bluuebunny/crossref_metadata_2025 huggingface dataset:
IBC-Oxford University2023_BJSOral_14Onco-metabolic Surgery: The Metabolic Effects and Effectiveness of the Different Reconstruction Methods used in Gastric Cancer Surgery. A Systematic Review and Meta-analysis
Authors: Pinho Costa M , Santos-Sousa H , Rodrigues Oliveira C , Amorim-Cruz F , Bouça R , Barbosa E , Carneiro S , Sousa-Pinto B
Published: December 2023

Introduction

Gastric Cancer (GC) is the fifth most common cancer worldwide. With the development of screening programmes, early stages of GC began being detected, giving rise to a new concern: Quality of Life. Traditional surgical techniques for GC can be tailored and adjusted based on the principles of metabolic and bariatric surgery to optimise therapeutic benefits without sacrificing oncological safety. This study aimed to systematically assess the effects of different GC reconstruction techniques on postoperative type 2 diabetes mellitus (T2DM), hypertension (HT), and body mass index (BMI) reduction rate and to provide an overview of recent research on Onco-metabolic Surgery (OS).

Methods

We performed a systematic review and meta-analysis by searching three databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We performed a metaanalysis of risk ratios and mean differences to estimate the impact of duodenal bypass, Roux-en-Y (RY) reconstruction, and residual stomach on T2DM, HT and BMI reduction rate. Heterogeneity was assessed using the I2 statistics.

Results

We included 31 studies in the qualitative synthesis and 18 in the quantitative synthesis. At the end of the follow-up, the duodenal bypass group compared to Billroth I had a significantly higher postoperative partial and complete remission of T2DM and HBP, with a relative risk (RR) of 1.43 (95% confidence interval (95%CI) [1.27; 1.62]) and 1.3 (95%CI [1.00; 1.69]), respectively. Compared with the Billroth II group, RY reconstruction had significantly greater T2DM remission after gastrectomy (RR=1.19; 95%CI [1.08; 1.31]), while HBP showed no statistically significant differences. Regarding improvement in HT, total gastrectomy was significantly superior to subtotal gastrectomy (95%CI [1.01; 2.64]). Although there were no significant differences in the extent of gastrectomy, a trend towards RY oesophagojejunostomy as the best option for T2DM remission was observed (95%CI [0.98; 2.77]; p=0.06).

Conclusion

Gastrectomy with Roux-en-Y reconstruction appears to be the most effective treatment for T2DM remission. Gastrectomy with long-limb Roux-en-Y reconstruction should be considered for patients with early-stage GC, concomitant metabolic diseases, and no surgery contraindications. Further research is needed to assess the impact of OS on metabolic diseases.
IBC-Oxford University2023_BJSOral_16Surgical Outcomes of Totally Robotic Versus Laparoscopic Primary Bariatric Metabolic Surgeries
Authors: Smith D , Lopez C , Krzyzanowski S , Santos C , Buffington C
Published: December 2023

Background

Over the past several years, the numbers of bariatric metabolic surgeries (BMS) performed robotic have been steadily increasing. Recent meta-analyses and registry reports find that primary surgeries performed robotic have similar outcomes to conventional laparoscopy but with longer operative times and higher costs. Most of the robotic surgeries in these reports, however, have been robot-assisted rather than totally (fully) robotic. The introduction of robotic staplers and conversion of the robotic system to the Xi platform now allow surgeons to perform bariatric surgeries totally robotic.

Objectives

To compare surgical outcomes of total robotic (TR) versus laparoscopic (LAP) primary bariatric metabolic surgeries (BMS) including sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and the biliopancreatic diversion with duodenal switch (DS).

Methods

The study is a retrospective analysis of 600 (302 TR and 298 LAP) primary BMS performed by a single surgeon between January 2020 and January 2023. Primary surgeries included 332 SG, 214 RYGB and 54 DS cases. Outcome measures included: 1) patient characteristics (age, weight, BMI, gender), 2) total number and incidence of preoperative co-morbidities, 3) operative time, 4) length of hospital stay (LOS), 5) complications, readmissions, and reoperations.

Results

Characteristics of the TR and LAP patients were similar, i.e., age = 45.5 vs. 44.9 y, respectively; BMI = 46.3 vs. 46.1; number major co-morbidities = 2.73 and 2.75. Operative times did not differ significantly between the TR and LAP approaches (84.3 vs. 88.2 min, respectively). LOS, however, was significantly (p<0.0001) less following surgeries performed totally robotic (1.16 days TR vs. 1.36 days LAP). There were no differences between the TR and LAP surgeries as regards 30-day readmission or reoperation rates but there was a trend toward fewer TR 30-day complications (2.3% TR vs. 5.0% LAP). With the RYGB, operative times were significantly lower for the totally robotic approach (99.6 min TR vs. 115.1 min LAP, p<0.0001) and LOS was significantly less (1.18 days TR vs. 1.38 days LAP, p<0.0001). For the SG, there were no significant differences between the TR and LAP approaches regarding operative times, but TR LOS was significantly (p<0.0001) less (1.13 days TR vs. 1.31 days LAP). Postoperative recovery rates (LOS) with the DS were also enhanced with the totally robotic approach (1.24 days TR vs. 1.58 days LAP, p=0.02), but operative times did not significantly differ (188.7 min TR, 176.5 min LAP).

