Miracle-dz/UniFAR-FTUs huggingface dataset:
Bees exposed to climate change are more sensitive to pesticides

Bee populations are exposed to multiple stressors, including land‐use change, biological invasions, climate change, and pesticide exposure, that may interact synergistically. We analyze the combined effects of climate warming and sublethal insecticide exposure in the solitary bee Osmia cornuta. Previous Osmia studies show that warm wintering temperatures cause body weight loss, lipid consumption, and fat body depletion. Because the fat body plays a key role in xenobiotic detoxification, we expected that bees exposed to climate warming scenarios would be more sensitive to pesticides. We exposed O. cornuta females to three wintering treatments: current scenario (2007–2012 temperatures), near‐future (2021–2050 projected temperatures), and distant‐future (2051–2080). Upon emergence in spring, bees were orally exposed to three sublethal doses of an insecticide (Closer, a.i. sulfoxaflor; 0, 4.55 and 11.64 ng a.i./bee). We measured the combined effects of wintering and insecticide exposure on phototactic response, syrup consumption, and longevity. Wintering treatment by itself did not affect winter mortality, but body weight loss increased with increasing wintering temperatures. Similarly, wintering treatment by itself hardly influenced phototactic response or syrup consumption. However, bees wintered at the warmest temperatures had shorter longevity, a strong fecundity predictor in Osmia. Insecticide exposure, especially at the high dose, impaired the ability of bees to respond to light, and resulted in reduced syrup consumption and longevity. The combination of the warmest winter and the high insecticide dose resulted in a 70% longevity decrease. Smaller bees, resulting from smaller pollen–nectar provisions, had shorter longevity suggesting nutritional stress may further compromise fecundity in O. cornuta. Our results show a synergistic interaction between two major drivers of bee declines, and indicate that bees will become more sensitive to pesticides under the current global warming scenario. Our findings have important implications for pesticide regulation and underscore the need to consider multiple stressors to understand bee declines.
Activation of mitogen-activated protein kinase signaling and development of papillary thyroid carcinoma in thyroid-stimulating hormone receptor D633H knockin mice

Objective Nonautoimmune hyperthyroidism (NAH) is rare and occurs due to a constitutively activating thyroid stimulating hormone receptor (TSHR) mutation. In contrast to other thyroid nodules, no further evaluation for malignancy is recommended for hot thyroid nodules. In the first model for NAH in mice nearly all homozygous mice had developed papillary thyroid cancer by 12 months of age. Methods To further evaluate these mice, whole exome sequencing and phosphoproteome analysis were employed in a further generation of mice to identify any other mutations potentially responsible and to identify the pathways involved in thyroid carcinoma development. Results Only three genes (Nrg1, Rrs1, Rasal2) were mutated in all mice examined, none of which were known primary drivers of papillary thyroid cancer development. Wild-type and homozygous TSHR D633H knockin mice showed distinct phosphoproteome profiles with an enrichment of altered phosphosites found in ERK/mitogen-activated protein kinase (MAPK) signaling. Most importantly, phosphosites with known downstream effects included BRAF p.S766, which forms an inhibitory site: a decrease of phosphorylation at this site suggests an increase in MEK/ERK pathway activation. The decreased phosphorylation at BRAF p.S766 would suggest decreased AMP-activated protein kinase (AMPK) signaling, which is supported by the decreased phosphorylation of STIM1 p.S257, a downstream AMPK target. Conclusion The modified phosphoproteome profile of the homozygous mice in combination with human literature suggests a potential signaling pathway from constitutive TSHR signaling and cAMP activation to the activation of ERK/MAPK signaling. This is the first time that a specific mechanism has been identified for a possible involvement of TSH signaling in thyroid carcinoma development.
Creating a utopian future by asking uncomfortable questions

The interprofessional movement thrives where conditions are conducive; where openness and mutual support in the workplace characterize relations; where democratization in universities liber-alizes learning; where the need for change to improve health and social care is addressed. Sustaining progress depends . on the readiness of interprofessional exponents to set aside professional protectionism and academic rivalry as they support each other across borders and boundaries
THE DIFFERENCES IN SPINAL KINEMATICS AND LOADING IN HIGH PERFORMANCE FEMALE ROWERS DURING ERGOMETER AND ON WATER ROWING

