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Owing to their similarities with giant exoplanets, brown dwarf companions of stars provide insights into the fundamental processes of planet formation and evolution. From their orbits, several brown dwarf companions are found to be more massive than theoretical predictions given their luminosities and the ages of their host stars 1-3 . Either the theory is incomplete or these objects are not single entities. For example, they could be two brown dwarfs each with a lower mass and intrinsic luminosity 1,4 . The most problematic example is Gliese 229 B (refs.  5,6 ), which is at least 2-6 times less luminous than model predictions given its dynamical mass of 71.4 ± 0.6 Jupiter masses (M Jup ) (ref.  1 ). We observed Gliese 229 B with the GRAVITY interferometer and, separately, the CRIRES+ spectrograph at the Very Large Telescope. Both sets of observations independently resolve Gliese 229 B into two components, Gliese 229 Ba and Bb, settling the conflict between theory and observations. The two objects have a flux ratio of 0.47 ± 0.03 at a wavelength of 2 μm and masses of 38.1 ± 1.0 and 34.4 ± 1.5 M Jup , respectively. They orbit each other every 12.1 days with a semimajor axis of 0.042 astronomical units (AU). The discovery of Gliese 229 BaBb, each only a few times more massive than the most massive planets, and separated by 16 times the Earth-moon distance, raises new questions about the formation and prevalence of tight binary brown dwarfs around stars., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Aims of the Study: Health equity is a key component of quality of care and an objective for a growing number of quality improvement projects for deontological, ethical, public health and economic reasons. To monitor equity in the delivery of health services in Switzerland, there is a need to implement valid, measurable and actionable equity indicators, along with vulnerability stratifiers such as migrant status, which could lead to differences in quality of care. The aim of this study was to develop a set of healthcare equity indicators and stratifiers targeting inpatient and outpatient populations and to test their feasibility., Methods: A scoping literature review and inputs from a national interprofessional expert taskforce provided a set of indicators and vulnerability stratifiers. The most valid and measurable indicators and stratifiers were retained using a Delphi process. They were then operationalised, and their implementation tested in three Swiss hospitals from the three language regions., Results: A taskforce of 18 experts, including a patient representative, selected 11 indicators that evaluate structures, processes and outcomes, and five vulnerability stratifiers. Although most indicators and stratifiers could be implemented in all three hospitals, data availability was limited for some variables, including patient satisfaction and access to interpreters for foreign-language patients., Conclusions: The equity indicators and stratifiers identified by this two-stage process have content validity, wide patient coverage and are focused on inequities in the healthcare system that are actionable through improvement projects. Both the indicators and the project methodology could be replicated in institutions aiming for more equitable care.

Long COVID is a chronic and often disabling illness with long-term consequences. Although progress has been made in the clinical characterization of long COVID, no approved treatments exist and disconnects between patients and researchers threaten to hinder future progress. Incorporating patients as active collaborators in long COVID research can bridge the gap and accelerate progress toward treatments and cures., Competing Interests: Declaration of interests The authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In the neurosciences, concepts play an important role in the conception and direction of research. Among the theoretical notions and direction of research, plasticity stands out because of the multiple ways in which scientists use it to describe and interpret how the nervous system changes and adapts to different requirements. The occurrence of different conceptualizations of plasticity in the scientific literature during the second half of the twentieth century and up to the present was investigated using bibliometric methods. Throughout the period analyzed, synaptic plasticity has remained the dominant conceptualization of plasticity. However, scientists have continued to introduce novel plasticity concepts reflecting the scientific advances they have made in understanding the dynamic nature of the nervous system. The conceptual evolution of plasticity documents that the view of the adult nervous system as immutable has been replaced by an understanding of the nervous system as capable of lifelong change and adaptation.

