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Following resection of colorectal liver metastasis, most patients have disease recurrence, most commonly intrahepatic. Although the role of resection in colorectal liver metastasis is well-established, there have been limited investigations assessing the benefit of repeat hepatic resection compared with systemic treatment alone for intrahepatic recurrence.A retrospective single-institution cohort study of patients with recurrent colorectal liver metastasis following curative-intent hepatectomy was performed from 2003 to 2019. The oncologic outcomes, including post-recurrence overall survival, were evaluated using Kaplan-Meier and Cox proportional hazards modeling. Patients undergoing repeat hepatic resection were propensity-matched with patients receiving systemic treatment alone based on relevant clinicopathologic variables.There were 338 patients treated with hepatic resection for colorectal liver metastasis over the study period. Liver recurrence was observed in 147 (43%) patients at a median time of 10 months from prior resection, with a median post-recurrence overall survival of 29 months. There were 37 patients managed with repeat hepatic resection; 33 (89%) received perioperative chemotherapy. On propensity matching, there were no significant clinicopathologic differences between 37 patients having repeat hepatic resection and 37 patients treated with systemic treatment alone. Repeat hepatic resection was independently associated with improved 5-year post-recurrence overall survival compared with systemic treatment alone (median overall survival 41 vs 35 months, 5-year overall survival 19% vs 3%, P = .048).Disease characteristics of patients with intrahepatic recurrence of colorectal liver metastasis, specifically the number of liver lesions and size of the largest lesion, are most predictive of survival and response to systemic therapy. Patients who recur with oligometastatic liver disease experience improved outcomes and derive benefit from curative-intent repeat hepatic resection with integrated perioperative systemic therapy.

Background Five to ten percent of the global population have unruptured intracranial aneurysms, and ruptured brain aneurysms cause approximately 500,000 deaths a year. Flow-diverting stent treatment is a less invasive intracranial aneurysm treatment that induces aneurysm thrombosis. The imaging characteristics of a novel primarily bioresorbable flow-diverting stent (BFDS) are assessed in comparison to the leading metal stent using fluoroscopy, CT, and MRI. Methods X-ray/fluoroscopic images of stents were taken using a human cadaveric skull model. CT and MRI were acquired using silicone flow models of residual aneurysms. Images were analyzed with Likert scales in anonymous surveys by neurointerventionalists. Quantitative measurements of radiographic density (CT) and artifact boundary size (CT & MRI) were also obtained. Results Visibility of the BFDS on X-ray was less than the metal stent but deemed adequate for deployment and intraprocedural assessment. The metal stent was more radiopaque than the BFDS on CT, but qualitative assessment was not significantly different for the two stents. MRI imaging was significantly better using the BFDS in terms of overall artifact and intraluminal assessment. Conclusions The BFDS has adequate visualization on X-ray/fluoroscopy and should be clinically acceptable for fluoroscopic deployment. On MRI, there is less quantitative artifact as well as overall improved qualitative assessment that will allow for more detailed non-invasive imaging follow-up of treated aneurysms, potentially reducing the need for digital subtraction catheter angiography.

Background: Whereas the beneficial effect of antiplatelet therapy for recurrent stroke prevention has been well established, uncertainties remain regarding the optimal antithrombotic regimen for recently symptomatic carotid stenosis. We sought to explore the approaches of stroke physicians to antithrombotic management of patients with symptomatic carotid stenosis. Methods: We employed a qualitative descriptive methodology to explore the decision-making approaches and opinions of physicians regarding antithrombotic regimens for symptomatic carotid stenosis. We conducted semi-structured interviews with a purposive sample of 22 stroke physicians (11 neurologists, 3 geriatricians, 5 interventional-neuroradiologists, and 3 neurosurgeons) from 16 centers on four continents to discuss symptomatic carotid stenosis management. We then conducted thematic analysis on the transcripts. Results: Important themes revealed from our analysis included limitations of existing clinical trial evidence, competing surgeon versus neurologist/internist preferences, and the choice of antiplatelet therapy while awaiting revascularization. There was a greater concern for adverse events while using multiple antiplatelet agents (e.g., dual-antiplatelet therapy (DAPT)) in patients undergoing carotid endarterectomy compared to carotid artery stenting. Regional variations included more frequent use of single antiplatelet agents among European participants. Areas of uncertainty included antithrombotic management if already on an antiplatelet agent, implications of nonstenotic features of carotid disease, the role of newer antiplatelet agents or anticoagulants, platelet aggregation testing, and timing of DAPT. Conclusion: Our qualitative findings can help physicians critically examine the rationale underlying their own antithrombotic approaches to symptomatic carotid stenosis. Future clinical trials may wish to accommodate identified variations in practice patterns and areas of uncertainty to better inform clinical practice.

