Hybridization and reticulate evolution in Diphasiastrum (flat-branched clubmosses, Lycopodiaceae) - New data from the island of Taiwan and Vietnam.

In the species groups related to Diphasiastrum multispicatum and D. veitchii, hybridization was investigated in samples from northern and southern Vietnam and the island of Taiwan, including available herbarium specimens from southeast Asia. The accessions were analyzed using flow cytometry (living material only), Sanger sequencing and multiplexed inter-simple sequence repeat genotyping by sequencing. We detected two cases of ancient hybridization involving different combinations of parental species; both led via subsequent duplication to tetraploid taxa. A cross D. multispicatum × D. veitchii from Malaysia represents D. wightianum, a tetraploid taxon according to reported DNA content measurements of dried material (genome formulas MM, VV and MMVV, respectively). The second case involves D. veitchii and an unknown diploid parent (genome formula XX). Three hybridogenous taxa (genome formulas VVX, VVXX, VVVX) were discernable by a combination of flow cytometry and molecular data. Taxon I (VVX, three clones found on Taiwan island) is apparently triploid. Taxon II represents another genetically diverse and sexual tetraploid species (VVXX) and can be assigned to D. yueshanense, described from Taiwan island but occurring as well in mainland China and Vietnam. Taxon III is as well most likely tetraploid (VVVX) and represented by at least one, more likely two, clones from Taiwan island. Taxa I and III are presumably asexual and new to science. Two independently inherited nuclear markers recombine only within, not between these hybrids, pointing towards reproductive isolation. We present an evolutionary scheme which explains the origin of the hybrids and the evolution of new and fully sexual species by hybridization and subsequent allopolyploidization in flat-branched clubmosses.

A closer look to the timing of orchidopexy in undescended testes and adherence to the AWMF-guideline.

BACKGROUND: To lower the risk of testicular malignancies and subfertility, international guidelines recommend orchidopexy for undescended testis (UDT) before the age of 12-18 months. Previous studies reported low rates of 5-15% of timely surgery. Most of these studies are based on DRG and OPS code-based data from healthcare system institutions that do not distinguish between congenital and acquired UDT. METHODS: In a retrospective study data of all boys who underwent orchidopexy in a university hospital and two outpatient surgical departments from 2009 to 2022 were analyzed. The data differentiates congenital from acquired UDT. RESULTS: Out of 2694 patients, 1843 (68.4%) had congenital and 851 (31.6%) had acquired UDT. In 24.9% of congenital cases surgery was performed before the age of 12 months. The median age at surgery for congenital UDT was 16 months (range 7-202). Over the years there was an increased rate of boys operated on before the age of 2 (40% in 2009, 60% in 2022). The median age fluctuated over the years between 21 and 11 months without a trend to younger ages.. The covid pandemic did not lead to an increase of the median age at surgery. The median time between referral and surgery was 46 days (range 1-1836). Reasons for surgery after 12 months of age were a delayed referral to pediatric surgeries (51.2%), followed by relevant comorbidities (28.2%). CONCLUSION: Compared to recent literature, out data show that a closer look at details enables a more realistic approach. Still, there is no trend towards the recommended age for surgical treatment observable, but the rate of timely operated boys with congenital UDT is significantly higher than stated in literature.

Paramagnetic Singularities of the Orbital Magnetism in Graphene with a Moiré Potential.

The recent detection of the singular diamagnetism of Dirac electrons in a single graphene layer paved a new way of probing 2D quantum materials through the measurement of equilibrium orbital currents which cannot be accessed in usual transport experiments. Among the theoretical predictions is an intriguing orbital paramagnetism at saddle points of the dispersion relation. Here we present magnetization measurements in graphene monolayers aligned on hexagonal boron nitride crystals. Besides the sharp diamagnetic McClure response at the Dirac point, we detect extra diamagnetic singularities at the satellite Dirac points of the moiré lattice. Surrounding these diamagnetic satellite peaks, we also observe paramagnetic peaks located at the chemical potential of the saddle points of the graphene moiré band structure and relate them to the presence of van Hove logarithmic singularities in the density of states. These findings reveal the long ago predicted anomalous paramagnetic orbital response in 2D systems when the Fermi energy is tuned to the vicinity of saddle points.