Background and Objectives: The human papillomavirus (HPV) is one of the most common viruses transmitted through intimate contact, causing many benign and malignant diseases. Vaccination protects against these diseases. Despite the HPV vaccination being recommended by the Standing Committee on Vaccination (STIKO), knowledge and vaccination rates in Germany are very low. Therefore, the aim of the study was to assess the HPV knowledge among German students., Materials and Methods: Between 06/2019 and 01/2024, a nationwide online survey on HPV knowledge among students in Germany was distributed via the respective student councils. The survey included two aspects: 1) basic characteristics of the participants and 2) knowledge questions about HPV (e.g., transmission routes, effectiveness, and side effects of vaccination, knowledge about the HPV subtypes). Data collection was anonymous., Results: A total of 459 students took part in the study. Of these, 335 (72.98%) were female, 122 (26.57%) were male, and 2 (0.45%) did not specify their gender. The average age of the students was 24.02 years, and most of the participants were in their 6th (23.31%/107) semester. In all, 75.82% (348) of the participants were medical students followed by law students with 19.61% (90) participants. The most represented study location was Aachen, with 270 (58.82%) participants. Only about half (48.80%/223) of the students knew that approximately 8000 new cancer cases in Germany are HPV-associated annually. Regarding the HPV vaccination, more than a third (35.82%/163) of participants did not know that it also protects against genital warts, while 21.93% (100) did not know that boys can also benefit from the HPV vaccination and that it does not only improve HPV protection of girls against cervical cancer., Conclusion: Despite several years of HPV vaccination recommendation by the Standing Committee on Vaccination (STIKO), knowledge about HPV among college students still remains very low. Further prevention and educational efforts are needed to address HPV knowledge gaps, with the additional goal of improving HPV vaccination rates., (© 2024. The Author(s).)

Introduction: Translation is a fundamental process of life. In eukaryotes, the elongation step of translation is highly conserved and is driven by eukaryotic translation elongation factors (eEF)1A and eEF2. A significant variation of the elongation is the activity of eukaryotic elongation factor (eEF) 3 in Saccharomyces cerevisiae encoded by the gene yeast elongation factor ( YEF3 ) with orthologs in all fungal species, a few algae, and some protists. In S. cerevisiae, YEF3 is an essential gene and eEF3 plays a critical role in translation elongation, as it promotes binding of the ternary complex acylated-Transfer RNA (tRNA)-eEF1A-Guanosine-5'-triphosphate (GTP) to the aminoacyl (A) site of the ribosome, the release of uncharged tRNAs after peptide translocation, and ribosome recycling. Even though YEF3 was discovered more than 40 years ago, eEF3 has been characterized almost exclusively in S. cerevisiae ., Methods: We undertook an in vivo genetic approach to assess the functional conservation of eEF3 across phylogenetically distant fungal species., Results: We found that eEF3 from Zygosaccharomyces rouxii and Candida glabrata (both belonging to phylum Ascomycota), Ustilago maydis ( phylum Basidiomycota), and Gonapodya prolifera ( phylum Monoblepharomycota), but not Aspergillus nidulans ( phylum Ascomycota), supported the growth of S. cerevisiae lacking the endogenous YEF3 gene. We also proved that eEF3 is an essential gene in the ascomycetes C. glabrata and A. nidulans ., Discussion: Given that most existing knowledge on fungal translation has only been obtained from S. cerevisiae , our findings beyond this organism showed variability in the elongation process in Fungi. We also proved that eEF3 is essential in pathogenic fungi, opening the possibility of using eEF3 as a target to fight candidiasis., Competing Interests: The C. glabrata strain ura3Δ::KANMX, eEF3Δ::NATMX is claimed by the patent MX/a/2019/000406, application file MX/E/2019/001890, 10th January of 2019, property of Instituto Nacional de Cancerología, Mexico. GH declared that he was an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Maldonado, García, Herrero, Castaño, Altmann, Fischer and Hernández.)

