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Background: The utilization of hemodynamic parameters, whose estimation is often cumbersome, can fasten diagnostics and decision-making related to congenital heart diseases. The main goal of this study is to investigate the relationship between hemodynamic and morphometric features of the thoracic aorta and to construct corresponding predictive models. Methods: Multi-slice spiral computed tomography images of the aortas of patients with coarctation diagnoses and patients without cardiac or vascular diseases were evaluated to obtain numerical models of the aorta and branches of the aortic arch. Hemodynamic characteristics were estimated in key subdomains of the aorta and three branches using computational fluid dynamics methods. The key morphometric features (diameters) were calculated at locations in proximity to the domains, where hemodynamic characteristics are evaluated. Results: The functional dependencies for velocities and pressure on the corresponding diameters have been fitted, and a metamodel has been constructed employing the predicted values from these models. Conclusions: The metamodel demonstrated high accuracy in classifying aortas into their respective types, thereby confirming the adequacy of the predicted hemodynamic characteristics by morphometric characteristics. The proposed methodology is applicable to other heart diseases without fundamental changes.

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Donor-specific anti-HLA antibodies (DSA) are an important cause of engraftment failure and may negatively impact survival outcomes of patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) using an HLA-mismatched allograft. The incidence of DSA varies across studies, depending on individual factors, detection or identification methods and thresholds considered clinically relevant. Although DSA testing by multiplex bead arrays remains semiquantitative, it has been widely adopted as a standard test in most transplant centers. Additional testing to determine risk of allograft rejection may include assays with HLA antigens in natural conformation, such as flow cytometric crossmatch, and/or antibody binding assays, such as C1q testing. Patients with low level of DSA (<2,000 mean fluorescence intensity; MFI) may not require treatment, while others with very high level of DSA (>20,000 MFI) may be at very high-risk for engraftment failure despite current therapies. By contrast, in patients with moderate or high level of DSA, desensitization therapy can successfully mitigate DSA levels and improve donor cell engraftment rate, with comparable outcomes to patients without DSA. Treatment is largely empirical and multimodal, involving the removal, neutralization, and blocking of antibodies, as well as inhibition of antibody production to prevent activation of the complement cascade. Desensitization protocols are based on accumulated multicenter experience, while prospective multicenter studies remain lacking. Most patients require a full intensity protocol that includes plasma exchange, while protocols relying only on rituximab and intravenous immunoglobulin may be sufficient for patients with lower DSA levels and negative C1q and/or flow cytometric crossmatch. Monitoring DSA levels before and after HSCT could guide preemptive treatment when high levels persist after stem cell infusion. This paper aims to standardize current evidence-based practice and formulate future directions to improve upon current knowledge and advance treatment for this relatively rare, but potentially serious complication in allogeneic HSCT recipients.

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Formaldehyde has been found to decrease virus concentrations in feed and ingredient matrices. Continued research is needed to identify the appropriate inclusion levels and application time for different viruses in these matrices. The objective was to evaluate different inclusion levels of formaldehyde when applied either pre- or postinoculation of porcine epidemic diarrhea virus (PEDV), type 2 porcine reproductive and respiratory syndrome virus (PRRSV), and Seneca Valley virus 1 (SVV1) to complete feed or soybean meal. The experiment was designed in a 2 × 2 factorial with a formaldehyde-based product (Termin-8, Anitox Corporation, Lawrenceville, GA) applied either before virus inoculation (preinoculation) or after inoculation (postinoculation) at either a 2 or 3 kg/MT. On day 0, samples of the respective matrices were weighed in 50 g aliquots and added to 500 mL bottles. Formaldehyde was applied to the preinoculation samples at the respective inclusion levels and 50 µL of each virus were added to the postinoculation samples. All bottles were shaken and allowed to sit at room temperature for 24 h. On day 1, virus was added to the preinoculation samples and formaldehyde was added to the postinoculation bottles. Half of the samples were immediately processed (0 h) and the other half were incubated at room temperature for an additional 24 h. Samples were processed and aliquots were analyzed via triplex PCR. An application time × inclusion level interaction was observed for PEDV at 0 h and SVV1 and PEDV at 24 h in complete feed, where less viral RNA (P < 0.05) was detected in the postinoculation samples at either inclusion level as compared to the positive controls. In soybean meal, the same interaction was observed in PEDV and PRRSV at 0 h and SVV1 and PEDV at 24 h with less detectable RNA observed (P < 0.05) in the postinoculation samples regardless of inclusion level than the preinoculation counterparts and the controls. Overall, an application time effect was noticed in each matrix where less RNA was detected in the postinoculation samples at 0 h (P < 0.05) compared to the preinoculation samples and the control, and at 24 h, both the pre- and postinoculation samples had less detectable RNA (P < 0.05) than the control. Overall, formaldehyde can reduce detectable RNA immediately in contaminated complete feed and soybean meal, with greater decreases observed as mitigant contact time increases.

