bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hallucinations Are Real to Patients With Dementia
Authors: Hamdy R. C. , Kinser A. , Lewis J. V. , Copeland R. , Depelteau A. , Kendall-Wilson T. , Whalen K. 
Published: November 2017

In this case study, we present a patient with preexistent posttraumatic stress disorder and psychosis who has been recently diagnosed with Dementia with Lewy Bodies. He is experiencing vivid hallucinations. What went wrong between him and his wife as a result of these hallucinations is presented. Alternative actions that could have been used are suggested. Objectives At the end of this case study, readers will know the following: The characteristic clinical features of Dementia with Lewy Bodies (DLB). Patients experiencing hallucinations should not be contradicted, to them, these hallucinations are real. Easy distractibility and short attention span can be exploited to avert or defuse potentially catastrophic situations. Patients with dementia should not have access to loaded guns.
Tympanometric Patterns of Children with Allergic Rhinitis Treated at a Tertiary Health Institution
Authors: Fasunla Ayotunde James , Ijitola Julius Olowo , Nwaorgu Onyekwere George 
Published: November 2017

ObjectivesTo determine the prevalence of otitis media with effusion (OME) and compare patterns of tympanogram between children with and without allergic rhinitis in Ibadan, Nigeria.Study DesignA case‐control study of children (2‐7 years) with AR from May 2015 to March 2016.SettingTertiary hospital.Subjects and MethodsConsecutive 86 children with AR and 86 healthy controls (nonallergic) participated in the study. A structured questionnaire was administered to parents or caregivers of the participants to obtain relevant sociodemographic and clinical information. Diagnosis of AR was by symptomatology and nasal cytology. Both groups had ear, nose, and throat examination and tympanometric evaluation. OME was diagnosed according to Jerger’s tympanometric patterns.ResultsThe mean ± SD ages of cases and controls were 3.80 ± 1.72 and 3.78 ± 1.71 years, respectively. All cases presented with watery nasal discharge, bouts of sneezing, and nasal itching. The duration of AR symptoms was 18 ± 13 months. Among cases and controls, Jerger’s type A tympanogram was the most common pattern, while type C was the least common. Thirty‐nine (45.3%) children with AR had OME, as compared with 8 (9.3%) controls, and the difference was statistically significant (P <. 001; odds ratio = 8.090; 95% CI = 3.48‐18.79).ConclusionPrevalence of OME was significantly high among children with AR. Jerger’s type B and C tympanograms were more common among children with AR than the healthy pediatric population. This background information supports the need for routine tympanometric evaluation of children with AR.
Aging of hematopoietic stem cells
Authors: de Haan Gerald , Lazare Seka Simone 
Published: November 2017

AbstractHematopoietic stem cells (HSCs) ensure a balanced production of all blood cells throughout life. As they age, HSCs gradually lose their self-renewal and regenerative potential, whereas the occurrence of cellular derailment strongly increases. Here we review our current understanding of the molecular mechanisms that contribute to HSC aging. We argue that most of the causes that underlie HSC aging result from cell-intrinsic pathways, and reflect on which aspects of the aging process may be reversible. Because many hematological pathologies are strongly age-associated, strategies to intervene in aspects of the stem cell aging process may have significant clinical relevance.
Anemia at older age: etiologies, clinical implications, and management
Authors: Stauder Reinhard , Valent Peter , Theurl Igor 
Published: November 2017

Abstract
Anemia is quite frequently diagnosed in older individuals and is a key indicator of various reactive and clonal conditions. Many underlying diseases, like myelodysplastic syndrome (MDS), develop preferentially in elderly individuals. The prevalence of anemia at older age is increasing, and this is mainly attributable to more frequently applied diagnostics and demographic changes in our societies. The etiology of anemia at older age is complex and ranges from bone marrow failure syndromes to chronic kidney disease, and from nutritional deficiencies to inflammatory processes including inflammaging in immunosenescence. In a smaller number of cases, no clear-cut etiology is identified. These patients are referred to as unexplained anemia or idiopathic cytopenia of unknown significance. In others, somatic mutations in leukocytes are found, but diagnostic criteria for MDS or other hematologic diseases are not fulfilled, a condition termed clonal cytopenia of undetermined significance. Management of anemias at older age depends on (1) the severity of the anemia, (2) underlying condition(s), and (3) patient-related factors, including comorbidities. Even a mild anemia may substantially affect physical and cognitive capacities and quality of life. An underestimated aspect is that because of age-related changes, organ function such as erythropoietin production in the kidney may become suboptimal. Management and treatment of anemia in older patients often require a multidisciplinary approach and detailed investigations of organ function. In this article, we review current concepts around anemias at older age, with special emphasis on etiologies, clinical implications, and innovative concepts in the management of these patients.
Age-related clonal hematopoiesis
Authors: Shlush Liran I. 
Published: November 2017

