bluuebunny/crossref_metadata_2025 huggingface dataset:
Angiotensin‐converting enzyme inhibitor and angiotensin II type 1 receptor blocker: Potential agents to reduce post‐surgical scar formation in humans
Authors: Hu Yan‐Yan , Fang Qing‐Qing , Wang Xiao‐Feng , Zhao Wan‐Yi , Zheng Bin , Zhang Ding‐Ding , Tan Wei‐Qiang
Published: June 2020

Studies on the effectiveness and mechanisms of reducing scar formation by interfering with the renin‐angiotensin‐aldosterone‐system (RAAS) have been demonstrated in animals, but not in humans due to the lack of clinical support. Our aim was to investigate whether angiotensin‐converting enzyme inhibitor (ACEI) and angiotensin II type 1 receptor blocker (ARB) could inhibit scar formation in humans. Thus, an observational and hypothesis‐generating study using a designed questionnaire was carried out. A total of 347 patients with postoperative scars secondary to thyroid tumours were enrolled. They were divided into four groups: ACEI group, ARB group, other antihypertensive drugs control group and blank control group according to the administration of antihypertensive drugs. The width of scar was measured, and the Scar Cosmesis Assessment and Rating (SCAR) Scale was filled out. Results showed that patients of ACEI group (mean scar width 1.60 mm) and ARB group (mean scar width 1.57 mm) formed smaller scars than those of other antihypertensive drugs control group (mean scar width 2.09 mm) and blank control group (mean scar width 2.0 mm). Oral administration of ACEI and ARB may be associated with better post‐surgical scar formation in humans. These two kinds of antihypertensive drugs may be active components of anti‐scar medicine.
Randomised trial of telephone counselling to improve participants' adherence to prescribed drugs in a vascular screening trial
Authors: Qvist Ina , Lindholt Jes S. , Søgaard Rikke , Lorentzen Vibeke , Hallas Jesper , Frost Lars
Published: June 2020

A total of 1446 participants, 65‐ to 74‐year‐old men diagnosed with abdominal aortic aneurysm (AAA), peripheral arterial disease (PAD) or high blood pressure (HB) in the Viborg Vascular (VIVA) screening trial, were consecutively included and randomised to a telephone counselling (TC) or no TC 3 months after being screened positive. Data from VIVA were linked to data from Danish registers from 2007 to 2016. The primary outcome was a composite outcome of proportion of days covered by statin, antithrombotic drugs and antihypertensive agents and for each specific drug class at 6‐month follow‐up. The same outcomes were assessed at 12 and 60 months and considered secondary outcomes. Outcome measures are reported as risk differences (RD). There were no differences between the groups in relation to the composite of all three drug classes over 6 months of follow‐up, RD = 4.1 (95% CI: −1.0; 9.1). A significant increase in redeemed statin prescriptions was observed in the intervention group at 6 months, RD = 9.8% (CI 95%: 0.5; 19.0). There was no intervention effect observed after 12 and 60 months. TC 3 months after screening improved adherence to statin at 6‐month follow‐up, but had no effect on the composite treatment, statins, antithrombotic or antihypertensive treatment over 60 months of follow‐up.
A taxonomy of clinical response to mood stabilizers
Authors: Scott Jan , Etain Bruno , Nierenberg Andrew , Bellivier Frank
Published: June 2020

Introduction

Although clinical practice guidelines (CPG) identify first, second‐ and third‐line mood stabilizer (MS) treatments, they rarely define clinical response to prophylaxis or the core issues to be considered. This project aimed to develop a template for describing how clinical response may be classified and a framework to assist decision‐making and monitoring of response in day‐to‐day practice.

Method

A scoping exercise was undertaken followed by narrative synthesis of (a) qualitative and quantitative definitions of MS response applied in clinical and research practice and (b) potential confounders (eg, non‐adherence; tolerability issues) of relevance to routine practice, for example, the concepts are applicable to individuals with bipolar disorder for whom sustained remission is a less realistic goal. Expert consensus was employed to develop a taxonomy of response and key concepts that inform clinical judgements about MS response.

Results

Five core constructs can be used to systematize clinical judgements regarding MS response and its monitoring: (a) quantitative, qualitative and/or patient‐reported outcome measures (PROMS), (b) personalized assessment of the acceptable benefit‐to‐harm ratio of a proposed treatment, (c) adequacy of treatment exposure (dose, duration, therapeutic monitoring and adherence), (d) illness activity pre‐ and post‐MS initiation, and (e) other potential confounders (co‐prescription of MS; polypharmacy) or protective factors (eg, psychosocial factors).

Conclusions

This heuristic framework might be used as a teaching aid or by clinicians who wish to take a more systematic approach to developing shared criteria for judging MS response that better match patient expectations and preferences. Heuristic approaches also allow seamless introduction of new evidence.
Measuring circadian function in bipolar disorders: Empirical and conceptual review of physiological, actigraphic, and self‐report approaches
Authors: Murray Greg , Gottlieb John , Hidalgo Maria Paz , Etain Bruno , Ritter Philipp , Skene Debra J. , Garbazza Corrado , Bullock Ben , Merikangas Kathleen , Zipunnikov Vadim , Shou Haochang , Gonzalez Robert , Scott Jan , Geoffroy Pierre A. , Frey Benicio N.
Published: June 2020

Background

Interest in biological clock pathways in bipolar disorders (BD) continues to grow, but there has yet to be an audit of circadian measurement tools for use in BD research and practice.

