bluuebunny/crossref_metadata_2025 huggingface dataset:
Faecal Biomarkers in Inflammatory Bowel Diseases: Calprotectin Versus Lipocalin-2—a Comparative Study
Authors: Zollner Andreas , Schmiderer Andreas , Reider Simon J , Oberhuber Georg , Pfister Alexandra , Texler Bernhard , Watschinger Christina , Koch Robert , Effenberger Maria , Raine Tim , Tilg Herbert , Moschen Alexander R
Published: June 2020

Background and Aims

Faecal biomarkers, particularly calprotectin [FCAL], have become important diagnostic and monitoring tools in inflammatory bowel diseases [IBD]. As FCAL is mainly produced by neutrophils, we hypothesised that faecal lipocalin-2 [FLCN2], also expressed by intestinal epithelial cells [IEC], could be beneficial in specific clinical situations.

Methods

We compared clinical and endoscopic activity-related correlations between FCAL and FLCN2, assayed from the same sample, in a cohort of 132 patients (72 Crohn’s disease [CD]) and 40 controls. A detailed analysis of cellular origins was done by confocal microscopy and flow cytometry. To evaluate the potential to detect low-grade inflammation, we studied faecal and tissue concentrations in a cohort with clinical, endoscopic, and histological remission.

Results

There was an excellent correlation between FCAL and FLCN2 [rS = 0.87, p <0.001] and comparable sensitivity and specificity to predict clinical and endoscopic disease activity, with optimal thresholds for endoscopic activity of 73.4 and 1.98 µg/g in ulcerative colitis [UC] and 78.4 and 0.56 µg/g in Crohn’s disease for FCAL and FLCN2, respectively. Strong co-expression of both proteins was observed in granulocytes and macrophages. IECs expressed LCN2 but not CAL. In our IBD cohort in deep remission neither FCAL nor FLCN2 was different from controls; yet mucosal LCN2 but not CAL expressions remained elevated in the rectum of UC and the ileum of CD patients.

Conclusions

This study corroborates the diagnostic equivalence of FLCN2 and FCAL in IBD. In remission, persistent mucosal overexpression renders LCN2 an attractive candidate for molecular inflammation warranting further investigation.
Management of Pregnant Inflammatory Bowel Disease Patients During the COVID-19 Pandemic
Authors: De Lima-Karagiannis A , Juillerat P , Sebastian S , Pedersen N , Bar-Gil Shitrit A , van der Woude C J
Published: June 2020

The rapid emergence of the novel coronavirus [SARS-CoV2] and the coronavirus disease 2019 [COVID-19] has caused significant global morbidity and mortality. This is particularly concerning for vulnerable groups such as pregnant women with inflammatory bowel disease [IBD]. Care for pregnant IBD patients in itself is a complex issue because of the delicate balance between controlling maternal IBD as well as promoting the health of the unborn child. This often requires continued immunosuppressive maintenance medication or the introduction of new IBD medication during pregnancy. The current global COVID-19 pandemic creates an additional challenge in the management of pregnant IBD patients. In this paper we aimed to answer relevant questions that can be encountered in daily clinical practice when caring for pregnant women with IBD during the current COVID-19 pandemic.

Podcast

This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast
Endocarditis-related stroke is not a contraindication for early cardiac surgery: an investigation among 440 patients with left-sided endocarditis
Authors: Ruttmann Elfriede , Abfalterer Hannes , Wagner Julian , Grimm Michael , Müller Ludwig , Bates Katie , Ulmer Hanno , Bonaros Nikolaos
Published: June 2020

OBJECTIVES

A treatment dilemma arises when surgery is indicated in patients with infective endocarditis (IE) complicated by stroke. Neurologists recommend surgery to be postponed for at least 1 month. This study aims to investigate the neurological complication rate and neurological recovery potential in patients with IE-related stroke.

METHODS

A total of 440 consecutive patients with left-sided IE undergoing surgery were investigated. During follow-up, neurological recovery was assessed using the modified Rankin scale and the Barthel index. Mortality was assessed with regression models adjusting for age.

RESULTS

The median follow-up time was 9.0 years. Patients with previous strokes were more likely to suffer from mitral valve endocarditis (29.5% vs 47.4%, P < 0.001). Symptomatic stroke was found in 135 (30.7%) patients; of them, 42 patients presented with complicated stroke (additional meningitis, haemorrhagic stroke or intracranial abscess). Driven by symptomatic stroke, the age-adjusted hospital mortality risk was 1.4-fold [95% confidence interval (CI) 0.74–2.57; P = 0.31] higher and the long-term mortality risk was 1.4-fold higher (95% CI 1.003–2.001; P = 0.048). Hospital mortality was higher in patients with complicated stroke (21.4% vs 9.7%; P = 0.06) only; however, mortality rates were similar comparing uncomplicated stroke versus no stroke. Among patients with complicated ischaemic strokes, the observed risk for intraoperative cerebral haemorrhage was 2.3% only and the increased hospital mortality was not driven by cerebral complications. In the long-term follow-up, full neurological recovery was observed in 84 out of 118 survivors (71.2%), and partial recovery was observed in 32 (27.1%) patients. Neurological recovery was lower in patients with complete middle cerebral artery stroke compared to other localization (52.9% vs 77.6%; P = 0.003).

CONCLUSIONS

Contrary to current clinical practice and neurological recommendations, early surgery in IE is safe and neurological recovery is excellent among patients with IE-related stroke.

Clinical registration number local IRB

UN4232 382/3.1 (retrospective study).
Effect of aortic stiffness versus stenosis on ventriculo-arterial interaction in an experimental model of coarctation repair
Authors: Panzer Joseph , De Somer Filip , Segers Patrick , De Wolf Daniel , Bove Thierry
Published: June 2020

OBJECTIVES

The aim of this study was to investigate the effect of short- versus long-segment aortic stiffness and stenosis on ventriculo-arterial interaction in a porcine model of coarctation repair.

