bluuebunny/crossref_metadata_2025 huggingface dataset:
Candida biofilm production is associated with higher mortality in patients with candidaemia
Authors: Vitális Eszter , Nagy Fruzsina , Tóth Zoltán , Forgács Lajos , Bozó Aliz , Kardos Gábor , Majoros László , Kovács Renátó
Published: January 2020

Background

Candidaemia is a common life‐threatening disease among hospitalised patients, but the effect of the Candida biofilm‐forming ability on the clinical outcome remains controversial.

Objective

The aim was to determine the impact of biofilms, specifically focusing on biofilm mass and metabolic activity, on the mortality in candidaemia.

Patients/Methods

The clinical data of patients (n = 127) treated at the University of Debrecen, Clinical Centre, between January 2013 and December 2018, were investigated retrospectively. Biofilm formation was assessed using the crystal violet and XTT assays, measuring the biofilm mass and metabolic activity, respectively. Isolates were classified as low, intermediate and high biofilm producers both regarding biofilm mass and metabolic activity. The susceptibility of one‐day‐old biofilms to fluconazole, amphotericin B, anidulafungin, caspofungin and micafungin was evaluated and compared to planktonic susceptibility.

Results

Intermediate/high biofilm mass was associated with significantly higher mortality (61%). All Candida tropicalis, Candida parapsilosis and Candida glabrata isolates originating from fatal infections were intermediate/high biofilm producers, whereas this ratio was 85% for Candida albicans. Solid malignancy was associated with intermediate/high biofilm producers (P = .043). The mortality was significantly higher in infections caused by Candida strains producing biofilms with intermediate/high metabolic activity (62% vs. 33%, P = .010). The ratio of concomitant bacteraemia was higher for isolates forming biofilms with low metabolic activity (53% vs 28%, P = .015).

Conclusions

This study provides evidence that the Candida biofilms especially with intermediate/high metabolic activity are related to higher mortality in candidaemia.
Synchronous and asynchronous root and shoot phenology in temperate woody seedlings
Authors: Makoto Kobayashi , Wilson Scott D. , Sato Takao , Blume‐Werry Gesche , Cornelissen Johannes H. C.
Published: January 2020

Understanding variation in root and shoot growth phenology among species is crucial to understanding underlying mechanisms of temporal niche differentiation. However, little is known about the relationship between root and shoot phenology, or how this relationship varies among functional traits. We examined fine root and shoot phenology of 42 seedlings representing a variety of woody species that inhabit the cool temperate forests of northern Japan. Some aspects of phenology were common to the pool of species examined: we found positive relationships between root and shoot phenology for the end of growth, and for the duration of growth, but not for the start of growth. Further, seedlings that started root growth relatively early also ended root growth relatively late. Other aspects of phenology varied predictably with functional traits, i.e. leaf habit and successional status: first, root growth in evergreen species started significantly earlier and ended later than in deciduous species; second, early successional species had the longest duration of shoot growth among all successional types. Our results suggest that niche differentiation may be promoted by differences in phenology between root and shoots, likely contributing to the co‐existence of woody seedlings in temperate forests.
On the scaling of activity in tropical forest mammals
Authors: Cid Bruno , Carbone Chris , Fernandez Fernando A. S. , Jansen Patrick A. , Rowcliffe J. Marcus , O'Brien Timothy , Akampurira Emmanuel , Bitariho Robert , Espinosa Santiago , Gajapersad Krishna , Santos Thiago M. R. , Gonçalves André L. S. , Kinnaird Margaret F. , Lima Marcela G. M. , Martin Emanuel , Mugerwa Badru , Rovero Francesco , Salvador Julia , Santos Fernanda , Spironello Wilson R. , Wijntuin Soraya , Oliveira‐Santos Luiz Gustavo R.
Published: January 2020

Activity range – the amount of time spent active per day – is a fundamental aspect contributing to the optimization process by which animals achieve energetic balance. Based on their size and the nature of their diet, theoretical expectations are that larger carnivores need more time active to fulfil their energetic needs than do smaller ones and also more time active than similar‐sized non‐carnivores. Despite the relationship between daily activity, individual range and energy acquisition, large‐scale relationships between activity range and body mass among wild mammals have never been properly addressed. This study aimed to understand the scaling of activity range with body mass, while controlling for phylogeny and diet. We built simple empirical predictions for the scaling of activity range with body mass for mammals of different trophic guilds and used a phylogenetically controlled mixed model to test these predictions using activity records of 249 mammal populations (128 species) in 19 tropical forests (in 15 countries) obtained using camera traps. Our scaling model predicted a steeper scaling of activity range in carnivores (0.21) with higher levels of activity (higher intercept), and near‐zero scaling in herbivores (0.04). Empirical data showed that activity ranges scaled positively with body mass for carnivores (0.061), which also had higher intercept value, but not for herbivores, omnivores and insectivores, in general, corresponding with the predictions. Despite the many factors that shape animal activity at local scales, we found a general pattern showing that large carnivores need more time active in a day to meet their energetic demands.
Politicized policy access: The effect of politicization on interest group access to advisory councils
Authors: Willems Evelien
Published: January 2020

