Maternal and neonatal outcomes associated with illness severity of maternal COVID-19.

BACKGROUND: Several reports demonstrated that perinatal SARS-CoV-2 has significant impact on maternal and neonatal health outcomes. However, the relationship between severity of maternal illness with outcomes remains less clear. METHODS: This is a single-center retrospective cohort study of mother/infant dyads with positive maternal test for SARS-CoV-2 between 14 days prior and 3 days after delivery from 3/30/2020 to 12/28/2021. RESULTS: Among 538 mothers, those with moderate/severe/critical illness were more likely to undergo induction, receive oxygen, mechanical ventilation or ECMO. Mortality was significantly higher among the mothers with severe illness than asymptomatic and those with mild illness (6% vs 0% and 0%, respectively, P < 0.05). Neonates born to mothers with moderate/severe/critical illness were more likely to be preterm with lower birth weight, and to be admitted to the NICU (P < 0.05) but not to be small for gestational age. Mild maternal illness was only associated with NICU admission for isolation precaution and decreased rate of breastfeeding. CONCLUSIONS: Maternal illness severity was significantly associated with prematurity and several adverse maternal and neonatal outcomes.

[Rare case of reconstruction of the anterior thigh compartment after resection of high-grade sarcoma by hybrid technique: Latissimus dorsi free flap associated with a medial gastrocnemius pedicled flap]. / Cas rare de reconstruction de la loge antérieure de cuisse après résection d'un sarcome de haut grade par technique hybride : lambeau libre de grand dorsal associé à un lambeau gastrocnémien médial pédiculé.

INTRODUCTION: The soft tissue sarcomas of the limbs require extensive surgical excision. Reconstructive surgery plays an essential role in its management to preserve the limb, as exposed in a case of thigh sarcoma. CLINICAL CASE: A 73-year-old patient has a large sarcoma within the quadriceps. Its excision requires resection of the entire anterior thigh compartment. Preservation of the limb is permitted by reconstruction by latissimus dorsi free flap and medial gastrocnemius pedicled flap. The patient resumed walking using an orthosis at 3 months. CONCLUSION: Surgery to remove a sarcoma of a limb can threaten the integrity of the limb. Plastic surgery, with all the reconstruction techniques, contributes to the preservation of a functional limb.

Endoscopic vacuum therapy significantly improves clinical outcomes of anastomotic leakages after 2-stage, 3-stage, and transhiatal esophagectomies.

BACKGROUND: Anastomotic leakages after esophagectomies continue to constitute significant morbidity and mortality. Intrathoracic anastomoses pose a high risk for mediastinitis, sepsis, and death, if a leak is not addressed timely and appropriately. However, there are no standardized treatment recommendations or algorithms as for how to treat these leakages. METHODS: The study included all patients at the University Hospital Regensburg, who developed an anastomotic leakage after esophagectomy with gastric pull-up reconstruction from 2007 to 2022. Patients receiving conventional treatment options for an anastomotic leakage (stents, drainage tubes, clips, etc.) were compared to patients receiving endoscopic vacuum-assisted closure (eVAC) therapy as their mainstay of treatment. Treatment failure was defined as cervical esophagostomy formation or death. RESULTS: In total, 37 patients developed an anastomotic leakage after esophagectomy with a gastric pull-up reconstruction. Twenty patients were included into the non-eVAC cohort, whereas 17 patients were treated with eVAC. Treatment failure was observed in 50% of patients (n = 10) in the non-eVAC cohort and in 6% of patients (n = 1) in the eVAC cohort (p < 0.05). The 90-day mortality in the non-eVAC cohort was 15% (n = 3) compared to 6% (n = 1) in the eVAC cohort. Cervical esophagostomy formation was required in 40% of cases (n = 8) in the non-eVAC cohort, whereas no patient in the eVAC cohort underwent cervical esophagostomy formation. CONCLUSION: eVAC therapy for leaking esophagogastric anastomoses appears to be superior to other treatment strategies as it significantly reduces morbidity and mortality. Therefore, we suggest eVAC as an essential component in the treatment algorithm for anastomotic leakages following esophagectomies, especially in patients with intrathoracic anastomoses.