METHODS

Short–long aortic stiffness was created by transection/suture [coarctation (CoA) suture, n = 6] and stenting (stent, n = 5) of the proximal descending aorta. Short–long aortic stenosis was achieved by wrapping a prosthetic graft around the aorta to 1/3-circumference reduction, over a segment length of 1 cm (CoA suture stenosis, n = 5) and 4.5 cm (stent stenosis, n = 6). After 3 months, aortic pressure-flow haemodynamics, aortic distensibility by intravascular ultrasound and left ventricular performance by pressure–volume loops were compared to a Sham group (n = 5) at baseline and during dobutamine administration.

RESULTS

The aortic impedance increased with 30.3 (12.6%) and 41.3 (20.9%) (P < 0.001) in CoA stenosis and stent stenosis during inotropic response. Impaired haemodynamic aortic compliance was associated with lower aortic distensibility by intravascular ultrasound, specifically in long-segment stenosis. The ventriculo-arterial coupling was disturbed in both groups with stenosis, with blunted contractile response [Sham 140.3 (19.8%), CoA suture 101.3 (14.5%), CoA suture stenosis 75.0 (8.4%), stent 115.5 (12.7%), stent stenosis 55.1 (14.6%), P < 0.001] and increased myocardial stiffness during dobutamine in the long-segment aortic stenosis group [Sham −26.0 (12.9%), CoA suture −27.5 (15.9%), CoA stenosis −9.5 (8.6%), stent −23.4 (4.8%), stent stenosis 19.9 (23.1%), P < 0.001].

CONCLUSIONS

This animal study on the sequelae of coarctation repair demonstrated that aortic stiffness had little effect on aortic pressure-flow characteristics in the absence of stenosis. However, the negative chronic effect of stenosis on aortic haemodynamics—especially a longer segment—leads to the rapid impairment of ventriculo-arterial interaction, which is accentuated by inotropy. Therefore, therapeutical management needs to focus on improving aortic remodelling after coarctation repair, preferably by minimizing residual stenosis, even at the cost of inducing aortic stiffness.
Poor preoperative quality of life predicts prolonged hospital stay after VATS lobectomy for lung cancer
Authors: Pompili Cecilia , McLennan Battleday Finn , Chia Wei Ling , Chaudhuri Nilanjan , Kefaloyannis Emmanuel , Milton Richard , Papagiannopoulos Kostas , Tcherveniakov Peter , Brunelli Alessandro
Published: June 2020

OBJECTIVES

The aim of this study was to assess whether quality of life (QoL) scales are associated with postoperative length of stay (LoS) following video-assisted thoracoscopic surgery (VATS) lobectomy for lung cancer.

METHODS

This is a single-centre retrospective analysis on 250 consecutive patients submitted to VATS lobectomies (233) or segmentectomies (17) over a period of 3 years. QoL was assessed in all patients by the self-administration of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 questionnaire. The individual QoL scales were tested for possible association with LoS along with other objective baseline and surgical parameters using univariable and multivariable analyses.

RESULTS

Thirty-day cardiopulmonary and mortality rates were 22% and 2.4%. The median LoS was 4 days [interquartile range (IQR) 3–7]. Fifty-one (20%) patients remained in hospital longer than 7 days after surgery (upper quartile). General health [global health score (GHS)] (P = 0.019), physical function (P = 0.014) and role functioning (P = 0.016) scales were significantly worse in patients with prolonged stay. They were highly correlated between each other and tested separately in different logistic regression analyses. The best model resulted the one containing GHS (P = 0.032) along with age, low force expiratory volume in 1 s and carbon monoxide lung diffusion capacity and history of cerebrovascular disease. Fifty-nine patients had GHS <58 (lower interquartile value). Thirty-one percent of them experienced prolonged hospital stay (vs 17% of those with higher GHS, P = 0.027).

CONCLUSIONS

Preoperative patient-reported QoL was associated with prolonged postoperative hospital stay. Baseline QoL status should be taken into consideration to implement psychosocial supportive programmes in the context of enhanced recovery after surgery.
Multicentre, randomized comparison of two-stent and provisional stenting techniques in patients with complex coronary bifurcation lesions: the DEFINITION II trial
Authors: Zhang Jun-Jie , Ye Fei , Xu Kai , Kan Jing , Tao Ling , Santoso Teguh , Munawar Muhammad , Tresukosol Damras , Li Li , Sheiban Imad , Li Feng , Tian Nai-Liang , Rodríguez Alfredo E , Paiboon Chotnoparatpat , Lavarra Francesco , Lu Shu , Vichairuangthum Kitigon , Zeng Hesong , Chen Lianglong , Zhang Ruiyan , Ding Shiqin , Gao Fengtang , Jin Zening , Hong Lang , Ma Likun , Wen Shangyu , Wu Xueming , Yang Song , Yin Wei-Hsian , Zhang Jun , Wang Yan , Zheng Yonghong , Zhou Lei , Zhou Limin , Zhu Yuansheng , Xu Tan , Wang Xin , Qu Hong , Tian Yulong , Lin Song , Liu Lijun , Lu Qinghua , Li Qihua , Li Bo , Jiang Qing , Han Leng , Gan Guojun , Yu Mengyue , Pan Defeng , Shang Zhenglu , Zhao Yanfang , Liu Zhizhong , Yuan Ye , Chen Cynthia , Stone Gregg W , Han Yaling , Chen Shao-Liang
Published: June 2020

Aim

The present study aimed to assess the benefits of two-stent techniques for patients with DEFINITION criteria-defined complex coronary bifurcation lesions.

