Miracle-dz/UniFAR-FTUs huggingface dataset:
New treatment options have changed the survival of patients with follicular lymphoma.

BACKGROUND The natural history of follicular lymphoma is believed not to have changed over the last 30 years. Median survivals have ranged from 7 to 10 years, and the disease is considered incurable. However, multiple new treatment options have been developed in the last decade, and their impact on survival of follicular lymphoma remains unknown. PATIENTS AND METHODS In the current analysis, we identified all previously untreated, advanced-stage, follicular lymphoma patients treated with the following three sequential treatment approaches: cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy +/- nonspecific immunostimulants (Southwest Oncology Group [SWOG] 7426 and 7713: 1974 to 1983); prednisone, methotrexate, doxorubicin, cyclophosphamide, and etoposide (ProMACE) plus mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) +/- interferon (SWOG 8809: 1988 to 1994); and CHOP followed by monoclonal antibody (MoAb) therapy (SWOG 9800 and 9911: 1998 to 2000). We assessed the patients' progression-free survival (PFS) and overall survival (OS). The MoAb trials included CHOP followed by rituximab (SWOG 9800) and CHOP followed by (131)I-tositumomab (SWOG 9911). RESULTS The PFS curves for the CHOP and ProMACE-MOPP studies are overlapping, with 4-year PFS estimates of 46% and 48%, respectively. However, the PFS rate of the CHOP + MoAb studies is significantly improved at 61% (P = .005). The OS curves show improvement with each succeeding study. The 4-year estimate of OS is 69% for the CHOP regimens, 79% for the ProMACE-MOPP study, and 91% for the CHOP + MoAb regimens (P < .001). These conclusions were retained after adjusting for differences in prognostic factors between the study groups. CONCLUSION The results of this study suggest that OS for patients with follicular lymphoma has improved over time and that the choice of initial therapy may matter.
Pathophysiology of glia in perinatal white matter injury

Injury to the preterm brain has a particular predilection for cerebral white matter. White matter injury (WMI) is the most common cause of brain injury in preterm infants and a major cause of chronic neurological morbidity including cerebral palsy. Factors that predispose to WMI include cerebral oxygenation disturbances and maternal–fetal infection. During the acute phase of WMI, pronounced oxidative damage occurs that targets late oligodendrocyte progenitors (pre‐OLs). The developmental predilection for WMI to occur during prematurity appears to be related to both the timing of appearance and regional distribution of susceptible pre‐OLs that are vulnerable to a variety of chemical mediators including reactive oxygen species, glutamate, cytokines, and adenosine. During the chronic phase of WMI, the white matter displays abberant regeneration and repair responses. Early OL progenitors respond to WMI with a rapid robust proliferative response that results in a several fold regeneration of pre‐OLs that fail to terminally differentiate along their normal developmental time course. Pre‐OL maturation arrest appears to be related in part to inhibitory factors that derive from reactive astrocytes in chronic lesions. Recent high field magnetic resonance imaging (MRI) data support that three distinct forms of chronic WMI exist, each of which displays unique MRI and histopathological features. These findings suggest the possibility that therapies directed at myelin regeneration and repair could be initiated early after WMI and monitored over time. These new mechanisms of acute and chronic WMI provide access to a variety of new strategies to prevent or promote repair of WMI in premature infants. GLIA 2014;62:1790–1815
Macrophages transfer antigens to dendritic cells by releasing exosomes containing dead‐cell‐associated antigens partially through a ceramide‐dependent pathway to enhance CD4+ T‐cell responses

