Miracle-dz/UniFAR-FTUs huggingface dataset:
Gonadotropinomas

Advances in immunocytochemistry, electron microscopy, cell culture, and molecular techniques have demonstrated that 80 to 90% of the clinically nonfunctioning pituitary adenomas are gonadotrope-derived and recently recognized as gonadotropinomas, which account for as many as 40 to 50% of all pituitary macroadenomas. Patients usually present with mass effects including visual field loss and headache, hypogonadism, and hypopituitarism. Commonly, the tumor is found incidentally. Recently, a few patients with gonadotropinomas were reported to have hormonal hypersecretion syndromes such as ovarian hyperstimulation, testicular enlargement, and precocious puberty.The tumors can be divided into two broad categories: functioning gonadotropinomas with positive immunostaining for follicle-stimulating hormone, leutinizing hormone, and/or their sub-units; and nonfunctioning gonadotropinomas or null cell tumors with negative immuno-staining for all pituitary hormones but positive nuclear immunostaining for steroid factor-1 or DAX-1 characteristic of gonadotrope differentiation, with evidence of gonadotropin production or gene expression at the mRNA level. Gonadotropinomas are monoclonal in origin but the pathogenesis of these tumors is unknown and factors that stimulate clonal proliferation not yet determined. A new pituitary oncogene, pituitary tumor transforming gene, has recently been found to be overexpressed in about two thirds of these tumors but it is also detected in all other pituitary tumor subtypes. Alterations of tumor hormone receptors and local growth factors may also play a role in the tumor development and/or progression. Transphenoidal surgery remains the principal therapy for the macroadeno-mas. Radiosurgery using gamma knife, the linear accelerator, or proton beam therapy showed promising results, especially for controlling the residual or recurrent tumors. Medical therapy with somatostatin analogs, dopamine agonists, and gonadotropin-releasing hormone agonists and antagonists are rarely effective in reducing tumor size. Experimental therapy with intraoperative local chemotherapy or potential gene therapy requires further investigation.
Predictors of Response to Therapy for Chronic Hepatitis C

Pretreatment prediction of successful interferon-based therapy is less accurate than is prediction based on serum hepatitis C virus (HCV) RNA measurements taken during the ﬁrst few weeks of therapy. Virological response, deﬁned as loss of detectable virus RNA during the ﬁrst weeks of treatment, identiﬁes interferon-sensitive virus strains. Studies on viral decline kinetics have shown that interferon-based therapies produce a two-phase reduction in viral RNA levels. Sustained virological response is associated with rapid biphasic viral decline kinetics, resulting in elimination of virus from the blood within 4 to 12 weeks. Rapid viral elimination correlates positively with low incidence of relapse in end-of-treatment virological responders and is, therefore, an important parameter for determining duration or type of therapy. This article reviews the various patient and viral factors that help predict response to various interferon-based therapies, ranging from interferon alone to the new pegylated interferons.
In Utero Stem Cell Transplantation

Successful in utero stem cell transplantations with hematopoietic or other stem cells should represent a major step forward in the management of patients with congenital, hematological, metabolic, and immunological disorders. The possibility of performing cell transplantations with stem cells across histoincompatibility barriers without chemotherapy has great potential for both pre and postnatal transplantations. The present article includes an overview of this topic with special reference to different animal models and the experience in humans in regard to fetal stem cell transplantations. This area of research holds great promise for the future, and development of efﬁcient intrauterine stem cell treatment may enable the relative new speciality of fetal medicine to progress from a mainly diagnostic to a therapeutic medical subject.
Cruciate and Posterolateral Corner Injuries in the Athlete: Clinical and Magnetic Resonance Imaging Features