Methods and results

In total, 653 patients with complex bifurcation lesions at 49 international centres were randomly assigned to undergo the systematic two-stent technique (two-stent group) or provisional stenting (provisional group). The primary endpoint was the composite of target lesion failure (TLF) at the 1-year follow-up, including cardiac death, target vessel myocardial infarction (TVMI), and clinically driven target lesion revascularization (TLR). The safety endpoint was definite or probable stent thrombosis. At the 1-year follow-up, TLF occurred in 37 (11.4%) and 20 (6.1%) patients in the provisional and two-stent groups, respectively [77.8%: double-kissing crush; hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.30–0.90; P = 0.019], largely driven by increased TVMI (7.1%, HR 0.43, 95% CI 0.20–0.90; P = 0.025) and clinically driven TLR (5.5%, HR 0.43, 95% CI 0.19–1.00; P = 0.049) in the provisional group. At the 1 year after indexed procedures, the incidence of cardiac death was 2.5% in the provisional group, non-significant to 2.1% in the two-stent group (HR 0.86, 95% CI 0.31–2.37; P = 0.772).

Conclusion

For DEFINITION criteria-defined complex coronary bifurcation lesions, the systematic two-stent approach was associated with a significant improvement in clinical outcomes compared with the provisional stenting approach. Further study is urgently warranted to identify the mechanisms contributing to the increased rate of TVMI after provisional stenting.

Study registration

http://www.clinicaltrials.com; Identifier: NCT02284750.
Risk of syncopal recurrences in patients treated with permanent pacing for bradyarrhythmic syncope: role of correlation between symptoms and electrocardiogram findings
Authors: Palmisano Pietro , Pellegrino Pier Luigi , Ammendola Ernesto , Ziacchi Matteo , Guerra Federico , Aspromonte Vittorio , Laffi Mattia , Pimpini Lorenzo , Santoro Francesco , Boggio Enrico , Guido Alessandro , Patti Giuseppe , Brunetti Natale Daniele , Nigro Gerardo , Biffi Mauro , Dello Russo Antonio , Gaggioli Germano , Accogli Michele , Dell’Era Gabriele
Published: June 2020

Aims 

To evaluate the risk of syncopal recurrences after pacemaker implantation in a population of patients with syncope of suspected bradyarrhythmic aetiology.

Methods and results 

Prospective, multicentre, observational registry enrolling 1364 consecutive patients undergoing pacemaker implantation for syncope of bradyarrhythmic aetiology (proven or presumed). Before pacemaker implantation, all patients underwent a cardiac work-up in order to establish the bradyarrhythmic aetiology of syncope. According to the results of the diagnostic work-up, patients were divided into three groups: Group A, patients in whom a syncope-electrocardiogram (ECG) correlation was established (n = 329, 24.1%); Group B, those in whom clinically significant bradyarrhythmias were detected without a documented syncope-ECG correlation (n = 877, 64.3%); and Group C, those in whom bradyarrhythmias were not detected and the bradyarrhythmic origin of syncope remained presumptive (n = 158, 11.6%). During a median follow-up of 50 months, 213 patients (15.6%) reported at least one syncopal recurrence. Patients in Groups B and C showed a significantly higher risk of syncopal recurrences than those in Group A [hazard ratios (HRs): 1.60 and 2.66, respectively, P < 0.05]. Failure to establish a syncope-ECG correlation during diagnostic work-up before pacemaker implantation was an independent predictor of syncopal recurrence on multivariate analysis (HR: 1.90; P = 0.002).

Conclusion

In selecting patients with syncope of suspected bradyarrhythmic aetiology for pacemaker implantation, establishing a correlation between syncope and bradyarrhythmias maximizes the efficacy of pacing and reduces the risk of syncopal recurrences.
Obesity and thinness prevalence trends in Spanish schoolchildren: are they two convergent epidemics?
Authors: Garrido-Miguel Miriam , Martínez-Vizcaíno Vicente , Herráiz-Adillo Ángel , Martínez-Hortelano Jose Alberto , Soriano-Cano Alba , Díez-Fernández Ana , Solera-Martínez Montserrat , Sánchez-López Mairena
Published: June 2020

Background

The objective of this study was to analyse the secular trends in body composition variables and weight status among Spanish schoolchildren from 1992 to 2017, and to examine the persistence in the same weight status category from 2013 to 2017 of the birth cohort in 2007–08.

Methods

The data for the prevalence/trend analysis were taken from cross-sectional analyses conducted in 1992 (n = 308), 1996 (n = 307), 1998 (n = 275), 2004 (n = 1119), 2010 (n = 912), 2013 (n = 352) and 2017 (n = 275) using similar procedure methods among schoolchildren (aged 4–6 y and 8–11 years) from 22 public schools in the province of Cuenca, Spain. The data for the longitudinal analysis were obtained from cross-sectional analyses of measurements gathered in 2013 and 2017 in the same cohort of children (n = 275) born in 2007 and 2008. Weight, height, body fat percentage (by electronic bioimpedance) and waist circumference were measured by trained personnel. Weight status was defined according to the BMI cut-offs proposed by the International obesity task force (IOTF) criteria.

Results

In schoolchildren, the overall prevalence of thinness increased from 5.9% in 1992 to 14.5% in 2017, P < 0.001. Whereas, the overall prevalence of obesity/overweight remained relatively steady between the same time period (from 25.2% to 26.9%), P = 0.599. In relation to the longitudinal analyses, we observed that 70.9% of schoolchildren in 2017 remained in the same weight status category as in 2013.