Abstract
Age-related alterations in the human blood system occur in B cells, T cells, cells of the innate system, as well as hematopoietic stem and progenitor cells (HSPCs). Interestingly, age-related, reduced genetic diversity can be identified at the stem cell level and also independently in B cells and T cells. This reduced diversity is most probably related to somatic mutations or to changes in the microenvironmental niche. Either process can select for specific clones or cause repeated evolutionary bottlenecks. This review discusses the age-related clonal expansions in the human HSPC pool, which was termed in the past age-related clonal hematopoiesis (ARCH). ARCH is defined as the gradual, clonal expansion of HSPCs carrying specific, disruptive, and recurrent genetic variants, in individuals without clear diagnosis of hematological malignancies. ARCH is associated not just with chronological aging but also with several other, age-related pathological conditions, including inflammation, vascular diseases, cancer mortality, and high risk for hematological malignancies. Although it remains unclear whether ARCH is a marker of aging or plays an active role in these various pathophysiologies, it is suggested here that treating or even preventing ARCH may prove to be beneficial for human health. This review also describes a decision tree for the diagnosis and follow-up for ARCH in a research setting.
Frailty and the management of hematologic malignancies
Authors: Abel Gregory A. , Klepin Heidi D. 
Published: November 2017

Abstract
The majority of blood cancers occur in the elderly. This fact conspires with an aging population in many countries to make rigorous assessment for frailty increasingly important for hematologic oncologists. In this review, we first define frailty and its relevance for patients with hematologic malignancy. Next, we review current data regarding the effect of domains of frailty on outcomes for blood cancers including myelodysplastic syndromes, acute leukemia, non-Hodgkin lymphomas such as chronic lymphocytic leukemia, and multiple myeloma. Finally, after presenting assessment and treatment options for the practicing hematologist, we propose elements of a new research agenda for geriatric hematology: the exchange of age limits for rigorous frailty screening, development of disease-specific measures, and inclusion of functional and patient-reported outcomes alongside survival.
A phase 1 study of romidepsin and pralatrexate reveals marked activity in relapsed and refractory T-cell lymphoma
Authors: Amengual Jennifer E. , Lichtenstein Renee , Lue Jennifer , Sawas Ahmed , Deng Changchun , Lichtenstein Emily , Khan Karen , Atkins Laine , Rada Aishling , Kim Hye A. , Chiuzan Codruta , Kalac Matko , Marchi Enrica , Falchi Lorenzo , Francescone Mark A. , Schwartz Lawrence , Cremers Serge , O’Connor Owen A. 
Published: November 2017

Key Points
The combination of romidepsin and pralatrexate is safe and well tolerated in patients with relapsed/refractory lymphoma. The combination led to an overall response rate of 71% (10/14, with 4/14 complete responses) in patients with relapsed/refractory T-cell lymphoma.
Management of newly diagnosed immune thrombocytopenia: can we change outcomes?
Authors: Neunert Cindy E. 
Published: November 2017