With an increasing number of people participating in recreational and competitive sporting activities, sports-related injuries of the knee and knee ligaments have increased in incidence. The extent and severity of such injuries may have important impliations with regard to potential return to atheletic pursuits as well as impacting upon activities of daily life. This article discusses the MR imaging and clinical features of sports-related injuries of the cruciate ligaments and posterolateral corner of the knee, highlighting the implications of such injuries on joint function. MR imaging has the potential to accurately identify these ligamentous injuries, as well as other potential associated combined injuries of the knee, with information from MR imaging examination assisting in decision-making and planning with regard to potential clinical and/or surgical patient management.
Implantation in the Baboon: Endometrial Responses

— Blastocyst implantation in the baboon usually occurs between 8 and 10 days post ovulation. Changes that occur within this window of receptivity and immediately fol lowing implantation can be divided into three distinct phases. The first phase, regulated by estrogen and progesterone, is characterized primarily by changes in both the luminal and glandular epithelial cells in preparation for blastocyst apposition and attachment. The sec ond phase is the further modulation of these steroid induced changes in both epithelial and stromal cells by embryonic signals. The final phase is associated with trophoblast invasion and the remodeling of the endometrial stromal compartment. During the initial phase, the actions of estrogen and progesterone are dependent on the presence of specific receptors. Es trogen up-regulates both its own receptor (ER) and the progesterone receptor (PR), while progesterone down-regulates this expression pattern. However, the pattern of progesterone-induced down-regulation of ER and PR is confined to the epithelial cells and demonstrates a gradient effect from the functionalis to the basalis. What is most intriguing is that the loss of epithelial PR is closely correlated with the establishment of uterine receptivity. Coincident with the changes in ER and PR expression, epithelial cells undergo alterations in their cytoskeletal architecture and secretory profile. These changes can be counteracted by PR antag onist treatment during the luteal phase. Although estrogen and progesterone play a critical role in establishing the initial phase of uterine receptivity, it is becoming increasingly evi dent that the embryo induces functional receptivity in ruminants and rodents. In our studies in the primate, we demonstrate that chorionic gonadotrophin when infused in a
Anterior Ankle Impingement Syndromes

Ankle impingement syndromes are painful conditions that may complicate ankle trauma and are characterized by chronic, progressive pain, swelling, and limitation of movement. These disorders are subclassiﬁed according to anatomical location about the tibiotalar joint. This article reviews the various forms of anterior ankle impingement, detailing the unique clinical features, anatomical considerations
Four Individually Identified Paired Dopamine Neurons Signal Taste Punishment in Larval Drosophila

Dopaminergic neurons (DANs) carry out multiple tasks in the brain, including the transmission of information related to rewards and punishments across various animal species. They are responsible for evaluating sensory input, storing resultant associations as memory, and continuously updating them based on their relevance and reliability. Accurate comprehension of the dopaminergic system’s operation necessitates an understanding of the specific functions mediated by individual DANs. To this end, our research employs Drosophila larvae, which possess approximately 12,000 neurons in their brains, of which only around 1% (approximately 120) are DANs. The presynaptic projections to the mushroom body (MB) - a brain region pivotal for associative olfactory learning in insects - are limited to only eight larval dopaminergic neurons. These DANs are further subdivided into two clusters: the primary protocerebral anterior medial cluster (pPAM) comprises four cells, and the dorsolateral 1 cluster (DL1) comprises the remaining four cells. Our findings confirm previous research that demonstrates that the pPAM DANs innervating the MB’s medial lobe encode for a gustatory sugar reward signal. Furthermore, we have identified four DANs in the DL1 cluster - DAN-c1, DAN-d1, DAN-f1, and DAN-g1 - each of which innervates distinct compartments of the MB peduncle, lateral appendix, and vertical lobe. Optogenetic activation of DAN-f1 and DAN-g1 alone suffices to substitute for salt punishment. Furthermore, optogenetic inhibition, calcium imaging results and electron microscopy-based reconstruction of all sensory input circuits to the four DL1 DANs demonstrate that each DAN encodes a different aspect of salt punishment, with DAN-g1 being of central importance. To summarize, our investigation has revealed the existence of a cellular division of labor among larval DANs concerning the transmission of dopaminergic reward (pPAM cluster) and punishment signals (DL1 cluster). Individual DANs in each cluster encode for distinct but partially overlapping aspects of the teaching signal. The striking resemblance in the organizing principle of larval DANs with that of its adult counterpart and the mammalian basal ganglion suggests that there may be a limited number of efficient neural circuit solutions available to address more complex cognitive challenges in nature.
The Rise in Adrenal Androgen Biosynthesis: Adrenarche