Conclusions

The child obesity epidemic in Spain has remained relatively stable over the last two decades. However, the prevalence of thinness shows a worrying upward trend.
GlgA plays an important role in the induction of hydrosalpinx byChlamydia muridarum
Authors: Hu Chunmin , Wu Haoqing , Sun Yina , Kong Jie , Shao LiLi , Chen Xiaojun , Liu Quanzhong , Liu Yuanjun
Published: June 2020

While glycogen synthase A deficiency can reduce the growth and proliferation of Chlamydia muridarum, the effect of glycogen synthase A on the pathogenic process of C. muridarum remains unclear. To characterize the effect of glycogen synthase A deficiency on the pathogenicity of C. muridarum in the genital tract, BALB/c mice were intravaginally inoculated with wild-type, plasmid-free and glycogen synthase A-deficient C. muridarum, and the genital tract tissue was isolated to assess the severity of hydrosalpinx and the levels of oviduct dilatation at day 60 after infection. The glycogen storage capacity and in vitro infection ability of different C. muridarum strains were analyzed by periodic acid-Schiff staining and quantification of progeny elementary body(EB) formation. The tissue homogenate was used to determine the recovery of different C. muridarum strains. The results show that glycogen synthase A-deficient C. muridarum induced reduction of hydrosalpinx and attenuated the extent of oviduct dilatation in mice, and exhibited reduced growth and proliferation in the mouse lower genital tract. In addition, glycogen synthase A point mutations at different sites reduced the glycogen storage capacity and in vitro infectivity of C. muridarum to different degrees. Glycogen synthase A deficiency also reduced the host inflammatory reaction and ascending infection of C. muridarum.
Pulses and delays, anticipation and memory: seeing bacterial stress responses from a single-cell perspective
Authors: Lagage Valentine , Uphoff Stephan
Published: June 2020

Stress responses are crucial for bacteria to survive harmful conditions that they encounter in the environment. Although gene regulatory mechanisms underlying stress responses in bacteria have been thoroughly characterised for decades, recent advances in imaging technologies helped to uncover previously hidden dynamics and heterogeneity that become visible at the single-cell level. Despite the diversity of stress response mechanisms, certain dynamic regulatory features are frequently seen in single cells, such as pulses, delays, stress anticipation and memory effects. Often, these dynamics are highly variable across cells. While any individual cell may not achieve an optimal stress response, phenotypic diversity can provide a benefit at the population level. In this review, we highlight microscopy studies that offer novel insights into how bacteria sense stress, regulate protective mechanisms, cope with response delays and prepare for future environmental challenges. These studies showcase developments in the single-cell imaging toolbox including gene expression reporters, FRET, super-resolution microscopy and single-molecule tracking, as well as microfluidic techniques to manipulate cells and create defined stress conditions.
Therapeutic efficacy of ramucirumab after lenvatinib for post-progression treatment of unresectable hepatocellular carcinoma
Authors: Hiraoka Atsushi , Kumada Takashi , Tada Toshifumi , Ogawa Chikara , Tani Joji , Fukunishi Shinya , Atsukawa Masanori , Hirooka Masashi , Tsuji Kunihiko , Ishikawa Toru , Takaguchi Koichi , Kariyama Kazuya , Itobayashi Ei , Tajiri Kazuto , Shimada Noritomo , Shibata Hiroshi , Ochi Hironori , Kawata Kazuhito , Toyoda Hidenori , Ohama Hideko , Nouso Kazuhiro , Tsutsui Akemi , Nagano Takuya , Itokawa Norio , Hayama Korenobu , Arai Taeang , Imai Michitaka , Koizumi Yohei , Nakamura Shinichiro , Michitaka Kojiro , Hiasa Yoichi , Kudo Masatoshi ,   the Real-life Practice Experts for HCC (RELPEC) Study Group and HCC 48 Group (hepatocellular-carcinoma experts from 48 clinics in Japan)
Published: June 2020

Background

Lenvatinib is used for unresectable hepatocellular carcinoma (u-HCC) as first-line, as well as second- and third-line therapy in Japan. We evaluated the therapeutic efficacy of newly developed ramucirumab when given after lenvatinib for post-progression treatment.

Methods

Of 385 patients with u-HCC and treated with lenvatinib at 16 different institutions in Japan between May 2018 and January 2020, 28 who received ramucirumab as the next treatment were enrolled and therapeutic responses were evaluated in a retrospective manner.

Results

The median age of the 28 patients given ramucirumab was 70 years and the median albumin-bilirubin score was −2.19. Of the 28 patients, 23 were male, 21 were classified as Child–Pugh A and 7 as Child–Pugh B, and 25 were Barcelona Clinic Liver Cancer Stage C. Ramucirumab was given as second-line therapy in 14, third-line in 9, and fourth-line in 5. Therapeutic response was obtained in only 26 patients; the objective response rate was 3.8% (1/26) and the disease-control rate was 42.3% (11/26), with a median period to progression of 2.0 months. The reasons for discontinuation of ramucirumab were progression of disease in 16 and Grade 3 adverse events (gastrointestinal bleeding, ascites) in 2.

Conclusions

The anticipated therapeutic efficacy of ramucirumab for post-progression treatment following lenvatinib was not seen in our early experience.
Germline PTEN mutations are associated with a skewed peripheral immune repertoire in humans and mice
Authors: Jaini Ritika , Loya Matthew G , King Alexander T , Thacker Stetson , Sarn Nicholas B , Yu Qi , Stark George R , Eng Charis
Published: June 2020

