Miracle-dz/UniFAR-FTUs huggingface dataset:
A case of primary aldosteronism caused by unilateral multiple adrenocortical micronodules presenting as muscle cramps at rest: The importance of functional histopathology for identifying a culprit lesion

Unilateral multiple adrenocortical micronodules (UMNs) constitute a rare subset of primary aldosteronism (PA) characterized by the hypersecretion of aldosterone derived from multiple small nodules in the zona glomerulosa of the unilateral adrenal grand. This case study describes a 49‐year‐old man with PA and UMNs who presented with muscle cramps at rest due to hypokalemia. The patient had a 6‐year history of hypertension treated with antihypertensive drugs. Imaging studies revealed bilateral adrenal nodules as large as 5 mm. Adrenal venous sampling confirmed unilateral PA; therefore, the patient underwent the removal of the affected adrenal gland. Macroscopically, the removed adrenal gland exhibited irregular adrenocortical thickening accompanied by ill‐defined, adrenocortical macronodules as large as 6 mm. The zona glomerulosa was histologically hyperplastic. However, an immunohistochemistry test of the steroidogenic enzymes revealed that these macronodules and the hyperplastic glomerular layer tested negative for CYB11B2. Moreover, we observed adrenocortical micronodules as large as 0.5 mm that tested immunohistochemically positive for CYP11B2 and HSD3B2 but negative for CYP17A1 and CYP11B1. Thus, UMNs were diagnosed. This case instructively indicates that a grossly or histologically detectable nodular lesion is not necessarily a culprit lesion for PA. Therefore, functional histopathology is indispensable for the correct subclassification of PA.
Lenvatinib for the Treatment of Radioiodine-Refractory Thyroid Cancer in Real-Life Practice.

BACKGROUND In the Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) phase 3 trial on advanced radioactive iodine-refractory differentiated thyroid cancer (rDTC), lenvatinib improved median progression-free survival over placebo by almost 15 months and induces an objective response rate of 64.8%, but adverse events occurred in almost all patients. The present study evaluates the efficacy and toxicity of lenvatinib treatment in real-life practice. METHODS Clinical charts of 88 consecutive patients treated with lenvatinib from July 2015 to June 2016 in 27 French centers were retrospectively reviewed. Patients treated for other thyroid cancer types (n = 11) or previously treated with lenvatinib within a trial (n = 2) were excluded and the remaining 75 rDTC patients formed the basis of this report. RESULTS 75 rDTC patients were analyzed (33 females, median age 65 years [range, 35-88 years]), 12 had an Eastern Cooperative Oncology Group performance status ≥2; 24 cases received lenvatinib as first line systemic treatment; 47 (63%) patients had documented progressive disease prior to treatment initiation. Distant metastases were located in lungs, bones, and lymph nodes (89%, 60%, and 69%, respectively). The initial treatment dose was 24 mg in 54 patients and was lower in the other 21 patients. The median follow-up was 7 months, with a median duration of treatment of 6 months [0.3-15]. Median progression-free survival was 10 months. Among the 65 patients with evaluation of tumor response during treatment, best tumor response was a partial response in 23 patients (31%) and stable disease in 38 (51%). Eleven patients (14.7%) discontinued lenvatinib because of disease progression. Forty-four (59%) and 23 (31%) patients had dose reductions or an interruption of lenvatinib for adverse events (AEs). The most frequent AEs related to treatment were fatigue, hypertension, weight loss, diarrhea, and anorexia. Eleven deaths occurred during the study (one considered to be drug related). Pneumothorax occurred in 2 patients with lung metastases. CONCLUSIONS Real-life patients with rDTC can benefit from lenvatinib treatment. AEs are frequent and should be closely monitored.
Mechanistic target of rapamycin (MTOR) signaling during ovulation in mice