Dynamics of Nanosecond Laser Pulse Propagation and of Associated Instabilities in a Magnetized Underdense Plasma.

The propagation and energy coupling of intense laser beams in plasmas are critical issues in inertial confinement fusion. Applying magnetic fields to such a setup has been shown to enhance fuel confinement and heating. Here we report on experimental measurements demonstrating improved transmission and increased smoothing of a high-power laser beam propagating in a magnetized underdense plasma. We also measure enhanced backscattering, which our kinetic simulations show is due to magnetic confinement of hot electrons, thus leading to reduced target preheating.

Beyond image defined risk factors (IDRFs): a delphi survey highlighting definition of the surgical complexity index (SCI) in neuroblastoma.

PURPOSE: Preoperative evaluation of Image Defined Risk Factors (IDRFs) in neuroblastoma (NB) is crucial for determining suitability for upfront resection or tumor biopsy. IDRFs do not all carry the same weighting in predicting tumor complexity and surgical risk. In this study we aimed to assess and categorize a surgical complexity (Surgical Complexity Index, SCI) in NB resection. METHODS: A panel of 15 surgeons was involved in an electronic Delphi consensus survey to identify and score a set of shared items predictive and/or indicative of surgical complexity, including the number of preoperative IDRFs. A shared agreement included the achievement of at least 75% consensus focused on a single or two close risk categories. RESULTS: After 3 Delphi rounds, agreement was established on 25/27 items (92.6%). A severity score was established for each item ranging from 0 to 3 with an overall SCI range varying from a minimum score of zero to a maximum score of 29 points for any given patient. CONCLUSIONS: A consensus on a SCI to stratify the risks related to neuroblastoma tumor resection was established by the panel experts. This index will now be deployed to critically assign a better severity score to IDRFs involved in NB surgery.

Enhancement of the Nonresonant Streaming Instability by Particle Collisions.

Streaming cosmic rays can power the exponential growth of a seed magnetic field by exciting a nonresonant instability that feeds on their bulk kinetic energy. By generating the necessary turbulent magnetic field, it is thought to play a key role in the confinement and acceleration of cosmic rays at shocks. In this Letter we present hybrid-particle-in-cell simulations of the nonresonant mode including Monte Carlo collisions, and investigate the interplay between the pressure anisotropies produced by the instability and particle collisions in the background plasma. Simulations of poorly ionized plasmas confirm the rapid damping of the instability by proton-neutral collisions predicted by linear fluid theory calculations. In contrast we find that Coulomb collisions in fully ionized plasmas do not oppose the growth of the magnetic field, but under certain conditions suppress the pressure anisotropies and actually enhance the magnetic field amplification.

Stabilized Radiation Pressure Acceleration and Neutron Generation in Ultrathin Deuterated Foils.

Premature relativistic transparency of ultrathin, laser-irradiated targets is recognized as an obstacle to achieving a stable radiation pressure acceleration in the "light sail" (LS) mode. Experimental data, corroborated by 2D PIC simulations, show that a few-nm thick overcoat surface layer of high Z material significantly improves ion bunching at high energies during the acceleration. This is diagnosed by simultaneous ion and neutron spectroscopy following irradiation of deuterated plastic targets. In particular, copious and directional neutron production (significantly larger than for other in-target schemes) arises, under optimal parameters, as a signature of plasma layer integrity during the acceleration.

Analysis of the small chromosomal Prionium serratum (Cyperid) demonstrates the importance of reliable methods to differentiate between mono- and holocentricity.

For a long time, the Cyperid clade (Thurniceae-Juncaceae-Cyperaceae) was considered a group of species possessing holocentromeres exclusively. The basal phylogenetic position of Prionium serratum (Thunb.) Drège (Thurniceae) within Cyperids makes this species an important specimen to understand the centromere evolution within this clade. In contrast to the expectation, the chromosomal distribution of the centromere-specific histone H3 (CENH3), alpha-tubulin and different centromere-associated post-translational histone modifications (H3S10ph, H3S28ph and H2AT120ph) demonstrate a monocentromeric organisation of P. serratum chromosomes. Analysis of the high-copy repeat composition resulted in the identification of two centromere-localised satellite repeats. Hence, monocentricity was the ancestral condition for the Juncaceae-Cyperaceae-Thurniaceae Cyperid clade, and holocentricity in this clade has independently arisen at least twice after differentiation of the three families, once in Juncaceae and the other one in Cyperaceae. In this context, methods suitable for the identification of holocentromeres are discussed.