Defects in rapid clearance of apoptotic cells lead to an accumulation of dead cells (late apoptotic or secondary necrotic cells), which results in an aberrant immune response. However, little is known about whether and how macrophages (Mφs) cooperate with dendritic cells (DCs) in the presentation of dead‐cell‐associated antigens in this process. By transferring high numbers of dead cells to mimic a failure of apoptotic cell clearance in vivo, we found that Mφs and neutrophils were the predominant phagocytes in the uptake of dead cells in the spleen. Moreover, both Mφs and DCs were required for an optimal CD4+ T‐cell response triggered by dead‐cell‐associated antigens. Importantly, although Mφs alone had a poor capacity for antigen presentation, they could transfer phagocytosed antigens to DCs for potent antigen presentation to enhance T‐cell responses. Finally, we found that exosomes released from Mφs acted as a transmitter to convey antigens to DCs partially in a ceramide‐dependent manner, since treatment with the neutral sphingomyelinase inhibitor GW4869 and spiroepoxide resulted in a significant reduction of T‐cell proliferation in vitro and in vivo. These findings point to a novel pathway of cross‐talk between Mφs and DCs, which will be helpful to explain possible mechanisms for autoimmune diseases characterized by increased rates of apoptosis.
The Polymorphic Evolution Sequence for Populations with Phenotypic Plasticity

In this paper we study a class of stochastic individual-based models that describe the evolution of haploid populations where each individual is characterised by a phenotype and a genotype. The phenotype of an individual determines its natural birth- and death rates as well as the competition kernel, $c(x,y)$ which describes the induced death rate that an individual of type $x$ experiences due to the presence of an individual or type $y$. When a new individual is born, with a small probability a mutation occurs, i.e. the offspring has different genotype as the parent. The novel aspect of the models we study is that an individual with a given genotype may express a certain set of different phenotypes, and during its lifetime it may switch between different phenotypes, with rates that are much larger then the mutation rates and that, moreover, may depend on the state of the entire population. The evolution of the population is described by a continuous-time, measure-valued Markov process. In our last paper [4], such a model was proposed to describe tumor evolution under immunotherapy. In the present paper we consider a large class of models which comprises the example studied in [4] and analyse their scaling limits as the population size tends to infinity and the mutation rate tends to zero. Under suitable assumptions, we prove convergence to a Markov jump process that is a generalisation of the polymorphic evolution sequence (PES) as analysed by Champagnat and Meleard [8, 10].
Development of resistance in Cronobacter sakazakii ATCC 29544 to thermal and nonthermal processes after exposure to stressing environmental conditions

Aims: The objective was to study the response of Cronobacter sakazakii ATCC 29544 cells to heat, pulsed electric fields (PEF), ultrasound under pressure (Manosonication, MS) and ultraviolet light (UV‐C) treatments after exposure to different sublethal stresses that may be encountered in food‐processing environments.
A serpentinite-hosted ecosystem in the Southern Mariana Forearc

Several varieties of seafloor hydrothermal vents with widely varying fluid compositions and temperatures and vent communities occur in different tectonic settings. The discovery of the Lost City hydrothermal field in the Mid-Atlantic Ridge has stimulated interest in the role of serpentinization of peridotite in generating H2- and CH4-rich fluids and associated carbonate chimneys, as well as in the biological communities supported in highly reduced, alkaline environments. Abundant vesicomyid clam communities associated with a serpentinite-hosted hydrothermal vent system in the southern Mariana forearc were discovered during a DSV Shinkai 6500 dive in September 2010. We named this system the “Shinkai Seep Field (SSF). ” The SSF appears to be a serpentinite-hosted ecosystem within a forearc (convergent margin) setting that is supported by fault-controlled fluid pathways connected to the decollement of the subducting slab. The discovery of the SSF supports the prediction that serpentinite-hosted vents may be widespread on the ocean floor. The discovery further indicates that these serpentinite-hosted low-temperature fluid vents can sustain high-biomass communities and has implications for the chemical budget of the oceans and the distribution of abyssal chemosynthetic life.
Tularemia: History, Epidemiology, Pathogen Physiology, and Clinical Manifestations