Background: COVID 19 affects not only patients’ physical health but also mental well-being. Objective: To explore how hermeneutics, i.e., the theory and practice of interpretation, promotes person-centered mental health during the COVID-19 pandemic. Method: An excerpt of a dialogue between a patient with depression and his psychiatrist was used to illustrate how hermeneutics promotes person-centered mental health. Results: The case study, reviewed through the perspective of hermeneutics, showed that the patient needs a personal narrative to voice his COVID-19-related physical worries as well as associated psychosocial difficulties, mental health distress, and spiritual concerns. Discussion: A multi-layered personal narrative, informed by hermeneutics, ensures mental health needs are not overlooked/neglected in individuals affectedby COVID-19. Conclusion: Hermeneutics, when properly and clinically applied, promotes person-centered mental health in pandemic times.

It is uncertain whether biological therapies would increase the risk of hepatitis among patients with past hepatitis B virus (HBV) infection. This study aimed to evaluate the risk of alanine aminotransferase (ALT) flare in patients with past HBV infection while using biological therapies.Patients who received biological therapies for ≥3 months from 2000 to 2019 were identified from a population-based database in Hong Kong. Patients with past HBV infection were compared with a control group without prior HBV exposure. The primary endpoint was development of ALT flare within 5 years of starting biological therapies, defined as ALT 80 IU/L.There were 2471 and 2394 patients with and without past HBV infection respectively. There was a non-significant increase in risk of ALT flare among the HBV-exposed group (27.6% vs. 23.7%, p = .055). In multivariable analysis, using prednisolone-equivalent dose of20 mg daily, male sex and concomitant immunosuppressants were risk factors for ALT flare. The risk of ALT flare was significantly higher with anti-CD20 when compared to other biological agents (36.1% vs. 14.5%, p .01), but was not significantly different among anti-tumour necrosis factor, anti-cytokine, Janus kinase inhibitors and T cell/B cell inhibitors or anti-integrin (15.2% vs. 14.6% vs. 11.7% vs. 11.1%, p = .82). Among patients with documented hepatitis B surface antigen seroreversion, 96% were on anti-CD20.Our study further supports the current suggestion of prophylactic anti-viral before starting anti-CD20 in HBV-exposed patients. While other biological therapies appear to have a lower risk for ALT flare, this result needs further confirmation.

Encapsulation into nanoparticles (NPs) is a potential method to deliver pharmaceutical/cosmetic actives deep into the skin. However, understanding the NP formulations and underlying mechanism of active delivery to skin has scarcely been studied. We report a

Low-dose aspirin and metformin have been individually associated with a reduced risk of cancer. Whether their concurrent use in adults with type 2 diabetes mellitus (T2DM) is associated with a reduced risk of colorectal cancer (CRC) is unclear.Among individuals with T2DM taking metformin, we sought to evaluate the association between low-dose aspirin versus no aspirin and the risk of CRC.A multiple-database new-user cohort study of patients with T2DM taking metformin was conducted between 2007-2010 (Clinical Data Analysis and Reporting System [CDARS], Hong Kong) and 2007-2016 (The Health Improvement Network [THIN], UK). The primary outcome was incident CRC. Patients were followed from index date of prescription until the earliest occurrence of an outcome of interest, an incident diagnosis of any cancer, death, or until December 31, 2019. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Estimates were pooled using an inverse variance random effects model, and heterogeneity was assessed using IAfter one-to-one propensity-score matching, 57,534 patients were included (CDARS = 16,276; THIN = 41,258). The median (IQR) follow-up was 9.3 (6.5-10.7) years in CDARS and 3.2 (1.1-5.8) years in THIN. The concurrent use of low-dose aspirin and metformin was not associated with a lower risk of CRC compared to metformin only (HR = 0.89, 95% CI 0.75-1.05, ILow-dose aspirin was not associated with a lower risk of CRC in patients with T2DM taking metformin. Our study does not support the routine use of low-dose aspirin in this population. This article is protected by copyright. All rights reserved.

