Microsporidia:a new taxonomic, evolutionary, and ecological synthesis

Microsporidian diversity is vast. There is a renewed drive to understand how microsporidian pathological, genomic, and ecological traits relate to their phylogeny. We comprehensively sample and phylogenetically analyse 125 microsporidian genera for which sequence data are available. Comparing these results with existing phylogenomic analyses, we suggest an updated taxonomic framework to replace the inconsistent clade numbering system, using informal taxonomic names: Glugeida (previously clades 5/3), Nosematida (4a), Enterocytozoonida (4b), Amblyosporida (3/5), Neopereziida (1), and Ovavesiculida (2). Cellular, parasitological, and ecological traits for 281 well-defined species are compared with identify clade-specific patterns across long-branch Microsporidia. We suggest that future taxonomic circumscriptions of Microsporidia should involve additional markers (SSU/ITS/LSU), and that a comprehensive suite of phenotypic and ecological traits help to predict broad microsporidian functional and lineage diversity

Methyl 4′,5-dichloro-2-hy­droxy-4,6-dimethyl­biphenyl-3-carboxyl­ate

In the title compound, C16H14Cl2O3, the dihedral angle between the mean planes of the two benzene rings is 55.30 (5)°. The methyl ester group lies within the ring plane due to an intra­molecular O—H⋯O hydrogen bond [maximum deviation from the C8O2 mean plane is 0.0383 (13) Å]. In the crystal, mol­ecules are held together by rather weak C—H⋯O hydrogen bonds

Predictors and outcomes of crossover to surgery from physical therapy for meniscal tear and osteoarthritis a randomized trial comparing physical therapy and surgery

BACKGROUND: Arthroscopic partial meniscectomy (APM) combined with physical therapy (PT) have yielded pain relief similar to that provided by PT alone in randomized trials of subjects with a degenerative meniscal tear. However, many patients randomized to PT received APM before assessment of the primary outcome. We sought to identify factors associated with crossing over to APM and to compare pain relief between patients who had crossed over to APM and those who had been randomized to APM. METHODS: We used data from the MeTeOR (Meniscal Tear in Osteoarthritis Research) Trial of APM with PT versus PT alone in subjects ≥45 years old who had mild-to-moderate osteoarthritis and a degenerative meniscal tear. We assessed independent predictors of crossover to APM among those randomized to PT. We also compared pain relief at 6 months among those randomized to PT who crossed over to APM, those who did not cross over, and those originally randomized to APM. RESULTS: One hundred and sixty-four subjects were randomized to and received APM and 177 were randomized to PT, of whom 48 (27%) crossed over to receive APM in the first 140 days after randomization. In multivariate analyses, factors associated with a higher likelihood of crossing over to APM among those who had originally been randomized to PT included a baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score of ≥40 (risk ratio [RR] = 1.99; 95% confidence interval [CI] = 1.00, 3.93) and symptom duration of <1 year (RR = 1.74; 95% CI = 0.98, 3.08). Eighty-one percent of subjects who crossed over to APM and 82% of those randomized to APM had an improvement of ≥10 points in their pain score at 6 months, as did 73% of those who were randomized to and received only PT. CONCLUSIONS: Subjects who crossed over to APM had presented with a shorter symptom duration and greater baseline pain than those who did not cross over from PT. Subjects who crossed over had rates of surgical success similar to those of the patients who had been randomized to surgery. Our findings also suggest that an initial course of rigorous PT prior to APM may not compromise surgical outcome. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence

