Search

The advent of QCT (quantitative computed tomography) and AI (artificial intelligence) using high-resolution computed tomography (HRCT) data has revolutionized the way interstitial diseases are studied. These quantitative methods provide more accurate and precise results compared to previous semi-quantitative methods, which were limited by human error such as interobserver disagreement or low reproducibility. The integration of QCT and AI and the development of digital biomarkers has facilitated not only diagnosis but also prognostication and prediction of disease behaviour not just in idiopathic pulmonary fibrosis (IPF) where they were initially studied but also in other fibrotic lung diseases. These tools provide reproducible, objective prognostic information which may facilitate clinical decision-making. However, despite the benefits of QCT and AI, there are still obstacles that need to be addressed. Important issues include optimal data management, data sharing and maintaining data privacy. In addition, the development of explainable AI will be essential to develop trust within the medical community and facilitate implementation in routine clinical practice.

In brief Developing novel therapies to cure and manage endometriosis is a major unmet need that will benefit over 180 million women worldwide. Results from the current study suggest that inhibitors of oxidative phosphorylation may serve as novel agents for the treatment of endometriosis. Abstract Current therapeutic strategies for endometriosis focus on symptom management and are not curative. Here, we provide evidence supporting the inhibition of oxidative phosphorylation (OXPHOS) as a novel treatment strategy for endometriosis. Additionally, we report an organotypic organ-on-a-chip luminal model for endometriosis. The OXPHOS inhibitors, curcumin, plumbagin, and the FDA-approved anti-malarial agent, atovaquone, were tested against the endometriosis cell line, 12Z, in conventional as well as the new organotypic model. The results suggest that all three compounds inhibit proliferation and cause cell death of the endometriotic cells by inhibiting OXPHOS and causing an increase in intracellular oxygen radicals. The oxidative stress mediated by curcumin, plumbagin, and atovaquone causes DNA double-strand breaks as indicated by the elevation of phospho-γH2Ax. Mitochondrial energetics shows a significant decrease in oxygen consumption in 12Z cells. These experiments also highlight differences in the mechanism of action as curcumin and plumbagin inhibit complex I whereas atovaquone blocks complexes I, II, and III. Real-time assessment of cells in the lumen model showed inhibition of migration in response to the test compounds. Additionally, using two-photon lifetime imaging, we demonstrate that the 12Z cells in the lumen show decreased redox ratio (NAD(P)H/FAD) and lower fluorescence lifetime of NAD(P)H in the treated cells confirming major metabolic changes in response to inhibition of mitochondrial electron transport. The robust chemotoxic responses observed with atovaquone suggest that this anti-malarial agent may be repurposed for the effective treatment of endometriosis.

ObjectiveThe use of chemoradiation in patients with stage IVB cancer of the cervix was evaluated to determine if definitive treatment offers benefit.MethodsA database of 546 patients with cancer of the cervix treated between January 2005 and May 2021 at a tertiary academic medical center was reviewed retrospectively to identify patients with stage IVB disease. Log rank test, regression analysis, and the Kaplan–Meier method were used to identify and compare variables and estimate progression free survival and overall survival.ResultsThirty-three patients with stage IVB cervical cancer were identified. Median age was 53 years (range 28–78). Pathology subtypes were squamous cell (n=22, 67%), adenocarcinoma (n=8, 24%), and clear cell (n=3, 9%). Metastases were classified as lymphatic (n=14, 42%) or hematogenous (n=19, 58%). Following treatment to all sites with chemoradiotherapy and selected use of surgery (n=23), six patients (26%, lymphatic n=4, hematogenous n=2) remained disease free for a median duration of 4 years (range 3–17 years). Recurrences in the remaining patients were distant (n=13) or local (n=4). All patients in the chemotherapy group (n=10, 100%) progressed. Kaplan–Meier analysis showed that median progression free survival was longer for patients treated at all disease sites than for patients treated with chemotherapy alone (19 vs 11 months, p=0.01). However, this was not the case for overall survival (49 vs 33 months, p=0.15). Patients with metastases limited to lymph nodes also had longer median progression free survival (22 vs 11 months, p=0.04) but not overall survival (p=0.68).ConclusionsPatients with stage IVB cancer of the cervix may benefit from treatment to all sites of disease, if feasible and safe, as demonstrated by improved progression free survival.

