Background & Aims A randomized trial that compared endoscopic and surgical drainage of the pancreatic duct in patients with advanced chronic pancreatitis reported a significant benefit of surgery ...after a 2-year follow-up period. We evaluated the long-term outcome of these patients after 5 years. Methods Between 2000 and 2004, 39 symptomatic patients were randomly assigned to groups that underwent endoscopic drainage or operative pancreaticojejunostomy. In 2009, information was collected regarding pain, quality of life, morbidity, mortality, length of hospital stay, number of procedures undergone, changes in pancreatic function, and costs. Analysis was performed according to an intention-to-treat principle. Results During the 79-month follow-up period, one patient was lost and 7 died from unrelated causes. Of the patients treated by endoscopy, 68% required additional drainage compared with 5% in the surgery group ( P = .001). Hospital stay and costs were comparable, but overall, patients assigned to endoscopy underwent more procedures (median, 12 vs 4; P = .001). Moreover, 47% of the patients in the endoscopy group eventually underwent surgery. Although the mean difference in Izbicki pain scores was no longer significant (39 vs 22; P = .12), surgery was still superior in terms of pain relief (80% vs 38%; P = .042). Levels of quality of life and pancreatic function were comparable. Conclusions In the long term, symptomatic patients with advanced chronic pancreatitis who underwent surgery as the initial treatment for pancreatic duct obstruction had more relief from pain, with fewer procedures, than patients who were treated endoscopically. Importantly, almost half of the patients who were treated with endoscopy eventually underwent surgery.
Dark sectors charged under a new Abelian interaction have recently received much attention in the context of dark matter models. These models introduce a light new mediator, the so-called dark photon ...(A^{'}), connecting the dark sector to the standard model. We present a search for a dark photon in the reaction e^{+}e^{-}→γA^{'}, A^{'}→e^{+}e^{-}, μ^{+}μ^{-} using 514 fb^{-1} of data collected with the BABAR detector. We observe no statistically significant deviations from the standard model predictions, and we set 90% confidence level upper limits on the mixing strength between the photon and dark photon at the level of 10^{-4}-10^{-3} for dark photon masses in the range 0.02-10.2 GeV. We further constrain the range of the parameter space favored by interpretations of the discrepancy between the calculated and measured anomalous magnetic moment of the muon.
Since the start of the COVID-19 pandemic, multiple waves of SARS-CoV-2 variants have emerged. Of particular concern is the omicron variant, which harbors 28 mutations in the spike glycoprotein ...receptor binding and N-terminal domains relative to the ancestral strain. The high mutability of SARS-CoV-2 therefore poses significant hurdles for development of universal assays that rely on spike-specific immune detection. To address this, more conserved viral antigens need to be targeted. In this work, we comprehensively demonstrate the use of nucleocapsid (N)-specific detection across several assays using previously described nanobodies C2 and E2. We show that these nanobodies are highly sensitive and can detect divergent SARS-CoV-2 ancestral, delta and omicron variants across several assays. By comparison, spike-specific antibodies S309 and CR3022 only disparately detect SARS-CoV-2 variant targets. As such, we conclude that N-specific detection could provide a standardized universal target for detection of current and emerging SARS-CoV-2 variants of concern.
The New Horizons mission has provided resolved measurements of Pluto's moons Styx, Nix, Kerberos, and Hydra. All four are small, with equivalent spherical diameters of approx.40 kilometers for Nix ...and Hydra and approx. 10 kilometers for Styx and Kerberos. They are also highly elongated, with maximum to minimum axis ratios of approx. 2. All four moons have high albedos (approx.50 to 90%) suggestive of a water-ice surface composition. Crater densities on Nix and Hydra imply surface ages of at least 4 billion years. The small moons rotate much faster than synchronous, with rotational poles clustered nearly orthogonal to the common pole directions of Pluto and Charon. These results reinforce the hypothesis that the small moons formed in the aftermath of a collision that produced the Pluto-Charon binary.
The process e+e−→π+π−2π0γ is investigated by means of the initial-state radiation technique, where a photon is emitted from the incoming electron or positron. Using 454.3 fb−1 of data collected ...around a center-of-mass energy of s=10.58 GeV by the BABAR experiment at SLAC, approximately 150000 signal events are obtained. The corresponding nonradiative cross section is measured with a relative uncertainty of 3.6% in the energy region around 1.5 GeV, surpassing all existing measurements in precision. Using this new result, the channel’s contribution to the leading order hadronic vacuum polarization contribution to the anomalous magnetic moment of the muon is calculated as (gμπ+π−2π0−2)/2=(17.9±0.1stat±0.6syst)×10−10 in the energy range 0.85 GeV<ECM<1.8 GeV. In the same energy range, the impact on the running of the fine-structure constant at the Z0-pole is determined as Δαπ+π−2π0(MZ2)=(4.44±0.02stat±0.14syst)×10−4. Furthermore, intermediate resonances are studied and especially the cross section of the process e+e−→ωπ0→π+π−2π0 is measured.