AbstractImmune thrombocytopenia resulting from antibody-mediated platelet destruction combined with impaired platelet production is a common cause of thrombocytopenia. The decision to treat newly diagnosed patients is based on several factors including ceasing hemorrhagic manifestations, increasing the platelet count, prevention of bleeding, and inducing remission. Current standard first-line therapy is a course of corticosteroids. Although this treatment paradigm increases the platelet count in the majority of patients, a high percentage relapse after discontinuation of corticosteroid therapy. For this reason, intensification of first-line therapy that results in superior long-term remission rates would be desirable. This manuscript focuses primarily on adults with idiopathic thrombocytopenic purpura (ITP), highlighting pediatric data and practice when applicable. The primary aim is to outline upfront strategies for treatment-naive patients with ITP to enhance remission rates, taking into account assessment of the risks and benefits of these approaches.
Anisotropic Müller glial scaffolding supports a multiplex lattice mosaic of photoreceptors in zebrafish retina
Authors: Nagashima Mikiko , Hadidjojo Jeremy , Barthel Linda K. , Lubensky David K. , Raymond Pamela A. 
Published: November 2017

Abstract

Background
The multiplex, lattice mosaic of cone photoreceptors in the adult fish retina is a compelling example of a highly ordered epithelial cell pattern, with single cell width rows and columns of cones and precisely defined neighbor relationships among different cone types. Cellular mechanisms patterning this multiplex mosaic are not understood. Physical models can provide new insights into fundamental mechanisms of biological patterning. In earlier work, we developed a mathematical model of photoreceptor cell packing in the zebrafish retina, which predicted that anisotropic mechanical tension in the retinal epithelium orients planar polarized adhesive interfaces to align the columns as cone photoreceptors are generated at the retinal margin during post-embryonic growth.

Methods
With cell-specific fluorescent reporters and in vivo imaging of the growing retinal margin in transparent juvenile zebrafish we provide the first view of how cell packing, spatial arrangement, and cell identity are coordinated to build the lattice mosaic. With targeted laser ablation we probed the tissue mechanics of the retinal epithelium.

Results
Within the lattice mosaic, planar polarized Crumbs adhesion proteins pack cones into a single cell width column; between columns, N-cadherin-mediated adherens junctions stabilize Müller glial apical processes. The concentration of activated pMyosin II at these punctate adherens junctions suggests that these glial bands are under tension, forming a physical barrier between cone columns and contributing to mechanical stress anisotropies in the epithelial sheet. Unexpectedly, we discovered that the appearance of such parallel bands of Müller glial apical processes precedes the packing of cones into single cell width columns, hinting at a possible role for glia in the initial organization of the lattice mosaic. Targeted laser ablation of Müller glia directly demonstrates that these glial processes support anisotropic mechanical tension in the planar dimension of the retinal epithelium.

Conclusions
These findings uncovered a novel structural feature of Müller glia associated with alignment of photoreceptors into a lattice mosaic in the zebrafish retina. This is the first demonstration, to our knowledge, of planar, anisotropic mechanical forces mediated by glial cells.
Prenatal High Estradiol Exposure Induces Sex-Specific and Dietarily Reversible Insulin Resistance Through Decreased Hypothalamic INSR
Authors: Wang Hui-Hui , Zhou Cheng-Liang , Lv Min , Yang Qian , Li Ju-Xue , Hou Min , Lin Jing , Liu Xin-Mei , Wu Yan-Ting , Sheng Jian-Zhong , Huang He-Feng 
Published: November 2017

AbstractAn adverse intrauterine environment may induce adult disease in offspring, but the mechanisms are not well understood. It is reported that fresh embryo transfer (ET) in assisted reproductive technology leads to high maternal estradiol (E2), and prenatal high E2 exposure increases the risk of organ disorders in later life. We found that male newborns and children of fresh ET showed elevated fasting insulin and homeostasis model of assessment for insulin resistance index (HOMA-IR) scores. Male mice with high prenatal estradiol exposure (HE) grew heavier than control mice and developed insulin resistance; they also showed increased food intake, with increased orexigenic hypothalamic neuropeptide Y (NPY) expression. The hypothalamic insulin receptor (INSR) was decreased in male HE mice, associated with elevated promoter methylation. Chronic food restriction (FR) in HE mice reversed insulin resistance and rescued hypothalamic INSR expression by correcting the elevated Insr promoter methylation. Our findings suggest that prenatal exposure to high E2 may induce sex-specific metabolic disorders in later life through epigenetic programming of hypothalamic Insr promoter, and dietary intervention may reverse insulin resistance by remodeling its methylation pattern.
The resurrection of the PIDDosome – emerging roles in the DNA-damage response and centrosome surveillance
Authors: Sladky Valentina , Schuler Fabian , Fava Luca L. , Villunger Andreas 
Published: November 2017