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INTRODUCTION: Femoral shaft nonunion negatively affects patient quality of life. Although multiple risk factors have been identified for femoral shaft nonunion after intramedullary nail (IMN) fixation, there is no quantitative model for predicting nonunion. STUDY DESCRIPTION: The study is a retrospective cohort study of patients with femoral shaft fractures treated at two level one trauma centers who were followed to fracture union or nonunion. Patient, injury, and surgical characteristics were analyzed to create a quantitative model for nonunion risk after intramedullary nailing. METHODS: Eight hundred one patients aged 18 years and older with femoral shaft fractures treated with reamed, locked IMNs were identified. Risk factors including demographics, comorbidities, surgical variables, and injury-related characteristics were evaluated. Multivariate analysis was conducted, and several variables were included in a scoring system to predict nonunion risk. RESULTS: The overall nonunion rate was 7.62% (61/801). Multivariate analysis showed significant association among pulmonary injury (odds ratio [OR] = 2.19, P = 0.022), open fracture (OR=2.36, P = 0.02), current smoking (OR=3.05, P < 0.001), postoperative infection (OR=12.1, P = 0.007), AO/OTA fracture pattern type A or B (OR=0.43, P = 0.014), and percent cortical contact obtained intraoperatively ≥25% (OR=0.41, P = 0.021) and nonunion. The scoring system created to quantitatively stratify nonunion risk showed that a score of 3 or more yielded an OR of 6.38 for nonunion (c-statistic = 0.693, P < 0.0001). CONCLUSIONS: Femoral shaft nonunion risk is quantifiable based on several independent injury, patient, and surgical factors. This scoring system is an additional tool for clinical decision making when caring for patients with femoral shaft fractures treated with IMNs.

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Fracture-related infections are significant postoperative complications that carry substantial patient burden and additional healthcare costs. Despite their impact on outcome, early diagnosis of these infections remains challenging due to current available tests lacking acceptable diagnostic parameters. This review compiles existing information on blood-based biomarkers that have been evaluated as early diagnostic tools and highlights the challenges in their reliability. To begin to overcome these challenges new avenues of biomarker discovery utilizing "omics" technologies and novel analytical methods are being investigated in recent years. It appears that, despite their complexity, these newer approaches may be the future in biomarker discovery for fracture-related infection diagnosis.