Spillover effects are considered important in evaluating the impacts of food, energy and water (FEW) conservation behaviors for limiting global greenhouse gas emissions and climate change. Failure to account for all possible spillovers, or indirect and unintended results of an intervention, not only obscures valuable information pertaining to the dynamic interactions across domains but also results in biased estimates. In this study, we first systematically reviewed articles that investigate the idea that the performance of one pro-environmental behavior influences the conduct of subsequent behaviors(s) from the FEW domains. From our review of 48 studies in the last decade, we note that a big part of the discussion on spillover concerns the nature and direction of causal relationships between individual FEW conservation behaviors. We identify a critical gap in the literature regarding the distinction between spillover effects caused by the interventions as distinct from those caused by the primary behaviors. Next, we conducted a quantitative meta-analysis of the reviewed empirical studies to find a modest but overall positive spillover effect. Finally, we reviewed the theoretical and methodological plurality in the FEW spillover literature using a systemic thinking lens to summarize what is already known and identify future challenges and research opportunities with significant policy implications.

Poor prenatal sleep quality is associated with increased risk for depressive symptoms but may go undetected in brief, busy prenatal care visits. Among non-depressed pregnant participants, we evaluated whether 1) the endorsement of sleep disturbance on a depression questionnaire predicted postpartum depressive symptoms, 2) the strength of these associations was higher than other somatic symptoms of pregnancy and depression (i.e., fatigue, appetite disturbance), and 3) the endorsement of prenatal sleep disturbance varied by participant characteristics. In this retrospective cohort study, participants had a live birth and completed Patient Health Questionnaire (PHQ-9) during pregnancy and within 8 weeks postpartum between 2012 and 2017. Participants who were non-depressed during pregnancy (PHQ-9 < 10) were included (n = 3619). We operationalized sleep disturbance, fatigue, and appetite disturbance as endorsement of item 3, 4, and 5 on the PHQ-9, respectively, and postpartum depressive symptoms as PHQ-9 total score ≥ 10. Participant characteristic variables included age, race, ethnicity, parity, gestational age at delivery, and preterm birth. Prenatal sleep disturbance was associated with higher odds of postpartum depressive symptoms (aORs 1.9, 95% CI 1.2–3.1 for first trimester; 3.7, 95% CI 1.5–11.5 for second trimester; 3.4, 95% CI 1.9–6.8 for third trimester). Fatigue and appetite disturbance in the first and third trimesters were associated with higher odds of postpartum depressive symptoms. Sleep disturbance varied by race during the first and second trimesters (p < 0.05) and was highest among Black or African American participants (61.8–65.1%). A routinely administered single-item measure of sleep disturbance could identify otherwise lower-risk pregnant individuals who may benefit from depression prevention efforts.

The mole crab Emerita portoricensis Schmitt, 1935 was originally described solely on the basis of few key characters that were not precisely defined, giving reason to question subsequent reports of its distribution. The present study, prompted by recent collections documenting coloration in life, undertakes a comprehensive redescription of the species based on specimens of varied sizes from Puerto Rico, Belize, Costa Rica, and Panama. Collections from the northern Caribbean that at first take appear to represent a northernmost record of E. brasiliensis Schmitt, 1935 or southernmost occurrence of E. talpoida (Say, 1817), may be assignable E. portoricensis as now recognized. Among western Atlantic species, E. portoricensis and E. benedicti have to date been considered to have the dactylus of the first pereopod terminally subacute or sharply pointed, which purportedly separates them from E. brasiliensis and E. talpoida, western Atlantic species in which this article is terminally rounded. However, in E. portoricensis this character varies with specimen size and the magnification at which the distal extreme of the dactylus is examined, being rounded to varying degrees in all but the largest specimens. Even in sexually mature specimens of less than maximum size, this rounded tip is armed by a minute corneous spine in E. portoricensis, although it is less prominent than the terminal spine on the consistently more acute dactylus of E. benedicti at all adult sizes. Also, the carapace color in live specimens of E. portoricensis, as documented for specimens collected in both Belize and Panama, differs from that of E. brasiliensis, E. talpoida, and E. benedicti by typically including longitudinal and diagonal dark bars of olive brown on the branchial regions and a light longitudinal bar marking the posterior quarter of the median line. Posterior to the cervical groove, fine rugae of the carapace that form broken transverse lines are at most little diminished across the mid-dorsal longitudinal line in E. portoricensis and E. benedicti, somewhat more broken in E. brasiliensis, and distinctly diminished to all but absent at the midline in E. talpoida. Previously reported BINs in the Barcode of Life database include sequenced specimens from Costa Rica herein accepted as E. portoricensis. We exclude populations from Brazil that have been mis-assigned to E. portoricensis.