A two-ward acute care hospital outbreak of SARS-CoV-2 delta variant including a point-source outbreak associated with the use of a mobile vital signs cart and sub-optimal doffing of personal protective equipment.

BACKGROUND: The arrival of the Delta variant of SARS-CoV-2 was associated with increased transmissibility and illness of greater severity. Reports of nosocomial outbreaks of Delta variant COVID-19 in acute care hospitals have been described but control measures varied widely. AIM: Epidemiological investigation of a linked two-ward COVID-19 Delta variant outbreak was conducted to elucidate its source, risk factors, and control measures. METHODS: Investigations included epidemiologic analysis, detailed case review serial SARS-CoV-2 reverse transcriptase-polymerase chain reaction (RT-PCR) testing of patients and healthcare workers (HCWs), viral culture, environmental swabbing, HCW-unaware personal protective equipment (PPE) audits, ventilation assessments, and the use of whole genome sequencing (WGS). FINDINGS: This linked two-ward outbreak resulted in 17 patient and 12 HCW cases, despite an 83% vaccination rate. In this setting, suboptimal adherence and compliance to PPE protocols, suboptimal hand hygiene, multi-bedded rooms, and a contaminated vital signs cart with potential fomite or spread via the hands of HCWs were identified as significant risk factors for nosocomial COVID-19 infection. Sudden onset of symptoms, within 72 h, was observed in 79% of all Ward 2 patients, and 93% of all cases (patients and HCWs) on Ward 2 occurred within one incubation period, consistent with a point-source outbreak. RT-PCR assays showed low cycle threshold (CT) values, indicating high viral load from environmental swabs including the vital signs cart. WGS results with ≤3 SNP differences between specimens were observed. CONCLUSION: Outbreaks on both wards settled rapidly, within 3 weeks, using a `back-to-basics' approach without extraordinary measures or changes to standard PPE requirements. Strict adherence to recommended PPE, hand hygiene, education, co-operation from HCWs, including testing and interviews, and additional measures such as limiting movement of patients and staff temporarily were all deemed to have contributed to prompt resolution of the outbreak.

Long-term care, care needs and wellbeing of individuals after cancer in childhood or adolescence (VersKiK): study protocol of a large scale multi-methods non-interventional study.

BACKGROUND: It has been shown previously that a relevant proportion of childhood cancer survivors suffers from late effects, which are often directly related to the cancer itself or its therapy, resulting in particular follow-up needs, additionally burdening healthcare systems. Being diagnosed with cancer at a vulnerable stage of development, this group of cancer survivors is at comparatively higher risk of relapse or subsequent cancer. Although national and international follow-up guidelines based on treatment modalities have been developed, their implementation seems to leave room for improvement. Additionally, they lack a sufficient consideration of the survivors' psychosocial needs, affecting their adherence to them. The aim of the VersKiK study is to provide representative information on late effects in childhood and adolescence cancer survivors in Germany. The main research objectives are: (1) to describe the state of follow-up care among survivors after a cancer diagnosis in childhood or adolescence; (2) to quantify the occurrence of late effects among this group of survivors; (3) to examine the adherence to selected audiological and cardiological follow-up guidelines and to identify factors affecting it; (4) to explore actual follow-up needs of paediatric cancer survivors; (5) to review selected follow-up guidelines with the aim to improve and expand them. METHODS: VersKiK is designed as a mixed-methods non-interventional study. We will use claims data from statutory health insurance companies in combination with individually linked population-based registry data from the German Childhood Cancer Registry (GCCR). This data base will permit us to quantify diagnoses and procedures in comparison to the general population as well as the adherence to existing follow-up guidelines. Additional information will be obtained through interviews with childhood and adolescence cancer survivors and their informal caregivers, as well as in focus groups with healthcare professionals. DISCUSSION: The present study aims to research the actual needs of individuals after cancer diagnosis and treatment in childhood or adolescence - physical, psychological and organisational - in order to improve existing follow-up guidelines. These improvements might further positively affect not only actual care provided to paediatric cancer survivors, but also benefit healthcare systems in general while decreasing consequent medical visits in this group of patients. TRIAL REGISTRATION: Registered at German Clinical Trial Register (ID: DRKS00025960 and DRKS00026092).

