furthermore, we contest that this support is conditional on partisanship, with this relationship holding for opposition partisans while government partisans are generally opposed to international courts’ judicial power. We support our expectations using original survey data collected from Hungary before their 2022 national legislative elections, and examining citizens’ support for judicial power for the Court of Justice of the European Union.

Metaverse technology is assumed as the future of digital healthcare because this technology has the potential to contribute a lot. Despite the extensive exploration of this concept in various domains, including healthcare, there remains a notable gap in addressing security concerns within virtual worlds. This vulnerability arises from several factors, including wireless communication, open-area deployment, the adoption of new devices and users, and authentication processes. These factors make the technology susceptible to various internal and external threats, such as tampering attacks, jamming attacks, spoofing attacks, blackhole attacks, sinkhole attacks and many more. Considering the importance of this topic, in this study, we start our discussion with the privacy and security concerns of the Metaverse technology, focusing on its applications in the healthcare domain. We extend this talk to virtual reality (VR), augmented reality (AR), extended reality (XR), and mixed reality (MR), as these technologies constitute the foundational components of the Metaverse. Subsequently, our attention shifts to the evaluation of primary security authentication methods deployed in VR, AR, MR, and other associated technologies. These methods include information-based authentication, biometric-based authentication, password-based authentication, context-based authentication, PIN-based authentication, and multi-model-based authentication paradigm, etc. Furthermore, we analyze the advantages and disadvantages of the relevant literature, laying the groundwork for future research directions. Finally, we conclude the paper with what work needs to be done for the improved safety and security of this technology in healthcare.

Mismatch repair (MMR) is a highly conserved DNA repair pathway that recognizes mispairs that occur spontaneously during DNA replication and coordinates their repair. In Saccharomyces cerevisiae, Msh2-Msh3 and Msh2-Msh6 initiate MMR by recognizing and binding insertion deletion loops (in/dels) up to ∼ 17 nucleotides (nt.) and base-base mispairs, respectively; the two complexes have overlapping specificity for small (1-2 nt.) in/dels. The DNA-binding specificity for the two complexes resides in their respective mispair binding domains (MBDs) and have distinct DNA-binding modes. Msh2-Msh3 also plays a role in promoting CAG/CTG trinucleotide repeat (TNR) expansions, which underlie many neurodegenerative diseases such as Huntington’s Disease and Myotonic Dystrophy Type 1. Models for Msh2-Msh3’s role in promoting TNR tracts expansion have invoked its specific DNA-binding activity and predict that the TNR structure alters its DNA binding and downstream activities to block repair. Using a chimeric Msh complex that replaces the MBD of Msh6 with the Msh3 MBD, we demonstrate that Msh2-Msh3 DNA-binding activity is not sufficient to promote TNR expansions. We propose a model for Msh2-Msh3-mediated TNR expansions that requires a fully functional Msh2-Msh3 including DNA binding, coordinated ATP binding and hydrolysis activities and interactions with Mlh complexes that are analogous to those required for MMR.

Objectives This cross-sectional study aimed to evaluate the occurrence of Streptococcus spp., Streptococcus mutans, its serotypes (c, e, f, and k), collagen-binding genes (cnm/cbm), and Candida albicans in medium deep (D2) and deep (D3) dentin carious lesions of permanent teeth. Materials and methods Carious dentin was collected from D2 (n = 23) and D3 (n = 24) lesions in posterior teeth from 31 individuals. DNA was extracted and analyzed using polymerase chain reaction (PCR). Results Streptococcus spp. exhibited a high prevalence in both D2 and D3 lesions, with a 100% occurrence rate in D3. Although S. mutans was prevalent in both lesion types, serotype distribution highlighted differences in complexity. Serotype e was the most frequently detected in D2 samples. Serotype c was absent in D2 but present in 19.0% of D3; serotype k was exclusively found in multi-serotype D3 alongside f, c, and e. The cbm gene and undetermined serotypes were detected only in D3. Candida albicans was not found in any samples, regardless of lesion depth. Conclusion Dentinal lesions exhibited a complex array of S. mutans serotypes, with a notable prevalence of the genus Streptococcus and an overall S. mutans prevalence of approximately 35%. Candida albicans was absent. In addition, a high diversity of serotypes was observed, including multiple and indeterminate serotypes, along with the presence of the collagen-binding cbm gene. Clinical relevance The identification of diverse Streptococcus mutans serotypes and the cbm gene in carious dentin from permanent teeth offers insights into microbial factors potentially linked to dentinal caries lesions. Additionally, the absence of Candida albicans suggests a limited role in this context.

