bluuebunny/crossref_metadata_2025_split huggingface dataset:
Postmetamorphic ontogenetic allometry and the evolution of skull shape in Nest‐building frogs Leptodactylus (Anura: Leptodactylidae)
Authors: Duport‐Bru Ana S. , Ponssa María L. , Vera Candioti Florencia 
Published: July 2019

AbstractAllometry constitutes an important source of morphological variation. However, its influence in head development in anurans has been poorly explored. By using geometric morphometrics followed by statistical and comparative methods we analyzed patterns of allometric change during cranial postmetamorphic ontogeny in species of Nest‐building frogs Leptodactylus (Leptodactylidae). We found that the anuran skull is not a static structure, and allometry plays an important role in defining its shape in this group. Similar to other groups with biphasic life‐cycle, and following a general trend in vertebrates, ontogenetic changes mostly involve rearrangement in rostral, otoccipital, and suspensorium regions. Ontogenetic transformations are paralleled by shape changes associated with evolutionary change in size, such that the skulls of species of different intrageneric groups are scaled to each other, and small and large species show patterns of paedomorphic/peramorphic features, respectively. Allometric trajectories producing those phenotypes are highly evolvable though, with shape change direction and magnitude varying widely among clades, and irrespective of changes in absolute body size. These results reinforce the importance of large‐scale comparisons of growth patterns to understand the plasticity, evolution, and polarity of morphological changes in different clades.
Developmental noise and ecological opportunity across space can release constraints on the evolution of plasticity
Authors: Draghi Jeremy 
Published: July 2019

AbstractPhenotypic plasticity is a potentially definitive solution to environment heterogeneity, driving biologists to understand why it is not ubiquitous in nature. While costs and constraints may limit the success of plasticity, we are still far from a complete theory of when these limitations actually proscribe adaptive plasticity. Here I use a simple model of plasticity incorporating developmental noise to explore the competitive and evolutionary relationships of specialist and generalist genotypes spreading across a heterogeneous landscape. Results show that plasticity can arise in the context of specialism, preadapting genotypes to later evolve toward plastic generalism. Developmental noise helps a mutant with imperfect plasticity successfully compete against its ancestor, providing an evolutionary path by which subsequent mutations can refine plasticity toward its optimum. These results address how the complex selection pressures across a heterogeneous environment can help evolution find paths around constraints arising from developmental mechanisms.
Spiders, microbes and sex: Bacterial exposure on copulatory organs alters mating behaviour in funnel‐web spiders
Authors: Spicer Michelle Elise , Pruitt Jonathan N. , Keiser Carl N. 
Published: July 2019

AbstractEnvironmental microbes have the potential to be involved in nearly all behavioural processes. For example, mating systems where males use intromittent organs to transfer sperm to females represent a means by which environmental microbes collected by males can breach entry into females' body cavities during mating. However, the degree to which the acquisition of environmental microbes onto important sex structures alters courtship behaviours remains unknown. Here, we collected bacteria from the copulatory organs of Agelenopsis pennsylvanica funnel‐weaving spiders in situ to test whether exposure to bacteria on copulatory organs can alter hosts' courtship behaviour, reproductive success and survival. We used a standardized assay to repeatedly measure each spider's aggressiveness, a behavioural component of both male courtship and female sexual receptivity. Then, we experimentally altered the bacteria present on male and female spiders' copulatory organs with an application of either (a) a mixture of bacteria collected from conspecifics to increase bacterial presence, (b) an antibiotic to reduce bacterial presence or (c) a procedural control. Each spider was paired with a size‐matched spider of the opposite sex whose copulatory organs were unaltered, and we measured the latency until the onset and the duration of courtship. Spiders were then isolated, and we measured each individual's time until death and female fecundity over the next 40 days. We found that female exposure to bacteria had multiple effects on mating dynamics. Males took over four times longer to begin courting females that had been exposed to bacteria compared to unexposed and antibiotic‐treated females. Only when courting these bacteria‐exposed females, males began courtship sooner when females were more aggressive. Lastly, females whose mate had been exposed to bacteria experienced reduced survival. These data suggest that bacteria present on animals' copulatory organs can alter courtship behaviours, female survivorship, and may potentially play a role in mating dynamics.
Perioperative haemostasis with full‐length, PEGylated, recombinant factor VIII with extended half‐life (rurioctocog alfa pegol) in patients with haemophilia A: Final results of a multicentre, single‐arm phase III trial
Authors: Gruppo Ralph , López‐Fernández Maria‐Fernanda , Wynn Tung T. , Engl Werner , Sharkhawy Marlies , Tangada Srilatha 
Published: July 2019