The effects of pazopanib on doxorubicin pharmacokinetics in children and adults with non-rhabdomyosarcoma soft tissue sarcoma: a report from Children's Oncology Group and NRG Oncology study ARST1321.

PURPOSE: The use of tyrosine kinase inhibitors for the treatment for soft tissue sarcomas is increasing given promising signals of activity in a variety of tumor types. The recently completed study in non-rhabdomyosarcoma soft tissue sarcomas, ARST1321, demonstrated that the addition of pazopanib to neoadjuvant ifosfamide, doxorubicin, and radiation improved the pathological near complete response rate compared with chemoradiotherapy alone. Pharmacokinetic (PK) evaluation of doxorubicin with pazopanib has not been previously reported. As an exploratory aim, doxorubicin PK data were collected during the dose-finding phase of the study in patients receiving chemotherapy and pazopanib to assess the effect of pazopanib on doxorubicin PK parameters. METHODS: Blood samples were collected during cycle 2 (week 4) of chemotherapy at the following time points from doxorubicin administration: predose, 5, 30, and 60 min, and 2, 4, 8, 24 ± 3, and 48 ± 3 h after dosing. The population pharmacokinetic and individual post hoc estimates of doxorubicin and doxorubicinol were determined by nonlinear mixed-effects modeling. RESULTS: There were 52 doxorubicin and doxorubicinol samples from 7 individuals in this study (median age: 17 years; range 14-23). The doxorubicin clearance was 26.9 (16.1, 36.4, and 33.9) L/h/m2 (post hoc median and range) and 25.8 (23.3%) L/h/m2 [population estimate and IIV (CV%)]. The doxorubicinol apparent clearance was 67.5 (18.2, 1701) L/h/m2 (post hoc median and range) and 58.7 (63.7%) L/h/m2 [population estimate and IIV (CV%)]. CONCLUSION: The PK data of seven patients treated on ARST1321 is consistent with previously reported population and post hoc doxorubicin clearance and doxorubicinol apparent clearance estimates, showing that the addition of pazopanib does not significantly alter doxorubicin pharmacokinetics. These data support the safety of administration of pazopanib with doxorubicin-containing chemotherapy.

Writhed Analytical Magnetic Flux Rope Model.

Observations of magnetic clouds, within interplanetary coronal mass ejections (ICMEs), are often well described by flux rope models. Most of these assume either a cylindrical or toroidal geometry. In some cases, these models are also capable of accounting for non-axisymmetric cross-sections but they generally all assume axial invariance. It can be expected that any ICME, and its flux rope, will be deformed along its axis due to influences such as the solar wind. In this work, we aim to develop a writhed analytical magnetic flux rope model which would allow us to analytically describe a flux rope structure with varying curvature and torsion so that we are no longer constrained to a cylindrical or toroidal geometry. In this first iteration of our model we will solely focus on a circular cross-section of constant size. We describe our flux rope geometry in terms of a parametrized flux rope axis and a parallel transport frame. We derive expressions for the axial and poloidal magnetic field components under the assumption that the total axial magnetic flux is conserved. We find an entire class of possible solutions, which differ by the choice of integration constants, and present the results for a specific example. In general, we find that the twist of the magnetic field locally changes when the geometry deviates from a cylinder or torus. This new approach also allows us to generate completely new types of in situ magnetic field profiles which strongly deviate from those generated by cylindrical or toroidal models.

A novel tropoelastin-based resorbable surgical mesh for pelvic organ prolapse repair.

