Non-Tobacco Nicotine Dependence and Rates of Postoperative Complications in Total Knee Arthroplasty: A Propensity-Matched Comparison.

INTRODUCTION: Tobacco use elevates the incidence of postoperative complications and remains a key modifiable risk factor of perioperative surgical optimization. It remains unclear whether non-tobacco nicotine dependence confers an increased risk of surgical complications. This study evaluates postoperative complications in patients with non-tobacco nicotine dependence for total knee arthroplasty (TKA). METHODS: We queried the TriNetX health database using Current Procedural Terminology and International Classification of Diseases, 10th Revision (ICD-10) codes and identified two cohorts for evaluation. Cohort A was defined as patients who had a TKA; had a dependence on nicotine; did not have nicotine dependence to cigarettes, chewing tobacco, other tobacco products; and were between the ages of 35 and 90 years. Cohort B was defined as patients who had a TKA but did not have a dependence on nicotine or a personal history of nicotine dependence and were between the ages of 35 and 90 years. RESULTS: This study analyzed a total of 10,594 non-tobacco nicotine-dependent patients and 175,079 non-dependent patients who underwent TKA. In the analysis of propensity-matched cohorts, non-tobacco nicotine-dependent patients demonstrated an increased rate of various postoperative complications within 90 days. Dependent patients saw a significantly increased risk of infection after a procedure (P < 0.001), deep vein thrombosis (P < 0.001), pulmonary embolism (P < 0.001), sepsis (P = 0.0065), and prosthetic joint infection (P = 0.0361) and a higher 3-year revision rate (P = 0.0084). DISCUSSION: Non-tobacco nicotine dependence demonstrated an increased associated risk of postoperative surgical complications for patients undergoing TKA. Orthopaedic surgeons should consider evaluating non-tobacco nicotine dependence within their surgical optimization protocol. LEVEL OF EVIDENCE: Level III, Prognostic.

Unifying community-wide whole-brain imaging datasets enables robust automated neuron identification and reveals determinants of neuron positioning in C. elegans.

We develop a data harmonization approach for C. elegans volumetric microscopy data, still or video, consisting of a standardized format, data pre-processing techniques, and a set of human-in-the-loop machine learning based analysis software tools. We unify a diverse collection of 118 whole-brain neural activity imaging datasets from 5 labs, storing these and accompanying tools in an online repository called WormID ( wormid.org ). We use this repository to generate a statistical atlas that, for the first time, enables accurate automated cellular identification that generalizes across labs, approaching human performance in some cases. We mine this repository to identify factors that influence the developmental positioning of neurons. To facilitate communal use of this repository, we created open-source software, code, web-based tools, and tutorials to explore and curate datasets for contribution to the scientific community. This repository provides a growing resource for experimentalists, theorists, and toolmakers to investigate neuroanatomical organization and neural activity across diverse experimental paradigms, develop and benchmark algorithms for automated neuron detection, segmentation, cell identification, tracking, and activity extraction, and inform models of neurobiological development and function.

Phaseolus vulgaris STP13.1 is an H+-coupled monosaccharide transporter, present in source leaves and seed coats, with higher substrate affinity at depolarized potentials.

Sugar transport proteins (STPs) are high-affinity H+-coupled hexose symporters. Recently, the contribution of STP13 to bacterial and fungal pathogen resistance across multiple plant species has garnered significant interest. Quantitative PCR analysis of source leaves, developing embryos, and seed coats of Phaseolus vulgaris L. (common bean) revealed that PvSTP13.1 was expressed in source leaves and seed coats throughout seed development. In contrast, PvSTP13.1 transcripts were detected at exceedingly low levels in developing embryos. To characterize the transport mechanism, PvSTP13.1 was expressed in Xenopus laevis oocytes, and inward-directed currents were analyzed using two-electrode voltage clamping. PvSTP13.1 was shown to function as an H+-coupled monosaccharide symporter exhibiting a unique high affinity for hexoses and aldopentoses at depolarized membrane potentials. Specifically, of the 31 assessed substrates, which included aldohexoses, deoxyhexoses, fructose, 3-O-methyl-D-glucose, aldopentoses, polyols, glycosides, disaccharides, trisaccharides, and glucuronic acid, PvSTP13.1 displayed the highest affinity (K 0.5) for glucose (43 µM), mannose (92 µM), galactose (145 µM), fructose (224 µM), xylose (1.0 mM), and fucose (3.7 mM) at pH 5.6 at a depolarized membrane potential of -40 mV. The results presented here suggest PvSTP13.1 contributes to retrieval of hexoses from the apoplasmic space in source leaves and coats of developing seeds.

