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The International Society of Differentiation was born from the First International Conference on Cell Differentiation conceived by D.V. and held in Nice, France in 1971. The conference also resulted in the creation of the journal of the Society named Differentiation. The Society advocates for the field of differentiation through the journal Differentiation, organizing and supporting international scientific conferences, honoring scientific achievements, and supporting trainees.

Aims Quality of care (QoC) is a fundamental tenet of modern healthcare and has become an important assessment tool for healthcare authorities, stakeholders and the public. However, QoC is difficult to measure and quantify because it is a multifactorial and multidimensional concept. Comparison of clinical institutions can be challenging when QoC is estimated solely based on clinical outcomes. Thus, measuring quality through quality indicators (QIs) can provide a foundation for quality assessment and has become widely used in this context. QIs for the evaluation of QoC in acute myocardial infarction are now well-established, but no such indicators exist for the process from resuscitation of cardiac arrest and post-resuscitation care in Europe. Methods and results The Association of Acute Cardiovascular Care of the European Society Cardiology, the European Resuscitation Council, European Society of Intensive Care Medicine and the European Society for Emergency Medicine, have reflected on the measurement of QoC in cardiac arrest. A set of QIs have been proposed, with the scope to unify and evolve QoC for the management of cardiac arrest across Europe. Conclusion We present here the list of QIs (6 primary QIs and 12 secondary Qis), with descriptions of the methodology used, scientific justification and motives for the choice for each measure with the aim that this set of QIs will enable assessment of the quality of postout-of-hospital cardiac arrest management across Europe.

This scoping review aims to provide a comprehensive overview of biological mechanisms underlying the menstrual cycle’s impact on various performance-determining anatomical and physiological parameters. It is intended to identify the various proposed vital concepts and theories that may explain performance changes following hormonal fluctuations. The review was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews protocol. A framework of six groups was built such as skeletal muscle physiology, muscle damage, tendons and ligaments, neuromuscular control, cardiovascular system, and exercise metabolism to cluster studies thematically and to specify the concept of “performance.” Original research studies published between 1970 and 2021 that were conducted with a naturally menstruating population were considered. Changes in performance regarding the menstrual cycle phase were crucial for inclusion. Topic-specific reviews and systematic reviews were included if they addressed the impact of female steroid hormones on any structure or part of the human body. The review indicates that the impact of estrogen and progesterone is primarily responsible for observed changes in athletic performance during the menstrual cycle. Estrogen seems capable of fostering protein synthesis, diminishing collagen metabolism, preventing muscle damage due to its antioxidant effects, and restraining inhibitory, while promoting excitatory, control by interacting with neurotransmitters. Progesterone is assumed to increase thermoregulation and enhance ventilatory drive by interacting with hypothalamic pathways and may further amplify inhibitory control by interacting with neurotransmitters. The female steroid hormones and the endocrinologic system collaborate in complex interrelationships with biological systems to maintain homeostasis. However, proposed mechanisms are often derived from animal studies and studies conducted in vitro and still remain to be proven true in the human regularly menstruating population. In the future, it is crucial to rely on studies that followed the methodology for cycle monitoring recommendations thoroughly. Otherwise, it is not possible to determine whether hormonal fluctuations cause observed changes in performance or not.

Zusammenfassung Die hochmobile und stark persistente Trifluoressigsäure (TFA) ist ein Abbauprodukt vieler fluorierter Kohlenwasserstoffe, die insbesondere als Kältemittel eingesetzt werden. TFA reichert sich als Trifluoracetat in steigender Konzentration in Grund- und Trinkwasser an. Da mögliche negative Folgen einer dauerhaften Exposition zunehmender Mengen an Trifluoracetat für Mensch und Umwelt nicht hinreichend bekannt sind, sollte der Einsatz TFA-bildender Kohlenwasserstoffe umgehend unterbunden werden.

Anti-CD38 monoclonal antibodies have consistently shown increased efficacy when added to standard of care for patients with multiple myeloma. We aimed to assess the efficacy of isatuximab in addition to lenalidomide, bortezomib, and dexamethasone in patients with newly diagnosed transplantation-eligible multiple myeloma.This open-label, multicentre, randomised, active-controlled, phase 3 trial was done at 67 academic and oncology practice centres in Germany. This study is ongoing and divided into two parts; herein, we report results from part 1. Eligible patients were aged 18-70 years; had a confirmed diagnosis of untreated multiple myeloma requiring systemic treatment and a WHO performance status of 0-2; and were eligible for induction therapy, high-dose melphalan and autologous haematopoietic stem-cell transplantation, and maintenance treatment. Patients were randomly assigned (1:1) to receive three 42-day cycles of induction therapy either with isatuximab plus lenalidomide, bortezomib, and dexamethasone (isatuximab group) or lenalidomide, bortezomib, and dexamethasone alone (control group) using a web-based system and permuted blocks. Patients in both groups received lenalidomide (25 mg orally on days 1-14 and 22-35), bortezomib (1·3 mg/mBetween Oct 23, 2018, and Sep 22, 2020, 660 patients were included in the ITT analysis (331 in the isatuximab group and 329 in the control group). 654 (99%) patients were White, two were African, one was Arabic, and three were Asian. 250 (38%) were women and 410 (62%) were men. The median age was 59 years (IQR 54-64). MRD negativity after induction therapy was reached in 166 (50%) patients in the isatuximab group versus 117 (36%) in the control group (OR 1·82 [95% CI 1·33-2·48]; p=0·00017). Median follow-up time from start to end of induction therapy was 125 days (IQR 125-131) versus 125 days (125-132). At least one grade 3 or 4 adverse event occurred in 208 (63%) of 330 patients versus 199 (61%) of 328 patients. Neutropenia of grade 3 or 4 occurred in 77 (23%) versus 23 (7%) patients and infections of grade 3 or 4 occurred in 40 (12%) versus 32 (10%) patients. Among 12 deaths during induction therapy, one death due to septic shock in the isatuximab group and four deaths (one cardiac decompensation, one hepatic and renal failure, one cardiac arrest, and one drug-induced enteritis) in the control group were considered treatment-related.Addition of isatuximab to lenalidomide, bortezomib, and dexamethasone for induction therapy improved rates of MRD negativity with no new safety signals in patients with newly diagnosed transplantation-eligible multiple myeloma.Sanofi and Bristol Myers Squibb (Celgene).