Individuals with germline mutations in the gene encoding phosphatase and tensin homolog on chromosome ten (PTEN) are diagnosed with PTEN hamartoma tumor syndrome (PHTS) and are at high risk for developing breast, thyroid and other cancers and/or autoimmunity or neurodevelopmental issues including autism spectrum disorders. Although well recognized as a tumor suppressor, involvement of PTEN mutations in mediating such a diverse range of phenotypes indicates a more central involvement for PTEN in immunity than previously recognized. To address this, sequencing of the T-cell receptor variable-region β-chain was performed on peripheral blood from PHTS patients. Based on patient findings, we performed mechanistic studies in two Pten knock-in murine models, distinct from each other in cell compartment-specific predominance of Pten. We found that PTEN mutations in humans and mice are associated with a skewed T- and B-cell gene repertoire, characterized by increased prevalence of high-frequency clones. Immunological characterization showed that Pten mutants have increased B-cell proliferation and a proclivity towards increased T-cell reactivity upon Toll-like-receptor stimulation. Furthermore, decreases in nuclear but not cytoplasmic Pten levels associated with a reduction in expression of the autoimmune regulator (Aire), a critical mediator of central immune tolerance. Mechanistically, we show that nuclear PTEN most likely regulates Aire expression via its emerging role in splicing regulation. We conclude that germline disruption of PTEN, both in human and mouse, results in compromised central immune tolerance processes that may significantly impact individual stress responses and therefore predisposition to autoimmunity and cancer.
Passive Smoking Increases the Risk for Intestinal Surgeries in Patients With Crohn’s Disease
Authors: Scharrer Susanna , Lissner Donata , Primas Christian , Reinisch Walter , Novacek Gottfried , Reinisch Sieglinde , Papay Pavol , Dejaco Clemens , Vogelsang Harald , Miehsler Wolfgang
Published: June 2020

Background

Despite substantial evidence on the negative effect of active smoking, the impact of passive smoking on the course of Crohn’s disease (CD) remains largely unclear. Our aim was to assess passive smoking as a risk factor for intestinal surgeries in CD.

Methods

The study was conducted in a university-based, monocentric cohort of 563 patients with CD. Patients underwent a structured interview on exposure to passive and active smoking. For clinical data, chart review was performed. Response rate was 84%, leaving 471 cases available for analysis. For evaluation of the primary objective, which was the impact of exposure to passive smoking on the risk for intestinal surgery, only never actively smoking patients were included.

Results

Of 169 patients who never smoked actively, 91 patients (54%) were exposed to passive smoking. Exposed patients were more likely to undergo intestinal surgery than nonexposed patients (67% vs 30%; P < 0.001). Multivariate Cox regression analysis revealed that passive smoking was an independent risk factor for intestinal surgeries (hazard ratio, 1.7; 95% CI, 1.04–2.9; P = 0.034) after adjustment for ileal disease at diagnosis (hazard ratio, 2.9; 95% CI, 1.9–4.5; P < 0.001) and stricturing or penetrating behavior at diagnosis (hazard ratio, 1.9; 95% CI, 1.2–3.1; P = 0.01). Passive smoking during childhood was a risk factor for becoming an active smoker in later life (odds ratio, 2.2; 95% CI, 1.5–3.2; P < 0.001).

Conclusion

Passive smoking increases the risk for intestinal surgeries in patients with CD.
IL-10 and Its Related Superfamily Members IL-19 and IL-24 Provide Parallel/Redundant Immune-Modulation in Loa loa Infection
Authors: Ricciardi Alessandra , Nutman Thomas B
Published: June 2020

Background

Interleukin-10 (IL-10) has been implicated as the major cytokine responsible for the modulation of parasite-specific responses in filarial infections; however, the role of other IL-10 superfamily members in filarial infection is less well studied.

Methods

Peripheral blood mononuclear cells from loiasis patients were stimulated with or without filarial antigen. Cytokine production was quantified using a Luminex platform and T-cell expression patterns were assessed by flow cytometry.

Results

All patients produced significant levels of IL-10, IL-13, IL-5, IL-4, and IL-9 in response to filarial antigen, indicating a common infection-driven response. When comparing microfilaria (mf)-positive and mf-negative patients, there were no significant differences in spontaneous cytokine nor in parasite-driven IL-10, IL-22, or IL-28a production. In marked contrast, mf-positive individuals had significantly increased filarial antigen-driven IL-24 and IL-19 compared to mf-negative subjects. mf-positive patients also demonstrated significantly higher frequencies of T cells producing IL-19 in comparison to mf-negative patients. T-cell expression of IL-19 and IL-24 was positively regulated by IL-10 and IL-1β. IL-24 production was also regulated by IL-37.

Conclusion

These data provide an important link between IL-10 and its related family members IL-19 and IL-24 in the modulation of the immune response in human filarial infections.

Clinical Trials Registration

NCT00001230.
Detection of Respiratory Syncytial Virus or Rhinovirus Weeks After Hospitalization for Bronchiolitis and the Risk of Recurrent Wheezing
Authors: Mansbach Jonathan M , Geller Ruth J , Hasegawa Kohei , Piedra Pedro A , Avadhanula Vasanthi , Gern James E , Bochkov Yury A , Espinola Janice A , Sullivan Ashley F , Camargo Carlos A
Published: June 2020

Background

In severe bronchiolitis, it is unclear if delayed clearance or sequential infection of respiratory syncytial virus (RSV) or rhinovirus (RV) is associated with recurrent wheezing.

Methods

In a 17-center severe bronchiolitis cohort, we tested nasopharyngeal aspirates (NPA) upon hospitalization and 3 weeks later (clearance swab) for respiratory viruses using PCR. The same RSV subtype or RV genotype in NPA and clearance swab defined delayed clearance (DC); a new RSV subtype or RV genotype at clearance defined sequential infection (SI). Recurrent wheezing by age 3 years was defined per national asthma guidelines.

Results

Among 673 infants, RSV DC and RV DC were not associated with recurrent wheezing, and RSV SI was rare. The 128 infants with RV SI (19%) had nonsignificantly higher risk of recurrent wheezing (hazard ratio [HR], 1.31; 95% confidence interval [CI], .95–1.80; P = .10) versus infants without RV SI. Among infants with RV at hospitalization, those with RV SI had a higher risk of recurrent wheezing compared to children without RV SI (HR, 2.49; 95% CI, 1.22–5.06; P = .01).