Low back pain (LBP) is the most prevalent injury in rowing. The high use of ergometers has been associated win increased LBP and sliding ergometers are proposed to reduce this stress. The purpose of this study was to examine the lumbar flexion angles on fixed and sliding ergometers versus on water conditions. Four elite female adult rowers volunteered for this study and completed a 1,000 meter maximal test on the stationary and fixed ergometers and then on water. Lumbar curvature (% flexion) was calculated) for the first 0.47 s following the catch position. Standardized mean differences (effect size) were calculated to examine differences in %ROM over time for each condition and between conditions. Results found that fixed rowers ergometers induced the greatest amount if lumbar flexion, with some reduction for sliding ergometers compared to on water.
Prosthetic resurfacing of engaging posterior capitellar defects in recurrent posterolateral rotatory instability of the elbow

Background Posterolateral rotatory instability (PLRI) is a common mechanism of recurrent elbow instability. While the essential lesion is a deficiency in the lateral ulnar collateral ligament (LUCL), there are often associated concomitant bony lesions, such as an Osborne-Cotterill lesions (posterior capitellar fractures) and marginal radial head fractures, that compromise stability. Currently, there is no standard treatment for posterior capitellar deficiency associated with recurrent PLRI. Methods We conducted a retrospective review of five patients with recurrent PLRI of the elbow associated with a posterior capitellar impaction fracture engaging with the radial head during normal range of motion. The patients were treated surgically with LUCL reconstruction or repair and off-label reconstruction of the capitellar joint surface using a small metal prosthesis designed for metatarsal head resurfacing (HemiCAP toe classic). Results Five patients (three adolescent males, two adult females) were treated between 2007 and 2018. At a median follow-up of 5 years, all patients had complete relief of their symptomatic instability. No patients had pain at rest, but two patients had mild pain (visual analog scale 1–3) during physical activity. Three patients rated their elbow as normal, one as almost normal, and one as greatly improved. On short-term radiographic follow-up there were no signs of implant loosening. None of the patients needed reoperation. Conclusions Recurrent PLRI of the elbow associated with an engaging posterior capitellar lesion can be treated successfully by LUCL reconstruction and repair and filling of the capitellar defect with a metal prosthesis. This treatment option has excellent clinical results in the short-medium term. Level of evidence IV.
Age-Dependent Association of Height Loss with Incident Fracture Risk in Postmenopausal Korean Women

Background Height loss is a simple clinical measure associated with increased fracture risk. However, limited data exists on the association between height loss and fracture risk in postmenopausal Korean women. It is unknown whether this association varies with age. Methods Data on height loss over a 6-year period were collected from a community-based longitudinal follow-up cohort (Ansung cohort of the Korean Genome and Epidemiology Study). Incident fractures were defined based on self-reported fractures after excluding those due to severe trauma or toes/fingers. The association between incident fractures and height loss was investigated using a Cox proportional hazards model. Results During a median follow-up of 10 years after the second visit, 259/1,806 participants (median age, 64 years) experienced incident fractures. Overall, a 1 standard deviation (SD) decrease in height (1.6 cm/median 5.8 years) was associated with 9% increased risk of fracture (hazard ratio [HR], 1.09; P=0.037), which lost statistical significance after adjustment for covariates. When stratified into age groups (50–59, 60–69, 70 years or older), a 1 SD decrease in height remained a robust predictor of fracture in the 50 to 59 years age group after adjusting for covariates (adjusted hazard ratio [aHR], 1.52; P=0.003), whereas height loss was not an independent predictor of fracture in the 60 to 69 (aHR, 1.06; P=0.333) or the 70 years or older age groups (aHR, 1.05; P=0.700; P for interaction <0.05, for all). Conclusion Height loss during the previous 6 years was associated with an increased 10-year fracture risk in postmenopausal women in their 50s.
Detailed characterization of Redondovirus in saliva of SARS-CoV-2-infected individuals in Sao Paulo, Brazil

