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14-3-3 proteins activate Pseudomonas exotoxins-S and -T by chaperoning a hydrophobic surface

Pseudomonas are a common cause of hospital-acquired infections that may be lethal. ADP-ribosyltransferase activities of Pseudomonas exotoxin-S and -T depend on 14-3-3 proteins inside the host cell. By binding in the 14-3-3 phosphopeptide binding groove, an amphipathic C-terminal helix of ExoS and ExoT has been thought to be crucial for their activation. However, crystal structures of the 14-3-3β:E

Tertiary lymphoid structures in high-grade serous tubo-ovarian carcinoma : anatomical site matters

Tertiary lymphoid structures (TLS) in the tumor microenvironment are prognostically beneficial in many solid cancer types. Reports on TLS in high-grade serous tubo-ovarian carcinoma (HGSC) are few, and the prognostic impact is unclear. We investigated mature TLS (mTLS), immature TLS (iTLS) and lymphoid aggregates (LA) in primary adnexal tumors (PTs) and synchronous omental/peritoneal metastases (p

A 1D imaging soft X-ray spectrometer for the small quantum systems instrument at the European XFEL

A 1D imaging soft X-ray spectrometer installed on the small quantum systems (SQS) scientific instrument of the European XFEL is described. It uses movable cylindrical constant-line-spacing gratings in the Rowland configuration for energy dispersion in the vertical plane, and Wolter optics for simultaneous 1D imaging of the source in the horizontal plane. The soft X-ray fluorescence spectro-imaging

The impact of hypoglycaemia on daily functioning among adults with diabetes : a prospective observational study using the Hypo-METRICS app

Aims/hypothesis: The aim of this work was to examine the impact of hypoglycaemia on daily functioning among adults with type 1 diabetes or insulin-treated type 2 diabetes, using the novel Hypo-METRICS app. Methods: For 70 consecutive days, 594 adults (type 1 diabetes, n=274; type 2 diabetes, n=320) completed brief morning and evening Hypo-METRICS ‘check-ins’ about their experienced hypoglycaemia a

Bowel cleansing quality evaluation in colon capsule endoscopy : what is the reference standard?

Background: The diagnostic accuracy of colon capsule endoscopy (CCE) depends on a well-cleansed bowel. Evaluating the cleansing quality can be difficult with a substantial interobserver variation. Objectives: Our primary aim was to establish a standard of agreement for bowel cleansing in CCE based on evaluations by expert readers. Then, we aimed to investigate the interobserver agreement on bowel

Redshifted Sodium Transient near Exoplanet Transit

Neutral sodium (Na i) is an alkali metal with a favorable absorption cross section such that tenuous gases are easily illuminated at select transiting exoplanet systems. We examine both the time-averaged and time-series alkali spectral flux individually, over 4 nights at a hot Saturn system on a ∼2.8 day orbit about a Sun-like star WASP-49 A. Very Large Telescope/ESPRESSO observations are analyzed

Hg 178 and asymmetric fission of neutron-deficient pre-actinides

Fission at low excitation energy is an ideal playground to probe the impact of nuclear structure on nuclear dynamics. While the importance of structural effects in the nascent fragments is well established in the (trans-)actinide region, the observation of asymmetric fission in several neutron-deficient pre-actinides can be explained by various mechanisms. To deepen our insight into that puzzle, a

Integrating daylighting and lighting in practice : Lessons learned from international case studies

This report presents lessons learned from twenty-five worldwide real-life case studies implementing the integration of daylighting and electric lighting. The case studies were monitored with respect to energy use for lighting, visual performance, non-visual performance, and users’ satisfaction. The monitoring is largely based on field measurements, but it is also complemented with simulations and

High rate of recurrent venous thromboembolism in patients with myeloproliferative neoplasms and effect of prophylaxis with Vitamin K antagonists

The optimal duration of treatment with vitamin K antagonists (VKA) after venous thromboembolism (VTE) in patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) is uncertain. To tackle this issue, we retrospectively studied 206 patients with MPN-related VTE (deep venous thrombosis of the legs and/or pulmonary embolism). After this index event, we recorded over 695 pt-years 45 recur

Initial seeding of the embryonic thymus by immune-restricted lympho-myeloid progenitors

