bluuebunny/crossref_metadata_2025 huggingface dataset:
Lactate predicts the 28‐day survival rate in patients with septic shock treated with the combination of PMX‐DHP and rTM
Authors: Yamato Masafumi , Asahina Yuta , Koizumi Shintaro , Shigeki Takatomo , Yajima Ayako , Kimura Yoshiki , Iwatani Hirotsugu
Published: June 2020

We have previously reported that combination therapy with polymyxin‐B direct hemoperfusion (PMX‐DHP) and recombinant thrombomodulin (rTM) is effective in patients with septic shock accompanied by disseminated intravascular coagulation (DIC). Two previous studies reporting the favorable effect of early initiation of PMX‐DHP for septic shock did not focus on the combination therapy of PMX‐DHP and rTM. This retrospective study included 47 consecutive patients who underwent the combination therapy of PMX‐DHP and rTM for septic shock with DIC from August 2011 to August 2016. Main exposure was early or late initiation of PMX‐DHP. PMX‐DHP initiated within 12 hours after catecholamine administration was designated as early group (N = 25) and later than 12 hours as late group (N = 22). Main outcome was 28‐day survival rate. The patient characteristics were age median 73 (IQR 68‐78) years, 26 men (55%), APACHE II score 32.7 ± 7.7 and lactate 26.0 (18.0‐41.0) mg/dL. The 28‐day survival rate after PMX‐DHP initiation was 76.6% and was not significantly different in the two groups. In the early group, APACHE II score was lower (P = .02), and lactate was higher (P = .005) than in the late group. Lactate was the only predictor of 28‐day mortality [odds ratio (95%CI) per 1 mg/dL, 1.08 (1.03‐1.19); P = .037] in multivariate logistic regression analysis adjusted with age, sex, APACHE II score, lactate and timing of PMX‐DHP initiation. Late PMX‐DHP initiation did not lead to statistically worse 28‐day survival rate in this combination therapy. The combination therapy of PMX‐DHP and rTM may improve the therapeutic effect of PMX‐DHP and modify the effect of early PMX‐DHP on the prognosis. Lactate may be an appropriate indicator rather than time after catecholamine administration if we discuss when to start PMX‐DHP in this combination therapy.
Cross‐culture adaptation and validation of English version of Rheumatoid Arthritis Knowledge Assessment Scale (RAKAS) in patients with rheumatoid arthritis
Authors: Naqvi Atta Abbas , Hassali Mohamed Azmi , Iffat Wajiha , Shakeel Sadia , Zia Madiha , Fatima Mustajab , Iqbal Muhammad Shahid , Iqbal Muhammad Zahid , Imam Mohammad Tarique , Hossain Mohammad Akbar , Ali Majid , Haseeb Abdul
Published: June 2020

Aim

To carry out cross‐culture adaptation and validation of the English version of Rheumatoid Arthritis Knowledge Assessment Scale (RAKAS) in patients with rheumatoid arthritis (RA).

Methods

A cross‐sectional study was conducted for 2 months in 2 tertiary care hospitals in Karachi, Pakistan. Sample size was calculated based on item‐subject ratio. The translation was carried out using standard procedures for translation and cross‐culture adaptation. The validation process included estimation of discrimination power, item difficulty index, factorial, convergent, construct and known group validities and reliability. Reliability of the scale was estimated using Kuder‐Richardson Formula 20 and a value of σ2 ≥ 0.6 was acceptable. SPSS v23, Remark Classic OMR v6 software and MedCalc Statistical Software v16.4.3, were used to analyze the data. The study was approved by the relevant ethics committee (IRB#NOV:15).

Results

The mean score was 7.68 ± 2.52 (95% CI: 7.31‐8.05) for 177 patients. The σ2 = 0.601, that is, >0.6, test‐retest reliability ρ = .753, P < .05. The average discrimination power = 47.27, average Item Difficulty Index = 0.557. The fit indices were acceptable in a range that established its factorial validity and average factor loading was ≥0.7 which established convergent validity. A significant association (χ2 = 33.074, P < .01) between score interpretation and previous counseling by pharmacists established its construct validity. A significant association (χ2 = 19.113, P < .05) between score interpretation and patient occupation established known group validity.

Conclusion

The English version of RAKAS was deemed a reliable and validated tool to measure knowledge about disease in Pakistani patients with RA.
Combination effects of ellagic acid with erlotinib in a Ba/F3 cell line expressing EGFR H773_V774 insH mutation
Authors: Xie Chuanqi , Kong Jindong , Miao Fujun , Wang Xuanjun , Sheng Jun
Published: June 2020

Background

Epidermal growth factor receptor H773_V774 insH (EGFR‐insH) is an EGFR exon 20 insertion mutation in non‐small cell lung cancer (NSCLC), which is naturally resistant to available EGFR tyrosine kinase inhibitors (TKIs) and lacks a patient‐derived cell line.

Methods

A Ba/F3 cell line expressing EGFR‐insH mutation (Ba/F3‐insH cell line) was generated using an IL3‐deprivation method. A cell proliferation assay was performed to screen natural compounds that exhibit a synergistic effect with erlotinib. Trypan blue staining was used to assess cell growth and crystal violate staining was recruited to evaluate clonogenic potential. Flow cytometry was used to detect EGFR expression and cell apoptosis. A xenograft model was created to evaluate the effect of ellagic acid (EA) with erlotinib on tumor growth.

