Miracle-dz/UniFAR-FTUs huggingface dataset:
Blocking immunosuppression by human Tregs in vivo with antibodies targeting integrin αVβ8

Significance Immunosuppression by regulatory T cells (Tregs) is essential for the maintenance of self-tolerance, but it is detrimental in cancer because Tregs inhibit antitumor immunity. Development of therapeutic tools to block Tregs in patients with cancer requires a precise understanding of how human Tregs suppress immune responses. We recently identified an important mechanism implicating release of the active form of TGF-β1, a potently immunosuppressive cytokine, from GARP/latent TGF-β1 complexes on the surface of human Tregs. Here we unravel the molecular process leading to this release. We identify integrin αVβ8 as indispensable for TGF-β1 activation from GARP/latent TGF-β1 complexes. We show that anti-β8 monoclonals block immunosuppression by human Tregs in vivo and could thus serve in cancer immunotherapy. Human regulatory T cells (Tregs) suppress other T cells by converting the latent, inactive form of TGF-β1 into active TGF-β1. In Tregs, TGF-β1 activation requires GARP, a transmembrane protein that binds and presents latent TGF-β1 on the surface of Tregs stimulated through their T cell receptor. However, GARP is not sufficient because transduction of GARP in non-Treg T cells does not induce active TGF-β1 production. RGD-binding integrins were shown to activate TGF-β1 in several non-T cell types. Here we show that αVβ8 dimers are present on stimulated human Tregs but not in other T cells, and that antibodies against αV or β8 subunits block TGF-β1 activation in vitro. We also show that αV and β8 interact with GARP/latent TGF-β1 complexes in human Tregs. Finally, a blocking antibody against β8 inhibited immunosuppression by human Tregs in a model of xenogeneic graft-vs.-host disease induced by the transfer of human T cells in immunodeficient mice. These results show that TGF-β1 activation on the surface of human Tregs implies an interaction between the integrin αVβ8 and GARP/latent TGF-β1 complexes. Immunosuppression by human Tregs can be inhibited by antibodies against GARP or against the integrin β8 subunit. Such antibodies may prove beneficial against cancer or chronic infections.
Análisis morfométrico del proceso de diferenciación in vitro de neuronas del hipocampo.

Los cultivos neuronales del sistema nervioso central se han venido usando ampliamente para el estudio de los mecanismos que conducen el proceso de diferenciacion neuronal, asi como tambien se han empleado como modelos in vitro para evaluar drogas y desarrollar nuevas terapias, de alli la importancia profundizar en la caracterizacion de dicho proceso. En este estudio, se prepararon cultivos primarios de celulas del hipocampo para estudiar los tipos celulares desarrollados, el desarrollo de dendritas y axones, la densidad de vesiculas sinapticas y el desarrollo de los conos de crecimiento. Mediante inmunofluorescencia usando anticuerpos y marcadores no inmunologicos, se observaron los cambios experimentados por las estructuras de interes durante diferentes estadios temporales (1-21 dias). Observamos una mayor proporcion de neuronas sobre glias, desarrollo normal de las redes neuronales (conformadas por dendritas y axones), incremento en la longitud de dendritas y el establecimiento de sinapsis. Las vesiculas sinapticas tambien experimentaron un incremento en su densidad a medida que aumentaba el tiempo de cultivo. Finalmente, se estudiaron los cambios morfologicos de los conos de crecimiento observandose que al inicio del cultivo en su mayoria se encontraban cerrados, pero a medida que maduraban las neuronas la proporcion de conos de crecimiento abiertos aumento. Este trabajo representa un avance en la caracterizacion morfometrica de los cultivos neuronales puesto que recoge de manera simultanea y cuantitativa los principales aspectos que marcan el proceso de diferenciacion neuronal. En este estudio, la medicion de estas caracteristicas morfologicas hizo posible establecer parametros cuantitativos que ayudaran a distinguir las principales etapas de la diferenciacion neuronal.
Indoor radon and lung cancer in radium-dial workers