Current scholarship often concludes that technical expertise is one of the most important commodities for interest groups wishing to gain access to political‐administrative venues. Less attention has been given to politicization and the scope of societal support that interest groups bring to bear. Specifically, I hypothesize that the capacity of interest groups to supply broad societal support is decisive for gaining access in highly politicized policy domains. To test this expectation, the article combines a mapping of interest group membership in 616 Belgian advisory councils with survey data from more than 400 organized interests. The empirical analyses demonstrate that interest groups with broad support are more likely to gain access to advisory councils in highly politicized policy domains, but this effect is negatively moderated when interest groups involve their constituencies intensely in advocacy processes.
Expression of the CCCH‐tandem zinc finger protein gene OsTZF5 under a stress‐inducible promoter mitigates the effect of drought stress on rice grain yield under field conditions
Authors: Selvaraj Michael Gomez , Jan Asad , Ishizaki Takuma , Valencia Milton , Dedicova Beata , Maruyama Kyonoshin , Ogata Takuya , Todaka Daisuke , Yamaguchi‐Shinozaki Kazuko , Nakashima Kazuo , Ishitani Manabu
Published: January 2020

Increasing drought resistance without sacrificing grain yield remains an ongoing challenge in crop improvement. In this study, we report that Oryza sativa CCCH‐tandem zinc finger protein 5 (OsTZF5) can confer drought resistance and increase grain yield in transgenic rice plants. Expression of OsTZF5 was induced by abscisic acid, dehydration and cold stress. Upon stress, OsTZF5‐GFP localized to the cytoplasm and cytoplasmic foci. Transgenic rice plants overexpressing OsTZF5 under the constitutive maize ubiquitin promoter exhibited improved survival under drought but also growth retardation. By introducing OsTZF5 behind the stress‐responsive OsNAC6 promoter in two commercial upland cultivars, Curinga and NERICA4, we obtained transgenic plants that showed no growth retardation. Moreover, these plants exhibited significantly increased grain yield compared to non‐transgenic cultivars in different confined field drought environments. Physiological analysis indicated that OsTZF5 promoted both drought tolerance and drought avoidance. Collectively, our results provide strong evidence that OsTZF5 is a useful biotechnological tool to minimize yield losses in rice grown under drought conditions.
Approach‐oriented coping strategy level may be related to volume of the whole hippocampus in the elderly
Authors: Kida Hisashi , Nakajima Shinichiro , Shikimoto Ryo , Ochi Ryo , Noda Yoshihiro , Tsugawa Sakiko , Fujii Shinya , Takayama Midori , Mimura Masaru , Niimura Hidehito
Published: January 2020

Aim

Stress‐related disorders and severe stress exposure can cause atrophy of the whole hippocampus and its subfields. However, the impact of stress coping strategies on the hippocampus remains unclear. Therefore, we aimed to examine the relation between approach‐ and avoidance‐oriented coping strategies and hippocampal volume in elderly persons.

Methods

A total of 1045 elderly persons living in Arakawa‐ward, Tokyo (mean ± SD age: 72.8 ± 5.2 years; 569 females [54.4%]) were included in the study and completed several questionnaires and face‐to‐face interviews and underwent magnetic resonance imaging. Approach‐ or avoidance‐oriented coping strategies were assessed with the Stress and Coping Inventory, while cognitive function and depressive symptoms were assessed with the Mini‐Mental State Examination and Geriatric Depression Scale, respectively. The volume of the whole hippocampus on T1‐weighted images was delineated and calculated using FreeSurfer 6.0. Multiple regression analyses were performed to examine the relation between Stress and Coping Inventory scores and whole hippocampal volume.

Results

Approach‐oriented coping strategy scores were positively correlated with whole hippocampal volume. Furthermore, these relations remained significant after controlling for the influence of cognitive function and depressive symptoms on these volumetric variables. In contrast, avoidance‐oriented coping strategy scores were not correlated with whole hippocampal volume.

Conclusion

This study demonstrated that hippocampal volume may be associated with the approach‐oriented coping strategy; therefore, this strategy may preserve hippocampal volume in the elderly.
Pediatric cellular neurothekeoma: Seven cases and systematic review of the literature
Authors: Murphrey Morgan , Huy Nguyen Austin , White Kevin P. , Krol Alfons , Bernert Richard , Yarbrough Kevin
Published: January 2020

Background/Objectives

Neurothekeoma is a rare, benign, cutaneous neoplasm consisting of Schwann cells and perineural cells in myxoid stroma. Cellular neurothekeoma (CNT) was previously thought to represent a morphologic variant of neurothekeoma, but recent studies have shown that CNTs are unrelated to neurothekeomas and are more likely of histiocytic lineage.

Methods

Herein, we describe seven cases of CNT in pediatric patients. A comprehensive search of PubMed was performed, and 71 cases of cellular neurothekeoma in pediatric patients were reviewed.

Results

The clinical differential diagnosis for these lesions included Spitz nevi, keloid, juvenile xanthogranuloma, cutaneous lymphoid hyperplasia, and lymphomatoid papulosis. All cases were treated by excision or excisional biopsy. Histopathologically, all demonstrated multilobular, primarily intradermal neoplasms composed of plump spindled or epithelioid mononuclear cells with abundant eosinophilic pale‐staining cytoplasm. Immunophenotypic findings included CD68 and NKI/C3 positivity, and negative staining with cytokeratin, S‐100, Melan‐A, and SOX‐10.