Pelvic organ prolapse is a common condition that affects 1 in 4 women across all age groups. It is mainly caused by vaginal birth injury and can be exacerbated by obesity and increased age. Until recently, treatment strategies often used non-degradable synthetic meshes for reconstructive surgery. However, owing to their frequent, unacceptable rate of adverse events such as mesh erosion, transvaginal meshes have been banned in many countries. Recent reports have highlighted the urgent need for biocompatible design of meshes for a safe and effective treatment in the long term. This study reports the design and evaluation of a novel, elastin based degradable mesh using an ovine model of POP as a potential surgical treatment. Elastin is a protein component of the ECM and provides elasticity to tissues throughout the body. Tropoelastin, the monomer subunit of elastin, has been used with success in electrospun constructs as it is a naturally cell interactive polymer. Biomaterials that incorporate tropoelastin support cell attachment and proliferation, and have been proven to encourage elastogenesis and angiogenesis in vitro and in vivo. The biological properties of tropoelastin were combined with the physical properties of PCL, a degradable synthetic polymer, with the aim of producing, characterizing and assessing the performance of continuous tropoelastin:PCL electrospun yarns. Using a modified spinneret electrospinning system and adjusting settings based on relative humidity, four blends of tropoelastin:PCL yarns were fabricated with concentration ratios of 75:25, 50:50, 25:75 and 0:100. Yarns were assessed for ease of manufacture, fibrous architecture, protein/polymer content, yarn stability - including initial tropoelastin release, mechanical strength, and ability to support cell growth. Based on overall favorable properties, a mesh woven from the 50:50 tropoelastin:PCL yarn was implanted into the vagina of a parous ewe with vaginal wall weakness as a model of pelvic organ prolapse. This mesh showed excellent integration with new collagen deposition by SEM and a predominant M2 macrophage response with few pro-inflammatory M1 macrophages after 30 days. The woven tropoelastin:PCL electrospun mesh shows potential as an alternative to non-degradable, synthetic pelvic organ prolapse mesh products.

A multi-stop time-of-flight spectrometer for the measurement of positron annihilation-induced electrons in coincidence with the Doppler-shifted annihilation gamma photon.

In this study, we describe an advanced multi-functional, variable-energy positron beam system capable of measuring the energies of multiple "positron-induced" electrons in coincidence with the Doppler-shifted gamma photon resulting from the annihilation of the correlated positron. The measurements were carried out using the unique characteristics of the digital time-of-flight spectrometer and the gamma spectrometer available with the advanced positron beam system. These measurements have resulted in (i) the first digital time-of-flight spectrum of positron annihilation-induced Auger electrons generated using coincident signals from a high-purity Ge detector and a micro-channel plate, (ii) a two-dimensional array of the energy of Doppler-broadened annihilation gamma and the time-of-flight of positron-annihilation induced Auger electrons/secondary electrons measured in coincidence with the annihilation gamma photon, and (iii) the time-of-flight spectra of multiple secondary electrons ejected from a bilayer graphene surface as a result of the impact and/or annihilation of positrons. The novelty of the gamma-electron coincidence spectroscopy has been demonstrated by extracting the Doppler-broadened spectrum of gamma photons emitted due to the annihilation of positrons exclusively with 1s electrons of carbon. The width of the extracted Doppler-broadened gamma spectrum has been found to be consistent with the expected broadening of the annihilation gamma spectrum due to the momentum of the 1s electrons in carbon.

[RABBIT-SpA: a new disease register for axial spondyloarthritis and psoriatic arthritis]. / RABBIT-SpA: ein neues Krankheitsregister für axiale Spondyloarthritis und Psoriasisarthritis.