AbstractIntroductionRurioctocog alfa pegol (BAX 855, TAK‐660) is a PEGylated, full‐length, recombinant factor VIII (rFVIII) with extended half‐life developed from unmodified rFVIII (antihaemophilic factor [recombinant]).AimTo determine the perioperative haemostatic efficacy and safety of rurioctocog alfa pegol in male previously treated patients (PTPs) with severe haemophilia A.MethodsThis multicentre, single‐arm, phase III study included PTPs who were to undergo major or minor elective or minor emergency surgical, dental or other invasive procedures. Rurioctocog alfa pegol dose and frequency were individualized based on patients’ pharmacokinetic profiles for major surgeries and by rurioctocog alfa pegol incremental recovery for minor surgeries. Haemostatic efficacy was assessed using the Global Haemostatic Efficacy Assessment score.ResultsTwenty‐one patients aged 16‐61 years underwent 21 major and five minor surgeries. For all 24 evaluable surgeries, overall haemostatic efficacy was rated as excellent and blood loss comparable to that expected in non‐haemophilic patients. No blood transfusions were required intraoperatively but were administered postoperatively for four surgeries in three patients. Five injury‐related postoperative bleeding episodes occurred in five patients, of which two required additional rurioctocog alfa pegol treatment. Two non‐serious adverse events of mild severity (increased ALT level and headache) were considered possibly related to rurioctocog alfa pegol. There were no deaths or treatment‐related serious adverse events. No patients developed inhibitory antibodies to FVIII or persistent IgG‐ or IgM‐binding antibodies to FVIII, PEG‐FVIII or PEG.ConclusionRurioctocog alfa pegol was well tolerated and effective for perioperative use in patients with haemophilia A and showed no signs of immunogenicity.
C‐C chemokine receptor 4 expression in CD8+ cutaneous T‐cell lymphomas and lymphoproliferative disorders, and its implications for diagnosis and treatment
Authors: Geller Shamir , Hollmann Travis J , Horwitz Steven M , Myskowski Patricia L , Pulitzer Melissa 
Published: July 2019

AimsPatients with aggressive CD8+ cutaneous T‐cell lymphomas (CTCLs) progress rapidly and respond poorly to therapy. Confounding treatment planning, there is clinicopathological overlap between aggressive CD8+ CTCLs and other lymphoproliferative disorders (LPDs). Hence, improved diagnostic methods and therapeutic options are needed. The aim of this study was to examine C‐C chemokine receptor 4 (CCR4) expression as a diagnostic and therapeutic biomarker in CD8+ CTCLs/LPDs.Methods and resultsForty‐nine cases (41 patients) with CD8+ CTCLs/LPDs were examined, including CD8+ mycosis fungoides (MF) (n = 14), aggressive epidermotropic CD8+ cytotoxic T‐cell lymphoma (AETCL) (n = 8), subcutaneous panniculitis‐like T‐cell lymphoma (SPTCL) (n = 7), CD30+ LPDs (n = 6), primary cutaneous γδ T‐cell lymphoma (GDTCL) (n = 6), and others (n = 8). Immunohistochemical tissue staining was performed with a CCR4 monoclonal antibody on formalin‐fixed paraffin‐embedded tissue sections. CCR4 immunostaining was graded as percentage infiltrate, i.e. high (>25%) and low (≤25%), and the results were correlated with clinicopathological diagnoses. CCR4 expression was seen in 69% of the studied cases. Any CCR4 positivity was seen in all CD8+ MF cases, in 83% of CD30+ LPD cases, in 75% of AETCL cases, in 33% of GDTCL cases, and in none of the SPTCL cases. High CCR4 expression was seen in 79% of CD8+ MF cases versus 33% of CD30+ LPD cases, in 17% of GDTCL cases, and in 12.5% of AETCL cases. Patients with more advanced MF stage had higher CCR4 expression.ConclusionsCCR4 immunohistochemistry may be an adjunct in distinguishing advanced CD8+ MF from other CD8+ CTCLs/LPDs. Although CCR4 expression may justify therapeutic targeting of this receptor in CD8+ MF, the role of such therapies in other CD8+ CTCLs/LPDs is not yet clear.
Systemic administration of probiotics reduces the severity of apical periodontitis
Authors: Cosme‐Silva L. , Dal‐Fabbro R. , Cintra L. T. A. , dos Santos V. R. , Duque C. , Ervolino E. , Mogami Bomfim S. , Gomes‐Filho J. E. 
Published: July 2019