Challenges for the effective management of interstitial lung diseases (ILDs) include difficulties with the early detection of disease, accurate prognostication with baseline data, and accurate and precise response to therapy. The purpose of this Review is to describe the clinical and research gaps in the diagnosis and prognosis of ILD, and how machine learning can be applied to image biomarker research to close these gaps. Machine-learning algorithms can identify ILD in at-risk populations, predict the extent of lung fibrosis, correlate radiological abnormalities with lung function decline, and be used as endpoints in treatment trials, exemplifying how this technology can be used in care for people with ILD. Advances in image processing and analysis provide further opportunities to use machine learning that incorporates deep-learning-based image analysis and radiomics. Collaboration and consistency are required to develop optimal algorithms, and candidate radiological biomarkers should be validated against appropriate predictors of disease outcomes.

International audience; Due to their unique three-dimensional framework and intriguing electronic properties, [2.2]paracyclophanes (pCps) have been employed over the years as building blocks in materials science for the development of organic light-emitting diodes and non-linear optical systems. In addition, depending on their substitution patterns, [2.2]paracyclophanes can display planar chirality and are nowadays considered as useful scaffolds for the development of original circularly poliarized luminescence (CPL) emitters. This perspective gives an overview on the synthesis and characterization of different families of compact luminescent compounds derived from planar chiral [2.2]paracyclophanes. The chiroptical properties of these small molecules are described, with a particular focus on their ability to emit circularly polarized luminescence in solution. Some future prospects on the design and potential applications of CPL emitters derived from pCps are finally presented.

This study (1) assessed the psychometric properties of a pregnancy-related COVID worry scale, (2) explored variations in pregnancy-related COVID worry over the course of the pandemic, and (3) examined associations between pregnancy-related COVID worry and depressive symptom severity, and evaluated sleep disturbance as a mediator.Data were drawn from an ongoing randomized trial comparing the effectiveness of two enhanced forms of prenatal care. The current analysis includes baseline pre-randomization data collected from participants who enrolled November 2020-November 2021 (n = 201). Participants were pregnant individuals with low income and primarily Latinx.Our 7-item scale was valid and reliable for assessing pregnancy-related COVID worry. Pregnancy-related COVID worry did not vary significantly by any participant characteristic or pandemic stage. Pregnancy-related COVID worry was significantly associated with depressive symptom severity in multivariate analysis (p = .002). For each unit increase on the 10-point pregnancy-related COVID worry scale, the odds of mild-to-severe depression increased by 16% (odds ratio = 1.16, 95% confidence interval 1.02-1.32, p = .02), holding all other variables constant. Sleep disturbance mediated the pregnancy-related COVID worry-depressive symptom relationship (48% of the total effect mediated).Worry about how COVID may impact their baby, birth, and postpartum experiences was associated with higher depressive symptom severity, partly through its effect on sleep. These findings suggest that interventions related to improving sleep quality among perinatal populations may reduce depressive symptoms.ClinicalTrials.gov NCT04154423, "Engaging MothersBabies; Reimagining Antenatal Care for Everyone (EMBRACE) Study".

This study describes a novel, neutralizing monoclonal antibody (mAb), 11D7, discovered by mouse immunization and hybridoma generation, against the parental Wuhan-Hu-1 RBD of SARS-CoV-2. We further developed this mAb into a chimeric human IgG and recombinantly expressed it in plants to produce a mAb with human-like, highly homogenous N-linked glycans that has potential to impart greater potency and safety as a therapeutic. The epitope of 11D7 was mapped by competitive binding with well characterized mAbs, suggesting that it is a Class 4 RBD-binding mAb that binds to the RBD outside the ACE2 binding site. Of note, 11D7 maintains recognition against the B.1.1.529 (Omicron) RBD, as well neutralizing activity. We also provide evidence that this novel mAb may be useful in providing additional synergy to established antibody cocktails, such as Evusheld™ containing the antibodies tixagevimab and cilgavimab, against the Omicron variant. Taken together, 11D7 is a unique mAb that neutralizes SARS-CoV-2 through a mechanism that is not typical among developed therapeutic mAbs and by being produced in ΔXFT Nicotiana benthamiana plants, highlights the potential of plants to be an economic and safety-friendly alternative platform for generating mAbs to address the evolving SARS-CoV-2 crisis.