Background Redondovirus (ReDoV) is a DNA virus present in the respiratory tract of many healthy individuals. Since SARS-CoV-2, the virus responsible for COVID-19, also primarily infects the same site, we evaluated whether ReDoV was present at increased frequency in patients with COVID-19 and influenced infection parameters. Methods Saliva samples were collected weekly from 59 individuals with COVID-19 and from 132 controls. ReDoV was detected by polymerase chain reaction and the genotypes were identified by metagenomics. Torque Teno Virus (TTV) in these samples were previously reported. Results ReDoV was detected in saliva more frequently from COVID-19 patients (72.9%) than from controls (50.0%) (p = 0.0015). There were no associations between ReDoV detection and either continuous or intermittent SARS-CoV-2 shedding, the duration of SARS-CoV-2 detection in saliva, patients’ sex or if infection was by the B1 or Gamma strain. The two ReDoV strains, Brisavirus and Vientovirus, were present in equivalent frequencies in ReDoV-positive COVID-19 patients and controls. Phylogenetic analysis suggested that the two ReDoV strains in Brazil were similar to strains previously detected on other continents. Conclusion ReDoV expression in saliva is increased in males and females in Brazil with mild COVID-19 but its presence does not appear to influence properties of the SARS-CoV-2 infection.
Theranostic gold-in-gold cage nanoparticles enable photothermal ablation and photoacoustic imaging in biofilm-associated infection models

Biofilms are structured communities of microbial cells embedded in a self-produced matrix of extracellular polymeric substances. Biofilms are associated with many health issues in humans, including chronic wound infections and tooth decay. Current antimicrobials are often incapable of disrupting the polymeric biofilm matrix and reaching the bacteria within. Alternative approaches are needed. Here, we described a complex structure of a dextran-coated gold-in-gold cage nanoparticle that enabled photoacoustic and photothermal properties for biofilm detection and treatment. Activation of these nanoparticles with a near infrared laser could selectively detect and kill biofilm bacteria with precise spatial control and in a short timeframe. We observed a strong biocidal effect against both Streptococcus mutans and Staphylococcus aureus biofilms in mouse models of oral plaque and wound infections, respectively. These effects were over 100 times greater than those seen with chlorhexidine, a conventional antimicrobial agent. Moreover, this approach did not adversely affect surrounding tissues. We concluded that photothermal ablation using theranostic nanoparticles is a rapid, precise, and nontoxic method to detect and treat biofilm-associated infections.
The Influence of Physical and Mental Health Mediators on the Relationship Between Combat-Related Traumatic Injury and Ultra-Short-Term Heart Rate Variability in a U.K. Military Cohort: A Structural Equation Modeling Approach

ABSTRACT Introduction Combat-related traumatic injury (CRTI) adversely affects heart rate variability (HRV). The mediating effect of mental and physical health factors on the relationship between CRTI, its severity and HRV has not been previously studied and investigated. Materials and Methods A cross-sectional mediation analysis of the ArmeD SerVices TrAuma and RehabilitatioN OutComE (ADVANCE) prospective cohort study was performed. The sample consisted of injured and uninjured British male servicemen who were frequency-matched based on their age, rank, role-in-theater, and deployment to Afghanistan (2003-2014). CRTI and injury severity (the New Injury Severity Scores [NISS] [NISS < 25 and NISS ≥ 25]) were included as exposure variables. HRV was quantified using the root mean square of successive differences (RMSSD) obtained using pulse waveform analysis. Depression and anxiety mediators were quantified using the Patient Health Questionnaire and Generalized Anxiety Disorder, respectively. Body mass index and the 6-minute walk test (6MWT) represented physical health measures. Two mediation pathways between exposure and outcome variables were examined in comparison with the uninjured group using structural equation modeling. Results Of 862 servicemen, 428 were injured and 434 were uninjured with the mean age at assessment of 33.9 ± 5.4 (range 23-59) years. Structural equation modeling revealed that depression, anxiety, and body mass index did not significantly mediate the relationship between injury/injury severity and RMSSD. However, the 6MWT significantly mediated the relationship between CRTI and RMSSD (27% mediation). The indirect effect of 6MWT on the relationship between injury severity (NISS ≥ 25 vs. uninjured) and RMSSD was −0.06 (95% CI: −0.12, −0.00, P < .05). Conclusions The findings suggest that greater physical function may improve HRV following CRTI. Longitudinal studies are warranted to further validate these findings.
Endothelial VEGFR2-PLCγ signaling regulates vascular permeability and antitumor immunity through eNOS/Src

