How dispersal rates depend on the prey capture strategy: A case study of Georgia's spiders.

Large-scale barcoding projects help to aggregate information on genetic variability of multiple species throughout their ranges. Comparing DNA sequences of both non-conspecific and conspecific individuals from distant parts of their ranges helps to compare level of genetic isolation-by-distance patterns in different species and adaptive types. We compared mitochondrial CO1 gene sequences of 223 spiders from Georgia (Caucasus), representing 124 species and eight families, with 3097 homological sequences from spiders mostly from Europe, but also from other parts of the World. In most families, a significant isolation-by distance pattern was observed on family level. On species level, a significant isolation-by-distance was observed in 40 species, although this low proportion is most likely related to a lack of data. Simultaneously, remarkable differences in spatial structure were shown for different species. Although the majority of the studied species have a broad western Palearctic range, web-building spiders from families Araneidae, Theridiidae, and Linyphiidae are less isolated spatially than flower spiders (Thomisidae), jumping spiders (Salticidae), wolf spiders (Lycosidae), sac spiders (Clubionidae), and ground spiders (Gnaphosidae). This pattern is related with more common ballooning in web building than in actively hunting spiders, which commonly remain isolated since preglacial time. Ground spiders build the most isolated populations in the Caucasus.

Precursor-Engineered Volatile Inks Enable Reliable Blade-Coating of Cesium-Formamidinium Perovskites Toward Fully Printed Solar Modules.

Reliable fabrication of large-area perovskite films with antisolvent-free printing techniques requires high-volatility solvents, such as 2-methoxyethanol (2ME), to formulate precursor inks. However, the fabrication of high-quality cesium-formamidinium (Cs-FA) perovskites has been hampered using volatile solvents due to their poor coordination with the perovskite precursors. Here, this issue is resolved by re-formulating a 2ME-based Cs0.05FA0.95PbI3 ink using pre-synthesized single crystals as the precursor instead of the conventional mixture of raw powders. The key to obtaining high-quality Cs-FA films lies in the removal of colloidal particles from the ink and hence the suppression of colloid-induced heterogeneous nucleation, which kinetically facilitates the growth of as-formed crystals toward larger grains and improved film crystallinity. Employing the precursor-engineered volatile ink in the vacuum-free, fully printing processing of solar cells (with carbon electrode), a power conversion efficiency (PCE) of 19.3%, a T80 (80% of initial PCE) of 1000 h in ISOS-L-2I (85 °C/1 Sun) aging test and a substantially reduced bill of materials are obtained. The reliable coating methodology ultimately enables the fabrication of carbon-electrode mini solar modules with a stabilized PCE of 16.2% (average 15.6%) representing the record value among the fully printed counterparts and a key milestone toward meeting the objectives for a scalable photovoltaic technology.

Bounds to electron spin qubit variability for scalable CMOS architectures.

Spins of electrons in silicon MOS quantum dots combine exquisite quantum properties and scalable fabrication. In the age of quantum technology, however, the metrics that crowned Si/SiO2 as the microelectronics standard need to be reassessed with respect to their impact upon qubit performance. We chart spin qubit variability due to the unavoidable atomic-scale roughness of the Si/SiO2 interface, compiling experiments across 12 devices, and develop theoretical tools to analyse these results. Atomistic tight binding and path integral Monte Carlo methods are adapted to describe fluctuations in devices with millions of atoms by directly analysing their wavefunctions and electron paths instead of their energy spectra. We correlate the effect of roughness with the variability in qubit position, deformation, valley splitting, valley phase, spin-orbit coupling and exchange coupling. These variabilities are found to be bounded, and they lie within the tolerances for scalable architectures for quantum computing as long as robust control methods are incorporated.

Cows with diverging haplotypes show differences in differential milk cell count, milk parameters and vaginal temperature after S. aureus challenge but not after E. coli challenge.