OBJECTIVE Flow-diverting stents with a resorbable component have significant theoretical benefits over full metal stents, although currently there are none in clinical use. In this study, the authors sought to determine the immediate flow-diversion characteristics of a novel primarily bioresorbable flow-diverting stent. METHODS Bioresorbable stents were deployed into glass tube models to determine porosity and pore density. In vitro flow diversion behavior was evaluated using high frame rate angiography under pulsatile flow conditions in a patient-specific silicone aneurysm model treated with the resorbable stent as well as the Surpass Evolve stent. In vivo flow diversion was characterized by deployment into 20 rabbit saccular aneurysm models, and grading was based on the O’Kelly-Marotta scale and the 4F-flow diversion predictive score. RESULTS Porosities and pore densities of the bioresorbable stent were in the flow-diverting range for all target vessel diameters. Quantified results of immediate angiography after placement of the bioresorbable stent into a silicone aneurysm model demonstrated greater flow diversion compared to the Evolve stent. Bioresorbable stent placement in saccular aneurysm models resulted in an immediate O’Kelly-Marotta grade of A3 or better and a 4F-flow diversion predictive score of 4 or better in all cases. CONCLUSIONS The bioresorbable stent has immediate flow-diversion characteristics that are comparable to commercially available metal stents. Longer-term studies are underway to determine the ability of the resorbable fibers to act as a neointimal scaffold and result in long-term aneurysm occlusion.

Data on the effectiveness of oral antivirals in patients with mild-to-moderate COVID-19 are urgently needed. This retrospective cohort study aimed to evaluate the clinical and virological outcomes associated with molnupiravir or nirmatrelvir-ritonavir use in hospitalised patients with mild-to-moderate COVID-19 during a pandemic wave dominated by the omicron BA.2 subvariant.We analysed data from a territory-wide retrospective cohort of patients in Hong Kong who were hospitalised with a confirmed diagnosis of SARS-CoV-2 infection between Feb 26 and April 26, 2022. Data were extracted from the Hospital Authority, the Department of Health, and the Hong Kong Death Registry. Patients were eligible for inclusion if their admission date was within 3 days before or after confirmation of their COVID-19 diagnosis. Those who were admitted to hospital more than 5 days after symptom onset, were younger than 18 years, had a history of oral antiviral use before admission, required supplemental oxygen on admission, had drug-related contraindications to nirmatrelvir-ritonavir use, or had severe renal or severe liver impairment were excluded. Patients who received the oral antivirals molnupiravir or nirmatrelvir-ritonavir were matched with controls using propensity-score matching in a ratio of 1:1. The primary outcome was all-cause mortality and secondary outcomes included a composite outcome of disease progression (all-cause mortality, initiation of invasive mechanical ventilation [IMV], intensive care unit [ICU] admission, or the need for oxygen therapy) and each of these individual disease progression outcomes, and time to reaching a low viral burden (RT-PCR cycle threshold value ≥30). For each event outcome, crude incidence rates were calculated and hazard ratios (HRs) estimated using Cox regression models.We identified 40 776 patients hospitalised with SARS-CoV-2 infection during the study period, with a mean follow-up of 41·3 days (total 925 713 person-days). After exclusions and propensity-score matching, we included 1856 molnupiravir recipients and 1856 matched controls, and 890 nirmatrelvir-ritonavir recipients and 890 matched controls. A lower risk of all-cause mortality was observed in molnupiravir recipients (crude incidence rate per 10 000 person-days 19·98 events [95% CI 16·91-23·45]) versus matched controls (38·07 events [33·85-42·67]; HR 0·48 [95% CI 0·40-0·59], p0·0001) and in nirmatrelvir-ritonavir recipients (10·28 events [7·03-14·51]) versus matched controls (26·47 events [21·34-32·46]; HR 0·34 [0·23-0·50], p0·0001). Oral antiviral recipients also had lower risks of the composite disease progression outcome (molnupiravir HR 0·60 [95% CI 0·52-0·69], p0·0001; nirmatrelvir-ritonavir 0·57 [0·45-0·72], p0·0001) and need for oxygen therapy (molnupiravir 0·69 [0·57-0·83], p=0·0001; nirmatrelvir-ritonavir 0·73 [0·54-0·97], p=0·032) compared with controls. Time to achieving a low viral burden was significantly shorter among oral antiviral recipients than matched controls (molnupiravir HR 1·38 [95% CI 1·15-1·64], p=0·0005; nirmatrelvir-ritonavir 1·38 [1·07-1·79], p=0·013). Significant differences in initiation of IMV and ICU admission were not found.During a wave of SARS-CoV-2 omicron BA.2, initiation of novel oral antiviral treatments in hospitalised patients not requiring oxygen therapy on admission showed substantial clinical benefit. Our findings support the early use of oral antivirals in this population of patients.Health and Medical Research Fund (Health Bureau, Government of the Hong Kong Special Administrative Region).For the Chinese translation of the abstract see Supplementary Materials section.