Modern interest in muscarinic acetylcholine receptor (mAChR) activators for schizophrenia began in the 1990s when xanomeline, an M

Zusammenfassung Poly- und Perfluorierte Alkylsubstanzen (PFAS) gehören zu den aufkommenden Schadstoffen des 21. Jahrhunderts. Vor dem Hintergund neuer Grenzwerte und zunehmender Daten über ihre Verbreitung und den von ihnen ausgehende Gesundheitsgefahren können lokale Sreenings helfen, Hintergrundbelastungen zu verstehen und Hotspots zu identifizieren. In unserem Beispiel wurden 17 Oberflächengewässer auf ihre Belastung mit PFAS hin untersucht. Es konnten Konzentrationen zwischen 2,4 ng/l und 41 ng/l für die Summe von 21 Substanzen ermittelt werden.

Zusammenfassung Das Abwasser von Krankenhäusern ist für Patienten und medizinisches Personal nicht sichtbar, für die Betrachtung von Antibiotikaresistenzen im klinischen Umfeld aber von großer Bedeutung. Denn Siphons in Nasszellen sind in der Lage, Antibiotikarückstände über einen längeren Zeitraum zu speichern. In diesen Systemen besteht das Risiko der Verbreitung und Neuentwicklung von Antibiotikaresistenzen. Krankenhausabwasser emittiert darüber hinaus Antibiotikarückstände und antibiotikaresistente Bakterien in das kommunale Abwasser und stellt somit einen Punktemittenten für den weiterführenden Eintrag in die aquatische Umwelt dar.

Antibiotics are essential for modern medicine, they are employed frequently in hospitals and, therefore, present in hospital wastewater. Even in concentrations, that are lower than the minimum inhibitory concentrations (MICs) of susceptible bacteria, antibiotics may exert an influence and select resistant bacteria, if they exceed the MSCs (minimal selective concentrations) of resistant strains. Here, we compare the MSCs of fluorescently labelled Acinetobacter baylyi strains harboring spontaneous resistance mutations or a resistance plasmid with antibiotic concentrations determined in hospital wastewater. Low MSCs in the μg/L range were measured for the quinolone ciprofloxacin (17 μg/L) and for the carbapenem meropenem (30 μg/L). A 24 h continuous analysis of hospital wastewater showed daily fluctuations of the concentrations of these antibiotics with distinctive peaks at 7-8 p.m. and 5-6 a.m. The meropenem concentrations were always above the MSC and MIC values of A. baylyi. In addition, the ciprofloxacin concentrations were in the range of the lowest MSC for about half the time. These results explain the abundance of strains with meropenem and ciprofloxacin resistance in hospital wastewater and drains.

ObjectiveEvidence on long-term costs of atrial fibrillation (AF) and associated factors is scarce. As part of the Swiss-AF prospective cohort study, we aimed to characterise AF costs and their development over time, and to assess specific patient clusters and their cost trajectories.MethodsSwiss-AF enrolled 2415 patients with variable duration of AF between 2014 and 2017. Patient clusters were identified using hierarchical cluster analysis of baseline characteristics. Ongoing yearly follow-ups include health insurance clinical and claims data. An algorithm was developed to adjudicate costs to AF and related complications.ResultsA subpopulation of 1024 Swiss-AF patients with available claims data was followed up for a median (IQR) of 3.24 (1.09) years. Average yearly AF-adjudicated costs amounted to SFr5679 (€5163), remaining stable across the observation period. AF-adjudicated costs consisted mainly of inpatient and outpatient AF treatment costs (SFr4078; €3707), followed by costs of bleeding (SFr696; €633) and heart failure (SFr494; €449). Hierarchical analysis identified three patient clusters: cardiovascular (CV; N=253 with claims), isolated-symptomatic (IS; N=586) and severely morbid without cardiovascular disease (SM; N=185). The CV cluster and SM cluster depicted similarly high costs across all cost outcomes; IS patients accrued the lowest costs.ConclusionOur results highlight three well-defined patient clusters with specific costs that could be used for stratification in both clinical and economic studies. Patient characteristics associated with adjudicated costs as well as cost trajectories may enable an early understanding of the magnitude of upcoming AF-related healthcare costs.

