Treatment for Peritoneal Metastasis of Patients With Colorectal Cancer

From the perspective of survival outcomes, the cancer survival of colorectal cancer (CRC) in the whole stage has improved. Peritoneal metastasis (PM) is found in approximately 8% to 15% of patients with CRC, with a poorer prognosis than that associated with other sites of metastases. Randomized controlled trials and up-to-date meta-analyses provide firm evidence that cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) could significantly improve overall survival compared with systemic chemotherapy alone in selected patients with CRC-PM. Practical guidelines recommend that the management of CRC-PM should be led by a multidisciplinary team carried out in experienced centers and consider CRS plus HIPEC for selected patients. In this review, we aim to provide the latest results of land mark studies and an overview of recent insights with regard to the management of CRC-PM.

The Effect of Conservative Oxygen Therapy in Reducing Mortality in Critical Care Patients: A Meta-Analysis and Trial Sequential Analysis

Background: Conservative oxygen therapy can prevent both hypoxemia and hyperoxemia, but the effect on the prognosis of patients admitted to the intensive care unit (ICU) remains controversial.Methods: All controlled studies comparing conservative oxygen therapy and conventional oxygen therapy in adult patients admitted to the ICU were searched. The primary outcome was mortality, and the secondary outcomes were length of ICU stay (ICU LOS), length of hospital stay (hospital LOS), length of mechanical ventilation (MV) hours, new organ failure during ICU stay, and new infections during ICU stay.Results: Nine trials with a total of 5,759 patients were pooled in our final studies. Compared with conventional oxygen therapy, conservative oxygen therapy did not reduce overall mortality (Z = 0.31, p = 0.75) or ICU LOS (Z = 0.17, p = 0.86), with firm evidence from trial sequential analysis, or hospital LOS (Z = 1.98, p = 0.05) or new infections during the ICU stay (Z = 1.45, p = 0.15). However, conservative oxygen therapy was associated with a shorter MV time (Z = 5.05, p < 0.00001), reduction of new organ failure during the ICU stay (Z = 2.15, p = 0.03) and lower risk of renal replacement therapy (RRT) (Z = 2.18, p = 0.03).Conclusion: Conservative oxygen therapy did not reduce mortality but did decrease MV time, new organ failure and risk of RRT in critically ill patients.Systematic Review Registration: identifier [CRD42020171055].

Is Perioperative Dexmedetomidine Associated With a Reduced Risk of Perioperative Neurocognitive Disorders Following Cardiac Surgery? A Systematic Review and Meta-Analysis With Trial Sequential Analysis of Randomized Controlled Trials

Background: To assess the effect of dexmedetomidine on the reducing risk of perioperative neurocognitive disorders (PNDs) following cardiac surgery.Methods: A systematic review and meta-analysis with trial sequential analysis (TSA) of randomized controlled trials were performed. PubMed, Embase, Cochrane Library, and CNKI databases (to August 16, 2020) were searched for relevant articles to analyze the incidence of PND for intraoperative or postoperative dexmedetomidine administration after cardiac surgery. PND included postoperative cognitive dysfunction (POCD) and postoperative delirium (POD).Results: A total of 24 studies with 3,610 patients were included. Compared with the control group, the incidence of POD in the dexmedetomidine group was significantly lower (odds ratio [OR]: 0.59, 95% CI: 0.43–0.82, P = 0.001), with firm evidence from TSA. Subgroup analyses confirmed that dexmedetomidine reduced the incidence of POD with firm evidence following coronary artery bypass grafting surgery (OR: 0.45, 95% CI: 0.26–0.79, P = 0.005), and intervention during the postoperative period (OR: 0.48, 95% CI: 0.34–0.67, P < 0.001). Furthermore, the incidence of POD in the dexmedetomidine group was also decreased in mixed cardiac surgery (OR: 0.68, 95% CI: 0.47–0.98, P = 0.039). Irrespective of whether “Confusion Assessment Method/Confusion Assessment Method for intensive care unit” or “other tools” were used as diagnostic tools, the results showed a decreased risk of POD in the dexmedetomidine group. There was no significant difference in the incidence of POCD (OR: 0.47, 95% CI: 0.22–1.03, P = 0.060) between the two groups, but this result lacked firm evidence from TSA.Conclusion: The administration of dexmedetomidine during the perioperative period reduced the incidence of POD in patients after cardiac surgery, but there was no significant benefit in the incidence of POCD. The effect of dexmedetomidine on the incidence of POD or POCD following different types of surgery and the optimal dose and timing of dexmedetomidine warrant further investigation.Trial registration: PROSPERO registration number: CRD42020203980. Registered on September 13, 2020.