Procedure

The International Society for Bipolar Disorders Chronobiology Task Force conducted a critical integrative review of circadian methods that have real‐world applicability. Consensus discussion led to the selection of three domains to review—melatonin assessment, actigraphy, and self‐report.

Results

Measurement approaches used to quantify circadian function in BD are described in sufficient detail for researchers and clinicians to make pragmatic decisions about their use. A novel integration of the measurement literature is offered in the form of a provisional taxonomy distinguishing between circadian measures (the instruments and methods used to quantify circadian function, such as dim light melatonin onset) and circadian constructs (the biobehavioral processes to be measured, such as circadian phase).

Conclusions

Circadian variables are an important target of measurement in clinical practice and biomarker research. To improve reproducibility and clinical application of circadian constructs, an informed systematic approach to measurement is required. We trust that this review will decrease ambiguity in the literature and support theory‐based consideration of measurement options.
Does private education make nicer people? The influence of school type on social–emotional development
Authors: von Stumm Sophie , Plomin Robert
Published: June 2020

In a longitudinal sample from Britain, we tested if attending private, fee‐charging schools rather than non‐selective state schools benefitted children’s social–emotional development. State (N = 2,413) and private school children (N = 269) showed no differences in well‐being across adolescence, but private school children reported fewer behaviour problems and greater peer victimisation over time than state schoolers. These results were independent of schools’ selection criteria, including family background, and prior academic and cognitive performance. At age 21, private and state school students differed marginally in social–emotional behaviours, such as self‐control, volunteering, sexual conduct, and substance use. After considering schools’ selection criteria, only risk taking and age at having the first alcoholic drink differed between private and state school children, with the privately educated ones being less risk averse and drinking at younger ages than those attending state school. Our results suggest that private education adds little positive value to children’s social–emotional development.
The recurrence and progression risk after simultaneous endoscopic surgery of urothelial bladder tumour and benign prostatic hyperplasia: a systematic review and meta‐analysis
Authors: Sari Motlagh Reza , Mori Keiichiro , Miura Noriyoshi , Quhal Fahad , Aydh Abdulmajeed , Laukhtina Ekaterina , Pradere Benjamin , Karakiewicz Pierre I. , Enikeev Dmitry V. , Deuker Marina , Shariat Shahrokh F.
Published: June 2020

Objectives

To evaluate recurrence and progression risk after simultaneous endoscopic surgery of bladder cancer and benign prostatic hyperplasia (BPH), as simultaneous surgery is not an unusual scenario and theoretically simultaneous transurethral resection of bladder tumour (TURBT) and transurethral resection of the prostate (TURP) can lead to an increased risk of recurrence in the bladder neck and prostatic urethra (BN/PU).

Methods

We conducted a systematic review and meta‐analysis to assess the risk of recurrence (i.e. whole bladder and/or BN/PU) and tumour progression as outcomes after a simultaneous endoscopic surgery of bladder tumour and BPH, as compared to TURBT alone. We queried PubMed and Web of Science database on 1 January 2020. We used random‐ and/or fixed‐effects meta‐analytic models in the presence or absence of heterogeneity according to the I2 statistic, respectively.

Results

Nine retrospective and three clinical trial studies were selected after considering inclusion and exclusion criteria. We conducted the meta‐analysis on retrospective and randomised controlled trials (RCTs) separately. Eight retrospective and three RCT studies were included to assess the BN/PU recurrence risk and the summarised risk ratio (RR) was 1.02 (95% confidence interval [CI] 0.74–1.41) and 0.93 (95% CI 0.47–1.84), respectively. Five retrospective and two RCT studies were included to assess the progression risk and the summarised RR was 0.91 (95% CI 0.56–1.48) and 1.16 (95% CI 0.30–4.51), respectively. Eight retrospective and three RCT studies were included to assess the whole bladder recurrence risk and the summarised RR was 0.87 (95% CI 0.78–0.97) and 0.89 (95% CI 0.65–1.21), respectively.

Conclusion

We did not observe any increased risk of total bladder recurrence, BN/PU recurrence, or progression after a simultaneous endoscopic surgery of bladder tumour and BPH, as compared to TURBT alone.
Single‐ vs multiple‐layer wound closure for flank incisions: results of a prospective, randomised, double‐blinded multicentre study
Authors: Kriegmair Maximilian C. , Younsi Nina , Hiller Kiriaki , Leitsmann Conrad , Kowalewski Karl F. , Siegel Fabian , Rothamel Martin , Ritter Manuel , Bolenz Christian , Kriegmair Martin , Trojan Lutz , Michel Maurice S.
Published: June 2020

Objective

To compare the incidence of postoperative flank bulges between patients with multiple‐layer closure and single superficial‐layer closure after retroperitoneal surgery via open flank incision in the SIngle versus MUltiple‐LAyer wound Closure for flank incision (SIMULAC) trial.

Patients and Methods

The study was a randomised controlled, patient‐ and assessor‐blinded, multicentre trial. Between May 2015 and February 2017, 225 patients undergoing flank incisions were randomised 1:1 to a multiple‐layer closure (SIMULAC‐I) or a single superficial‐layer closure (SIMULAC‐II) group. The primary outcome was the occurrence of a flank bulge 6 months after surgery.