Endothelial phospholipase Cγ (PLCγ) is essential for vascular development; however, its role in healthy, mature, or pathological vessels is unexplored. Here, we show that PLCγ was prominently expressed in vessels of several human cancer forms, notably in renal cell carcinoma (RCC). High PLCγ expression in clear cell RCC correlated with angiogenic activity and poor prognosis, while low expression correlated with immune cell activation. PLCγ was induced downstream of vascular endothelial growth factor receptor 2 (VEGFR2) phosphosite Y1173 (pY1173). Heterozygous Vegfr2Y1173F/+ mice or mice lacking endothelial PLCγ (Plcg1iECKO) exhibited a stabilized endothelial barrier and diminished vascular leakage. Barrier stabilization was accompanied by decreased expression of immunosuppressive cytokines, reduced infiltration of B cells, helper T cells and regulatory T cells, and improved response to chemo- and immunotherapy. Mechanistically, pY1173/PLCγ signaling induced Ca2+/protein kinase C–dependent activation of endothelial nitric oxide synthase (eNOS), required for tyrosine nitration and activation of Src. Src-induced phosphorylation of VE-cadherin at Y685 was accompanied by disintegration of endothelial junctions. This pY1173/PLCγ/eNOS/Src pathway was detected in both healthy and tumor vessels in Vegfr2Y1173F/+ mice, which displayed decreased activation of PLCγ and eNOS and suppressed vascular leakage. Thus, we believe that we have identified a clinically relevant endothelial PLCγ pathway downstream of VEGFR2 pY1173, which destabilizes the endothelial barrier and results in loss of antitumor immunity.
Spatial whole transcriptome profiling of primary tumor from patients with metastatic prostate cancer

Prostate cancer (PCa) is a highly heterogeneous disease in terms of its molecular makeup and clinical prognosis. The prostate tumor microenvironment (TME) is hypothesized to play an important role in driving disease aggressiveness, but precise mechanisms remain elusive. In our study, we used spatial transcriptomics to explore for the first time the spatial gene expression heterogeneity within primary prostate tumors from patients with metastatic disease. In total, we analyzed 5459 tissue spots from three PCa patients comprising castration‐resistant (CRPC) and neuroendocrine (NEPC) disease stages. Within CRPC, we identified a T cell cluster whose activity might be impaired by nearby regulatory T cells, potentially mediating the aggressive disease phenotype. Moreover, we identified Hallmark signatures of epithelial‐mesenchymal transition in a cancer‐associated fibroblast (CAF) cluster, indicating the aggressive characteristic of the primary TME leading to metastatic dissemination. Within NEPC, we identified active immune‐stroma cross‐talk exemplified by significant ligand‐receptor interactions between CAFs and M2 macrophages. Further, we identified a malignant cell population that was associated with the down‐regulation of an immune‐related gene signature. Lower expression of this signature was associated with higher levels of genomic instability in advanced PCa patients (SU2C cohort, n = 99) and poor recurrence free survival in early‐stage PCa patients (TCGA cohort, n = 395), suggesting prognostic biomarker potential. Taken together, our study reveals the importance of whole transcriptome profiling at spatial resolution for biomarker discovery and for advancing our understanding of tumor biology.
The atypical ‘hippocampal’ glutamate receptor coupled to phospholipase D that controls stretch‐sensitivity in primary mechanosensory nerve endings is homomeric purely metabotropic GluK2