Background: Psychosocial care of cancer patients is an important aspect throughout the entire course of oncological treatment. Since 2015, psychosocial screening has been implemented in the outpatient clinics of the Skin Cancer Center in Freiburg. We present here a post hoc analysis in the context of a quality management program., Question: Acceptance, psychosocial distress and desire for counseling were evaluated. Exploratively, we investigated which patient and disease characteristics are related to increased subjective distress., Materials and Methods: In a full survey from 06/2015 to 12/2015, we evaluated acceptance, psychosocial distress by distress thermometer (DT), and desire for counseling., Results: Of 753 patients, 345 (45.8%) participated in psychosocial screening and data from 310 (174 men, 136 women; 89.7% melanoma patients, mean time since initial diagnosis 4.7 ± 3.9 years) could be analyzed. The mean burden on the DT was 2.97 ± 2.83 (median 2, range 0-10). High distress (DT ≥ 5) was reported by 84 patients (28.8%). Thirty-four patients (11%) indicated a desire for counseling, and 23 patients took up the counseling offer. The patient group with high distress was younger, more often under ongoing or recently completed systemic therapy, and had more often a desire for counseling., Conclusion: In addition to assessing psychosocial distress with validated screening instruments, the survey of the subjective desire for care represents an important parameter for the identification of patients in need of care. Young patients and patients with ongoing systemic therapy should be the focus of attention., (© 2024. The Author(s).)

We report the first double-differential neutrino-argon cross section measurement made simultaneously for final states with and without protons for the inclusive muon neutrino charged-current interaction channel. The proton kinematics of this channel are further explored with a differential cross section measurement as a function of the leading proton's kinetic energy that extends across the detection threshold. These measurements use data collected with the MicroBooNE detector from 6.4×10^{20} protons on target from the Fermilab booster neutrino beam with a mean neutrino energy of ∼0.8  GeV. Extensive data-driven model validation utilizing the conditional constraint formalism is employed. This motivates enlarging the uncertainties with an empirical reweighting approach to minimize the possibility of extracting biased cross section results. The extracted nominal flux-averaged cross sections are compared to widely used event generator predictions revealing severe mismodeling of final states without protons for muon neutrino charged-current interactions, possibly from insufficient treatment of final state interactions. These measurements provide a wealth of new information useful for improving event generators which will enhance the sensitivity of precision measurements in neutrino experiments.

Competing Interests: English: Jochen Schmitt reports institutional grants for investigator-initiated research from the German GBA, BMG, BMBF, EU, Federal State of Saxony, Novartis, Sanofi, ALK, and Pfizer. He also participated in advisory board meetings as a paid consultant for Sanofi, Lilly, and ALK. JS is a member of the Expert Council on Health and Care at the Federal Ministry of Health and a member of the government commission for modern and needs-based hospital care of the current German Coalition. Julia Hoffmann and Lorenz Harst has received funding from the Volkswagen Foundation to participate in a workshop on organizational health services research. Deutsch: Jochen Schmitt erhielt institutionelle Zuwendungen für wissenschaftlich initiierte Forschung vom G-BA, BMG, BMBF, EU, Bundesland Sachsen, Novartis, Sanofi, ALK und Pfizer. Außerdem nahm er als Honorarberater für Sanofi, Lilly und ALK an Beiratssitzungen teil. Er ist Mitglied im Sachverständigenrat Gesundheit und Pflege des BMG und Mitglied der Regierungskommission für eine moderne und bedarfsgerechte Krankenhausversorgung der aktuellen deutschen Ampelkoalition. Julia Hoffmann und Lorenz Harst erhielten von der Volkswagen-Stiftung eine Förderung für die Teilnahme an einem Workshop zur Versorgungsforschung.

Background: Cavernous malformations of the dura, especially of the tentorium, are exceedingly rare. In the available literature, only 10 cases have been described to date., Observations: The authors present the case of a 46-year-old male patient with a 1-cm infratentorial lesion suspicious for meningioma that was found on routine magnetic resonance imaging (MRI) performed for vertigo. The lesion was followed for 1.5 years with no change in signal and size. Nevertheless, the patient was concerned about the lesion and requested removal. The removal was successful and without any neurological sequelae. However, histological evaluation demonstrated a cavernous malformation. Postoperative computed tomography and MRI showed complete removal. Preoperative MRI characteristics, intraoperative images, and a video, as well as histological evaluation, are shown. The case is discussed with respect to the literature., Lessons: Cavernous malformations of the tentorium are extremely rare and mimic meningiomas; thus, they need to be taken into account. DOTATOC positron emission tomography may help to differentiate in these cases. Considering the cases reported in the literature, in cases of large tumors, preoperative angiography and possibly embolization may be helpful. https://thejns.org/doi/10.3171/CASE24168.