Results

Overall, 177 patients (90 in SIMULAC‐I, 87 in SIMULAC‐II) were eligible for final assessment. The cumulative incidence of a flank bulge was significantly higher in the SIMULAC‐II group (51.7%) compared to the SIMULAC‐I group [34.4%; odds ratio (OR) 2.04, 95% confidence interval (CI) 1.11–3.73; P = 0.02]. Rate of severe postoperative complications (4.4% SIMULAC‐I vs 10.3% SIMULAC‐II; P = 0.21) or hernia (6.7% SIMULAC‐I vs 10.3% SIMULAC‐II; P = 0.59) was similar between the groups. There was no difference in pain (visual analogue scale) and the requirement for pain medication at 6 months postoperatively. Quality of life assessed with the European Quality of Life 5 Dimensions Questionnaire was higher in the SIMULAC‐I group compared to the SIMULAC‐II group at 6 months postoperatively, with a (median range) score of 80 (30–100) vs 75 (5–100) (P = 0.012).

Conclusion

The overall risk of a flank bulge after flank incision is high. Multiple‐layer closure after flank incision should be performed as a standard procedure.
Profiling ocular surface responses to preserved and non‐preserved topical glaucoma medications: A 2‐year randomized evaluation study
Authors: Mohammed Imran , Kulkarni Bina , Faraj Lana A. , Abbas Ali , Dua Harminder S. , King Anthony J.
Published: June 2020

Background

Use of topical glaucoma medications has been reported to cause ocular surface (OS) discomfort and inflammation. This study explores the profile of inflammatory cytokines and OS symptoms induced in response to preserved and non‐preserved drops.

Methods

Prospective, randomized evaluation on 36 treatment‐naïve patients over 24 months of three differently preserved glaucoma drop preparations: Preservative‐free (PF), polyquad (PQ) and benzalkonium chloride (BAK). Study participants were evaluated at baseline and then at 1, 3, 6, 12 and 24 months while on medication. At each visit, participants completed the OS disease index (OSDI) questionnaire, had basal tear sampling and impression cytology (IC) of the conjunctival epithelium. Quantitative polymerase chain reaction was performed to measure the gene expression of inflammatory cytokines [interleukin (IL)‐6, IL‐8, IL‐10, IL‐12A, IL‐12B, IL‐17A, IL‐1β and tumour necrosis factor‐α] in the IC samples. Corresponding protein expression of cytokines in tear samples was assessed by the Becton‐Dickinson cytometric bead arrays.

Results

Compared to PF and PQ groups, mRNA and protein expression of IL‐6, IL‐8 and IL‐1β increased in samples from the BAK group in a time‐dependent fashion, whereas all other cytokines showed a non‐significant increase. In the BAK group, there was a strong correlation between OSDI and the levels of IC/IL‐1β (r = .832, R2 = .692 and P = .040); IC/IL‐10 (r = .925, R2 = .856 and P = .008) and tear/IL‐1β (r = .899, R2 = .808 and P = .014).

Conclusions

BAK‐preserved topical drops stimulate a sterile inflammatory response on the OS within 3 months which is maintained thereafter, whereas PF‐drops and PQ‐preserved drops showed no significant OS inflammation.
Photofunctionalization as a suitable approach to improve the osseointegration of implants in animal models—A systematic review and meta‐analysis
Authors: Dini Caroline , Nagay Bruna Egumi , Magno Marcela Baraúna , Maia Lucianne Cople , Barão Valentim Adelino Ricardo
Published: June 2020

Objectives

To determine whether photofunctionalization influences dental implant osseointegration.

Material and methods

Data on osseointegration rates were extracted from 8 databases, based on bone‐to‐implant contact (BIC) and pushout tests. Internal validity was accessed through the SYRCLE risk of bias tool for animal experimental studies. Meta‐analyses were performed for investigation of the influence of photofunctionalization on implant osseointegration, with a random effect and a confidence interval of 95%. The certainty of evidence was accessed through the GRADE approach.

Results

Thirty‐four records were identified, and 10 were included in the meta‐analysis. Photofunctionalized implants showed higher mean values for BIC in rabbits (MD 6.92 [1.01, 12.82], p = .02), dogs (MD 23.70 [10.23, 37.16], p = .001), rats (MD 20.93 [12.91, 28.95], p < .0001), and in the pooled BIC analyses (MD 14.23 [7.80, 20.66], p < .0001) compared to those in control implants in the overall assay. Conversely, at late healing periods, the pooled BIC meta‐analyses showed no statistically significant differences (p > .05) for photofunctionalized and control implants at 12 weeks of follow‐up. For pushout analysis, photofunctionalized implants presented greater bone strength integration (MD 19.92 [13.88, 25.96], p < .0001) compared to that of control implants. The heterogeneity between studies ranged from “not important” to “moderate” for rabbits I2 = 24%, dogs I2 = 0%, rats I2 = 0%, and pooled BIC (I2 = 49%), while considerable heterogeneity was observed for pushouts (I2 = 90%).

Conclusion

Photofunctionalization improves osseointegration in the initial healing period of implants, as summarized from available data from rabbit, dog, and rat in vivo models.
The effect of inadequate access to peri‐implant hygiene on marginal bone level. A 4‐year cohort prospective study
Authors: Tormena Mariana , Matarazzo Flávia , de Oliveira Bruna Medeiros , Pereira Omar , Previdelli Isolde , Araújo Maurício G.
Published: June 2020

Objective

The objective of this four‐year cohort prospective study was to evaluate the effect of inadequate access to peri‐implant hygiene on marginal bone level (MBL).

