Neoadjuvant therapy is recommended for locally advanced esophageal cancer, but the optimal strategy remains unclear. We aimed to evaluate the safety and efficacy of neoadjuvant chemoradiotherapy ...(nCRT) versus neoadjuvant chemotherapy (nCT) followed by minimally invasive esophagectomy (MIE) for locally advanced esophageal squamous cell carcinoma (ESCC).
Eligible patients staged as cT3-4aN0-1M0 ESCC were randomly assigned (1 : 1) to the nCRT or nCT group stratified by age, cN stage, and centers. The chemotherapy, based on paclitaxel and cisplatin, was administered to both groups, while concurrent radiotherapy was added for the nCRT group; then MIE was carried out. The primary endpoint was 3-year overall survival. This study is registered with ClinicalTrials.gov (NCT03001596).
A total of 264 patients were eligible for the intention-to-treat analysis. By 30 November 2021, 121 deaths had occurred. The median follow-up was 43.9 months (interquartile range 36.6-49.3 months). The overall survival in the intention-to-treat population was comparable between the nCRT and nCT strategies hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.58-1.18; P = 0.28, with a 3-year survival rate of 64.1% (95% CI 56.4% to 72.9%) versus 54.9% (95% CI 47.0% to 64.2%), respectively. There were also no differences in progression-free survival (HR 0.83, 95% CI 0.59-1.16; P = 0.27) and recurrence-free survival (HR 1.07, 95% CI 0.71-1.60; P = 0.75), although the pathological complete response in the nCRT group (31/112, 27.7%) was significantly higher than that in the nCT group (3/104, 2.9%; P < 0.001). Besides, a trend of lower risk of recurrence was observed in the nCRT group (P = 0.063), while the recurrence pattern was similar (P = 0.802).
NCRT followed by MIE was not associated with significantly better overall survival than nCT among patients with cT3-4aN0-1M0 ESCC. The results underscore the pending issue of the best strategy of neoadjuvant therapy for locally advanced bulky ESCC.
•The CMISG1701 trial assessed the safety and efficacy of nCRT versus nCT followed by MIE for locally advanced bulky ESCC.•The nCRT followed by MIE strategy could not improve survival significantly compared with the nCT strategy.•The best strategy of neoadjuvant therapy for locally advanced bulky ESCC remains a pending issue.
Three structural designs for ceramic membranes have been achieved for the first time through the co-extrusion of polymeric and ceramic layers. During co-extrusion, micro-channels are initiated due to ...the Rayleigh–Taylor instability and they propagate through the different layers. The polymeric layer(s) is then calcined off during the heat treatment step, which opens the micro-channels and following sintering a ceramic membrane with open micro-channels ranging from a few to a few tens of micrometres in diameter can be formed. These long, straight and non-tortuous micro-channels can be controlled to be open at any or all of the surfaces. Design 1 has open micro-channels passing through the entire membrane wall, Design 2 has a separation layer at the lumen and open micro-channels at the shell side, and Design 3 has open micro-channels from both lumen and shell sides sandwiching a separation layer of sponge-like structure. Aside from having much improved mass transfer property due to the reduced effective membrane thickness, they can be easily incorporated into hybrid systems with anticipated improvements in unit compactness and performance. The pure water permeation of Design 2 reached up to 159,000L/m2hbar with pore sizes in the micro-filtration range. The micro-channels are easily accessible from the shell/lumen side; therefore catalysts or adsorbents can be easily deposited into the micro-channels. Examples of possible applications include a high-efficiency dispersing device realised with Design 1; a gas chromatography column for gas separation with very low pressure drop realised with Design 2 and a highly compact membrane micro-reactor for consecutive reactions proposed with Design 3.
•3 new structural ceramic membrane designs were achieved.•Phase inversion hollow fibres fabricated by co-extruding polymer and ceramic layers.•Polymer layers are burnt off, membranes with open micro-channels are formed.•Large geometric surface area provided by the micro-channels is now easily accessible.