A metabotropic glutamate receptor coupled to phospholipase D (PLD‐mGluR) was discovered in the hippocampus over three decades ago. Its pharmacology and direct linkage to PLD activation are well established and indicate it is a highly atypical glutamate receptor. A receptor with the same pharmacology is present in spindle primary sensory terminals where its blockade can totally abolish, and its activation can double, the normal stretch‐evoked firing. We report here the first identification of this PLD‐mGluR protein, by capitalizing on its expression in primary mechanosensory terminals, developing an enriched source, pharmacological profiling to identify an optimal ligand, and then functionalizing it as a molecular tool. Evidence from immunofluorescence, western and far‐western blotting indicates PLD‐mGluR is homomeric GluK2, since GluK2 is the only glutamate receptor protein/receptor subunit present in spindle mechanosensory terminals. Its expression was also found in the lanceolate palisade ending of hair follicle, also known to contain the PLD‐mGluR. Finally, in a mouse model with ionotropic function ablated in the GluK2 subunit, spindle glutamatergic responses were still present, confirming it acts purely metabotropically. We conclude the PLD‐mGluR is a homomeric GluK2 kainate receptor signalling purely metabotropically and it is common to other, perhaps all, primary mechanosensory endings.
A Reflection Symmetry Approximation of Multilook Polarimetric SAR Data and its Application to Freeman–Durden Decomposition

Freeman–Durden decomposition is a frequently used technique to analyze the scattering characteristics of multilook Polarimetric Synthetic Aperture Radar (POLSAR) data. When it is applied to the real POLSAR data, two problems emerge, namely, the volume scattering overestimation and negative powers. Many researchers think these two problems are caused by the insufficient decomposition algorithm, and several improvements are proposed. However, the improved decomposition algorithms become more and more complicated, and some new problems such as the decomposed component is not model based also emerge. In this paper, we try to solve the two problems through another way. We think they are caused not by the insufficient decomposition algorithm but by the dogmatic input. Freeman–Durden decomposition explicitly assumes reflection symmetry. Its input is a direct truncation of the measured coherency matrix. The truncation can be regarded as a reflection symmetry approximation (RSA) of the measured coherency matrix. We first show some reasons why we do not think the truncation is a good RSA. Then, a new RSA is proposed based on the sum of three reflection symmetry components derived from the measured coherency matrix. Experimental results with several real POLSAR images show that, if the new RSA is used as the input of Freeman–Durden decomposition, the above-mentioned two problems no longer exist.
Cost-effectiveness of combination therapy of polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisolone for previously untreated diffuse large B-cell lymphoma in Japan

Abstract Aim The POLARIX trial showed that Pola + R-CHP (polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisolone) prolongs progression-free survival (PFS) in patients with previously untreated diffuse large B-cell lymphoma (DLBCL) compared with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone), the conventional standard of care, with a similar safety profile. However, Pola + R-CHP has not been evaluated from the viewpoint of health economics in Japan. This study evaluates the cost-effectiveness of Pola + R-CHP for previously untreated DLBCL from a Japanese public healthcare payer’s perspective. Methods A partitioned survival analysis model was constructed to estimate lifetime costs and effectiveness of Pola + R-CHP and R-CHOP in previously untreated DLBCL who had an International Prognostic Index score (IPI) score of ≥2. A parametric survival model was applied to data analyzed in the POLARIX trial to estimate the lifetime overall survival (OS) and PFS for each treatment. The parameters required for the model were based on the results of a literature search and expert opinion. Results The incremental cost-effectiveness ratio (ICER) of Pola + R-CHP vs. R-CHOP was JPY2,710,238 per quality-adjusted life year (QALY), less than the ICER of JPY7.5 million per QALY that is considered to be cost-effective based on the threshold of the Japanese cost-effectiveness evaluation system. One-way sensitivity analysis showed that the parameters influencing the results of the analysis were median PFS and the total cost per regimen of salvage chemotherapy, patient weight, and patient age. Probabilistic sensitivity analysis showed that the probability of Pola + R-CHP having superior cost-effectiveness was 99.2% when the reference value was JPY7.5 million. The results of scenario analysis suggested that prolongation of PFS was an important factor in the evaluation of cost-effectiveness in previously untreated DLBCL with or without prolongation of OS. Conclusions This study suggests that Pola + R-CHP is a cost-effective treatment for previously untreated DLBCL in Japan under the public health insurance system.