Electrochemical Glycosylation via Halogen-Atom-Transfer for C-Glycoside Assembly.

Glycosyl donor activation emerged as an enabling technology for anomeric functionalization, but aimed primarily at O-glycosylation. In contrast, we herein disclose mechanistically distinct electrochemical glycosyl bromide donor activations via halogen-atom transfer and anomeric C-glycosylation. The anomeric radical addition to alkenes led to C-alkyl glycoside synthesis under precious metal-free reaction conditions from readily available glycosyl bromides. The robustness of our e-XAT strategy was further mirrored by C-aryl and C-acyl glycosides assembly through nickela-electrocatalysis. Our approach provides an orthogonal strategy for glycosyl donor activation with expedient scope, hence representing a general method for direct C-glycosides assembly.

Hemoglobin level, degree of mobilization, and pneumonia are associated with the development of postoperative delirium in cemented hemiarthroplasty after femoral neck fracture.

PURPOSE: The aim of this retrospective study was to identify independent prognostic factors for developing a postoperative delirium (POD) in patients suffering from a proximal femoral neck fracture and treated by implantation of a hemiprosthesis. METHODS: A retrospective study, including patients with hip hemiarthroplasty due to a femoral neck fracture between 2011 and 2020 was performed. Demographic data, preexisting conditions, intra-/postoperative complications, mobilization and laboratory results were extracted from the patients' charts. The different parameters were analyzed comparing patients with and without POD. RESULTS: 412 patients, mean age of 81 ± 9.58 years were included, 66.5% (n = 274) were female, 18.2% (n = 75) of them developed a POD. Significantly higher incidence of POD was associated with older age (p < 0.001), lower level of haemoglobin (p < 0.001), higher post-surgery interleukin 6 (IL 6) level (p = 0.008), higher postoperative level of leukocytes (p = 0.01). Patients with POD received more units of packed red blood cells (PRBC) (p = 0.007). Patients with no mobility limitations pre-operatively developed POD less frequently (p = 0.01), whereas suffering from pneumonia (p = 0.03) or limited mobility postoperatively increased the risk of POD (p < 0.001). CONCLUSION: This study could help to identify patients with a risk for developing POD after a hemiarthroplasty in femoral neck fractures. As a consequence, frequent controls of Hb, IL 6 and leucocytes levels to avoid anemia and infections, as well as the well surgical treatment to guarantee a good postoperative outcome.

Clinician Note Documentation of Parental Justice Involvement: Preliminary Evidence from Pediatric Electronic Health Records.

Little is known about clinical documentation for youth exposed to parental justiceinvolvement (e.g., parole, probation, jail, prison). We reviewed the electronic health records of 100 youth with at least one mention of parental incarceration between 2011-2019 from a large Midwestern pediatric hospital-based institution to describe clinical documentation and health characteristics. Within the sample, youth more commonly experienced incarceration of a father-identified figure (68%) as opposed to a mother-identified figure (32%). Seventeen percent (17%) of the youth were between zero and four years of age when clinicians documented exposure to a parent's incarceration. Nearly one-third of youth charts had no documentation regarding service referrals or follow-up from providers upon disclosure of parental incarceration. Few clinician documentation details were present related to the context of parental justice involvement (timing, type, and duration). Future research is needed to better understand the intersection of parental justice involvement and child health and service connection.

Enantioselective Cobaltaphotoredox-Catalyzed C-H Activation.

The quest for sustainable strategies in molecular synthesis has spurred the emergence of photocatalysis as a particularly powerful technique. In recent years, the application of photocatalysis in this context has greatly promoted the development of asymmetric catalysis. Despite the impressive advances, enantioselective photoinduced strong arene C-H activations by cobalt catalysis remain unexplored. Herein, we report a strategy that merges organic photoredox catalysis and enantioselective cobalt-catalyzed C-H activation, enabling the regio- and stereoselective dual functionalization of indoles in an enantioselective fashion. Thereby, the assembly of various chiral indolo[2,3-c]isoquinolin-5-ones was realized with high enantioselectivities of up to 99%. The robustness of the cobaltaphotoredox catalysis was demonstrated through enantioselective C-H activation and annulations in a continuous flow to provide straightforward access to central and axially chiral molecules.