Total thyroidectomy: reduction in postoperative hypoparathyroidism

Objective: Total thyroidectomy is associated with a high risk of postoperative hypoparathyroidism, mainly due to the unintended surgical damage to the parathyroid glands or their blood supply. It is possible that surgeons who also perform parathyroid surgery see lower rates of postoperative hypoparathyroidism. In a single institution, we investigated the effects of restricting total thyroidectomy oper ations for Graves’ disease to two surgeons who performed both thyroid and parathyroid surgeries. We aimed to evaluate the rates of postoperative hypoparathyroidism in a 10-year period with primary attention toward patients with Graves’ disease. Design: Retrospective cohort study from a single institution. Methods: We defined the rate of permanent hypoparathyroidism after total thyroidectomy as the need for active vitamin D 6 months postoperatively. Between 2012 and 2016, seven surgeons performed all thyroidectomies. From January 2017, only surgeons also performing parathyroid surgery carried out thyroidectomies for Graves’ disease. Results: We performed total thyroidectomy in 543 patients. The rate of permanent hypoparathyroidism decreased from 28% in 2012–2014 to 6% in 2020–2021. For patients with Graves’ disease, the rate of permanent hypoparathyroidism decreased from 36% (13 out of 36) in 2015–2016 to 2% (1 out of 56) in 2020–2021. In cancer patients, the rate of permanent hypoparathyroidism decreased from 30% (14 out of 46) in 2012–2014 to 10% (10 out of 51) in 2020–2021. Conclusion: Restricting thyroidectomy to surgeons who also performed parathyroid operations reduced postoperative hypoparathyroidism markedly. Accordingly, we recommend centralisation of the most difficult thyroid operations to centres and surgeons with extensive experience in parathyroid surgery. Significance statement: Thyroid surgery is performed by many different surgeons with marked differences in outcome. Indeed, the risk of postoper ative permanent hypoparathyroidism may be very high in low-volume centres. This serious condition affects the quality of life and increases long-term morbidity and the patients develop a life-long dependency of medical treatments. We encountered a high risk of hypoparathyroidism after the operation for Graves’ disease and restricted the number of surgeons to two for these operations. Further, these surgeons were experienced in both thyroid and parathyroid surgeries. We show a dramatic reduction in postoperative hypoparathyroidism after this change. Accordingly, we recommend centralisation of total thyroidectomy to surgeons with experience in both thyroid and parathyroid procedures

Frequency and prognostic implications of KMT2A rearrangements in children with precursor B-cell lymphoma

Our analysis is limited regarding to the molecular features of BCP-L, since pediatric BCP-L is rare compared to BCP-ALL, and we were limited to archival BCP-L tissue that were small and preserved in FFPE blocks. Nevertheless, our data suggest that BCP-L is a valuable model for studying pathogenic mechanisms of BCP neoplasms, especially those with KMT2A aberrations. Detailed molecular genetic analysis will be required to understand which mechanisms lead to the clinical presentation as lymphoma instead of leukemia, and whether this clinical presentation is driven by genetic features of the tumor, or host dependent factors such as immunological status

Risk-Stratified Cardiovascular Screening Including Angiographic and Procedural Outcomes of Percutaneous Coronary Interventions in Renal Transplant Candidates

Background. Benefits of cardiac screening in kidney transplant candidates (KTC) will be dependent on the availability of effective interventions. We retrospectively evaluated characteristics and outcome of percutaneous coronary interventions (PCI) in KTC selected for revascularization by a cardiac screening approach. Methods. In 267 patients evaluated 2003 to 2006, screening tests performed were reviewed and PCI characteristics correlated with major adverse cardiovascular events (MACE) during a follow-up of 55 months. Results. Stress tests in 154 patients showed ischemia in 28 patients (89% high risk). Of 58 patients with coronary angiography, 38 had significant stenoses and 18 cardiac interventions (6.7% of all). 29 coronary lesions in 17/18 patients were treated by PCI. Angiographic success rate was 93.1%, but procedural success rate was only 86.2%. Long lesions (P=0.029) and diffuse disease (P=0.043) were associated with MACE. In high risk patients, cardiac screening did not improve outcome as 21.7% of patients with versus 15.5% of patients without properly performed cardiac screening had MACE (P=0.319). Conclusion. The moderate procedural success of PCI and poor outcome in long and diffuse coronary lesions underscore the need to define appropriate revascularization strategies in KTC, which will be a prerequisite for cardiac screening to improve outcome in these high-risk patients

Reverted exhaustion phenotype of circulating lymphocytes as immune correlate of anti-PD1 first-line treatment in Hodgkin lymphoma