Securing an airway enables the oxygenation and ventilation of the lungs and is a potentially life-saving medical procedure. Adverse and critical events are common during airway management, particularly in neonates and infants. The multifactorial reasons for this include patient-dependent, user-dependent and also external factors. The recently published joint ESAIC/BJA international guidelines on airway management in neonates and infants are summarized with a focus on the clinical application. The original publication of the guidelines focussed on naming formal recommendations based on systematically documented evidence, whereas this summary focusses particularly on the practicability of their implementation., (© 2024. The Author(s).)

The release of Ca 2+ ions from intracellular stores plays a crucial role in many cellular processes, acting as a secondary messenger in various cell types, including cardiomyocytes, smooth muscle cells, hepatocytes, and many others. Detecting and classifying associated local Ca 2+ release events is particularly important, as these events provide insight into the mechanisms, interplay, and interdependencies of local Ca 2+ release events underlying global intracellular Ca 2+ signaling. However, time-consuming and labor-intensive procedures often complicate analysis, especially with low signal-to-noise ratio imaging data. Here, we present an innovative deep learning-based approach for automatically detecting and classifying local Ca 2+ release events. This approach is exemplified with rapid full-frame confocal imaging data recorded in isolated cardiomyocytes. To demonstrate the robustness and accuracy of our method, we first use conventional evaluation methods by comparing the intersection between manual annotations and the segmentation of Ca 2+ release events provided by the deep learning method, as well as the annotated and recognized instances of individual events. In addition to these methods, we compare the performance of the proposed model with the annotation of six experts in the field. Our model can recognize more than 75 % of the annotated Ca 2+ release events and correctly classify more than 75 %. A key result was that there were no significant differences between the annotations produced by human experts and the result of the proposed deep learning model. We conclude that the proposed approach is a robust and time-saving alternative to conventional full-frame confocal imaging analysis of local intracellular Ca 2+ events., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

We present a first search for dark-trident scattering in a neutrino beam using a dataset corresponding to 7.2×10^{20} protons on target taken with the MicroBooNE detector at Fermilab. Proton interactions in the neutrino target at the main injector produce π^{0} and η mesons, which could decay into dark-matter (DM) particles mediated via a dark photon A^{'}. A convolutional neural network is trained to identify interactions of the DM particles in the liquid-argon time projection chamber (LArTPC) exploiting its imagelike reconstruction capability. In the absence of a DM signal, we provide limits at the 90% confidence level on the squared kinematic mixing parameter ϵ^{2} as a function of the dark-photon mass in the range 10≤M_{A^{'}}≤400  MeV. The limits cover previously unconstrained parameter space for the production of fermion or scalar DM particles χ for two benchmark models with mass ratios M_{χ}/M_{A^{'}}=0.6 and 2 and for dark fine-structure constants 0.1≤α_{D}≤1.