Conclusion

Cellular neurothekeoma is distinguished from conventional neurothekeoma by increased cellularity, a lack of myxoid stroma, and a lack of neural expression with immunohistochemical stains. These uncommon neoplasms should be included in the differential diagnosis of dermal nodules in children. Accurate diagnosis of these lesions is essential, as they can be mistaken for malignancy leading to unnecessary treatment.
Intralesional immunotherapy for pediatric warts: A review
Authors: Fields Jaime R. , Saikaly Sami K. , Schoch Jennifer J.
Published: January 2020

Cutaneous warts are a common pediatric complaint with modest response to first‐line treatments. Warts are a manifestation of human papillomavirus (HPV) infection and are cleared by cell‐mediated immunity (CMI). Intralesional immunotherapy treatments have been studied as alternative therapies, particularly for recalcitrant or multiple warts, including Candida antigen, mumps antigen, the combined measles, mumps, and rubella (MMR) vaccine, tuberculin purified protein derivative (PPD), and bacille Calmette‐Guerin (BCG) vaccine. These treatments are thought to increase HPV recognition by stimulating CMI. In this review, we evaluate and compare the efficacy and adverse effects of intralesional immunotherapy in the treatment of pediatric warts. Articles met inclusion criteria if they specifically evaluated the effects of intralesional immunotherapy (candida, MMR, tuberculin PPD, or BCG) as treatment for cutaneous warts in a pediatric population, and if they quantified treatment effect in a reproducible manner. Twenty‐one studies met criteria. Many studies demonstrated complete clearance of injected common warts in pediatric patients with clearance rates ranging from 23.3% to 95.2%. Distant wart resolution was common. Intralesional immunotherapy is a promising treatment option for cutaneous warts in children.
Clinicopathological features of hepatocellular carcinoma with fatty change: Tumors with macrovesicular steatosis have better prognosis and aberrant expression patterns of perilipin and adipophilin
Authors: Kubota Naoto , Ojima Hidenori , Hatano Mami , Yamazaki Ken , Masugi Yohei , Tsujikawa Hanako , Fujii‐Nishimura Yoko , Ueno Akihisa , Kurebayashi Yutaka , Shinoda Masahiro , Kitago Minoru , Abe Yuta , Kitagawa Yuko , Sakamoto Michiie
Published: January 2020

The clinicopathological characteristics of steatosis in hepatocellular carcinoma (HCC) remain unclear. Here, we elucidate the features of macrovesicular steatosis (MaS) and microvesicular steatosis (MiS) in HCC and their relationships with background liver steatosis. A total of 165 HCC lesions were classified as MaS‐HCC, MiS‐HCC, or conventional HCC (cHCC) according to the cutoff value of 30% MaS or MiS in tumor cells. We analyzed the clinicopathological differences among these groups. MaS‐HCC had less portal vein invasion, a higher proportion of HCC with intratumoral fibrosis, and a lower cumulative risk of recurrence than MiS‐HCC or cHCC. Moreover, both MaS‐HCC and MiS‐HCC had lower incidences of hepatitis virus infection and higher levels of HbA1c than cHCC. Background liver steatosis was also higher in MaS‐HCC than in cHCC. Immunohistochemical expression of perilipin (Plin1) and adipophilin (ADRP), major proteins expressed on lipid droplet membranes, revealed that almost all lipid droplets in HCC were Plin1 negative, whereas those in background liver were positive. In contrast, ADRP was expressed on lipid droplets in both HCC and background liver. We concluded that MaS‐HCC and MiS‐HCC were associated with metabolic abnormalities but exhibited different biologic behaviors. Furthermore, lipid droplets in HCC were pathophysiologically different from those in background liver.
Gramineous weeds near paddy fields are alternative hosts for the Fusarium graminearum species complex that causes fusarium head blight in rice
Authors: Dong Fei , Xu Jianhong , Zhang Xiao , Wang Shufang , Xing Yujun , Mokoena Mduduzi P. , Olaniran Ademola O. , Shi Jianrong
Published: January 2020

The objective of this study was to evaluate the potential role of gramineous weeds present near paddy fields as alternative hosts for the Fusarium graminearum species complex (FGSC) that causes fusarium head blight (FHB) in rice. A total of 142 weed samples were collected from 10 gramineous weed species near paddy fields from August to October 2018 in Jiangsu Province, China. Of the 145 isolates of seven Fusarium species isolated from the weed samples, F. asiaticum was the most abundant (86.9%), followed by F. fujikuroi (5.5%), F. proliferatum (2.8%), F. graminearum (2.1%), F. tricinctum (1.4%), F. acuminatum (0.7%), and F. sporotrichioides (0.7%). Genotype and mycotoxin analyses confirmed that 72.2% of F. asiaticum isolates were producers of deoxynivalenol (DON) with 3‐acetyl deoxynivalenol (3ADON), and the remainder were nivalenol (NIV) producers. Pathogenicity assays showed that both 3ADON and NIV chemotypes of F. asiaticum could cause FHB in rice, but NIV chemotypes were significantly (p < .05) more aggressive than 3ADON chemotypes. Three Fusarium mycotoxins, DON, NIV, and zearalenone, occurred naturally at low concentrations in the weed samples. Taken together, this study provides insight into the mycotoxin production and aggressiveness of F. asiaticum isolates from gramineous weeds in China.
Symptom development and latent period of Austropuccinia psidii (myrtle rust) in relation to host species, temperature, and ontogenic resistance
Authors: Beresford Robert M. , Shuey Louise S. , Pegg Geoff S.
Published: January 2020

