bluuebunny/crossref_metadata_2025 huggingface dataset:
Pomalidomide‐bortezomib‐dexamethasone in relapsed or refractory multiple myeloma: Japanese subset analysis of OPTIMISMM
Authors: Sunami Kazutaka , Matsue Kosei , Suzuki Kenshi , Takezako Naoki , Shinagawa Atsushi , Sakurai Sanae , Tamakoshi Hiromi , Biyukov Tsvetan , Peluso Teresa , Richardson Paul
Published: April 2020

In the phase 3 OPTIMISMM trial, pomalidomide, bortezomib and dexamethasone (PVd) significantly improved the progression‐free survival (PFS) and the overall response rate (ORR) vs bortezomib and dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma. All patients were previously treated with lenalidomide (70% refractory to lenalidomide) and had received one to three prior regimens. Here we report the first efficacy and safety analysis of PVd vs Vd in Japanese patients with relapsed or refractory multiple myeloma. Seventeen patients enrolled in the OPTIMISMM trial in Japan. With a median follow‐up of 14.8 months, the median PFS was 17.6 months with PVd (n = 12) vs 4.4 months with Vd (n = 5), and the ORR was 100% vs 60.0%, respectively. The safety profile was as expected for PVd. Toxicities were managed with dose reductions and interruptions, and no patients discontinued PVd due to treatment‐emergent adverse events. These results are consistent with those in the overall OPTIMISMM patient population and confirm the clinical benefit of PVd in Japanese patients.
New method of endoscopic injection sclerosis for esophageal varices using by modified endoscopic hood
Authors: Miyamoto Shuichi , Yamamoto Yoshiya , Takagi Tomofumi
Published: April 2020

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A qualitative study exploring the expectations of people living with type 1 diabetes regarding prospective use of a hybrid closed‐loop system
Authors: Quintal A. , Messier V. , Rabasa‐Lhoret R. , Racine E.
Published: April 2020

Aim

To identify the expectations of a diversified sample of informed adults with type 1 diabetes on their prospective use of a hybrid closed‐loop system.

Methods

Semi‐structured interviews were conducted with 16 adults with type 1 diabetes who shared their expectations on an experimental hybrid closed‐loop system after receiving information on its design, functioning and capability. The sample had equal representation of genders and diabetes management methods and was diversified according to age, education and occupation when possible. Qualitative content analysis of the interview transcripts with MaxQDA was used to identify expected benefits, expected inconveniences and concerns, expected improvements to design and functionalities, and interest and trust in the system.

Results

Participants expected benefits regarding diabetes management, clinical outcomes, psychosocial aspects of their lives, nutrition and meals, and physical activity. Participants expected inconveniences or shared concerns regarding wearability, costs and technical limitations. According to participants, improvements could be made to the system’s physical appearance, practical convenience, functionalities, and software integration. Overall, 12 participants would use the system. While participants’ trust could be immediate or grow over time, it could ultimately be conditional on the system’s performance.

Conclusion

Prospective users’ general enthusiasm and trust foster the clinical and commercial success of hybrid closed‐loop systems. However, poor user satisfaction caused by unrealistic expectations and plausible inconveniences and concerns may limit this success. Providing prospective users with comprehensive information while validating their understanding could mitigate unrealistic expectations. Improvements to design and coverage policies could favour uptake.
Evaluation of a pelleted diet for larval mass‐rearing of Anastrepha ludens and Anastrepha obliqua
Authors: Aceituno‐Medina Marysol , Rivera‐Ciprian José Pedro , Hernández Emilio
Published: April 2020

Most artificial diets used for mass‐rearing of fruit fly larvae involve the purchase and independent weighing of each ingredient of the formulation, followed by mixing and diet preparation process. A ready‐to‐use formulation would avoid this time‐consuming task and simplify the preparation procedure, leading to a more standardized diet. In this work, we compared life‐history traits and survival and developmental parameters of Anastrepha ludens Loew and Anastrepha obliqua (Macquart) (Diptera: Tephritidae) reared on two formulations of an artificial diet. Two experiments were performed; first, a conventional non‐pelleted diet was compared to a newly developed pelleted diet, which was mixed with water before being given to the larvae. The second experiment consisted of a comparison between the pelleted diet which was stirred in a mixer with water and dissolved preservatives and a pelleted diet which was only soaked in water with dissolved preservatives. We found that the pelleted diet allowed the mass‐rearing of A. ludens and A. obliqua. Moreover, feeding larvae with pelleted diet led to increased weight of the larva by 7.4 and 11.8%, and of the pupa by 9.5 and 16.7% for A. ludens and A. obliqua, respectively, compared to conventional diet. For process evaluation, the number of activities, handling time, reception, storage, and larval diet preparation were recorded. The pelleted diet only needed soaking in water containing preservatives, thereby simplifying the mass‐rearing process and saving time, space, and labour. Pelletizing is a versatile technology that can be adjusted for better physicochemical quality and reduced microbiological risk. This diet should be of particular interest for the mass‐rearing process in ‘sterile insect technique’ applications.
Food recognition as reflected in seed handling by Messor arenarius ants
Authors: Warburg Ittai
Published: April 2020

This research assessed whether food recognition in Messor arenarius ants is impacted by their food handling.

Food choice experiments between whole‐wheat seeds and halves of wheat seeds cut longitudinally were conducted in the same nest on two consecutive days.