Toward Interpretable Sleep Stage Classification Using Cross-Modal Transformers.

Accurate sleep stage classification is significant for sleep health assessment. In recent years, several machine-learning based sleep staging algorithms have been developed, and in particular, deep-learning based algorithms have achieved performance on par with human annotation. Despite improved performance, a limitation of most deep-learning based algorithms is their black-box behavior, which have limited their use in clinical settings. Here, we propose a cross-modal transformer, which is a transformer-based method for sleep stage classification. The proposed cross-modal transformer consists of a cross-modal transformer encoder architecture along with a multi-scale one-dimensional convolutional neural network for automatic representation learning. The performance of our method is on-par with the state-of-the-art methods and eliminates the black-box behavior of deep-learning models by utilizing the interpretability aspect of the attention modules. Furthermore, our method provides considerable reductions in the number of parameters and training time compared to the state-of-the-art methods. Our code is available at https://github.com/Jathurshan0330/Cross-Modal-Transformer. A demo of our work can be found at https://bit.ly/Cross_modal_transformer_demo.

Centrocortin potentiates co-translational localization of its mRNA to the centrosome via dynein.

Centrosomes rely upon proteins within the pericentriolar material to nucleate and organize microtubules. Several mRNAs also reside at centrosomes, although less is known about how and why they accumulate there. We previously showed that local Centrocortin (Cen) mRNA supports centrosome separation, microtubule organization, and viability in Drosophila embryos. Here, using Cen mRNA as a model, we examine mechanisms of centrosomal mRNA localization. We find that while the Cen N'-terminus is sufficient for protein enrichment at centrosomes, multiple domains cooperate to concentrate Cen mRNA at this location. We further identify an N'-terminal motif within Cen that is conserved among dynein cargo adaptor proteins and test its contribution to RNA localization. Our results support a model whereby Cen protein enables the accumulation of its own mRNA to centrosomes through a mechanism requiring active translation, microtubules, and the dynein motor complex. Taken together, our data uncover the basis of translation-dependent localization of a centrosomal RNA required for mitotic integrity.

Relational conflicts during COVID-19: Impact of loss and reduction of employment due to prevention measures and the influence of sex and stress (in the iCARE study).

This study explored the association between pandemic-related loss/reduction of employment, sex, COVID-19-related stress and relational conflicts. A sample of 5103 Canadians from the iCARE study were recruited through an online polling firm between October 29, 2020, and March 23, 2021. Logistic regressions revealed that participants with loss/reduction of employment were 3.6 times more likely to report increased relational conflicts compared to those with stable employment (OR = 3.60; 95% CIs = 3.03-4.26). There was a significant interaction between employment status and sex (x2 = 10.16; p < 0.005), where loss/reduction of employment was associated with more relational conflicts in males compared to females. There was a main effect of COVID-19-related stress levels on relational conflicts (increased stress vs no stress : OR = 9.54; 95% CIs = 6.70-13.60), but no interaction with loss/reduction of employment (x2 = 0.46, p = 0.50).

Clinical features and outcomes of horses presenting with presumed equine immune mediated keratitis to two veterinary hospitals in the United Kingdom and Finland: 94 cases (2009-2021).