Purpose: To explore the structural-functional loss relationship from optic-nerve-head- and macula-centred spectral-domain (SD) Optical Coherence Tomography (OCT) images in the full spectrum of glaucoma patients using deep-learning methods., Methods: A cohort comprising 5238 unique eyes classified as suspects or diagnosed with glaucoma was considered. All patients underwent ophthalmologic examination consisting of standard automated perimetry (SAP), macular OCT, and peri-papillary OCT on the same day. Deep learning models were trained to estimate G-pattern visual field (VF) mean deviation (MD) and cluster MD using retinal thickness maps from seven layers: retinal nerve fiber layer (RNFL), ganglion cell layer and inner plexiform layer (GCL + IPL), inner nuclear layer and outer plexiform layer (INL + OPL), outer nuclear layer (ONL), photoreceptors and retinal pigmented epithelium (PR + RPE), choriocapillaris and choroidal stroma (CC + CS), total retinal thickness (RT)., Results: The best performance on MD prediction is achieved by RNFL, GCL + IPL and RT layers, with R2 scores of 0.37, 0.33, and 0.31, respectively. Combining macular and peri-papillary scans outperforms single modality prediction, achieving an R2 value of 0.48. Cluster MD predictions show promising results, notably in central clusters, reaching an R2 of 0.56., Conclusions: The combination of multiple modalities, such as optic-nerve-head circular B-scans and retinal thickness maps from macular SD-OCT images, improves the performance of MD and cluster MD prediction. Our proposed model demonstrates the highest level of accuracy in predicting MD in the early-to-mid stages of glaucoma., Translational Relevance: Objective measures recorded with SD-OCT can optimize the number of visual field tests and improve individualized glaucoma care by adjusting VF testing frequency based on deep-learning estimates of functional damage.

Urinary tract infections vary widely in their clinical spectrum, ranging from uncomplicated cystitis to septic shock. Urosepsis accounts for 9-31% of all cases of septicemia and is often associated with nosocomial infections. A major risk factor for urosepsis is the presence of obstructive uropathy, caused by conditions such as urolithiasis, tumors, or strictures. The severity and course of urosepsis depend on both the virulence of the pathogen and the patient's specific immune response. Prompt therapy, including antimicrobial treatment and eradication of the infection source, along with supportive measures for circulatory and respiratory stabilization, and adjunctive therapies such as hemodialysis and glucocorticoid therapy, is crucial. Due to demographic changes, an increase in cases of urosepsis is expected-thus, it is of utmost importance for urologists to be familiar with targeted diagnostics and effective treatment., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: The diagnosis of third window syndromes often poses a challenge in clinical practice., Objective: This paper provides an up-to-date overview of diagnostic procedures in third window syndromes, with special emphasis on superior canal dehiscence syndrome (SCDS), large vestibular aqueduct syndrome (LVAS), and X-chromosomal malformation of the cochlea., Materials and Methods: A literature search was performed in PubMed up to December 2023. Furthermore, a selection of the authors' own cases is presented., Results: Audiovestibular tests for the diagnosis of third window syndromes are most often reported for patients with SCDS in the literature. In this context, cut-off values with different sensitivities and specificities have been defined for different outcome parameters of vestibular evoked myogenic potentials. Current developments include the application of electrocochleography, broadband tympanometry, video head impulse testing, and vibration-induced nystagmus. Genetic analyses are increasingly applied in LVAS., Conclusion: The diagnosis of third window syndromes is always based on the synthesis of patients' symptoms, clinical signs, audiovestibular test results, and imaging., (© 2024. The Author(s).)

Background: Communication skills are among the most important key qualifications of the medical profession. To what extent these can also be acquired online in medical education in otolaryngology is investigated in this study., Objective: A voluntary online training for the teaching of communication skills was compared with a corresponding face-to-face format. The question of the extent to which acceptance of the two formats and students' self-assessment of their communicative skills differed was investigated., Materials and Methods: In the online training, students were prepared for the topic asynchronously via a video. Thereafter, they were able to conduct consultations with simulation patients online and synchronously. The face-to-face training was comparable in structure and duration and took place in an earlier semester. The acceptance of both seminars was assessed by a questionnaire with 19 items on a five-point Likert scale. Self-assessment of communication skills was measured by a 10-cm visual analog scale pre/post with 16 items., Results: Both formats achieved high acceptance with an average score (M) of 2.08 (standard deviation, SD = 0.54) for the online format and M = 1.97 (SD = 0.48) for the face-to-face event. Students' self-assessments of communication skills showed a twofold increase in the online group (M = 1.54, SD = 0.94) compared to the face-to-face group (M = 0.75, SD = 0.87)., Conclusion: This study shows that teaching communication skills in the online format was well accepted and resulted in significant changes in students' self-assessment of communication skills., (© 2024. The Author(s).)