A low level of CD4+ lymphocyte cells makes end-stage HIV/AIDS patients highly susceptible to microbial infections. We have adopted the next generation sequencing method to identify the spectrum of ...bacterial plasma and viral elements that might be present in these patients. The HIV/AIDS plasma microbiome was dominated by bacterial elements in the taxonomical order Pseudomonadales, while healthy people carried fewer bacterial DNA in the plasma. We have found that many of the bacterial elements in HIV/AIDS plasma are similar to those of the microbes found in the human gut, suggesting potential acquisition of microbial elements from the gut. The HIV/AIDS and normal plasma DNA virome shared some similarities in the presence of common ubiquitous eukaryotic viruses. The normal DNA virome was mainly composed of viruses from Anelloviridae. In contrast, the HIV/AIDS DNA virome contained a large proportion of bacteriophages, endogenous retroviruses and a non-human virus. In addition, several sequences, which might belong to novel bacteria or endogenous retroviruses, were identified. Taken together, the use of high-throughput sequencing technology in unveiling microbial metagenomics may facilitate future research in combating HIV/AIDS and its associated microbial complications.
Abstract
We analyse observations of eight quiescent low-mass X-ray binaries in globular clusters and combine them to determine the neutron star mass–radius curve and the equation of state of dense ...matter. We determine the effect that several uncertainties may have on our results, including uncertainties in the distance, the atmosphere composition, the neutron star maximum mass, the neutron star mass distribution, the possible presence of a hotspot on the neutron star surface, and the prior choice for the equation of state of dense matter. The distance uncertainty is implemented in a new Gaussian blurring method that can be directly applied to the probability distribution over mass and radius. We find that the radius of a 1.4 solar mass neutron star is most likely from 10 to 14 km and that tighter constraints are only possible with stronger assumptions about the nature of the neutron stars, the systematics of the observations, or the nature of dense matter. Strong phase transitions in the equation of state are preferred, and in this case, the radius is likely smaller than 12 km. However, radii larger than 12 km are preferred if the neutron stars have uneven temperature distributions.
A highly pathogenic avian influenza virus, H5N1, caused disease outbreaks in poultry in China and seven other east Asian countries between late 2003 and early 2004; the same virus was fatal to humans ...in Thailand and Vietnam. Here we demonstrate a series of genetic reassortment events traceable to the precursor of the H5N1 viruses that caused the initial human outbreak in Hong Kong in 1997 and subsequent avian outbreaks in 2001 and 2002. These events gave rise to a dominant H5N1 genotype (Z) in chickens and ducks that was responsible for the regional outbreak in 2003-04. Our findings indicate that domestic ducks in southern China had a central role in the generation and maintenance of this virus, and that wild birds may have contributed to the increasingly wide spread of the virus in Asia. Our results suggest that H5N1 viruses with pandemic potential have become endemic in the region and are not easily eradicable. These developments pose a threat to public and veterinary health in the region and potentially the world, and suggest that long-term control measures are required.
Dementias are prevalent brain disorders in the aged population. Dementias pose major socio‐medical burden, but currently there is no cure available. Novel proteomics approaches hold promise to ...identify alterations of the brain proteome that could provide clues on disease etiology, and identify candidate proteins to develop further as a biomarker. In this review, we focus on recent proteomics findings from brains affected with Alzheimer's Disease, Parkinson Disease Dementia, Frontotemporal Dementia, and Amyotrophic Lateral Sclerosis. These studies confirmed known cellular changes, and in addition identified novel proteins that may underlie distinct aspects of the diseases.
This article is part of the special issue "Proteomics".
Mass spectrometry based proteomics is an ideal technology to elucidate aberrant protein expression in disease‐affected brain. In this review, we describe the recent proteomics findings from brains affected with Alzheimer's Disease, Parkinson Disease Dementia, Frontotemporal Dementia, and Amyotrophic Lateral Sclerosis. Brain is collected. Proteins are digested by trypsin, and the resulting peptides are analysed by LC‐MS/MS. Results are validated by alternative means, for example immunohistochemistry.
This article is part of the special issue "Proteomics".
Colorectal cancer (CRC) remains one of the most prevalent cancers worldwide. In sporadic CRC, mutations frequently occur in the DNA mismatch repair (MMR) pathway. In addition, germline MMR mutations ...have been linked to Lynch syndrome, the most common form of hereditary CRC. Although genetic mutations, diet, inflammation, and the gut microbiota can influence CRC, it is unclear how MMR deficiency relates to these factors to modulate disease. In this review, the association of MMR to the etiology of CRC is examined, particularly in the context of microRNAs (miRNAs), inflammation, and the microbiome. We also discuss the most current targeted therapies, methods of prevention, and molecular biomarkers against MMR-deficient CRC, all of which are encouraging advancements in the field.