The final stages of restriction to the T cell lineage occur in the thymus after the entry of thymus-seeding progenitors (TSPs). The identity and lineage potential of TSPs remains unclear. Because the first embryonic TSPs enter a non-vascularized thymic rudiment, we were able to directly image and establish the functional and molecular properties of embryonic thymopoiesis-initiating progenitors (T-

Safety and efficacy of pomalidomide plus low-dose dexamethasone in STRATUS (MM-010) : A phase 3b study in refractory multiple myeloma

Patients with relapsed and/or refractory multiple myeloma (RRMM) have poor prognosis. The STRATUS study assessed safety and efficacy of pomalidomide plus low-dose dexamethasone in the largest cohort to date of patients with RRMM. Patients who failed treatment with bortezomib and lenalidomide and had adequate prior alkylator therapy were eligible. Pomalidomide 4 mg was given on days 1-21 of 28-day

Secondary cytoreductive surgery and peri-operative intraperitoneal chemotherapy for peritoneal recurrence of colorectal and appendiceal peritoneal carcinomatosis following prior primary cytoreduction

PURPOSE: Primary cytoreductive surgery (CRS) and peri-operative intraperitoneal chemotherapy (PIC) is the only curative option for patients with colorectal cancer peritoneal carcinomatosis (PC). A significant proportion of patients develop peritoneal recurrence. Outcomes of patients undergoing secondary CRS and PIC for recurrent PC were examined.METHODS: All patients undergoing second procedures w

Molecular alterations associated with liver metastases development in colorectal cancer patients

BACKGROUND: Understanding the molecular biology of colorectal cancer (CRC) provides opportunities for effective personalised patient management. We evaluated whether chromosomal aberrations, mutations in the PI(3)K signalling pathway and the CpG-island methylator phenotype (CIMP) in primary colorectal tumours can predict liver metastases.METHODS: Formalin-fixed paraffin-embedded material from prim

Challenging the dogma of colorectal peritoneal metastases as an untreatable condition : Results of a population-based study

PURPOSE: To determine the impact of the implementation of novel systemic regimens and locoregional treatment modalities on survival at population level in colorectal cancer (CRC) patients presenting with peritoneal metastases (PMs).METHODS: All consecutive CRC patients with synchronous PM (<3 months) between 1995 and 2014 were extracted from the Eindhoven area of the Netherlands Cancer Registry. T

Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer

PURPOSE: To confirm the findings from uncontrolled studies that aggressive cytoreduction in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) is superior to standard treatment in patients with peritoneal carcinomatosis of colorectal cancer origin.PATIENTS AND METHODS: Between February 1998 and August 2001, 105 patients were randomly assigned to receive either standard treatment co

Quality assessment of radiotherapy in the prospective randomized SENOMAC trial

Background and purpose: Recommendations for regional radiotherapy (RT) of sentinel lymph node (SLN)-positive breast cancer are debated. We here report a RT quality assessment of the SENOMAC trial. Materials and Methods: The SENOMAC trial randomized clinically node-negative breast cancer patients with 1–2 SLN macrometastases to completion axillary lymph node dissection (cALND) or SLN biopsy only be

MiDAS 5 : Global diversity of bacteria and archaea in anaerobic digesters

Anaerobic digestion of organic waste into methane and carbon dioxide (biogas) is carried out by complex microbial communities. Here, we use full-length 16S rRNA gene sequencing of 285 full-scale anaerobic digesters (ADs) to expand our knowledge about diversity and function of the bacteria and archaea in ADs worldwide. The sequences are processed into full-length 16S rRNA amplicon sequence variants

The role of echocardiography in sports cardiology : An expert opinion statement of the Italian Society of Sports Cardiology (SIC sport)

Transthoracic echocardiography (TTE) is routinely required during pre-participation screening in the presence of symptoms, family history of sudden cardiac death or cardiomyopathies <40-year-old, murmurs, abnormal ECG findings or in the follow-up of athletes with a history of cardiovascular disease (CVD). TTE is a cost-effective first-line imaging modality to evaluate the cardiac remodeling due to

A temporal developmental map separates human NK cells from noncytotoxic ILCs through clonal and single-cell analysis

Natural killer (NK) cells represent the cytotoxic member within the innate lymphoid cell (ILC) family that are important against viral infections and cancer. Although the NK cell emergence from hematopoietic stem and progenitor cells through multiple intermediate stages and the underlying regulatory gene network has been extensively studied in mice, this process is not well characterized in humans