Material and Methods

Forty‐one partially edentulous patients (16 males and 25 females, aged 49.8 ± 11.9 years) who had implants with at least one year in function were selected. Patients were clinically and radiographically evaluated at three different times: baseline (T0), 2‐year (T1), and 4‐year (T2) follow‐up intervals. At baseline, implants were classified and allocated into two groups: those presenting adequate access (ACC) and inadequate access (no‐ACC) to peri‐implant hygiene. A linear mixed‐effects model for clustered longitudinal data was used to analyze MBL, probing depth (PD), plaque index (PI), and bleeding on probing (BoP).

Results

Of 131 implants, 74 were considered as having ACC, and 57 as having no‐ACC at T0. Implants in the no‐ACC group presented a statistically greater mean MBL measurement at T2 than implants in the ACC group (p = .011). In the no‐ACC group, a significant reduction in PD from T0 to T1 (p = .019) and from T0 to T2 (p = .010) was observed. Regardless of the group, PI significantly increased at both T1 (p = .00001) and T2 (p = .00004). Regardless of time, the prevalence of BoP was significantly higher in the no‐ACC group than in the ACC group (p = .012).

Conclusion

Inadequate access to peri‐implant hygiene frequently resulted in more peri‐implant inflammation and MBL over time. Proper accessibility to peri‐implant hygiene should be carefully considered during planning of implant restoration, and patients properly motivated into maintenance care.
The Role of Attention in Word Recognition: Results from OB1‐Reader
Authors: Meeter Martijn , Marzouki Yousri , Avramiea Arthur E. , Snell Joshua , Grainger Jonathan
Published: June 2020

When reading, orthographic information is extracted not only from the word the reader is looking at, but also from adjacent words in the parafovea. Here we examined, using the recently introduced OB1‐reader computational model, how orthographic information can be processed in parallel across multiple words and how orthographic information can be integrated across time and space. Although OB1‐reader is a model of text reading, here we used it to simulate single‐word recognition experiments in which parallel processing has been shown to play a role by manipulating the surrounding context in flanker and priming paradigms. In flanker paradigms, observers recognize a central word flanked by other letter strings located left and right of the target and separated from the target by a space. The model successfully accounts for the finding that such flankers can aid word recognition when they contain bigrams of the target word, independent of where those flankers are in the visual field. In priming experiments, in which the target word is preceded by a masked prime, the model accounts for the finding that priming occurs independent of whether the prime and target word are in the same location or not. Crucial to these successes is the key role that spatial attention plays within OB1‐reader, as it allows the model to receive visual input from multiple locations in parallel, while limiting the kinds of errors that can potentially occur under such spatial pooling of orthographic information.
Network Connectivity Dynamics, Cognitive Biases, and the Evolution of Cultural Diversity in Round‐Robin Interactive Micro‐Societies
Authors: Segovia‐Martín José , Walker Bradley , Fay Nicolas , Tamariz Monica
Published: June 2020

The distribution of cultural variants in a population is shaped by both neutral evolutionary dynamics and by selection pressures. The temporal dynamics of social network connectivity, that is, the order in which individuals in a population interact with each other, has been largely unexplored. In this paper, we investigate how, in a fully connected social network, connectivity dynamics, alone and in interaction with different cognitive biases, affect the evolution of cultural variants. Using agent‐based computer simulations, we manipulate population connectivity dynamics (early, mid, and late full‐population connectivity); content bias, or a preference for high‐quality variants; coordination bias, or whether agents tend to use self‐produced variants (egocentric bias), or to switch to variants observed in others (allocentric bias); and memory size, or the number of items that agents can store in their memory. We show that connectivity dynamics affect the time‐course of variant spread, with lower connectivity slowing down convergence of the population onto a single cultural variant. We also show that, compared to a neutral evolutionary model, content bias accelerates convergence and amplifies the effects of connectivity dynamics, while larger memory size and coordination bias, especially egocentric bias, slow down convergence. Furthermore, connectivity dynamics affect the frequency of high‐quality variants (adaptiveness), with late connectivity populations showing bursts of rapid change in adaptiveness followed by periods of relatively slower change, and early connectivity populations following a single‐peak evolutionary dynamic. We evaluate our simulations against existing data collected from previous experiments and show how our model reproduces the empirical patterns of convergence.
Cutaneous adnexal carcinosarcoma: Immunohistochemical and molecular evidence of epithelial mesenchymal transition
Authors: Kwon DongHyang , Ronen Shira , Giubellino Alessio , Keiser Elizabeth , Aung Phyu P. , Nagarajan Priyadharsini , Tetzlaff Michael T. , Ivan Doina , Curry Jonathan L. , Prieto Victor G. , Torres‐Cabala Carlos A.
Published: June 2020

Cutaneous carcinosarcomas are rare biphenotypic tumors that simultaneously show epithelial and mesenchymal differentiation. The most common carcinomatous components in skin carcinosarcomas are basal cell carcinoma and squamous cell carcinoma; adnexal carcinomas are rarely encountered. We report a case of an adnexal carcinoma with ductal and squamous differentiation and spindle cell component, which is interpreted as carcinosarcoma. Loss of immunohistochemical expression of E‐cadherin and β‐catenin detected in the sarcomatous component suggested epithelial mesenchymal transition (EMT). RNA sequencing analysis identified several gene mutations and alterations such as translocations and upregulations/downregulations, either shared by the two components of the tumor or differentially present in the carcinoma or the sarcoma parts. Thus, mutations in genes, such as TP53, were found in both components of the tumor while mutations in PDGFRA and RB1 (a pathogenic missense mutation) were exclusively present in the sarcomatous areas, further supporting EMT. EMT is a dynamic process by which tumors acquire mesenchymal phenotype while simultaneously losing epithelial properties. Although the pathways involved in EMT have been extensively studied, this phenomenon still needs to be investigated in cutaneous tumors of adnexal origin for a better understanding of their pathogenesis. These molecular changes may represent promising targets for personalized therapies.
Calcified mass in the right atrium extending into the inferior vena cava with pulmonary artery embolization. Typical or atypical myxoma?
Authors: Selvaganesan Sajith , S. Khidr Shimaa , Biederman Robert W. W.
Published: June 2020