Results

EA was identified to synergistically inhibit the proliferation of Ba/F3‐insH cells with erlotinib. The growth and clonogenic potential of Ba/F3‐insH cells were definitely constrained by EA with erlotinib, whereas, the apoptosis of Ba/F3‐insH cells was dramatically promoted by the combination. In a xenograft model of the Ba/F3‐insH cell line, the combination treatment also exhibited a synergistic reduction in tumor growth.

Conclusions

In this study, we generated a Ba/F3 cell line expressing EGFR H773_V774 insH mutation and identified a synergistic treatment (EA with erlotinib) that markedly inhibited the viability of Ba/F3‐insH cells in vitro and in vivo.

Key points

Our results indicated that the combination of ellagic acid with erlotinib has synergistic effects against EGFR H773_V774 insH mutation.
Cannabinoid 1 Receptor Antagonists Play a Neuroprotective Role in Chronic Alcoholic Hippocampal Injury Related to Pyroptosis Pathway
Authors: Zhang Dingang , Liu Xiaochen , Dong Xiaoru , Zhu Rongzhe , Jiang Jieqing , Ye Yonghong , Jiang Yan
Published: June 2020

Background

Alcohol use disorders affect millions of people worldwide, and there is growing evidence that excessive alcohol intake causes severe damage to the brain of both humans and animals. Numerous studies on chronic alcohol exposure in animal models have identified that many functional impairments are associated with the hippocampus, which is a structure exhibiting substantial vulnerability to alcohol exposure. However, the precise mechanisms that lead to structural and functional impairments of the hippocampus are poorly understood. Herein, we report a novel cell death type, namely pyroptosis, which accounts for alcohol neurotoxicity in mice.

Methods

For this study, we used an in vivo model to induce alcohol‐related neurotoxicity in the hippocampus. Adult male C57BL/6 mice were treated with 95% alcohol vapor either alone or in combination with selective cannabinoid receptor antagonists or agonists, and VX765 (Belnacasan), which is a selective caspase‐1 inhibitor.

Results

Alcohol‐induced in vivo pyroptosis occurs because of an increase in the levels of pyroptotic proteins such as nucleotide‐binding domain (NOD)–like receptor protein 3 (NLRP3), caspase‐1, gasdermin D (GSDMD), and amplified inflammatory response. Our results indicated that VX765 suppressed the expression of caspase‐1 and inhibited the maturation of the proinflammatory cytokines interleukin‐1β (IL‐1β) and IL‐18. Additionally, chronic alcohol intake created an imbalance in the endocannabinoid system and regulated 2 cannabinoid receptors (CB1R and CB2R) in the hippocampus. Specific antagonists of CB1R (AM251 and AM281) significantly ameliorated alcohol‐induced pyroptosis signaling and inactivated the inflammatory response.

Conclusions

Alcohol induces hippocampal pyroptosis, which leads to neurotoxicity, thereby indicating that pyroptosis may be an essential pathway involved in chronic alcohol–induced hippocampal neurotoxicity. Furthermore, cannabinoid receptors are regulated during this process, which suggests promising therapeutic strategies against alcohol‐induced neurotoxicity through pharmacologic inhibition of CB1R.
Genetic and phenotypic consequences of early domestication in black soldier flies (Hermetia illucens)
Authors: Rhode C. , Badenhorst R. , Hull K. L. , Greenwood M. P. , Bester‐van der Merwe A. E. , Andere A. A. , Picard C. J. , Richards C.
Published: June 2020

The black soldier fly, Hermetia illucens, is an emerging biotechnological agent with its larvae being effective converters of organic waste into usable bio‐products including protein and lipids. To date, most operations use unimproved commercial populations produced by mass rearing, without cognisance of specific breeding strategies. The genetic and phenotypic consequences of these commercial practices remain unknown and could have a significant impact on long‐term population viability and productivity. The aim of this study was thus to assess the genetic and phenotypic changes during the early phases of colony establishment and domestication in the black soldier fly. An experimental colony was established from wild founder flies and a new microsatellite marker panel was developed to assess population genetic parameters along with the phenotypic characteristics of each generational cohort under captive breeding. The experimental colony was characterised by a small effective population size, subsequent loss of genetic diversity and rapid genetic and phenotypic differentiation between the generational cohorts. Ultimately, the population collapsed by the fifth generation, most likely owing to the adverse effect of inbreeding depression following the fixation of deleterious alleles. Species with r‐selected life history characteristics (e.g. short life‐span, high fecundity and low larval survival) are known to pose particular challenges for genetic management. The current study suggests that sufficient genetic and phenotypic variations exist in the wild population and that domestication and strain development could be achieved with careful population augmentation and selection during the early stages of colony establishment.
Exosomal miR‐21/Let‐7a ratio distinguishes non‐small cell lung cancer from benign pulmonary diseases
Authors: Yang Guofeng , Wang Tao , Qu Xiangyun , Chen Shuchen , Han Ziyang , Chen Sui , Chen Mingduan , Lin Jihong , Yu Shaobin , Gao Lei , Peng Kaiming , Kang Mingqiang
Published: June 2020

Aim

To assess the exosomal miR‐21/Let‐7a ratio, a noninvasive method, in distinguishing non‐small cell lung cancer (NSCLC) from benign pulmonary diseases.

Methods

The exosomes were extracted from the peripheral blood serum using serum exosomal extraction kit. miR‐21 and Let‐7a levels were evaluated by quantitative reverse transcription polymerase chain reaction.