Autoantibodies against NMDA receptor 1 modify rather than cause encephalitis

The etiology and pathogenesis of “anti-N-methyl-D-aspartate-receptor (NMDAR) encephalitis” and the role of autoantibodies (AB) in this condition are still obscure. While NMDAR1-AB exert NMDAR-antagonistic properties by receptor internalization, no firm evidence exists to date that NMDAR1-AB by themselves induce brain inflammation/encephalitis. NMDAR1-AB of all immunoglobulin classes are highly frequent across mammals with multiple possible inducers and boosters. We hypothesized that “NMDAR encephalitis” results from any primary brain inflammation coinciding with the presence of NMDAR1-AB, which may shape the encephalitis phenotype. Thus, we tested whether following immunization with a “cocktail” of 4 NMDAR1 peptides, induction of a spatially and temporally defined sterile encephalitis by diphtheria toxin-mediated ablation of pyramidal neurons (“DTA” mice) would modify/aggravate the ensuing phenotype. In addition, we tried to replicate a recent report claiming that immunizing just against the NMDAR1-N368/G369 region induced brain inflammation. Mice after DTA induction revealed a syndrome comprising hyperactivity, hippocampal learning/memory deficits, prefrontal cortical network dysfunction, lasting blood brain-barrier impairment, brain inflammation, mainly in hippocampal and cortical regions with pyramidal neuronal death, microgliosis, astrogliosis, modest immune cell infiltration, regional atrophy, and relative increases in parvalbumin-positive interneurons. The presence of NMDAR1-AB enhanced the hyperactivity (psychosis-like) phenotype, whereas all other readouts were identical to control-immunized DTA mice. Non-DTA mice with or without NMDAR1-AB were free of any encephalitic signs. Replication of the reported NMDAR1-N368/G369-immunizing protocol in two large independent cohorts of wild-type mice completely failed. To conclude, while NMDAR1-AB can contribute to the behavioral phenotype of an underlying encephalitis, induction of an encephalitis by NMDAR1-AB themselves remains to be proven.

Physical experiments in geomorphology

An experiment is a program of observations specially constructed to provide a critical test of theory or generalization about nature. It is designed to acquire firm evidence for or against the effect in question. Accordingly, it must be arranged to control all sources of variability contributing to the phenomena under examination save those it is intended to study. In the natural environment this is difficult to achieve. Consequently, classical geomorphology had no established tradition of experimentation. However, in the latter third of the 20th century, geomorphologists began to explore experimentation as a means to resolve questions that arise in the study of geomorphological processes. In the period 1976-84 an IGU commission on field experiments in geomorphology formally established an interest in the approach. Although few field studies before the turn of the century achieved experimental status, valuable experience was gained in laboratory experiments, scaled and unscaled, leading to present wide acceptance of experimentation as a means to approach questions about geomorphological processes.