Background & Aims Stem cells of normal tissues have resistance mechanisms that allow them to survive genotoxic insults. The stem cell–like cells of tumors are defined by their tumor-initiating ...capacity and may have retained these resistance mechanisms, making them resistant to chemotherapy. We studied the relationship between resistance to the topoisomerase I inhibitor irinotecan and tumor-initiating potential in human colonosphere cultures and in mice with colorectal xenograft tumors. Methods Colonosphere cultures were established from human colorectal tumor specimens obtained from patients who underwent colon or liver resection for primary or metastatic adenocarcinoma. Stem cell and differentiation markers were analyzed by immunoblotting and fluorescence-activated cell sorting. Clone- and tumor-initiating capacities were assessed by single-cell cloning and in immune-deficient mice. Sensitivity to irinotecan was assessed in vitro and in tumor-bearing mice. The relationship between drug resistance and tumor-initiating capacity was tested by fluorescence-activated cell sorting of colonosphere cells, based on expression of ABCB1 and aldehyde dehydrogenase (ALDH) activity. Results Colonosphere cultures had a high capacity to initiate tumors in mice and were resistant to irinotecan. Inhibition of the drug-efflux pump ABCB1 by PSC-833 allowed irinotecan to eradicate tumor-initiating cells. However, ABCB1 was expressed only by a subpopulation of differentiated tumor cells that did not form clones or tumors. Conversely, tumor-initiating cells were ABCB1-negative and were identified by high ALDH activity. Tumorigenic ALDHhigh /ABCB1negative cells generated nontumorigenic ALDHlow /ABCB1positive daughter cells in vitro and in tumor xenografts. PSC-833 increased the antitumor efficacy of irinotecan in mice. Conclusions The resistance of colorectal tumors to irinotecan requires the cooperative action of tumor-initiating ALDHhigh /ABCB1negative cells and their differentiated, drug-expelling, ALDHlow /ABCB1positive daughter cells.
Basal cell nevus syndrome (BCNS) is a rare genetic disorder accompanied by a broad variety of tumours, of which basal cell carcinomas and odontogenic keratocysts are the most common. BCNS is caused ...by a germline or postzygotic mutation in either
or
As BCNS is a rare disease, it is difficult to establish whether less frequently occurring tumours are actually part of the syndrome. In this study, the molecular mechanism behind four extracutaneous tumours in patients with BCNS was elucidated. A leiomyoma of the testis and meningioma were confirmed to be associated with BCNS in two patients by presence of a second mutation or loss of heterozygosity in
In a meningioma of a patient with a mosaic postzygotic
mutation an association could not be conclusively confirmed.
was probably not involved in the development of a thyroid carcinoma in a patient with a germline
mutation. Hence, we have proven that meningioma and leiomyoma of the testis are rare extracutaneous tumours that are part of BCNS.
The cold pressor test (CPT) is a widely used pain provocation test to investigate both pain tolerance and cardiovascular responses. We hypothesize, that performing multi-omic analyses during CPT ...gives the opportunity to home in on molecular mechanisms involved. Twenty-two females were phenotypically assessed before and after a CPT, and blood samples were taken. RNA-Sequencing, steroid profiling and untargeted metabolomics were performed. Each 'omic level was analyzed separately at both single-feature and systems-level (principal component PCA and partial least squares PLS regression analysis) and all 'omic levels were combined using an integrative multi-omics approach, all using the paired-sample design. We showed that PCA was not able to discriminate time points, while PLS did significantly distinguish time points using metabolomics and/or transcriptomic data, but not using conventional physiological measures. Transcriptomic and metabolomic data revealed at feature-, systems- and integrative- level biologically relevant processes involved during CPT, e.g. lipid metabolism and stress response. Multi-omics strategies have a great potential in pain research, both at feature- and systems- level. Therefore, they should be exploited in intervention studies, such as pain provocation tests, to gain knowledge on the biological mechanisms involved in complex traits.
Background
Robot‐assisted total mesorectal excision (TME) might offer benefits in less morbidity, better functional and long‐term outcome over laparoscopic TME.
Methods
All consecutive patients ...undergoing robot‐assisted TME for rectal cancer during implementation between May 2015 and December 2019 performed by five surgeons in a single centre were included. Outcomes included local recurrence rate at 3 years, conversion rate, circumferential resection margin (CRM) positivity rate, 30‐day postoperative morbidity and outcomes of low anterior resection syndrome (LARS) questionnaires.
Results
In 105 robot‐assisted TME, local recurrence rate at 3 years was 7.4%, conversion to open surgery rate was 8.6%, CRM positivity rate was 5.7%, 73.3% had good quality specimen, postoperative morbidity rate was 47.6% and anastomotic leakage rate was 9.0%. Incidence of major LARS was 55.3%.
Conclusions
results of this study described acceptable morbidity, functional and long‐term outcome during implementation of robotic TME for rectal cancer by multiple surgeons in a single centre.
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