This study investigated the effects of a relatively high- versus moderate-volume resistance training program on changes in lean mass during caloric restriction. Thirty-eight resistance-trained males were randomized to perform either a high-volume (HVG; 5 sets/exercise) or a moderate-volume (MVG; 3 sets/exercise) resistance training program. Both groups were supervised during lower body training. Participants consumed 30 kcal/kg for 6 weeks after 1 week of weight maintenance (45 kcal/kg), with protein intake fixed at 2.8 g/kg fat-free mass. Muscle thickness of the m. rectus femoris, body composition, contractile properties, stiffness, mood, and sleep status were assessed at pre-, mid-, and post-study. No significant group × time interaction was observed for muscle thickness of the m. rectus femoris at 50% (∆ [post-pre] 0.36 ± 0.93 mm vs. ∆ -0.01 ± 1.59 mm; p = 0.226) and 75% length (∆ -0.32 ± 1.12 mm vs. ∆ 0.08 ± 1.14 mm; p = 0.151), contractility, sleep, and mood in the HVG and MVG, respectively. Body mass (HVG: ∆ -1.69 ± 1.12 kg vs. MVG: ∆ -1.76 ± 1.76 kg) and lean mass (∆ -0.51 ± 2.30 kg vs. ∆ -0.92 ± 1.59 kg) decreased significantly in both groups (p = 0.022), with no between-group difference detected (p = 0.966). High-volume resistance training appears to have neither an advantage nor disadvantage over moderate-volume resistance training in terms of maintaining lean mass or muscle thickness. Given that both groups increased volume load and maintained muscle contractility, sleep quality, and mood, either moderate or higher training volumes conceivably can be employed by resistance-trained individuals to preserve muscle during periods of moderate caloric restriction.

Advanced airway management (AAM) is part of the standard treatment during advanced cardiac life support (ACLS). Current studies underline the importance of a first-pass intubation success (FPS) during in-hospital ACLS. It was shown that a failed initial intubation attempt in out-of-hospital cardiac arrest (OHCA) patients in the emergency department is an independent risk factor for the decreased effectiveness of ACLS measured by the return of spontaneous circulation (ROSC).This study first examines the association between prehospital FPS and ROSC in adults with OHCA and second identifies factors associated with FPS and ROSC. The initial hypothesis was that FPS would increase the probability of ROSC as well as decrease the time to ROSC.A retrospective multicenter analysis of 180 adult non-traumatic OHCA patients on whom advanced airway management (AAM) was performed between July 2017 and December 2018 in five different German physician-staffed ambulance stations. For information on FPS the Intubation Registry, and for information on ROSC the German Resuscitation Registry were used. In addition to yes/no questions, multiple answers and free text answers are possible in those questionnaires. The main outcome variables were 'FPS', 'ROSC' and 'time to ROSC'. Mann-Whitney tests, χAn FPS was recorded in 150 patients (83.3%), and ROSC was achieved in 82 patients (45.5%) after an average time of 22.16 min. There was a positive association between FPS and ROSC (p = 0.027). In patients with FPS, a trend for shorter time to ROSC was observed (p = 0.059; FPS 18 min; no FPS 28 min). The use of capnography (odds ratio, OR = 7.384, 95% confidence interval, CI 1.886-28.917) and complications during AAM (OR = 0.033, 95% CI: 0.007-0.153) were independently associated with FPS. The independent factor associated with ROSC was FPS (OR = 5.281, 95% CI: 1.800-15.494).In prehospitally resuscitated adult OHCA patients with AAM, FPS is associated with a higher chance of ROSC.HINTERGRUND: Das erweiterte Atemwegsmanagement (AAM) ist Teil der Standardbehandlung bei erweiterten Reanimationsmaßnahmen (ACLS). Aktuelle Studien betonen die Relevanz eines erfolgreichen ersten Intubationsversuches (FPS) während ACLS. Bei Patienten mit außerklinischem Herz-Kreislauf-Stillstand (OHCA) erwies sich ein fehlgeschlagener erster Intubationsversuch als unabhängiger Risikofaktor für die verminderte Wirksamkeit des ACLS – gemessen am Wiedereinsetzen des Spontankreislaufs (ROSC).Diese Studie untersucht den präklinischen Zusammenhang zwischen dem FPS und ROSC bei Erwachsenen mit OHCA. Die initiale Hypothese war, dass bei erzieltem FPS die Wahrscheinlichkeit des ROSC steigt und sich die Zeit bis zum ROSC verringert.Eine retrospektive multizentrische Analyse von 180 erwachsenen Patienten mit nichttraumatischem OHCA, bei denen zwischen Juli 2017 und Dezember 2018 in fünf verschiedenen deutschen ärztlich besetzten Rettungswachen ein AAM durchgeführt wurde. Für Informationen zum FPS wurde das Intubationsregister und für Informationen zum ROSC das Deutsche Reanimationsregister verwendet. Neben Ja/Nein-Fragen sind in diesen Fragebögen auch Mehrfachantworten und Freitextantworten möglich. Die wichtigsten Ergebnisvariablen waren „FPS“, „ROSC“ und „Zeit bis zum ROSC“. Für die statistische Auswertung wurden Mann-Whitney-Tests, χBei 150 Patienten (83,3 %) wurde ein FPS, bei 82 Patienten (45,5 %) ein ROSC beobachtet. Beide Variablen standen korrelierten positiv miteinander (p = 0,027). Bei erzieltem FPS verringerte sich die Zeit bis zum ROSC (p = 0,059; FPS 18 min; kein FPS 28 min). Der FPS wurde als unabhängige Variable für den ROSC (OR = 5,281; 95 % KI 1,800–15,494) identifiziert.Bei präklinisch wiederbelebten OHCA-Patienten mit AAM ist der FPS mit einer höheren ROSC-Wahrscheinlichkeit assoziiert.

