Toward Microbiome Engineering: Expanding the Repertoire of Genetically Tractable Members of the Human Gut Microbiome.

Genetic manipulation is necessary to interrogate the functions of microbes in their environments, such as the human gut microbiome. Yet, the vast majority of human gut microbiome species are not genetically tractable. Here, we review the hurdles to seizing genetic control of more species.

Comparison of Hepatic Arterial Infusion Pump Chemotherapy vs Resection for Patients With Multifocal Intrahepatic Cholangiocarcinoma.

Importance: Intrahepatic cholangiocarcinoma (iCCA) is often multifocal (ie, satellites or intrahepatic metastases) at presentation.

Objective: To compare the overall survival (OS) of patients with multifocal iCCA after hepatic arterial infusion pump (HAIP) floxuridine chemotherapy vs resection.

Design, Setting, And Participants: In this cohort study, patients with histologically confirmed, multifocal iCCA were eligible.

Microbiome engineering: Taming the untractable.

In this issue of Cell, Jin et al. describe several innovative tools for microbiome engineering to enable in situ editing of complex communities. However, challenges remain to overcome the widespread genetic intractability of microbiome constituents.

EFFECTIVE DOSE COEFFICIENTS FOR RADON AND PROGENY: A REVIEW OF ICRP AND UNSCEAR VALUES.

The International Commission on Radiological Protection (ICRP) publishes guidance on protection against radon exposure in homes and workplaces. ICRP Publication 137 recommends a dose coefficient of 3 mSv per mJ h m-3 (~10 mSv WLM-1) to be used in most circumstances of radon exposure, for workers in buildings and in underground mines. Recently, United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) reviewed radon epidemiology and dosimetry and concluded that its established dose coefficient of 1.

Development of a Senior Medical Student Robotic Surgery Training Elective.

As robotic surgery has become more widespread, early exposure to the robotic platform is becoming increasingly important, not only to graduate medical education, but also for medical students pursuing surgical residency. In an effort to orient students to robotic technology and decrease the learning curve for what is likely to become an integral part of residency training, we created a formal, elective robotic surgery curriculum for senior medical students. Throughout this 2-week fourth year rotation, students completed online training modules and assessment; mastered exercises on the simulator system related to the console, camera, energy, dexterity, and suturing skills; attended didactics; utilized the dual console during one-on-one simulation lab sessions with attending robotic surgery experts; and translated new skills to biotissue anastomoses as well as bedside-assisting in the operating room.

Chromatin accessibility dynamics of Chlamydia-infected epithelial cells.

Chlamydia are Gram-negative, obligate intracellular bacterial pathogens responsible for a broad spectrum of human and animal diseases. In humans, Chlamydia trachomatis is the most prevalent bacterial sexually transmitted infection worldwide and is the causative agent of trachoma (infectious blindness) in disadvantaged populations. Over the course of its developmental cycle, Chlamydia extensively remodels its intracellular niche and parasitises the host cell for nutrients, with substantial resulting changes to the host cell transcriptome and proteome.

Changes in Performance of More Than 1000 Minimally Invasive Liver Resections.

This cohort study examines changes in laparoscopic liver resection procedures in more than 1000 patients in a single center over a period of 17 years.

Early Transcriptional Landscapes of -Infected Epithelial Cells at Single Cell Resolution.

are Gram-negative obligate intracellular bacterial pathogens responsible for a variety of disease in humans and animals worldwide. causes trachoma in disadvantaged populations, and is the most common bacterial sexually transmitted infection in humans, causing reproductive tract disease. Antibiotic therapy successfully treats diagnosed chlamydial infections, however asymptomatic infections are common.

Sleep problems in advanced cancer patients and their caregivers: Who is disturbing whom?

Background The aims of the study were to understand sleep problems and their effects in advanced cancer patients and spousal and intimate partner caregivers and to examine the directionality of the link between patients' and caregivers' sleep problems. Methods Fifty-four advanced cancer patients and their spousal and intimate partners were administered a battery of questionnaires that included the Pittsburgh Sleep Quality Index and the Center for Epidemiological Studies at the patients' cancer diagnosis and at 2, 4, and 6 months after diagnosis. Results Patients' and caregivers' sleep duration was significantly related.