A joint physics and radiobiology DREAM team vision - Towards better response prediction models to advance radiotherapy.

Radiotherapy developed empirically through experience balancing tumour control and normal tissue toxicities. Early simple mathematical models formalized this practical knowledge and enabled effective cancer treatment to date. Remarkable advances in technology, computing, and experimental biology now create opportunities to incorporate this knowledge into enhanced computational models. The ESTRO DREAM (Dose Response, Experiment, Analysis, Modelling) workshop brought together experts across disciplines to pursue the vision of personalized radiotherapy for optimal outcomes through advanced modelling. The ultimate vision is leveraging quantitative models dynamically during therapy to ultimately achieve truly adaptive and biologically guided radiotherapy at the population as well as individual patient-based levels. This requires the generation of models that inform response-based adaptations, individually optimized delivery and enable biological monitoring to provide decision support to clinicians. The goal is expanding to models that can drive the realization of personalized therapy for optimal outcomes. This position paper provides their propositions that describe how innovations in biology, physics, mathematics, and data science including AI could inform models and improve predictions. It consolidates the DREAM team's consensus on scientific priorities and organizational requirements. Scientifically, it stresses the need for rigorous, multifaceted model development, comprehensive validation and clinical applicability and significance. Organizationally, it reinforces the prerequisites of interdisciplinary research and collaboration between physicians, medical physicists, radiobiologists, and computational scientists throughout model development. Solely by a shared understanding of clinical needs, biological mechanisms, and computational methods, more informed models can be created. Future research environment and support must facilitate this integrative method of operation across multiple disciplines.

Repair of leukemia-associated single nucleotide variants via interallelic gene conversion.

CRISPR-Cas9 is a useful tool for inserting precise genetic alterations through homology-directed repair (HDR), although current methods rely on provision of an exogenous repair template. Here, we tested the possibility of repairing heterozygous single nucleotide variants (SNVs) using the cell's own wild-type allele rather than an exogenous template. Using high-fidelity Cas9 to perform allele-specific CRISPR across multiple human leukemia cell lines as well as in primary hematopoietic cells from patients with leukemia, we find high levels of reversion to wild-type in the absence of exogenous template. Moreover, we demonstrate that bulk treatment to revert a truncating mutation in ASXL1 using CRISPR-mediated interallelic gene conversion (IGC) is sufficient to prolong survival in a human cell line-derived xenograft model (median survival 33 days vs 27.5 days; p = 0.0040). These results indicate that IGC can be applied to numerous types of leukemia and can meaningfully alter cellular phenotypes at scale. Because our method targets single-base mutations, rather than larger variants targeted by IGC in prior studies, it greatly expands the pool of risk-increasing genetic lesions which could potentially be targeted by IGC. This technique may reduce cost and complexity for experiments modeling phenotypic consequences of SNVs. The principles of SNV-specific IGC demonstrated in this proof-of-concept study could be applied to investigate the phenotypic effects of targeted clonal reduction of leukemogenic SNV driver mutations.

The education of experience: Mixed methods evidence demonstrates the benefit of multiparity.