This article examines US military reactions to violence during the Russian Civil War in the Far East (1918 - 1922). Paying close attention to US descriptions of anti-Bolshevik-perpetrated atrocities, it demonstrates that American military officers fell back on stereotypes of Russians and other ethnicities as having an “Asiatic” propensity for barbarism. This reasoning caused some American observers to misunderstand the dynamics of violence in the Far Eastern theatre. By relying on these accounts to describe the violence of the Russian Civil War, historians of the US intervention have at times perpetuated myths and misunderstandings, rather than exploring the relationship between perceptions and violence. This article thus shows how a critical examination of primary sources that also analyses various forms of violence can improve our understanding of the Russian Civil War in the Far East.

Two factors are crucial for the effective operation of modern-day smart services: Initially, IoT-enabled technologies have to capture and combine huge amounts of data on data subjects. Then, all these data have to be processed exhaustively by means of techniques from the area of big data analytics. With regard to the latter, thorough data refinement in terms of data cleansing and data transformation is the decisive cornerstone. Studies show that data refinement reaches its full potential only by involving domain experts in the process. However, this means that these experts need full insight into the data in order to be able to identify and resolve any issues therein, e.g., by correcting or removing inaccurate, incorrect, or irrelevant data records. In particular for sensitive data (e.g., private data or confidential data), this poses a problem, since these data are thereby disclosed to third parties such as domain experts. To this end, we introduce SMARTEN, a sample-based approach towards privacy-friendly data refinement to smarten up big data analytics and smart services. SMARTEN applies a revised data refinement process that fully involves domain experts in data pre-processing but does not expose any sensitive data to them or any other third-party. To achieve this, domain experts obtain a representative sample of the entire data set that meets all privacy policies and confidentiality guidelines. Based on this sample, domain experts define data cleaning and transformation steps. Subsequently, these steps are converted into executable data refinement rules and applied to the entire data set. Domain experts can request further samples and define further rules until the data quality required for the intended use case is reached. Evaluation results confirm that our approach is effective in terms of both data quality and data privacy.

Many marine habitats are at risk due to increasing frequency, intensity, and persistence of harmful algal blooms. Repeated cyanobacterial harmful algal blooms (cyanoHABs) in Florida Bay, USA, kill sponges, resulting in reduced filtration and loss of shelter for benthic species. The loss of these key ecosystem functions can impact disease dynamics if fewer pathogens are filtered from the water column (dilution), if shelter loss increases host density in remaining shelters and a directly transmitted disease is present (host regulation), or if shelter loss changes species distributions and foraging patterns (trophic exposure). We show persistent impacts to hard-bottom communities relative to non-impacted communities 2 yr after a significant cyanoHAB. We compared benthic structure, invertebrate epibenthic/infaunal community composition, and parasitism among macroinvertebrates, stone crab Menippe mercenaria, and Caribbean spiny lobster Panulirus argus. On sites degraded by cyanoHABs, we found more, smaller sponges, indicating regrowth. Despite this evidence of recovery, epibenthic/infaunal invertebrate communities were distinct and more diverse on unimpacted sites. Additionally, there were fewer, smaller bivalves on impacted sites. The bivalve Tucetona pectinata, prey for stone crabs, was nearly absent on impacted sites, resulting in decreased prevalence of the apicomplexan gregarine Nematopsis sp., which is trophically transmitted from T. pectinata to M. mercenaria. Panulirus argus virus 1 also appears to be affected by cyanoHABs, as it was absent on impacted sites but present in 26.5% of spiny lobster on unimpacted sites. Impacts remain evident 2 yr after significant cyanoHABs, which does not bode well for these areas considering the frequent reoccurrence of blooms.