We present a measurement of η production from neutrino interactions on argon with the MicroBooNE detector. The modeling of resonant neutrino interactions on argon is a critical aspect of the neutrino oscillation physics program being carried out by the DUNE and Short Baseline Neutrino programs. η production in neutrino interactions provides a powerful new probe of resonant interactions, complementary to pion channels, and is particularly suited to the study of higher-order resonances beyond the Δ(1232). We measure a flux-integrated cross section for neutrino-induced η production on argon of 3.22±0.84(stat)±0.86(syst) 10^{-41}  cm^{2}/nucleon. By demonstrating the successful reconstruction of the two photons resulting from η production, this analysis enables a novel calibration technique for electromagnetic showers in GeV accelerator neutrino experiments.

Purpose: This study aimed to investigate the association between age, immune response, and clinical presentation of ocular toxoplasmosis (OT)., Design: This was a monocentric, retrospective, observational cohort study., Methods: A review of the medical records of patients with active OT at the Uveitis Center, Charité Universitätsmedizin, was conducted. Baseline parameters included age at presentation, visual acuity, intraocular pressure (IOP), size and location of active lesions, inflammatory activity, antibody index (AI), and complications of intraocular inflammation. The data were presented as the mean ± standard deviation (SD). The level of significance was set at a p -value of <0.05., Results: Between 1998 and 2019, 290 patients with active OT were diagnosed at our tertiary reference center. The mean age of the participants was 37.7 ± 17.1 years, 53.8% of them were female individuals, and 195 patients (70.9%) showed recurrent disease. Older age was associated with lower baseline visual acuity ( p  = 0.043), poor visual outcome ( p  = 0.019), increased inflammatory activity ( p  < 0.005), and larger retinal lesions ( p  < 0.005). Older patients presented a lower AI (<35 years: 45.1 ± 82.7, median: 12.1; ≥35 years: 18.6 ± 50.5, median: 5.8; p  = 0.046), confirmed by a decrease in AI with increasing age ( R 2  = 0.045; p  = 0.024). Finally, AI was correlated with lesion size (multiple linear regression analysis: p  = 0.043). Macular involvement (24.3% of patients) was positively correlated with complications (macular/peripapillary edema and retinal detachment, p  < 0.005) and poor visual outcome ( p  < 0.005) and was negatively correlated with inflammatory activity ( p  < 0.005)., Conclusion: We found a strong and clinically relevant impact of age on the clinical presentation and course of OT. While an unspecific inflammatory response increased with age, the specific, local humoral immune response declined. These findings are well in line with the concept of immunosenescence and inflammaging in uveitis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Eraghi, Garweg and Pleyer.)

Objective: To compare four commercially available Essix-type retainers in terms of longevity, wear characteristics, stiffness and their range of rigidity., Materials and Methods: An in vitro study was conducted at Queen Mary University of London. Four groups of thermoplastic materials were included: Duran (PETG), Essix C + (Polypropylene), Vivera and Zendura (Polyurethane). A working typodont was fabricated to evaluate surface wear characteristics using a wear machine with a customized jig. Retainers were measured for tensile test, and water absorption was measured at five different time points up to 6 months after initial immersion in two different physical states and two different solutions. Hydrolytic degradation was also evaluated using FTIR spectroscopy., Results: Essix C + was the most flexible retainer with Vivera the stiffest material. Zendura and Essix C + had the most surface wear (413 μm ± 80 and 652 μm ± 12, respectively) with absorption rates of up to 15 wt% in artificial saliva occurring with Zendura. Only Essix C + displayed signs of degradation following water absorption., Conclusions: All materials had characteristic levels of flexibility and were susceptible to water absorption. Duran 1.5 mm performed similarly to Vivera in relation to stiffness and wear properties. While Zendura and Vivera have similar chemical structures, they exhibited differences concerning wear resistance and water absorption. Further clinical research evaluating the clinical relevance of these laboratory findings is required., Clinical Relevance: Characteristic patterns of wear and rigidity of four commercially available Essix-type retainers were observed. This information should help in the tailoring of retainer material on a case-by-case basis considering treatment-related factors and patient characteristics including parafunctional habits., (© 2024. The Author(s).)