BACKGROUND: The treatment of axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) has changed enormously in recent years due to market authorization of a number of new biologicals with different modes of action and the increasing use of biosimilars. Real-world data on long-term safety and efficacy under routine daily conditions is not yet sufficient. Therefore, the German Rheumatism Research Center has initiated a new cohort study covering axSpA and PsA. OBJECTIVE: Presentation of initial results from the new register RABBIT-SpA, which was started in May 2017. MATERIAL AND METHODS: This is a prospective longitudinal cohort study with a similar study design to the German biologics register RABBIT. Patients can be included at the start of a new treatment either in the so-called index drug group or in the comparison group (conventional systemic treatment, including non-steroidal anti-inflammatory drugs, NSAID). Follow-up per patient should be at least 5 years and preferably 10 years. The RABBIT-SpA uses a web-based documentation system. RESULTS: Up to mid-December 2018 a total of 514 axSpA patients had been documented in RABBIT-SpA, 410 with an index drug and 104 with conventional treatment. There are differences between these treatment groups, e. g. in the duration of the disease and in parameters of disease activity. It is also noticeable that in axSpA patients, approximately 5 years lie between the onset of the symptoms and confirmation of the diagnosis. Of the 355 PsA patients, 265 were included with an index drug and 90 with conventional treatment. Of the PsA patients 86% have a dominant peripheral manifestation. The average number of pressure tender joints is 8 and the average number of swollen joints is 4. CONCLUSION: The online register RABBIT-SpA is well-received by the participating rheumatological institutions. The electronic recording of patient data can be carried out in a reasonable time. Participation in the RABBIT-SpA is open to new rheumatological institutions at any time.

Facial width-to-height ratio is associated with agonistic and affiliative dominance in bonobos (Pan paniscus).

Facial width-to-height ratio (fWHR) is associated with social dominance in human and non-human primates, which may reflect the effects of testosterone on facial morphology and behaviour. Given that testosterone facilitates status-seeking motivation, the association between fWHR and behaviour should be contingent on the relative costs and benefits of particular dominance strategies across species and socioecological contexts. We tested this hypothesis in bonobos (Pan paniscus), who exhibit female dominance and rely on both affiliation and aggression to achieve status. We measured fWHR from facial photographs, affiliative dominance with Assertiveness personality scores and agonistic dominance with behavioural data. Consistent with our hypothesis, agonistic and affiliative dominance predicted fWHR in both sexes independent of age and body weight, supporting the role of status-seeking motivation in producing the link between fWHR and socioecologically relevant dominance behaviour across primates.

Osteophyte growth in early thumb carpometacarpal osteoarthritis.

OBJECTIVE: Osteophyte formation is a critical part of the degeneration of a joint with osteoarthritis (OA). While often qualitatively described, few studies have succeeded in quantifying osteophyte growth over time. Using computed tomography (CT) image data from a longitudinal, observational study of thumb carpometacarpal (CMC) OA, our aim was to quantify osteophyte growth volume and location over a three-year period in men and women. METHOD: Ninety patients with early thumb OA were recruited and assessed at baseline, 1.5 years, and 3 years with CT imaging. Osteophyte volume and location on the trapezium and first metacarpal were determined using a library of 46 healthy subjects as a nonarthritic reference database. RESULTS: There was a significant increase in osteophyte volume for women and men over the three-year follow-up in the trapezium (86.8 mm3-120.5 mm3 and 165.1 mm3-235.3 mm3, means respectively) and in the proximal metacarpal (63 mm3-80.4 mm3, and 115.8 mm3-161.7 mm3, respectively). The location of osteophyte initiation and growth was consistent across subjects and was located in non-opposing regions on the trapezium and first metacarpal. Osteophyte growth occurred about the radial and ulnar margins of the trapezial facet, while on the proximal metacarpal, growth occurred principally about the volar and dorsal margins of the facet. CONCLUSION: Osteophyte growth occurred in early thumb osteoarthritis over three years. Growth was localized in specific, non-opposing regions on the trapezium and metacarpal, raising intriguing questions about the triggers for their formation, whether the mechanisms are mechanical, biological or a combination of both.

Coarse-grained model of tropoelastin self-assembly into nascent fibrils.