ZusammenfassungVagheit wird in der öffentlichen Debatte über angemessenen Sprachgebrauch häufig als ein Problem dargestellt. Die Diagnose sprachlicher Vagheit in Bezug auf ein Lexem oder eine Äußerung unterstellt in der Regel eine Absicht – so auch der Titel dieses Themenheftes »Veruneindeutigungen« mit dem Verweis auf »Uneindeutigkeit als Strategie« (Call for Paper, S. 1). Veruneindeutigung präsupponiert einen (aktiven) Agens, der veruneindeutigt – vermutlich intentional. Hierbei wird das Eindeutige als Standard-/default-Wert sprachlicher Kommunikation insinuiert. Pragmalinguistisch gewendet fokussiert dies strukturell paradigmatische und mentalistisch kontrastive Aspekte von Bestimmtheit und Nicht-Bestimmtheit beim Sprachhandeln. Gegenstand dieses Beitrages ist die in Sprache angelegte Eigenschaft der Vagheit, die durch die Arbitrarität von Ausdrucksseite und Inhaltsseite gegeben ist und durch Konventionalisierung des Sprachgebrauchs entschärft wird. Es werden daher zwei Seiten der Vereindeutigung, der pragma-semiotischen Erdung aufgezeigt. Dazu wird die aktive Rolle der rezipierenden Individuen beim Verstehen von uneindeutigen bzw. veruneindeutigten Kommunikationsprozessen fokussiert.

Purpose: Vowels and consonants play different roles in language acquisition and speech recognition, yet standard clinical tests do not assess vowel and consonant perception separately. As a result, opportunities for targeted intervention may be lost. This study evaluated closed-set word recognition tests designed to rely predominantly on either vowel or consonant perception and compared results with sentence recognition scores. Method: Participants were children (5–17 years of age) and adults (18–38 years of age) with normal hearing and children with sensorineural hearing loss (7–17 years of age). Speech reception thresholds (SRTs) were measured in speech-shaped noise. Children with hearing loss were tested with their hearing aids. Word recognition was evaluated using a three-alternative forced-choice procedure, with a picture-pointing response; monosyllabic target words varied with respect to either consonant or vowel content. Sentence recognition was evaluated for low- and high-probability sentences. In a subset of conditions, stimuli were low-pass filtered to simulate a steeply sloping hearing loss in participants with normal hearing. Results: Children's SRTs improved with increasing age for words and sentences. Low-pass filtering had a larger effect for consonant-variable words than vowel-variable words for both children and adults with normal hearing, consistent with the greater high-frequency content of consonants. Children with hearing loss tested with hearing aids tended to perform more poorly than age-matched children with normal hearing, particularly for sentence recognition, but consonant- and vowel-variable word recognition did not appear to be differentially affected by the amount of high- and low-frequency hearing loss. Conclusions: Closed-set recognition of consonant- and vowel-variable words appeared to differentially evaluate vowel and consonant perception but did not vary by configuration of hearing loss in this group of pediatric hearing aid users. Word scores obtained in this manner do not fully characterize the auditory abilities necessary for open-set sentence recognition, but they do provide a general estimate.

Perfluoroalkyl acids (PFAA) are among the leading chemical pollutants in the twenty-first century. Of these, perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) have been widely detected in a large number of animal and environmental samples. Wild boars accumulate PFAA in their livers, but it has not yet been clarified to what extent wild boars of the same population accumulate different PFAA in their livers or whether any conclusions can be drawn from any differences found in regard to environmental contamination. In this study, liver samples from wild boars killed during driven hunts in 2019 and 2020 from a defined forest area in North Rhine-Westfalia, Germany were analyzed for 13 different PFAA. A mean load of 493 µg/kg (± 168 µg/kg) PFAA was measured in 2020. Perfluorosulfonic acids accounted for 87% of the total load in both years, with PFOS dominating this group. These results were similar to those of 14 liver samples collected from other regions of Germany for comparison. In addition, the livers of hunted pregnant sows and fetuses were examined. The load of short-chain perfluorocarboxylic acids (

Funding communities through mini-grant programs builds community capacity by fostering leadership among community members, developing expertise in implementing evidence-based practices, and increasing trust in partnerships. The South Carolina Cancer Prevention and Control Research Network (SC-CPCRN) implemented the Community Health Intervention Program (CHIP) mini-grants initiative to address cancer-related health disparities among high-risk populations in rural areas of the state. One community-based organization and one faith-based organization were funded during the most recent call for proposals. The organizations implemented National Cancer Institute evidence-based strategies and programs focused on health and cancer screenings and physical activity and promotion of walking trails. Despite the potential for the COVID-19 pandemic to serve as a major barrier to implementation, grantees successfully recruited and engaged community members in evidence-based activities. These initiatives added material benefits to their local communities, including promotion of walking outdoors where it is less likely to contract the virus when socially distanced and provision of COVID-19 testing and vaccines along with other health and cancer screenings. Future mini-grants programs will benefit from learning from current grantees' flexibility in program implementation during a pandemic as well as their intentional approach to modifying program aspects as needed.