Myrtle rust (Austropuccinia psidii) is an invasive species causing damage to Myrtaceae species in natural and managed ecosystems in many countries. To better understand myrtle rust epidemiology we studied latent period (LP) and ontogenic resistance in relation to temperature on three susceptible hosts (Metrosideros excelsa, Lophomyrtus bullata × L. obcordata and Syzygium jambos). The latent period curve was U‐shaped, with latent development >0 from between 8 and 10 °C, depending on the host, to 32 °C. Optimum range was 22–28 °C with minimum LP of 5–7 days. Peak spore production occurred over about 2 weeks, starting about 1 week after the LP ended. Some spore production continued for 1–2 months. Comparison of the LP data with field temperatures indicated that the uredinial stage of A. psidii can overwinter in the latent phase in temperate areas of New Zealand and southern Australia and, therefore, uredinial or telial reinfection is not required during winter. The LP information was used to correct the LP function in a New Zealand myrtle rust climatic risk model. The transition of emergent leaf and stem tissues in susceptible Myrtaceae genotypes from susceptible to immune (ontogenic resistance) was characterized in terms of uredinium density and LP. Onset of ontogenic resistance was closely linked to the degree of leaf expansion, with fully expanded leaves being immune to infection. Because ontogenic resistance restricts infection to periods when growth flushes occur, understanding it is crucial for explaining the seasonality of myrtle rust development in the natural environment.
Ecological momentary assessment of stress, racism and other forms of discrimination during pregnancy using smartphone technology
Authors: Mendez Dara D. , Sanders Sarah A. , Lai Yu‐Hsuan , Wallace Meredith L. , Rathbun Stephen L. , Gary‐Webb Tiffany L. , Davis Esa M. , Burke Lora E.
Published: January 2020

Background

In the United States, there are considerable racial inequities in adverse perinatal outcomes. Exposure to racism, sexism, and other forms of oppression may help explain these inequities.

Objectives

To describe the application of real‐time data collection using ecological momentary assessment (EMA) and smartphone technology to assess exposure to stress, racism, sexism, microaggressions, and other forms of oppression.

Methods

The Postpartum Mothers Mobile Study (PMOMS) is an ongoing longitudinal cohort study that began recruitment in December 2017. Participants delivering at a hospital in Pittsburgh, PA are recruited by 29 weeks' gestation. Using smartphones and smart scales, participants complete daily surveys related to psychosocial, behavioural, and contextual factors and weigh themselves weekly for approximately 15 months. We provide a preliminary descriptive analysis of EMA self‐reported measures of stress, racism, sexism, and microaggressions; and non‐EMA measures of stress and major discrimination.

Results

The sample (n = 230) is 63.5% White, 24.8% Black/African American, and 7% Hispanic origin. The most commonly reported item from the Major Discrimination Scale is being unfairly fired (18.1% of the sample). Of those, 31.7% and 17.1% attribute unfair firing to their gender and race, respectively. From the random EMA measures, on average, participants report experiences of racism and sexism at least once daily, in an average 12‐hour day over the 4‐week period. Black participants indicate about two experiences per day of racism, and White participants indicate more than 1 per day of sexism. Mean stress levels from the EMA measures were similar to the stress measures collected at baseline.

Conclusions

The methods applied in PMOMS provide real‐time data regarding how participants' daily experiences of stress and discrimination influence their lives. Future work will include understanding if and how these EMA measures may relate to already established measures of racism, sexism, and stress; and ultimately understanding associations with perinatal inequities.
Uncovering and defragmenting the role of the Toll pathway in the innate immune responses of cultured crustaceans against viral pathogens
Authors: Sánchez‐Paz Arturo , Muhlia‐Almazán Adriana
Published: January 2020

Shrimp farming is considered the fastest growing aquaculture industry in the last decades, with an average growth in production of ~15% per year. Unfortunately, this industry has been affected by the emergence of viral diseases, and currently, there are no commercially available therapeutics against these pathogens. Therefore, a deeper understanding of the immune system components induced by viruses is imperative for the development of antiviral therapies in these species. It is well known that the Toll‐like receptor (TLR) signalling is involved in activating the innate immune responses in crustaceans. Although numerous research papers deal with the response of the individual components of this pathway involved in the antiviral response on different crustacean species, the information is highly fragmented. This review provides a detailed picture of the general structure and role of Spätzle, Toll receptors, MyD88, Tollip, Tube, Pelle, Pellino, Dorsal, Cactus and DIF, the elements constituting the Toll‐like receptor participating in the innate immune response against viral diseases in crustaceans. It summarizes the current knowledge progress about the influence of the Toll pathway components on the expression of antimicrobial peptides involved in the antiviral response of crustaceans. In addition, this review compares the structural and functional roles of the elements identified in crustaceans, with those of the popular model organism Drosophila. This systematic review may contribute to identify the existing gaps in the knowledge of the Toll pathway in crustaceans and help to carry out further studies that may be useful for the management of viral diseases.
Making small firms happy? The heterogeneous effect of trade facilitation measures
Authors: Fontagné Lionel , Orefice Gianluca , Piermartini Roberta
Published: January 2020

The different facets of trade facilitation may impact heterogeneously exporters of different size and productivity. Using the cross‐sectional variation in procedures at the border, we identify how red tape affects trade through the extensive and/or the intensive margin and show that small and large exporters are affected differently. We observe that while information availability benefits both small and large exporters, other measures like advance ruling, appeal procedures and the automation of border formalities tend to favor large exporters. This result suggests that trade facilitation policies affect exporters through channels other than simply the fixed or variable cost component of the red tape barriers. Beyond affecting the size and composition of trade flows, uncertainty about the conditions of crossing borders plays an important role in shaping the demography of exporters across different destinations.
Taxing Flaring and the Politics of State Methane Release Policy
Authors: Rabe Barry , Kaliban Claire , Englehart Isabel
Published: January 2020