PROBLEM: Existing quantitative data is conflicting concerning whether multiparous birthing parents (individuals with an older child(ren)) experience an easier postpartum transition compared to primiparous birthing parents (first time parents). AIM: This convergent mixed methods study leverages the depth of qualitative inquiry to seek a clearer understanding of the way in which acquired parenting experience contributes to observed quantitative differences in outcomes between parity groups. This work can serve as a first step in planning for supportive interventions that effectively address the postpartum needs of both parity groups. METHODS: Thirty birthing parents (43.3% multiparous; 46.7% racial minorities) completed measures of postpartum functioning, perceived stress, anxiety symptoms, and depression symptoms as well as an interview inquiring about factors impacting postpartum functioning. Scores on postpartum functioning and emotional wellbeing were compared between parity groups, and these findings were merged with the qualitative data on firsthand parenting experience to clarify how acquired experience impacts functioning and emotional wellbeing during the postpartum transition. FINDINGS: Primiparous parents reported significantly: worse postpartum functioning, higher perceived stress, higher levels of depression symptoms, and higher levels of anxiety symptoms. Participants' qualitative report of how acquired parenting experience impacts wellbeing suggests that experience grants parents skills, knowledge, and the opportunity to disconfirm maladaptive cognitions about parenting which allows for increased comfort and confidence in the parental role. CONCLUSIONS: The practical and psychological resources gained from acquiring parenting experience during one's first postpartum period appear to be brought forward into subsequent pregnancies and protect against threats to functioning and emotional wellbeing.

Enigmatic persistence of aerobic methanotrophs in oxygen-limiting freshwater habitats.

Methanotrophic bacteria mitigate emissions of the potent greenhouse gas methane (CH4) from a variety of anthropogenic and natural sources, including freshwater lakes, which are large sources of CH4 on a global scale. Despite a dependence on dioxygen (O2) for CH4 oxidation, abundant populations of putatively aerobic methanotrophs have been detected within microoxic and anoxic waters and sediments of lakes. Experimental work has demonstrated active aerobic methanotrophs under those conditions, but how they are able to persist and oxidize CH4 under O2 deficiency remains enigmatic. In this review, we discuss possible mechanisms that underpin the persistence and activity of aerobic methanotrophs under O2-limiting conditions in freshwater habitats, particularly lakes, summarize experimental evidence for microbial oxidation of CH4 by aerobic bacteria under low or no O2, and suggest future research directions to further explore the ecology and metabolism of aerobic methanotrophs in O2-limiting environments.

Barriers and facilitators to consuming pulses: a qualitative exploration including effects of trying recipes at home.

Pulses are a healthy, sustainable, low cost food, but consumption levels are low for a variety of reasons, including practical and cooking concerns. This work aimed to explore barriers and facilitators towards pulse consumption and increasing consumption, and the potential value of cooking suggestions and recipes for changing these perceptions. Two qualitative studies were undertaken. In Study 1, 21 participants (10 males, 11 females, of a range of ages, cooking responsibilities, and experiences with pulses) were interviewed both before and after receiving cooking suggestions and recipes. In Study 2, 12 participants (2 males, 10 females, as above) were interviewed once after trying recipes. Interviews were audio-recorded, transcribed, and analysed using thematic analysis. Seven themes described barriers and facilitators towards pulse consumption: 'Enjoyment and Sensory properties'; 'Benefits and Recommendations'; 'Practical Concerns'; 'Cooking Concerns'; 'Compatibility with current diet'; 'Personal Influences'; and 'External Influences'. Some similar themes also referred to increasing consumption: 'Willingness'; 'Awareness, Knowledge of Benefits'; 'Knowledge of Cooking and Practical Concerns'; and 'Compatibility with current diet'. Cooking suggestions and recipe use resulted in themes on 'Awareness'; 'Willingness, Trying New Things'; 'Small Changes'; and facilitators associated with 'Enjoyment, Sensory Properties, Practical Concerns, Benefits' and 'Knowledge, Cooking Ideas and Confidence, Incorporation, Cooking Solutions'. Barriers related to 'Risk and Preconceptions'; 'Awareness, but' inaction and additional considerations were also found. Our findings demonstrate a positive role for pulse consumption for increased experience, familiarity, and confidence with preparing, cooking, and consuming these healthy and sustainable foods.

Severe epistaxis after posterior nasal nerve ablation requiring surgical intervention: A multi-center case series.

KEY POINTS: Severe epistaxis occurs in 2% of PNN ablation cases, independent of method or device type. Major epistaxis requiring intervention after PNN ablation can occur on average 20 days post-procedure.

Desulfoferula mesophilus gen. nov. sp. nov., a mesophilic sulfate-reducing bacterium isolated from a brackish lake sediment.