Prior studies have demonstrated robotic excision of cardiac tumors as a safe and effective treatment option. The procedure is performed with five incisions: three robotic arm ports, one atrial retractor port, and one working port. We report our unique initial experience in robotic tumor removal. To our knowledge, this is one of the first reports demonstrating cardiac myxoma and fibroelastoma removal with use of exclusively 8-mm ports.All data for robotic cardiac tumor resection at our institution from June 2019 to December 2021 were retrospectively collected; 18 cases were included, including 13 cardiac myxomas and five fibroelastomas. Baseline demographics, intraoperative characteristics, and surgical outcomes were recorded. Descriptive statistics were calculated; continuous variables were reported as median [interquartile range], and categorical variables were reported as percentages.Median patient age was 64 [55, 70] years old. The cohort consisted of primarily female (67%) and white (83%) patients. Median body mass index was 26.3 [23.0, 31.5] kg/mIn our study, the robotic platform facilitated safe and effective cardiac tumor excision. Our results highlight the efficacy of 8-mm port sizing and the concurrent use of other minimally invasive techniques, including percutaneous cannulation, in this patient population. In general, patients prefer the least invasive treatment option available. Our findings emphasize the importance of training cardiac surgeons to perform robotic procedures using the least invasive means possible to provide patients with various options for their treatment.

Considerable research has documented the impact of teacher perceptions on students’ academic-related outcomes (e.g., classroom performance). This body of literature clearly shows that teacher perceptions (resulting from direct interactions with students) can have both positive and negative effects with respect to student behaviors and experiences in the classroom. What remains unclear is whether teachers perceive changes that result from interventions administered outside of their classrooms. The purpose of this study was to examine changes in teacher perceptions of working memory and executive function concerns (two important predictors of academic success) among students who participated in a computerized cognitive training program designed to enhance working memory skills. The current results indicate that teachers perceived fewer concerns following students’ participation in the training; this outcome was supplemented with significant improvements in the students’ working memory capabilities following the training program. These findings have important implications given the literature highlighting the relation between teacher perceptions and student outcomes as a function of a school-based computerized cognitive training intervention.

The poorly known pilumnid crab Cryptocoeloma haswelli Rathbun, 1923, is redescribed and figured at length on the basis of fresh specimens from Hong Kong and Taiwan, both of which constitute new local records. The male is redescribed and figured as the only previous account of it had been based on a gynandromorph. The species is also compared in detail with Heteropilumnus fimbriatus (H. Milne Edwards, 1834) with which it has been previously confused.