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The earliest evidence for complex tool use in the archaeological record dates to 3.3 Ma. While wooden tools may have been used by our earliest ancestors, the evidence is absent due to poor preservation. However, insights into possible early hominin wooden tool use can be gained from observing the tool-use practices of our closest living relatives, chimpanzees (Pan troglodytes). By using stone hammers used to crack various nuts, chimpanzees leave a durable material signature comprised of formal tools and associated diagnostic fragments. While the archaeological evidence of chimpanzee wooden tool use is temporary, the combination of stone hammers and wooden anvils can create a more enduring lithic record. This study explores the lithic assemblages associated with wooden and stone anvil use at nut-cracking sites in Taï National Park, Côte d'Ivoire, using technological and use-wear analyses. Our results indicate clear differences in density, fracture patterns, and use-wear in the lithic records between wooden anvil and stone anvil sites. New archaeological excavations at six chimpanzee nut-cracking sites reveal that the anvils' material directly influences the visibility of nut-cracking evidence in the archaeological record. By examining the nature of the lithic signatures associated with wooden anvil and stone anvil use by chimpanzees, we can formulate hypotheses about the probability of such behaviors being preserved and identifiable in the Plio-Pleistocene hominin archaeological record. The variability in material signatures from nut-cracking on different anvils suggests that stone anvils leave a clear archaeological record. Evidence for wooden anvil use is likely underrepresented due to the more ephemeral nature of the associated percussive damage and material signature. It may, however, still be possible, albeit challenging, to identify wooden anvil use in the archaeological record.

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INTRODUCTION: The therapeutic approach to pain in hemophilia should be multimodal. Intra-articular injections are a good option when joint lesions do not respond to hematological treatment or rehabilitation and orthopedic surgery is not yet indicated. Performing these procedures under ultrasound guidance has been shown to improve their accuracy and efficacy. AREAS COVERED: This article provides a practical overview of the most frequently employed ultrasound-guided intra-articular procedures on the joints of people with hemophilia. The article describes the key elements for performing the technique on the elbow, knee and ankle as the most affected joints. The particularities of the most frequent indications, arthrocentesis, synoviorthesis and analgesic injections with various products are detailed. EXPERT OPINION: Current hematological treatments have made it possible to incorporate new therapeutic tools for pain relief for people with hemophilia, including ultrasound-guided joint procedures, which offer excellent results.

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The rapid evolution of mass spectrometry-based single-cell proteomics now enables the cataloging of several thousand proteins from single cells. We investigated whether we could discover cellular heterogeneity beyond proteome, encompassing post-translational modifications (PTM), protein-protein interaction, and variants. By optimizing the mass spectrometry data interpretation strategy to enable the detection of PTMs and variants, we have generated a high-definition dataset of single-cell and nuclear proteomic-states. The data demonstrate the heterogeneity of cell-states and signaling dependencies at the single-cell level and reveal epigenetic drug-induced changes in single nuclei. This approach enables the exploration of previously uncharted single-cell and organellar proteomes revealing molecular characteristics that are inaccessible through RNA profiling.

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Treatment of volumetric muscle loss (VML) faces challenges due to its unique pathobiology and lower priority in severe musculoskeletal injury management. Consequently, a need exists for multi-stage VML treatment strategies to accommodate delayed interventions owing to comorbidity management or prolonged casualty care in combat settings. To this end, polyvinyl alcohol (PVA) was used at concentrations of 5%, 7.5%, and 10% to generate provisional muscle void fillers (MVFs) of varying stiffness values (1.125 kPa, 3.700 kPa, and 7.699 kPa) to stabilize VML injuries as part of a two-stage approach. These were implanted into a rat model for a duration of 4 weeks, then explanted and either left untreated (control) or treated through minced muscle grafting (MMG). Additional benchmarks included acute MMG and unrepaired groups. At the MVF explant, the 7.5% PVA group exhibited superior neuromuscular function compared to the 5% and 10% PVA groups, the least fibrosis, and the largest median myofiber size among all groups at the 12-week endpoint. Despite the 7.5% PVA's superiority amongst the two-stage treatment groups, neuromuscular function was neither improved nor impaired relative to acute treatment benchmarks. This suggests that the future success of a two-stage VML treatment strategy will necessitate a more effective definitive intervention.