Results

We found that miR‐21/Let‐7a ratio of NSCLC patients was significantly higher than that of healthy people, patients with pulmonary inflammation diseases, and benign pulmonary nodules, respectively. Receiver‐operating characteristic analysis revealed that as compared with healthy controls, miR‐21/Let‐7a produced the area under the curve (AUC) at 0.8029 in patients with NSCLC, which helped to distinguish NSCLC from healthy controls with 81.33% sensitivity and 69.57% specificity. In addition, the AUC of miR‐21/Let‐7a in NSCLC patients was 0.8196 in comparison to patients with pulmonary inflammation diseases. Meanwhile, the sensitivity and specificity were 56.00% and 100%, respectively. Furthermore, compared with patients with benign pulmonary nodules, the AUC of miR‐21/Let‐7a in NSCLC patients was 0.7539. The sensitivity and specificity were 56.00% and 82.61%, respectively.

Conclusion

In the present study, our findings revealed that exosomal miR‐21/Let‐7a ratio holds considerable promise as a noninvasive biomarker for the diagnosis of NSCLC from benign pulmonary diseases.
Targeting the NO‐cGMP‐PDE5 pathway in COVID‐19 infection. The DEDALO project
Authors: Isidori Andrea M. , Giannetta Elisa , Pofi Riccardo , Venneri Mary A. , Gianfrilli Daniele , Campolo Federica , Mastroianni Claudio M. , Lenzi Andrea , d’Ettorre Gabriella
Published: June 2020

Background

A pandemic outbreak of COVID‐19 has been sweeping the world since December. It begins as a respiratory infection that, mainly in men with diabetes or renal impairment, evolves into a systemic disease, with SARDS, progressive endothelial cell damage, abnormal clotting and impaired cardiovascular and liver function. Some clinical trials are testing biological drugs to limit the immune system dysregulation, “cytokines storm,” that causes the systemic complications of COVID‐19. The contraindications of these drugs and their cost raise concerns over the implications of their widespread availability.

Objectives

Numerous clinical and experimental studies have revealed a role for the nitric oxide (NO)‐cyclic GMP‐phosphodiesterase type 5 (PDE5) pathway in modulating low‐grade inflammation in patients with metabolic diseases, offering cardiovascular protection. PDE5 inhibition favors an anti‐inflammatory response by modulating activated T cells, reducing cytokine release, lowering fibrosis, increasing oxygen diffusion, stimulating vascular repair. PDE5 is highly expressed in the lungs, where its inhibition improves pulmonary fibrosis, a complication of severe COVID‐19 disease.

Materials and methods

We performed a systematic review of all evidence documenting any involvement of the NO‐cGMP‐PDE5 axis in the pathophysiology of COVID‐19, presenting the ongoing clinical trials aimed at modulating this axis, including our own “silDEnafil administration in DiAbetic and dysmetaboLic patients with COVID‐19 (DEDALO trial).”

Results

The reviewed evidence suggests that PDE5 inhibitors could offer a new strategy in managing COVID‐19 by (i) counteracting the Ang‐II‐mediated downregulation of AT‐1 receptor; (ii) acting on monocyte switching, thus reducing pro‐inflammatory cytokines, interstitial infiltration and the vessel damage responsible for alveolar hemorrhage‐necrosis; (iii) inhibiting the transition of endothelial and smooth muscle cells to mesenchymal cells in the pulmonary artery, preventing clotting and thrombotic complications.

Discussion and Conclusion

If the ongoing trials presented herein should provide positive findings, the low cost, wide availability and temperature stability of PDE5 inhibitors could make them a major resource to combat COVID‐19 in developing countries.
Maternal arterial blood gas values during delivery: Effect of mode of delivery, maternal characteristics, obstetric interventions and correlation to fetal umbilical cord blood
Authors: Zaigham Mehreen , Helfer Sara , Kristensen Karl Heby , Isberg Per‐Erik , Wiberg Nana
Published: June 2020

Introduction

Obstetricians routinely use biochemical parameters from non‐pregnant women to assess the condition of the laboring mother. However, it is well known that pregnancy leads to significant physiological changes in most organ systems. The aim of this study was to determine normal values for maternal arterial blood gases during vaginal deliveries as compared with control values from planned cesarean sections. We also wanted to elucidate the effect of various maternal characteristics, mode of delivery and obstetric interventions on blood gas values.

Material and methods

We carried out a randomly selected, prospective‐observational cohort study of 250 women undergoing vaginal delivery and 58 women undergoing planned cesarean section at the Department of Obstetrics and Gynecology, Skåne University Hospital, Malmö, Sweden.

Results

We found significant differences for gestational age, parity, umbilical venous blood pH, pCO2 and lactate values between the two study groups (P < .005). Significantly lower pH, pCO2, pO2 and sO2 were found in mothers delivering vaginally. Higher base deficit, hemoglobin, bilirubin, potassium, glucose and lactate were found in vaginal deliveries than in planned cesarean sections (P < .02). Maternal body mass index (BMI), smoking and hypertension were not significantly correlated to acid base parameters in women with vaginal deliveries. On the other hand, multiple regression showed significant associations for the use of epidural anesthesia on maternal pH (P < .05) and pO2 (P < .01); and synthetic oxytocin on pCO2 (P = .08), glucose (P < .00) and lactate (P < .02) levels in maternal arterial blood. Maternal arterial pH, pCO2 and lactate values correlated significantly to values in venous umbilical cord blood (P < .000).