This article draws on ethnographic research to conceptualise how nurses mobilise assemblages of caring to organise and deliver COVID care; particularly so by reorganising organisational infrastructures and practices of safe and good care. Based on participatory observations, interviews and nurse diaries, all collected during the early phase of the pandemic, the research shows how the organising work of nurses unfolds at different health-care layers: in the daily care for patients and their families, in the coordination of care in and between hospitals, and at the level of the health-care system. These findings contrast with the dominant pandemic-image of nurses as ‘heroes at the bedside’, which fosters the classic and microlevel view of nursing and leaves the broader contribution of nurses to the pandemic unaddressed. Theoretically, the study adds to the literature on translational mobilisation and assemblage theory by focussing on the layered and often invisible organising work of nurses in health care.

Side effects associated with using antibodies as therapeutics can limit systemic administration at the high concentrations often needed for therapeutic impact. Thus, therapeutic antibodies are usually considered for targeted delivery. Antibody encapsulation in polymeric nanoparticles via the emulsion-based nanofabrication methods typically yields low loading efficiencies. Therefore, the fabrication techniques need to be modified to maximize the loading efficiency of antibodies. In this work, we utilized various cosolvents with the emulsion solvent evaporation technique to improve the loading efficiency of anti-CD47, a therapeutic antibody used to block CD47 activity in atherosclerotic plaques and cancer lesions.The double emulsion solvent evaporation technique was used to fabricate anti-CD47-loaded polymeric nanoparticles. The primary oil phase solvent, chloroform, was doped with different cosolvents, including ethyl acetate, acetonitrile, ethanol, and methanol, to investigate the impact of cosolvents on the loading efficiency of anti-CD47. The release profile and loading efficiency were quantified by measuring the fluorescence signal of the released antibody. The activity of the antibody released from particles fabricated in the presence of the cosolvent was confirmed by quantifying its adherence to red blood cells. Ethyl acetate was the optimum cosolvent, improving the loading efficiency of anti-CD47 in poly(lactic-co-glycolic acid), PLGA, nanoparticles to 90% or higher, and the antibody was found to retain its activity after being released from nanoparticles.Our results demonstrate that a minimum amount of a cosolvent with minimal hydrophilicity can stabilize the antibody in the oil phase; thus, improving the antibody's loading efficiency significantly.

DAPHNE4NFDI focuses on research with photons and neutrons at large-scale research facilities. The main goal of DAPHNE4NFDI is to make data from these experiments "FAIR", thereby making scientific work more efficient and gaining more knowledge from the data. The overall goals of DAPHNE4NFDI are Improve metadata capture through consistent workflows supported by user-driven online logbooks that are linked to the data collection, thus enabling a richer capture of information about the experiments than is currently possible; Establish a community repository of processed data, new reference databases and analysis code for published results, linked, where possible, to raw data sources, to sustainably improve access to research data and enable data and software re-use; Develop, curate and deploy user-developed analysis software on facility computing infrastructure so that ordinary users can benefit from and repeat the analysis performed by leading power user groups through common data analysis portals. This is the public version of the proposal of DAPHNE4NFDI. For more information please visit the project website., This work is supported in the context of the work of the NFDI e.V. The consortium DAPHNE4NFDI is funded by the DFG - project number 460248799.

A recent molecular phylogenetic analysis that focused on selected species of western Atlantic Paguristes Dana, 1851, Areopaguristes Rahayu & McLaughlin, 2010, and Pseudopaguristes McLaughlin, 2002 was somewhat inconclusive regarding relationships among those genera, but it revealed two new unrecognized species genetically related to members of the Paguristes tortugae complex. One of the new species is sister to A. hummi (Wass, 1955), which is readily separated from Wass’ taxon by significant differences in coloration. However, no definitive characters have been found for its identification on the basis of structural morphology. A second new species is genetically sister to P. tortugae Schmitt, 1933, even though it was regarded in earlier literature as no more than an ecomorphic variant expressing protective coloration related to habitat substrate color. In addition to its unique coloration, subtle distinctions are evident in structural morphology. Both species are formally named with accompanying morphological and color descriptions.