Conclusions

Among infants with severe bronchiolitis, those with RV at hospitalization followed by a new RV infection had the highest risk of recurrent wheezing.
Switch from parenteral to oral antibiotics for brain abscesses: a retrospective cohort study of 109 patients
Authors: Asquier-Khati Antoine , Deschanvres Colin , Boutoille David , Lefebvre Maeva , Le Turnier Paul , Gaborit Benjamin , Lakhal Karim , Buffenoir Kevin , Khatchatourian Lydie , Asseray Nathalie ,   the Nantes Brain Abscesses study group, Orain Jérémie , Lecomte Raphael , Brochard Julia , Biron Charlotte , Raffi François , Juvin Marie-Emmanuelle , Roualdes Vincent , Riem Tanguy , Ngohou Chan , Orain Jérémie , Lecomte Raphael , Brochard Julia , Biron Charlotte , Raffi François , Juvin Marie-Emmanuelle , Roualdes Vincent , Riem Tanguy , Ngohou Chan
Published: June 2020

Objectives

Brain abscess is one of the most serious diseases of the CNS and is associated with high morbidity and mortality. With regard to the lack of data supporting an optimal therapeutic strategy, this study aimed to explore the prognostic factors of brain abscess, putting emphasis on the impact of therapeutic decisions.

Methods

We retrospectively included patients hospitalized for brain abscess during a period of 13 years. Comorbidities (Charlson scale), clinical presentation, microbiology culture, radiological features and therapeutic management were collected. Glasgow Outcome Scale (GOS) at 3 months and length of hospital stay were, respectively, the main and the secondary outcomes. Logistic regression was used to determine factors associated with outcome independently.

Results

Initial Glasgow Coma Scale (GCS) ≤14 and comorbidities (Charlson scale ≥2) were associated with poor neurological outcome while oral antibiotic switch was associated with better neurological outcome. Oral switch did not appear to be associated with an unfavourable evolution in the subset of patients without initial neurological severity (GCS >14) on admission. Duration of IV regimen and time to oral switch were associated with the length of inpatient stay.

Conclusions

This study confirms the role of GCS and comorbidities as prognostic factors and presents reassuring data regarding the safety of oral switch for the antibiotic treatment of brain abscesses. Oral switch could prevent catheter-induced iatrogenic complications and allow a higher quality of life for patients.
Probabilistic forecasting of surgical case duration using machine learning: model development and validation
Authors: Jiao York , Sharma Anshuman , Ben Abdallah Arbi , Maddox Thomas M , Kannampallil Thomas
Published: June 2020

Objective

Accurate estimations of surgical case durations can lead to the cost-effective utilization of operating rooms. We developed a novel machine learning approach, using both structured and unstructured features as input, to predict a continuous probability distribution of surgical case durations.

Materials and Methods

The data set consisted of 53 783 surgical cases performed over 4 years at a tertiary-care pediatric hospital. Features extracted included categorical (American Society of Anesthesiologists [ASA] Physical Status, inpatient status, day of week), continuous (scheduled surgery duration, patient age), and unstructured text (procedure name, surgical diagnosis) variables. A mixture density network (MDN) was trained and compared to multiple tree-based methods and a Bayesian statistical method. A continuous ranked probability score (CRPS), a generalized extension of mean absolute error, was the primary performance measure. Pinball loss (PL) was calculated to assess accuracy at specific quantiles. Performance measures were additionally evaluated on common and rare surgical procedures. Permutation feature importance was measured for the best performing model.

Results

MDN had the best performance, with a CRPS of 18.1 minutes, compared to tree-based methods (19.5–22.1 minutes) and the Bayesian method (21.2 minutes). MDN had the best PL at all quantiles, and the best CRPS and PL for both common and rare procedures. Scheduled duration and procedure name were the most important features in the MDN.

Conclusions

Using natural language processing of surgical descriptors, we demonstrated the use of ML approaches to predict the continuous probability distribution of surgical case durations. The more discerning forecast of the ML-based MDN approach affords opportunities for guiding intelligent schedule design and day-of-surgery operational decisions.
Rumen-protected arginine in ewe lambs: effects on circulating serum amino acids and carotid artery hemodynamics
Authors: Peine Jena L , Neville Tammi L , Klinkner Erin E , Egeland Kelsey E , Borowicz Pawel P , Meyer Allison M , Reynolds Lawrence P , Caton Joel S
Published: June 2020