Conclusions

Maternal arterial blood gas parameters varied significantly according to mode of delivery, the use of epidural anesthesia and synthetic oxytocin.
Review article: bugs, inflammation and mood—a microbiota‐based approach to psychiatric symptoms in inflammatory bowel diseases
Authors: Thomann Anne K. , Mak Joyce W. Y. , Zhang Jing Wan , Wuestenberg Torsten , Ebert Matthias P. , Sung Joseph J. Y. , Bernstein Çharles N. , Reindl Wolfgang , Ng Siew C.
Published: June 2020

Background

Psychiatric co‐morbidities including depression and anxiety are common in inflammatory bowel diseases (IBD). Emerging evidence suggests that interactions between the gut microbiota and brain may play a role in the pathogenesis of psychiatric symptoms in IBD.

Aim

To review the literature on microbiota‐brain‐gut interactions in gut inflammation, psychosocial stress and mental disorders and to discuss the putative mediating role of gut microbiota in the development of psychiatric symptoms or co‐morbidities in IBD.

Methods

A literature search was conducted on Ovid and Pubmed to select relevant animal and human studies reporting an association between IBD, mental disorders and gut microbiota.

Results

Gut microbial alterations are frequently reported in subjects with IBD and with mental disorders. Both have been associated with reduced faecal bacterial diversity, decreased taxa within the phylum Firmicutes and increased Gammaproteobacteria. In animal studies, microbial perturbations induce behavioural changes and modulate inflammation in mice. Anxiety‐ and depression‐like behaviours in animals can be transferred via faecal microbiota. In humans, modulation of the gut microbiota with probiotics is associated with behavioural and mood changes. Recent data show correlations in changes of faecal and mucosal microbiota and psychological distress in patients with IBD independent of disease activity.

Conclusion

Both IBD and mental disorders are associated with gut microbial alterations. Preclinical and preliminary human studies have shown a mediating role of the gut microbiota in intestinal inflammation and anxiety, depression and stress. Targeting the gut microbiota may represent a useful therapeutic approach for the treatment of psychiatric co‐morbidities in IBD.
Migration, urbanisation and emergence of the individual: Same‐sex desiring migrant men constructing spaces and cultivating their self in a big Chinese city
Authors: Miège Pierre
Published: June 2020

The emergence of the individual is one of the most profound and significant evolutions of Chinese society that has accompanied economic reforms since the late 1970s. Existing research frequently uses a dual concept of ‘individualist’ versus ‘collectivist’ societies to approach the lives of urban Chinese. In the case of same‐sex attracted persons, as they often hide their sexual orientation in most of their social life and must respect social norms of filial piety and marriage, it is easy to conclude that today's urban China continues to be primarily a ‘collectivist’ society where the individual remains fragile. Using a long‐term ethnography of same‐sex attracted migrant men who gather in a public park to create a community of friends and invent some shared cultural and social traits, this paper proposes to deepen the analysis by borrowing the distinction between three different attitudes towards individualism developed by Michel Foucault. It will argue that these men actively construct specific spaces where they can live a private life, as well as experiment and explore their self. Therefore, these men display a more complex articulation between some aspects of a ‘collectivist’ ethos and the strengthening of individual traits.
The Comprehension Boost in Early Word Learning: Older Infants Are Better Learners
Authors: Bergelson Elika
Published: June 2020

Recent research has revealed that infants begin understanding words at around 6 months. After that, infants’ comprehension vocabulary increases gradually in a linear way over 8–18 months, according to data from parental checklists. In contrast, infants’ word comprehension improves robustly, qualitatively, and in a nonlinear way just after their first birthday, according to data from studies on spoken word comprehension. In this review, I integrate observational and experimental data to explain these divergent results. I argue that infants’ comprehension boost is not well‐explained by changes in their language input for common words, but rather by proposing that they learn to take better advantage of relatively stable input data. Next, I propose potentially complementary theoretical accounts of what makes older infants better learners. Finally, I suggest how the research community can expand our empirical base in this understudied area, and why doing so will inform our knowledge about child development.
Investor protection and cost of debt: Evidence from dividend commitment in firm bylaws
Authors: Yang Dan , Cheng Linyin , Wang Guojun , Wang Yuetang , Zhang Lu
Published: June 2020

Research Question/Issue

This study seeks to explore a new type of investor protection mechanism—dividend commitment in firm bylaws—that has emerged from a new Chinese dividend regulation. Dividend commitment, forcing firms to make an explicit commitment to maintain a given dividend level, may affect the benefit and risk of debtholders and, accordingly, their required returns.

Research Findings/Insights

Using a sample of Chinese listed firms between 2006 and 2017, we find a significantly lower cost of debt for high‐commitment firms than for low‐commitment firms. The differences are pronounced for firms that actively respond to the regulation, those that operate in a weaker information environment, those that suffer from higher agency costs due to insider control, and those with lower debt ratios.

Theoretical/Academic Implications

This study provides empirical evidence of the economic consequences of dividend commitment. The results suggest that dividend commitment is associated with changes in the benefits and risks of debtholders and that such an association is conditional on firm‐level factors; thus, the findings contribute to investor protection theory.