Adrenarche is characterized by the increase in adrenal androgen production, namely dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) that occurs around 6 years of age. These steroids are secreted by the zona reticularis (ZR) of the adrenal gland. This is associated with pubarche or the increase in androgen-dependent hair growth at the time of puberty. The increase in adrenal androgen production can be explained by the increase in the expression of DHEA-synthesizing steroidogenic enzymes in the ZR. Adrenarche is an event independent of gonadarche and is found only in humans and select nonhuman primates. Although numerous prenatal and postnatal factors are important in the onset of adrenarche, a speciﬁc adrenal cortical androgen-stimulating hormone has not been identiﬁed. Evidence also exists for a role for adrenarche in behavior, skeletal maturation, and postpubertal well-being. Adrenarche is inﬂuenced by sex and race, and some of this variation may be related to the insulin and insulin-like growth factor (IGF) signaling pathways. In addition, children with premature and exaggerated adre-narche may be predisposed to certain diseases later in life.
Generalizations of the centroid with an application in stochastic geometry

The centroid of a subset of Rd with positive volume is a well‐known characteristic. An interesting task is to generalize its definition to at least some sets of zero volume. In the presented paper we propose two possible ways how to do that. The first is based on the Hausdorff measure of an appropriate dimension. The second is given by the limit of centroids of ε‐neighbourhoods of the particular set when ε goes to 0. For both generalizations we discuss their existence and basic properties. Then we focus on sufficient conditions of existence of the second generalization and on conditions when both generalizations coincide. It turns out that they can be formulated with the help of the Minkowski content, rectifiability, and self‐similarity. Since the centroid is often used in stochastic geometry as a centre function for certain particle processes, we present properties that are needed for both generalizations to be valid centre functions. Finally, we also show their continuity on compact convex m‐sets with respect to the Hausdorff metric topology.
Onco-Retroviral and Lentiviral Vector-Based Gene Therapy for Hemophilia: Preclinical Studies

Hemophilia A and B gene therapy requires long-term and stable expression of coagulation factor VIII (FVIII) or factor IX (FIX), respectively, and would need to compare favorably with protein replacement therapy. Onco-retroviral and lentiviral vectors are attractive vectors for gene therapy of hemophilia. These vectors have the potential for long-term expression because they integrate stably in the target cell genome. Whereas onco-retroviral vectors can only transduce dividing cells, lentiviral vectors can transduce a broad variety of cell types irrespective of cell division. Several preclinical and clinical studies have explored the use of onco-retroviral and, more recently, lentiviral vectors for gene therapy of hemophilia A or B. Both ex vivo and in vivo gene therapy approaches have been evaluated, resulting in therapeutic FVIII or FIX levels in preclinical animal models. Whereas in vivo gene therapy using onco-retroviral or lentiviral vectors often led to long-term FVIII or FIX expression from transduced hepatocytes, ex vivo approaches were generally hampered by either low or transient expression of FVIII or FIX levels in vivo and/ or inefﬁcient engraftment. Furthermore, immune responses against the transgene product remain a major issue that must be resolved before the full potential of these vectors eventually can be exploited clinically. Nevertheless, the continued progress in vector design combined with a better understanding of vector biology may ultimately yield more effective gene therapy approaches using these integrating vectors.
Inherited Thrombocytopenias: Molecular Mechanisms