BACKGROUND: There is limited literature regarding equine immune mediated keratitis (IMMK) in Europe. North America-based publications describe minimal blepharospasm, rare corneal ulceration and no uveitis; clinical impression suggests these are seen in Europe. OBJECTIVES: Assess the prevalence of blepharospasm, corneal ulceration and uveitis and their impact on outcome in horses diagnosed with IMMK in Europe (UK and Finland). STUDY DESIGN: Retrospective case series. METHODS: Clinical records of 94 horses with IMMK were evaluated. The UK and Finland populations were comparable; therefore, descriptive statistics were performed on combined data on subtypes of IMMK and clinical features. Odds ratios (OR) and confidence intervals (CI) were calculated for impact of blepharospasm, ulceration or presence of uveitis on the outcome of enucleation and treatment duration. RESULTS: IMMK subtype was classified as 10/94 (10.6%) epithelial, 50/94 (53.2%) anterior stromal, 14/94 (14.9%) mid-stromal, 4/94 (4.25%) endothelial and 16/94 (17.0%) unrecorded. After excluding three horses with incidental corneal ulceration, blepharospasm was documented in 34/91 (37.4%), corneal ulceration in 26/91 (28.6%), and signs of uveitis in 23/91 (25.3%) horses. Increased odds of enucleation were significantly associated with the presence of blepharospasm (OR 5.5, 95% CI 1.6-19.4, p = 0.008) and signs of uveitis (OR 8.9, 95% CI 2.6-30.8, p < 0.001), but not corneal ulceration. The presence of blepharospasm, corneal ulceration or uveitis did not significantly alter the odds of ongoing medication. MAIN LIMITATIONS: Data were collected over a wide timeframe; the diagnosis was mainly made without histopathology; a broad definition of uveitis was used and there was a bias towards complicated cases being retained for follow-up. CONCLUSIONS: The clinical features of IMMK were similar between two European countries but differed to USA descriptions. Blepharospasm, corneal ulceration and signs of uveitis can occur with IMMK; presence of blepharospasm and uveitis increase the odds of enucleation.

Surface modification of extracellular vesicles with polyoxazolines to enhance their plasma stability and tumor accumulation.

Extracellular vesicles (EVs) are future promising therapeutics, but their instability in vivo after administration remains an important barrier to their further development. Many groups evaluated EV surface modification strategies to add a targeting group with the aim of controlling EV biodistribution. Conversely, fewer groups focused on their stabilization to obtain "stealth" allogenic EVs. Modulating their stabilization and biodistribution is an essential prerequisite for their development as nano-therapeutics. Here, we explored polyoxazolines with lipid anchors association to the EV membrane (POxylation as an alternative to PEGylation) to stabilize EVs in plasma and control their biodistribution, while preserving their native properties. We found that this modification maintained and seemed to potentiate the immunomodulatory properties of EVs derived from mesenchymal stem/stromal cells (MSC). Using a radiolabeling protocol to track EVs at a therapeutically relevant concentration in vivo, we demonstrated that POxylation is a promising option to stabilize EVs in plasma because it increased EV half-life by 6 fold at 6 h post-injection. Moreover, EV accumulation in tumors was higher after POxylation than after PEGylation.

Validation and clinical application of implantable loop recorders for diagnosis of atrial fibrillation in horses.

BACKGROUND: Paroxysmal atrial fibrillation (pAF) occurs sporadically and can impair athletic performance. Gold standard for diagnosis is surface electrocardiography (ECG), however, this requires AF to be sustained. Implantable loop recorders (ILRs) are routinely used for AF detection in human medicine. While ILR placement has been studied in horses, its AF detection performance is unknown. OBJECTIVES: (I) Validation of ILRs for AF detection in horses. (II) Determining pAF incidence using ILRs and estimate the positive predictive value (PPV). STUDY DESIGN: (I) Experimental study; (II) Longitudinal observational study. METHODS: (I) Implantation of ILRs in 15 horses with AF and 13 horses in sinus rhythm. Holter ECGs were recorded at: 1, 4, 8, 12 and 16 weeks of AF. The ILR ECGs were compared with surface ECGs to assess diagnostic sensitivity and specificity. (II) Eighty horses (43 Warmbloods, 37 Standardbreds) with ILRs were monitored for 367 days [IQR 208-621]. RESULTS: (I) ILRs detected AF on all recording days, in horses with AF, with a sensitivity of 66.1% (95% CI: 65.8-66.5) and a specificity of 99.99% (95% CI: 99.97-99.99). The sensitivity remained consistent across all time points. (II) The incidence of pAF was 6.3% (5/80). In horses with pAF, the PPV ranged from 8% to 87%. Increased body condition score (BCS > 6/9) was associated with an increased number of false positive episodes (p = 0.005). MAIN LIMITATIONS: (I) Horses were stabled during the ECG recordings, and AF was induced, rather than naturally occurring pAF. (II) Integrated algorithm in this ILR is optimised for AF detection in humans using remote monitors. Additionally, sensing is affected by motion artefacts. CONCLUSION: The ILR reliably detected AF in resting horses, particularly in horses with normal BCS (6/9). The ILR proved useful to detect pAF and is recommended alongside Holter monitoring for diagnostic workup of horses with suspected pAF.