In these experiments, it was found that the proportion of touches of these ants using their antennae on both food items within a collection point during first day of the experiment was significantly higher than the same proportion on the second day of the experiment in the same nest.

The proportion of touches by the ants' forelegs was also higher on the first day of the experiment than on the second day in the same nest, but not significantly.

These findings seem to account for a possible effect of learning, that is, food recognition.
A systematic review evaluating the efficacy and safety of a combination of ablative treatment and self administered treatment versus ablative treatment alone for external anogenital warts
Authors: Feng Cheng , Li Wei , Wang Xiaojun , Zhang Hailin , Si Loubin , Chen Zhixiong , Bai Ming
Published: April 2020

Background

External anogenital warts are proliferative lesions. Till now, there is no consensus on the standard treatment of external anogenital warts. The combination of ablative therapy and self‐administered treatment has been reported to achieve sustained complete clearance than ablative therapy. The aim of this review was to compare the efficacy on achieving complete clearance of warts between the combination of ablative therapy with self‐administered therapy and ablative therapy alone.

Methods

We conducted a systematic review to evaluate the efficacy and safety of the combination of ablative therapy and self‐administered treatment for external anogenital warts. The Cochrane Central Register of Controlled Trials, Medline, Embase and Science Citation Index Expanded, China National Knowledge Infrastructure and Wanfang were searched.

Results

Of 1138 initially identified publications, 37 studies in English and Chinese were included. The combination of ablative therapy and self‐administered treatment therapy showed significantly high complete clearance rates at 4, 8, 12, or 24 weeks after treatment compared to ablative therapy alone. In a subgroup analysis based on the treatment duration of imiquimod cream therapy, 4 and 8 weeks of imiquimod 5% cream plus CO2 laser produced similar efficacy on clearance. The combination therapy is tolerable for patients.

Conclusions

In conclusion, this review provided evidence to support the use of the combination of ablative therapy and self‐administered treatment for external anogenital warts to maintain sustained clearance.
Development of a genomic DNA reference material panel for thalassemia genetic testing
Authors: Yin Zhenzhen , Qu Shoufang , Huang Chuanfeng , Chen Fang , Li Jianbiao , Chen Shiping , Ye Jingyu , Yang Ying , Zheng Yu , Zhang Xi , Yang Xuexi , Xie Longxu , Wei Jitao , Wei Fengxiang , Guo Jian , Huang Jie
Published: April 2020

Introduction

Thalassemia is one of the most common autosomal recessive inherited diseases worldwide, and it is also highly prevalent and variable in southern China. Various types of genetic testing technologies have been developed for diagnosis and screening of thalassemia. Characterized genomic DNA reference materials (RMs) are necessary for assay development, validation, proficiency testing, and quality assurance. However, there are no publicly available RMs for thalassemia genetic testing as yet.

Methods

To address the need for the publicly available DNA RMs for thalassemia genetic testing, the National Institutes for Food and Drug Control and the China National GeneBank established 32 new cell lines with three wild‐type genotypes and 29 distinct genotypes of thalassemia which account for approximately 90% thalassemia carriers in China. The genomic DNA of 32 cell lines was characterized by four clinical genetic testing laboratories using different genetic testing methods and technology platforms.

Results

The genotyping results are concordant among four laboratories. In addition, the results of stability test demonstrated that the genotypes of these DNA samples are not influenced by preanalytical conditions such as long‐term exposure to high‐temperature (37°C) environment and repeated freeze‐thawing.

Conclusion

We developed the first national panel of 32 genomic DNA RMs which are renewable and publicly available for the quality assurance of various genetic testing methods and will facilitate research and development in thalassemia genetic testing.
Whole‐genome resequencing reveals diversity, global and local ancestry proportions in Yunling cattle
Authors: Chen Qiuming , Zhan Jingxi , Shen Jiafei , Qu Kaixing , Hanif Quratulain , Liu Jianyong , Zhang Jicai , Chen Ningbo , Chen Hong , Huang Bizhi , Lei Chuzhao
Published: April 2020

Yunling cattle, a three‐breed cross consisting of 1/2 Brahman cattle, 1/4 Murray Grey cattle and 1/4 Yunnan Yellow cattle, has advantage of rapid growth, good meat quality, enhanced tolerance towards a hot and humid climate, tick resistance and crude feed forbearance. Here, we investigated the genetic diversity, global and local ancestry proportions by sequencing the genomes of 131 Yungling cattle and 31 Brahman cattle (for control). Furthermore, we used 35 published genomes of ancestry breeds (including Angus cattle [ancestry of Murray Grey], Wannan cattle [ancestry of Yunnan Yellow cattle: Wenshan and Dianzhong], Wenshan and Dianzhong cattle) to characterize the formation process of Yunling cattle. The highest nucleotide diversity was found in the Wannan cattle, followed by Wenshan, Dianzhong, Brahman, Yunling and Angus cattle. The results of LD decay in each breed was largely consistent with the results of nucleotide diversity, except for the faster decay in Angus cattle out of a smaller effective population size and a strong bottleneck during the breed formation. The population‐structure analysis revealed that the cross‐breed Yunling cattle harboured the ancestry with Angus (0.44), Brahman (0.48) and Wannan cattle (0.08). Subsequently, we used RFmix to infer local ancestry in Yunling cattle and then performed chi‐squared test to obtain the segments whose proportions of a certain ancestry were excessive compared with the whole‐genome level, leading to 391 Angus, 49 Brahman and 2,312 Wannan segments. Gene annotation and KEGG enrichment analysis revealed that the excessive Angus, Brahman and Wannan segments might contribute to the rapid growth, immune resistance and indigenous adaptation, respectively, in Yunling cattle. Our results help understand ancestry components and formation process in Yunling cattle and will provide an opportunity for selective breeding by molecular approaches in future.
Progression to hypertension in youth and young adults with type 1 or type 2 diabetes: The SEARCH for Diabetes in Youth Study
Authors: Koebnick Corinna , Imperatore Giuseppina , Jensen Elizabeth T. , Stafford Jeanette M. , Shah Amy S. , Mottl Amy K. , Bell Ronny A. , Dabelea Dana , Liese Angela D. , Marcovina Santica M. , D’Agostino Ralph B. , Urbina Elaine M. , Lawrence Jean M.
Published: April 2020