Practitioner/Policy Implications

This study provides insights to policy makers interested in evaluating investor protection in an emerging economy. The results highlight the financial implications of an innovative investor protection mechanism.
Impact of a multidisciplinary multimodal opioid minimization initiative in kidney transplant recipients
Authors: Rohan Vinayak S. , Taber David J. , Patel Neha , Perez Caroline , Pilch Nicole , Parks Sara , Bolin Eric , Nadig Satish N. , Baliga Prabhakar K. , Fleming James N.
Published: June 2020

Opioid use after kidney transplant has been shown to be a risk factor for chronic opioid use, which leads to an increased risk of mortality. The purpose of this study was to evaluate the early impact of a multimodal pain regimen and education quality improvement program on opioid use after kidney transplant 2 months after implementation. This was a retrospective, single‐center analysis of post‐operative opioid use, comparing the average daily Morphine milligram equivalents (MME) of the patients who received education on opioids and a multimodal pain regimen (preoperative TAP/QL block, scheduled APAP and gabapentin) compared to a historical control group. Despite having no differences in pre‐transplant opioid exposure, daily and overall inpatient opioid utilization was significantly reduced in the multimodal pain protocol cohort (38.6 vs 8.0 MME/day; P < .001); 5% of patients in the multimodal pain protocol cohort were discharged with an opioid prescription, compared to 96% of controls (P < .001). Our early results demonstrate that a multimodal pain protocol can effectively and dramatically reduce short‐term opioid utilization in kidney transplant recipients.
Role of hematopoietic cell transplantation in relapsed acute promyelocytic leukemia
Authors: Hashmi Hamza , Nishihori Taiga
Published: June 2020

The use of all trans‐retinoic acid and arsenic trioxide combination as the induction regimen for acute promyelocytic leukemia (APL) has revolutionized the management and outcomes of this disease. Modern risk‐adapted frontline therapy has provided excellent therapeutic results. However, significant numbers of APL patients relapse after frontline therapy, and the optimal management strategy for relapsed APL, specifically the role and type of hematopoietic cell transplantation (HCT) are still to be defined. Both autologous and allogeneic HCTs are associated with durable remission and prolonged survival when utilized in appropriate disease settings. Once remission has been achieved, consolidation with autologous HCT for APL patients with negative minimal residual disease (MRD) status, and with allogeneic HCT for APL patients with positive MRD status appear to offer the best long‐term outcomes. In this article, we provide a comprehensive review of existing literature on the efficacy of HCT in treatment of relapse/refractory APL and we discuss the appropriate use of this modality.
Hematopoietic cell transplantation for Diamond Blackfan anemia: A report from the Pediatric Group of the Brazilian Bone Marrow Transplantation Society
Authors: Darrigo Luiz Guilherme , Loth Gisele , Kuwahara Cilmara , Vieira Ana , Colturato Vergilio , Rodrigues Ana Luiza , Arcuri Leonardo , Fernandes Juliana , Macedo Antonio , Tavares Rita , Gomes Alessandra , Ribeiro Lisandro , Seber Adriana , Zecchin Victor , de Souza Mair , Calixto Rodolfo , Pasquini Ricardo , Flowers Mary , Rocha Vanderson , Bonfim Carmem
Published: June 2020

Objectives

The aim of this study was to analyze the outcomes of children with Diamond‐Blackfan anemia (DBA) treated in Brazil with hematopoietic cell transplantation (HCT).

Methods

We performed a retrospective analysis of 44 pediatrics patients transplanted between 1990 and 2018. The median age of patients was 5 years, and 57% were male. Twenty‐five received their first HCT from an HLA‐matched sibling donor (MSD), 12 from a HLA matched unrelated bone marrow donor (MUD 10/10, n = 12) and 7 other HLA mismatched donors (MMD).

Results

After a median follow‐up of 4 years, estimate 5‐year overall survival (OS) for the entire cohort was 70%, 80% for MSD group, 73% for MUD, and 29% for MMD. Thirty‐eight out of the 44 evaluable patients engrafted successfully. Primary and secondary graft failure was observed in five and three patients, respectively. Rates of grade II‐IV and III‐IV acute graft‐versus‐host disease (aGVHD) were 25% and 18%, respectively. Nine patients developed chronic GVHD (cGVHD).

Conclusion

Overall survival rates observed after HLA matched donors transplant for DBA were comparable to those reported from higher‐income countries and international registries.
Livedo racemosa in neurological diseases: an update on the differential diagnoses
Authors: Mitri F. , Enk A. , Bersano A. , Kraemer M.
Published: June 2020

Livedo is a net‐like violaceous skin pattern. It can be classified as physiological or pathological. The physiological livedo reticularis usually appears in cold conditions, whereas the pathological and irregular livedo, which persists in warm temperatures, is often labeled as ‘livedo racemosa’. Some neurological pathologies are associated with livedo, most commonly those with an inflammatory component or those derived from systemic disorders. The present review summarizes the most important central and peripheral neurological diseases in pediatric and adult age groups associated with livedo, providing physicians with an overview of the clinical presentation, etiology, diagnosis and management of these conditions.
Lower bioenergetic costs but similar immune responsiveness under a heat wave in urban compared to rural damselflies
Authors: Tüzün Nedim , Stoks Robby
Published: June 2020