Structure-activity analysis of peptidic Chlamydia HtrA inhibitors.

Chlamydia trachomatis high temperature requirement A (CtHtrA) is a serine protease that performs proteolytic and chaperone functions in pathogenic Chlamydiae; and is seen as a prospective drug target. This study details the strategies employed in optimizing the irreversible CtHtrA inhibitor JO146 [Boc-Val-Pro-Val(OPh)] for potency and selectivity. A series of adaptations both at the warhead and specificity residues P and P yielded 23 analogues, which were tested in human neutrophil elastase (HNE) and CtHtrA enzyme assays as well as Chlamydia cell culture assays.

Dual RNA-Seq of Chlamydia and Host Cells.

During the infection of a host cell by a bacterial pathogen, a cascading series of gene expression changes occurs as each organism manipulates or responds to the other via defense or survival strategies. Unraveling this complex interplay is key for our understanding of bacterial virulence and host response pathways for the development of novel therapeutics. Dual RNA sequencing (dual RNA-Seq) has recently been developed to simultaneously capture host and bacterial transcriptomes from an infected cell.

Socioeconomic disparities of depressive symptoms and cytokines in hepatocellular carcinoma.

Objective: To examine the associations among socioeconomic factors, depressive symptoms, and cytokines in patients diagnosed with hepatocellular carcinoma (HCC).

Methods: A total of 266 patients diagnosed with HCC were administered a battery of questionnaires including a sociodemographic questionnaire and the Center for Epidemiologic StudiesDepression (CES-D) scale. Blood samples were collected to assess serum levels of cytokines using Luminex.

Prospective Analyses of Cytokine Mediation of Sleep and Survival in the Context of Advanced Cancer.

Objective: The aims of this study were to examine the potential association between sleep problems, symptom burden, and survival in patients with advanced cancer.

Methods: A prospective study of 294 patients with gastrointestinal cancer administered questionnaires assessing sleep, depression, anxiety, stress, pain, fatigue, and health-related quality of life. Serum levels of cytokines including interleukin (IL)-1α, IL-1β, tumor necrosis factor α, IL-10, IL-2, and interferon-γ were measured to assess biological mediation between sleep and survival.

A Laboratory Methodology for Dual RNA-Sequencing of Bacteria and their Host Cells .

Dual RNA-Sequencing leverages established next-generation sequencing (NGS)-enabled RNA-Seq approaches to measure genome-wide transcriptional changes of both an infecting bacteria and host cells. By simultaneously investigating both organisms from the same biological sample, dual RNA-Seq can provide unique insight into bacterial infection processes and reciprocal host responses at once. However, the difficulties involved in handling both prokaryotic and eukaryotic material require distinct, optimized procedures.

Preoperative next-generation sequencing of pancreatic cyst fluid is highly accurate in cyst classification and detection of advanced neoplasia.

Objective: DNA-based testing of pancreatic cyst fluid (PCF) is a useful adjunct to the evaluation of pancreatic cysts (PCs). Mutations in / are highly specific for intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs), while // alterations are associated with advanced neoplasia. A prospective study was performed to evaluate preoperative PCF DNA testing.

Copper(II)-bis(thiosemicarbazonato) complexes as anti-chlamydial agents.

Lipophilic copper (Cu)-containing complexes have shown promising antibacterial activity against a range of bacterial pathogens. To examine the susceptibility of the intracellular human pathogen Chlamydia trachomatis to copper complexes containing bis(thiosemicarbazone) ligands [Cu(btsc)], we tested the in vitro effect of CuII-diacetyl- and CuII-glyoxal-bis[N(4)-methylthiosemicarbazonato] (Cu(atsm) and Cu(gtsm), respectively) on C. trachomatis.

CtHtrA: the lynchpin of the chlamydial surface and a promising therapeutic target.