ABSTRACT
The PIDDosome is often used as the alias for a multi-protein complex that includes the p53-induced death domain protein 1 (PIDD1), the bipartite linker protein CRADD (also known as RAIDD) and the pro-form of an endopeptidase belonging to the caspase family, i.e. caspase-2. Yet, PIDD1 variants can also interact with a number of other proteins that include RIPK1 (also known as RIP1) and IKBKG (also known as NEMO), PCNA and RFC5, as well as nucleolar components such as NPM1 or NCL. This promiscuity in protein binding is facilitated mainly by autoprocessing of the full-length protein into various fragments that contain different structural domains. As a result, multiple responses can be mediated by protein complexes that contain a PIDD1 domain. This suggests that PIDD1 acts as an integrator for multiple types of stress that need instant attention. Examples are various types of DNA lesion but also the presence of extra centrosomes that can foster aneuploidy and, ultimately, promote DNA damage. Here, we review the role of PIDD1 in response to DNA damage and also highlight novel functions of PIDD1, such as in centrosome surveillance and scheduled polyploidisation as part of a cellular differentiation program during organogenesis.
Live imaging reveals distinct modes of neutrophil and macrophage migration within interstitial tissues
Authors: Barros-Becker Francisco , Lam Pui-Ying , Fisher Robert , Huttenlocher Anna 
Published: November 2017

ABSTRACT
Cell motility is required for diverse processes during immunity and inflammation. Classically, leukocyte motility is defined as an amoeboid type of migration, however some leukocytes, like macrophages, also employ a more mesenchymal mode of migration. Here, we sought to characterize the mechanisms that regulate neutrophil and macrophage migration in vivo by using real-time imaging of leukocyte motility within interstitial tissues in zebrafish larvae. Neutrophils displayed a rounded morphology and rapid protease-independent motility, lacked defined paxillin puncta, and had persistent rearward polarization of stable F-actin and the microtubule network. By contrast, macrophages displayed an elongated morphology with reduced speed and increased directional persistence and formed paxillin-containing puncta but had a less-defined polarization of the microtubule and actin networks. We also observed differential effects of protease inhibition, microtubule disruption and ROCK inhibition on the efficiency of neutrophil and macrophage motility. Taken together, our findings suggest that larval zebrafish neutrophils and macrophage display distinct modes of migration within interstitial tissues in vivo.
TFCP2L1 represses multiple lineage commitment of mouse embryonic stem cells through MTA1 and LEF1
Authors: Liu Kuisheng , Zhang Yan , Liu Dahai , Ying Qi-Long , Ye Shoudong 
Published: November 2017

ABSTRACT
TFCP2L1 is a transcription factor that is crucial for self-renewal of mouse embryonic stem cells (mESCs). How TFCP2L1 maintains the pluripotent state of mESCs, however, remains unknown. Here, we show that knockdown of Tfcp2l1 in mESCs induces the expression of endoderm, mesoderm and trophectoderm markers. Functional analysis of mutant forms of TFCP2L1 revealed that TFCP2L1 depends on its N-terminus and CP2-like domain to maintain the undifferentiated state of mESCs. The N-terminus of TFCP2L1 is mainly associated with the suppression of mesoderm and trophectoderm differentiation, while the CP2-like domain is closely related to the suppression of endoderm commitment. Further studies showed that MTA1 directly interacts with TFCP2L1 and is indispensable for the TFCP2L1-mediated self-renewal-promoting effect and endoderm-inhibiting action. TFCP2L1-mediated suppression of mesoderm and trophectoderm differentiation, however, seems to be due to downregulation of Lef1 expression. Our study thus provides an expanded understanding of the function of TFCP2L1 and the pluripotency regulation network of ESCs.
Multiple pathways facilitate the biogenesis of mammalian tail-anchored proteins
Authors: Casson Joseph , McKenna Michael , Haßdenteufel Sarah , Aviram Naama , Zimmerman Richard , High Stephen 
Published: November 2017