BACKGROUND: In dairy cattle, mastitis causes high financial losses and impairs animal well-being. Genetic selection is used to breed cows with reduced mastitis susceptibility. Techniques such as milk cell flow cytometry may improve early mastitis diagnosis. In a highly standardized in vivo infection model, 36 half-sib cows were selected for divergent paternal Bos taurus chromosome 18 haplotypes (Q vs. q) and challenged with Escherichia coli for 24 h or Staphylococcus aureus for 96 h, after which the samples were analyzed at 12 h intervals. Vaginal temperature (VT) was recorded every three minutes. The objective of this study was to compare the differential milk cell count (DMCC), milk parameters (fat %, protein %, lactose %, pH) and VT between favorable (Q) and unfavorable (q) haplotype cows using Bayesian models to evaluate their potential as improved early indicators of differential susceptibility to mastitis. RESULTS: After S. aureus challenge, compared to the Q half-sibship cows, the milk of the q cows exhibited higher PMN levels according to the DMCC (24 h, p < 0.001), a higher SCC (24 h, p < 0.01 and 36 h, p < 0.05), large cells (24 h, p < 0.05) and more dead (36 h, p < 0.001) and live cells (24 h, p < 0.01). The protein % was greater in Q milk than in q milk at 0 h (p = 0.025). In the S. aureus group, Q cows had a greater protein % (60 h, p = 0.048) and fat % (84 h, p = 0.022) than q cows. Initially, the greater VT of S. aureus-challenged q cows (0 and 12-24 h, p < 0.05) reversed to a lower VT in q cows than in Q cows (48-60 h, p < 0.05). Additionally, the following findings emphasized the validity of the model: in the S. aureus group all DMCC subpopulations (24 h-96 h, p < 0.001) and in the E. coli group nearly all DMCC subpopulations (12 h-24 h, p < 0.001) were higher in challenged quarters than in unchallenged quarters. The lactose % was lower in the milk samples of E. coli-challenged quarters than in those of S. aureus-challenged quarters (24 h, p < 0.001). Between 12 and 18 h, the VT was greater in cows challenged with E. coli than in those challenged with S. aureus (3-h interval approach, p < 0.001). CONCLUSION: This in vivo infection model confirmed specific differences between Q and q cows with respect to the DMCC, milk component analysis results and VT results after S. aureus inoculation but not after E. coli challenge. However, compared with conventional milk cell analysis monitoring, e.g., the global SCC, the DMCC analysis did not provide refined phenotyping of the pathogen response.

Correction: Long-term Follow-up and Safety of Patients after an Upfront Therapy with Letrozole for Early Breast Cancer in Routine Clinical Care - The PreFace Study.

[This corrects the article DOI: 10.1055/a-2238-3153.].

A new era in the science and care of kidney diseases.

Notable progress in basic, translational and clinical nephrology research has been made over the past five decades. Nonetheless, many challenges remain, including obstacles to the early detection of kidney disease, disparities in access to care and variability in responses to existing and emerging therapies. Innovations in drug development, research technologies, tissue engineering and regenerative medicine have the potential to improve patient outcomes. Exciting prospects include the availability of new drugs to slow or halt the progression of chronic kidney disease, the development of bioartificial kidneys that mimic healthy kidney functions, and tissue engineering techniques that could enable transplantable kidneys to be created from the cells of the recipient, removing the risk of rejection. Cell and gene therapies have the potential to be applied for kidney tissue regeneration and repair. In addition, about 30% of kidney disease cases are monogenic and could potentially be treated using these genetic medicine approaches. Systemic diseases that involve the kidney, such as diabetes mellitus and hypertension, might also be amenable to these treatments. Continued investment, communication, collaboration and translation of innovations are crucial to realize their full potential. In addition, increasing sophistication in exploring large datasets, implementation science, and qualitative methodologies will improve the ability to deliver transformational kidney health strategies.

Exposure to Polybrominated Diphenyl Ethers and Risk of All-Cause and Cause-Specific Mortality.