Cardiac masses are divided into neoplastic and non‐neoplastic. They usually represent a diagnostic challenge given their relative rarity, their infrequent symptoms, and the overall difficulty with dynamic imaging of the heart. While echocardiography is useful in the initial evaluation of a suspected mass, cardiac magnetic resonance (CMR) imaging is the best imaging modality to characterize cardiac tumors due to its superior tissue characterization and its higher contrast resolution. For neoplastic, primary cardiac tumors are rare (0.05%). Atrial myxoma is the most common cardiac (50%) mass. About 75%‐80% of myxoma are seen in the left atrium. Atypical myxoma is a term describing myxoma arising in other nonleft atrial locations. 20%‐25% myxomas arise from the right atrium and 5% or less from the ventricles. We present a case of a 59‐year‐old female patient presenting with severe dyspnea. Her chest noncontrast CT showed a calcified mass lesion in the right atrium extending into the inferior vena cava. She underwent cardiac MRI for better tissue characterization. The cardiac MRI revealed a very irregular, highly spiculated, heavily calcified, heterogeneous, and nonenhancing lesion within the right atrium extending into the inferior vena cava. Via dynamic imaging, no evidence of mobile components was present. Via T1, T2 along with pre‐ and postcontrast imaging, the mass was confirmed to be calcified without a fibrotic component or evidence of thrombus. The above findings raised the possibility of atypical myxoma.
Electoral uncertainty and financial volatility: Evidence from two‐round presidential races in emerging markets
Authors: Carnahan Daniel , Saiegh Sebastian
Published: June 2020

We study how the predictability and the decisiveness of electoral outcomes affect financial volatility. We argue that traders’ optimal investment strategies depend on their ability to make accurate electoral forecasts and the prospective losses associated with placing a bet on the wrong candidate. Using a triple difference‐in‐difference approach and data from two‐round presidential elections in five Latin American countries between 1999 and 2018, we find that financial volatility is greatest in the days immediately following unpredictable, decisive, elections. Postelectoral volatility also occurs following predictable, indecisive elections. The effect of learning the identity of the winning candidate on financial volatility is null when the election is unpredictable and indecisive, as well as when the election is decisive, but the outcome is predictable. These findings offer insights into investors seeking to hedge price risk around elections. They also have important implications regarding the relationship between public opinion polls and postelectoral financial volatility.
Patient outcomes in light chain (AL) amyloidosis: The clock is ticking from symptoms to diagnosis
Authors: Schulman Amanda , Connors Lawreen H , Weinberg Janice , Mendelson Lisa M , Joshi Tracy , Shelton Anthony C , Sanchorawala Vaishali
Published: June 2020

Introduction

Symptomology of AL amyloidosis can be vague, with a broad range of manifestations and potential etiologies. We sought to determine whether time from initial patient‐reported symptom onset to diagnosis was associated with survival.

Methods

The Boston University Amyloidosis Patient Database was queried for patients with AL amyloidosis who presented to the Center for initial evaluation from 2010 to 2015.

Results

A total of 324 patients with AL amyloidosis were evaluated for initial evaluation. The median time to diagnosis from initial symptom onset was 7.1 months (range, 0‐61). At data cutoff, 60.2% (n = 195) of patients were alive; of those, the majority were diagnosed <6 months from initial symptoms (52.3%, n = 102). In contrast, time to diagnosis from symptom onset was >6 months in 63.6% (n = 82) of patients who did not survive at the time of data cutoff (P = .0005). Survival analysis of time from diagnosis to death or data cutoff stratified by time from patient‐reported symptom onset to diagnosis (<6, 6‐12, and >12 months) showed significant differences among groups (P = .001). Additionally, multivariable regression demonstrated that an increase in time from self‐reported symptom onset to diagnosis was significantly associated with an increased risk of death (HR = 1.02, 95% CI = 1.01‐1.04, P = .002).

Conclusion

These results support the importance of early diagnosis for patients with AL amyloidosis.
Clinical efficacy of mogamulizumab for relapsed/refractory aggressive adult T‐cell leukemia/lymphoma: A retrospective analysis
Authors: Satake Atsushi , Konishi Akiko , Azuma Yoshiko , Tsubokura Yukie , Yoshimura Hideaki , Hotta Masaaki , Nakanishi Takahisa , Fujita Shinya , Nakaya Aya , Ito Tomoki , Ishii Kazuyoshi , Nomura Shosaku
Published: June 2020

Objectives

Although phase 2 studies have confirmed the efficacy of mogamulizumab for adult T‐cell leukemia/lymphoma (ATL), real‐world data on its benefits are limited. We assessed the benefits of mogamulizumab for relapsed/refractory ATL in clinical practice.

Methods

We retrospectively analyzed patients with acute‐ and lymphoma‐type ATL. Among 57 patients diagnosed with ATL between January 2008 and August 2018, 42 who received salvage therapy were eligible, including 24 who received mogamulizumab.