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Raman spectroscopy enables the non-destructive characterization of chemical composition, crystallinity, defects, or strain in countless materials. However, the Raman response of surfaces or thin films is often weak and obscured by dominant bulk signals. Here we overcome this limitation by placing a transferable porous gold membrane, (PAuM) on the surface of interest. Slot-shaped nanopores in the membrane act as plasmonic antennas and enhance the Raman response of the surface or thin film underneath. Simultaneously, the PAuM suppresses the penetration of the excitation laser into the bulk, efficiently blocking its Raman signal. Using graphene as a model surface, we show that this method increases the surface-to-bulk Raman signal ratio by three orders of magnitude. We find that 90% of the Raman enhancement occurs within the top 2.5 nm of the material, demonstrating truly surface-sensitive Raman scattering. To validate our approach, we quantify the strain in a 12.5 nm thin Silicon film and analyze the surface of a LaNiO3 thin film. We observe a Raman mode splitting for the LaNiO3 surface-layer, which is spectroscopic evidence that the surface structure differs from the bulk. These results validate that PAuM gives direct access to Raman signatures of thin films and surfaces.

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Understanding spin-lattice interactions in antiferromagnets is a critical element of the fields of antiferromagnetic spintronics and magnonics. Recently, coherent nonlinear phonon dynamics mediated by a magnon state were discovered in an antiferromagnet. Here, we suggest that a strongly coupled two-magnon-one phonon state in this prototypical system opens a novel pathway to coherently control magnon-phonon dynamics. Utilizing intense narrow-band terahertz (THz) pulses and tunable magnetic fields up to µ0Hext = 7 T, we experimentally realize the conditions of magnon-phonon Fermi resonance in antiferromagnetic CoF2. These conditions imply that both the spin and the lattice anharmonicities harvest energy from the transfer between the subsystems if the magnon eigenfrequency fm is half the frequency of the phonon 2fm = fph. Performing THz pump-infrared probe spectroscopy in conjunction with simulations, we explore the coupled magnon-phonon dynamics in the vicinity of the Fermi-resonance and reveal the corresponding fingerprints of nonlinear interaction facilitating energy exchange between these subsystems.

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OBJECTIVES: Chimpanzees (Pan troglodytes) are patrilocal, with males remaining in their natal community and females dispersing when they reach sexual maturity. However, the details of female chimpanzee dispersal, such as their possible origin, are difficult to assess, even in habituated communities. This study investigates the utility of 87Sr/86Sr analysis for (1) assessing Sr baseline differences between chimpanzee territories and (2) identifying the status (immigrant or natal) of females of unknown origin within the territories of five neighboring communities in Taï National Park (Côte d'Ivoire). MATERIALS AND METHODS: To create a local Sr isoscape for the Taï Chimpanzee Project (TCP) study area, we sampled environmental samples from TCP-established territories (n = 35). To assess dispersal patterns, 34 tooth enamel samples (one per individual) were selected from the Taï chimpanzee skeletal collection. 87Sr/86Sr analysis was performed on all 69 samples at the W.M. Keck Lab. The theoretical density and overlap of chimpanzee communities as well as generalized linear mixed models (GLMMs) were used to test each question. RESULTS: 87Sr/86Sr ratios for natal male chimpanzees ranged from 0.71662 to 0.72187, which is well within the corresponding environmental baseline range of 0.70774-0.73460. The local Sr isoscapes fit was estimated with the root-mean-square error value, which was 0.0048 (22% of the whole 87Sr/86Sr data range). GLMMs identified significant differences in 87Sr/86Sr ratios between natal and unknown North community origin groups, suggesting that after 1980, females of unknown origin could be immigrants to North community (n = 7, z-ratio = -4.08, p = 0.0001, power = 0.94). DISCUSSION: This study indicates that 87Sr/86This study indicates that 87Sr/86Sr analysis can successfully identify immigrant females in skeletal collections obtained from wild chimpanzee communities, enabling the tracking of female dispersal patterns historically. There are, however, significant limitations within the scope of this study, such as (1) the absence of reliable maps for the TCP study area, (2) limited capacity for environmental sampling, (3) small sample sizes, and (4) tooth formation in wild chimpanzees.