The diffuse presence of small copper ore deposits in the Alpine area, mostly exploited since Late Medieval times, led most scholars to assume that these deposits may actually be active much earlier and that many of the circulating prehistoric metal objects found in the area were produced with local copper sources. This assumption was recently validated for the Recent Bronze Age through the use of lead isotope tracers, and well supported by the archaeometallurgical evidences found in the South-Eastern Alps. However, the scarcity of available lead isotope data for pre-Bronze Age metals precluded to date the reconstruction of the metal flow through the Late Neolithic and Eneolithic (or Copper Age). Based on 49 new analyses of important archaeological objects from the Alpine region, the Po River Valley and Central Italy, mostly axes dated from the Late Neolithic to the Late Eneolithic, here we show that the diffusion of copper in Northern Italy (approximately 4500-2200 BC) includes three major periods of metal use and/or production, each related to specific ore sources. The South Alpine copper was massively used only starting from the middle of the 3rd millennium BC, in connection or slightly earlier than the Beaker event., (© 2024. The Author(s).)

Introduction: The Koraga tribe are an isolated endogamous tribal group found in the southwest coastal region of India. The Koraga language shares inherited grammatical features with North Dravidian languages. To seek a possible genetic basis for this exceptionality and understand the maternal lineage pattern, we have aimed to reconstruct the inter-population and intra-population relationships of the Koraga tribal population by using mtDNA markers for the hypervariable regions along with a partial coding region sequence analysis. Methods and Results: Amongst the 96 individuals studied, we observe 11 haplogroups, of which a few are shared and others are unique to the clans Soppu, Oṇṭi and Kuṇṭu. In addition to several deep rooted Indian-specific lineages of macrohaplogroups M and U, we observe a high frequency of the U1 lineage (∼38%), unique to the Koraga. A Bayesian analysis of the U1 clade shows that the Koraga tribe share their maternal lineage with ancestral populations of the Caucasus at the cusp of the Last Glacial Maximum. Discussion: Our study suggests that the U1 lineage found in the Indian subcontinent represents a remnant of a post-glacial dispersal. The presence of West Asian U1 when viewed along with historical linguistics leads us to hypothesise that Koraga represents a mother tongue retained by a vanquished population group that fled southward at the demise of the Indus civilisation as opposed to a father tongue, associated with a particular paternal lineage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sequeira, Vinuthalakshmi, Das, van Driem and Mustak.)

Neuroendocrine neoplasms (NENs) originate from various epithelial or neuroectodermal tissues, can occur in any organ, including the pancreas, and are characterized by the expression of the neuroendocrine markers synaptophysin and chromogranin A. Pancreatic neuroendocrine tumors (PanNETs) are well-differentiated epithelial neoplasms with morphological and immunohistochemical features of neuroendocrine differentiation of low, intermediate, or high grade. Pancreatic neuroendocrine carcinomas (PanNECs) are clinically aggressive, high-grade (poorly differentiated) carcinomas with morphologic features suggesting neuroendocrine differentiation, a high proliferative rate (> 20 mitoses per 2 mm 2 and Ki67 index > 20%), and immunohistochemical labeling for neuroendocrine markers. They include the small cell neuroendocrine carcinoma and the large cell neuroendocrine carcinoma categories.Neuroendocrine-like morphology coupled with immunohistochemical markers of neuroendocrine differentiation are highly specific. However, neuroendocrine markers may also be expressed in non-neuroendocrine neoplasms, which can therefore be confused with NENs. Mimickers of pancreatic NENs comprise a number of important pitfall tumors, including epithelial and non-epithelial neoplasms, such as acinar cell carcinomas, solid pseudopapillary neoplasms (SPNs), or even non-neoplastic lesions. All of these lesions have the expression of neuroendocrine markers in common, such as synaptophysin and chromogranin A, and although they are comparatively rare, they can cause considerable diagnostic problems. This review article deals with some of the most important mimickers of pancreatic neuroendocrine neoplasms and even non-neoplastic lesions, such as islet aggregation. The similarities and differences between these entities and pancreatic neuroendocrine neoplasms are highlighted, and key findings that facilitate the correct diagnosis are discussed., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