We previously demonstrated that natural product-inspired 3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-ones derivatives delivered potent and selective PIM kinases inhibitors however with non-optimal ADME/PK properties and modest oral bioavailability. Herein, we describe a structure-based scaffold decoration and a stereoselective approach to this chemical class. The synthesis, structure-activity relationship studies, chiral analysis, and pharmacokinetic data of compounds from this inhibitor class are presented herein. Compound 20c demonstrated excellent potency on PIM1 and PIM2 with exquisite kinases selectivity and PK properties that efficiently and dose-dependently promoted c-Myc degradation and appear to be promising lead compounds for further development.

This study aimed to present a case of first-trimester uterine rupture and perform a systematic review to identify common presentations, risk factors, and management strategies.Searches were performed in PubMed, Ovid, and Scopus using a combination of key words related to "uterine rupture," "first trimester," and "early pregnancy" from database inception to September 30, 2020.English language descriptions of uterine rupture at ≤14 weeks of gestation were included, and cases involving pregnancy termination and ectopic pregnancy were excluded.Outcomes for the systematic review included maternal demographics, description of uterine rupture, and specifics of uterine rupture diagnosis and management. Data were extracted to custom-made reporting forms. Median values were calculated for continuous variables, and percentages were calculated for categorical variables. The risk of bias was assessed using the Joanna Briggs Institute critical appraisal checklist for case reports and case series.Overall, 61 cases of first-trimester uterine rupture were identified, including our novel case. First-trimester uterine ruptures occurred at a median gestation of 11 weeks. Most patients (59/61 [97%]) had abdominal pain as a presenting symptom, and previous uterine surgery was prevalent (44/61 [62%]), usually low transverse cesarean delivery (32/61 [52%]). The diagnosis of uterine rupture was generally made after surgical exploration (37/61 [61%]), with rupture noted in the fundus in 26 of 61 cases (43%) and in the lower segment in 27 of 61 cases (44%). Primary repair of the defect was possible in 40 of 61 cases (66%), whereas hysterectomy was performed in 18 of 61 cases (30%). Continuing pregnancy was possible in 4 of 61 cases (7%).Uterine rupture is an uncommon occurrence but should be considered in patients with an acute abdomen in early pregnancy, especially in women with previous uterine surgery. Surgical exploration is typically needed to confirm the diagnosis and for management. Hysterectomy is not always necessary; primary uterine repair is sufficient in more than two-thirds of the cases to achieve hemostasis. Continuing pregnancy, although uncommon, is also possible.

This investigation demonstrated a routine of evaluation and training of an athlete of the SL3 class of parabadminton for 2 days continuously monitored by a metabolic analyzer with measurements of oxygen consumption (V̇O2), carbon dioxide production, and heart rate (HR). The results showed HR and V̇O2 responses varying between 50% and 99.54% of HRmax (mean HR 80.92 bpm), and 6% and 104% (mean V̇O2 35.25 mL/kg/min) of V̇O2max, during the simulated game. The exercise test and the simulated training session showed significant changes in HR and V̇O2, reinforcing the need for considerable energy input to training and assessment.

Zeitschrift für medizinische Physik 32(3), 334-345 (2022). doi:10.1016/j.zemedi.2021.12.003, Published by Elsevier, Amsterdam [u.a.]

Malignant small bowel obstruction (mSBO) is a common consequence of advanced malignancies. Surgical consultation is common, however data on the outcomes following an operation are lacking. We investigated a specific operative approach-intestinal bypass-to determine the outcomes associated with this intervention.Patients with a preoperative diagnosis of mSBO who underwent intestinal bypass between 2015 and 2021 were included. Isolated colonic obstruction was excluded as was gastric outlet obstruction. Perioperative and postoperative outcomes were measured, including complications, overall survival, return to oral intake, and return to intended oncologic therapy. Patients were additionally grouped as to whether the operation was performed as elective or as inpatient.Overall, 55 patients were identified, with a mean age of 61.2 ± 14 years. The most common primary malignancy was colorectal cancer (65.5%) and 80% of patients had a preoperative diagnosis of metastatic disease. Small bowel to colon was the most common bypass procedure (51%). Severe complications occurred in 25.5% of patients with three in-hospital mortalities (5.5%). Survival rates at 30, 90, and 180 days were 91%, 80%, and 62%, respectively. The majority of patients were discharged to home (85.5%) and were tolerating an oral diet (74.6%). Twenty-seven patients (49.1%) returned to some form of oncologic treatment.Patients with mSBO face a potentially terminal condition. In this study, approximately 75% of patients who underwent intestinal bypass were able to regain the ability to eat, and 49% returned to oncologic therapy. Although retrospective, these data suggest the approach is efficacious for palliation of this difficult sequela of advanced cancer.