Endogenous anandamide and self-reported pain are significantly reduced after a 2-week multimodal treatment with and without radon therapy in patients with knee osteoarthritis: a pilot study.

Multimodal therapies comprising spa applications are widely used as non-pharmaceutical treatment options for musculoskeletal diseases. The purpose of this randomized, controlled, open pilot study was to elucidate the involvement of the endocannabinoid system in a multimodal therapy approach. Twenty-five elderly patients with knee osteoarthritis (OA) received a 2-week spa therapy with or without combination of low-dose radon therapy in the Bad Gastein radon gallery. A 10-point numerical rating scale (pain in motion and at rest), WOMAC questionnaire, and the EuroQol-5D (EQ-5D) questionnaire were recorded at baseline, and during treatment period at weeks one and two, and at 3-month and 6-month follow-ups. Plasma levels of the endocannabinoid anandamide (AEA) were determined at baseline and at 2 weeks, and serum levels of several cartilage metabolism markers at all five time-points. A significant and sustained reduction of self-reported knee pain was observed in the study population, but no further significant effect of the additional radon therapy up and above base therapy. This pain reduction was accompanied by a significant reduction of AEA plasma levels during treatment in both groups. No significant differences were seen in serum marker concentrations between the groups treated with or without radon, but a small reduction of serum cartilage degradation markers was observed during treatment in both groups. This is the first study investigating AEA levels in the context of a non-pharmacological OA treatment. Since the endocannabinoid system represents a potential target for the development of new therapeutics, further studies will have to elucidate its involvement in OA pain.

[Imaging of renal tumors in children]. / Bildgebung renaler Tumoren im Kindesalter.

CLINICAL/METHODOLOGICAL ISSUE: Renal tumors in children are treated according to the guidelines of the Renal Tumor Study Group of the International Society of Pediatric Oncology (SIOP-RTSG). Nephroblastoma is the most frequent renal tumor in children. STANDARD RADIOLOGICAL METHODS: After sonography, magnetic resonance imaging (MRI) is the preferred imaging modality. The task of imaging includes differential diagnosis with the help of morphological and epidemiological criteria. Thorax computed tomography (CT) is introduced for initial staging. METHODOLOGICAL INNOVATIONS: Current studies of diffusion-weighted imaging (DWI)-MRI with analysis of the apparent diffusion coefficient (ADC) histogram indicate the potential to differentiate blastemal or anaplastic high-risk histology nephroblatoma subtypes. Imaging criteria for nephron-sparing surgery are defined and allow an individual therapy option in unilateral and especially in bilateral renal nephroblastoma. PERFORMANCE: In addition to nephroblastoma, the differential diagnosis includes congenital mesoblastic nephroma, malignant rhabdoid tumor of the kidney, clear cell sarcoma and renal cell carcinoma. The diagnosis of nephrogenic rests and nephroblastomatosis is challenging. ACHIEVEMENTS: Diagnostic standardization improves diagnosis and therapy of renal childhood tumors, and new prognostic markers may be introduced in the near future.

Novel small molecule IL-6 inhibitor suppresses autoreactive Th17 development and promotes Treg development.