Internally deposited radium has long been known to have tumorigenic effects in the form of sarcomas of the bone and carcinomas of the paranasal sinuses and mastoid air cells. However, radium-dial workers were also exposed to radiation hazards other than that occurring from ingestion of the radium paint, namely, external gamma radiation and elevated concentrations of airborne radon. Uranium miners were also exposed to high concentrations of radon in the 1950s and later and numerous cases of lung cancer have occurred in that population. However, unlike the atmosphere in the uranium mines, the air in the dial painting plants was probably rather clean and perhaps not much different from the air in many houses. In view of the current concern over the possibility of lung cancer in the general population being caused by radon (progeny) in houses, it is important to examine the mortality due to this usually fatal disease in the dial workers and to attempt to relate it to their exposure to radon, to the extent that is possible.
Non-contrast Magnetic Resonance Angiography for Evaluation of Peripheral Arterial Disease

Non-contrast Magnetic Resonance Angiography for Evaluation of Peripheral Arterial Disease Iliyana P Atanasova Peripheral arterial disease (PAD) is a major cause of morbidity and mortality in the USA with an estimated prevalence of up to 20% in those over 75 years. Vascular disease and kidney impairment frequently coexist; prevalence of moderate to severe renal dysfunction in PAD patientsis estimated at 27-36%. Knowledge of location, severity, and extent of PAD is imperative for accurate diagnosis and treatment planning. However, all established imaging modalities that are routinely used for treatment planning are contra-indicated in kidney disease patients. Contrast-enhanced x-ray and CT angiography are unsafe due to exposure to nephrotoxic contrast material and ionizing radiation. Recently, the FDA has also warned against the use of gadolinium-enhanced MRA (Gd-MRA) due to evidence that gadolinium could trigger a lifethreatening condition known as nephrogenic systemic fibrosis (NSF) in patients with moderate to severe kidney dysfunction. There is a clinical need to develop vascular imaging techniques that are safe in patients with coexisting PAD and renal insufficiency. The focus of this thesis was the development of a non-contrast alternative to Gd-MRA for imaging of peripheral vessels from renal to pedal arteries. A new imaging sequence for noncontrast visualization of the abdominal and pelvic arteries was designed, implemented, and validated in a small cohort of PAD patients against Gd-MRA. In addition, an existing fast spinecho based technique for unenhanced imaging of the lower extremities was optimized for improved performance in a clinical setting.
The association between the ratio of visceral fat to thigh muscle area and metabolic syndrome: the Korean Sarcopenic Obesity Study (KSOS)

Objective A relationship between visceral fat accumulation and metabolic syndrome (MetS) has been established. However, the effect of a relative increase in visceral fat and a decrease in muscle mass on metabolic disorders has not been investigated. The aim of the present study was to examine the association between the ratio of visceral fat to thigh muscle area (VMR) and MetS in Korean adults.
Vitamin D status and PTH in young men: a cross‐sectional study on associations with bone mineral density, body composition and glucose metabolism

Objective Although vitamin D and bone metabolism are closely related, few studies have addressed the effects of vitamin D status on bone in men at time of peak bone mass. The objectives of this study were to evaluate the prevalence of vitamin D inadequacy in a cross‐sectional study in young men and the effects of vitamin D and parathyroid hormone (PTH) on bone mass, bone markers and metabolic function.
What is the best approach to an apparently nonmetastatic adrenocortical carcinoma?