Background Understanding the fundamental differences between the human and pre‐human brain is a prerequisite for designing meaningful models and therapies for AD. Expressed CHRFAM7A, a human restricted gene with carrier frequency of 75% in the human population predicts profound translational significance. Method The physiological role of CHRFAM7A in human brain is explored using multiomics approach on 600 post mortem human brain tissue samples (ROSMAP). The emerging pathways are tested and validated in an isogenic hiPSC model of CHRFAM7A knock‐in neurons and monocytes. In vivo validation is performed in a double blind pharmacogenetic study on the effect of nicotinic acetyl‐choline esterase inhibitor therapy. The effect of CHRFAM7A carrier status was assessed in two paradigms: response to drug initiation and disease modifying therapy (DMT) effect over an 8 year observation period. Fitted general linear model independent variables included age, sex, and medication regimen at the time of the first MMSE, APOE4 carrier status (0, 1 or 2 alleles as categorical variables) and CHRFAM7A genotype. Result CHRFAM7A is identified as a modulator of intracellular calcium dynamics and an upstream regulator of Rac1. Rac1 activation re‐designs the actin cytoskeleton leading to dynamic actin driven remodeling of membrane protrusion and a switch from filopodia to lamellipodia. Phenotypic readouts in both the neuronal and monocytic lineages confirm actin cytoskeleton gain of function. The actin cytoskeleton reorganization shifts dendritic spine differentiation from filopodia towards spines with increased head area to stem diameter ratio resulting in increased synapse clustering (“high quality wellcro”) in neurons. In monocytes, the reorganized actin cytoskeleton leads to increased invasion, phagocytosis and cytokine release. These data suggest a shift from neurodegenerative to neuroinflammatory mechanism in 75% of AD patients. From the cholinergic treatment perspective incorporation into the a7 nAChR pentamer results in a hypomorphic receptor, which has diminished response to pharmacological modulation. Proof of principle pharmacogenetic study found a CHRFAM7A effect on treatment response both in the acute response and DMT paradigms. Conclusion Human restricted CHRFAM7A defines the biological background for AD pathology by shifting neurodegeneration to neuroinflammation in a 25‐75% split. Introducing a CHRFAM7A model into the target selection workflow may increase clinical trial success.