Results

The overall response rate to mogamulizumab was 54.2%. Median survival time (MST) and 1‐year overall survival (OS) rate from mogamulizumab initiation were 7.7 months and 42.0%, respectively. Patients with acute‐type ATL showed longer MST (15.1 months) and higher 1‐year OS (63.6%). MST without skin rash was 5.0 months, and 1‐year OS was 34.3%; however, MST with skin rash was not reached and 1‐year OS was 66.7%. Among patients who received the salvage therapy, longer MST and higher 1‐year OS were observed with mogamulizumab than without mogamulizumab (P = .078; 9.2 vs. 3.9 months; 47.9% vs. 17.6%, respectively). Mogamulizumab administration improved prognosis in patients with acute‐type ATL and skin rash.

Conclusions

In clinical practice, mogamulizumab improved OS in patients with relapsed/refractory ATL, especially those with acute‐type ATL and skin rash.
A biologically constrained spiking neural network model of the primate basal ganglia with overlapping pathways exhibits action selection
Authors: Girard Benoît , Lienard Jean , Gutierrez Carlos Enrique , Delord Bruno , Doya Kenji
Published: June 2020

Action selection has been hypothesized to be a key function of the basal ganglia, yet the nuclei involved, their interactions and the importance of the direct/indirect pathway segregation in such process remain debated. Here, we design a spiking computational model of the monkey basal ganglia derived from a previously published population model, initially parameterized to reproduce electrophysiological activity at rest and to embody as much quantitative anatomical data as possible. As a particular feature, both models exhibit the strong overlap between the direct and indirect pathways that has been documented in non‐human primates. Here, we first show how the translation from a population to an individual neuron model was achieved, with the addition of a minimal number of parameters. We then show that our model performs action selection, even though it was built without any assumption on the activity carried out during behaviour. We investigate the mechanisms of this selection through circuit disruptions and found an instrumental role of the off‐centre/on‐surround structure of the MSN‐STN‐GPi circuit, as well as of the MSN‐MSN and FSI‐MSN projections. This validates their potency in enabling selection. We finally study the pervasive centromedian and parafascicular thalamic inputs that reach all basal ganglia nuclei and whose influence is therefore difficult to anticipate. Our model predicts that these inputs modulate the responsiveness of action selection, making them a candidate for the regulation of the speed–accuracy trade‐off during decision‐making.
The impact of drought and rewetting on N2O emissions from soil in temperate and Mediterranean climates
Authors: Barrat Harry A. , Evans Jess , Chadwick David R. , Clark Ian M. , Le Cocq Kate , M. Cardenas Laura
Published: June 2020

The potential for soils to produce nitrous oxide (N2O) is impacted by past moisture conditions; however, the extent of this impact is not fully understood. We conducted the first review of this, using two literature searches and a meta‐analysis. We found 36 studies out of a possible 735 that described experiments where soil moisture conditions had been controlled, such that the impact of antecedent moisture levels could be separated from contemporary moisture levels and attributed to N2O emissions. Of those studies, 14 (130 data points) used the appropriate experimental design and presented suitable data that could be standardized for the meta‐analysis. We found that the degree to which the soil was rewetted and the water filled pore space (WFPS) the soil was brought to were significant explanatory variables (p = < 0.0001). The larger the difference between the dry and wet states of the soil and the higher the WFPS of the soil after rewetting, the larger the hot moment, with an exponential increase once the soil is anaerobic. Substrate availability and fertiliser quantity and type were also important controls on the amount of N2O emitted during the hot moment (p = < 0.0001). However, controls with a constant WFPS can have the same anaerobicity and substrate concentrations, yet much lower emissions, so we suggest that it is the bioavailability of and how the substrates are utilized by the microbial community, and thus how they are primed by the drought, that is the main causal mechanism. Unfortunately, there is still a large uncertainty regarding how microbial population structure, relative gene abundances and gene expression profiles change according to antecedent dry/wet cycles. We suggest several areas of improvement for future studies and the development of drought‐impact curves. These would show the relationship between N2O emissions and the length of drought (we found no studies that have investigated this) and N2O emissions and the severity of drought (e.g. the difference between 20% and 40% WFPS).

Highlights

We investigated the main causal mechanisms of N2O hot moments after soil is rewetted.

This is the first meta‐analysis and synthesis of the literature regarding N2O hot moments.

The more anaerobic the soil and the more C and N substrates, the larger the hot moment.

We provide recommendations for future studies and outline key gaps in the research.
A field system for measuring plant and soil carbon fluxes using stable isotope methods
Authors: McCloskey Christopher S. , Otten Wilfred , Paterson Eric , Ingram Ben , Kirk Guy J. D.
Published: June 2020