In suspected nonmetastatic adrenocortical carcinoma (ACC) a careful preoperative diagnostic work up is needed including comprehensive endocrine analysis as recommended by the European Network for the Study of Adrenal Tumors (http://www.ENSAT.org/ACC.htm). Staging prior surgery, in particular chest CT, is indispensable to exclude distant metastases. Open surgery is still the recommended approach in ACC. However, in localized non‐invasive ACC with a diameter <10 cm laparoscopic adrenalectomy by an expert surgeon is probably similarly effective and safe. As many patients will suffer from tumor recurrence after seemingly complete removal of ACC, adjuvant treatment based on the individual risk status is recommended. Key factors for risk assessment are tumor stage, resection status and the proliferation marker Ki67. All patients considered at high risk for recurrence should receive adjuvant mitotane for a minimum of 2 years aiming at a drug level of 14–20 mg/l. In selected patients (e.g. R1 resection) we recommend additional radiotherapy of the tumor bed. Patients with a low/intermediate risk for recurrence should be included in the Adiuvo trial comparing adjuvant mitotane with observation only (http://www.adiuvo‐trial.org). In low/intermediate risk patients who cannot be included in this trial observation only can be justified in cases with a tumor diameter of <8 cm and no microscopic evidence for invasion of blood vessels or tumor capsule. In all patients a structured follow‐up for 10 years is strongly recommended.
Diagnosis and management of pituitary abscess: experiences from 33 cases

Objective Pituitary abscess is a rare disorder with nonspecific presenting manifestations, often making a correct preoperative diagnosis difficult. To better determine the salient signs and symptoms of pituitary abscess and to evaluate the effectiveness of surgical and antibiotic therapies, we conducted a review of patients treated for pituitary abscess at the Peking Union Medical College Hospital (PUMCH).
Cognitive functioning in patients treated for nonfunctioning pituitary macroadenoma and the effects of pituitary radiotherapy

Context and objective Cognitive deterioration is reported in patients with a nonfunctioning pituitary macroadenoma (NFA) and after pituitary radiotherapy. However, reported results are inconsistent and are potentially confounded by different underlying pituitary disorders. The aim of this study was to examine cognitive functions in patients previously treated for NFA with or without radiotherapy.
Low testosterone concentrations and the symptoms of testosterone deficiency according to the Androgen Deficiency in Ageing Males (ADAM) and Ageing Males’ Symptoms rating scale (AMS) questionnaires

Objective First, to assess the association between the concentration of serum testosterone and the symptoms of testosterone deficiency according to two screening questionnaires. Second, to investigate the effects in elderly men with a low‐normal testosterone concentration of testosterone supplementation over a period of 6 months on symptoms of testosterone deficiency according to the screening questionnaires.
Complications of Emergency Tracheostomy

To find various complications of tracheostomy and their causes and mean / ways for there preventions. This study was conducted from 1st March 1996 to 28th February 1997 at LRH, Peshawar. This study included fifty patients with respiratory distress due to various reasons. All the tracheostomies were performed in OT either under General Anaesthesia or local anaesthesia. in 68% patients Portex cuffed tracheostomy tubes were used and in 32% of cases silver tubes were used. Haemorrhage is the most common intra operative complication, which could be prevented / reduced by good surgical techniques. While tubal obstruction is the commonest post operative complication which needs meticulous post operative care.
Pituitary apoplexy in non‐functioning pituitary adenomas: long term follow up is important because of significant numbers of tumour recurrences

Objectives The frequency of pituitary tumour regrowth after an episode of classical pituitary apoplexy is unknown. It is thus unclear whether regrowth, if it occurs, does so less frequently than with non‐apoplectic non‐functioning pituitary macroadenomas that have undergone surgery without postoperative irradiation. This has important repercussions on follow up protocols for these patients.
Plasma FGF21 displays a circadian rhythm during a 72‐h fast in healthy female volunteers

Objective Fibroblast growth factor (FGF21) is a potent regulator of glucose and lipid metabolism. In rodents, the hepatic expression of FGF21 is controlled by fasting and a circadian regulation, but the physiological role and regulation of FGF21 in humans is not well established. Therefore, the objective of this study was to elucidate the 24‐h profiling of plasma FGF21 during a 72‐h fast.
TRPM4 and TRPM5 are both required for normal signaling in taste receptor cells