Abstract: Francisella tularensis has been recognized as a human pathogen for almost 100 years and is the etiological agent of the zoonotic disease tularemia. Soon after its discovery, it became recognized as an important pathogen in several parts of the world, for example, in the United States and Soviet Union. The number of tularemia cases in the two countries peaked in the 1940s and has thereafter steadily declined. Despite this decline, there was still much interest in the pathogen in the 1950s and 1960s since it is highly infectious and transmissible by aerosol, rendering it a potent biothreat agent. In fact, it was one of the agents that was given the highest priority in the offensive programs of the United States and Soviet Union. After termination of the offensive programs in the 1960s, the interest in F. tularensis diminished significantly and little research was carried out for several decades. Outbreaks of tularemia during the last decade in Europe, for example, in Kosovo, Spain, and Scandinavia, led to a renewed public interest in the disease. This, together with a massive increase in the research funding, in particular in the United States since 2001, has resulted in a significant increase in the number of active Francisella researchers. This article summarizes, predominantly with a historical perspective, the epidemiology and clinical manifestations of tularemia and the physiology of F. tularensis.
Higher social distress and lower psycho-social wellbeing: examining the coping capacity and health of people with hearing impairment

Abstract Purpose: The objectives of this paper are as follows: (1) propose an explanatory model as to how hearing disability may impact on health and (2) examine the model’s utility. Methods: Data were collected on the psycho-social wellbeing, disability and physical health of farmers (n = 56) participating in an intervention to manage the social impacts of hearing disability. Two models were proposed and examined using multiple hierarchical linear regression. Model 1 used self-rated quality of life and model 2 used capacity to manage hearing and listening impairments, as dependent variables. Results: The analyses found that physical measures of hearing impairment (audiograms) were not correlated with physical or mental health outcomes. However, in model 1, self-confidence and self-rated ability to manage hearing impairment were most closely associated with reduced quality of life (anxiety and diastolic blood pressure were positively associated with quality of life). In model 2, higher anxiety and reduced self-confidence were associated with decreasing ability to successfully manage one’s hearing impairment. Conclusions: The findings support the explanatory model that stress is higher and wellbeing lower when the fit between the person’s coping capacity and environmental demands is poor. Implications for Rehabilitation This paper demonstrates that anxiety is associated with coping with the psycho-social aspects of hearing disability. This finding has important implications for the many hearing services, which only provide assessment and devices. To negate anxiety and its long-term impacts, rehabilitation providers need to ensure people with hearing disability have the capacity to manage the psycho-social aspects of communication breakdown.
Armut in West- und Ostdeutschland: ein differenzierter Vergleich

Von 1992 bis 2000 war fur Ostdeutschland eine niedrige - und sich uber die Jahre kaum verandernde - Einkommensungleichheit zu beobachten. Zugleich waren dort - gemessen an der fur Ostdeutschland "regional" definierten Armutsgrenze - weniger Personen als im Westen von Armut betroffen. Fur beide Teile Deutschlands gilt, dass etwa die Halfte der im Beobachtungszeitraum begonnenen Armutsphasen ein Jahr spater beendet war. Die Wahrscheinlichkeit fur Menschen, die schon einmal arm waren, wieder unter die Armutsgrenze zu gelangen, ist in Westdeutschland hoher als in Ostdeutschland. In beiden Regionen nimmt jedoch die Wahrscheinlichkeit, erneut arm zu werden, mit jedem weiteren Jahr auserhalb von Armut ab. Deren Bekampfung sollte deshalb nicht ausschlieslich darauf gerichtet sein, Menschen aus der Armut herauszuholen, sondern auch darauf zielen, dem (Wieder-)Eintritt in Armut vorzubeugen.
Co-Representation of Others’ Task Constraints in Joint Action

Previous research has demonstrated that humans tend to represent each other’s tasks even if no interpersonal coordination is required. The present study asked whether coactors in a joint action rely on task co-representation to achieve temporal coordination even if this implies increased movement effort for an unconstrained actor. Pairs of participants performed reaching movements back and forth between two targets, with the aim of synchronizing their landing times. One of the participants needed to move over an obstacle while the other had no obstacle. The results of four experiments showed that the participant without obstacle moved as if an obstacle was obstructing her way. Further amplifying the demands on interpersonal coordination led to a significant increase of this effect, indicating that unconstrained actors represented their coactor’s task constraint and adjusted their own actions accordingly, particularly under high coordination demands. The findings also showed that unconstrained actors represented the object property constraining their coactor’s movement rather than parameters of this movement. We conclude that joint action partners rely on task co-representation to achieve temporal coordination in a task with asymmetric task constraints.
Advanced reliability study of TSV interposers and interconnects for the 28nm technology FPGA