Multiple sclerosis (MS) is the leading cause of non-traumatic neurological disability in the United States in young adults, but current treatments are only partially effective, making it necessary to develop new, innovative therapeutic strategies. Myelin-specific interleukin (IL)-17-producing T helper type 17 (Th17) cells are a major subset of CD4 T effector cells (Teff ) that play a critical role in mediating the development and progression of MS and its mouse model, experimental autoimmune encephalomyelitis (EAE), while regulatory T cells (Treg ) CD4 T cells are beneficial for suppressing disease. The IL-6/signal transducer and activator of transcription 3 (STAT-3) signaling pathway is a key regulator of Th17 and Treg cells by promoting Th17 development and suppressing Treg development. Here we show that three novel small molecule IL-6 inhibitors, madindoline-5 (MDL-5), MDL-16 and MDL-101, significantly suppress IL-17 production in myelin-specific CD4 T cells in a dose-dependent manner in vitro. MDL-101 showed superior potency in suppressing IL-17 production compared to MDL-5 and MDL-16. Treatment of myelin-specific CD4 T cells with MDL-101 in vitro reduced their encephalitogenic potential following their subsequent adoptive transfer. Furthermore, MDL-101 significantly suppressed proliferation and IL-17 production of anti-CD3-activated effector/memory CD45RO+ CD4+ human CD4 T cells and promoted human Treg development. Together, these data demonstrate that these novel small molecule IL-6 inhibitors have the potential to shift the Teff  : Treg balance, which may provide a novel therapeutic strategy for ameliorating disease progression in MS.

Laser-Produced Magnetic-Rayleigh-Taylor Unstable Plasma Slabs in a 20 T Magnetic Field.

Magnetized laser-produced plasmas are central to many novel laboratory astrophysics and inertial confinement fusion studies, as well as in industrial applications. Here we provide the first complete description of the three-dimensional dynamics of a laser-driven plasma plume expanding in a 20 T transverse magnetic field. The plasma is collimated by the magnetic field into a slender, rapidly elongating slab, whose plasma-vacuum interface is unstable to the growth of the "classical," fluidlike magnetized Rayleigh-Taylor instability.

Dynamics of the Electromagnetic Fields Induced by Fast Electron Propagation in Near-Solid-Density Media.

The propagation of fast electron currents in near solid-density media was investigated via proton probing. Fast currents were generated inside dielectric foams via irradiation with a short (∼0.6 ps) laser pulse focused at relativistic intensities (Iλ^{2}∼4×10^{19} W cm^{-2} µm^{2}). Proton probing provided a spatially and temporally resolved characterization of the evolution of the electromagnetic fields and of the associated net currents directly inside the target. The progressive growth of beam filamentation was temporally resolved and information on the divergence of the fast electron beam was obtained. Hybrid simulations of electron propagation in dense media indicate that resistive effects provide a major contribution to field generation and explain well the topology, magnitude, and temporal growth of the fields observed in the experiment. Estimations of the growth rates for different types of instabilities pinpoints the resistive instability as the most likely dominant mechanism of beam filamentation.

[Treatment principles and outcome after fractures of the lateral humeral condyle in children]. / Therapieprinzipien und Outcome nach Frakturen des Condylus radialis im Wachstumsalter.

BACKGROUND: Fractures of the lateral humeral condyle with displacement (>2 mm; <2 mm articular gap) require open reduction and stabilization. Non-displaced fractures should be treated conservatively; however, there are difficulties in the differentiation of complete (potentially unstable) an incomplete (stable) articular fractures. The aim of this study was to analyze the frequency of conservative and operative treatment approaches as well as the accuracy of treatment decisions based on fracture stability displayed on repetitive X­rays. MATERIAL AND METHODS: A retrospective data analysis of all lateral humeral condyles in children <16 years old treated between 2005 and 2014 was carried out. The patients were classified according to the fracture stability at the time of the incident (primarily stable or unstable) and after 4 days (secondarily stable or unstable) using conventional X­ray images. RESULTS: A total of 89 fractures of the lateral humeral condyle were treated (mean age 6.4 years, range 0.9-14 years). Of the fractures 52 (58%) were initially not displaced and 37 (42%) were initially displaced. The latter underwent open reduction and stabilization by osteosynthesis (primarily stable). Of the 52 initially not displaced fractures 35 remained stable and conservative treatment in a plaster cast was performed (primarily and secondarily stable). In 8 out of 52 cases a secondary displacement (>2 mm articular gap) occurred after an average of 6 days (range 3-10 days) and operative treatment was initiated (primarily stable and secondarily unstable). No follow-up x­ray could be performed in 2 of the 52 fractures and at the end of treatment the fractures healed with displacement (primarily stable and secondarily unstable). In 7 of the 52 fractures operative treatment was performed although no displacement (primarily stable) was initially documented (overtreatment). The outcome of the whole study cohort was comparable with that described in the literature. CONCLUSION: Treatment decisions in pediatric lateral humeral condyle fractures are based on the primary and secondary fracture stability as observed in staged follow-up radiographs. Stable fractures, whether complete or incomplete, healed with good results after conservative treatment and overtreatment could be avoided. Unstable fractures, whether primary or secondary during the course, need to be recognized as such and operative treatment with a stable osteosynthesis must be initiated.