Central obesity may contribute to the development of hypertension in youths with diabetes. The SEARCH for Diabetes in Youth Study followed 1518 youths with type 1 diabetes (T1D) and 177 with type 2 diabetes (T2D) diagnosed when <20 years of age for incident hypertension. Incident hypertension was defined as blood pressure ≥95th percentile (or ≥130/80 mm Hg) or reporting antihypertensive therapy among those without hypertension at baseline. Poisson regression models were stratified by diabetes type and included demographic and clinical factors, clinical site, and waist‐to‐height ratio (WHtR). Youths with T2D were more likely to develop hypertension than those with T1D (35.6% vs 14.8%, P < .0001). For each 0.01 unit of annual increase in WHtR, adjusted relative risk for hypertension was 1.53 (95% CI 1.36‐1.73) and 1.20 (95% CI 1.00‐1.43) for youths with T1D and T2D, respectively. Effective strategies targeted toward reducing central obesity may reduce hypertension among youths with diabetes.
Low birthweight is associated with type 2 diabetes mellitus in Japanese adults: The Toon Health Study
Authors: Yokoyama Maki , Saito Isao , Ueno Megumi , Kato Hiroaki , Yoshida Ayaka , Kawamura Ryoichi , Maruyama Koutatsu , Takata Yasunori , Osawa Haruhiko , Tanigawa Takeshi , Sugiyama Takashi
Published: April 2020

Aims/Introduction

Low birthweight is reportedly associated with type 2 diabetes mellitus; however, this association has not been confirmed in the Japanese population, and whether high birthweight is associated with type 2 diabetes mellitus is controversial. We aimed to investigate the association between birthweight and type 2 diabetes mellitus among a general Japanese population.

Materials and Methods

Overall 1,135 middle‐ to old‐aged Japanese men and women were enrolled in the Toon Health Study. A 75‐g oral glucose tolerance test was used to diagnose type 2 diabetes mellitus, and a questionnaire survey about birthweight was administered. The association between birthweight and the prevalence of type 2 diabetes mellitus in later life of the participants was examined using multivariable logistic regression analysis. Stratified analysis by current body mass index was also carried out.

Results

The mean age was 56.5 ± 12.2 years. Type 2 diabetes mellitus was observed in 9.3% of the participants in this study. Compared with the reference group (2,500–3,999 g), the adjusted odds ratio of the low‐birthweight group (<2,500 g) for type 2 diabetes mellitus was 2.46 (95% confidence interval 1.48–4.10). The association between the high‐birthweight group (≥4000 g) and type 2 diabetes mellitus was not significant after including family history of diabetes in the multivariable model. The odds ratio of the low‐birthweight group for type 2 diabetes mellitus was higher in the overweight/obese group than in the non‐overweight group.

Conclusions

Low birthweight was associated with an increased risk of type 2 diabetes mellitus in a Japanese population, especially in overweight/obese individuals.
Vertical differentiation, product innovation, and dynamic competition
Authors: Baron David P.
Published: April 2020

This paper presents an infinite horizon dynamic model in which two firms compete in a market vertically differentiated by the qualities of their products and consumers have heterogeneous preferences for quality. Given the product qualities offered, the firms engage in price competition that segments the market. In each period each firm can spend on product innovation that if successful increases the quality of its product. Three types of Markov perfect equilibria are identified. A running–coasting equilibrium exhibits increasing quality dominance with one firm undertaking innovation and the other coasting to free ride on the innovation by the first firm. The firm that coasts can have the larger dynamic payoff, so quality dominance does not imply payoff dominance. A second is a leap‐frog equilibrium in which the trailing firm undertakes innovation to leap into the lead. The trailing firm never innovates solely to narrow the gap with the leader, so catch up strategies are never used. In the third both firms undertake innovation, but if both have innovation successes, product differentiation remains the same and profits are reduced by the cost of innovation. The rivalry between Intel and AMD in microprocessors for personal computers provides a motivating example.
Brood parasitism of an open‐water spawning cichlid by the cuckoo catfish
Authors: Takahashi Tetsumi , Koblmüller Stephan
Published: April 2020