Importance: Polybrominated diphenyl ethers (PBDEs) are an important group of persistent organic pollutants with endocrine-disrupting properties. However, prospective cohort studies regarding the association of PBDE exposure with long-term health outcomes, particularly mortality, are lacking. Objective: To examine the association of environmental exposure to PBDEs with risk of all-cause and cause-specific mortality. Design, Setting, and Participants: This nationally representative cohort study used data from the National Health and Nutrition Examination Survey 2003 to 2004 and linked mortality information through December 31, 2019. Adults aged 20 years or older with available data on PBDE measurements and mortality were included. Statistical analysis was performed from February 2022 to April 2023. Exposures: PBDE analytes in serum samples were measured using solid phase extraction and isotope dilution gas chromatography high-resolution mass spectrometry. Main Outcomes and Measures: All-cause mortality, cancer mortality, and cardiovascular mortality. Results: This study included 1100 participants (mean [SE] age, 42.9 [0.6] years; proportion [SE] female, 51.8% [1.6%]; proportion [SE] Hispanic, 12.9% [2.7%]; proportion [SE] non-Hispanic Black, 10.5% [1.6%]; proportion [SE] non-Hispanic White, 70.8% [3.7%]; proportion [SE] other race and ethnicity, 5.8% [1.1%]). During 16 162 person-years of follow-up (median [IQR] follow-up, 15.8 [15.2-16.3] years; maximum follow-up, 17 years), 199 deaths occurred. Participants with higher serum PBDE levels were at higher risk for death. After adjustment for age, sex, and race and ethnicity, lifestyle and socioeconomic factors, and body mass index, participants with the highest tertile of serum PBDE levels had an approximately 300% increased risk of cancer mortality (HR, 4.09 [95% CI, 1.71-9.79]) compared with those with the lowest tertile of serum PBDE levels. No significant association of PBDE exposure with all-cause mortality (HR, 1.43 [95% CI, 0.98-2.07]) or cardiovascular mortality (HR, 0.92 [95% CI, 0.41-2.08]) was observed. Conclusions and Relevance: In this nationally representative cohort study, PBDE exposure was significantly associated with an increased risk of cancer mortality. Further studies are needed to replicate the findings and determine the underlying mechanisms.

Erythrocytosis and CKD.

Erythrocytosis or polycythemia is defined as an increase in red blood cell concentration above the age- and sex-specific normal levels. Unlike anemia that is very common in chronic kidney disease (CKD) patients, erythrocytosis is less frequent but requires specific understanding by healthcare professionals in order to provide the best care. Erythrocytosis, especially when undiagnosed and untreated, can lead to serious thrombotic events and higher mortality. Classical causes of erythrocytosis associated with CKD include cystic kidney diseases, kidney or other erythropoietin-secreting neoplasms, high-altitude renal syndrome, overdosage of erythropoietin-stimulating agents, androgen therapy, heavy smoking, chronic lung disease, obstructive sleep apnea, IgA nephropathy, post-kidney transplant erythrocytosis, renal artery stenosis and congenital etiologies. After ruling out the common acquired causes of erythrocytosis, and/or in the presence of suggestive parameters, primary erythrocytosis or polycythemia vera (PV) should be considered and patients screened for JAK2V617F somatic mutation. The newest entity inducing erythrocytosis is linked to the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors that hypothetically activate hypoxia-inducible factor 2-alpha (HIF-2α), and in some cases unmask PV. This review focusses on the pathogenesis, renal manifestations and management of PV, the pathophysiology of erythrocytosis induced by SGLT2 inhibitors and the relevance of timely JAK2 mutation screening in these patients.

[Gustav Mahler: tragic life, mysterious illness, early death : Could intensive care medicine have saved him today?] / Gustav Mahler: tragisches Leben, rätselhafte Erkrankung, früher Tod : Hätte die Intensivmedizin ihn heute retten können?

BACKGROUND: Gustav Mahler was a composer of the late Romantic period, one of the most famous conductors of his time and, as opera director, one of the most important reformers of musical theatre. Mahler's life, illnesses, death and dying are little or not at all known to many. OBJECTIVES: Which illnesses determined Mahler's life? Could his early death have been avoided? From today's point of view, could modern intensive care medicine have helped him? MATERIAL AND METHODS: A detailed analysis of Mahler's diseases was performed using scientific databases (medline, pubmed). All published articles were examined in detail. RESULTS: Gustav Mahler was born in 1860 in Kalischt (Bohemia) and learned to play the accordion and piano at an early age. He studied music at the Vienna Conservatory from 1875 and completed his composition studies in 1878. Kapellmeister positions followed in several cities, from 1887 at the Vienna Court Opera and from 1908 at the Metropolitan Opera in New York. Mahler suffered from many illnesses, especially tonsillitis and haemorrhoids. In 1907 he was diagnosed with a mitral valve defect, in 1911 he developed bacterial endocarditis caused by streptococci, as a result of which Mahler died in Vienna in 1911. His life was marked by personal and health tragedies. DISCUSSION: Mahler was an outstanding personality who left behind an extensive oeuvre. Among the compositional highlights are his 10 symphonies and the song compositions. Recurrent streptococcal infections led to mitral valve disease and endocarditis, the consequences of which caused Mahler's untimely death. Today's modern cardiology and intensive care medicine could have prolonged his life, but unfortunately this was not possible at the time when he was diagnosed with endocarditis.