Towards an in vitro fibrogenesis model of human vocal fold scarring.

BACKGROUND: Vocal fold (VF) scarring remains a therapeutic dilemma and challenge in modern laryngology. To facilitate corresponding research, we aimed to establish an in vitro fibrogenesis model employing human VF fibroblasts (hVFF) and the principles of macromolecular crowding (MMC). METHODS: Fibrogenesis was promoted by addition of transforming growth factor-ß1 to standard medium and medium containing inert macromolecules (MMC). Hepatocyte growth factor (HGF) and Botox type A were tested for their antifibrotic properties in various doses. Experiments were analyzed with respect to the biosynthesis of collagen, fibronectin, and α-smooth muscle actin using immunofluorescence, silver stain and western blot. RESULTS: MMC led to favourable enhanced deposition of collagen and other extracellular matrix components, reflecting fibrotic conditions. Low doses of HGF were able to dampen profibrotic effects. This could not be observed for higher HGF concentrations. Botox type A did not show any effects. CONCLUSION: Based on the principles of MMC we could successfully establish a laryngeal fibrogenesis model employing hVFF. Our finding of dose-dependent HGF effects is important before going into clinical trials in humans and has never been shown before. Our model provides a novel option to screen various potential antifibrotic compounds under standardized conditions in a short time.

Enhancement of Quasistationary Shocks and Heating via Temporal Staging in a Magnetized Laser-Plasma Jet.

We investigate the formation of a laser-produced magnetized jet under conditions of a varying mass ejection rate and a varying divergence of the ejected plasma flow. This is done by irradiating a solid target placed in a 20 T magnetic field with, first, a collinear precursor laser pulse (10^{12} W/cm^{2}) and, then, a main pulse (10^{13} W/cm^{2}) arriving 9-19 ns later. Varying the time delay between the two pulses is found to control the divergence of the expanding plasma, which is shown to increase the strength of and heating in the conical shock that is responsible for jet collimation. These results show that plasma collimation due to shocks against a strong magnetic field can lead to stable, astrophysically relevant jets that are sustained over time scales 100 times the laser pulse duration (i.e., >70 ns), even in the case of strong variability at the source.

Competition between Spin Echo and Spin Self-Rephasing in a Trapped Atom Interferometer.

We perform Ramsey interferometry on an ultracold ^{87}Rb ensemble confined in an optical dipole trap. We use a π pulse set at the middle of the interferometer to restore the coherence of the spin ensemble by canceling out phase inhomogeneities and creating a spin echo in the contrast. However, for high atomic densities, we observe the opposite behavior: the π pulse accelerates the dephasing of the spin ensemble leading to a faster contrast decay of the interferometer. We understand this phenomenon as a competition between the spin-echo technique and an exchange-interaction driven spin self-rephasing mechanism based on the identical spin rotation effect. Our experimental data are well reproduced by a numerical model.

Signatures of the Self-Similar Regime of Strongly Coupled Stimulated Brillouin Scattering for Efficient Short Laser Pulse Amplification.

Plasma-based laser amplification is considered as a possible way to overcome the technological limits of present day laser systems and achieve exawatt laser pulses. Efficient amplification of a picosecond laser pulse by stimulated Brillouin scattering (SBS) of a pump pulse in a plasma requires to reach the self-similar regime of the strongly coupled (SC) SBS. In this Letter, we report on the first observation of the signatures of the transition from linear to self-similar regimes of SC-SBS, so far only predicted by theory and simulations. With a new fully head-on collision geometry, subpicosecond pulses are amplified by a factor of 5 with energy transfers of few tens of mJ. We observe pulse shortening, frequency spectrum broadening, and down-shifting for increasing gain, signatures of SC-SBS amplification entering the self-similar regime. This is also confirmed by the power law dependence of the gain on the amplification length: doubling the interaction length increases the gain by a factor 1.4. Pump backward Raman scattering (BRS) on SC-SBS amplification has been measured for the first time, showing a strong decrease of the BRS amplitude and frequency bandwidth when SBS seed amplification occurs.