The impact of insect herbivory on biogeochemical cycling in broadleaved forests varies with temperature.

Herbivorous insects alter biogeochemical cycling within forests, but the magnitude of these impacts, their global variation, and drivers of this variation remain poorly understood. To address this knowledge gap and help improve biogeochemical models, we established a global network of 74 plots within 40 mature, undisturbed broadleaved forests. We analyzed freshly senesced and green leaves for carbon, nitrogen, phosphorus and silica concentrations, foliar production and herbivory, and stand-level nutrient fluxes. We show more nutrient release by insect herbivores at non-outbreak levels in tropical forests than temperate and boreal forests, that these fluxes increase strongly with mean annual temperature, and that they exceed atmospheric deposition inputs in some localities. Thus, background levels of insect herbivory are sufficiently large to both alter ecosystem element cycling and influence terrestrial carbon cycling. Further, climate can affect interactions between natural populations of plants and herbivores with important consequences for global biogeochemical cycles across broadleaved forests.

Probing perfection: The relentless art of meddling for pulmonary airway segmentation from HRCT via a human-AI collaboration based active learning method.

In the realm of pulmonary tracheal segmentation, the scarcity of annotated data stands as a prevalent pain point in most medical segmentation endeavors. Concurrently, most Deep Learning (DL) methodologies employed in this domain invariably grapple with other dual challenges: the inherent opacity of 'black box' models and the ongoing pursuit of performance enhancement. In response to these intertwined challenges, the core concept of our Human-Computer Interaction (HCI) based learning models (RS_UNet, LC_UNet, UUNet and WD_UNet) hinge on the versatile combination of diverse query strategies and an array of deep learning models. We train four HCI models based on the initial training dataset and sequentially repeat the following steps 1-4: (1) Query Strategy: Our proposed HCI models selects those samples which contribute the most additional representative information when labeled in each iteration of the query strategy (showing the names and sequence numbers of the samples to be annotated). Additionally, in this phase, the model selects the unlabeled samples with the greatest predictive disparity by calculating the Wasserstein Distance, Least Confidence, Entropy Sampling, and Random Sampling. (2) Central line correction: The selected samples in previous stage are then used for domain expert correction of the system-generated tracheal central lines in each training round. (3) Update training dataset: When domain experts are involved in each epoch of the DL model's training iterations, they update the training dataset with greater precision after each epoch, thereby enhancing the trustworthiness of the 'black box' DL model and improving the performance of models. (4) Model training: Proposed HCI model is trained using the updated training dataset and an enhanced version of existing UNet. Experimental results validate the effectiveness of this Human-Computer Interaction-based approaches, demonstrating that our proposed WD-UNet, LC-UNet, UUNet, RS-UNet achieve comparable or even superior performance than the state-of-the-art DL models, such as WD-UNet with only 15 %-35 % of the training data, leading to substantial reductions (65 %-85 % reduction of annotation effort) in physician annotation time.

A force-sensitive mutation reveals a non-canonical role for dynein in anaphase progression.