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T helper 1 (TH1) cell identity is defined by the expression of the lineage-specifying transcription factor T-bet. Here, we examine the influence of T-bet expression heterogeneity on subset plasticity by leveraging cell sorting of distinct in vivo-differentiated TH1 cells based on their quantitative expression of T-bet and interferon-γ. Heterogeneous T-bet expression states were regulated by virus-induced type I interferons and were stably maintained even after secondary viral infection. Exposed to alternative differentiation signals, the sorted subpopulations exhibited graded levels of plasticity, particularly toward the TH2 lineage: T-bet quantities were inversely correlated with the ability to express the TH2 lineage-specifying transcription factor GATA-3 and TH2 cytokines. Reprogramed TH1 cells acquired graded mixed TH1 + TH2 phenotypes with a hybrid epigenetic landscape. Continuous presence of T-bet in differentiated TH1 cells was essential to ensure TH1 cell stability. Thus, innate cytokine signals regulate TH1 cell plasticity via an individual cell-intrinsic rheostat to enable T cell subset adaptation to subsequent challenges.

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Long-standing questions about human brain evolution may only be resolved through comparisons with close living evolutionary relatives, such as chimpanzees. This applies in particular to structural white matter (WM) connectivity, which continuously expanded throughout evolution. However, due to legal restrictions on chimpanzee research, neuroscience research currently relies largely on data with limited detail or on comparisons with evolutionarily distant monkeys. Here, we present a detailed magnetic resonance imaging resource to study structural WM connectivity in the chimpanzee. This open-access resource contains (1) WM reconstructions of a postmortem chimpanzee brain, using the highest-quality diffusion magnetic resonance imaging data yet acquired from great apes; (2) an optimized and validated method for high-quality fiber orientation reconstructions; and (3) major fiber tract segmentations for cross-species morphological comparisons. This dataset enabled us to identify phylogenetically relevant details of the chimpanzee connectome, and we anticipate that it will substantially contribute to understanding human brain evolution.

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Tool use is considered a driving force behind the evolution of brain expansion and prolonged juvenile dependency in the hominin lineage. However, it remains rare across animals, possibly due to inherent constraints related to manual dexterity and cognitive abilities. In our study, we investigated the ontogeny of tool use in chimpanzees (Pan troglodytes), a species known for its extensive and flexible tool use behavior. We observed 70 wild chimpanzees across all ages and analyzed 1,460 stick use events filmed in the Taï National Park, Côte d'Ivoire during the chimpanzee attempts to retrieve high-nutrient, but difficult-to-access, foods. We found that chimpanzees increasingly utilized hand grips employing more than 1 independent digit as they matured. Such hand grips emerged at the age of 2, became predominant and fully functional at the age of 6, and ubiquitous at the age of 15, enhancing task accuracy. Adults adjusted their hand grip based on the specific task at hand, favoring power grips for pounding actions and intermediate grips that combine power and precision, for others. Highly protracted development of suitable actions to acquire hidden (i.e., larvae) compared to non-hidden (i.e., nut kernel) food was evident, with adult skill levels achieved only after 15 years, suggesting a pronounced cognitive learning component to task success. The prolonged time required for cognitive assimilation compared to neuromotor control points to selection pressure favoring the retention of learning capacities into adulthood.

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Nematodes belonging to the genus Oesophagostomum frequently infect wild chimpanzees (Pan troglodytes) across widely separated field sites. Nodular lesions (granulomas) containing Oesophagostomum are commonly seen in the abdomen of infected chimpanzees post-mortem. At Taï National Park, Côte d'Ivoire, previous studies have identified larvae of a variety of Oesophagostomum spp. in wild chimpanzee stool, based on sequencing of larval DNA, and nodular lesions associated with Oesophagostomum, identified morphologically to the genus level but not sequenced. Here we present three recent cases of parasitic granulomas found post-mortem in chimpanzees at Taï. We complement descriptions of gross pathology, histopathology and parasitology with PCR and sequencing of DNA isolated from the parasitic nodules and from adult worms found inside the nodules. In all three cases, we identify Oesophagostomum stephanostomum as the causative agent. The sequences from this study were identical to the only other published sequences from nodules in nonhuman primates-those from the wild chimpanzees of Gombe, Tanzania.