Each megakaryocyte forms 10(3) platelets and 10(11) platelets are replenished daily. The unique and amazing mechanisms that allow megakaryocytes to become giant and polyploid and to release such a large number of platelets are still poorly understood. The study of inherited thrombocytopenias offers the possibility to gain new information on these processes because several different forms, deriving from defective megakaryocytic commitment, differentiation, maturation, or platelet formation, have been identified. Moreover, in the presence of some genetic defects, megakaryocytes produce platelets with a shortened life span. In this review, we summarize what we have learned about inherited thrombocytopenias in the last few years.
Perspectives on Liver Failure: Past and Future

Acute liver failure (ALF) remains a potentially devastating syndrome with a high mortality rate. Much interest continues to center upon the possibility of providing effective liver support through various artiﬁcial and bioartiﬁcial extracorporeal devices. The development of purpose-designed intensive care units for the treatment of ALF allowed a better understanding of the clinical syndrome and its best management, through the ability to conduct detailed clinical observation and clinical trials of new interventions. Survival rates are substantially improved today compared with the mortality rate that approximated 100% when the syndrome was ﬁrst described nearly ﬁve decades ago. Nonetheless, these have plateaued in recent years, prompting one to consider whether major new advances in disease understanding are needed to further improve the overall outcome. A major challenge to a broader understanding of disease pathogenesis and the ability to direct appropriate therapy remains the substantial number of cases of ALF for which no speciﬁc etiology can be identiﬁed. Much is now known about the basic molecular mechanisms underlying hepatocyte cell death in ALF and an important issue is whether these cell death pathways can, in the future, be interrupted for therapeutic gain. Such considerations would seem most relevant in the early stages of the clinical course, when damage to the liver is not so severe but perhaps programmed to so evolve. A particular challenge will be to reduce hepatocellular death without inhibiting the liver’s regenerative potential, given the pleiotropic functions of some of the molecules involved in both processes.
Involvement of Plasminogen Activator and Plasminogen Activator Inhibitor Type 1 in Spermatogenesis, Sperm Capacitation, and Fertilization

Increasing evidence suggests that local ﬁbrinolysis generated by plasminogen activator (PA) and modulated by plasminogen activator inhibitor type 1 (PAI-1) is essential for mammalian spermatogenesis, sperm capacitation, and fertilization. Tissue-type PA (t-PA), urokinase-type PA (u-PA), and PAI-1 have been reported in the testes of various animals. Sertoli cells within the seminiferous epithelium are believed to play a central role in the control and maintenance of spermatogenesis by producing regulatory factors, including PA/PAI-1. Fertilization is a unique and exquisitely choreographed cellular interaction between male and female gametes, in which some basic biochemical mechanisms remain unresolved. A key issue is the molecular basis of sperm–egg recognition, binding, and penetration. Sperm capacitation and the acrosomal reaction appear to rely on local ﬁbrinolysis generated by the PA/PAI-1 system. Ejaculated spermatozoa from various species carry u-PA activity. The u-PA receptor (uPAR) and the inhibitor PAI-1 have also been reported to bind on the sperm membrane surface. Thus, it is possible that uPAR and PAI-1 function in a counterbalanced and coordinated way on the surface of spermatozoa to regulate the u-PA binding capacity. This review summarizes evidence for the involvement of PA/PAI-1 system in spermatogenesis, sperm capacitation, and fertilization.
Probability Functions which are Proportional to Characteristic Functions and the Infinite Divisibility of the von Mises Distribution

Reciprocal pairs of continuous random variables on the line are considered, such that the density function of each is, to within a norming factor, the characteristic function of the other. The analogous reciprocal relationship between a discrete distribution on the line and a continuous distribution on the circle is also considered. A conjecture is made regarding infinite divisibility properties of such pairs of random variables. It is shown that the von Mises distribution is infinitely divisible for sufficiently small values of the concentration parameter.
Developmental Language Impairments: Their Transactions with Other Neurodevelopmental Factors During the Adolescent Years