The diverse roles of the dynein motor in shaping microtubule networks and cargo transport complicate in vivo analysis of its functions significantly. To address this issue, we have generated a series of missense mutations in Drosophila Dynein heavy chain. We show that mutations associated with human neurological disease cause a range of defects, including impaired cargo trafficking in neurons. We also describe a novel microtubule-binding domain mutation that specifically blocks the metaphase-anaphase transition during mitosis in the embryo. This effect is independent from dynein's canonical role in silencing the spindle assembly checkpoint. Optical trapping of purified dynein complexes reveals that this mutation only compromises motor performance under load, a finding rationalized by the results of all-atom molecular dynamics simulations. We propose that dynein has a novel function in anaphase progression that depends on it operating in a specific load regime. More broadly, our work illustrates how in vivo functions of motors can be dissected by manipulating their mechanical properties.

Canine ovarian epithelial tumours: histopathological and immunohistochemical evaluation with proposed histopathological classification system.

Canine ovarian epithelial tumours (OETs) are currently divided into ovarian adenomas and carcinomas, which are further inconsistently subclassified as papillary or cystic, whereas in human medicine, OETs are subdivided into several subtypes. This study aimed to establish clear morphological features enabling more consistent distinction between benign OETs and ovarian carcinomas (OvCas) as well as defining different histopathological patterns of canine OvCas. Analysis revealed a mitotic count threshold of >2 as a potential criterion for differentiating OvCas from benign OETs. Alongside ovarian adenomas, ovarian borderline tumours were introduced as a distinct category among benign OETs. OvCas exhibited five different histopathological patterns, namely papillary, solid with tubular differentiation, micropapillary, cystic and sarcomatous. Since some OvCas can morphologically overlap with other ovarian tumours, the expression of cytokeratin 7, a cytokeratin expressed in ovarian epithelium, was assessed and proved helpful, although it was not expressed in all cases. Furthermore, we investigated the expression of 14-3-3σ and cyclooxygenase 2 (COX-2). Based on the frequent expression of 14-3-3σ, this marker appears to have a role in canine OETs since it is not expressed in normal canine ovaries. The infrequent expression of COX-2 suggests that it is a poor candidate as a potential therapeutic target in canine OvCas.

The enduring world forest carbon sink.

The uptake of carbon dioxide (CO2) by terrestrial ecosystems is critical for moderating climate change1. To provide a ground-based long-term assessment of the contribution of forests to terrestrial CO2 uptake, we synthesized in situ forest data from boreal, temperate and tropical biomes spanning three decades. We found that the carbon sink in global forests was steady, at 3.6 ± 0.4 Pg C yr-1 in the 1990s and 2000s, and 3.5 ± 0.4 Pg C yr-1 in the 2010s. Despite this global stability, our analysis revealed some major biome-level changes. Carbon sinks have increased in temperate (+30 ± 5%) and tropical regrowth (+29 ± 8%) forests owing to increases in forest area, but they decreased in boreal (-36 ± 6%) and tropical intact (-31 ± 7%) forests, as a result of intensified disturbances and losses in intact forest area, respectively. Mass-balance studies indicate that the global land carbon sink has increased2, implying an increase in the non-forest-land carbon sink. The global forest sink is equivalent to almost half of fossil-fuel emissions (7.8 ± 0.4 Pg C yr-1 in 1990-2019). However, two-thirds of the benefit from the sink has been negated by tropical deforestation (2.2 ± 0.5 Pg C yr-1 in 1990-2019). Although the global forest sink has endured undiminished for three decades, despite regional variations, it could be weakened by ageing forests, continuing deforestation and further intensification of disturbance regimes1. To protect the carbon sink, land management policies are needed to limit deforestation, promote forest restoration and improve timber-harvesting practices1,3.

Perceived Stress, but Not Rumination, Mediates the Relationship Between Trait Mindfulness and Sleep Quality in Young Adults.