Background: The inappropriate usage of terms and concepts and/or unclear definitions provided in the scientific literature hinder progress in any scientific field. This risk is especially noticeable in applied fields of research such as sports science and physical education. Objective: This study explored existing literature that uses the term ‘motor performance skills’ and aimed to propose a comprehensive definition to be applied in future research. Method: Following an adapted scoping approach grounded in the rapid review model, we searched electronic databases Pub-Med/Medline, Web of Science, and Scopus until February 2022. The primary demographic focus was sports science and physical education disciplines. After screening of titles and abstracts, 184 papers were identified for a full review. Twenty-two papers met the inclusion criteria from the full review and received qualitative content analysis. The qualitative content analysis focused on the elaborated qualities of the term ‘motor performance skill’. Coding was used to identify and extract content, identify patterns, and observe the depth of interpretation of the term. Results: Only six papers used descriptive language, and three used explanatory language to convey aspects of the term’s meaning. All included papers extrapolated or provided examples to demonstrate the term’s meaning. Based on a collaborative process, the study reached a proposed definition that has the potential to be coined for the term ‘motor performance skills’ and used in future research. Conclusion: Thus, the current analysis revealed the need to collaboratively address the conceptual ambiguity and develop a comprehensive definition of ‘motor performance skills’

Blood-based biomarkers can provide an objective individualized measure of training load, recovery, and health status in order to reduce injury risk and maximize performance. Despite enormous potentials, especially owing to currently evolving technology, such as point-of-care testing, and advantages, in terms of objectivity and non-interference with the training process, there are several pitfalls in the use and interpretation of biomarkers. Confounding variables such as preanalytical conditions, inter-individual differences, or an individual chronic workload can lead to variance in resting levels. In addition, statistical considerations such as the detection of meaningful minimal changes are often neglected. The lack of generally applicable and individual reference levels further complicates the interpretation of level changes and thus load management via biomarkers. Here, the potentials and pitfalls of blood-based biomarkers are described, followed by an overview of established biomarkers currently used to support workload management. Creatine kinase is discussed in terms of its evidence for workload management to illustrate the limited applicability of established markers for workload management to date. We conclude with recommendations for best practices in the use and interpretation of biomarkers in a sport-specific context.

As environmental changes exacerbate the threat coming from infectious diseases in wild mammal species, monitoring their health and gaining a better understanding of the immune functioning at the species level have become critically important. Neopterin is a biomarker of cell-mediated immune responses to intracellular infections. We investigated the variation of urinary neopterin (uNeo) levels of wild, habituated bonobos (Pan paniscus) in relation to individual and environmental factors. We used 309 urine samples collected between 2010 and 2018 at the LuiKotale field site, DRC. Based on current knowledge on zoo-housed conspecifics and closely related species, we predicted uNeo levels to increase (1) during infections, (2) with increasing age, (3) over the gestation period and in estrous females; and (4) to vary seasonally. Our results showed uNeo levels varied over a one-year period and increased in individuals showing respiratory symptoms. Contrary to chimpanzees, uNeo levels did not vary with age or female reproductive status, possibly due to our small sample size. Our study provides a baseline for a better understanding of bonobo’s immunocompetence in the context of socio-ecological pressures and for monitoring the health of wild populations.

Alluvial forests in the temperate zone of Europe are frequently changing drastically in their hydrological regime, vegetation composition and structure, and disturbance dynamics. Causes are river regulations, historic land use, recent forest management, and introduced species such as Solidago canadensis agg. or the pathogenic fungus Hymenoscyphus fraxineus causing ash dieback. Climate change increases the scale of these changes. As a result, like in the present case study, pre-mature stands dominated by Pica abies or Fraxinus excelsior have to be clearcut. In order to achieve a tree species composition which is adapted to the altered site conditions and still economically desirable, tree planting in a larger scale is inevitable. To control competing vegetation (e.g., Solidago, Clematis, Rubus…), site preparation (mulching and tilling of planting strips) was deemed to be necessary but is discussed controversially. Effects of site preparation on indicators for soil functions were compared for the two dominating soil types, Fluvisols and Rendzic Leptosols, using a chronosequence approach. The following key results were obtained: (1) Soil type has a significant effect upon most indicators. (2) Areas treated ≥5 years ago have a significantly higher bulk density (and thus, despite partly decreased C-concentration, higher C-stocks) in the 20 cm topsoil indicating compaction. (3) Tilling strips significantly impact anecic earthworm abundance (+) compared to areas only mulched. (4) Effects of site preparation on organic C concentration (-), C/N-ratio (-), ratio of microbial to organic carbon (+), abundance of anecic earthworms (+) and hydraulic conductivity estimated from pedotransfer functions (-) were mainly significant for Rendzic Leptosols. This may reflect the mobilization of accumulated forest floor, which was present in mature spruce stands on Rendzic Leptosols but not on Fluvisols. (5) The ground vegetation shows an expected response to clearing (increased cover of light demanding species including Solidago canadensis agg.). Effects of site preparation could not be separated from clearing effects. (6) Nitrate concentrations in seepage are below drinking water standards and show no clear treatment effect, though highest values were found in declining spruce stands on Leptosols.