Elastin is the dominant building block of elastic fibers that impart structural integrity and elasticity to a range of important tissues, including the lungs, blood vessels, and skin. The elastic fiber assembly process begins with a coacervation stage where tropoelastin monomers reversibly self-assemble into coacervate aggregates that consist of multiple molecules. In this paper, an atomistically based coarse-grained model of tropoelastin assembly is developed. Using the previously determined atomistic structure of tropoelastin, the precursor molecule to elastic fibers, as the basis for coarse-graining, the atomistic model is mapped to a MARTINI-based coarse-grained framework to account for chemical details of protein-protein interactions, coupled to an elastic network model to stabilize the structure. We find that self-assembly of monomers generates up to ∼70 â€‹nm of dense aggregates that are distinct at different temperatures, displaying high temperature sensitivity. Resulting assembled structures exhibit a combination of fibrillar and globular substructures within the bulk aggregates. The results suggest that the coalescence of tropoelastin assemblies into higher order structures may be reinforced in the initial stages of coacervation by directed assembly, supporting the experimentally observed presence of heterogeneous cross-linking. Self-assembly of tropoelastin is driven by interactions of specific hydrophobic domains and the reordering of water molecules in the system. Domain pair orientation analysis throughout the self-assembly process at different temperatures suggests coacervation is a driving force to orient domains for heterogeneous downstream cross-linking. The model provides a framework to characterize macromolecular self-assembly for elastin, and the formulation could easily be adapted to similar assembly systems.

Fast molecular outflow from a dusty star-forming galaxy in the early Universe.

Galaxies grow inefficiently, with only a small percentage of the available gas converted into stars each free-fall time. Feedback processes, such as outflowing winds driven by radiation pressure, supernovae, or supermassive black hole accretion, can act to halt star formation if they heat or expel the gas supply. We report a molecular outflow launched from a dust-rich star-forming galaxy at redshift 5.3, 1 billion years after the Big Bang. The outflow reaches velocities up to 800 kilometers per second relative to the galaxy, is resolved into multiple clumps, and carries mass at a rate within a factor of 2 of the star formation rate. Our results show that molecular outflows can remove a large fraction of the gas available for star formation from galaxies at high redshift.

Early morphologic changes in trapeziometacarpal joint bones with osteoarthritis.

OBJECTIVE: Characterising the morphological differences between healthy and early osteoarthritic (EOA) trapeziometacarpal (TMC) joints is important for understanding osteoarthritis onset, and early detection is important for treatment and disease management. This study has two aims: first, to characterise morphological differences between healthy and EOA TMC bones. The second aim was to determine the efficacy of using a statistical shape model (SSM) to detect early signs of osteoarthritis (OA). METHODS: CT image data of TMC bones from 22 asymptomatic volunteers and 47 patients with EOA were obtained from an ongoing study and used to generate a SSM. A linear discriminant analysis (LDA) classifier was trained on the principal component (PC) weights to characterise features of each group. Multivariable statistical analysis was performed on the PC to investigate morphologic differences. Leave-one-out classification was performed to evaluate the classifiers performance. RESULTS: We found that TMC bones of EOA subjects exhibited a lower aspect ratio (P = 0.042) compared with healthy subjects. The LDA classifier predicted that protrusions (up to 1.5 mm) at the volar beak of the first metacarpal were characteristic of EOA subjects. This was accompanied with widening of the articular surface, deepening of the articular surface, and protruding bone growths along the concave margin. These characteristics resulted in a leave-one-out classification accuracy of 73.9% (95% CI [61.9%, 83.8%]), sensitivity of 89.4%, specificity of 40.9%, and precision of 75.9%. CONCLUSION: Our findings indicate that morphological degeneration is well underway in the EOA TMC joint, and shows promise for a clinical tool that can detect these features automatically.

Author Correction: A massive core for a cluster of galaxies at a redshift of 4.3.

Change history: In this Letter, the Acknowledgements section should have included the following sentence: "The National Radio Astronomy Observatory is a facility of the National Science Foundation operated under cooperative agreement by Associated Universities, Inc.". This omission has been corrected online.

A massive core for a cluster of galaxies at a redshift of 4.3.