Objective: Poor sleep among young adults is prevalent, yet the mediating variables are largely understudied, and there is limited relevant work utilizing objective sleep measures. The present study investigated the mediating effects of perceived stress and rumination in the relationship between trait mindfulness and subjective and objective sleep quality in young adults. Methods: A total of 170 healthy adults (aged 18-37, M = 20.8, SD = 2.9) self-reported on trait mindfulness, perceived stress, and rumination. The primary (N = 140) and secondary (N = 30) samples both completed the Pittsburgh Sleep Quality Index (PSQI) to assess subjective sleep quality. The secondary sample (N = 30) additionally provided sleep diaries, as well as wrist-worn actigraphy data for assessing objective sleep quality. A mediation analysis was conducted to assess the effect of trait mindfulness on sleep quality with perceived stress and rumination as mediators. Results: Trait mindfulness was positively associated with better subjective sleep quality; this was fully mediated by perceived stress, b = -0.08, 95% CI [-.12, -0.06]. Rumination was negatively associated with subjective sleep quality but did not mediate the relationship between trait mindfulness and sleep quality, b = -0.01, 95% CI [-.03, 0.02]. Only trait mindfulness was correlated with diary-based sleep ratings, and none of the measures were associated with actigraphy-based sleep quality. Conclusion: This study indicates that perceived stress is an important mediator in the relationship between trait mindfulness and subjective sleep quality among young adults, rather than rumination. These findings have implications for mindfulness-based therapeutic approaches to address the high prevalence of sleep disorders among young adults, adding mechanistic detail to the literature.

Cordyceps cateniannulata: An endophyte of coffee, a parasite of coffee leaf rust and a pathogen of coffee pests.

Here, we report on a Cordyceps species entering into a multi-trophic, multi-kingdom association. Cordyceps cateniannulata, isolated from the stem of wild Coffea arabica in Ethiopia, is shown to function as an endophyte, a mycoparasite and an entomopathogen. A detailed polyphasic taxonomic study, including a multilocus phylogenetic analysis, confirmed its identity. An emended description of C. cateniannulata is provided herein. Previously, this species was known as a pathogen of various insect hosts in both the Old and New World. The endophytic status of C. cateniannulata was confirmed by re-isolating it from inoculated coffee plants. Inoculation studies have further shown that C. cateniannulata is a mycoparasite of Hemileia vastatrix, as well as an entomopathogen of major coffee pests; infecting and killing Hypothenemus hampei and Leucoptera coffeella. This is the first record of C. cateniannulata from Africa, as well as an endophyte and a mycoparasite. The implications for its use as a biocontrol agent are discussed.

Training physicians in motivational communication: An integrated knowledge transfer study protocol.

OBJECTIVE: While behavior change counseling (BCC) targeting health risk behaviors has shown efficacy for improving patient health outcomes, barriers to knowledge translation have resulted in poor uptake among health care providers (HCPs). This article outlines the development of a new BCC training framework for HCPs, from inception to readiness for efficacy testing. It provides an example of integrated knowledge translation (iKT) used in alignment with the obesity-related behavioral intervention trials model. METHOD: (a) A modified Delphi process identified essential BCC skills for HCPs; (b) a survey assessed HCP attitudes and training needs; (c) an online competency assessment tool was developed using iKT mixed methods; (d) a training program was developed and refined using a logic model; and (e) the program was optimized using iterative rounds of participant feedback. A future proof-of-concept trial (f) will determine the program's readiness for full efficacy testing. RESULTS: A Delphi panel (n = 46) identified 11 core BCC competencies for HCPs, defining "motivational communication." The HCP survey (n = 80) showed willingness to devote 4 hr to introductory training in BCC. The Motivational Communication Competency Assessment Test (MC-CAT: an online, interactive evaluation tool) and a motivational communication training program (MOTIVATOR: accredited for continuing education by the Royal College of Physicians and Surgeons of Canada) were collaboratively developed with knowledge users. The optimization process (n = 11) provided key feedback, with minor changes being made to the program. CONCLUSIONS: In developing a new BCC framework, obstacles to BCC implementation were addressed through an iterative iKT process. This should improve eventual intervention uptake. (PsycInfo Database Record (c) 2024 APA, all rights reserved).