The cuckoo catfishSynodontis multipunctatusandS. grandiopsare endemic to Lake Tanganyika and the only known nonavian vertebrates that exhibit obligate interspecific brood parasitism. Seven maternal mouth‐brooding cichlid fish species are reported to be natural hosts of the parasitic catfish and share a common reproductive behaviour that the catfish exploits: cichlid females spawn eggs on the bottom, allowing the catfish female to place her eggs near the cichlid eggs, and the cichlid females collect the catfish eggs by mouth together with their own eggs. However, so far it has not been reported that the cuckoo catfish exploit different spawning behaviours. The genusCyprichromisconsists of five maternal mouth‐brooding species endemic to Lake Tanganyika, most of which spawn and collect eggs in open water. This study reports that the cuckoo catfish also parasitizes the open‐water spawningCyprichromis coloratus, although it may not be a regular host.
Living with diabetes and disadvantage: A qualitative, geographical case study
Authors: Power Tamara , Kelly Ray , Usher Kim , East Leah , Travaglia Jo , Robertson Hamish , Wong Ann , Jackson Debra
Published: April 2020

Aims and objectives

To elucidate the experiences of people living with diabetes, residing in an urban diabetogenic area.

Background

Community‐level social and environmental factors have a role to play in the development of type 2 diabetes mellitus. Socio‐economic deprivation; high obesity rates; high access to fast foods; and multiculturalism contribute to higher rates of diabetes in some geographical areas. However, there is a lack of research examining people's experiences of living with diabetes in diabetogenic areas. The word diabetogenic implies that the phenomenon of interest contributes to the development of diabetes.

Design

Qualitative, geographical case study approach.

Methods

A convenience sample of 17 people living with diabetes in a diabetogenic, low‐socio‐economic urban area participated in face‐to‐face, semi‐structured interviews. Interviews were audio‐recorded, transcribed and analysed thematically. This paper adheres to the COREQ guidelines.

Findings

Four main themes were identified: 1. Diabetes fatalism: Inevitability and inertia; 2. Living with Inequity: Literacy and intersectionality; 3. Impersonal services: Intimidating and overwhelming; and, 4. Education in the community: Access and anecdotes.

Conclusions

This study has highlighted the need to develop local solutions for local problems. In this geographical area, solutions need to address generally lower health literacy, how the community would prefer to receive diabetes education and the issue of diabetes fatalism.

Relevance to clinical practice

Findings from this study have highlighted a need to re‐examine how diabetes education is delivered in communities that are already experiencing multiple disadvantages. There are research and practice connotations for how fatalism is positioned for people at high risk of developing diabetes.
Long‐term biological variability and the generation of a new reference interval for plasma N‐terminal pro‐B‐type natriuretic peptide in Labrador retrievers
Authors: Gomart S. , Allaway D. , Harrison M. , Dickson D. , Seo J. , Ferasin L. , Payne J. R. , Hezzell M. J. , Borgeat K.
Published: April 2020

Objectives

First, to investigate the biological variability of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) in healthy Labrador retrievers and compare this with current laboratory recommendations for dilated cardiomyopathy screening. Second, to calculate a breed‐specific reference interval and validate it in a retrospective cohort.

Materials and Methods

Plasma NT‐proBNP was measured in 51 clinically healthy Labrador retrievers at 0, 2, 4, 6 and 8 weeks. Coefficient of variation for individual dogs over time, the coefficient of variation for the group at each time point and the index of individuality were calculated. A reference interval was derived and tested on a clinical dataset available from four UK cardiology referral centres.

Results

Median NT‐proBNP was 865 pmol/L (315 to 2064 pmol/L). Mean individual coefficient of variation was 19% (95% CI: 16 to 21%) and group coefficient of variation was 43% (95% CI: 41 to 46%), with index of individuality at 0.44. The breed‐specific reference interval was 275 to 2100 pmol/L. In the validation group, 93% of NT‐proBNP measurements from healthy dogs were within the reference interval. NT‐proBNP measurements exceeded the reference interval in 82% of dogs with dilated cardiomyopathy. The upper bound of the reference interval (2100 pmol/L) had a positive predictive value of 90% and a negative predictive value of 87% for identification of dilated cardiomyopathy in this population.

Clinical Significance

Breed‐specific reference intervals might improve the diagnostic accuracy of NT‐proBNP measurement. Applying the currently recommended general cut‐off value to Labradors is likely to result in frequent false positives and diagnosis would be improved by application of the new breed‐specific reference interval calculated here.
Acute sleep deprivation elevates brain and body temperature in rats
Authors: Vishwakarma Lal Chandra , Sharma Binney , Singh Vishwajeet , Jaryal Ashok Kumar , Mallick Hruda Nanda
Published: April 2020

Available sleep deprivation studies lack data on simultaneous changes in hypothalamic, cortical and body temperature during sleep deprivation and recovery. Ten adult male Wistar rats chronically implanted with electroencephalogram, electro‐oculogram and electromyogram electrodes for recording sleep were used in this study. Hypothalamic and cortical temperatures were measured by pre‐implanted thermocouples. A radio transmitter (TA10TAF‐40, DSI USA) was implanted intraperitoneally to measure body temperature. All the temperatures were measured simultaneously at 15‐s intervals during baseline conditions, sleep deprivation and recovery sleep. Sleep deprivation was carried out for 24 hr by the gentle handling method; however, sleep and temperature were only recorded during the first 12 hr of deprivation. During sleep deprivation the body, hypothalamic and cortical temperatures increased significantly as compared to baseline. During recovery sleep, body and cortical temperature recovered earlier than the hypothalamic temperature. Hypothalamic temperature remained higher than the baseline values throughout 12 hr of recovery sleep. In the recovery sleep, cortical temperature decreased immediately and reached near baseline by 4 hr. We observed a quicker return of cortical temperature towards control temperature during recovery sleep compared with hypothalamic and body temperature. The results of the present study show that acute sleep deprivation results in a rise in both cortical and hypothalamic temperature, along with body temperature. A rise in cortical temperature may be a contributing factor for cognitive dysfunction resulting from sleep deprivation.
Acute effects of vagus nerve stimulation parameters on gastric motility assessed with magnetic resonance imaging
Authors: Lu Kun‐Han , Cao Jiayue , Phillips Robert , Powley Terry L. , Liu Zhongming
Published: April 2020