There is a lack of field methods for measuring plant and soil processes controlling soil organic matter (SOM) turnover over diurnal, seasonal and longer timescales with which to develop datasets for modelling. We describe an automated field system for measuring plant and soil carbon fluxes over such timescales using stable isotope methods, and we assess its performance. The system comprises 24 large (1‐m deep, 0.8‐m diameter) cylindrical lysimeters connected to gas‐flux chambers and instruments. The lysimeters contain intact, naturally structured C3 soil planted with a C4 grass. Fluxes of CO2 and their 13C isotope composition are measured three times daily in each lysimeter, and the isotope composition is used to partition the fluxes between plant and soil sources. We investigate the following potential sources of error in the measurement system and show they do not significantly affect the measured CO2 fluxes or isotope signatures: gas leaks, the rate of gas flow through sampling loops, instrument precision and drift, the concentration dependence of isotope measurements, and the linearity of CO2 accumulation in the chambers and associated isotope fractionation resulting from different rates of 13CO2 and 12CO2 diffusion from the soil. For the loamy grassland soil and US prairie grass (Bouteloua dactyloides) tested, the precision of CO2 flux measurements was ±0.04% and that of the flux partitioning ±0.40%. We give examples of diurnal and seasonal patterns of plant and soil C fluxes and soil temperature and moisture. We discuss the limitations of the isotope methodology for partitioning fluxes as applied in our system. We conclude that the system is suitable for measuring net ecosystem respiration fluxes and their plant and soil components with sufficient precision to resolve diurnal and seasonal patterns.

Highlights

We describe an automated system for measuring plant and soil carbon fluxes under field conditions.

We exploit the large difference in isotope signatures between C3 and C4 soils and plants to partition the net flux.

Possible sources of error are quantified and shown to be small.

The system is capable of resolving diurnal and seasonal patterns.
Anatomy‐guided injections of botulinum neurotoxin in neck muscles: how accurate is needle placement?
Authors: Kreisler A. , Simonin C. , Degardin A. , Mutez E. , Defebvre L.
Published: June 2020

Background and purpose

In cervical dystonia, the accuracy of botulinum neurotoxin (BoNT) injections may influence the response to the treatment.

Methods

We used ultrasound to evaluate the accuracy of anatomy‐guided injections of BoNT in the neck muscles.

Results

A total of 56 consecutive patients and 332 injections were evaluated. The overall accuracy was 76.6%. The lowest accuracy (67.9%) was observed for the splenius capitis muscle.

Conclusions

Anatomic guidance of BoNT injections in the neck muscles is often inaccurate. Imaging guidance may improve the accuracy of BoNT injections in cervical dystonia.
Who seizes longest? Impact of clinical and demographic factors
Authors: Kaufmann Elisabeth , Seethaler Magdalena , Lauseker Michael , Fan Min , Vollmar Christian , Noachtar Soheyl , Rémi Jan
Published: June 2020

Objective

To investigate the impact of clinical and demographic parameters on the duration of focal onset seizures with and without secondary generalization using precise duration measurements from intracranial electroencephalographic (iEEG) recordings.

Methods

Patients with unifocal epilepsy syndromes and iEEG recording were retrospectively identified from the database of the local epilepsy center (2006‐2016). Seizure duration was defined as time difference of iEEG seizure pattern onset and cessation. The seizure semiology was classified based on video recordings. Clinical and demographic data were extracted from patient reports.

Results

In total, 69 adults were included, and 654 focal onset seizures were analyzed. Focal to bilateral tonic‐clonic seizures (FBTCSs; 98/654) were significantly longer than focal seizures (FSs) without generalization (FS‐BTCs; 556/654, P < .001), and most FSs (545/654, 83.3%) terminated within 2 minutes. The duration of FSs was prolonged with increasing age of the patients (P = .003) and was significantly shortened (P < .001) by evolution into an FBTCS. FBTCSs with lateralizing semiologies like version (P = .015) and sign of four (P = .043) were associated with longer bilateral tonic‐clonic manifestations. Furthermore, FBTCSs with preceding aura, frontal origin, or onset during sleep were by trend shorter. Age (P < .001) and disease duration (P = .028) were essential for prediction of FS‐BTC duration, whereas the vigilance state (P = .085) was the main prediction factor for the duration of FBTCSs.

Significance

The identified modifiers of seizure duration are of great relevance for clinical risk evaluation, especially in the aging epilepsy patient suffering from temporal lobe epilepsy with secondary generalized seizures.
Association of retinol binding protein4 (RBP4) and ghrelin plasma levels with insulin resistance and disease severity in non‐diabetic patients with hidradenitis suppurativa
Authors: González‐López Marcos A. , Ocejo‐Viñals J. Gonzalo , Mata Cristina , Vilanova Iosune , Guiral Sandra , Portilla Virginia , Blanco Ricardo , Hernández José L.
Published: June 2020

Hidradenitis suppurativa (HS) is a chronic inflammatory disease associated with insulin resistance (IR). Retinol binding protein 4 (RBP4) and ghrelin are two bioactive proteins that have been involved in glucose metabolism and IR, but also in the regulation of immune and inflammatory processes. The aim of this study was to determine the serum levels of RBP4 and ghrelin in patients with HS, and to assess the possible relationship between these levels and IR, disease severity and HS risk. A total of 137 subjects (77 HS patients and 60 controls) without diabetes mellitus were enrolled in this cross‐sectional study. Patients with HS had significantly higher RBP4 but lower ghrelin plasma levels than controls, independently of body mass index (BMI). Serum RBP4 levels were positively correlated to disease severity and IR in HS patients. However, we found no association between ghrelin levels and any clinical or laboratory parameters. Moreover, high serum RBP4 and low ghrelin levels were associated with an increased risk for HS. Our results suggest that high RBP4 levels may be a surrogate biomarker for IR in patients with HS. Moreover, increased RBP4 and decreased ghrelin levels could also be independent risk factors for the development of HS.
Cannabinoid hyperemesis syndrome in two French emergency departments: a prospective cohort
Authors: Weiss Julie , Torrents Romain , Verhamme Baptiste , Roch Antoine , Lazerges Pierre , Jego Maeva , Michelet Pierre , Simon Nicolas
Published: June 2020