Objectives: We analyze how shortages led to changes in access to and expenditure for pharmaceutical care in the Swiss health system between 2015 and 2020. Methods: We combined cross-sectional and longitudinal data to study medicine shortages by incidence, duration, intensity, and pharmaceutical expenditure. We assessed 4119 markets defined by active ingredient, dosage form, and strength. We classified markets by essential medicine status and other characteristics. We differentiated shortages by the degree to which alternative options are still available. We investigated the first lockdown period of the pandemic, considering also the shortage of COVID-19–specific medicines. Results: A total of 1964 markets never reported shortages, and 1336 markets reported some shortages; 819 markets reported shortages lasting at least 14 days. Markets with a higher number of manufacturers, a lower co-payment share, and lower prices more frequently reported shortages. We did not find differences by essential medicine status. In 50% of instances, the average price of substitutes available was lower than the price of the product on shortage. The total pharmaceutical expenditure attributed to shortages increased by CHF 17.00 million (€15.63 million) in 2018. Conclusions: Medicine shortages have substantially reduced access to pharmaceuticals. Switzerland has experienced shortages on a scale similar to that in other countries. Prices of substitutes available at the time of shortages can be higher or lower, indicating an unelastic demand for medicines.

PURPOSE OF REVIEW: To review the etiology of inverse salt sensitivity of blood pressure (BP). RECENT FINDINGS: Both high and low sodium (Na(+)) intake can be associated with increased BP and cardiovascular morbidity and mortality. However, little is known regarding the mechanisms involved in the increase in BP in response to low Na(+) intake, a condition termed inverse salt sensitivity of BP, which affects approximately 15% of the adult population. The renal proximal tubule is important in regulating up to 70% of renal Na(+) transport. The renin-angiotensin and renal dopaminergic systems play both synergistic and opposing roles in the regulation of Na(+) transport in this nephron segment. Clinical studies have demonstrated that individuals express a “personal salt index” (PSI) that marks whether they are salt-resistant, salt-sensitive, or inverse salt-sensitive. Inverse salt sensitivity results in part from genetic polymorphisms in various Na(+) regulatory genes leading to a decrease in natriuretic activity and an increase in renal tubular Na(+) reabsorption leading to an increase in BP. SUMMARY: This article reviews the potential mechanisms of a new pathophysiologic entity, inverse salt sensitivity of BP, which affects approximately 15% of the general adult population.

Objectives Although laboratory result presentation may lead to information overload and subsequent missed or delayed diagnosis, little has been done in the past to improve this post-analytical issue. We aimed to investigate the efficiency, efficacy and user satisfaction of alternative report formats. Methods We redesigned cumulative (sparkline format) and single reports (improved tabular and z-log format) and tested these on 46 physicians, nurses and medical students in comparison to the classical tabular formats, by asking standardized questions on general items on the reports as well as on suspected diagnosis and follow-up treatment or diagnostics. Results Efficacy remained at a very high level both in the new formats as well as in the classical formats. We found no significant difference in any of the groups. Efficiency improved in all groups when using the sparkline cumulative format and marginally when showing the improved tabular format. When asking medical questions, efficiency and efficacy remained similar between report formats and groups. All alternative reports were subjectively more attractive to the majority of participants. Conclusions Showing cumulative reports as a graphical display led to faster detection of general information on the report with the same level of correctness. Considering the familiarity bias of the classical single report formats, the borderline-significant improvement of the alternative tabular format and the non-inferiority of the z-log format, suggests that single reports might benefit from some improvements derived from basic information design.

Modern Physics intertwines active learning pedagogy with the material typically covered in an introductory survey, from the basics of relativity and quantum mechanics through recent developments in particle physics and cosmology. The flexible approach taken by the authors allows instructors to easily incorporate as much or as little active learning into their teaching as they choose. Chapters are enhanced by 'Discovery' and 'Active Reading' exercises to guide students through key ideas before or during class, while 'ConcepTests' help check student understanding and stimulate classroom discussions. Each chapter also includes extensive assessment material, with a range of basic comprehension questions, drill and practice calculations, computer-based problems, and explorations of advanced applications. A test bank and interactive animations as well as other support for instructors and students are available online. Students are engaged by an accessible and lively writing style, thorough explanations, 'Math Interludes' which account for varying levels of skill and experience, and advanced topics to further pique their interest in physics.