Massive galaxy clusters have been found that date to times as early as three billion years after the Big Bang, containing stars that formed at even earlier epochs1-3. The high-redshift progenitors of these galaxy clusters-termed 'protoclusters'-can be identified in cosmological simulations that have the highest overdensities (greater-than-average densities) of dark matter4-6. Protoclusters are expected to contain extremely massive galaxies that can be observed as luminous starbursts 7 . However, recent detections of possible protoclusters hosting such starbursts8-11 do not support the kind of rapid cluster-core formation expected from simulations 12 : the structures observed contain only a handful of starbursting galaxies spread throughout a broad region, with poor evidence for eventual collapse into a protocluster. Here we report observations of carbon monoxide and ionized carbon emission from the source SPT2349-56. We find that this source consists of at least 14 gas-rich galaxies, all lying at redshifts of 4.31. We demonstrate that each of these galaxies is forming stars between 50 and 1,000 times more quickly than our own Milky Way, and that all are located within a projected region that is only around 130 kiloparsecs in diameter. This galaxy surface density is more than ten times the average blank-field value (integrated over all redshifts), and more than 1,000 times the average field volume density. The velocity dispersion (approximately 410 kilometres per second) of these galaxies and the enormous gas and star-formation densities suggest that this system represents the core of a cluster of galaxies that was already at an advanced stage of formation when the Universe was only 1.4 billion years old. A comparison with other known protoclusters at high redshifts shows that SPT2349-56 could be building one of the most massive structures in the Universe today.

Galaxy growth in a massive halo in the first billion years of cosmic history.

According to the current understanding of cosmic structure formation, the precursors of the most massive structures in the Universe began to form shortly after the Big Bang, in regions corresponding to the largest fluctuations in the cosmic density field. Observing these structures during their period of active growth and assembly-the first few hundred million years of the Universe-is challenging because it requires surveys that are sensitive enough to detect the distant galaxies that act as signposts for these structures and wide enough to capture the rarest objects. As a result, very few such objects have been detected so far. Here we report observations of a far-infrared-luminous object at redshift 6.900 (less than 800 million years after the Big Bang) that was discovered in a wide-field survey. High-resolution imaging shows it to be a pair of extremely massive star-forming galaxies. The larger is forming stars at a rate of 2,900 solar masses per year, contains 270 billion solar masses of gas and 2.5 billion solar masses of dust, and is more massive than any other known object at a redshift of more than 6. Its rapid star formation is probably triggered by its companion galaxy at a projected separation of 8 kiloparsecs. This merging companion hosts 35 billion solar masses of stars and has a star-formation rate of 540 solar masses per year, but has an order of magnitude less gas and dust than its neighbour and physical conditions akin to those observed in lower-metallicity galaxies in the nearby Universe. These objects suggest the presence of a dark-matter halo with a mass of more than 100 billion solar masses, making it among the rarest dark-matter haloes that should exist in the Universe at this epoch.

An oncogenic axis of STAT-mediated BATF3 upregulation causing MYC activity in classical Hodgkin lymphoma and anaplastic large cell lymphoma.

Classical Hodgkin lymphoma (cHL) and anaplastic large cell lymphoma (ALCL) feature high expression of activator protein-1 (AP-1) transcription factors, which regulate various physiological processes but also promote lymphomagenesis. The AP-1 factor basic leucine zipper transcription factor, ATF-like 3 (BATF3), is highly transcribed in cHL and ALCL; however, its functional importance in lymphomagenesis is unknown. Here we show that proto-typical CD30+ lymphomas, namely cHL (21/30) and primary mediastinal B-cell lymphoma (8/9), but also CD30+ diffuse large B-cell lymphoma (15/20) frequently express BATF3 protein. Mass spectrometry and co-immunoprecipitation established interactions of BATF3 with JUN and JUNB in cHL and ALCL lines. BATF3 knockdown using short hairpin RNAs was toxic for cHL and ALCL lines, reducing their proliferation and survival. We identified MYC as a critical BATF3 target and confirmed binding of BATF3 to the MYC promoter. JAK/STAT signaling regulated BATF3 expression, as chemical JAK2 inhibition reduced and interleukin 13 stimulation induced BATF3 expression in cHL lines. Chromatin immunoprecipitation substantiated a direct regulation of BATF3 by STAT proteins in cHL and ALCL lines. In conclusion, we identified STAT-mediated BATF3 expression that is essential for lymphoma cell survival and promoted MYC activity in cHL and ALCL, hence we recognized a new oncogenic axis in these lymphomas.