The Effects of Endometriosis on Ovarian Functions

Infertility is a main manifestation of endometriosis, though the exact pathogenesis of endometriosis-associated infertility remains unclear. Compromised ovarian functions may be one of the causes of endometriosis related infertility. The ovarian function can be classified into three basic elements, (1) production of ovarian hormones, (2) maintenance of follicular development until ovulation, and (3) reservoir of dormant oocytes (ovarian reserve). The effects of endometriosis on ovarian hormone production and follicular development are inconclusive. Ovarian endometrioma is common phonotype of endometriosis. Development of endometrioma per se may affect ovarian reserve. Surgery for endometriomas further diminish ovarian reserve, especially women with bilateral involvement. Early intervention with surgery and/or medical treatment may be beneficial, though firm evidence is lacking. When surgery is chosen in women at reproductive age, specific techniques that spare ovarian function should be considered.

A revised multilocus phylogeny of Old World sparrows (Aves: Passeridae)

The Old World sparrows include some of the best-studied passerine species, such as the cosmopolitan human commensal, the house sparrow (Passer domesticus) as well as poorly studied narrow-range endemics like the Iago sparrow (P. iagoensis) from the Cape Verde Archipelago or specialists from extreme environments like the desert sparrow (P. simplex). It is therefore notable that to date the most complete phylogenetic hypothesis for the Old World sparrows comprised only ten of 43 currently accepted species. With this study we provide an updated phylogeny of Passeridae covering about two third of the family’s species richness. Though still being far from taxon-complete, this new phylogenetic hypothesis provides firm evidence to clarify some open taxonomic questions. All genus-level taxa were reciprocally monophyletic with strong support. Contrary to previous classifications, bush sparrows and rock sparrows were not sister taxa, and therefore their classification in separate genera Gymnoris and Petronia is justified. Plumage color traits like the yellow throat patch of the latter two genera or head color pattern in Passer species do not provide reliable phylogenetic information, except for the large-sized African grey-headed sparrows that resulted as a monophyletic group (P. diffusus, P. griseus, P. gongoensis). Unexpectedly, two small-sized species, P. eminibey and P. luteus that to date are regarded as close relatives were firmly nested in two separate clades of Passer sparrows. Therefore, their separate generic treatment under Sorella eminibey and Auripasser luteus (together with A. euchlorus) does not seem justified.

Single individual structural variant detection uncovers widespread hemizygosity in molluscs

The advent of complete genomic sequencing has opened a window into genomic phenomena obscured by fragmented assemblies. A good example of these is the existence of hemizygous regions of autosomal chromosomes, which can result in marked differences in gene content between individuals within species. While these hemizygous regions, and presence/absence variation of genes that can result, are well known in plants, firm evidence has only recently emerged for their existence in metazoans. Here, we use recently published, complete genomes from wild-caught molluscs to investigate the prevalence of hemizygosity across a well-known and ecologically important clade. We show that hemizygous regions are widespread in mollusc genomes, not clustered in individual chromosomes, and often contain genes linked to transposition, DNA repair and stress response. With targeted investigations of HSP70-12 and C1qDC , we also show how individual gene families are distributed within pan-genomes. This work suggests that extensive pan-genomes are widespread across the conchiferan Mollusca, and represent useful tools for genomic evolution, allowing the maintenance of additional genetic diversity within the population. As genomic sequencing and re-sequencing becomes more routine, the prevalence of hemizygosity, and its impact on selection and adaptation, are key targets for research across the tree of life. This article is part of the Theo Murphy meeting issue ‘Molluscan genomics: broad insights and future directions for a neglected phylum’.

Ergodic sampling of the topological charge using the density of states

In lattice calculations, the approach to the continuum limit is hindered by the severe freezing of the topological charge, which prevents ergodic sampling in configuration space. In order to significantly reduce the autocorrelation time of the topological charge, we develop a density of states approach with a smooth constraint and use it to study SU(3) pure Yang Mills gauge theory near the continuum limit. Our algorithm relies on simulated tempering across a range of couplings, which guarantees the decorrelation of the topological charge and ergodic sampling of topological sectors. Particular emphasis is placed on testing the accuracy, efficiency and scaling properties of the method. In their most conservative interpretation, our results provide firm evidence of a sizeable reduction of the exponent z related to the growth of the autocorrelation time as a function of the inverse lattice spacing.