Background

Vagus nerve stimulation (VNS) is an emerging bioelectronic therapy for regulating food intake and controlling gastric motility. However, the effects of different VNS parameters and polarity on postprandial gastric motility remain incompletely characterized.

Methods

In anesthetized rats (N = 3), we applied monophasic electrical stimuli to the left cervical vagus and recorded compound nerve action potential (CNAP) as a measure of nerve response. We evaluated to what extent afferent or efferent pathway could be selectively activated by monophasic VNS. In a different group of rats (N = 13), we fed each rat a gadolinium‐labeled meal and scanned the rat stomach with oral contrast‐enhanced magnetic resonance imaging (MRI) while the rat was anesthetized. We evaluated the antral and pyloric motility as a function of pulse amplitude (0.13, 0.25, 0.5, 1 mA), width (0.13, 0.25, 0.5 ms), frequency (5, 10 Hz), and polarity of VNS.

Key Results

Monophasic VNS activated efferent and afferent pathways with about 67% and 82% selectivity, respectively. Primarily afferent VNS increased antral motility across a wide range of parameters. Primarily efferent VNS induced a significant decrease in antral motility as the stimulus intensity increased (R = −.93, P < .05 for 5 Hz, R = −.85, P < .05 for 10 Hz). The VNS with either polarity tended to promote pyloric motility to a greater extent given increasing stimulus intensity.

Conclusions and Inferences

Monophasic VNS biased toward the afferent pathway is potentially more effective for facilitating occlusive contractions than that biased toward the efferent pathway.
Plant small heat shock proteins – evolutionary and functional diversity
Authors: Waters Elizabeth R. , Vierling Elizabeth
Published: April 2020

Small heat shock proteins (sHSPs) are an ubiquitous protein family found in archaea, bacteria and eukaryotes. In plants, as in other organisms, sHSPs are upregulated by stress and are proposed to act as molecular chaperones to protect other proteins from stress‐induced damage. sHSPs share an ‘α‐crystallin domain’ with a β‐sandwich structure and a diverse N‐terminal domain. Although sHSPs are 12–25 kDa polypeptides, most assemble into oligomers with ≥ 12 subunits. Plant sHSPs are particularly diverse and numerous; some species have as many as 40 sHSPs. In angiosperms this diversity comprises ≥ 11 sHSP classes encoding proteins targeted to the cytosol, nucleus, endoplasmic reticulum, chloroplasts, mitochondria and peroxisomes. The sHSPs underwent a lineage‐specific gene expansion, diversifying early in land plant evolution, potentially in response to stress in the terrestrial environment, and expanded again in seed plants and again in angiosperms. Understanding the structure and evolution of plant sHSPs has progressed, and a model for their chaperone activity has been proposed. However, how the chaperone model applies to diverse sHSPs and what processes sHSPs protect are far from understood. As more plant genomes and transcriptomes become available, it will be possible to explore theories of the evolutionary pressures driving sHSP diversification.
Experimental assessment of tree canopy and leaf litter controls on the microbiome and nitrogen fixation rates of two boreal mosses
Authors: Jean Mélanie , Holland‐Moritz Hannah , Melvin April M. , Johnstone Jill F. , Mack Michelle C.
Published: April 2020

Nitrogen (N2)‐fixing moss microbial communities play key roles in nitrogen cycling of boreal forests. Forest type and leaf litter inputs regulate moss abundance, but how they control moss microbiomes and N2‐fixation remains understudied. We examined the impacts of forest type and broadleaf litter on microbial community composition and N2‐fixation rates of Hylocomium splendens and Pleurozium schreberi.

We conducted a moss transplant and leaf litter manipulation experiment at three sites with paired paper birch (Betula neoalaskana) and black spruce (Picea mariana) stands in Alaska. We characterized bacterial communities using marker gene sequencing, determined N2‐fixation rates using stable isotopes (15N2) and measured environmental covariates.

Mosses native to and transplanted into spruce stands supported generally higher N2‐fixation and distinct microbial communities compared to similar treatments in birch stands. High leaf litter inputs shifted microbial community composition for both moss species and reduced N2‐fixation rates for H. splendens, which had the highest rates. N2‐fixation was positively associated with several bacterial taxa, including cyanobacteria.