Adolescence is a period of sustained stress for developing central nervous systems. The adolescent brain is compelled to contend with academic and social demands that are intense, implacable, and often rigidly uniform. The experience can be especially costly for secondary school students with learning disorders. These adolescents display a wide range of cognitive deficits and strengths, but they share the common reality that certain of their capacities are exceeded by the unremitting flow of new expectations and impositions in secondary school. A thorough understanding of adolescents with learning disorders requires first a keen awlzreness of the specific cognitive demands that confront these students. Table 1 lists some of the intensified academic expectations likely to beset students in this age group. IIeightened requirements for cognitive sophistication, precision, and efficiency during the adolescent years are inevitably complicated by the explosive growth of social pressures, personal concerns over pubertal development and body image, and the drive to experiment with various ventures that demonstrate personal autonomy. The struggle to meet such demands is especially intense, and often exasperating, for adolescents with learning disorders. Thcy are likely to be burdened with tenuous selfesteem and feelings of intellectual and sometimes social inadequacy as they fail to savor success in school. The plight of adolescents with learning disorders is aggravated by a shortage of appropriate diagnostic and remedial services in junior and senior high schools. Many students who benefited from special education services as youngsters are often deemed to be no longer eligible for such senices when they reach secondary school. In a sense, they are abandoned by the systern at a time when their educational experience may be the most confusing and tl~rbulerlt. Additionally, there are likely to be widespread misunderstandings regarding the nature of academic problems in this age group compared to those of younger students. Some likely differences are presented in Table 2. The complexity of learning disorders during adolescence challenges current
Using Protocols to Improve Patient Outcomes in the Intensive Care Unit: Focus on Mechanical Ventilation and Sepsis

The care of critically ill patients has become increasingly complex as severity of illness continues to increase, the number of patients requiring intensive care is on the rise, the amount of clinical information available at the bedside is growing, and the quantity of evidence supporting or refuting speciﬁc therapies and interventions for this population is escalating. It has become problematic for clinicians to master all of these tasks and to process the quantity of available clinical and scientiﬁc information in an effective and safe manner. Additionally, a culture promoting safety and accountability has emerged in the United States and throughout the world in regard to medical care. The expectation is that patients entering hospitals should receive the highest quality of care with minimal to no medical errors occurring. To accomplish this goal, as well as to allow more accurate monitoring of day to day medical practices, several strategies have been developed that have primarily been employed in the intensive care unit (ICU) setting. These strategies include the use of paper-based or electronic protocols for disease (e.g., severe sepsis and septic shock) or process of care (e.g., weaning of mechanical ventilation) management, national guidelines, and targeted clinician education with or without periodic feedback regarding compliance with best medical practices and resultant patient-based outcomes. This review focuses on the use of protocols in the ICU setting and how they can best be utilized to improve patient outcomes.
Stray Magnetic Field Detection and Imaging from Magnetic Particle with an Ensemble of Nitrogen Vacancy Center in Diamond

The spin-1 system in diamond with Nitrogen substitution and adjacent vacancy (NV center) enable us to detect localized stray magnetic field under ambient condition. By using an optical detection method based on magnetic resonance of electron spins, magnetic field direction and magnitude in the vicinity of the NV spins can be recovered [1-3]. Here we present stray magnetic field detection and imaging from NdFeB magnetic particle using ensemble of NV centers in a (001) bulk diamond. Electron spin resonance (ESR) spectrum is obtained by applying continuous irradiation of 532 nm laser while sweeping microwave excitation within the frequency range of the electron spin resonance (Fig. 1(a)). Magnetic particle of NdFeB placed on diamond NV ensemble was investigated and stray magnetic field surrounding the particle was recovered by analyzing ESR spectra. Owing to the lifting of ms = ± 1 states due to the Zeeman effect when magnetic field is projected along the NV spin axes, the ESR spectrum varies as magnetic field magnitude and direction changed [1, 2]. The direction of magnetization is decided from the position where shows the largest stray field, and the angle of magnetization respect to surface can be estimated from the stray field from symmetric position (Fig. 1(a)). A subtracted image with 2.89 GHz microwave field (Fig. 1(a)) and without is shown in Fig. 1(b), corresponding to spatial variation of stray fields.