Conclusions

Primary bariatric procedures (SG, RYGB, DS) performed totally robotic are as safe as conventional laparoscopy and have somewhat fewer complications, a faster rate of recovery, and,for the RYGB, shorter time in surgery.
IBC-Oxford University2023_BJSOral_24Comparison of postoperative GERD after LSG with omentopexy versus LSG without omentopexy, incidence of peri-operative GERD LSG in East Asia.
Authors: Hwang D , Yoo M , Park Y S
Published: December 2023

Background

Gastroesophageal Reflux Disease (GERD) is known as the most common long-term complication after laparoscopic sleeve gastrectomy (LSG). The pathophysiology is assumed that the sleeved stomach after LSG is prone to be herniated through the hiatus with high intra- abdominal pressure in obese patients. The omentopexy is thought to make the remnant stomach fixed in abdominal cavity to decrease GERD symptom.

Objectives

This study aims to compare postoperative GERD after LSG with omentopexy versus LSG without omentopexy as well as to report incidence of peri-operative GERD LSG in East Asia with obesity.

Methods

This was a single-center retrospective comparative study. Patients with severe obesity (BMI > 35 or > 30 with second metabolic disease) who underwent LSG between January 2019 and June 2021 in Seoul National University Bundang Hospital were enrolled. Patient data were collected preoperatively and at postoperative 1 year. At each time point, body weight, laboratory tests and esophagogastroduodenoscopy were assessed. The patients were asked if anti-reflux medication including proton-pump inhibitor was taken and responded to GERD questionnaire. The validated Korean version of GERD-Q questionnaire was utilized. Laparoscopic sleeve gastrectomy was performed in the usual manner, with or without omentopexy. Omentopexy was defined as the suturing the stapled stomach to the omentum which must include upper part of the sleeve. Electric medical and surgical records were evaluated by the surgeons who were specialized in gastrointestinal surgery. The primary outcome was GERD incidence evaluated by three criteria: LA classification on esophagogastroduod enoscopy, GERD-Q score and anti-reflux medication history.

Results

During the study period, 106 and 62 patients were enrolled in the LSG with omentopexy group (LSGO) and LSG without omentopexy group (LSGWO) respectively. The baseline demographics did not significantly differ from each group. The mean age of LSGO group was 37.8 years (standardized deviation [SD] 11.0 years] and that of LSGWO group was 38.4 years [SD 10.9 years] (p=0.959). The LSGO and LSGWO groups were comprised of 34.0% and 35.5% men (p=0.868). There were no significant differences in surgical outcomes and postoperative complications between two groups. On GERD, there was no significant difference in LA classification and anti-reflux medication proportion between two groups after postoperative 1 year. However, LSGO group showed significantly less GERD-Q score (mean, SD; 6.57, 1.56) than LSGWO group (mean, SD; 7.91, 3.0) (p=0.02), which represented less subjective GERD symptoms in LSGO group.

Conclusion

People with obesity who underwent laparoscopic sleeve gastrectomy combined with omentopexy showed less GERD symptoms 1 year after operation than those who without omentopexy.
IBC-Oxford University2023_BJSPoster_10Surgical management of intra-gastric balloon complications
Authors: Foula M S
Published: December 2023

In Saudi Arabia, the intra-gastric balloon (IGB) is the most used endoscopic modality. Surgical management for IGB complications has been reported for gastrointestinal perforation and/or obstruction. However, the literature seems to underestimate these complications. We aim to report our experience as a tertiary university hospital in the Eastern Province of Saudi Arabia in dealing with different complications of IGBs that necessitated any type of surgical interventions. A retrospective descriptive study was conducted in a tertiary hospital in Saudi Arabia for 5 years to include all patients with complicated IGB who necessitated any surgical procedure. Exclusion criteria were patients with complicated IGBs that were only managed conservatively, and any complications related to other bariatric procedures. Six patients were referred due to IGB complications that necessitated operative intervention. All patients were young females. Three patients had gastric wall perforation and were managed by endoscopic removal of the IGBs followed by exploratory laparotomy. One patient had an intestinal obstruction on top of a migrated IGB that was surgically removed. One patient had failed endoscopic retrieval of IGB and required a laparoscopic gastrostomy. Another patient had esophageal rupture that required left thoracotomy, pleural flap and insertion of an esophageal stent. All cases were discharged and followed up with no related complications.
IBC-Oxford University2023_BJSPoster_13Short-term outcomes of sleeve gastrectomy for morbid obesity: A single-center experience
Authors: Senol M , Kavlakoglu B
Published: December 2023

Background

Sleeve gastrectomy is a commonly performed procedure for individuals with morbid obesity. Short-term outcomes of sleeve gastrectomy are often assessed in terms of excess body mass index loss (EBMIL). These measures provide an indication of the amount of weight lost relative to the excess weight or excess body mass index prior to surgery.

Methods

In this study, we evaluated the short-term outcomes of sleeve gastrectomy in patients with morbid obesity. A retrospective analysis was conducted on a series of Laparoscopic Sleeve Gastrectomy (LSG) procedures performed between January 2020 and December 2022. The medical records of all patients who underwent LSG were reviewed and enrolled.

Results

The study included 162 patients with morbid obesity (mean age: 38 years; 72% female; mean preoperative body mass index: 41 kg/m²). At 6 months postoperatively, the percentage of excess body mass index loss was 69% with a follow-up rate of 81%. At 1 year, it was 83% with a follow-up rate of 72%, and at 2 years, it was 79% with a follow-up rate of 44%. These findings indicate that sleeve gastrectomy leads to substantial weight loss in the short term, as measured by EBMIL.