The moss microbiome and environmental conditions controlled N2‐fixation at the stand and transplant scales. Predicted shifts from spruce‐ to deciduous‐dominated stands will interact with the relative abundances of mosses supporting different microbiomes and N2‐fixation rates, which could affect stand‐level N inputs.
Optimization of the classical oral cancerization protocol in hamster to study oral cancer therapy
Authors: Santa Cruz Iara S. , Garabalino Marcela A. , Trivillin Verónica A. , Itoiz María E. , Pozzi Emiliano C. C. , Thorp Silvia , Curotto Paula , Guidobono Juan S. , Heber Elisa M. , Nigg David W. , Schwint Amanda E. , Monti Hughes Andrea
Published: April 2020

Objective(s)

The hamster carcinogenesis model recapitulates oral oncogenesis. Dimethylbenz[a]anthracene (DMBA) cancerization induces early severe mucositis, affecting animal's welfare and causing tissue loss and pouch shortening. “Short” pouches cannot be everted for local irradiation for boron neutron capture therapy (BNCT). Our aim was to optimize the DMBA classical cancerization protocol to avoid severe mucositis, without affecting tumor development. We evaluated BNCT in animals cancerized with this novel protocol.

Materials and methods

We studied: Classical cancerization protocol (24 applications) and Classical with two interruptions (completed at the end of the cancerization protocol). BNCT mediated by boronophenylalanine (BPA) was performed in both groups.

Results

The twice‐interrupted group exhibited a significantly lower percentage of animals with severe mucositis versus the non‐interrupted group (17% versus 71%) and a significantly higher incidence of long pouches (100% versus 53%). Tumor development and the histologic characteristics of tumor and precancerous tissue were not affected by the interruptions. For both groups, overall tumor response was more than 80%, with a similar incidence of BNCT‐induced severe mucositis.

Conclusion(s)

The twice‐interrupted protocol reduced severe mucositis during cancerization without affecting tumor development. This favored the animal's welfare and reduced the number of animals to be cancerized for our studies, without affecting BNCT response.
Management of infantile hemangiomas during the COVID pandemic
Authors: Frieden Ilona J. , Püttgen Katherine B. , Drolet Beth A. , Garzon Maria C. , Chamlin Sarah L. , Pope Elena , Mancini Anthony J. , Lauren Christine T. , Mathes Erin F. , Siegel Dawn H. , Gupta Deepti , Haggstrom Anita N. , Tollefson Megha M. , Baselga Eulalia , Morel Kimberly D. , Shah Sonal D. , Holland Kristen E. , Adams Denise M. , Horii Kimberly A. , Newell Brandon D. , Powell Julie , McCuaig Catherine C. , Nopper Amy J. , Metry Denise W. , Maguiness Sheilagh ,   For The Hemangioma Investigator Group
Published: April 2020

The COVID‐19 pandemic has caused significant shifts in patient care including a steep decline in ambulatory visits and a marked increase in the use of telemedicine. Infantile hemangiomas (IH) can require urgent evaluation and risk stratification to determine which infants need treatment and which can be managed with continued observation. For those requiring treatment, prompt initiation decreases morbidity and improves long‐term outcomes. The Hemangioma Investigator Group has created consensus recommendations for management of IH via telemedicine. FDA/EMA‐approved monitoring guidelines, clinical practice guidelines, and relevant, up‐to‐date publications regarding initiation and monitoring of beta‐blocker therapy were used to inform the recommendations. Clinical decision‐making guidelines about when telehealth is an appropriate alternative to in‐office visits, including medication initiation, dosage changes, and ongoing evaluation, are included. The importance of communication with caregivers in the context of telemedicine is discussed, and online resources for both hemangioma education and propranolol therapy are provided.
The prevalence of HPA‐1a alloimmunization and the potential risk of FNAIT depend on both the DRB3*01:01 allele and associated DR‐DQ haplotypes
Authors: Ahlen Maria Therese , Heide Gøril , Husebekk Anne , Skogen Bjørn , Kjeldsen‐Kragh Jens , Stuge Tor B.
Published: April 2020

Alloimmunization against human platelet antigen (HPA)‐1a during pregnancy can cause foetal/neonatal alloimmune thrombocytopenia (FNAIT) and severe bleeding in the foetus or newborn and likely depends on several factors. HPA‐1a alloimmunization is associated with DRB3*01:01, which is associated with several DR‐DQ haplotypes. However, it is not known to what extent these haplotypes contribute to the prevalence of HPA‐1a alloimmunization. HPA‐1a–alloimmunized women, identified in a prospective study, and random donors were typed for selected DRB3, DRB4, DRB1, DQA1 and DQB1 alleles to determine allele and DR‐DQ haplotype frequencies. DRB3*01:01 was carried by 94% HPA‐1a–immunized women compared to 27% in the general population. In the first population, the DR3‐DQ2 haplotype was overrepresented (P < .003). The prevalence of HPA‐1a alloimmunization was estimated to be about twice as frequent with DR3‐DQ2 compared to DR13‐DQ6, together accounting for about 90% of DRB3*01:01–positive individuals. Further, we examined DQB1*02 and DRB4*01:01 alleles for their reported association with HPA‐1a alloimmunization, in the context of DR‐DQ haplotypes. Since ~ 80% of DQB1*02 alleles are linked to the DR3‐DQ2 haplotype, the association might be coincidental. However, the DQB1*02:02–associated DR7‐DQ2 haplotype was also overrepresented in alloimmunized women, suggesting a role for this allele or haplotype in HPA‐1a alloimmunization. As DRB4*01:01 is predominantly associated with the DR7‐DQ2 haplotype in HPA‐1a–alloimmunized individuals, the reported association with FNAIT may be coincidental. Typing for DR‐DQ haplotypes revealed important genetic associations with HPA‐1a alloimmunization not evident from typing individual alleles, and the presence of different DRB3‐associated DR‐DQ haplotypes showed different prevalence of HPA‐1a alloimmunization.
Review of gynaecological malignant melanomas
Authors: Platt Sarah , Wilson Ewan , Pawade Joya , Walther Axel , Newton Claire
Published: April 2020

Key content

Gynaecological malignant melanomas are rare and are most commonly mucosal melanomas.