ABSTRACT
Tail-anchored (TA) proteins are transmembrane proteins with a single C-terminal transmembrane domain, which functions as both their subcellular targeting signal and membrane anchor. We show that knockout of TRC40 in cultured human cells has a relatively minor effect on endogenous TA proteins, despite their apparent reliance on this pathway in vitro. These findings support recent evidence that the canonical TRC40 pathway is not essential for TA protein biogenesis in vivo. We therefore investigated the possibility that other ER-targeting routes can complement the TRC40 pathway and identified roles for both the SRP pathway and the recently described mammalian SND pathway in TA protein biogenesis. We conclude that, although TRC40 normally plays an important role in TA protein biogenesis, it is not essential, and speculate that alternative pathways for TA protein biogenesis, including those identified in this study, contribute to the redundancy of the TRC40 pathway.
Lower limb biomechanical analysis during an unanticipated step on a bump reveals specific adaptations of walking on uneven terrains
Authors: Panizzolo Fausto A. , Lee Sangjun , Miyatake Taira , Rossi Denise Martineli , Siviy Christopher , Speeckaert Jozefien , Galiana Ignacio , Walsh Conor J. 
Published: November 2017

ABSTRACT
Although it is clear that walking over different irregular terrain is associated with altered biomechanics, there is little understanding of how we quickly adapt to unexpected variations in terrain. This study aims to investigate which adaptive strategies humans adopt when performing an unanticipated step on an irregular surface, specifically a small bump. Nine healthy male participants walked at their preferred walking speed along a straight walkway during five conditions: four involving unanticipated bumps of two different heights, and one level walking condition. Muscle activation of eight lower limb muscles and three-dimensional gait analysis were evaluated during these testing conditions. Two distinct adaptive strategies were found, which involved no significant change in total lower limb mechanical work or walking speed. An ankle-based strategy was adopted when stepping on a bump with the forefoot, whereas a hip-based strategy was preferred when stepping with the rearfoot. These strategies were driven by a higher activation of the plantarflexor muscles (6–51%), which generated a higher ankle joint moment during the forefoot conditions and by a higher activation of the quadriceps muscles (36–93%), which produced a higher knee joint moment and hip joint power during the rearfoot conditions. These findings provide insights into how humans quickly react to unexpected events and could be used to inform the design of adaptive controllers for wearable robots intended for use in unstructured environments that can provide optimal assistance to the different lower limb joints.
Transparent anemone shrimp (Ancylomenes pedersoni) become opaque after exercise and physiological stress in correlation with increased hemolymph perfusion
Authors: Bagge Laura E. , Kinsey Stephen T. , Gladman Justin , Johnsen Sönke 
Published: November 2017

ABSTRACT
Whole-body transparency, an effective camouflage strategy in many aquatic species, can be disrupted by environmental and/or physiological stressors. We found that tail-flip escape responses temporarily disrupt the transparency of the anemone shrimp Ancylomenes pedersoni. After as few as three tail flips, the previously transparent abdominal muscle became cloudy. Eliciting additional tail flips to the point of exhaustion (16±1 s.e.m.; n=23) resulted in complete opacity, though the original transparency returned after 20–60 min of inactivity. We hypothesized that an exercise-induced increase in blood volume between muscle fibers creates regions of low refractive index fluid between high refractive index muscles, thereby increasing light scattering. We documented pre- and post-contraction perfusion by injecting Alexa Fluor 594 wheat germ agglutinin that labeled sarcolemmal surfaces and endothelial cells in contact with hemolymph and found more hemolymph perfused through the abdominal tissue post-exercise, presumably owing to more capillaries opening. In addition, we altered salinity (to 55‰ and 8‰), perforated the abdomen and injected a vasodilator. All three treatments increased both perfusion and opacity, lending further support to our hypothesis that increased hemolymph perfusion to the abdomen is one mechanism that can disrupt a shrimp's transparency. The fact that transparent shrimp at rest have little to no evidence of perfusion to their abdominal musculature (unlike the opaque shrimp Lysmata pederseni, which had more perfusion even at rest) indicates that they may experience significant physiological trade-offs in order to maintain their transparency; specifically, limiting blood flow and thereby reducing oxygen delivery may result in reduced performance.