We present the first search for heavy neutral leptons (HNLs) decaying into νe^{+}e^{-} or νπ^{0} final states in a liquid-argon time projection chamber using data collected with the MicroBooNE detector. The data were recorded synchronously with the NuMI neutrino beam from Fermilab's main injector corresponding to a total exposure of 7.01×10^{20} protons on target. We set upper limits at the 90% confidence level on the mixing parameter |U&#95;{μ4}|^{2} in the mass ranges 10≤m&#95;{HNL}≤150  MeV for the νe^{+}e^{-} channel and 150≤m&#95;{HNL}≤245  MeV for the νπ^{0} channel, assuming |U&#95;{e4}|^{2}=|U&#95;{τ4}|^{2}=0. These limits represent the most stringent constraints in the mass range 35

Bacteria contain a wide variety of innate and adaptive immune systems which provide protection to the host against invading genetic material, including bacteriophages (phages). It is becoming increasingly clear that bacterial immune systems are frequently lost and gained through horizontal gene transfer. However, how and when new immune systems can become established in a bacterial population have remained largely unstudied. We developed a joint epidemiological and evolutionary model that predicts the conditions necessary for the spread of a CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated) immune system into a bacterial population lacking this system. We found that whether bacteria carrying CRISPR-Cas will spread (increase in frequency) into a bacterial population depends on the abundance of phages and the difference in the frequency of phage resistance mechanisms between bacteria carrying a CRISPR-Cas immune system and those not (denoted as ${f}&#95;{\Delta }$). Specifically, the abundance of cells carrying CRISPR-Cas will increase if there is a higher proportion of phage resistance (either via CRISPR-Cas immunity or surface modification) in the CRISPR-Cas-possessing population than in the cells lacking CRISPR-Cas. We experimentally validated these predictions in a model using Pseudomonas aeruginosa PA14 and phage DMS3vir. Specifically, by varying the initial ratios of different strains of bacteria that carry alternative forms of phage resistance, we confirmed that the spread of cells carrying CRISPR-Cas through a population can be predicted based on phage density and the relative frequency of resistance phenotypes. Understanding which conditions promote the spread of CRISPR-Cas systems helps to predict when and where these defences can become established in bacterial populations after a horizontal gene transfer event, both in ecological and clinical contexts., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Society for Microbial Ecology.)

The radius valley (or gap) in the observed distribution of exoplanet radii, which separates smaller super-Earths from larger sub-Neptunes, is a key feature that theoretical models must explain. Conventionally, it is interpreted as the result of the loss of primordial hydrogen and helium (H/He) envelopes atop rocky cores. However, planet formation models predict that water-rich planets migrate from cold regions outside the snowline towards the star. Assuming water to be in the form of solid ice in their interior, many of these planets would be located in the radius gap contradicting observations. Here we use an advanced coupled formation and evolution model that describes the planets' growth and evolution starting from solid, moon-sized bodies in the protoplanetary disk to mature Gyr-old planetary systems. Employing new equations of state and interior structure models to treat water as vapour mixed with H/He, we naturally reproduce the valley at the observed location. The model results demonstrate that the observed radius valley can be interpreted as the separation of less massive, rocky super-Earths formed in situ from more massive, ex situ, water-rich sub-Neptunes. Furthermore, the occurrence drop at larger radii, the so-called radius cliff, is matched by planets with water-dominated envelopes. Our statistical approach shows that the synthetic distribution of radii quantitatively agrees with observations for close-in planets, but only if low-mass planets initially containing H/He lose their atmosphere due to photoevaporation, which populates the super-Earth peak with evaporated rocky cores. Therefore, we provide a hybrid theoretical explanation of the radius gap and cliff caused by both planet formation (orbital migration) as well as evolution (atmospheric escape)., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2024.)