There is mounting evidence that the widespread phenotypic changes in response to urbanization may reflect adaptations caused by rapid evolutionary processes driven by urban‐related stressors. Compared to increased habitat fragmentation and pollution, adaptations towards another typical urban‐related stressor, that is higher and longer lasting very high temperatures (heat waves), are much less studied. Notably, the sensitivities to heat waves of life‐history traits and important fitness‐related physiological traits such as immune responsiveness and bioenergetic variables (energy availability, energy consumption and their balance) have never been contrasted between urban and rural populations. By conducting a laboratory common‐garden experiment, we compared effects of a simulated heat wave on life history (survival and growth rate), immune responsiveness and bioenergetic variables between three urban and three rural populations of the damselfly Coenagrion puella. Because energy‐mediated trade‐off patterns may only be detected under energetically costly manipulations, all larvae were immune‐challenged by simulating ectoparasitism by water mites. As expected, the simulated heat wave caused negative effects on nearly all response variables. The immune responsiveness, on the other hand, increased under the heat wave, consistent with a trade‐off pattern between immune function and growth, and this similarly between urban and rural populations. A key finding was that urban larvae suffered less from the simulated heat wave compared to the rural larvae in terms of a lower heat wave‐induced depletion in energy availability. This suggests an adaptation of urban populations to better cope with the stronger and more frequent heat waves in cities. Notably, this urbanization‐driven evolution in the bioenergetic variables was not apparent in the absence of a heat wave. Given that changes in energy budgets have strong fitness consequences, our findings suggest that the evolved higher ability to cope with heat waves is fundamental for the survival of urban damselfly populations.
Detection of hypoglycin A and MCPA‐carnitine in equine serum and muscle tissue: Optimisation and validation of a LC‐MS–based method without derivatisation
Authors: González‐Medina Sonia , Hyde Carolyne , Lovera Imogen , Piercy Richard J.
Published: June 2020

Background

Measurement of hypoglycin A (HGA) and its toxic metabolite, methylenecyclopropylacetic acid (MCPA), in equine serum confirms a diagnosis of atypical myopathy (AM), a pasture‐associated toxic rhabdomyolysis with high mortality linked to the ingestion of Acer trees plant material. Supportive diagnostic tests include plasma acyl‐carnitine profiling and urine organic acid testing, but these are not specific for AM. Previously reported HGA and MCPA analytical techniques used liquid chromatography–mass spectrometry (LC‐MS) with a derivatising step, but the latter prolongs testing and increases costs.

Objectives

To develop a rapid LCMS method for detection of serum and tissue HGA and MCPA that enables expedited diagnosis for horses with AM.

Study design

Analytical test validation.

Methods

Validation parameters to industry standards using as criteria precision, accuracy, linearity, reproducibility and stability in analyte‐spiked samples were calculated on 9‐calibration points and 3 different validation concentrations in both serum and muscle tissue.

Results

The test was successfully validated for the detection of HGA and MCPA‐carnitine in equine serum and muscle. Test linearity was excellent (r2 = .999), accuracy was very good for both analytes (93%‐108%), precision did not exceed 10% coefficient of variation and reproducibility met the requirements of the Horwitz equation. Stability was unaffected by storage at a range of temperatures.

Main limitations

The spectrum of the tested analytes was limited to only two relevant analytes in favour of a quick and easy analysis. Linearity of the muscle method was not evaluated as calibration curves were not produced in this matrix.

Conclusion

We report an optimised, simplified and validated method for detection of HGA and MCPA‐carnitine in equine serum and muscle suitable for rapid diagnosis of suspected AM cases. The serum‐based test should also enable risk assessment of toxin exposure in cograzing horses and assessment of horses with undiagnosed myopathies, while the tissue detection test should help to confirm cases post‐mortem and to determine toxin distribution, metabolism and clearance across different tissues.
Localisation of cannabinoid and cannabinoid‐related receptors in the equine dorsal root ganglia
Authors: Chiocchetti Roberto , Rinnovati Riccardo , Tagliavia Claudio , Stanzani Agnese , Galiazzo Giorgia , Giancola Fiorella , Silva Margherita De , Capodanno Ylenia , Spadari Alessandro
Published: June 2020

Background

Growing evidence recognises cannabinoid receptors as potential therapeutic targets for pain. Consequently, there is increasing interest in developing cannabinoid receptor agonists for treating pain. As a general rule, to better understand the actions of a drug, it would be of extreme importance to know the cellular distribution of its specific receptors. The localisation of cannabinoid receptors in the dorsal root ganglia of the horse has not yet been investigated.

Objectives

To localise the cellular distribution of canonical and putative cannabinoid receptors in the equine cervical dorsal root ganglia.

Study design

Qualitative and quantitative immunohistochemical study.

Methods

Cervical (C6‐C8) dorsal root ganglia were collected from six horses (1.5 years of age) at the slaughterhouse. The tissues were fixed and processed to obtain cryosections which were used to investigate the immunoreactivity of canonical cannabinoid receptors 1 (CB1R) and 2 (CB2R), and for three putative cannabinoid‐related receptors: nuclear peroxisome proliferator‐activated receptor alpha (PPARα), transient receptor potential ankyrin 1 (TRPA1) and serotonin 5‐HT1a receptor (5‐HT1aR).

Results

The neurons showed immunoreactivity for CB1R (100%), CB2R (80% ± 13%), PPARα (100%), TRPA1 (74% ± 10%) and 5‐HT1aR (84% ± 6%). The neuronal satellite glial cells showed immunoreactivity for CB2R, PPARα, TRPA1 and 5‐HT1aR.

Main limitations

The low number of horses included in the study.

Conclusions

This study highlighted the expression of cannabinoid receptors in the sensory neurons and glial cells of the dorsal root ganglia. These findings could be of particular relevance for future functional studies assessing the effects of cannabinoids in horses to manage pain.
Post‐operative pain behaviour associated with surgical castration in donkeys (Equus asinus)
Authors: de Oliveira Maria Gláucia Carlos , Luna Stelio P. L. , Nunes Talyta Lins , Firmino Paulo R. , de Lima Amara Gyane A. , Ferreira Josiel , Trindade Pedro H. E. , Júnior Raimundo A. B. , de Paula Valéria Veras
Published: June 2020

Background

Recognising pain in donkeys is challenging because they are stoic.