GDF-15 Suppresses Puromycin Aminonucleoside-Induced Podocyte Injury by Reducing Endoplasmic Reticulum Stress and Glomerular Inflammation.

GDF15, also known as MIC1, is a member of the TGF-beta superfamily. Previous studies reported elevated serum levels of GDF15 in patients with kidney disorder, and its association with kidney disease progression, while other studies identified GDF15 to have protective effects. To investigate the potential protective role of GDF15 on podocytes, we first performed in vitro studies using a Gdf15-deficient podocyte cell line. The lack of GDF15 intensified puromycin aminonucleoside (PAN)-triggered endoplasmic reticulum stress and induced cell death in cultivated podocytes. This was evidenced by elevated expressions of Xbp1 and ER-associated chaperones, alongside AnnexinV/PI staining and LDH release. Additionally, we subjected mice to nephrotoxic PAN treatment. Our observations revealed a noteworthy increase in both GDF15 expression and secretion subsequent to PAN administration. Gdf15 knockout mice displayed a moderate loss of WT1+ cells (podocytes) in the glomeruli compared to wild-type controls. However, this finding could not be substantiated through digital evaluation. The parameters of kidney function, including serum BUN, creatinine, and albumin-creatinine ratio (ACR), were increased in Gdf15 knockout mice as compared to wild-type mice upon PAN treatment. This was associated with an increase in the number of glomerular macrophages, neutrophils, inflammatory cytokines, and chemokines in Gdf15-deficient mice. In summary, our findings unveil a novel renoprotective effect of GDF15 during kidney injury and inflammation by promoting podocyte survival and regulating endoplasmic reticulum stress in podocytes, and, subsequently, the infiltration of inflammatory cells via paracrine effects on surrounding glomerular cells.

[Max Reger and his early death: could it have been avoided? : Would he have lived longer with adequate intensive care?] / Max Reger und sein früher Tod: Wäre er vermeidbar gewesen? : Hätte er bei adäquater Intensivtherapie länger gelebt?

BACKGROUND: Max Reger was an organist, university teacher and composer whose life, illnesses, death and dying are not or hardly known to many. OBJECTIVES: Which illnesses determined Reger's life and did his lifestyle and illnesses influence his compositional work? Could his early death have been avoided? From today's point of view, could modern intensive care medicine have helped him? MATERIAL AND METHODS: A detailed analysis of Reger's diseases was performed using scientific databases (medline, pubmed). All published articles were evaluated and examined in detail. RESULTS: Max Reger was born in Brand in 1873 and received early lessons in violin, piano and organ playing. From 1890 he studied at the conservatory in Sondershausen, later at the conservatory in Wiesbaden. In 1901 he moved to Munich, and in 1907 to Leipzig, where he became university director and professor at the conservatory. Four years later he took over the court chapel in Meiningen, but ended this activity again in 1914. A year later he moved to Jena and wrote his late works in the "Jenaish style". Reger suffered from many illnesses, especially bipolar disorder with manic and depressive phases. He had metabolic syndrome with arterial hypertension, was overweight and smoked incredibly heavily. Overeating ("binge eating" syndrome) and polydipsia were other prominent findings. Reger's life was characterized by alcohol abuse, often aggravated by professional and/or human crises. In 1916 Reger died suddenly and unexpectedly in Leipzig of cardiovascular failure. DISCUSSION: Reger was an outstanding personality who left behind an extensive oeuvre. Among the highlights of Max Reger's oeuvre are his chorale fantasies such as on "Ein' feste Burg ist unser Gott" (op. 27) or also the "Fantasia and Fugue on B A C H" (op. 46), but other compositions such as the Mozart Variations (op. 132) and the Clarinet Quintet (op. 146) are also world-famous. His lifestyle certainly favored coronary heart disease, the consequences of which caused Reger's sudden, unexpected and much too early death. Today's modern intensive care medicine could probably have prolonged his life.