Conclusion

Sleeve gastrectomy demonstrates favorable short-term outcomes in terms of excess body mass index loss (EBMIL) for individuals with morbid obesity. These measures provide evidence of significant weight reduction following the procedure, highlighting the effectiveness of sleeve gastrectomy as a treatment option for morbid obesity.
Expression profiling of cerebrospinal fluid identifies dysregulated antiviral mechanisms in multiple sclerosis
Authors: Ban Maria , Bredikhin Danila , Huang Yuanhua , Bonder Marc Jan , Katarzyna Kania , Oliver Amanda J , Wilson Nicola K , Coupland Paul , Hadfield James , Göttgens Berthold , Madissoon Elo , Stegle Oliver , Sawcer Stephen
Published: December 2023

Despite the overwhelming evidence that multiple sclerosis is an autoimmune disease, relatively little is known about the precise nature of the immune dysregulation underlying the development of the disease.

Reasoning that the CSF from patients might be enriched for cells relevant in pathogenesis, we have completed a high-resolution single-cell analysis of 96 732 CSF cells collected from 33 patients with multiple sclerosis (n = 48 675) and 48 patients with other neurological diseases (n = 48 057).

Completing comprehensive cell type annotation, we identified a rare population of CD8+ T cells, characterized by the upregulation of inhibitory receptors, increased in patients with multiple sclerosis. Applying a Multi-Omics Factor Analysis to these single-cell data further revealed that activity in pathways responsible for controlling inflammatory and type 1 interferon responses are altered in multiple sclerosis in both T cells and myeloid cells. We also undertook a systematic search for expression quantitative trait loci in the CSF cells. Of particular interest were two expression quantitative trait loci in CD8+ T cells that were fine mapped to multiple sclerosis susceptibility variants in the viral control genes ZC3HAV1 (rs10271373) and IFITM2 (rs1059091). Further analysis suggests that these associations likely reflect genetic effects on RNA splicing and cell-type specific gene expression respectively.

Collectively, our study suggests that alterations in viral control mechanisms might be important in the development of multiple sclerosis.
Widespread necrotic vesicles with genital involvement
Authors: Grau-Echevarría Andrés , Peñuelas-Leal Rodrigo , Labrandero-Hoyos Carolina , Blaya-Imbernón Daniel , Finello Malena , González-García Ángel , Pérez-Zafrilla Elena , Pérez-Ferriols Amparo , Hernández-Bel Pablo
Published: December 2023

We present a clinicopathological challenge consisting of disseminated herpes zoster that simulated mpox. We emphasize the utility of diagnosis with the Tzanck test and skin biopsy, as well as the importance of understanding the clinical picture, owing to its potential severity
Evaluation of dermatological conditions: the diagnostic potential of artificial intelligence in primary care
Authors: Ahuja Kripa , DeSena Grace , Lio Peter
Published: December 2023

We used publicly available images to determine ChatGPT’s diagnostic accuracy and potential to aid in primary care diagnostics of dermatological conditions. We found a lower diagnostic accuracy with publicly available images than with patient images, demonstrating that digital transparency and image retrieval play no role in ChatGPT’s diagnostic accuracy.
Low referral rate of overweight/obese patients with hidradenitis suppurativa to weight-management services: a missed opportunity?
Authors: Khalil Nada , Hussain Khawar , Patel Neil P
Published: December 2023

Hidradenitis suppurativa (HS) is associated with obesity and other cardiovascular risk factors. Referral of overweight/obese patients with HS to weight-management (WM) services is advised as this may help reduce HS disease severity and cardiovascular risk. A retrospective observational study of 50 patients with HS attending a specialist HS clinic was conducted to assess general practitioner referral patterns of overweight/obese patients with HS for WM. Forty-two patients (84%) were classified as overweight or obese. None of 6 overweight patients and none of 18 obese class 1 patients had been referred to WM prior to dermatology referral, while only 2 of 10 (20%) obese class 2 and 3 of 8 (38%) obese class 3 patients had been referred. The overall WM referral rate for overweight/obese patients was only 12% (n = 5/42). The low referral rate suggests that further efforts are required to diagnose overweight/obesity in primary care, improve the provision of WM services and educate medical professionals that HS is a weight-related comorbidity.
Management of cardiac implantable electronic devices around the time of dermatological procedures requiring electrosurgery: an important guidance update
Authors: James Mariel L , Wright Beth , Thomas Honey E , Turley Andrew J , Bray Adam P J J
Published: December 2023

In collaboration with the British Heart Rhythm Society (BHRS), the British Society for Dermatological Surgery (BSDS) has recently updated its guidance on the management of cardiac implantable electronic devices (CIEDs) around the time of dermatological procedures requiring electrosurgery. A section and comprehensive flowchart specific to dermatological surgery now exist in the national BHRS guidance. This letter brings the latest guidance to readers’ attention and outlines important changes that should streamline care for this cohort of patients.
Distinct processing of the state prediction error signals in frontal and parietal correlates in learning the environment model
Authors: Xu Shuyuan , Ren Wei
Published: December 2023