AbstractAimTo evaluate the effect of systemic administration of probiotics on the severity of apical periodontitis (AP).MethodologyTwenty‐four male Wistar rats were used. AP was induced in the maxillary left/right first molars. The animals were arranged into groups: Control, Lactobacillus rhamnosus, and Lactobacillus acidophilus. Probiotics were administered orally for gavage (109 colony‐forming units diluted in 5 mL of water for 30 days) during the development of AP. After 30 days, cardiac puncture was performed to analyse the complete blood count. Moreover, microbiological analysis of the root canal contents and saliva was performed. Then, the animals were euthanized and the jaw removed for histopathological and IL‐10, IL‐1β and IL‐6 immunolabeling analyses. After the Shapiro–Wilk test of normality, the Kruskal–Wallis followed by Dunn's test was performed for nonparametric data, and analysis of variance followed by the Tukey test was performed for parametric data (P < 0.05).ResultsNo significance difference was observed in the blood profiles and in the counts of microorganisms from the saliva samples among the groups (P > 0.05). Total microorganism counts in the root canal, the inflammatory infiltrate and the immunostaining for IL‐1β and IL‐6 in AP were significantly lower in the probiotic groups when compared with the control group (P < 0.05). IL‐10 was significantly more immunolabled in the probiotic groups than in the control group (P < 0.05).ConclusionSupplementation with probiotics (Lactobacillus rhamnosus and Lactobacillus acidophilus) had a significant effect on the severity of apical periodontitis in rats, demonstrating the anti‐inflammatory effect of probiotics on the development of apical periodontitis.
Optimal monetary and fiscal policy with social status seeking and liquidity constraints
Authors: Chang Juin‐Jen , Lin Hsieh‐Yu , Shieh Jhy‐Yuan 
Published: July 2019

AbstractWe study the optimal monetary (nominal interest rate) and fiscal (income tax) policy with both consumption‐ and wealth‐induced status seeking under a generalized liquidity constraint on consumption and investment. Our results suggest that monetary policy, in general, has an advantage in correcting status‐seeking‐induced distortions. A simple policy mix is incapable of leading the optimal allocation to be decentralized in the presence of wealth‐based (consumption‐based) status seeking under the cash constraint on consumption (investment) only. As for sub‐optimal policies, the monetary policy follows Friedman's rule while the optimal income tax corrects the consumption‐induced externality, leaving the wealth‐induced externality uncorrected.
Updates on CAR T‐cell therapy in B‐cell malignancies
Authors: Jacoby Elad , Shahani Shilpa A. , Shah Nirali N. 
Published: July 2019

AbstractBy increasing disease‐free survival and offering the potential for long‐term cure, chimeric antigen receptor (CAR) T‐cell therapy has dramatically expanded therapeutic options among those with high‐risk B‐cell malignancies. As CAR T‐cell utilization evolves however, novel challenges are generated. These include determining how to optimally integrate CAR T cells into standard of care and overcoming mechanisms of resistance to CAR T‐cell therapy, such as evolutionary stress induced on cancer cells leading to immunophenotypic changes that allow leukemia to evade this targeted therapy. Compounding these challenges are the limited ability to determine differences between various CAR T‐cell constructs, understanding the generalizability of trial outcomes from multiple sites utilizing unique CAR manufacturing strategies, and comparing distinct criteria for toxicity grading while defining optimal management. Additionally, as understanding of CAR behavior in humans has developed, strategies have appropriately evolved to proactively mitigate toxicities. These challenges offer complimentary insights and guide next steps to enhance the efficacy of this novel therapeutic modality. With a focus on B‐cell malignancies as the paradigm for effective CAR T‐cell therapy, this review describes advances in the field as well as current challenges and future directions.
Cellular therapy: Adoptive immunotherapy with expanded natural killer cells
Authors: Lee Dean A. 
Published: July 2019