Decoding spatiotemporal transcriptional dynamics and epithelial fibroblast crosstalk during gastroesophageal junction development through single cell analysis.

The gastroesophageal squamocolumnar junction (GE-SCJ) is a critical tissue interface between the esophagus and stomach, with significant relevance in the pathophysiology of gastrointestinal diseases. Despite this, the molecular mechanisms underlying GE-SCJ development remain unclear. Using single-cell transcriptomics, organoids, and spatial analysis, we examine the cellular heterogeneity and spatiotemporal dynamics of GE-SCJ development from embryonic to adult mice. We identify distinct transcriptional states and signaling pathways in the epithelial and mesenchymal compartments of the esophagus and stomach during development. Fibroblast-epithelial interactions are mediated by various signaling pathways, including WNT, BMP, TGF-ß, FGF, EGF, and PDGF. Our results suggest that fibroblasts predominantly send FGF and TGF-ß signals to the epithelia, while epithelial cells mainly send PDGF and EGF signals to fibroblasts. We observe differences in the ligands and receptors involved in cell-cell communication between the esophagus and stomach. Our findings provide insights into the molecular mechanisms underlying GE-SCJ development and fibroblast-epithelial crosstalk involved, paving the way to elucidate mechanisms during adaptive metaplasia development and carcinogenesis.

Range of international surgical strategies for adolescent idiopathic scoliosis: Evaluation of a multi-center survey.

Background: Surgical treatment of adolescent idiopathic scoliosis (AIS) is very complex and modern instrumentation techniques offer multiple possibilities. Despite numerous publications, there is no clear consensus on the optimal strategy for the correction of scoliotic deformities. The goal of this study was to summarize the current surgical strategies for specific AIS cases within various countries. Method: Thirty-two experienced scoliosis surgeons from 15 countries were asked to plan surgeries on 12 representative AIS cases. All AIS cases had an indication for surgery. A questionnaire was provided to document surgical planning. The surgeons were provided with the patients' age and sex, together with radiographs in the lateral and sagittal planes during upright standing and in lateral bending to the left and right, as well as with clinical images. The angles of the main spinal curvatures were specified in the questionnaire. The surgeons were asked to specify their preferred classification system, their surgical approach, the planned fusion length, the type of implants, the rod type, and the resection steps. The data were analyzed with respect to the inter-rater variability, which was quantified using the Fleiss-Kappa Method. Results: There was a good agreement (k = 0.61) between the surgeons in choosing the Lenke curve type, and a moderate agreement for the lumbar (0.41) and sagittal (0.56) modifiers. The most frequently planned resection procedure was complete facetectomy (67%). The posterior approach was the most commonly (91%) selected strategy to treat AIS. Anterior approaches were chosen most for Lenke 5 type with a rate of 20%. The upper instrumented vertebra (UIV) varied most for Lenke 1, 5, and 6 cases, with a vertebral level discrepancy of up to 10 levels at Lenke 6. The lowest instrumented vertebra varied most for Lenke 1 and 4 by up to five levels. Polyaxial screws were chosen most (56%), followed by monoaxial (20%) and uniplanar (19%) screws and hooks (5%). Conclusions: The results highlight the commonalities and discrepancy in the surgical treatment of AIS in between surgeons. The selected LIV and UIV can vary depending on the curve type and surgeon. Hook constructs appear to be generally replaced by transpedicular screws. The survey indicates open questions in the AIS treatment and in the understanding of scoliosis biomechanics.

Automatic grading of intervertebral disc degeneration in lumbar dog spines.