Chronic cannabis use can be associated with uncontrollable vomiting and abdominal pain. Diagnostic criteria for cannabinoid hyperemesis syndrome (CHS) were defined in 2012 by Simonetto et al. The objectives of this study were to describe the prevalence of CHS, the patients' epidemiological characteristics, and to show the difficulties encountered in caring for these patients in emergency departments, the extent of health care and an unsuitable follow‐up in general practices. A prospective cohort of patients with CHS was recruited among a target population of patients leaving the adult emergency services of the Marseille hospitals Nord and La Timone between October 2017 and July 2018, with abdominal pain syndrome of unidentified etiology. Inclusion criteria for the CHS cohort were chronic cannabis use associated with nausea and vomiting. There were 48 patients included in the CHS cohort who took cannabis daily, in a target population of 2 848 patients (i.e. 1.6%). A hot shower was the most effective symptomatic treatment in 54.2% of cases. Patients suffering from CHS spent significantly more hours in emergency departments (11 vs. 6.5), and, on average, visits were more frequent (4.9 vs. 3). 20.3% of them were hospitalized to continue pain medication. Once out of hospital, follow‐up was limited, and weaning off cannabis, the only etiological treatment, was difficult to set up. Informing patients about CHS is essential, and a hot shower could be systematically proposed, thus limiting an unnecessary extent of health care. CHS is genuine, medical staff should be made aware of it in occupational training, and it should be seriously considered in health policies.
Fentanyl inhibits acute myeloid leukemia differentiated cells and committed progenitors via opioid receptor‐independent suppression of Ras and STAT5 pathways
Authors: Dai Shuangbo , Zhang Xiaoqing , Zhang Peng , Zheng Xuesong , Pang Qiying
Published: June 2020

Fentanyl is a common sedative/analgesic used for intrathecal chemotherapy injection in children with acute leukemia. Given the contradictory findings that fentanyl has both inhibitory and stimulatory activities in cancer cells, we investigated the biological effects of fentanyl alone and its combination with standard of care in acute myeloid leukemia (AML) cells at all stages of development. We showed that fentanyl at clinically relevant concentration inhibited growth and colony formation of AML differentiated cells and committed progenitors without affecting their survival. Compared to AML cells without FLT3 mutation, cells harboring FLT3‐ITD mutation are likely to be more sensitive to fentanyl. However, fentanyl did not affect the most primitive AML stem cells. Fentanyl significantly augmented the efficacy of cytarabine but not midostaurin in AML differentiated cells and committed progenitors. We further demonstrated that fentanyl inhibited AML cells via suppressing Ras/Raf/MEK/ERK and STAT5 pathway, and this was not dependent on opioid receptor system. Our findings demonstrate the anti‐leukemia activity of fentanyl and synergistic effects between fentanyl and cytarabine in AML, via opioid receptor‐independent suppression of Ras and STAT5 pathways. Our work is the first to suggest the beneficial effects of fentanyl in children with leukemia.
Immunomodulation via macrophages to fight solid tumor malignancies
Authors: Dandia Hiren , Tayalia Prakriti
Published: June 2020

The paper ‘A C‐Terminal Fragment of Adhesion Protein Fibulin‐7 Inhibits Growth of Murine Breast Tumor by Regulating Macrophage Reprogramming’ by Chakraborty et al. highlights that Fbln7‐C could be explored as a potential immunomodulatory agent against various solid cancers and have shown its abilities to regulate tumor microenvironment reprogramming of TAMs in a breast cancer model. Fbln7, which is a secreted glycoprotein, has been shown to be anti‐angiogenic and has an immunomodulatory role regulating various functional properties of monocytes, macrophages, and neutrophils, thereby influencing inflammation. In this study, the authors have shown that in a murine breast tumor model, intravenous administration of Fbln7‐C significantly reduces the size of tumors via macrophage reprogramming.

Comment on: https://doi.org/10.1111/febs.15333.
Pantropical geography of lightning‐caused disturbance and its implications for tropical forests
Authors: Gora Evan M. , Burchfield Jeffrey C. , Muller‐Landau Helene C. , Bitzer Phillip M. , Yanoviak Stephen P.
Published: June 2020

Lightning is a major agent of disturbance, but its ecological effects in the tropics are unquantified. Here we used ground and satellite sensors to quantify the geography of lightning strikes in terrestrial tropical ecosystems, and to evaluate whether spatial variation in lightning frequency is associated with variation in tropical forest structure and dynamics. Between 2013 and 2018, tropical terrestrial ecosystems received an average of 100.4 million lightning strikes per year, and the frequency of strikes was spatially autocorrelated at local‐to‐continental scales. Lightning strikes were more frequent in forests, savannas, and urban areas than in grasslands, shrublands, and croplands. Higher lightning frequency was positively associated with woody biomass turnover and negatively associated with aboveground biomass and the density of large trees (trees/ha) in forests across Africa, Asia, and the Americas. Extrapolating from the only tropical forest study that comprehensively assessed tree damage and mortality from lightning strikes, we estimate that lightning directly damages c. 832 million trees in tropical forests annually, of which c. 194 million die. The similarly high lightning frequency in tropical savannas suggests that lightning also influences savanna tree mortality rates and ecosystem processes. These patterns indicate that lightning‐caused disturbance plays a major and largely unappreciated role in pantropical ecosystem dynamics and global carbon cycling.