Background Recent studies using single molecule, real-time (SMRT) sequencing revealed a substantial population of analyzable long cell-free DNA (cfDNA) in plasma. Potential clinical utilities of such long cfDNA in pregnancy and cancer have been demonstrated. However, the performance of different long-read sequencing platforms for the analysis of long cfDNA remains unknown. Methods Size biases of SMRT sequencing by Pacific Biosciences (PacBio) and nanopore sequencing by Oxford Nanopore Technologies (ONT) were evaluated using artificial mixtures of sonicated human and mouse DNA of different sizes. cfDNA from plasma samples of pregnant women at different trimesters, hepatitis B carriers, and patients with hepatocellular carcinoma were sequenced with the 2 platforms. Results Both platforms showed biases to sequence longer (1500 bp vs 200 bp) DNA fragments, with PacBio showing a stronger bias (5-fold overrepresentation of long fragments vs 2-fold in ONT). Percentages of cfDNA fragments 500 bp were around 6-fold higher in PacBio compared with ONT. End motif profiles of cfDNA from PacBio and ONT were similar, yet exhibited platform-dependent patterns. Tissue-of-origin analysis based on single-molecule methylation patterns showed comparable performance on both platforms. Conclusions SMRT sequencing generated data with higher percentages of long cfDNA compared with nanopore sequencing. Yet, a higher number of long cfDNA fragments eligible for the tissue-of-origin analysis could be obtained from nanopore sequencing due to its much higher throughput. When analyzing the size and end motif of cfDNA, one should be aware of the analytical characteristics and possible biases of the sequencing platforms being used.

Chronic obstructive pulmonary disease (COPD) is a leading cause of death and cigarette smoke is the main risk factor. Detecting its earliest stages and preventing a decline in lung function are key goals. The pathogenesis of COPD is complex but has some similarities to cystic fibrosis (CF), a disease caused by mutations in the cftr gene. CF leads to chronic inflammation, abnormal mucus, and cycles of infection. Cigarette smoke exposure also causes CFTR dysfunction, and it is probably not a coincidence that inflammation, mucus obstruction, and infections are also characteristics of COPD, although the exacerbations can be quite different. We review here the acute effects of cigarette smoke on CFTR function and its potential role in COPD. Understanding CFTR regulation by cigarette smoke may identify novel drug targets and facilitate the development of therapeutics that reduce the progression and severity of COPD.

To review the current literature regarding the health disparities in the prevalence, diagnosis, and management of pediatric food allergy and discuss possible interventions.Literature search of PubMed and Google Scholar databases regarding pediatric food allergy and health disparities.Original research articles, reviews, and guidelines on health disparities in pediatric food allergy were included in this review.The overall prevalence of food allergy appears to be increasing and disproportionately affecting minority groups. Racial and socioeconomic disparities are evident across all aspects of food allergy care: diagnosis, prevention, acute management (eg, access to epinephrine autoinjectors, visits to emergency department), and long-term management (eg, oral immunotherapy). Children of minority populations and those of low socioeconomic status are at a greater risk of food insecurity, which is further exacerbated by the high cost of allergen-free foods and limited support from food assistance programs.Racial, ethnic, and socioeconomic disparities in food allergy among children in the United States are evident and negatively affect the outcomes of children with food allergies. Active efforts to decrease racial and socioeconomic disparities, through education, research, and advocacy, will be important to help improve health outcomes in food allergy for all children, regardless of their race, ethnicity, or socioeconomic status.

Recent years have demonstrated the rise of localism worldwide. In an Asian context, we are witnessing an increasing number of protest events and numerous social movement documentaries being produced. In Hong Kong, Edward Tin-kei Leung 梁天琦 was the first self-proclaimed localist to participate in a democratic election and the first to be charged for riot since the Handover. The documentary film of Leung’s story,Lost in the Fumes, achieved an impressive degree of popularity among local people during the Anti-Extradition Law Amendment Bill (ELAB) movement. Analysing its storylines and plots, as well as filming techniques, from the perspectives of film studies and cultural studies, together with several interviews as a supplement, this article examines the emotional connections of films and protesting bodies in social movements. It explores the cinematic representation of Leung and how this representation was received by viewers to facilitate self-mobilization in the Anti-ELAB Movement. Hence, I will analyse the functions of films as a cultural or emotional foundation in social movements that facilitate the creation of a shared emotional engagement.