Goal-directed reinforcement learning constructs a model of how the states in the environment are connected and prospectively evaluates action values by simulating experience. State prediction error (SPE) is theorized as a crucial signal for learning the environment model. However, the underlying neural mechanisms remain unclear. Here, using electroencephalogram, we verified in a two-stage Markov task two neural correlates of SPEs: an early negative correlate transferring from frontal to central electrodes and a late positive correlate over parietal regions. Furthermore, by investigating the effects of explicit knowledge about the environment model and rewards in the environment, we found that, for the parietal correlate, rewards enhanced the representation efficiency (beta values of regression coefficient) of SPEs, whereas explicit knowledge elicited a larger SPE representation (event-related potential activity) for rare transitions. However, for the frontal and central correlates, rewards increased activities in a content-independent way and explicit knowledge enhanced activities only for common transitions. Our results suggest that the parietal correlate of SPEs is responsible for the explicit learning of state transition structure, whereas the frontal and central correlates may be involved in cognitive control. Our study provides novel evidence for distinct roles of the frontal and the parietal cortices in processing SPEs.
Clinical Features and Outcomes of Infections Caused by Metallo-β-Lactamase–Producing Enterobacterales: A 3-Year Prospective Study From an Endemic Area
Authors: Falcone Marco , Giordano Cesira , Leonildi Alessandro , Galfo Valentina , Lepore Aurelio , Suardi Lorenzo Roberto , Riccardi Niccolò , Barnini Simona , Tiseo Giusy
Published: December 2023

Background

Metallo-β-lactamase (MBL)–producing Enterobacterales are increasing worldwide. Our aim was to describe clinical features, treatments, and outcomes of infections by MBL-Enterobacterales.

Methods

A prospective observational study conducted in the Pisa University Hospital (January 2019 to October 2022) included patients with MBL-producing Enterobacterales infections. The primary outcome measure was the 30-day mortality rate. Multivariable Cox regression analysis was performed to identify factors associated with that mortality rate, and adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated.

Results

The study’s 343 patients included 15 with Verona integron-encoded MBL (VIM)- and 328 with New Delhi MBL (NDM)–producing Enterobacterales infections; there were 199 patients (58%) with bloodstream infections, 60 (17.5%) with hospital-acquired or ventilator-associated pneumonia, 60 (17.5%) with complicated urinary tract infections, 13 (3.8%) with intra-abdominal infections, and 11 (3.2%) with skin and soft-tissue infections. The 30-day mortality rate was 29.7%. Of 343 patients, 32 did not receive in vitro active antibiotic therapy, 215 (62.7%) received ceftazidime-avibactam plus aztreonam, 33 (9.6%) received cefiderocol-containing regimens, 26 (7.6%) received colistin-containing regimens, and 37 (10.8%) received other active antibiotics. On multivariable analysis, septic shock (aHR, 3.57 [95% CI, 2.05–6.23]; P < .001) and age (1.05 [1.03–1.08]; P < .001) were independently associated with the 30-day mortality rate, while in vitro active antibiotic therapy within 48 hours after infection (0.48 [.26–.8]; P = .007) and source control (0.43 [.26–.72]; P = .001) were protective factors. Sensitivity analysis showed that ceftazidime-avibactam plus aztreonam, compared with colistin, was independently associated with a reduced 30-day mortality rate (aHR, 0.39 [95% CI, .18–.86]; P = .02). Propensity score analyses confirmed these findings.

Conclusions

MBL-producing carbapenem-resistant Enterobacterales infections are associated with high 30-day mortality rates. Patients with MBL-producing Enterobacterales infections should receive early active antibiotic therapy.
The Clinical Relevance of an Inflamed Appendix in Crohn’s Disease
Authors: van der Does de Willebois Eline M L , Sari Cagla , Mookhoek Aart , Joustra Vincent , van Dieren Susan , D’Haens Geert R , Bemelman Willem A , Buskens Christianne J
Published: December 2023

Background and Aims

An appendectomy for appendiceal inflammation has been suggested to ameliorate the clinical course of patients with ulcerative colitis [UC]. In contrast, for Crohn’s disease [CD] an inverse association has been suggested with a higher incidence of CD and worse prognosis after appendectomy. The aim of this study was to analyse the clinical relevance of an inflamed appendix in CD patients undergoing ileocaecal resection [ICR].

Methods

All consecutive patients undergoing primary ICR between 2007 and 2018 were considered for inclusion. Microscopic data of available appendiceal resection specimens [n = 99] were revised by a dedicated inflammatory bowel disease [IBD] pathologist and scored as inflamed or not inflamed. Eighteen patients had a previous appendectomy. Pathological findings were correlated with disease characteristics and recurrence rates [clinical, endoscopic, and intervention-related].

Results

In total 117 patients were included, 77 [65.8%] females, with a median age of 30 years (interquartile range [IQR] 24–43), and a median follow up of 102 months [IQR 76–114]. Of patients without previous appendectomy [n = 99], 39% had an inflamed appendix. No significant differences in disease characteristics [eg, disease location, behaviour, time to surgery] or prognosis could be demonstrated between the two groups. In contrast, previous appendectomy [n = 18] was associated with penetrating disease and numerically shorter disease duration at the time of resection. Furthermore, a trend was seen towards a stronger association with postoperative recurrence.

Conclusion

The current study could not confirm a different prognosis for CD patients with and without an inflamed appendix. In contrast, in patients with a previous appendectomy, a trend was seen towards increased postoperative recurrence, which might be related to the higher incidence of penetrating disease.
Developing an artificial intelligence–based decision engine for disease-modifying therapy in heart failure: a pilot study
Authors: Gingele Arno J , Amin Hesam , De Wit Kurt , Jacobsen Malte , Hageman Arjan , van der Mierden Kay , Brandts Julia , Weerts Jerremy , Barrett Matthew , Dixon Lana J , Hill Loreena , Knackstedt Christian , Brunner-La Rocca Hans-Peter
Published: December 2023

Aims

Heart failure is an escalating burden on global healthcare systems. Modernizing heart failure care is inevitable, with eHealth products poised to play an important role. However, eHealth devices that can initiate and adjust heart failure medication are currently lacking. Consequently, this study aimed to develop an artificial intelligence–based decision engine to provide guideline-based recommendations for disease-modifying medication in heart failure patients.