Methane is a potent greenhouse gas but it has received strikingly less social science attention than carbon dioxide in examining climate policy options. This article explores American state policy toward methane that is not captured and instead released into the atmosphere during oil and gas production. It examines whether states have adopted market‐based approaches to price methane flaring and venting through long‐standing severance taxes on natural gas extraction. Such taxes exist in all but one production state, routinely materializing after prolonged adoption battles. Most states have maintained methane release exemptions from these taxes through either statute or administrative discretion between 1960 and 2000, although a few have allowed some form of pricing. Two state legislatures have explored applying these taxes to methane releases on multiple occasions since 2000, amid expanded shale era output and growing public concern about climate and air quality impacts. Steadfast production industry opposition, rather than technical feasibility, emerges as the primary factor leading to rejection in these cases. Even when framing releases as a conventional air contaminant or as permanent loss of a nonrenewable natural resource, states largely continue to exempt flared or vented methane from severance taxes.
Consolidation in dialysis Markets—Causes, consequences, and the role of policy
Authors: Saeed Maryam K. , Ho Vivian , Erickson Kevin F.
Published: January 2020

The dialysis industry is one of the most highly concentrated healthcare sectors in the United States. Despite decades of growth in the number of patients with end‐stage renal disease and in the size of dialysis markets, two large dialysis organizations currently care for more than two‐thirds of the dialysis population. Economies of scale, bargaining leverage with suppliers and private insurers, barriers to entry, and government regulations have contributed to highly concentrated dialysis markets by conferring advantages to larger organizations. Consolidated dialysis markets have coincided with both positive and negative trends in healthcare costs and outcomes. Costs per patient receiving dialysis have grown at a slower rate than per capita Medicare costs, while access to dialysis care remains available across a wide socioeconomic range. Mortality rates have declined despite a sicker dialysis patient population. Yet, concerns remain about the cost and quality of dialysis care. Evidence suggests that chain ownership, for profit status, and less market competition may negatively impact health outcomes. Future policies and innovations involving kidney health may temporarily disrupt consolidation. However, if the underlying mechanisms that contributed to past consolidation persist, dialysis markets may remain highly concentrated over the long term.
Epidemiology and risk factors associated with Pneumocystis jirovecii pneumonia in kidney transplant recipients after 6‐month trimethoprim‐sulfamethoxazole prophylaxis: A case‐control study
Authors: Park Se Yoon , Jung Joo Hee , Kwon Hyunwook , Shin Sung , Kim Young Hoon , Chong Yong‐Phil , Lee Sang‐Oh , Choi Sang‐Ho , Kim Yang Soo , Woo Jun Hee , Kim Sung‐Han , Han Duck Jong
Published: January 2020

Background

Pneumocystis jirovecii pneumonia (PCP) is an important cause of morbidity and mortality in kidney transplant recipients (KTRs), and prophylaxis with trimethoprim‐sulfamethoxazole (TMP‐SMX) is recommended. The aim of this study was to investigate incidence and risk factors for PCP in KTRs after 6‐month TMP‐SMX prophylaxis.

Methods

We conducted a case‐control study of patients with PCP who received 6‐month PCP prophylaxis with TMP‐SMX after kidney transplantation (KT). In cases of rejection, PCP prophylaxis was provided for six additional months after anti‐rejection therapy. Cytomegalovirus (CMV) infection was not considered an indication for PCP prophylaxis due to concerns of nephrotoxicity associated with TMP‐SMX.

Results

Among 3941 kidney or pancreas‐kidney transplant recipients, 67 (1.7%) developed PCP after discontinuing TMP‐SMX. A total of 47 patients with KT PCP and 94 controls were included. Duration of PCP prophylaxis was similar between cases and controls (median 6 months, P = .53). In multivariate analysis, rejection (OR 3.9; 95% CI 1.4‐11.1) and CMV infection (OR 2.4; 95% CI 1.0‐5.8) were independently associated with PCP development after TMP‐SMX. Rejection or CMV infection was observed in 70% of patients with PCP. Time to PCP development after rejection (median [IQR] 6 [5‐19] months) was slightly shorter than after CMV infection (median [IQR] 9 [5‐12] months; P = .18).

Conclusion

Post‐prophylaxis PCP occurred in <2% of KTRs, and about two‐thirds of these experienced rejection or CMV infection. These data suggest that at least 6 to 9‐month additional chemoprophylaxis may be needed to prevent PCP in KTRs with transplant rejection or CMV infection.
Preclinical safety assessment of pathogen reduced red blood cells treated with amustaline and glutathione
Authors: North Anne K. , Mufti Nina , Sullivan Theresa , Corash Laurence
Published: January 2020

BACKGROUND

The nucleic acid targeted pathogen reduction (PR) system utilizing amustaline (S‐303) and glutathione (GSH) is designed to inactivate blood‐borne pathogens and leukocytes in red blood cell concentrates (PR‐RBCC). Inactivation is attained after amustaline intercalates and forms covalent nucleic acid adducts preventing replication, transcription, and translation. After pathogen inactivation, amustaline spontaneously hydrolyzes to S‐300, the primary negatively charged reaction product; amustaline is below quantifiable levels in PR‐RBCC. GSH quenches free unreacted amustaline.