In the eutectic mixture of bis(2,2-dinitropropyl) acetal (BDNPA) and bis(2,2-dinitropropyl) formal (BDNPF), also known as nitroplasticizer (NP)

Let [Formula: see text] be a positive integer and let [Formula: see text] be the set of positive integers less than [Formula: see text] that are relatively prime to [Formula: see text]. If [Formula: see text] can be partitioned into two subsets of equal sum, then [Formula: see text] is called a super totient number. In this paper, we generalize this concept by considering when [Formula: see text] can be partitioned into [Formula: see text] subsets of equal sum. Integers that admit such a partition are called [Formula: see text]-fold super totient numbers. In this paper, we prove that for every odd positive integer [Formula: see text], there exists an integer [Formula: see text] such that for all [Formula: see text], [Formula: see text] is a [Formula: see text]-fold super totient numbers provided that some trivial necessary condition is satisfied. Furthermore, we determine the smallest allowable values for [Formula: see text] and [Formula: see text].

This article proposes resource extraction politics as a lens to analyze the relationship between Malaysian Chinese (or Mahua) literature and the global literary economy. Rather than ascribe Mahua literature to its present national boundaries and diasporic communities, the article locates its formation in inter-imperial nodes of trafficked labor and art production, as well as a global system of colonial plantations. The article revisits Zeng Huading's 曾華丁 (1906–1942) short story (1928) and Ba Ren's 巴人 (1901–1972) historical drama (1949) about the myth of five Chinese coolies and their execution in 1871 for murdering a Dutch foreman in a Deli tobacco plantation in East Sumatra. The Anglo-Dutch migration corridor, or the cross-straits coolie trade between the two imperial jurisdictions of Penang (Straits Settlements) and Medan (East Sumatra), now part of Malaysia and Indonesia respectively, was one Nanyang connection, but these writers have been discussed separately within Mahua and Yinhua 印華 (Indonesian Chinese) contexts. Ba Ren, in particular, is studied as a leftist writer who contributed artistically to the Indonesian and Chinese revolutions in the 1940s and 1950s. Here, the article rethinks Ba Ren's legacy within a Mahua corpus, and Zeng Huading's fiction within a cross-straits history of labor. This ecological reading of their works also highlights their critique of Mahua's peripheralization within a world economy and global literature.

A 33-year-old, 8 weeks pregnant, presented with severe upper abdominal pain with vomiting on a background of a previous laparoscopic Nissen fundoplication for reflux disease. An urgent MRI had shown herniation of the fundoplication wrap through the diaphragmatic hiatus. The cause of her symptoms was attributed to hyperemesis gravidarum. The plan was to manage this patient conservatively until the conclusion of her pregnancy. This plan was revised when she presented for the second time and developed worsening pain and haematemesis. An emergency gastroscopy showed ischaemic changes in most of the stomach requiring the patient to undergo an emergency laparotomy. In pregnant patients, presenting with abdominal pain, vomiting as well as haematemesis, having had previous antireflux surgery, incarceration of the stomach must be considered as a differential. Prompt assessment and early senior decision-making is extremely important in avoiding a potentially catastrophic outcome for such patients.

Purpose: Drug repurposing offers the opportunity for chemotherapy to be used to reestablish sensitivity to immune checkpoint blockade (ICB) therapy. Here we investigated the clinical and translational aspects of an early phase II study of azacitidine and carboplatin priming for anti-PDL1 immunotherapy (avelumab) in patients with advanced ICB-resistant melanoma. Experimental Design: A total of 20 participants with ICB-resistant metastatic melanoma received 2 × 4-week cycles of azacitidine and carboplatin followed by ICB rechallenge with anti-PD-L1 avelumab. The primary objective was overall response rate after priming and ICB rechallenge. Secondary objectives were clinical benefit rate (CBR), progression-free survival (PFS), and overall survival (OS). Translational correlation analysis of HLA-A and PD-L1 expression, RNA sequencing, and reduced representation bisulfite sequencing of biopsies at baseline, after priming and after six cycles of avelmuab was performed. Results: The overall response rate (ORR) determined after azacitidine and carboplatin priming was 10% (2/20) with two partial responses (PR). The ORR determined after priming followed by six cycles of avelumab (week 22) was 10%, with 2 of 20 participants achieving immune partial response (iPR). The CBR for azacitidine and carboplatin priming was 65% (13/20) and after priming followed by six cycles of avelumab CBR was 35% (n = 7/20). The median PFS was 18.0 weeks [95% confidence interval (CI): 14.87–21.13 weeks] and the median OS was 47.86 weeks (95% CI: 9.67–86.06 weeks). Translational correlation analysis confirmed HLA-A generally increased after priming with azacitidine and carboplatin, particularly if it was absent at the start of treatment. Average methylation of CpGs across the HLA-A locus was decreased after priming and T cells, in particular CD8+, showed the greatest increase in infiltration. Conclusions: Priming with azacitidine and carboplatin can induce disease stabilization and resensitization to ICB for metastatic melanoma. Significance: There are limited treatments for melanoma once resistance to ICB occurs. Chemotherapy induces immune-related responses and may be repurposed to reinstate the response to ICB. This study provides the first evidence that chemotherapy can provide clinical benefit and increase OS for ICB-resistant melanoma.