Methods and results

We developed the decision engine by converting the European Society of Cardiology (ESC) heart failure guidelines into Business Process Model and Notation, a visual modelling language suitable for developing complex decision engines. A safety evaluation, based on clinical parameters, was conducted to ascertain the system’s applicability to specific cases. The decision engine renders specific decisions concerning disease- modifying therapy for heart failure patients. We defined 72 virtual heart failure patient scenarios, encompassing a broad spectrum of baseline characteristics and background medication. All recommendations offered by the engine were evaluated by an independent heart failure specialist. All but three recommendations (94%) were identical to the treatment decisions by the heart failure specialist, and all (100%) were in line with the 2021 ESC heart failure guidelines.

Conclusion

The decision engine offers guideline-based recommendations for disease-modifying therapy, positioning it as a tool to enhance self-care among heart failure patients. To validate our results, the decision engine is being prospectively tested in real-world patients in a multicentre clinical trial (NCT04699253).
Immigration, Female Labour Supply and Local Cultural Norms
Authors: Jessen Jonas , Schmitz Sophia , Weinhardt Felix
Published: December 2023

We study the local evolution of female labour supply and cultural norms in West Germany in reaction to the sudden presence of East Germans who migrated to the West after reunification. These migrants grew up with high rates of maternal employment, whereas West German families mostly followed the traditional breadwinner-housewife model. We find that West German women increase their labour supply and that this holds within households. We provide additional evidence on stated gender norms, West-East friendships, intermarriage and child care infrastructure. The dynamic evolution of the effects on labour supply is best explained by local cultural learning.
Two pandemic years greatly reduced young people’s life satisfaction: evidence from a comparison with pre-COVID-19 panel data
Authors: Neugebauer Martin , Patzina Alexander , Dietrich Hans , Sandner Malte
Published: December 2023

How much did young people suffer from the COVID-19 pandemic? A growing number of studies address this question, but they often lack a comparison group that was unaffected by the pandemic, and the observation window is usually short. Here, we compared the 2-year development of life satisfaction of German high school students during COVID-19 (N = 2,698) with the development in prepandemic cohorts (N = 4,834) with a difference-in-differences design. We found a decline in life satisfaction in winter 2020/2021 (Cohen’s d = -0.40) that was approximately three times stronger than that in the general population and persisted until winter 2021/2022. Young people found some restrictions particularly burdensome, especially travel restrictions, bans on cultural events, and the closure of bars/clubs.
Macrophage P2Y6 receptor deletion attenuates atherosclerosis by limiting foam cell formation through phospholipase Cβ/store-operated calcium entry/calreticulin/scavenger receptor A pathways
Authors: Li Yehong , Zhou Mengze , Li Huanqiu , Dai Chen , Yin Li , Liu Chunxiao , Li Yuxin , Zhang Enming , Dong Xinli , Ji Hui , Hu Qinghua
Published: December 2023

Background and Aims

Macrophage-derived foam cells play a causal role during the pathogenesis of atherosclerosis. P2Y6 receptor (P2Y6R) highly expressed has been considered as a disease-causing factor in atherogenesis, but the detailed mechanism remains unknown. This study aims to explore P2Y6R in regulation of macrophage foaming, atherogenesis, and its downstream pathways. Furthermore, the present study sought to find a potent P2Y6R antagonist and investigate the feasibility of P2Y6R-targeting therapy for atherosclerosis.

Methods

The P2Y6R expression was examined in human atherosclerotic plaques and mouse artery. Atherosclerosis animal models were established in whole-body P2Y6R or macrophage-specific P2Y6R knockout mice to evaluate the role of P2Y6R. RNA sequencing, DNA pull-down experiments, and proteomic approaches were performed to investigate the downstream mechanisms. High-throughput Glide docking pipeline from repurposing drug library was performed to find potent P2Y6R antagonists.

Results

The P2Y6R deficiency alleviated atherogenesis characterized by decreasing plaque formation and lipid deposition of the aorta. Mechanically, deletion of macrophage P2Y6R significantly inhibited uptake of oxidized low-density lipoprotein through decreasing scavenger receptor A expression mediated by phospholipase Cβ/store-operated calcium entry pathways. More importantly, P2Y6R deficiency reduced the binding of scavenger receptor A to CALR, accompanied by dissociation of calreticulin and STIM1. Interestingly, thiamine pyrophosphate was found as a potent P2Y6R antagonist with excellent P2Y6R antagonistic activity and binding affinity, of which the pharmacodynamic effect and mechanism on atherosclerosis were verified.