Alzheimer’s disease (AD) is the most prevalent form of dementia and currently impacts ~50 million people worldwide. AD is associated with impaired cerebrovascular function which underscores diminished delivery of blood oxygen and nutrients to and throughout the brain. Thus, we hypothesized that cerebrovascular miRNAs indicate early onset of AD pathology while corresponding to pathways of cerebrovascular growth, structure, and function. Total RNA was isolated from brain vessels of 3xTg-AD mice [Young, 1-2 mo; cognitive impairment (CI), 4-5 mo; extracellular amyloid-β plaques (Aβ), 6-8 mo; plaques + neurofibrillary tangles (AβT), 12-15 mo; n=3 males & 3 females per group]. Fifty-four cerebrovascular miRNAs detected by NanoString technology (nCounter miRNA Expression panel) were mapped to their known mRNA targets using Ingenuity Pathway Analysis. With the premise that AD is a neurovascular disorder, we sought mRNA targets along both the canonical Cardiovascular (Cardio; 15±2 targets per miRNA) and Nervous System (Neuro; 19±2 targets per miRNA) signaling strings with an overlap of 9±1 targets per miRNA among respective pathways. We found that eleven miRNAs were significantly ( p NIH Grants: R00AG047198, R56AG062169 & R01AG073230 (EJB). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Background Through the evolution of novel wing structures, bats (Order Chiroptera) became the only mammalian group to achieve powered flight. This achievement preceded the massive adaptive radiation of bats into diverse ecological niches. We investigate some of the developmental processes that underlie the origin and subsequent diversification of one of the novel membranes of the bat wing: the plagiopatagium, which connects the fore- and hind limb in all bat species. Results Our results suggest that the plagiopatagium initially arises through novel outgrowths from the body flank that subsequently merge with the limbs to generate the wing airfoil. Our findings further suggest that this merging process, which is highly conserved across bats, occurs through modulation of the programs controlling the development of the periderm of the epidermal epithelium. Finally, our results suggest that the shape of the plagiopatagium begins to diversify in bats only after this merging has occurred. Conclusions This study demonstrates how focusing on the evolution of cellular processes can inform an understanding of the developmental factors shaping the evolution of novel, highly adaptive structures.

Purpose To determine potential quadriceps versus hamstring tendon autograft differences in neuromuscular function and return to sport (RTS)-success in participants after an anterior cruciate ligament (ACL) reconstruction. Methods Case–control study on 25 participants operated on with an arthroscopically assisted, anatomic ipsilateral quadriceps femoris tendon graft and two control groups of 25 participants each, operated on with a semitendinosus tendon or semitendinosus-gracilis (hamstring) tendon graft ACL reconstruction. Participants of the two control groups were propensity score matched to the case group based on sex, age, Tegner activity scale and either the total volume of rehabilitation since reconstruction (n = 25) or the time since reconstruction (n = 25). At the end of the rehabilitation (averagely 8 months post-reconstruction), self-reported knee function (KOOS sum scores), fear of loading the reconstructed knee during a sporting activity (RSI-ACL questionnaire), and fear of movement (Tampa scale of kinesiophobia) were followed by hop and jump tests. Front hops for distance (jumping distance as the outcome) were followed by Drop jumps (normalised knee joint separation distance), and concluded by qualitative ratings of the Balanced front and side hops. Between-group comparisons were undertaken using 95% confidence intervals comparisons, effect sizes were calculated. Results The quadriceps case group (always compared with the rehabilitation-matched hamstring graft controls first and versus time-matched hamstring graft controls second) had non-significant and only marginal higher self-reported issues during sporting activities: Cohen’s d = 0.42, d = 0.44, lower confidence for RTS (d = − 0.30, d = − 0.16), and less kinesiophobia (d = − 0.25, d = 0.32). Small and once more non-significant effect sizes point towards lower values in the quadriceps graft groups in the Front hop for distance limb symmetry values in comparison to the two hamstring control groups (d = − 0.24, d = − 0.35). The normalised knee joint separation distance were non-significantly and small effect sized higher in the quadriceps than in the hamstring groups (d = 0.31, d = 0.28). Conclusion Only non-significant and marginal between-graft differences in the functional outcomes at the end of the rehabilitation occurred. The selection of either a hamstring or a quadriceps graft type cannot be recommended based on the results. The decision must be undertaken individually. Level of evidence III.

Echinoderm mass mortality events shape marine ecosystems by altering the dynamics among major benthic groups. The sea urchin Diadema antillarum , virtually extirpated in the Caribbean in the early 1980s by an unknown cause, recently experienced another mass mortality beginning in January 2022. We investigated the cause of this mass mortality event through combined molecular biological and veterinary pathologic approaches comparing grossly normal and abnormal animals collected from 23 sites, representing locations that were either affected or unaffected at the time of sampling. Here, we report that a scuticociliate most similar to Philaster apodigitiformis was consistently associated with abnormal urchins at affected sites but was absent from unaffected sites. Experimentally challenging naïve urchins with a Philaster culture isolated from an abnormal, field-collected specimen resulted in gross signs consistent with those of the mortality event. The same ciliate was recovered from treated specimens postmortem, thus fulfilling Koch’s postulates for this microorganism. We term this condition D. antillarum scuticociliatosis.