Significance It is currently thought that the transduction of bitter, sweet, and umami stimuli in taste cells depends on G protein-coupled receptor signaling with transient receptor potential melastatin 5 (TRPM5) acting as a common downstream component. However, in the absence of TRPM5, mice have a reduced, but not abolished, ability to detect these stimuli, suggesting that a TRPM5-independent pathway also contributes to taste transduction. Here, we identify a critical role for the TRPM4 channel in the detection of these taste qualities. Deletion of either TRPM4 or TRPM5 impairs sensitivity to bitter, sweet, and umami stimuli, and loss of both TRPM4 and TRPM5 abolishes taste responses to these stimuli. Our results show that both TRPM4 and TRPM5 are required and sufficient for the transduction of bitter, sweet, and umami stimuli. Peripheral taste receptor cells use multiple signaling pathways to transduce taste stimuli into output signals that are sent to the brain. Transient receptor potential melastatin 5 (TRPM5), a sodium-selective TRP channel, functions as a common downstream component in sweet, bitter, and umami signaling pathways. In the absence of TRPM5, mice have a reduced, but not abolished, ability to detect stimuli, suggesting that a TRPM5-independent pathway also contributes to these signals. Here, we identify a critical role for the sodium-selective TRP channel TRPM4 in taste transduction. Using live cell imaging and behavioral studies in KO mice, we show that TRPM4 and TRPM5 are both involved in taste-evoked signaling. Loss of either channel significantly impairs taste, and loss of both channels completely abolishes the ability to detect bitter, sweet, or umami stimuli. Thus, both TRPM4 and TRPM5 are required for transduction of taste stimuli.
Epidemiology of Tobacco and Substance Abuse Among University Students in Mashhad, Northeast of Iran, in 2008

Background: Risky behaviors such as tobacco and substance abuse, which often begin in adolescence, have been considered as the most important cause of morbidity and mortality in the world. Objectives: This study was designed to assess the frequency of tobacco smoking, substance abuse and alcohol consumption among students of a university in Mashhad, Iran. Patients and Methods: In this cross-sectional study, 944 university students in Mashhad were randomly selected from 11 faculties with 12183 students in 2008 and filled out a self-administer questionnaire. Kaplan-Meier survival analysis and log rank statistics were used to evaluate the mean initiation age of the behaviors. Logistic regression analysis was performed for the prediction of the behaviors using SPSS software. Results: The overall frequency of smoking, alcohol drinking and substance abuse among students were 18.9%, 9.6% and 4.7%, respectively. Among students with a history of smoking, 69% had started smoking before 20 years of age. Moreover, 69.9% of individuals with a history of alcohol consumption and 56.5% of those with a history of substance abuse had reported their first use before 20 years of age. Older and human sciences students had a higher possibility to smoke tobacco (OR = 2.31 and OR = 1.27, respectively) and drink alcohol (OR = 2.20 and OR = 1.40, respectively). Conclusions: Present study demonstrated that the frequency of tobacco and substance abuse is considerable among Iranian university students who thought to be more knowledgeable and concerned about their health. Thus, efficient educational programs are needed to reduce the high-risk behaviors before students enter to university.
Default mode network can support the level of detail in experience during active task states

Significance Accounts of the default mode network (DMN) as task negative are partly based on evidence for a role of this system in off-task thought. We revisited the evidence for this assumption in a study combining experience sampling with functional neuroimaging. Whether thoughts were related or unrelated to an ongoing task was associated with patterns of neural activity in regions adjacent to unimodal sensorimotor cortex. In contrast, during periods of working-memory maintenance, activity patterns in the DMN were associated with whether thoughts were detailed. These results demonstrate that activity within the DMN encodes information associated with ongoing cognition that goes beyond whether attention is directed to the task, including detailed experiences during active task states. Regions of transmodal cortex, in particular the default mode network (DMN), have historically been argued to serve functions unrelated to task performance, in part because of associations with naturally occurring periods of off-task thought. In contrast, contemporary views of the DMN suggest it plays an integrative role in cognition that emerges from its location at the top of a cortical hierarchy and its relative isolation from systems directly involved in perception and action. The combination of these topographical features may allow the DMN to support abstract representations derived from lower levels in the hierarchy and so reflect the broader cognitive landscape. To investigate these contrasting views of DMN function, we sampled experience as participants performed tasks varying in their working-memory load while inside an fMRI scanner. We used self-report data to establish dimensions of thought that describe levels of detail, the relationship to a task, the modality of thought, and its emotional qualities. We used representational similarity analysis to examine correspondences between patterns of neural activity and each dimension of thought. Our results were inconsistent with a task-negative view of DMN function. Distinctions between on- and off-task thought were associated with patterns of consistent neural activity in regions adjacent to unimodal cortex, including motor and premotor cortex. Detail in ongoing thought was associated with patterns of activity within the DMN during periods of working-memory maintenance. These results demonstrate a contribution of the DMN to ongoing cognition extending beyond task-unrelated processing that can include detailed experiences occurring under active task conditions.
PERCEPTION OF THE RISK OF GETTING IN CONTACT WITH A SEXUALLY TRANSMISSIBLE DISEASE: EXPERIENCE FROM A GROUP OF TEENAGERS FROM TIRGU MURES, ROMANIA