Conclusions

Macrophage P2Y6R regulates phospholipase Cβ/store-operated calcium entry/calreticulin signalling pathway to increase scavenger receptor A protein level, thereby improving foam cell formation and atherosclerosis, indicating that the P2Y6R may be a potential therapeutic target for intervention of atherosclerotic diseases using P2Y6R antagonists including thiamine pyrophosphate.
Appropriate application of diagnostics for identifying patients in need of pacemaker therapy
Authors: Tawfik Mazen , Mousa Mohamed , Pokawattana Apichai , Jaroonpipatkul Surachat , Dung Kieu Ngoc
Published: December 2023

Pacemaker therapy is the cornerstone in treatment of bradycardia and conduction disorders. Several diagnostic tools are utilized to diagnose and guide the physicians for appropriate management and accordingly proper utilization of pacemaker therapy. The current article is discussing the different diagnostics used for appropriate evaluation and diagnosis of bradyarrhythmias and the suggested solutions to improve bradycardia diagnosis and pacemaker therapy utilization in underpenetrated areas.
Efficacy and safety of pulmonary vein isolation with pulsed field ablation vs. novel cryoballoon ablation system for atrial fibrillation
Authors: Badertscher Patrick , Weidlich Simon , Knecht Sven , Stauffer Niklas , Krisai Philipp , Voellmin Gian , Osswald Stefan , Sticherling Christian , Kühne Michael
Published: December 2023

Aims

Pulsed-field ablation (PFA) has emerged as a novel treatment technology for patients with atrial fibrillation (AF). Cryoballoon (CB) is the most frequently used single shot technology. A direct comparison to a novel CB system is lacking. We aimed to compare pulmonary vein isolation (PVI) using PFA vs. a novel CB system regarding efficiency, safety, myocardial injury, and outcomes.

Methods and results

One hundred and eighty-one consecutive patients underwent PVI and were included (age 64 ± 9.7 years, ejection fraction 0.58 ± 0.09, left atrial size 40 ± 6.4 mm, paroxysmal AF 64%). 106 patients (59%) underwent PFA (FARAPULSE, Boston Scientific) and 75 patients (41%) underwent CB ablation (PolarX, Boston Scientific). The median procedure time, left atrial dwell time and fluoroscopic time were similar between the PFA and the CB group with 55 [interquartile range (IQR) 43–64] min vs. 58 (IQR 48–69) min (P < 0.087), 38 (30–49) min vs. 37 (31–48) min, (P = 0.871), and 11 (IQR 9.3–14) min vs. 11 (IQR 8.7–16) min, (P < 0.81), respectively. Three procedural complications were observed in the PFA group (two tamponades, one temporary ST elevation) and three complications in the CB group (3× reversible phrenic nerve palsies). During the median follow-up of 404 days (IQR 208–560), AF recurrence was similar in the PFA group and the CB group with 24 vs. 30%, P = 0.406.

Conclusion

Procedural characteristics were very similar between PFA and CB in regard to procedure duration fluoroscopy time and complications. Atrial fibrillation free survival did not differ between the PFA and CB groups.
Deciphering the mannose transfer mechanism of mycobacterial PimE by molecular dynamics simulations
Authors: Bhattacharje Gourab , Ghosh Amit , Das Amit Kumar
Published: December 2023

Phosphatidyl-myo-inositol mannosides (PIMs), Lipomannan (LM), and Lipoarabinomannan (LAM) are essential components of the cell envelopes of mycobacteria. At the beginning of the biosynthesis of these compounds, phosphatidylinositol (PI) is mannosylated and acylated by various enzymes to produce Ac1/2PIM4, which is used to synthesize either Ac1/2PIM6 or LM/LAM. The protein PimE, a membrane-bound glycosyltransferase (GT-C), catalyzes the addition of a mannose group to Ac1PIM4 to produce Ac1PIM5, using polyprenolphosphate mannose (PPM) as the mannose donor. PimE-deleted Mycobacterium smegmatis (Msmeg) showed structural deformity and increased antibiotic and copper sensitivity. Despite knowing that the mutation D58A caused inactivity in Msmeg, how PimE catalyzes the transfer of mannose from PPM to Ac1/2PIM4 remains unknown. In this study, analyzing the AlphaFold structure of PimE revealed the presence of a tunnel through the D58 residue with two differently charged gates. Molecular docking suggested PPM binds to the hydrophobic tunnel gate, whereas Ac1PIM4 binds to the positively charged tunnel gate. Molecular dynamics (MD) simulations further demonstrated the critical roles of the residues N55, F87, L89, Y163, Q165, K197, L198, R251, F277, W324, H326, and I375 in binding PPM and Ac1PIM4. The mutation D58A caused a faster release of PPM from the catalytic tunnel, explaining the loss of PimE activity. Along with a hypothetical mechanism of mannose transfer by PimE, we also observe the presence of tunnels through a negatively charged aspartate or glutamate with two differently-charged gates among most GT-C enzymes. Common hydrophobic gates of GT-C enzymes probably harbor sugar donors, whereas, differently-charged tunnel gates accommodate various sugar-acceptors.
Relational maintenance among separated Latina/o/x/e immigrant families: exploring the lived experiences of parents and children
Authors: Mendez Murillo Roselia , Kam Jennifer A , Merolla Andy J
Published: December 2023