A novel sulfate-reducing bacterium (strain 12FAKT) was isolated from sediment sampled from a brackish lake in Japan. Respiratory growth was observed with formate and pyruvate as an electron donor. Sulfate, thiosulfate, elemental sulfur and dimethyl sulfoxide were utilized as an electron acceptor. The isolate grew over a temperature range of 18-42 °C (optimum 35-37 °C), a NaCl concentration range of 50-450 mM (optimum 150-300 mM) and a pH range of 6.6-7.5. The 12FAKT genome consists of a circular chromosome with a length of 4.5 Mbp and G + C content of 63.6%. Based on 16S rRNA gene sequence similarity, the closest cultured relative was Desulfarculus baarsii 2st14T (92.2%). Genome-based phylogenetic analysis placed strain 12FAKT within the family Desulfarculaceae but did not affiliate the strain with any existing genus. Taken together, we propose a novel species of a novel genus, Desulfoferula mesophilus gen. nov. sp. nov. with the type strain 12FAKT (= DSM 115219T = JCM 39399T).

Massive ossifying fibroma of mandible: A case report and review of the literature.

Key Clinical Message: Benign fibro-osseous neoplasm. Massive size is rarely reported. May be confused with other pathologies such as fibrous dysplasia or osteosarcoma. Aggressive nature and high recurrence pose management challenges. Treated by surgery. Abstract: Ossifying fibroma is a benign fibro-osseous neoplasm. It can affect both mandible and maxilla. Precise diagnosis can be challenging due to significant overlap of clinicopathological features with other neoplasms. Case reports with massive tumor sizes as presented in our case are uncommon. Huge tumor size can cause alarm for other pathologies such as osteosarcoma. The radiological tests should reassure the attending practitioner and histological examination confirm the diagnosis. The aim of the present report is to discuss a case of a giant ossifying fibroma in a 13-year-old male child. He presented with a progressive mandibular mass for 4 years. Clinical, radiological, and pathological characteristics and surgical treatment approaches are further discussed. This is one of the rare cases of massive ossifying fibroma in the English literature.

Discovery of the vector of visceral leishmaniasis, Phlebotomus (Artemievus) alexandri Sinton, 1928, in Kenya suggests complex transmission dynamics.

Visceral and cutaneous leishmaniasis are endemic to specific regions due to the ecological preferences of phlebotomine sand flies and Leishmania spp. transmission. Sand fly entomological data in northern Kenya are scarce due to limited studies and neglect of leishmaniasis. The aim of this study was to investigate: (i) sand fly diversity and distribution; (ii) occurrence of Leishmania DNA within sand flies; and (iii) blood-meal sources of sand flies in Laisamis, northern Kenya. We conducted an entomological survey during February and March of 2021 in five areas of Laisamis sub-county using standard CDC light traps. A total of 1009 sand flies (394 male and 615 female) were morphologically identified, and representative samples verified by PCR amplification and sequencing of the cytochrome c oxidase subunit 1 (cox1) gene. Similarly, we identified blood-meal sources and Leishmania DNA in female sand flies by PCR amplicon sequencing of the vertebrate cytochrome b (cyt b) gene and internal transcribed spacer 1 (ITS1) of the 28S rRNA gene, respectively. Sergentomyia clydei (59.8%) was the most abundant sand fly species. Though collected mainly from one locality (Tirgamo), 14.8% of samples belonged to Phlebotomus (Artemievus) alexandri Sinton, 1928. We detected DNA of Leishmania major in 5.19% of Ph. alexandri, whereas Leishmania adleri DNA was detected in S. clydei (7.51%), Sergentomyia squamipleuris (8.00%), and Sergentomyia africanus (8.33%). Nine of 13 blood-fed sand flies had obtained blood from humans, of which 33.3% had L. major DNA. Both Ph. alexandri and S. clydei primarily fed on humans and could potentially be involved in the transmission of cutaneous leishmaniasis. The findings of this study contribute to the understanding of sand fly vector populations and their potential to transmit leishmaniasis in the area.

Management of a giant pleomorphic adenoma of the soft palate: A case report.