AbstractAdoptive immunotherapy with natural killer cells was pioneered 30 years ago in human clinical trials with the development of cytokine‐induced killer cells—unfractionated peripheral blood mononuclear cell (PBMC) populations activated overnight with IL‐2. Higher doses were subsequently made possible through the advent of steady‐state apheresis, allowing the collection of PBMC numbers equivalent to an entire adult blood volume, and increased purity made feasible through magnetic CD3‐depletion and/or CD56‐selection methods. Still, these approaches rarely achieved clinical dosing above a single infusion of 108 NK cells/kg, except with substantial donor‐recipient size mismatch (eg, parents donating cells to children). To address this shortcoming, leukemia cell lines with NK cell‐like function or ex vivo expansion approaches centered on the homeostatic cytokine IL‐15 were developed. Here, we describe the development of an ex vivo expansion system based on a feeder cell expressing membrane‐bound IL‐21 that enables log‐phase growth of primary NK cells for many weeks without inducing senescence, and describe the biology, correlative science, and translation to clinical trials for patients with leukemia, brain tumors, and solid tumors.
Morphology, Morphogenesis, and Molecular Phylogeny of Neobakuella aenigmatica n. sp. (Ciliophora, Spirotrichea, Bakuellidae)
Authors: Moon Ji Hye , Kim Ji Hye , Quintela‐Alonso Pablo , Jung Jae‐Ho 
Published: July 2019

AbstractThe morphology and morphogenesis of a new ciliate species, Neobakuella aenigmatica n. sp., which was discovered in an estuary in Korea, were investigated, using live observation, protargol impregnation, and scanning electron microscopy. This new species is characterized by a large (185–300 × 55–105 μm in vivo), elongate‐ellipsoidal, flexible but not contractile body. It has ellipsoidal, yellowish cortical granules, 1.3 × 1.0 μm in size. The species has invariably 3 frontal and 2 frontoterminal cirri, about 5–10 buccal and 1–6 parabuccal cirri, 7 midventral rows, and 1 right and 2–4 left marginal rows. The outer left marginal row(s) consists of 1–7 short rows of cirri. The nuclear apparatus comprises 130 macronuclear nodules and 2 spherical micronuclei on average. The dorsal ciliature consists of 3 dorsal kineties. The leftmost left marginal row(s) likely develops from anlagen originating from both the rightmost and leftmost left marginal row(s). The molecular phylogenetic tree based on SSU rDNA suggests the nonmonophyly of the genus Neobakuella.
Patient and Caregiver Benefit From a Comprehensive Dementia Care Program: 1‐Year Results From the UCLA Alzheimer's and Dementia Care Program
Authors: Reuben David B. , Tan Zaldy S. , Romero Tahmineh , Wenger Neil S. , Keeler Emmett , Jennings Lee A. 
Published: July 2019

BACKGROUND/OBJECTIVESPersons with Alzheimer disease and related dementias (ADRDs) require comprehensive care that spans health systems and community‐based organizations. This study examined the clinical outcomes of a comprehensive dementia care program and identified subgroups who were more likely to benefit.DESIGNObservational, baseline and 1 year after intervention.SETTINGUrban, academic medical center.PARTICIPANTSA total of 554 persons with dementia and their caregivers who had 1‐year follow‐up evaluations and data on clinical outcomes.INTERVENTIONHealth system‐based comprehensive dementia care management program using nurse practitioner dementia care managers.MEASUREMENTSPatient measures included the Mini‐Mental State Examination (MMSE), the Functional Activities Questionnaire, Basic and Instrumental Activities of Daily Living scales, the Cornell Scale for Depression in Dementia, and the Neuropsychiatric Inventory Questionnaire (NPI‐Q) Severity. Caregiver measures included the Modified Caregiver Strain Index, the Patient Health Questionnaire‐9, NPI‐Q Distress, and the Dementia Burden Scale‐Caregiver). We used established minimal clinically important differences and lowest tertiles of baseline symptoms to define improving symptoms and maintaining low symptoms as clinical benefit for patients and caregivers.RESULTSAt year 1, persons with ADRD improved on all scales, except MMSE and functional status measures; caregivers improved on all scales. Using validated instruments, 314/543 (58%) of patients, 282/447 (63%) of caregivers, and 376/501 (75%) of patients or caregivers demonstrated clinical benefit. In adjusted multivariate models, at year 1, more behavioral symptoms and fewer depression symptoms at baseline were associated with patient improvement; and fewer baseline depression symptoms were associated with maintaining low behavioral symptoms. Male caregiver sex, higher baseline caregiver burden, and caring for patients with fewer baseline depression symptoms were associated with caregiver improvement. Male caregiver sex and patients with fewer depression symptoms, fewer behavioral symptoms, and more functional impairment at baseline were associated with caregivers maintaining low burden at 1 year.CONCLUSIONSHealth system‐based comprehensive dementia care management is a promising approach to improving clinical outcomes, with benefits for both patients and caregivers. J Am Geriatr Soc 67:2267–2273, 2019
Predictive Ability of a Serious Game to Identify Emergency Patients With Unrecognized Delirium
Authors: Lee Jacques S. , Tong Tiffany , Tierney Mary C. , Kiss Alex , Chignell Mark 
Published: July 2019