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ABSTRACT: The use of CD34+ selected stem cell boost (SCB) after allogeneic hematopoietic cell transplant (allo-HCT) has been increasing. Predictors of treatment failure after SCB, both in the context of poor graft function (PGF) or other settings, are not well characterized. We report among the largest single-center retrospective experiences of the use of SCB and evaluate potential predictors of response and outcomes. A total of 58 patients who underwent HCT between 2015 and 2022 and who received SCB, were identified. The indication for SCB was predominantly PGF, defined as the presence of ≥2 cytopenias for at least 2 consecutive weeks beyond day +14 after allo-HCT in the presence of ≤30% bone marrow cellularity and ≥90% donor myeloid chimerism in the absence of morphologic disease. The median dose of infused CD34+ selected SCB products was 3.88 × 106 CD34+ cells per kg (range, 0.99 × 106 to 9.92 × 106). The median 2-year overall survival and nonrelapse mortality after SCB was 47% and 38%, respectively. The cumulative incidences of 6-month grade 3 to 4 acute and 2-year moderate-severe chronic graft-versus-host disease after SCB were 3.4% and 12%, respectively. Overall response (complete response + partial response) was attained in 36 of 58 patients (62%) and in 69% of patients with PGF. On multivariable analysis, an active infection at the time of SCB was the greatest predictor of poor response and survival (P = .013) after SCB. SCB can restore hematopoiesis in the majority of patients, particularly for those with PGF and in whom there is no active infection at the time of infusion.

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OBJECTIVE: Aim: To investigate and analyze legal conflicts in forensic dentistry of Ukraine. PATIENTS AND METHODS: Materials and Methods: A comparative research method for determining the common and distinctive features of the legal regulation of forensic dental expertise as a subcluster in the legislation of Ukraine. The descriptive (monographic) method reveals the problematic aspects of forensic dental examination through the lens of local normative and general normative connotations. The structural-functional research method made it possible to systematize the peculiarities of forensic medical and forensic dental expert activity. CONCLUSION: Conclusions: The analysis of legal conflicts made it possible to come to the following conclusions, that in Ukraine today there is no specific legal act that would regulate the aspects of performing dental activities. Forensic dental examination in Ukraine, in accordance with the legislation, is an examination of the actions and inactions of the dentist. The adoption of normative legal acts in the field of dental activity and forensic dental examination in Ukraine would make it possible to determine the specifics of establishing facts and circumstances that indicate a violation of the patient's rights.

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For patients undergoing allogeneic hematopoietic cell transplantation (alloHCT), HLA-matched related donors (MRDs) have traditionally been the preferred donor source. However, as the age of recipients increases, their sibling donors are aging as well. In this study, we investigated whether younger matched unrelated donors (MUDs) might be a better donor source than similarly aged sibling donors for patients age >60 years with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). A total of 499 patients age 60 to 70 years with AML or MDS who underwent alloHCT from an older MRD (donor age ≥50 years) or a younger MUD (donor age ≤35 years) between 2010 and 2022 were evaluated. Of these, 360 patients (72%) received an MUD graft and 139 (28%) received an MRD graft. The median recipient age was 64 years in the MRD group and 66 years in the MUD group. With a median follow-up among survivors of 53 months (range, 9 to 147 months ), the 4-year progression-free survival was 40% in the MRD group and 41% in the MUD group (P = .79) and the 4-year overall survival was 50% and 44%, respectively (P = .15), with no between-group differences in nonrelapse mortality, relapse, and acute or chronic graft-versus-host disease. In the MUD group, we also compared the effect of donor age 18 to 24 years and donor age 25 to 35 years and found no differences in outcomes between the groups. We conclude that outcomes are comparable between the use of older MRDs and use of younger MUDs for elderly patients with AML or MDS, that there is no donor age effect among younger MUDs, and that the use of either donor type is reasonable.

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