Coral reefs are threatened both locally and globally by anthropogenic impacts, which to date have contributed to substantial declines in coral cover worldwide. However, some corals are more resilient to these environmental changes and therefore have increased relative abundance on local scales and may represent prominent members shaping future reef communities. Here, we provide the first draft reference genome for one such reef-building coral, the mustard hill coral, Porites astreoides. This reference genome was generated from a sample collected in Bermuda, with DNA sequenced via Pacific Biosciences HiFi long-read technology to provide an initial draft reference genome assembly. Assembly of the PacBio reads with FALCON UnZip resulted in a 678 Mbp assembly with 3,051 contigs with an N50 of 412,256. The genome BUSCO completeness analysis resulted in 90.9% of the metazoan gene set. An ab initio transcriptome was also produced with 64,636 gene models with a transcriptome BUSCO completeness analysis of 77.5% when compared to the metazoan gene set. The function annotation was obtained through a hierarchical approach of SwissProt, TrEMBL, and NCBI nr database of which 86.6% of proteins were annotated. Through our ab initio gene prediction for structural annotation and generation of a functional annotation for the P. astreoides draft genome assembly, we provide valuable resources for improving biological knowledge, which can facilitate comparative genomic analyses for corals, and enhance our capacity to test for the molecular underpinnings of adaptation and acclimatization to support evidence-based restoration and human assisted evolution of corals.ClassificationsGenetics and Genomics; Animal Genetics; Marine Biology

Agrobacterium tumefaciens is a plant pathogen commonly repurposed for genetic modification of crops. Despite its versatility, it remains inefficient at transferring DNA to many hosts, including to animal cells. Like many pathogens, physical contact between A. tumefaciens and host cells promotes infection efficacy. Thus, improving the strength and specificity of A. tumefaciens to target cells has the potential for enhancing DNA transfer for biotechnological and therapeutic purposes. Here we demonstrate a methodology for engineering genetically-encoded exogeneous adhesins at the surface of A. tumefaciens. We identified an autotransporter gene we named Aat, that is predicted to show canonical β-barrel and passenger domains. We engineered the β-barrel scaffold and linker (Aatβ) to display synthetic adhesins susceptible to rewire A. tumefaciens to alternative host targets. As a proof of concept, we leveraged the versatility of a VHH domain to rewire A. tumefaciens adhesion to yeast and mammalian hosts displaying a GFP target receptor. Finally, to demonstrate how synthetic A. tumefaciens adhesion can improve transfer to host cells, we showed improved protein translocation into HeLa cells using a sensitive split luciferase reporter system. Engineering A. tumefaciens adhesion has therefore a strong potential in generating complex heterogeneous cellular assemblies and in improving DNA transfer efficiency against non-natural hosts.

Pleural effusion can be caused by a wide range of benign and malignant conditions. Pleural biopsy and effusion cytology represent two key methods of pathological diagnosis. To compare the performance these two methods, a large cohort of matched pleural biopsy and effusion cytology with clinical follow-up was reviewed.Pleural biopsies and effusion cytology specimens over a period of 18 years were retrieved. Cytology specimens collected within 7 days of pleural biopsy were matched. Reports were reviewed, and the cause for pleural effusion was determined by hospital disease coding and clinical data.Totally, 3026 cases were included. The leading cause of benign effusion was tuberculosis (n = 650). Malignant pleural effusion (MPE) was more common in older females (p 0.001) and mostly due to lung cancer (n = 959), breast cancer (n = 64), and mesothelioma (n = 48). The inadequate/insufficient (B1/C1) rate of biopsy was higher than cytology (15.6% vs. 0.3%) but the rates for other diagnostic categories were similar. Biopsy and cytology showed a correlation coefficient of 0.315, improving to 0.449 when inadequate/insufficient (B1/C1) cases were excluded. The ROM for benign cytology (C2) was lower than biopsy (B2) (p 0.001). Compared with biopsy, the diagnostic accuracy was higher in cytology overall and for metastatic carcinomas (p 0.001) but lower for hematolymphoid malignancies (p = 0.014) and mesotheliomas (p = 0.002).These results suggest that effusion cytology may be better for confirming benignity and diagnosing carcinomatous MPE. In these cases, pleural biopsy may be withheld to reduce procedural risks. However, for suspected hematolymphoid malignancies and mesothelioma, biopsy should be considered.