Background: Intervertebral disc degeneration is frequent in dogs and can be associated with symptoms and functional impairments. The degree of disc degeneration can be assessed on T2-weighted MRI scans using the Pfirrmann classification scheme, which was developed for the human spine. However, it could also be used to quantify the effectiveness of disc regeneration therapies. We developed and tested a deep learning tool able to automatically score the degree of disc degeneration in dog spines, starting from an existing model designed to process images of human patients. Methods: MRI midsagittal scans of 5991 lumbar discs of dog patients were collected and manually evaluated with the Pfirrmann scheme and a modified scheme with transitional grades. A deep learning model was trained to classify the disc images based on the two schemes and tested by comparing its performance with the model processing human images. Results: The determination of the Pfirrmann grade showed sensitivities higher than 83% for all degeneration grades, except for grade 5, which is rare in dog spines, and high specificities. In comparison, the correspondent human model had slightly higher sensitivities, on average 90% versus 85% for the canine model. The modified scheme with the fractional grades did not show significant advantages with respect to the original Pfirrmann grades. Conclusions: The novel tool was able to accurately and reliably score the severity of disc degeneration in dogs, although with a performance inferior than that of the human model. The tool has potential in the clinical management of disc degeneration in canine patients as well as in longitudinal studies evaluating regenerative therapies in dogs used as animal models of human disorders.

Quality of orthodontic care-A multicenter cohort study in a German convenience sample : Part 2: Cross-sectional patient-reported outcomes after orthodontic treatment.

OBJECTIVES: In light of the growing interest in orthodontic care and its effectiveness in Germany, part 2 of this multicenter cohort study evaluated patient-reported outcomes such as oral health-related quality of life (OHRQoL), oral hygiene habits, oral health beliefs, and potential influencing factors. METHODS: Of 586 patients screened from seven German study centers, data from 343 patients were analyzed for this part of the study. At the end of their orthodontic treatment, study participants filled out a questionnaire of either the German long version of the Oral Health Impact Profile (OHIP-G 49) or the German short version of the Child Oral Health Impact Profile (COHIP-19), depending on their age, as well as questions about their oral hygiene behavior and beliefs. Patient-, treatment- and occlusion-related factors were analyzed to account for potential influencing factors with regard to patients' OHRQoL after orthodontic treatment. RESULTS: In all, 222 study participants filled out the OHIP-based and 121 the COHIP-based questionnaire. The mean OHIP-G 49 score was 12.68 and the mean OHIP-G 14 score was 3.09; the mean COHIP-19 score was 6.52 (inverted score 69.48). For OHIP-G 49 scores, a nonsignificant trend towards a higher score for male patients (14.45 vs 11.54; p = 0.061) was detected, while this trend was inverse for the COHIP-19 scores, i.e., female patients reported more impairment (total score 6.99 vs. 5.84; p = 0.099). Analyses suggested a trend towards better OHRQoL for patients who classified for the Peer Assessment Rating (PAR) Index improvement rate group 'greatly improved' as well as for nonsmokers. Oral hygiene habits and beliefs after orthodontic treatment were estimated to be good. CONCLUSION: In this German cohort, OHRQoL proved to be good and was rather unimpaired after orthodontic treatment. Furthermore, self-reported oral hygiene behavior and oral health beliefs represented good health awareness.

Gasdermin D drives focal Crystalline Thrombotic Microangiopathy by accelerating Immunothrombosis and Necroinflammation.

Thrombotic microangiopathy (TMA) is characterized by immunothrombosis and life-threatening organ failure, but the precise underlying mechanism driving its pathogenesis remains elusive. In this study, we hypothesized that gasdermin D (GSDMD), a pore-forming protein serving as the final downstream effector of pyroptosis/interleukin (IL)-1pathway, contributes to TMA and its consequences by amplifying neutrophil maturation and subsequent necrosis. Using a murine model of focal crystalline TMA, we found that Gsdmd-deficiency ameliorated immunothrombosis, acute tissue injury and failure. Gsdmd-/- mice exhibited a decrease in mature IL-1, as well as in neutrophil maturation, 2 integrin activation, and recruitment to TMA lesions, where they formed reduced neutrophil extracellular traps both in arteries and interstitial tissue. The GSDMD inhibitor disulfiram dose-dependently suppressed human neutrophil pyroptosis in response to cholesterol crystals. Experiments with GSDMD-deficient human induced pluripotent stem cell-derived neutrophils confirmed the involvement of GSDMD in neutrophil 2 integrin activation, maturation as well as pyroptosis. Both prophylactic and therapeutic administration of disulfiram protected mice from focal TMA, acute tissue injury and failure. Our data identify GSDMD as a key mediator of focal crystalline TMA and its consequences: ischemic tissue infarction and organ failure. GSDMD could potentially serve as a therapeutic target for systemic forms of TMA.