Supplementary Table 1 from Misregulated Wnt/β-Catenin Signaling Leads to Ovarian Granulosa Cell Tumor Development

Misregulation of the Wnt/β-catenin signaling pathway is a hallmark of several forms of cancer. Components of the Wnt/β-catenin pathway are expressed in ovarian granulosa cells; nevertheless, its potential involvement in granulosa cell tumorigenesis has not been examined. To this end, human (n = 6) and equine (n = 18) granulosa cell tumors (GCT) were analyzed for β-catenin expression by immunohistochemistry. Unlike granulosa cells of normal ovaries, most (15 of 24) GCT samples showed nuclear localization of β-catenin, suggesting that activation of the Wnt/β-catenin pathway plays a role in the etiology of GCT. To confirm this hypothesis, Catnbflox(ex3)/+; Amhr2cre/+ mice that express a dominant stable β-catenin mutant in their granulosa cells were generated. These mice developed follicle-like structures containing disorganized, pleiomorphic granulosa by 6 weeks of age. Even in older mice, these follicle-like lesions grew no larger than the size of antral follicles and contained very few proliferating cells. Similar to corpora lutea, the lesions were highly vascularized, although they did not express the luteinization marker Cyp11a1. Catnbflox(ex3)/+; Amhr2cre/+ females were also found to be severely subfertile, and fewer corpora lutea were found to form in response to exogenous gonadotropin compared with control mice. In older mice, the ovarian lesions often evolved into GCT, indicating that they represent a pretumoral intermediate stage. The GCT in Catnbflox(ex3)/+; Amhr2cre/+ mice featured many histopathologic similarities to the human disease, and prevalence of tumor development attained 57% at 7.5 months of age. Together, these studies show a causal link between misregulated Wnt/β-catenin signaling and GCT development and provide a novel model system for the study of GCT biology.

PDF file - 249K, Expression of PR protein and its target genes in Wnt7acre+ Mig-6f/f mice after P4 treatment.

PDF file - 250K, Steroid hormone regulation of epithelial Mig-6 in the murine uterus.

Supplementary Figure Legend from Misregulated Wnt/β-Catenin Signaling Leads to Ovarian Granulosa Cell Tumor Development

Supplementary Figure 1 from Misregulated Wnt/β-Catenin Signaling Leads to Ovarian Granulosa Cell Tumor Development

Endometrial cancer is preceded by endometrial hyperplasia, unopposed estrogen exposure, and genetic alterations, but the precise causes of endometrial cancer remain uncertain. Mig-6, mainly known as a negative regulator of the EGF receptor, is an important mediator of progesterone signaling in the uterus, where it mediates tumor suppression by modulating endometrial stromal–epithelial communications. In this study, we investigated the function of Mig-6 in the uterine epithelium using a tissue-specific gene knockout strategy, in which floxed Mig-6 (Mig-6f/f) mice were crossed to Wnt7a-Cre mice (Wnt7acre+Mig-6f/f). Wnt7acre+Mig-6f/f mice developed endometrial hyperplasia and estrogen-dependent endometrial cancer, exhibiting increased proliferation in epithelial cells as well as apoptosis in subepithelial stromal cells. We documented increased expression of NOTCH1 and BIRC3 in epithelial cells of Wnt7acre+Mig-6f/f mice and decreased expression of the progesterone receptor (PR) in stromal cells. Progesterone therapy controls endometrial growth and prevents endometrial cancer, but the effectiveness of progesterone as a treatment for women with endometrial cancer is less clear. We noted that the hyperplasic phenotype of Wnt7acre+Mig-6f/f mice was prevented by progesterone treatment, whereas this treatment had no effect in PRcre/+Mig-6f/f mice where Mig-6 was deleted in both the epithelial and stromal compartments of the uterus. In contrast, activation of progesterone signaling in the stroma regulated proliferation and apoptosis in the epithelium via suppression of ERα signaling. In summary, our results establish that epithelial Mig-6 functions as a critical tumor suppressor that mediates the ability of progesterone to prevent the development of endometrial cancer. Cancer Res; 73(16); 5090–9. ©2013 AACR.

Lateral flight membranes, or patagia, have evolved repeatedly in diverse mammalian lineages. While little is known about patagium development, its recurrent evolution may suggest a shared molecular basis. By combining transcriptomics, developmental experiments, and mouse transgenics, we demonstrate that lateral Wnt5a expression in the marsupial sugar glider ( Petaurus breviceps ) promotes the differentiation of its patagium primordium. We further show that this function of Wnt5a reprises ancestral roles in skin morphogenesis predating mammalian flight and has been convergently used during patagium evolution in eutherian bats. Moreover, we find that many genes involved in limb development have been redeployed during patagium outgrowth in both the sugar glider and bat. Together, our findings reveal that deeply conserved genetic toolkits contribute to the evolutionary transition to flight in mammals.