Prognosis is usually poor, with distant metastases often present at diagnosis.

The introduction of targeted molecular and immunotherapy treatments may improve disease‐free and overall survival rates.

Multidisciplinary management with involvement of gynaecological, dermatological and melanoma teams is imperative.

Learning objectives

To understand the initial presentation and how to investigate gynaecological melanomas.

To appreciate the treatment options available for primary and recurrent disease.

To understand and apply recommended follow‐up pathways.
An insight into neonatal unconjugated hyperbilirubinaemia from the transfusion medicine perspective
Authors: Routray Suman Sudha , Ray Gopal Krushna , Prakash Satya , Mishra Debasish , Das Pankaj Kumar , Mukherjee Somnath
Published: April 2020

Unconjugated hyperbilirubinaemia is a common cause of morbidity and mortality among neonates in Asian and African countries. The aetiology is multifactorial and has wide range of presentation ranging from simple physiological jaundice to severe HDN requiring prompt intervention to prevent long‐term neurological sequelae. Extensive detection of borderline raised bilirubin level in newborn is debatable as it may lead to inappropriately increased phototherapy and unnecessary increased hospital stay. However, those at risk like early presentation of hyperbilirubinaemia within 48 h, prolonged hyperbilirubinaemia, and family history in siblings or having history of HDN must be screened for immune as well as non‐immune causes to prevent the neonate from further severe form of complications. Along with direct antiglobulin test, elution, antibody screening/identification is performed to evaluate the immune causes. Improvement in the molecular technology leads to prompt diagnosis of non‐immune causes which were previously remained as idiopathic. This will aid in the early management like phototherapy or exchange transfusion as per the indication. This review will basically focus on the aetiopathogenesis of neonatal unconjugated hyperbilirubinaemia and approach to immune causes from transfusion medicine prospective.
Vibration attenuates spasm‐like activity in humans with spinal cord injury
Authors: DeForest Bradley A. , Bohorquez Jorge , Perez Monica A.
Published: April 2020

Key points

Cutaneous reflexes were tested to examine the neuronal mechanisms contributing to muscle spasms in humans with chronic spinal cord injury (SCI). Specifically, we tested the effect of Achilles and tibialis anterior tendon vibration on the early and late components of the cutaneous reflex and reciprocal Ia inhibition in the soleus and tibialis anterior muscles in humans with chronic SCI.

We found that tendon vibration reduced the amplitude of later but not earlier cutaneous reflex in the antagonist but not in the agonist muscle relative to the location of the vibration. In addition, reciprocal Ia inhibition between antagonist ankle muscles increased with tendon vibration and participants with a larger suppression of the later component of the cutaneous reflex had stronger reciprocal Ia inhibition from the antagonistic muscle.

Our study is the first to provide evidence that tendon vibration attenuates late cutaneous spasm‐like reflex activity, likely via reciprocal inhibitory mechanisms, and may represent a method, when properly targeted, for controlling spasms in humans with SCI.

The neuronal mechanisms contributing to the generation of involuntary muscle contractions (spasms) in humans with spinal cord injury (SCI) remain poorly understood. To address this question, we examined the effect of Achilles and tibialis anterior tendon vibration at 20, 40, 80 and 120 Hz on the amplitude of the long‐polysynaptic (LPR, from reflex onset to 500 ms) and long‐lasting (LLR, from 500 ms to reflex offset) cutaneous reflex evoked by medial plantar nerve stimulation in the soleus and tibialis anterior, and reciprocal Ia inhibition between these muscles, in 25 individuals with chronic SCI. We found that Achilles tendon vibration at 40 and 80 Hz, but not other frequencies, reduced the amplitude of the LLR in the tibialis anterior, but not the soleus muscle, without affecting the amplitude of the LPR. Vibratory effects were stronger at 80 than 40 Hz. Similar results were found in the soleus muscle when the tibialis anterior tendon was vibrated. Notably, tendon vibration at 80 Hz increased reciprocal Ia inhibition between antagonistic ankle muscles and vibratory‐induced increases in reciprocal Ia inhibition were correlated with decreases in the LLR, suggesting that participants with a larger suppression of later cutaneous reflex activity had stronger reciprocal Ia inhibition from the antagonistic muscle. Our study is the first to provide evidence that tendon vibration suppresses late spasm‐like activity in antagonist but not agonist muscles, likely via reciprocal inhibitory mechanisms, in humans with chronic SCI. We argue that targeted vibration of antagonistic tendons might help to control spasms after SCI.
Conditioned attenuation of dolphin monaural and binaural auditory evoked potentials after preferential stimulation of one ear
Authors: Finneran James J.
Published: April 2020