Despite over 150000 amputations of lower limbs annually, there remains a wide variation in tourniquet practice patterns and no consensus on their necessity, especially among orthopedic patient populations. The purpose of this study was to determine whether tourniquet use in orthopedic patients undergoing below knee amputation (BKA) was associated with a difference in calculated blood loss relative to no tourniquet use.To determine if tourniquet use in orthopedic patients undergoing BKA was associated with a difference in calculated blood loss relative to no tourniquet use.We performed a retrospective review of consecutive patients undergoing BKA by orthopedic surgeons at a tertiary care hospital from 2008 through 2018. Blood loss was calculated using a combination of the Nadler equation for preoperative blood volume and a novel formula utilizing preoperative and postoperative hemoglobin levels and transfusions. Univariate and forwards step-wise multivariate linear regressions were performed to determine the association between tourniquet use and blood loss. A Wilcoxon was used to determine the univariate relationship between tourniquet use and blood loss for in the restricted subgroups of patients who underwent BKA for trauma, tumor, and infection.Of 97 eligible patients identified, 67 underwent surgery with a tourniquet and 30 did not. In multivariate regression, tourniquet use was associated with a 488 mL decrease in calculated blood loss (CI 119-857,We found that tourniquet use during BKA is associated with decreased calculated intraoperative blood loss. We recommend that surgeons performing this procedure use a tourniquet to minimize blood loss.

Research that has examined the relationships between Internet gaming disorder (IGD) and personality traits has been limited by the use of instruments based on inappropriate criteria. Furthermore, the personality traits have seldom been studied concurrently, precluding an examination of the relative importance of each trait in predicting IGD. The current study aimed to address those limitations by concurrently examining the Big Five Personality Factors, sensation seeking, impulsivity, and aggression, as potential predictors of IGD. Participants were a convenience sample of 123 gamers (57.7% females). A hierarchical multiple regression was conducted with age and gender in Step 1 and the personality traits in Step 2. The results showed that only impulsivity and gender significantly predicted IGD. Limitations include the conceptualization of impulsivity as a negative construct and the unreliability of the openness to experience subscale. Future research directions include using impulsivity as a core characteristic of an individual and examine its interaction with a range of affective and cognitive factors.

Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell non-Hodgkin lymphoma and remains incurable in ~40% of patients. Coding-genome sequencing efforts identified several genes/pathways altered in this disease, including new potential therapeutic targets(1–5). However, the non-coding genome of DLBCL remains largely unexplored. Here we show that active super-enhancers (SEs) are highly and specifically hypermutated in 92% of DLBCL samples, display signatures of activation-induced cytidine deaminase (AID) activity, and are linked to genes encoding B-cell developmental regulators and oncogenes. As evidence of oncogenic relevance, we show that the hypermutated SEs linked to the BCL6, BCL2, and CXCR4 proto-oncogenes prevent the binding and transcriptional downregulation of the corresponding target gene by transcriptional repressors, including BLIMP1 (BCL6) and the steroid-receptor NR3C1 (BCL2 and CXCR4). Genetic correction of selected mutations restored repressor DNA-binding, downregulated target gene expression, and led to the counter-selection of cells harboring corrected alleles, indicating oncogenic dependency on the SE mutations. This pervasive SE mutational mechanism reveals a novel major set of genetic lesions deregulating gene expression, which expands the involvement of known oncogenes in DLBCL pathogenesis and identifies new deregulated gene targets of therapeutic relevance.