Key Clinical Message: Benign mixed salivary gland tumor is comprised of epithelial and myoepithelial cells and represents up to 80% of tumors of the parotid gland. It is relatively rare in the soft palate and in other minor salivary glands. Surgery is the standard care. Abstract: Salivary gland tumors are relatively rare and morphologically diverse group of lesions. Pleomorphic adenoma (PA) is the most common salivary gland tumor, accounting for approximately 80% of all major and minor salivary gland tumors. PA usually affects the parotid gland. Huge PA occurring in soft palate is extremely rare. Patients with these tumors are usually between at the age of 40 and 60 years. The tumors exhibit pleomorphic nature microscopically that may pose diagnostic challenges to pathologists as may confuse PA histopathologically with other salivary gland tumors. Surgery is the standard treatment. The purpose of writing this case study is to describe unusual case of a giant PA of the soft palate found in a 44-year-old male successfully managed at our facility.

The prevalence of equine odontoclastic tooth resorption and hypercementosis and the role of interincisal angulation in disease severity in a representative cohort of horses in Switzerland.

INTRODUCTION: Equine odontoclastic tooth resorption and hypercementosis (EOTRH) is an increasingly diagnosed degenerative dental disease in aged horses. The primary aim of this retrospective study was to determine the prevalence of EOTRH in horses admitted to the Equine Hospital, University of Zurich, for dental procedures from 2004 to 2017. A secondary goal was to measure and compare interincisal angles on two-dimensional radiographs of horses with EOTRH to determine whether the interincisal angle is associated with age and severity of the disease. Radiographs were assessed for the presence of lysis and/or hypercementosis, and the number and position of the teeth affected were determined. Each tooth was also evaluated using the modified classification system introduced by Rehrl et al. (2018), in which stage 0 indicates no radiographic abnormalities and stage 3 denotes severe abnormalities. The overall stage was defined by the tooth with the most severe lesions. The interincisal angle was determined in horses that had suitable radiographs. The medical records of 838 horses admitted for dental procedures were evaluated, and 85 (10,1 %) had clinical evidence of EOTRH. The mean interincisal angle was 136,06 ° in horses with mild to moderate EOTRH and 135,10 ° (SD = 11,90 °) in severely affected patients. In conclusion, the angle measurements on lateral radiographs were highly reproducible. However, the interincisal angle was not associated with age or the severity of EOTRH. The interincisal angle and the disease pattern were not correlated.

INTRODUCTION: La résorption et l'hypercémentose odontoclastique des dents chez le cheval (EOTRH) est une maladie dentaire dégénérative de plus en plus diagnostiquée chez les animaux âgés. L'objectif principal de cette étude rétrospective était de déterminer la prévalence de l'EOTRH chez les chevaux admis à l'Hôpital équin de l'Université de Zurich pour des interventions dentaires entre 2014 et 2017. Un objectif secondaire était de mesurer et de comparer les angles inter-incisifs sur des radiographies bidimensionnelles de chevaux atteints d'EOTRH afin de déterminer si cet angle est associé à l'âge et à la gravité de la maladie. Les radiographies ont été évaluées pour la présence de lyse et/ou d'hypercémentose, et le nombre et la position des dents affectées ont été déterminés. Chaque dent a également été évaluée à l'aide du système de classification modifié introduit par Rehrl et al. (2018), dans lequel le stade 0 indique l'absence d'anomalies radiographiques et le stade 3 indique des anomalies graves. Le stade global a été défini par la dent présentant les lésions les plus sévères. L'angle inter-incisif a été déterminé chez les chevaux qui avaient des radiographies appropriées. Les dossiers médicaux de 838 chevaux admis pour des interventions dentaires ont été évalués et 85 (10,1 %) présentaient des signes cliniques d'EOTRH. L'angle inter-incisif moyen était de 136,06° chez les chevaux présentant une EOTRH légère à modérée et de 135,10° (écart-type = 11,90°) chez les patients gravement atteints. En conclusion, les mesures d'angle sur les radiographies latérales étaient très reproductibles. Cependant, l'angle inter-incisif n'était pas associé à l'âge ou à la sévérité de l'EOTRH. L'angle inter-incisif et le profil de la maladie n'étaient pas corrélés.