Prior relational maintenance research primarily (a) considers only one family member’s perspective, (b) explores introspective communication, and (c) examines romantic relationships among highly resourced white samples in the United States. This study considered low-income, Latina/o/x/e immigrant families’ maintenance before, during, and after migration-related separation, using standpoint theory, social communication theory, and the long-distance relational maintenance model. We conducted semi-structured interviews with Latina/o/x/e parents and children who lived in separate countries (N = 20 dyads). Findings cast light on temporal (e.g., fathers often provided little to no notice to children of the upcoming separation, complicating the families’ ability to prospectively co-construct relational continuity) and cultural factors (e.g., endorsing traditional gender norms, relying on mothers to explain the separation to children after it had begun) in families’ maintenance processes. This study offers new insight into how families communicatively construct “ongoingness” in their bonds despite emotional, technological, and legal challenges posed by migration-related separation.
Plasma Human Immunodeficiency Virus 1 Soluble Glycoprotein 120 Association With Correlates of Immune Dysfunction and Inflammation in Antiretroviral Therapy–Treated Individuals With Undetectable Viremia
Authors: Benlarbi Mehdi , Richard Jonathan , Bourassa Catherine , Tolbert William D , Chartrand-Lefebvre Carl , Gendron-Lepage Gabrielle , Sylla Mohamed , El-Far Mohamed , Messier-Peet Marc , Guertin Camille , Turcotte Isabelle , Fromentin Rémi , Verly Myriam Maude , Prévost Jérémie , Clark Andrew , Mothes Walther , Kaufmann Daniel E , Maldarelli Frank , Chomont Nicolas , Bégin Philippe , Tremblay Cécile , Baril Jean-Guy , Trottier Benoit , Trottier Sylvie , Duerr Ralf , Pazgier Marzena , Durand Madeleine , Finzi Andrés
Published: December 2023

Background

Chronic inflammation persists in some people living with human immunodeficiency virus (HIV) during antiretroviral therapy and is associated with premature aging. The glycoprotein 120 (gp120) subunit of HIV-1 envelope sheds and can be detected in plasma, showing immunomodulatory properties even in the absence of detectable viremia. We evaluated whether plasma soluble gp120 (sgp120) and a family of gp120-specific anti–cluster A antibodies, linked to CD4 depletion in vitro, contribute to chronic inflammation, immune dysfunction, and subclinical cardiovascular disease in participants of the Canadian HIV and Aging Cohort Study with undetectable viremia.

Methods

Cross-sectional assessment of sgp120 and anti–cluster A antibodies was performed in 386 individuals from the cohort. Their association with proinflammatory cytokines and subclinical coronary artery disease was assessed using linear regression models.

Results

High levels of sgp120 and anti–cluster A antibodies were inversely correlated with CD4+ T cell count and CD4/CD8 ratio. The presence of sgp120 was associated with increased levels of interleukin 6. In participants with detectable atherosclerotic plaque and detectable sgp120, anti–cluster A antibodies and their combination with sgp120 levels correlated positively with the total volume of atherosclerotic plaques.

Conclusions

This study showed that sgp120 may act as a pan toxin causing immune dysfunction and sustained inflammation in a subset of people living with HIV, contributing to the development of premature comorbid conditions.
Efficacy and safety of raltegravir plus lamivudine maintenance therapy
Authors: Borjabad Beatriz , Inciarte Alexy , Chivite Ivan , Gonzalez-Cordon Ana , Mosquera Mar , Hurtado Carmen , Rovira Cristina , Gonzalez Tania , Sempere Abiu , Torres Berta , Calvo Julia , De La Mora Lorena , Martinez-Rebollar Maria , Laguno Montserrat , Foncillas Alberto , Ambrosioni Juan , Blanch Jordi , Rodriguez Ana , Solbes Estela , Llobet Roger , Berrocal Leire , Mallolas Josep , Miro Jose M , Alcami Jose , Blanco Jose L , Sanchez-Palomino Sonsoles , De Lazzari Elisa , Martinez Esteban
Published: December 2023

Background

Decreasing medication burden with raltegravir plus lamivudine in virologically suppressed persons with HIV (PWH) maintained efficacy and was well tolerated at 24 weeks, but more comprehensive data over longer follow-up are required.

Methods

Prospective 48 week extension phase of the raltegravir plus lamivudine arm from a previous 24 week pilot randomized clinical trial in which virologically suppressed PWH were randomized 2:1 to switch to fixed-dose combination 150 mg lamivudine/300 mg raltegravir twice daily or to continue therapy. In this 48 week extension phase, raltegravir was dosed at 1200 mg/day and lamivudine 300 mg/day. Primary outcome was the proportion of PWH with treatment failure at Week 48. Secondary outcomes were changes in ultrasensitive plasma HIV RNA, HIV DNA in CD4 cells, serum IL-6, ultrasensitive C-reactive protein and sCD14, body composition, sleep quality, quality of life and adverse effects.

Results

Between May 2018 and June 2019, 33 PWH were enrolled. One participant experienced virological failure without resistance mutations and re-achieved sustained virological suppression without therapy discontinuation, and two others discontinued therapy due to adverse effects. Treatment failure was 9% (95% CI 2%–24%) and 3% (95% CI 0%–17%) in the ITT and on-treatment populations. There were significant changes between baseline and Week 48 in serum cytokines but not in other secondary outcomes.

Conclusions

Switching to raltegravir and lamivudine in PWH with virological suppression maintains efficacy and is well tolerated. This maintenance regimen might be a cost-effective option for PWH at risk of drug–drug interactions or needing to avoid specific toxicities of certain antiretroviral drugs or their negative impact on comorbidities.
Enabling the clinical application of artificial intelligence in genomics: a perspective of the AMIA Genomics and Translational Bioinformatics Workgroup
Authors: Walton Nephi A , Nagarajan Radha , Wang Chen , Sincan Murat , Freimuth Robert R , Everman David B , Walton Derek C , McGrath Scott P , Lemas Dominick J , Benos Panayiotis V , Alekseyenko Alexander V , Song Qianqian , Gamsiz Uzun Ece , Taylor Casey Overby , Uzun Alper , Person Thomas Nate , Rappoport Nadav , Zhao Zhongming , Williams Marc S
Published: December 2023

Objective

Given the importance AI in genomics and its potential impact on human health, the American Medical Informatics Association—Genomics and Translational Biomedical Informatics (GenTBI) Workgroup developed this assessment of factors that can further enable the clinical application of AI in this space.