Previous studies have demonstrated that some species of odontocetes can be conditioned to reduce hearing sensitivity when warned of an impending intense sound; however, the underlying mechanisms remain poorly understood. In the present study, conditioned hearing attenuation was elicited in two bottlenose dolphins by pairing a 10-kHz tone (the conditioned stimulus) with a more intense tone (the unconditioned stimulus) at 28 kHz. Testing was performed in air, with sounds presented via contact transducers. Hearing was assessed via noninvasive measurement of monaural auditory nerve responses (ANR) and binaural auditory brainstem responses (ABR). ABRs/ANRs were measured in response to 40-kHz tone bursts, over 2 to 3-s time intervals before and after the conditioned and unconditioned stimuli. Results showed reductions in ABR/ANR amplitude and increases in latency after pairing the warning and more intense tones. Monaural ANRs from the left and right ears were attenuated by similar amounts when the warning and more intense sounds were preferentially applied to the right ear. The data support a neural mechanism operating at the level of the cochlea and/or auditory nerve and suggest the involvement of neural projections that can affect the contralateral ear.
The hunger forecast
Authors: Voosen Paul
Published: April 2020

How a team of scientists studying drought helped build the world's leading famine prediction model.
Comment on “Light-induced lattice expansion leads to high-efficiency perovskite solar cells”
Authors: Rolston Nicholas , Bennett-Kennett Ross , Schelhas Laura T. , Luther Joseph M. , Christians Jeffrey A. , Berry Joseph J. , Dauskardt Reinhold H.
Published: April 2020

Tsai
et al
. (Reports, 6 April 2018, p. 67) report a uniform light-induced lattice expansion of metal halide perovskite films under 1-sun illumination and claim to exclude heat-induced lattice expansion. We show that by controlling the temperature of the perovskite film under both dark and illuminated conditions, the mechanism for lattice expansion is in fact fully consistent with heat-induced thermal expansion during illumination.
Probing metabolism in time and space
Authors: Alexandrov Theodore
Published: April 2020

Mass spectrometry imaging detects hotspots of metabolite production within cells
Burning bridges in cancer genomes
Authors: Paiano Jacob , Nussenzweig André
Published: April 2020

Cytoskeletal forces break chromosomal fusions and trigger mutational avalanches
Coincidental retinal dysplasia in patients presenting with pseudohypopyon: a series of two cases
Authors: Jakati Saumya , Patel Anamika , Pathengay Avinash , Kaliki Swathi
Published: April 2020

Clinical diagnosis is always challenging in cases with atypical presentation. Herein, we present two cases which masqueraded as ocular infection/inflammation on presentation, were clinically suspicious for retinoblastoma, and histopathology revealed the diagnosis of retinal dysplasia. Case 1 had left corneal perforation with anterior chamber exudates on presentation. On ultrasound B-scan, ill-defined mass was noted, raising a suspicion of malignancy. MRI showed dilated ventricles with midline shift. Vitreous cytology was inconclusive. Enucleation was performed as malignancy could not be ruled out. Histopathology revealed detached retina with dysplastic rosettes in addition to inflammation and multinucleate giant cell reaction. Case 2 presented with right eye anterior chamber pseudohypopyon. Fundus examination revealed diffuse vitreous haze and a suspicious mass in the retinal periphery raising suspicion for retinoblastoma. Histopathology revealed the diagnosis of retinal dysplasia.
Case of neuromyelitis otica: bilateral sensorineural hearing loss and transverse myelopathy following intrathecal chemotherapy
Authors: Castillo-Torres Sergio A , Soto-Rincón Carlos A , Villarreal-Montemayor Héctor J , Chávez-Luévanos Beatriz
Published: April 2020

Neurotoxicity from intrathecally administered chemotherapeutic drugs is frequent, particularly with some agents like methotrexate, which are more prone to developing adverse effects. Myelopathy ranks among the most frequently reported neurological entities; with the diagnosis being straightforward, after ruling out infectious, metabolic, autoimmune or paraneoplastic causes. Scarcity of cases precludes evidence-based recommendations for the management of these complications. The most common therapeutic approach consists of the suspension of chemotherapy, exclusion of infectious and neoplastic causes, with prompt administration of high-dose steroids. We report a 21-year-old patient with acute lymphoblastic leukaemia, who developed acute transverse myelitis and bilateral sensorineural hearing loss, after five rounds of intrathecal methotrexate and cytarabine. Although neurotoxicity from both agents has been documented, this combination has not been previously reported.
Multiple myeloma and pulmonary aspergillosis: dental treatment prior to chemotherapy and management of post extraction complications
Authors: Patrick Amy , Saeed Khadeeja , Kumar Navdeep
Published: April 2020

This case study discusses the dental management of a patient with a history of multiple myeloma and pulmonary aspergillosis, whom was referred to a hospital-based dental service for urgent dental review. The patient had received a dental assessment in primary care prior to commencement of chemotherapy and had four teeth extracted without complications. However, following the commencement of chemotherapy, he presented with a significant infection associated with two of his wisdom teeth resulting in extraction. Despite atraumatic extraction, the upper right wisdom tooth socket developed an oroantral fistula. A multidisciplinary team approach was required to enable effective patient management in this complex patient regarding myeloma, aspergillosis and the medications used including bisphosphonates and chemotherapy. It highlights the higher risk of oral complications that can arise in myelosuppressed patients and emphasises the need to identify potential sources of dental infection prior to the commencement of chemotherapy.