Sixty nonpregnant, nulliparous Rambouillet ewes (51 ± 1.4 kg initial body weight) were used in a completely randomized design to determine 1) if rumen-protected l-Arg (RP-ARG) supplementation would increase serum concentrations of amino acids resulting from Arg supplementation and metabolism, and decrease serum concentrations of amino acids that compete with Arg for transporters, 2) if RP-ARG supplementation would alter carotid artery hemodynamics, and 3) the most effective oral dose of RP-ARG to positively increase both circulating amino acids and improve peripheral tissue blood perfusion as measured by carotid hemodynamics. Ewes were penned individually in a temperature-controlled facility. Ewes were randomly assigned to one of four treatments: a control group that received no supplemental Arg (CON; 50 g of finely ground corn, only), or Arg-supplemented groups that received 90 (90), 180 (180), or 360 (360) mg RP-ARG·kg BW−1·d−1 mixed in 50 g of finely ground corn. Supplements were administered once daily for 14 d and fully consumed before the delivery of a total pelleted diet at 0630 and 1830 hours daily. Baseline and final blood samples were collected at days 0 (before treatment initiation) and 15, respectively. Doppler ultrasound was used to assess carotid arterial hemodynamics at 0600 hours on days 0 (before treatment initiation), 5, 8, 12, and 15. After 14 d of supplementation, ewes fed 180 had greater Arg (P = 0.05) and Orn (P = 0.05) and tended (P = 0.08) to have greater Asp in serum than ewes fed 90, and for these amino acids, ewes fed 180 were similar (P ≥ 0.16) compared with ewes fed 360. All supplemented ewes (90, 180, and 360) had a negative change (P = 0.02) from baseline when normalized to CON for the pulsatility and resistance indices, which indicate greater distal tissue blood perfusion and lower vascular resistance of blood flow, respectively. Additionally, there were quadratic responses for the pulsatility and resistance indices (P = 0.03 and 0.01, respectively) where ewes fed 180 had the greatest change from baseline when normalized to CON. Results indicate that Arg supplementation increased serum amino acid concentrations and improved peripheral tissue blood perfusion. The 180 mg·kg BW−1·d−1 RP-ARG dose was determined to be the optimal dose for nonpregnant, nulliparous Rambouillet ewes.
The Justice Spring of the Judicial System in Guatemala and the Implementation of the Judgments Issued by the Inter-American Court of Human Rights
Authors: Maldonado Urbina Wendy Johara
Published: June 2020

This practice note explains how, despite persistent impunity in Guatemala for the serious human rights violations that took place during the armed conflict, important changes have taken place within the judiciary that have facilitated the fight against impunity. It shows how a new generation of human rights practitioners has been empowered by judges like Judge Barrientos who used international human rights law, and particularly the judgments of the Inter-American Court of Human Rights, to ensure justice was done.
Tidying-up the plant nuclear space: domains, functions, and dynamics
Authors: Santos Ana Paula , Gaudin Valérie , Mozgová Iva , Pontvianne Frédéric , Schubert Daniel , Tek Ahmet L , Dvořáčková Martina , Liu Chang , Fransz Paul , Rosa Stefanie , Farrona Sara
Published: June 2020

Understanding how the packaging of chromatin in the nucleus is regulated and organized to guide complex cellular and developmental programmes, as well as responses to environmental cues is a major question in biology. Technological advances have allowed remarkable progress within this field over the last years. However, we still know very little about how the 3D genome organization within the cell nucleus contributes to the regulation of gene expression. The nuclear space is compartmentalized in several domains such as the nucleolus, chromocentres, telomeres, protein bodies, and the nuclear periphery without the presence of a membrane around these domains. The role of these domains and their possible impact on nuclear activities is currently under intense investigation. In this review, we discuss new data from research in plants that clarify functional links between the organization of different nuclear domains and plant genome function with an emphasis on the potential of this organization for gene regulation.
What are we afraid of? Exploring risk and immigration detention
Authors: Lindley Anna
Published: June 2020

Risk assessment is a prominent feature of managed migration regimes. How risk is conceptualised and operationalised, however, is highly contested terrain. The extent to which immigration detention represents an appropriate response to specific risks posed by people with contingent or no legal status is particularly hotly debated. In the UK, an early adopter and until recently an eager developer of detention , the policy is that immigration officers carry out individualised risk assessments on each person detained, considering removal prospects, risk of flight, and offending as well as the risk of harm to the individual. Drawing on published reports, government statistics, and interviews with close observers, this article explores the premises, policy, practice, and outcomes of these processes. The analysis flags multiple issues, suggesting that risk evaluation in relation to immigration detention is far from a well-oiled and reliable machine, causes unnecessary human harm, operates in a way that generates unforeseen risks for wider society, and points to other logics shaping detention.
Atacama Compact Array observations of the pulsar-wind nebula of SNR 0540-69.3
Authors: Lundqvist P , Lundqvist N , Vlahakis C , Björnsson C-I , Dickel J R , Matsuura M , Shibanov Yu A , Zyuzin D A , Olofsson G
Published: June 2020

We present observations of the pulsar-wind nebula (PWN) region of SNR 0540-69.3. The observations were made with the Atacama Compact Array (ACA) in Bands 4 and 6. We also add radio observations from the Australia Compact Array at 3 cm. For 1.449–233.50 GHz, we obtain a synchrotron spectrum $F_{\nu } \propto \nu ^{-\alpha _{\nu }}$, with the spectral index αν = 0.17 ± 0.02. To conclude how this joins the synchrotron spectrum at higher frequencies, we include hitherto unpublished AKARI mid-infrared data, and evaluate published data in the ultraviolet (UV), optical, and infrared (IR). In particular, some broad-band filter data in the optical must be discarded from our analysis due to contamination by spectral line emission. For the UV/IR part of the synchrotron spectrum, we arrive at $\alpha _{\nu } = 0.87^{+0.08}_{-0.10}$. There is room for 2.5 × 10−3 M⊙ of dust with a temperature of ∼55 K if there are dual breaks in the synchrotron spectrum, one around ∼9 × 1010 Hz and another at ∼2 × 1013 Hz. The spectral index then changes at ∼9 × 1010 Hz from αν = 0.14 ± 0.07 in the radio to $\alpha _{\nu } = 0.35^{-0.07}_{+0.05}$ in the millimetre-to-far-IR range. The ACA Band 6 data marginally resolve the PWN. In particular, the strong emission $\text{$\sim$} 1\hbox{$.\!\!^{\prime \prime }$}5$ south-west of the pulsar, seen at other wavelengths, and resolved in the 3 cm data with its 0.″8 spatial resolution, is also strong in the millimetre range. The ACA data clearly reveal the supernova remnant shell ∼20–35 arcsec west of the pulsar, and for the shell we derive αν = 0.64 ± 0.05 for the range 8.6–145 GHz.
The chromatin landscape at the HIV-1 provirus integration site determines viral expression
Authors: Vansant Gerlinde , Chen Heng-Chang , Zorita Eduard , Trejbalová Katerina , Miklík Dalibor , Filion Guillaume , Debyser Zeger
Published: June 2020