A recent in-vivo experiment has shown that force can be transmitted between the gastrocnemius and the hamstring muscles due to a direct tissue continuity. However, it remains unclear if this mechanical interaction is affected by the stiffness of the structural connection. This study therefore aimed to investigate the impact of the knee angle on myofascial force transmission across the dorsal knee. A randomized, cross-over study was performed, including n = 56 healthy participants (25.36 ± 3.9 years, 25 females). On two separate days, they adopted a prone position on an isokinetic dynamometer (knee extended or 60° flexed). In each condition, the device moved the ankle three times from maximal plantarflexion to maximal dorsal extension. Muscle inactivity was ensured using EMG. High-resolution ultrasound videos of the semimembranosus (SM) and the gastrocnemius medialis (GM) soft tissue were recorded. Maximal horizontal tissue displacement, obtained using cross-correlation, was examined as a surrogate of force transmission. SM tissue displacement was higher at extended (4.83 ± 2.04 mm) than at flexed knees (3.81 ± 2.36 mm). Linear regression demonstrated significant associations between (1) SM and GM soft tissue displacement (extended: R2 = 0.18, p = 0.001; flexed: R2 = 0.17, p = 0.002) as well as (2) SM soft tissue displacement and ankle range of motion (extended: R2 = 0.103, p = 0.017; flexed: R2 = 0.095, p = 0.022). Our results further strengthen the evidence that local stretching induces a force transmission to neighboring muscles. Resulting remote exercise effects such as increased range of motion, seem to depend on the stiffness of the continuity.Trial registration: DRKS (Deutsches Register Klinischer Studien), registration number DRKS00024420, first registered 08/02/2021, https://drks.de/search/de/trial/DRKS00024420.

A dry-air intrusion induced by the tropopause folding split the deep cloud into two layers resulting in a shallow orographic cloud with a supercooled liquid cloud top at around −15°C and an ice cloud above it on 19 January 2017 during the Seeded and Natural Orographic Wintertime Clouds: The Idaho Experiment (SNOWIE). The airborne AgI seeding of this case was simulated by the WRF Weather Modification (WRF-WxMod) Model with different configurations. Simulations at different grid spacing, driven by different reanalysis data, using different model physics were conducted to explore the ability of WRF-WxMod to capture the properties of natural and seeded clouds. The detailed model–observation comparisons show that the simulation driven by ERA5 data, using Thompson–Eidhammer microphysics with 30% of the CCN climatology, best captured the observed cloud structure and supercooled liquid water properties. The ability of the model to correctly capture the wind field was critical for successful simulation of the seeding plume locations. The seeding plume features and ice number concentrations within them from the large-eddy simulations (LES) are in better agreement with observations than non-LES runs mostly due to weaker AgI dispersion associated with the finer grid spacing. Seeding effects on precipitation amount and impacted areas from LES seeding simulations agreed well with radar-derived values. This study shows that WRF-WxMod is able to simulate and quantify observed features of natural and seeded clouds given that critical observations are available to validate the model. Observation-constrained seeding ensemble simulations are proposed to quantify the AgI seeding impacts on wintertime orographic clouds.Significance StatementRecent observational work has demonstrated that the impact of airborne glaciogenic seeding of orographic supercooled liquid clouds is detectable and can be quantified in terms of the extra ground precipitation. This study aims, for the first time, to simulate this seeding impact for one well-observed case. The stakes are high: if the model performs well in this case, then seasonal simulations can be conducted with appropriate configurations after validations against observations, to determine the impact of a seeding program on the seasonal mountain snowpack and runoff, with more fidelity than ever. High–resolution weather simulations inherently carry uncertainty. Within the envelope of this uncertainty, the model compares very well to the field observations.

Zusammenfassung Hintergrund Vorausschauende Versorgungsplanung ist als notwendiger Bestandteil für eine bedürfniszentrierte Betreuung von Patient*innen mit fortgeschrittenen Krebserkrankungen anerkannt. Aufgrund des seit Langem von Pflegepersonal und Ärzt*innen thematisierten Bedarfs in der onkologischen Abteilung wurde das Konzept „Behandlung im Voraus Planen“ (BVP) u. a. wegen der klar strukturierten Vorgehensweise für die Implementierung ausgewählt. Methode Fortgeschrittenen Krebspatient*innen wurde ein BVP-Gespräch angeboten. Der Prozess vom Gesprächsangebot bis zur Erstellung einer BVP-Patientenverfügung (BVP-PV), der weitere gesundheitliche Verlauf und die Adhärenz gegenüber der in der BVP-PV dokumentierten Therapiegrenze wurden dokumentiert. Diskrepanzen zwischen Behandlungswünschen und ärztlicher Indikation wurden analysiert. Ergebnisse Zwischen März 2015 und August 2019 erhielten 230 Patienten ≥ 1 BVP-Gesprächsangebot. 126 Patienten nahmen ≥ 1 Gespräch wahr, 88 BVP-PV wurden erstellt. Zwischen Gesprächsangebot und Erstgespräch lagen im Median 56 Tage, zwischen Fertigstellung der BVP-PV und Erreichen des Endpunkts 107 Tage. Die mediane Erstgesprächsdauer betrug 60 min. Die Wünsche auf Therapieverzicht wurden berücksichtigt. Die Diskrepanz zwischen patientenseitigem Wunsch auf intensivmedizinische Maßnahmen und fehlender ärztlicher Indikation wurde in einigen Fällen nach erneuten ärztlichen Gesprächen angepasst. Diskussion BVP ist ein hilfreiches Instrument für die Wahrnehmung der individuellen Bedürfnisse bei fortgeschrittenen Krebspatient*innen. Es zeigte sich eine hohe Akzeptanz sowohl bei Patient*innen als auch im Behandlungsteam. Der Umgang mit belastenden Emotionen von Beratenden wurde durch abteilungsinterne Fürsorgestrukturen erleichtert. Schlussfolgerung Der routinemäßige Einsatz von BVP erfordert ein einrichtungsweites Umdenken und die Bereitstellung von Ressourcen, die über die vom BVP-Konzept vorgesehenen Instrumente hinausgehen, z. B. für den Umgang mit belastenden Emotionen. Vor dem Hintergrund des in der S3-Leitlinie hinterlegten Bedarfs und Nutzens der vorausschauenden Versorgungsplanung bei Patient*innen mit fortgeschrittenen Krebserkrankungen ist eine angemessene Finanzierung zwingend.