Objectives

To identify the responses of donkeys before and after surgical pain.

Study design

Prospective, short‐term longitudinal pre‐ and post‐intervention observations.

Methods

Forty adult donkeys underwent surgical castration after sedation with intravenous (IV) xylazine, induction with guaiphenesin/thiopental IV and maintenance of anaesthesia with isoflurane and local anaesthetic blockade. Four hours after recovery from anaesthesia, flunixin meglumine 1.1 mg/kg, dipyrone 10 mg/kg and morphine 0.2 mg/kg IV were administered. Behavioural responses exhibited by the animals housed in individual stalls were recorded in four 30‐min videos: before castration (M0), and 3.5‐4.0 hours (M1), 5.5‐6.0 hours (M2) and 23.5‐24.0 hours after recovery from anaesthesia (M3). To exclude the influence of insects, the behaviour of six apparently pain‐free donkeys was compared with and without the presence of faeces and urine in the stall.

Results

When compared with presurgical baseline behaviours (M0), after surgery (M1) donkeys raised their pelvic limbs more (P = .003). When compared with M1, after analgesia (M2), the median frequencies of ear movements (44 vs 16; P < .001), head shaking (7 vs 1; P < .001), head turning (5 vs 0; P < .001) and lifting of the both limbs (7 vs 0; P = .008) decreased; feeding (0 vs 29; P < .001) and water intake (0 vs 0, range 0‐1 vs 0‐7; P = .05) increased. The dirty stall increased tail (53 vs 80; P = .03), head (16 vs 30; P = .03) and ear movements (50 vs 78; P = .04).

Main limitations

The dirty stall and presence of insects possibly contributed to the expression of behaviours unrelated to pain.

Conclusion

Lifting the pelvic limbs was the only specific pain behaviour after castration in donkeys. Analgesia restored appetite and water intake and reduced the frequency of head shaking and turning, ear movement and lifting the limbs. Tail, head and ear movements are unspecific responses related both to pain and a dirty stall, and are confounding factors when pain is assessed in donkeys in the presence of insects.
Stimulation of isoprene emissions and electron transport rates as key mechanisms of thermal tolerance in the tropical species Vismia guianensis
Authors: Rodrigues Tayana B. , Baker Christopher R. , Walker Anthony P. , McDowell Nate , Rogers Alistair , Higuchi Niro , Chambers Jeffrey Q. , Jardine Kolby J.
Published: June 2020

Tropical forests absorb large amounts of atmospheric CO2 through photosynthesis, but high surface temperatures suppress this absorption while promoting isoprene emissions. While mechanistic isoprene emission models predict a tight coupling to photosynthetic electron transport (ETR) as a function of temperature, direct field observations of this phenomenon are lacking in the tropics and are necessary to assess the impact of a warming climate on global isoprene emissions. Here we demonstrate that in the early successional species Vismia guianensis in the central Amazon, ETR rates increased with temperature in concert with isoprene emissions, even as stomatal conductance (gs) and net photosynthetic carbon fixation (Pn) declined. We observed the highest temperatures of continually increasing isoprene emissions yet reported (50°C). While Pn showed an optimum value of 32.6 ± 0.4°C, isoprene emissions, ETR, and the oxidation state of PSII reaction centers (qL) increased with leaf temperature with strong linear correlations for ETR (ƿ = 0.98) and qL (ƿ = 0.99) with leaf isoprene emissions. In contrast, other photoprotective mechanisms, such as non‐photochemical quenching, were not activated at elevated temperatures. Inhibition of isoprenoid biosynthesis repressed Pn at high temperatures through a mechanism that was independent of stomatal closure. While extreme warming will decrease gs and Pn in tropical species, our observations support a thermal tolerance mechanism where the maintenance of high photosynthetic capacity under extreme warming is assisted by the simultaneous stimulation of ETR and metabolic pathways that consume the direct products of ETR including photorespiration and the biosynthesis of thermoprotective isoprenoids. Our results confirm that models which link isoprene emissions to the rate of ETR hold true in tropical species and provide necessary “ground‐truthing” for simulations of the large predicted increases in tropical isoprene emissions with climate warming.
The Hydraulic Profiling Tool for Hydrogeologic Investigation of Unconsolidated Formations
Authors: McCall Wesley , Christy Thomas M.
Published: June 2020

The hydraulic profiling tool (HPT) has become one of the basic tools for investigation of soils and unconsolidated formations over the last 10 years. The HPT is advanced into the subsurface using direct push methods. Clean water is injected into the formation from a small screened port on the side of the probe as it is steadily advanced into the subsurface. A downhole pressure sensor detects the pressure required to inject the water into the formation while an up‐hole flowmeter monitors the water flow rate. An electrical conductivity (EC) array included in the lower end of the probe provides a simultaneous EC log of the bulk formation. The EC log, HPT pressure, and flow rate are logged and displayed onscreen as the probe is advanced. These logs enable the investigator to evaluate vertical changes in relative formation permeability at high resolution. Pressure dissipation tests may be performed at selected depths in coarse‐grained materials to determine the piezometric pressure in saturated formations. This enables the operator to define the piezometric profile and determine the piezometric surface without a well. Post processing of the log in the viewing software provides for calculation of the corrected HPT pressure (Pc) and estimation of hydraulic conductivity (Est. K) within limits (~0.1 to 75 ft/d). In clean, coarse‐grained materials the tandem EC log may be used to estimate groundwater specific conductance based on an Archie's Law model. Cross sections of HPT logs provide an efficient means to define hydrostratigraphy. When combined with contaminant logging tools such as the membrane interface probe (MIP) the HPT data may help to define contaminant migration pathways or contaminated low permeability zones that may result in back diffusion. The HPT can be a useful tool for many geoenvironmental investigations in unconsolidated formations.
LIM domain only 2 (LMO2) expression distinguishes T‐lymphoblastic leukemia/lymphoma from indolent T‐lymphoblastic proliferations
Authors: Brar Nivaz , Butzmann Alexandra , Kumar Jyoti , Peerani Raheem , Morgan Elizabeth A , Grigoriadis George , Kumar Beena , Tatarczuch R Maciej , Warnke Roger A , Ohgami Robert S
Published: June 2020