HIV-1 persists lifelong in memory cells of the immune system as latent provirus that rebounds upon treatment interruption. Therefore, the latent reservoir is the main target for an HIV cure. Here, we studied the direct link between integration site and transcription using LEDGINs and Barcoded HIV-ensembles (B-HIVE). LEDGINs are antivirals that inhibit the interaction between HIV-1 integrase and the chromatin-tethering factor LEDGF/p75. They were used as a tool to retarget integration, while the effect on HIV expression was measured with B-HIVE. B-HIVE tracks insert-specific HIV expression by tagging a unique barcode in the HIV genome. We confirmed that LEDGINs retarget integration out of gene-dense and actively transcribed regions. The distance to H3K36me3, the marker recognized by LEDGF/p75, clearly increased. LEDGIN treatment reduced viral RNA expression and increased the proportion of silent provirus. Finally, silent proviruses obtained after LEDGIN treatment were located further away from epigenetic marks associated with active transcription. Interestingly, proximity to enhancers stimulated transcription irrespective of LEDGIN treatment, while the distance to H3K36me3 only changed after treatment with LEDGINs. The fact that proximity to these markers are associated with RNA expression support the direct link between provirus integration site and viral expression.
Early AGEing and metabolic diseases: is perinatal exposure to glycotoxins programming for adult-life metabolic syndrome?
Authors: Francisco Flávio A , Saavedra Lucas P J , Junior Marcos D F , Barra Cátia , Matafome Paulo , Mathias Paulo C F , Gomes Rodrigo M
Published: June 2020

Perinatal early nutritional disorders are critical for the developmental origins of health and disease. Glycotoxins, or advanced glycation end-products, and their precursors such as the methylglyoxal, which are formed endogenously and commonly found in processed foods and infant formulas, may be associated with acute and long-term metabolic disorders. Besides general aspects of glycotoxins, such as their endogenous production, exogenous sources, and their role in the development of metabolic syndrome, we discuss in this review the sources of perinatal exposure to glycotoxins and their involvement in metabolic programming mechanisms. The role of perinatal glycotoxin exposure in the onset of insulin resistance, central nervous system development, cardiovascular diseases, and early aging also are discussed, as are possible interventions that may prevent or reduce such effects.
The Party Abroad, the World of Professional Electoral and Democracy Assistance, and the Way Forward
Authors: van der Staak Sam , Rashkova Ekaterina R
Published: June 2020

This article presents developments around the party abroad phenomenon within the world of international democracy assistance. It provides an overview of where ‘the party abroad’ sits as a topic within the broader field of democracy assistance, and how democracy assistance providers have addressed it in the past. It argues that even though the party abroad has grown among political parties themselves, it has thus far received scant attention from democracy assistance providers. However, there are reasons to believe that the party abroad will continue to grow among political parties and that assistance providers will also include a stronger focus on the party abroad in their work in years to come.
Chronology and Causality in Africa’s HIV Pandemic: The Production of History Between the Laboratory and the Archive
Authors: Doyle Shane
Published: June 2020

By 2018 approximately 32 million deaths worldwide had been attributed to HIV/AIDS. Yet the impact of the AIDS pandemic has been profoundly uneven. In the Global North, HIV has been constructed as marginal; in much of Africa, it is pervasive and transformative, fundamentally reshaping local economies, civil society, state structures and the continent’s relations with the outside world. HIV is in reality a series of distinct epidemics, each with their own histories. In recent years, scientists have challenged historians’ understanding of HIV’s chronology and patterns of transmission, providing alternative histories of the virus’s origins, expansion and resilience within mature epidemic settings. Epidemiologists and geneticists have realigned the temporal focus of archival and oral research while conceptualizing change over time around moments of divergence and focusing on historical episodes rather than process, and on diffusion over intensification. This article analyses scientists’ historical understanding of sexually transmitted infections, migration and same-sex relationships, challenging narrow understandings of causality and the assumption that the contexts of the recent past can be applied backwards to more distant periods. Reconstructing HIV’s long history requires recognition of the evolving complexity of sex and marriage, morality and discretion, migrancy and displacement, ethnic and racial preconceptions, and locality and connection.
ESTIMATION OF HP(3) AMONG STAFF MEMBERS IN TWO NUCLEAR MEDICINE UNITS IN FINLAND
Authors: Lindholm C , Pekkarinen A , Sipilä O , Manninen A-L , Lehtinen M , Siiskonen T
Published: June 2020

The eye lens exposure among 16 technicians in two nuclear medicine departments at university hospitals in Finland was investigated by measuring the operational quantity Hp(3) using EYE-D dosemeters. For all workers, the annual mean Hp(3) was estimated to be 1.1 mSv (max. 3.9 mSv). The relation between Hp(3) to routinely monitored personal dose equivalent Hp(10) was clearly correlated. Considering individual dose measurement periods (2–4 weeks), the Hp(3)/Hp(10) ratio was 0.7 (Pearson’s coefficient r = 0.90, p < 0.001, variation of ratio 0.1–2.3). The variation decreased considerably with increasing Hp(10) (σ2 = 0.04 vs. 0.43 for Hp(10) > 0.1 mSv vs. < 0.1 mSv, respectively), i.e. higher Hp(10) predicts Hp(3) more reliably. Moreover, annual Hp(10) data from national dose register during 2009–2018 were used to derive the annual Hp(3) applying the Hp(3)/Hp(10) ratio. The data from Finnish nuclear medicine departments imply that routine measurements of Hp(3) among nuclear medicine technicians are not justified.