TSV interposer has emerged as a good solution to provide high wiring density interconnections, improved electrical performance due to shorter interconnection from the die to substrate, and minimized CTE mismatch between the chip and copper filled TSV interposer, resulting in high reliability micro bumps and more reliable low-k chip. Furthermore, for an interposer that does not contain any active device, already established process technology could be applied, TSV pitch could be coarser and a thicker interposer could be used. This paper presents the development of TSV interposer technology for a high-performance 28nm logic die that is mounted on a large silicon interposer with Cu through silicon via. A representative silicon interposer test chip with thousands of micro-bumps at 45um pitch has been fabricated. The silicon interposer is 100um thick, and is mounted on a 42.5mm×42.5mm substrate through 180um pitch C4 bumps. TSV fabrication process steps and assembly process of the large logic die mounted on the TSV interposer with lead-free micro-bumps have been optimized as well as assembly of the component on the organic substrate. 3D thermal-mechanical modeling and simulation for the packaged device with TSV interposer have been performed. The samples have been subjected to thermal cycling, electro-migration and moisture sensitivity tests. Effect of TSV interposer on the stress of the die, low-k layers and fatigue life of micro bumps and C4 bumps have been investigated. Several DOEs have been performed to optimize design and material selection in order to maximize yield and reliability. Finally, Si interposer seemed to be a low-risk 3D path to have a reliable package with acceptable warpage/coplanarity, passing 1000TCB without any crack, delamination or void being detected in low-k, TSV, micro bumps and C4 bumps.
Plant profilin isovariants are distinctly regulated in vegetative and reproductive tissues.

Profilin is a low-molecular weight, actin monomer-binding protein that regulates the organization of actin cytoskeleton in eukaryotes, including higher plants. Unlike the simple human or yeast systems, the model plant Arabidopsis has an ancient and highly divergent multi-gene family encoding five distinct profilin isovariants. Here we compare and characterize the regulation of these profilins in different organs and during microspore development using isovariant-specific monoclonal antibodies. We show that PRF1, PRF2, and PRF3 are constitutive, being strongly expressed in all vegetative tissues at various stages of development. These profilin isovariants are also predominant in ovules and microspores at the early stages of microsporogenesis. In contrast, PRF4 and PRF5 are late pollen-specific and are not detectable in other cell types of the plant body including microspores and root hairs. Immunocytochemical studies at the subcellular level reveal that both the constitutive and pollen-specific profilins are abundant in the cytoplasm. In vegetative cell types, such as root apical cells, profilins showed localization to nuclei in addition to the cytoplasmic staining. The functional diversity of profilin isovariants is discussed in light of their spatio-temporal regulation during vegetative development, pollen maturation, and pollen tube growth.
Intestinal gas in plain abdominal radiographs does not correlate with symptoms after lactulose challenge

Observation Intestinal gas production and abdominal discomfort can be triggered by the ingestion of carbohydrates such as lactulose. Using plain abdominal radiographs, we studied whether subjective complaints after a lactulose breath test would be quantitatively related to intestinal gas volumes. Methods Abdominal symptoms after the breath test were quantified by a written questionnaire and gas volumes were scored in plain abdominal radiographs, in 50 consecutive patients with unexplained, irritable bowel syndrome-like symptoms. Breath excretion of hydrogen and methane was determined in all patients. Results Forty-two (84%) of the patients claimed that their post-breath test symptoms were a true replicate of their customary discomfort. Total symptom scores (sum of scores for pain/discomfort, borborygmi, bloating, diarrhea, constipation) or any specific symptom score were not significantly correlated to gas volume scores (r=−0.04; P=0.8 for total symptom score). The 13 (26%) methane producers had significantly higher mean gas volume scores compared with nonproducers (0.38 vs. 0.24; P=0.0008), but fewer symptoms (total symptom score 11.9 vs. 18.2; P=0.17). Conclusion Intestinal gas volume, as scored in plain abdominal radiographs, is not correlated with abdominal discomfort after lactulose challenge. Intestinal gas may not be the major cause of abdominal discomfort following carbohydrate ingestion in patients with functional gut disorders.
Requirement for NK Cells in CD40 Ligand-Mediated Rejection of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Cells