We outline the history, implementation and clinical impact of the formation of an Airway Lead Network. Although recommendations to improve patient safety in airway management are published and revised regularly, uniform implementation of such guidelines are applied sporadically throughout the hospital and prehospital settings. The primary roles of an Airway Lead are to ensure supply, quality and storage of airway equipment, promote the use of current practice guidelines as well as the organisation of training and audits. Locally, the Airway Lead may chair a multi-disciplinary airway committee within their organisation; an Airway Lead Network enables Airway Leads to share common problems and solutions to promote optimal airway management on a national level. Support from governing bodies is an essential part of this structure.

Kelvin–Helmholtz instability (KH) waves have been broadly shown to affect the growth of hydrometeors within a region of falling precipitation, but formation and growth from KH waves at cloud top needs further attention. Here, we present detailed observations of cloud-top KH waves that produced a snow plume that extended to the surface. Airborne transects of cloud radar aligned with range height indicator scans from ground-based precipitation radar track the progression and intensity of the KH wave kinetics and precipitation. In situ cloud probes and surface disdrometer measurements are used to quantify the impact of the snow plume on the composition of an underlying supercooled liquid water (SLW) cloud and the snowfall observed at the surface. KH wavelengths of 1.5 km consisted of ∼750-m-wide up- and downdrafts. A distinct fluctus region appeared as a wave-breaking cloud top where the fastest updraft was observed to exceed 5 m s−1. Relatively weaker updrafts of 0.5–1.5 m s−1 beneath the fluctus and partially overlapping the dendritic growth zone were associated with steep gradients in reflectivity of −5 to 20 dBZe in as little as 500-m depths due to rapid growth of pristine planar ice crystals. The falling snow removed ∼80% of the SLW content from the underlying cloud and led to a twofold increase in surface liquid equivalent snowfall rate from 0.6 to 1.3 mm h−1. This paper presents the first known study of cloud-top KH waves producing snowfall with observations of increased snowfall rates at the surface.

Purpose 3 × 3 is a variation of classic basketball (BB) that imposes new demands on both athletes and coaches. The objective of this study was to comprehensively describe similarities and differences in load structures between 3 × 3 and BB. Method Between January 2020 and July 2021, internal and external load parameters of 90 elite BB and 3 × 3 athletes were monitored during 84 games using a local positioning system (10 Hz) and inertial movement sensors (100 Hz). Results Male BB games last about 90 min; female games are shorter (82 min). Game duration in 3 × 3 is about 16 min. Compared with BB, 3 × 3 athletes perform more medium- and high-intensity accelerations and decelerations, explosive efforts, jumps, and changes of direction (CODs) per min. Average heart rates do not differ between the two disciplines, yet 3 × 3 games are rated as more exhausting than BB games. During a 3 × 3 tournament, no decrease in load characteristics is found in the final games. However, ratings of perceived exertion increase consecutively. Average possession duration in 3 × 3 is 5.4 s in which 1.4 passes are played. Most 2-point shots and turnovers occur in the last minutes (11 min – end) of the game. Conclusion The findings of this study will help 3 × 3 coaches and athletes to design more effective training programmes and improve athletic performance. They indicate a need to focus on high accelerations, transitions, COD skills, and shooting under pressure in 3 × 3.

There is no clarity in the literature on the extent to which the personality and gender factors influence the propensity of individual employees to engage in corruption. This topic is gaining importance not only in theory but also in practice due to increasing scandals and violations of regulations. In this paper, the influence of personality and gender on corruption propensity and corrupt behavior is investigated using an experimental design of 2×2 groups. A study of 134 students from different universities in 2020 served as the sample. It was found that there are significant differences in corruption propensity and corrupt behavior between subjects. The case underlying the experiment involved a company where the subjects of the experiment worked. As a result, they were asked by the CEO of the company to hand over a suitcase of money containing bribes. It was found that women showed a higher degree of conscientiousness than men, but a significantly lower propensity to corruption overall than the male subjects.

Numerous functional factors may interactively contribute to the course of self-report functional abilities after anterior cruciate ligament (ACL)-reconstruction. This study purposes to identify these predictors using exploratory moderation-mediation models in a cohort study design. Adults with post unilateral ACL reconstruction (hamstring graft) status and who were aiming to return to their pre-injury type and level of sport were included. Our dependent variables were self-reported function, as assessed by the the KOOS subscales sport (SPORT), and activities of daily living (ADL). The independent variables assessed were the KOOS subscale pain and the time since reconstruction [days]. All other variables (sociodemographic, injury-, surgery-, rehabilitation-specific, kinesiophobia (Tampa Scale of Kinesiophobia), and the presence or absence of COVID-19-associated restrictions) were further considered as moderators, mediators, or co-variates. Data from 203 participants (mean 26 years, SD 5 years) were finally modelled. Total variance explanation was 59% (KOOS-SPORT) and 47% (KOOS-ADL). In the initial rehabilitation phase (