Aims

An indolent T‐lymphoblastic proliferation (iT‐LBP) is a benign, reactive expansion of immature terminal deoxynucleotidyl transferase (TdT)‐positive T cells found in extrathymic tissues. iT‐LBP can be challenging to distinguish from malignant processes, specifically T‐lymphoblastic lymphoma (T‐LBL), given the overlapping clinical and histological features. Recently, it has been shown that LIM domain only 2 (LMO2) is overexpressed in T‐LBL but not in reactive immature TdT+ T cells in the thymus. On the basis of these findings, the aim of this study was to investigate the expression of LMO2 by using immunohistochemistry and its role in differentiating iT‐LBPs from T‐LBLs.

Methods and results

We retrospectively identified cases of iT‐LBP and T‐LBL from the pathology archives of four institutions. Seven iT‐LBP cases (including five new cases that have not been reported in the literature) and 13 T‐LBL cases were analysed. Clinical, morphological, immunophenotypic and molecular data were analysed. Immunohistochemical staining with LMO2 was performed on all iT‐LBP and T‐LBL cases. A review of five new iT‐LBP cases showed similar morphological, immunophenotypic and molecular features to those of previously reported cases. All iT‐LBP cases were negative for LMO2 (0/7), whereas 92% of T‐LBL cases (12/13) expressed LMO2; the sensitivity was 92% (confidence interval 64–100%) and the specificity was 100% (confidence interval 59–100%).

Conclusion

We confirm previously published findings that iT‐LBP cases show highly overlapping morphological and immunophenotypic features with T‐LBL. Importantly, LMO2 expression is a sensitive and specific marker with which to rule out iT‐LBP.
Er3+‐doped CaF2 polycrystalline ceramic with perfect transparency for mid‐infrared laser
Authors: Jiang Yiguang , Jiang Benxue , Jiang Nan , Jiang Dapeng , Li Jiang , Su Liangbi , Zhang Long
Published: June 2020

Er3+‐doped CaF2 transparent ceramics are promising mid‐infrared gain materials because of their utra‐low phonon energy as well as excellent physical, chemical, and optical properties. However, existing hot‐pressed and hot‐formed CaF2 ceramics are very difficult to be used in practical applications due to residual pores and weak polycrystallization, respectively. Here, we developed the high quality Er3+‐doped CaF2 transparent polycrystalline ceramic by single crystal ceramization. The sample exhibits obvious polycrystalline structure, good mechanical properties, perfectly transmittance, and excellent mid‐infrared performance, which provides significant and wide‐ranging opportunities for advanced mid‐infrared gain materials.
The Post‐agencification Stage between Reforms and Crises. A Comparative Assessment of EU agencies' Budgetary Development
Authors: Migliorati Marta
Published: June 2020

The proliferation of European Union (EU) agencies, known as ‘agencification’, has been widely studied by scholars of EU governance. In spite of the success in explaining the roots of agencies' establishment, evidence is lacking about their development over time: have they been empowered through new resources, or have their capabilities remained the same? Which EU agencies grew the most, and why? Ultimately, how much do policymakers value these bodies? Through a newly collected longitudinal dataset, the analysis covers EU agencies' budgetary trends in the past three decades and assesses the determinants of their variation through a cross‐sectional time series regression analysis and a Traj group‐based model. The results show that trends in agencies’ budgetary allocation follow a punctuated equilibrium pattern. The observed variation is explained by EU‐level crisis response, by the expansion of agencies' tasks and by the type of agency under analysis.
Effects of global warming on sex ratios in fishes
Authors: Geffroy Benjamin , Wedekind Claus
Published: June 2020

In fishes, sex is determined by genetics, the environment or an interaction of both. Temperature is among the most important environmental factors that can affect sex determination. As a consequence, changes in temperature at critical developmental stages can induce biases in primary sex ratios in some species. However, early sex ratios can also be biased by sex‐specific tolerances to environmental stresses that may, in some cases, be amplified by changes in water temperature. Sex‐specific reactions to environmental stress have been observed at early larval stages before gonad formation starts. It is therefore necessary to distinguish between temperature effects on sex determination, generally acting through the stress axis or epigenetic mechanisms, and temperature effects on sex‐specific mortality. Both are likely to affect sex ratios and hence population dynamics. Moreover, in cases where temperature effects on sex determination lead to genotype–phenotype mismatches, long‐term effects on population dynamics are possible, for example temperature‐induced masculinization potentially leading to the loss of Y chromosomes or feminization to male‐biased operational sex ratios in future generations. To date, most studies under controlled conditions conclude that if temperature affects sex ratios, elevated temperatures mostly lead to a male bias. The few studies that have been performed on wild populations seem to confirm this general trend. Recent findings suggest that transgenerational plasticity could mitigate the effects of warming on sex ratios in some populations.