Subway systems are indispensable for urban societies, but microbiological characteristics of subway aerosols are relatively unknown. Previous studies investigating microbial compositions in subways ...employed methodologies that underestimated the diversity of microbial exposure for commuters, with little focus on factors governing subway air microbiology, which may have public health implications. Here, a culture-independent approach unraveling the bacterial diversity within the urban subway network in Hong Kong is presented. Aerosol samples from multiple subway lines and outdoor locations were collected. Targeting the 16S rRNA gene V4 region, extensive taxonomic diversity was found, with the most common bacterial genera in the subway environment among those associated with skin. Overall, subway lines harbored different phylogenetic communities based on α- and β-diversity comparisons, and closer inspection suggests that each community within a line is dependent on architectural characteristics, nearby outdoor microbiomes, and connectedness with other lines. Microbial diversities and assemblages also varied depending on the day sampled, as well as the time of day, and changes in microbial communities between peak and nonpeak commuting hours were attributed largely to increases in skin-associated genera in peak samples. Microbial diversities within the subway were influenced by temperature and relative humidity, while carbon dioxide levels showed a positive correlation with abundances of commuter-associated genera. This Hong Kong data set and communities from previous studies conducted in the United States formed distinct community clusters, indicating that additional work is required to unravel the mechanisms that shape subway microbiomes around the globe.
The efficacy of ustekinumab, an antagonist of the p40 subunit of interleukin-12 and interleukin-23, as induction and maintenance therapy in patients with ulcerative colitis is unknown.
We evaluated ...ustekinumab as 8-week induction therapy and 44-week maintenance therapy in patients with moderate-to-severe ulcerative colitis. A total of 961 patients were randomly assigned to receive an intravenous induction dose of ustekinumab (either 130 mg 320 patients or a weight-range-based dose that approximated 6 mg per kilogram of body weight 322) or placebo (319). Patients who had a response to induction therapy 8 weeks after administration of intravenous ustekinumab were randomly assigned again to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 12 weeks 172 patients or every 8 weeks 176) or placebo (175). The primary end point in the induction trial (week 8) and the maintenance trial (week 44) was clinical remission (defined as a total score of ≤2 on the Mayo scale range, 0 to 12, with higher scores indicating more severe disease and no subscore >1 range, 0 to 3 on any of the four Mayo scale components).
The percentage of patients who had clinical remission at week 8 among patients who received intravenous ustekinumab at a dose of 130 mg (15.6%) or 6 mg per kilogram (15.5%) was significantly higher than that among patients who received placebo (5.3%) (P<0.001 for both comparisons). Among patients who had a response to induction therapy with ustekinumab and underwent a second randomization, the percentage of patients who had clinical remission at week 44 was significantly higher among patients assigned to 90 mg of subcutaneous ustekinumab every 12 weeks (38.4%) or every 8 weeks (43.8%) than among those assigned to placebo (24.0%) (P = 0.002 and P<0.001, respectively). The incidence of serious adverse events with ustekinumab was similar to that with placebo. Through 52 weeks of exposure, there were two deaths (one each from acute respiratory distress syndrome and hemorrhage from esophageal varices) and seven cases of cancer (one each of prostate, colon, renal papillary, and rectal cancer and three nonmelanoma skin cancers) among 825 patients who received ustekinumab and no deaths and one case of cancer (testicular cancer) among 319 patients who received placebo.
Ustekinumab was more effective than placebo for inducing and maintaining remission in patients with moderate-to-severe ulcerative colitis. (Funded by Janssen Research and Development; UNIFI ClinicalTrials.gov number, NCT02407236.).
The self-healing of a GCL with artificial defects (circular holes and rectangular slits, both with and without the carrier geotextile preserved below the holes) upon hydration on a Godfrey silty sand ...(GSS) subgrade with wfdn = 5, 10 and 16% under 2–100 kPa is examined. Circular holes with the carrier geotextile missing below holes with diameters up to 25.4 mm self-healed on the wfdn = 5% and 10% GSS but not on 16% GSS, while none self-healed when carrier geotextile was preserved below the holes. When DI water was introduced to the surface under 100 kPa, circular holes with diameter up to 38.1 mm self-healed. Neither the single 15 mm-wide slit nor double 15 mm-wide parallel slits with 20 mm-wide strip of undamaged GCL between them resting on wfdn = 10% GSS under 20 kPa fully self-healed. The introduction of simulated synthetic landfill leachate (SSL) to the GCL surface under 70 kPa did not result in self-healing. Post-hydration k tests found that GCL without a carrier geotextile below a hole up to 25.4 mm in diameter would not have a significant adverse effect on the hydraulic conductivity compared with an intact GCL provided the permeant was tap water rather than SSL.
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