Chlamydia trachomatis is the most prevalent sexually transmitted bacterial infection worldwide and the leading cause of preventable blindness. Reports have emerged of treatment failure, suggesting a need to develop new antibiotics to battle Chlamydia infection. One possible candidate for a new treatment is the protease inhibitor JO146, which is an effective anti-Chlamydia agent that targets the CtHtrA protein.

Bioinformatic analysis of bacteria and host cell dual RNA-sequencing experiments.

Bacterial pathogens subvert host cells by manipulating cellular pathways for survival and replication; in turn, host cells respond to the invading pathogen through cascading changes in gene expression. Deciphering these complex temporal and spatial dynamics to identify novel bacterial virulence factors or host response pathways is crucial for improved diagnostics and therapeutics. Dual RNA sequencing (dRNA-Seq) has recently been developed to simultaneously capture host and bacterial transcriptomes from an infected cell.

RADON DOSIMETRY FOR WORKERS: ICRP'S APPROACH.

The International Commission on Radiological Protection (ICRP) has recently published two reports on radon exposure; Publication 115 on lung cancer risks from radon and radon progeny and Publication 126 on radiological protection against radon exposure. A specific graded approach for the control of radon in workplaces is recommended where a dose assessment is required in certain situations. In its forthcoming publication on Occupational Intakes of Radionuclides (OIR) document, Part 3, effective dose coefficients for radon and thoron will be provided.

Impact of major vascular resection on outcomes and survival in patients with intrahepatic cholangiocarcinoma: A multi-institutional analysis.

Background: Major vascular involvement (IVC or portal vein) for intrahepatic cholangiocarcinoma (ICC) has traditionally been considered a contraindication to resection. We sought to define perioperative outcomes and survival of ICC patients undergoing hepatectomy with major vascular resection in a large international multi-institutional database.

Methods: A total of 1087 ICC patients who underwent curative-intent hepatectomy between 1990 and 2016 were identified from 13 institutions.

Sleep duration is associated with survival in advanced cancer patients.

Objective: Sleep problems have been linked to increased risk of mortality in the general population. Limited evidence suggests similar relationships among people diagnosed with cancer. The aims of the present study were to investigate the type and rates of sleep problems in advanced cancer patients and examine whether sleep problems are associated with survival.

Leukaemia mortality and low-dose ionising radiation in the WISMUT uranium miner cohort (1946-2013).

Objectives: To examine the risk of death from leukaemia in relation to occupational chronic low-level external and internal radiation exposure in a cohort of 58 972 former German uranium miners with mortality follow-up from 1946 to 2013.

Methods: The red bone marrow (RBM) dose from low-linear energy transfer (LET) (mainly external γ-radiation) and high-LET (mainly radon gas) radiation was estimated based on a job-exposure matrix and biokinetic/dosimetric models. Linear excess relative risks (ERR) and 95% CIs were estimated via Poisson regression for chronic lymphatic leukaemia (CLL) and non-CLL.

Longterm survival outcomes of patients undergoing treatment with radiofrequency ablation for hepatocellular carcinoma and metastatic colorectal cancer liver tumors.

Background: We aim to investigate long-term survival outcomes in patients undergoing radiofrequency ablation (RFA), based on our longitudinal 5 and 10 year follow-up data.

Methods: All patients who underwent RFA for hepatocellular carcinoma (HCC) and colorectal liver metastasis (CLM) between 1999 and 2010.

Results: 320 patients were included with oncologic diagnoses of HCC in 122 (38.

Defining when to offer operative treatment for intrahepatic cholangiocarcinoma: A regret-based decision curves analysis.

Background: Regret-based decision curve analysis (DCA) is a framework that assesses the medical decision process according to physician attitudes (expected regret) relative to disease-based factors. We sought to apply this methodology to decisions around the operative management of intrahepatic cholangiocarcinoma (ICC).

Methods: Utilizing a multicentric database of 799 patients who underwent liver resection for ICC, we developed a prognostic nomogram.