THE OBJECTIVE of the study was focused on describing the perception of adolescents from an urban climate on their knowledge about sexually transmitted diseases, their sexual experiences, to identifying the level of knowledge regarding contraceptive methods and information sources. MATERIAL AND METHODS: We used a cross-sectional study, by applying an evaluation questionnaire about education and sexual behaviour to 200 students. The data were collected during the period of 01.10. 2012-15.12. 2012 in high schools from Tg Mures city. RESULTS: Boys were earlier to practice sex and had an earlier sexual debut compared to girls. At age of 17-18 years, we identified equal proportions between the sexes, with increasing numbers of girls who have had a sexual contact. Among questioned adolescents who had sexual contact 42.8 to 44.8% reported they had protected sex. Out of all the teenagers who have had sexual intercourse, 60% had received sexual education information. These were provided primarily by friends, and after by parents and physicians. Girls are more interested than boys to talk to their sexual partner about the risk of a possible pregnancy or methods of contraception. In conclusion, our result can provide useful information on the sexual behaviour of Romanian teenagers in urban areas, which can be beneficial for starting health programs in schools, with the aim to assist the young population to avoid unwanted pregnancy or sexually transmitted diseases. Keywords: sexually transmitted diseases, sexual behaviour, adolescent.
Light-induced dilation in nanosheets of charge-transfer complexes

Significance Photostrictive compounds are promising device materials because of their fundamental photophysical properties and light-induced strain applications. Although molecular charge-transfer crystals exhibiting light–matter interactions have been successfully deployed in optoelectronics, an air-stable molecular material that couples photons and electrons, achieving photostriction through the coupling of light and mechanical degrees of freedom, has not yet been discovered. Herein, we report a substantial light-induced dilation in a molecular material at room temperature, which is accompanied by simultaneous photocurrent generation. This finding opens avenues for coupling optical, electronic, and mechanical functionalities for possible use in remote wireless photoswitchable devices. We report the observation of a sizable photostrictive effect of 5.7% with fast, submillisecond response times, arising from a light-induced lattice dilation of a molecular nanosheet, composed of the molecular charge-transfer compound dibenzotetrathiafulvalene (DBTTF) and C60. An interfacial self-assembly approach is introduced for the thickness-controlled growth of the thin films. From photoabsorption measurements, molecular simulations, and electronic structure calculations, we suggest that photostriction within these films arises from a transformation in the molecular structure of constituent molecules upon photoinduced charge transfer, as well as the accommodation of free charge carriers within the material. Additionally, we find that the photostrictive properties of the nanosheets are thickness-dependent, a phenomenon that we suggest arises from surface-induced conformational disorder in the molecular components of the film. Moreover, because of the molecular structure in the films, which results largely from interactions between the constituent π-systems and the sulfur atoms of DBTTF, the optoelectronic properties are found to be anisotropic. This work enables the fabrication of 2D molecular charge-transfer nanosheets with tunable thicknesses and properties, suitable for a wide range of applications in flexible electronic technologies.