We have previously developed a murine model of Philadelphia chromosome-positive acute lymphoblastic leukemia by i.v. injection of a pre-B ALL cell line (BM185) derived from Bcr-Abl-transformed BALB/c bone marrow. We are studying the potential to elicit autologous antileukemic immune responses by introducing genes encoding immunomodulators (CD40 ligand (CD40L), CD80, and GM-CSF) into leukemia cells. BM185 cells expressing CD40L or CD80 alone, when injected into BALB/c mice, were rejected in approximately 25% of mice, whereas cohorts receiving BM185 cells expressing two or more immunomodulator genes rejected challenge 50–76% of the time. The greatest protection was conferred in mice receiving BM185 cells expressing all three immunomodulators. Addition of murine rIL-12 treatments in conjunction with BM185/CD80/CD40L/GM-CSF vaccination allowed rejection of preestablished leukemia. BM185 cell lines expressing CD40L were rejected in BALB/c nu/nu (nude) mice, in contrast to cell lines expressing CD80 and/or GM-CSF. Nude mice depleted of NK cells were no longer protected when challenged with BM185/CD40L, demonstrating a requirement for NK cells. Similarly, NK cell depletion in immunocompetent BALB/c mice resulted in a loss of protection when challenged with BM185/CD40L, confirming the data seen in nude mice. The ability of CD40L to act in a T cell-independent manner may be important for clinical applications in patients with depressed cellular immunity following chemotherapy.
Tumor angiogenesis in human lung adenocarcinoma

I found the study by Trevisani et al.’ to be of particular interest. The study was well written and thorough. However, I believe that some of their conclusions would have been different had they used more powerful, and perhaps more appropriate, statistical tests in analyzing some of their data. For example, the authors in their discussion stated that their study ”provides evidence that at the time of [hepatocelMar carcinoma] HCC diagnosis, the grade of cell anaplasia does not differ according to the underlying liver pathology” (in this case, the presence or absence of cirrhosis). A reanalysis of their data on Edmondson grades, as presented in Table 3, in fact, suggests the contrary. Using the chi-square test for trend, which is one of the tests most appropriate for analyzing data that have ordered categories,’ their data appear to show the following:
Trunk extensor and flexor strength of long-distance race car drivers and physically active controls

Abstract Seventy percent of motor sports athletes report low back pain. Information on the physical capacity of race car drivers is limited. The purpose of this study was to compare the maximum trunk extensor and flexor strength of elite race car drivers and physically active controls. Thirteen elite race car drivers and 13 controls were measured in concentric mode for maximal trunk flexion and extension at 60° · s−1 and 120° · s−1. Peak torque (mean ± s) at 60° · s−1 in trunk extension was 283 ± 80 N · m in the drivers and 260 ± 88 N · m in controls (P > 0.05). At 120° · s−1, drivers produced peak torques of 248 ± 55 N · m compared with 237 ± 74 N · m for controls (P > 0.05). Peak torques in flexion were less than in extension for both groups (60° · s−1: drivers 181 ± 56 N · m, controls 212 ± 54 N · m, P > 0.05; 120° · s−1: drivers 191 ± 57 N · m, controls 207 ± 48 N · m, P > 0.05). Individual ratios of flexion to extension forces exhibited ratios of 0.88 (60° · s−1) and 0.93 (120° · s−1) for controls and 0.66 (60° · s−1) and 0.77 (120° · s−1) for drivers (60° · s−1: P > 0.05; 120° · s−1: P > 0.05). The maximum strength performance capacity of the trunk muscles of elite motor sport athletes competing in long-distance racing did not differ from that of anthropometrically matched and physically active controls.