STUDY DESIGN AND METHODS

The genotoxic and carcinogenic potential of PR‐RBCC, the reaction by‐products, and S‐300 were assessed in accordance with the International Conference on Harmonization (ICH) guidelines and performed in compliance with the Food and Drug Administration (FDA) good laboratory practice standards, 21 CFR Part 58. in vitro bacterial reverse mutagenicity and chromosomal aberration assays were performed with and without exogenous S9 metabolic activation, and in in vivo clastogenicity and carcinogenic assays using validated murine models.

RESULTS

PR‐RBCCs were not genotoxic in vitro and in vivo and were non‐carcinogenic in p53+/− transgenic mice transfused over 26 weeks. Estimated safety margins for human exposure ranged from >90 to >36 fold for 2 to 5 PR‐RBCCs per day, respectively. PR‐RBCCs and S‐300 did not induce chromosome aberration in the in vivo murine bone marrow micronucleus assay at systemically toxic doses.

CONCLUSIONS

PR‐RBCCs did not demonstrate genotoxicity in vitro or in vivo and were not carcinogenic in vivo. These studies support the safety of PR‐RBCCs and suggest that there is no measurable genotoxic hazard associated with transfusion of PR‐RBCCs.
Adjuvant medical therapy provides no therapeutic benefit in the treatment of dogs with low‐grade mast cell tumours and early nodal metastasis undergoing surgery
Authors: Marconato Laura , Stefanello Damiano , Kiupel Matti , Finotello Riccardo , Polton Gerry , Massari Federico , Ferrari Roberta , Agnoli Chiara , Capitani Ombretta , Giudice Chiara , Aresu Luca , Vasconi Maria Elisabetta , Rigillo Antonella , Sabattini Silvia
Published: January 2020

Lymph node (LN) metastasis is a negative prognostic factor in dogs with cutaneous mast cell tumours (cMCTs). While elective lymphadenectomy of metastatic LNs improves outcome, the benefit of adjuvant medical therapy in dogs with early metastatic (HN2) LNs is debated. The aim of this retrospective multicentre study was to evaluate the therapeutic benefit of adjuvant medical therapy following surgical removal of the primary low‐grade cMCT (Patnaik grade 1‐2 and Kiupel low‐grade) and lymphadenectomy of HN2 LNs by analysing survival rates and patterns of recurrence. Seventy‐three dogs were included: 42 received adjuvant medical treatment (chemotherapy and/or kinase inhibitors), and 31 did not. The median follow‐up time for medically treated dogs was 619 days: two experienced local recurrence, three nodal relapse and four distant relapse. For dogs undergoing surgery only, the median follow‐up time was 545 days. None of them experienced local recurrence, nodal, or distant relapse. Time to progression was significantly shorter in dogs receiving adjuvant medical treatment (P = .021). A similar tendency was observed for overall survival (P = .056). The current study shows that dogs with low‐grade cMCTs, that undergo surgical excision of the primary tumour and elective lymphadenectomy of the HN2 regional LN harbour a good prognosis. The use of adjuvant medical treatment in these dogs does not seem to provide any benefit in terms of progression and survival.
Diagnostic needle arthroscopy of the tarsocrural joint in standing sedated horses
Authors: Kadic Dimitri T. N. , Bonilla Alvaro G.
Published: January 2020

Objective

To develop and assess a needle arthroscopic technique to diagnose conditions of the tarsocrural joint (TCj) in standing sedated horses.

Study design

Experimental study.

Sample population

Six cadaveric hind limbs (phase 1) and six healthy horses (Phase 2).

Methods

In phase 1, each TCj was examined with a 1.2‐mm‐needle arthroscope. Suitability of the needle arthroscope and degree of joint visualization with traditional arthroscopic approaches were assessed. In phase 2, the feasibility of the procedure was assessed in six standing healthy horses. A custom‐made splint and base were developed to maintain joint flexion during the procedure.

Results

Thorough evaluation of the dorsal intra‐articular structures of the TCj via dorsomedial and dorsolateral approaches was possible in both phases. The procedure was feasible, quickly performed, and well tolerated by all horses. Complications consisted of moderate movement (2/6 horses) and hemarthrosis (3/6 horses).

Conclusion

Diagnostic standing needle arthroscopy of the TCj allowed thorough evaluation of the dorsal aspect of the joint while avoiding the cost and risks associated with general anesthesia. Inadvertent puncture of the dorsomedial vasculature with the cannula and obturator led to significant hemarthrosis.

Clinical impact

Needle arthroscopy of the TCj offers an alternative diagnostic tool when traditional imaging techniques (radiography and ultrasonography) are unrewarding or nondiagnostic. The technique is conceived mainly for diagnostic purposes, but its use during short interventions warrants investigation.
Co‐transplantation of human adipose‐derived mesenchymal stem cells with neonatal porcine islets within a prevascularized subcutaneous space augments the xenograft function
Authors: Kuppan Purushothaman , Seeberger Karen , Kelly Sandra , Rosko Mandy , Adesida Adetola , Pepper Andrew R. , Korbutt Gregory S.
Published: January 2020

Background

Cell transplantation has been widely recognized as a curative treatment strategy for variety of diseases including type I diabetes (T1D). Broader patient inclusion for this therapeutic option is restricted by a limited supply of healthy human islet donors and significant loss of islets immediately postintrahepatic transplant due to immune activation. Neonatal porcine islets (NPIs) are a potential ubiquitous β‐cell source for treating T1D. Mesenchymal stem cells (MSCs) have the inherent capacity to secrete immunoregulatory, anti‐inflammatory, and proangiogenic factors and, thus, have the potential to improve islet engraftment, survival, and function.