The Extraordinary Case of a Woman with a 30-Year-Long Diffuse Leishmaniasis Cured with One Single Ampoule of Intranasal Pentavalent Antimoniate.

Infection with Leishmania amazonensis and L. mexicana may lead to diffuse cutaneous leishmaniasis. The cure is exceptional, especially for the strange case of this lady. Case report: The patient acquired the disease in childhood and remained with lesions for over 30 years, albeit several treatments. She worsened after a pregnancy, developing disseminated lesions. Miltefosine with amphotericin B and pentamidine resulted in remission. Lesions reappeared after one year, accompanied by intra-nasal infiltration of the disease. The nasal spraying of a single ampoule of pentavalent antimoniate resulted in the sustained disappearance of the nasal symptoms and all the cutaneous lesions. After over eight years, she remains disease-free, albeit under renal replacement therapy. The high nasal mucosal antimonial concentration may explain the long-lasting cure via new MHC class I epitope-specific CD8+ cell clones against L. amazonensis present in the nasal mucosa.

Extra-mandibular Osteoradionecrosis after the Treatment of Head and Neck Cancer.

AIMS: Osteoradionecrosis (ORN) is a serious toxicity of head and neck radiotherapy. It predominantly affects the mandible. Extra-mandibular ORN is rare. The aim of this study was to report the incidence and outcomes of extra-mandibular ORNs from a large institutional database. MATERIALS AND METHODS: In total, 2303 head and neck cancer patients were treated with radical or adjuvant radiotherapy. Of these, extra-mandibular ORN developed in 13 patients (0.5%). RESULTS: Maxillary ORNs (n = 8) were a consequence of the treatment of various primaries (oropharynx = 3, sinonasal = 2, maxilla = 2, parotid = 1). The median interval from the end of radiotherapy to the development of ORN was 7.5 months (range 3-42 months). The median radiotherapy dose in the centre of the ORN was 48.5 Gy (range 22-66.5 Gy). Four patients (50%) healed in 7, 14, 20 and 41 months. All temporal bone ORNs (n = 5) developed after treatment to the parotid gland (of a total of 115 patients who received radiotherapy for parotid gland malignancy). The median interval from the end of radiotherapy to the development of ORN was 41 months (range 20-68 months). The median total dose in the centre of the ORN was 63.5 Gy (range 60.2-65.3 Gy). ORN healed in only one patient after 32 months of treatment with repeated debridement and topical betamethasone cream. CONCLUSION: Extra-mandibular ORN is a rare late toxicity and this current study provides useful information on its incidence and outcome. The risk of temporal bone ORN should be considered in the treatment of parotid malignancies and patients should be counselled. More research is required to determine the optimal management of extra-mandibular ORN, particularly on the role of the PENTOCLO regimen.

Tool for automatic macrozone characterization from EBSD data sets of titanium alloys.

Microtexture heterogeneities are commonly found in titanium forgings because of the thermomechanical processing. Also known as macrozones, these regions can reach millimetres in length, with grains sharing a similar crystallographic orientation leading to less resistance to crack propagation. Since the link between macrozones and the reduction of cold-dwell-fatigue performance on rotative components in gas turbine engines was established, efforts have been put into macrozone definition and characterization. The electron backscatter diffraction (EBSD) technique, widely used for texture analysis, allows for a qualitative macrozone characterization; however, further processing is required to define the boundaries and disorientation spread of each macrozone. Current approaches often use c-axis misorientation criteria, but this can sometimes lead to a large disorientation spread within a macrozone. This article describes the development and application of a computational tool implemented in MATLAB for automatic macrozone identification from EBSD data sets on the basis of a more conservative approach where both the c-axis tilting and rotation are considered. The tool allows for detection of macrozones according to the disorientation angle and density-fraction criteria. The clustering efficiency is validated by pole-figure plots, and the effects of the key parameters defining the macrozone clustering (disorientation and fraction) are discussed. In addition, this tool was successfully applied to both fully equiaxed and bimodal microstructures of titanium forgings.