Differences between intrinsic and extrinsic ureteropelvic junction obstruction related to crossing vessels: histology and functional analyses.

PURPOSE: In children, ureteropelvic junction obstruction (UPJO) is mostly caused by intrinsic factors (IUPJO); extrinsic UPJO are rare and often due to crossing vessels (CVs). METHODS: We retrospectively reviewed all data of children with UPJO that underwent surgery in our institution from 2004 to 2011. Analyses included age at surgery, gender, preoperative and postoperative results of ultrasound and renal scans [differential renal function (DRF); signs of obstruction], and pathology reports. Available histological specimens of cases with CV were compared to a random selection of intrinsic cases in a blinded fashion. After additional Masson's trichrome staining, the specimens were scored for fibrosis, muscular hypertrophy, and chronic inflammation. RESULTS: Out of 139 patients with UPJO, 39 cases were associated with CV. Median age at surgery was 68 months (range 2-194) in the CV group and 11.5 months (range 0-188) in IUPJO group. Laparoscopic dismembered pyeloplasty (LDMP) was carried out in 134 and open DMP in five patients. Preoperative ultrasound identified 28/39 cases with CV. DRF below 40 % was more frequently seen in CV patients (p = 0.020). Histological analyses revealed no differences between the CV and IUPJO specimens in total. CV patients with higher grades of muscular hypertrophy had lower preoperative DRF, compared to those with higher preoperative DRF (p = 0.026). Functional recovery after (L)DMP was excellent in both groups. CONCLUSION: We could not find any significant histological differences between CV and IUPJO in children. To obtain excellent functional recovery, surgical procedures with a definite correction of the UPJ should be preferred in paediatric patients with CV.

Changes in physical functioning among men and women aged 50-79 years in Germany: an analysis of National Health Interview and Examination Surveys, 1997-1999 and 2008-2011.

BACKGROUND: This study examines changes in physical functioning among adults aged 50-79 years in Germany based on data from two German National Health Interview and Examination Surveys conducted in 1997-1999 (GNHIES98) and 2008-2011 (DEGS1). METHODS: Using cross-sectional data from the two surveys (GNHIES98, n = 2884 and DEGS1, n = 3732), we examined changes in self-reported physical functioning scores (Short Form-36 physical functioning subscale (SF-36 PF)) by sex and age groups (50-64 and 65-79 years). Covariables included educational level, living alone, nine chronic diseases, polypharmacy (≥5 prescribed medicines), body mass index, sports activity, smoking and alcohol consumption. Multimorbidity was defined as ≥2 chronic diseases. Multivariable models were fitted to examine consistency of changes in physical functioning among certain subgroups and to assess changes in mean SF-36 PF scores, adjusting for changes in covariables between surveys. RESULTS: Mean physical functioning increased among adults aged 50-79 years between surveys in unadjusted analyses, but this change was not as marked among men aged 65-79 years who experienced rising obesity (20.6 to 31.5%, p = 0.004) and diabetes (13.0 to 20.0%, p = 0.014). Prevalence of multimorbidity and polypharmacy use increased among men and women aged 65-79 years. In sex and age specific multivariable analyses, changes in physical functioning over time were consistent across subgroups. Gains in physical functioning were explained by improved education, lower body mass index and improved health-related behaviours (smoking, alcohol consumption, sports activity) in women, but less so among men. CONCLUSIONS: Physical functioning improved in Germany among adults aged 50-79 years. Improvements in the population 65-79 years were less evident among men than women, despite increases in multimorbidity prevalence among both sexes. Changes in health behaviours over time differed between sexes and help explain variations in physical functioning. Targeted health behaviour interventions are indicated from this study.