Methods

Herein, we assessed the effect of human adipose–derived MSCs (AdMSCs) on NPI metabolic outcomes in diabetic mice when co‐transplanted within the prevascularized subcutaneous deviceless (DL) space or kidney capsule (KC). Graft function has been evaluated by weekly blood glucose, stimulated porcine insulin, glucose tolerance, and total cellular graft insulin content.

Results

Compared with NPI alone, co‐transplantation of NPIs and AdMSCs resulted in significantly earlier normoglycemia (*P < .05), improved glucose tolerance (*P < .05), superior stimulated serum porcine insulin (**P < .01), and increased graft insulin content (*P < .05) in the DL site and not the KC.

Conclusions

Thus, our study demonstrates that co‐transplantation of human AdMSCs with NPIs is an effective tactic to augment islet xenograft function in a clinically relevant extrahepatic site.
Human‐infecting influenza A (H9N2) virus: A forgotten potential pandemic strain?
Authors: Song Wenjun , Qin Kun
Published: January 2020

Continuously emergence of human infection with avian influenza A virus poses persistent threat to human health, as illustrated in H5N1, H7N9 and recent surge of H9N2 infections. Long‐term prevalence of H9N2 avian influenza A virus in China and adjacent regions favours the interspecies transmissions from avian to human. Establishment of multiple genotypes of H9N2 variants in this region contributes to the emergence of novel H7N9 and H10N8 viruses which caused human fatalities. Recent increasing human infection with H9N2 virus in China highlights the necessity to closely monitor the interspecies transmission events. Available human H9N2 sequences revealed that Y280/G9 lineage was responsible for the most of human cases. Presence of adaptive mutations beyond the human‐like receptor binding was indicative of the capacity of readily infecting new hosts without prior adaptation. Moreover, enlarged host range of H9N2 virus in this region substantially increased the transmission among mammals. Meanwhile, serological surveys implied human was more susceptible to H9N2 infection, compared with panzootic H5 and H7 subtype avian influenza virus. Thus, control at the source will be the ultimate and effective option for H9N2 pandemic preparedness. This review comprehensively summarized recent updates on H9N2 human infections, aiming to shed light on the prevention strategies against this strain with pandemic potential.
A Witt Nadel vanishing theorem for threefolds
Authors: Nakamura Yusuke , Tanaka Hiromu
Published: January 2020

In this paper, we establish a vanishing theorem of Nadel type for the Witt multiplier ideals on threefolds over perfect fields of characteristic larger than five. As an application, if a projective normal threefold over$\mathbb{F}_{q}$is not klt and its canonical divisor is anti-ample, then the number of the rational points on the klt-locus is divisible by$q$.
Fractal spike dynamics and neuronal coupling in the primate visual system
Authors: Munn Brandon , Zeater Natalie , Pietersen Alexander N. , Solomon Samuel G. , Cheong Soon Keen , Martin Paul R. , Gong Pulin
Published: January 2020

Key points

We measured fractal (self‐similar) fluctuations in ongoing spiking activity in subcortical (lateral geniculate nucleus, LGN) and cortical (area MT) visual areas in anaesthetised marmosets.

Cells in the evolutionary ancient koniocellular LGN pathway and in area MT show high‐amplitude fractal fluctuations, whereas evolutionarily newer parvocellular and magnocellular LGN cells do not.

Spiking activity in koniocellular cells and MT cells shows substantial correlation to the local population activity, whereas activity in parvocellular and magnocellular cells is less correlated with local activity.

We develop a model consisting of a fractal process and a global rate modulation which can reproduce and explain the fundamental relationship between fractal fluctuations and population coupling in LGN and MT.

The model provides a unified account of apparently disparate aspects of neural spiking activity and can improve our understanding of information processing in evolutionary ancient and modern visual pathways.

The brain represents and processes information through patterns of spiking activity, which is influenced by local and widescale brain circuits as well as intrinsic neural dynamics. Whether these influences have independent or linked effects on spiking activity is, however, not known. Here we measured spiking activity in two visual centres, the lateral geniculate nucleus (LGN) and cortical area MT, in marmoset monkeys. By combining the Fano‐factor time curve, power spectral analysis and rescaled range analysis, we reveal inherent fractal fluctuations of spiking activity in LGN and MT. We found that the evolutionary ancient koniocellular (K) pathway in LGN and area MT exhibits strong fractal fluctuations at short (<1 s) time scales. Parvocellular (P) and magnocellular (M) LGN cells show weaker fractal fluctuations at longer (multi‐second) time scales. In both LGN and MT, the amplitude and time scale of fractal fluctuations can explain short and long time scale spiking dynamics. We further show differential neuronal coupling of LGN and MT cells to local population spiking activity. The population coupling is intrinsically linked to fractal fluctuations: neurons showing stronger fluctuations are more strongly correlated to the local population activity. To understand this relationship, we modelled spiking activity using a fractal inhomogeneous Poisson process with dynamic rate, which is the product of an intrinsic stochastic fractal rate and a global modulatory gain. Our model explains the intrinsic links between neuronal spike rate and population coupling in LGN and MT, and establishes a unified account of dynamic spiking properties in afferent visual pathways.
In situ real-time and ex situ spectroscopic analysis of Al2O3 films prepared by plasma enhanced atomic layer deposition
Authors: Naumann Franziska , Reck Johanna , Gargouri Hassan , Gruska Bernd , Blümich Adrian , Mahmoodinezhad Ali , Janowitz Christoph , Henkel Karsten , Flege Jan Ingo
Published: January 2020