Background CHRFAM7A is a human‐restricted gene associated with neuropsychiatric and neurodegenerative disorders. The translated CHRFAM7A protein incorporates into the α7 nicotinic acetylcholine receptor (α7nAChR) leading to a hypomorphic receptor. Mechanistic insight from isogenic iPSC derived neuronal and mononuclear cells demonstrated that CHRFAM7A affects Ca²⁺ signaling and activates small GTPase Rac1 leading to an actin cytoskeleton gain of function. Fundamental differences in tissue stiffness in human and rodent brain are emerging as a translational gap. Since the actin cytoskeleton is a driver of adaptation to tissue stiffness, we explored the role of CHRFAM7A in mechanobiology. Method Neuronal progenitors and monocytes were differentiated from isogenic iPSCs (null and CHRFAM7A knock‐in (KI)). Polyacrylamide hydrogels corresponding to Young’s modulus 2 kPa (soft) and 5 kPa (stiff) were used to model the mechanical properties of the tissue environment. Actin immunofluorescent morphological analysis and atomic force microscopy (AFM) were utilized to characterize cellular adaptation. Result AFM demonstrated intracellular stiffness adaptation to the soft and stiff environment in CHRFAM7A KI neuronal progenitors and monocytes. In CHRFAM7A KI neuronal progenitors, growth cone (GC) morphology adapted to the stiffness by reinforcing lamellipodia and maintaining directionality. In null MGE progenitors filopodia remained the actin structure in both the soft and stiff environment resulting in GC curvature in the stiff hydrogel. Polarization pattern favored the bipolar morphology in both the neuronal and monocytic lineage of CHRFAM7A KI cells in the stiff environment, while null cells retained the multipolar pattern. Cell polarity correlated with small GTPase activity: in null MGE progenitors, multipolar morphology is associated with high RhoA activity in the stiff environment. In contrast, CHRFAM7A KI MGE progenitors adapted to stiffness by activating both CDC42 and Rac1. Conclusion Human specific CHRFAM7A facilitates adaptation to matrix stiffness in both the neuronal and mononuclear lineage, bridging the gap between rodent and human brain stiffness and holding implications for physiological and pathological conditions. Human‐restricted CHRFAM7A needs to be taken into account to overcome the translational gap in drug development for neurodegenerative and neuroinflammatory diseases.

The study quantitatively analyzes and compares the pharmacokinetics (PK) of methylprednisolone (MPL) in humans upon administration of various dosage forms. The PK parameters and profiles of MPL in healthy subjects were collected from 22 literature sources. A minimal physiologically based pharmacokinetic (mPBPK) model consisting of blood and two tissue (lumped liver and kidney, remainder) compartments with nonlinear tissue partitioning was applied to describe MPL disposition. Overall 18 plasma concentration profiles were well captured and 85% of PK parameters reasonably estimated. The clearance (CL) of MPL averaged 336 mL/h/kg and appeared slightly nonlinear across a dosage range of 5 to 800 mg, the distribution volume (Vd) averaged 1.17 L/kg, and the model predicted elimination half-life (t1/2) was 2.6 h. Rapid prodrug conversion was found for intravenous MPL sodium succinate (MPSS) with a t1/2 of 1.7 min, and followed by MPL phosphate (MPPS) 3.8 min, MPL hemisuccinate (MPHS) 16 min, and MPL suleptanate (MPSP) 2.9 h. Their bioavailabilities (F) varied slightly from 60 to 73%. Intramuscular doses showed an absorption rate constant (ka) of 1.5 h−1 for MPSS and 96 h−1 for MPSP. Oral doses of 5 formulations were examined. Medrol exhibited greatest absorption with F of 74% and ka of 2.1 h−1, while one generic product had F of 32.6%. This study demonstrated the utility of a mechanistic mPBPK disposition model for comparing MPL formation from various esters, absorption from several oral dose formulations, and modest variability across numerous PK studies in healthy humans.

Background Previous research observed links between prenatal air pollution and risk of childhood obesity but the timing of the exposure is understudied. Aim: We examined prenatal particulate matter (PM10, PM2.5) exposure and child anthropometry. Materials & Methods Children's body mass index z‐scores (zBMI) at 0–3 (N = 4370) and 7–9 (n = 1191) years were derived from reported anthropometry at paediatric visits. We ran linear mixed models for six windows, adjusting for maternal, child, and neighbourhood factors. Results PM10 exposure across pregnancy and at multiple windows was associated with higher zBMI in both early and middle childhood. For instance, one interquartile range increase in PM10 exposure during the first 2 weeks of pregnancy was associated with higher zBMI at 0–3 (0.05, 95% CI: 0.01, 0.10) and 7–9 (0.14, 95% CI: 0.02, 0.23). PM2.5 exposure during the final 2 weeks of gestation was associated with higher zBMI at 7–9 years (B: 0.12, 95% CI: 0.04, 0.22). Conclusion Even at low levels of air pollution, prenatal PM10 exposure was associated with higher zBMI in childhood.