OBJECTIVESRecognition of delirium in the emergency department (ED) is poor. Our objectives were to assess: (1) the diagnostic accuracy of the Predicting Emergency department Delirium with an Interactive Computer Tablet (PrEDICT) “serious game” to identify older ED patients with delirium compared to clinical recognition and (2) the feasibility of the PrEDICT application compared to existing tests of attention.DESIGNProspective observational study.SETTINGED of a Canadian tertiary care center.PARTICIPANTSWe included ED patients, aged 70 years and older, with a minimum 4‐hour stay. We excluded anyone with critical illness, communication barriers, and visual impairment or those unable to use a computer tablet. None had prevalent delirium by ED clinicians' routine clinical assessment.MEASUREMENTSParticipants were asked to tap targets on a tablet at four difficulty levels. Time and accuracy were automatically recorded. Other measures included the Confusion Assessment Method, the Delirium Severity Index, the Digit Vigilance Test (DVT), and the Choice Reaction Test (CRT).RESULTSWe enrolled 203 patients. Their average age was 80.6 years, 49.8% were female, and their average ED length of stay was 15.9 hours. Sixteen subjects had clinically unrecognized delirium, and 14 of them completed the PrEDICT game (87.5%). We developed a threshold score with 100% sensitivity (95% confidence interval [CI] = 76.8%‐100.0%) and 59.7% specificity (95% CI = 52.3%‐66.6%) to identify patients with clinically unrecognized delirium. The area under the curve was 0.86 (95% CI = 0.77‐0.94). Completion rates were 196/203 (96.6%) for the PrEDICT serious game compared to 128/203 (63.1%) for the CRT and 51/203 (25.1%) for the DVT.CONCLUSIONOlder ED patients were able to use our serious game, including 87.5% of those with clinically unrecognized delirium. The PrEDICT application has potential to act as a sensitive screening tool to identify older ED patients with clinically unrecognized delirium. J Am Geriatr Soc 67:2370–2375, 2019
Sleep problems in Korean children with Down syndrome and parental quality of life
Authors: Choi E. K. , Jung E. , Van Riper M. , Lee Y. J. 
Published: July 2019

AbstractBackgroundSleep problems are common among children with Down syndrome (DS), and they can have a serious impact on children with DS as well as their parents and other family members. Specific aims of this study were to evaluate parent‐reported sleep problems in children with DS and to examine the relationship between the sleep behaviour of children with DS and their parents' quality of life (QOL).MethodA cross‐sectional survey was conducted in September and October of 2017. Parents of children with DS were recruited from an online self‐support community for parents of children with DS in South Korea. The mean age of the parents and children with DS was 40.40 years (SD = 5.09) and 7.89 years (SD = 3.03), respectively. Children's sleep problems and parents' QOL were assessed using the Children's Sleep Habits Questionnaire and the abbreviated version of the World Health Organization Quality of Life scale, respectively.ResultsResults revealed that 83% of the parents reported that their child with DS experienced sleep problems. Children with DS had significantly more bedtime resistance, night waking, parasomnias and sleep‐disordered breathing than did typically developing children. In addition, their Children's Sleep Habits Questionnaire scores were higher than those of typically developing children. Moreover, being older, being male and having more severe developmental delays were significant risk factors for sleep problems among children with DS. Furthermore, sleep problems in children with DS negatively affected parents' QOL.ConclusionsSleep problems negatively affect children with DS as well as their parents; therefore, health care providers should be aware of these issues and help parents manage sleep problems proactively.