In situ real-time ellipsometry (irtE) with a very high time resolution of 24 ms was applied to monitor the inductively coupled plasma enhanced atomic layer deposition (ALD) process of Al2O3 thin films to precisely resolve each step of the ALD process and its complete cycle. The influence of plasma power, plasma pulse duration, and deposition temperature on the film growth characteristics was investigated. Ex situ ellipsometry [UV-VIS-NIR-SE (ultraviolet-visible-nearinfrared-spectroscopic ellipsometry) and IR-SE (infrared spectroscopic ellipsometry)] and x-ray photoelectron spectroscopy revealed the bulk properties (thickness, refractive index, chemical composition, and carbon incorporation) of the films, which together with the in situ results are compared to those of the films prepared by thermal ALD (T-ALD). The ICPEALD (inductively coupled plasma enhanced ALD) films were deposited at substrate temperatures between 80 and 250 °C and the role of plasma power (50–300 W) and its pulse duration (1–20 s) was investigated at 250 °C. The reference T-ALD layers were prepared at 200 °C. The ICPEALD process of Al2O3 shows an increased growth rate, and the produced films exhibit higher carbon contaminations than the T-ALD Al2O3 films. Plasma pulse times of up to 15 s further increase the content of carbon and CH species; at the same time, the refractive index decreases. The optical properties of ICPEALD deposited Al2O3 films are comparable with those of the T-ALD films for low plasma power and short plasma pulse durations. For the ICPEALD films, UV absorption is found and it is dependent on the deposition parameters. irtE resolves process effects that correlate with the bulk properties of Al2O3, such as impurities and oxygen deficiencies.
A model of auditory brainstem response wave I morphology
Authors: Kamerer Aryn M. , Neely Stephen T. , Rasetshwane Daniel M.
Published: January 2020

Use of the auditory brainstem response (ABR) in research has increased in the search for physiological correlates of noise-induced damage to the cochlea. The extraction of data from the ABR has traditionally relied on visual determination of peaks and troughs to calculate metrics such as wave amplitude. Visual determination can be reliable when evaluated by trained, experienced personnel, but noisy waveforms and overlapping waves produce uncertain data. The present study proposes and validates a method of fitting summed Gaussian functions to the summating potential and wave I of the ABR. This method could be useful to the research community studying these potentials by providing more accurate measures of wave amplitude than by visual determination.
Mindfulness in Sport: An Intervention for a Choking-Susceptible Athlete
Authors: Hussey Jenna , Weinberg Robert , Assar Arash
Published: January 2020

Although antecedents of choking under pressure have been studied, prevention efforts have been somewhat inconsistent. Current choking-susceptibility criteria include trait anxiety (TA), self-consciousness (SC), and coping style. In the present case study, a college track-and-field athlete was self-identified as choking susceptible (CS), and a sport-specific mindfulness intervention to reduce levels of TA, SC, and alter coping to reduce choking susceptibility was implemented. The athlete identified as CS completed the 6-wk Mindful Sport Performance Enhancement (MSPE) program. Trait and state mindfulness were assessed throughout the program, with a follow-up 6 wk postintervention to gain further insight into the continuing effects of the mindfulness training. Visual analysis and quantitative and qualitative data demonstrated increases in mindfulness levels and changes in TA, SC, and coping, resulting in the participant’s failing to meet the choking-susceptibility criteria postintervention, indicating a reduced likelihood of choking in future performances. Enhanced mindfulness levels promoted greater awareness and acceptance, which may help counter the negative effects of stressful sport performances.
Suppression of β-Lactam Resistance by Aspergillomarasmine A Is Influenced by both the Metallo-β-Lactamase Target and the Antibiotic Partner
Authors: Rotondo Caitlyn M. , Sychantha David , Koteva Kalinka , Wright Gerard D.
Published: January 2020

The rise of Gram-negative pathogens expressing metallo-β-lactamases (MBLs) is a growing concern, threatening the efficacy of β-lactam antibiotics, in particular, the carbapenems. There are no inhibitors of MBLs in current clinical use. Aspergillomarasmine A (AMA) is an MBL inhibitor isolated from
Aspergillus versicolor
with the ability to rescue meropenem activity in MBL-producing bacteria both
in vitro
and
in vivo
. Here, we systematically explored the pairing of AMA with six β-lactam antibiotic partners against 19 MBLs from three subclasses (B1, B2, and B3).
Drug Development against Smallpox: Present and Future
Authors: Delaune Déborah , Iseni Frédéric
Published: January 2020

Forty years after the last endemic smallpox case, variola virus (VARV) is still considered a major threat to humans due to its possible use as a bioterrorism agent. For many years, the risk of disease reemergence was thought to solely be through deliberate misuse of VARV strains kept in clandestine laboratories. However, recent experiments using synthetic biology have proven the feasibility of recreating a poxvirusde novo, implying that VARV could, in theory, be resurrected. Because of this new perspective, the WHO Advisory Committee on VARV Research released new recommendations concerning research on poxviruses that strongly encourages pursuing the development of new antiviral drugs against orthopoxviruses.