While classical Hodgkin lymphoma (HL) is highly susceptible to anti-programmed death protein 1 (PD1) antibodies, the exact modes of action remain controversial. To elucidate the circulating lymphocyte phenotype and systemic effects during anti-PD1 1st-line HL treatment we applied multicolor flow cytometry, FluoroSpot and NanoString to sequential samples of 81 HL patients from the NIVAHL trial (NCT03004833) compared to healthy controls. HL patients showed a decreased CD4 T-cell fraction, a higher percentage of effector-memory T cells and higher expression of activation markers at baseline. Strikingly, and in contrast to solid cancers, expression for 10 out of 16 analyzed co-inhibitory molecules on T cells (e.g., PD1, LAG3, Tim3) was higher in HL. Overall, we observed a sustained decrease of the exhausted T-cell phenotype during anti-PD1 treatment. FluoroSpot of 42.3% of patients revealed T-cell responses against ≥1 of five analyzed tumor-associated antigens. Importantly, these responses were more frequently observed in samples from patients with early excellent response to anti-PD1 therapy. In summary, an initially exhausted lymphocyte phenotype rapidly reverted during anti-PD1 1st-line treatment. The frequently observed IFN-y responses against shared tumor-associated antigens indicate T-cell-mediated cytotoxicity and could represent an important resource for immune monitoring and cellular therapy of HL

Quasi-coherent fluctuations limiting the pedestal growth on Alcator C-Mod: experiment and modelling

Performance predictions for future fusion devices rely on an accurate model of the pedestal structure. The candidate for predictive pedestal structure is EPED, and it is imperative to test the underlying hypotheses to further gain confidence for ITER projections. Here, we present experimental work testing one of the EPED hypotheses, namely the existence of a soft limit set by microinstabilities such as the kinetic ballooning mode. This work extends recent work on Alactor C-Mod (Diallo et al 2014 Phys. Rev. Lett. 112 115001), to include detailed measurements of the edge fluctuations and comparisons of edge simulation codes and experimental observations

Correlation ECE diagnostic in Alcator C-Mod

Correlation ECE (CECE) is a diagnostic technique that allows measurement of small amplitude electron temperature, T[subscript e], fluctuations through standard cross-correlation analysis methods. In Alcator C-Mod, a new CECE diagnostic has been installed[Sung RSI 2012], and interesting phenomena have been observed in various plasma conditions. We find that local T[subscript e] fluctuations near the edge (ρ ~ 0:8) decrease across the linearto- saturated ohmic confinement transition, with fluctuations decreasing with increasing plasma density[Sung NF 2013], which occurs simultaneously with rotation reversals[Rice NF 2011]. T[subscript e] fluctuations are also reduced across core rotation reversals with an increase of plasma density in RF heated L-mode plasmas, which implies that the same physics related to the reduction of T[subscript e] fluctuations may be applied to both ohmic and RF heated L-mode plasmas. In I-mode plasmas, we observe the reduction of core T[subscript e] fluctuations, which indicates changes of turbulence occur not only in the pedestal region but also in the core across the L/I transition[White NF 2014]. The present CECE diagnostic system in C-Mod and these experimental results are described in this paper

Nonlinear gyrokinetic simulations of the I-mode high confinement regime and comparisons with experimenta)

For the first time, nonlinear gyrokinetic simulations of I-mode plasmas are performed and compared with experiment. I-mode is a high confinement regime, featuring energy confinement similar to H-mode, but without enhanced particle and impurity particle confinement [D. G. Whyte et al., Nucl. Fusion 50, 105005 (2010)]. As a consequence of the separation between heat and particle transport, I-mode exhibits several favorable characteristics compared to H-mode. The nonlinear gyrokinetic code GYRO [J. Candy and R. E. Waltz, J Comput. Phys. 186, 545 (2003)] is used to explore the effects of E × B shear and profile stiffness in I-mode and compare with L-mode. The nonlinear GYRO simulations show that I-mode core ion temperature and electron temperature profiles are more stiff than L-mode core plasmas. Scans of the input E × B shear in GYRO simulations show that E × B shearing of turbulence is a stronger effect in the core of I-mode than L-mode. The nonlinear simulations match the observed reductions in long wavelength density fluctuation levels across the L-I transition but underestimate the reduction of long wavelength electron temperature fluctuation levels. The comparisons between experiment and gyrokinetic simulations for I-mode suggest that increased E × B shearing of turbulence combined with increased profile stiffness are responsible for the reductions in core turbulence observed in the experiment, and that I-mode resembles H-mode plasmas more than L-mode plasmas with regards to marginal stability and temperature profile stiffness.United States. Department of Energy (Contract No. DE-FC02-99ER54512-CMOD)United States. Department of Energy. Office of Science (Contract No. DE-AC02- 05CH11231