Process

A list of relevant factors was developed through GenTBI workgroup discussions in multiple in-person and online meetings, along with review of pertinent publications. This list was then summarized and reviewed to achieve consensus among the group members.

Conclusions

Substantial informatics research and development are needed to fully realize the clinical potential of such technologies. The development of larger datasets is crucial to emulating the success AI is achieving in other domains. It is important that AI methods do not exacerbate existing socio-economic, racial, and ethnic disparities. Genomic data standards are critical to effectively scale such technologies across institutions. With so much uncertainty, complexity and novelty in genomics and medicine, and with an evolving regulatory environment, the current focus should be on using these technologies in an interface with clinicians that emphasizes the value each brings to clinical decision-making.
Xanti Schawinsky and the Fascist Plebiscitary Elections of 1934: Everyday Design Practice and Visual Culture in Early 1930’s Italy
Authors: Barbieri Chiara , Fornari Davide
Published: December 2023

With Hitler’s seizure of power in 1933, the Bauhausler Xanti Schawinsky sought refuge in fascist Italy until the uncertain political situation and a career choice prompted him to move to the United States in 1936. Identified as the link between Italy and the Bauhaus, Schawinsky holds a special place in the history of Italian graphic design. However, his key role as promoter of modernism has not been subjected to scrutiny by looking at the work he did, networks he established, and design exchange he fostered.

Schawinsky’s propaganda poster for the plebiscitary elections of 1934 is the focus of this article. Drawing on photographic documents and primary sources—including correspondences, archival documents, and autobiographic accounts—we seek to clarify the circumstances under which someone fleeing Nazi Germany eventually designed works that served as vehicles for fascist propaganda. To this end, we ground the poster “1934-XII SI” within the larger sociocultural and professional context, historical and political circumstances of early 1930’s Italy. We pair close visual analysis with a contextualized understanding to employ the poster as a case study to explore how fascist ideology was ingrained in everyday practice and show how the line between political and commercial discourses was blurred.
Validation of CSF-1 receptor (CD115) staining for analysis of murine monocytes by flow cytometry
Authors: Kapanadze Tamar , Gamrekelashvili Jaba , Sablotny Stefan , Schroth Frauline Nicole , Xu Yuangao , Chen Rongjun , Rong Song , Shushakova Nelli , Gueler Faikah , Haller Hermann , Limbourg Florian P
Published: December 2023

CD115, the receptor for colony stimulating factor 1, is essential for survival and differentiation of monocytes and macrophages and is therefore frequently used to define monocyte subsets and their progenitors in immunological assays. However, CD115 surface expression and detection by flow cytometry is greatly influenced by cell isolation and processing methods, organ source, and disease context. In a systematic analysis of murine monocytes, we define experimental conditions that preserve or limit CD115 surface expression and staining by flow cytometry. We also find that, independent of conditions, CD115 surface levels are consistently lower in Ly6Clo monocytes than in Ly6Chi monocytes, with the exception of Ly6Clo monocytes in the bone marrow. Furthermore, in contrast to IL-34, the presence of colony stimulating factor 1 impairs CD115 antibody staining in a dose-dependent manner, which, in a model of ischemic kidney injury with elevated levels of colony stimulating factor 1, influenced quantification of kidney monocytes. Thus, staining and experimental conditions affect quantitative and qualitative analysis of monocytes and may influence experimental conclusions.
VISTA nonredundantly regulates proliferation and CD69low γδ T cell accumulation in the intestine in murine sepsis
Authors: Gray Chyna C , Armstead Brandon E , Chung Chun-Shiang , Chen Yaping , Ayala Alfred
Published: December 2023

Sepsis is a dysregulated systemic immune response to infection i.e. responsible for ∼35% of in-hospital deaths at a significant fiscal healthcare cost. Our laboratory, among others, has demonstrated the efficacy of targeting negative checkpoint regulators (NCRs) to improve survival in a murine model of sepsis, cecal ligation and puncture (CLP). B7-CD28 superfamily member, V-domain immunoglobulin suppressor of T cell activation (VISTA), is an ideal candidate for strategic targeting in sepsis. VISTA is a 35 to 45 kDa type 1 transmembrane protein with unique biology that sets it apart from all other NCRs. We recently reported that VISTA−/− mice had a significant survival deficit post-CLP, which was rescued upon adoptive transfer of a VISTA-expressing pMSCV-mouse Foxp3-EF1α-GFP-T2A-puro stable Jurkat cell line (Jurkatfoxp3 T cells). Based on our prior study, we investigated the effector cell target of Jurkatfoxp3 T cells in VISTA−/− mice. γδ T cells are a powerful lymphoid subpopulation that require regulatory fine-tuning by regulatory T cells to prevent overt inflammation/pathology. In this study, we hypothesized that Jurkatfoxp3 T cells nonredundantly modulate the γδ T cell population post-CLP. We found that VISTA−/− mice have an increased accumulation of intestinal CD69low γδ T cells, which are not protective in murine sepsis. Adoptive transfer of Jurkatfoxp3 T cells decreased the intestinal γδ T cell population, suppressed proliferation, skewed remaining γδ T cells toward a CD69high phenotype, and increased soluble CD40L in VISTA−/− mice post-CLP. These results support a potential regulatory mechanism by which VISTA skews intestinal γδ T cell lineage representation in murine sepsis.