A complex network of endocrine/paracrine signals regulates granulosa‐cell function in ovarian follicles. Mechanistic target of rapamycin (MTOR) has recently emerged as a master intracellular integrator of extracellular signals and nutrient availability. The objectives of the present study were to characterize the expression pattern and kinase activity of MTOR during follicular and corpus luteum development, and to examine how inhibition of MTOR kinase activity affects preovulatory maturation of ovarian follicles. MTOR expression was constitutive throughout follicular and corpus luteum development. Gonadotropins induced MTOR kinase activity in the ovary, which was inhibited by rapamycin treatment (10 µg/g body weight, intraperitoneal injection). Inhibition of human chorionic gonadotropin (hCG)‐induced MTOR activity during preovulatory follicle maturation did not change key events of ovulation. Granulosa cells of rapamycin‐treated mice showed reduced MTOR kinase activity at 1 and 4 hr post‐hCG and overexpression of hCG‐induced ovulation genes at 4 hr post‐hCG. Overexpression of these ovulatory genes was associated with hyper‐activation of extracellular signal‐regulated kinase 1/2 (ERK1/2), which occurred in response to inhibition of MTOR with rapamycin and suggested that MTOR may function as a negative regulator of the mitogen‐activated protein kinase (MAPK) pathway. Indeed, simultaneous inhibition of MTOR and ERK1/2 activities during preovulatory follicle maturation caused anovulation. Inhibition of hCG‐induced ERK1/2 activity alone suppressed MTOR kinase activity, indicating that MAPK pathway is upstream of MTOR. Thus, normal ovulation appears to be a result of complex interactions between MTOR and MAPK signaling pathways in granulosa cells of ovulating follicles in mice. Mol. Reprod. Dev. 81: 655–665, 2014. © 2014 Wiley Periodicals, Inc.
Evaluation of heat‐shock protein A2 (HSPA2) in male rats before and after varicocele induction

Varicocele is a major cause of infertility and may impair spermatogenesis. This study evaluated the molecular consequences of varicocele on the induction of heat‐shock proteins, intracellular chaperones involved in stress responses, and of the ubiquitin‐proteasome system, which is participates in the removal of defective sperm in the testis and epididymis. Wistar rats were randomly divided into three groups: surgically induced left varicocele, sham‐operated, and untreated controls. Two months after surgery, we observed significantly reduced sperm parameters, DNA integrity, and protamine content in the sperm retrieved from the left epididymis compared to the right epididymis in the varicocele group, as well as compared to sperm retrieved from the left epididymis of the sham and control groups. According to Western blot analysis, we observed significantly higher HSPA2 expression in testicular tissue from the left testis compared to the right testis in the varicocele group or the left testis of the control group. Immunohistochemical analysis showed that expression of HSPA2 was higher in the round spermatid and sperm from the left varicocele compared to the control group. There was normally less HSPA2 expressed in the caput and corpus compared to the cauda of the epididymis in the control group, but this pattern was altered in the caput epididymis of the varicocele group. Levels of ubiquitination were also remarkably lower in the left testis of the varicocele group. Therefore, varicocele impacts expression of HSPA2 and ubiquitination. Mol. Reprod. Dev. 81: 766–776, 2014. © 2014 Wiley Periodicals, Inc.
Present and future of aesthetic plastic surgery in Korea

Due to Confucian ethics and socioeconomic factors, aesthetic plastic surgery came late to Korea. However, the field of aesthetic plastic surgery developed rapidly after the establishment of the Korean Society of Aesthetic Plastic Surgeons in 1985. At present, Korean aesthetic plastic surgeons have achieved world leading surgical skills and research abilities. This article review the history and current state of Korean aesthetic plastic surgery with the follow-up study of statics and numerical data. Over the period of 10 years (2001-2010), the Korean plastic surgeons contributed 607 papers to SCI & SCI(E) journals. Among them, the number of pure cosmetic surgical papers was 133 (21.9%). According to biannual survey data from the International Society of Aesthetic Plastic Surgery in 2009, the number of plastic surgeons and aesthetic procedures in Korea became the highest contrast to percentage of the population in the world. As dynamic forces of development for Korean aesthetic plastic surgery, this advocate the medical tourism, non-surgical cosmetic procedures, and adipose-derived stem cells. With developing these items, Korean plastic surgeons will create the brilliant future of the aesthetic plastic surgery in Korea.
Transport in technicolor: Mapping ATP‐binding cassette transporters in sea urchin embryos

One quarter of eukaryotic genes encode membrane proteins. These include nearly 1,000 transporters that translocate nutrients, signaling molecules, and xenobiotics across membranes. While it is well appreciated that membrane transport is critical for development, the specific roles of many transporters have remained cryptic, in part because of their abundance and the diversity of their substrates. Multidrug resistance ATP‐binding cassette (ABC) efflux transporters are one example of cryptic membrane proteins. Although most organisms utilize these ABC transporters during embryonic development, many of these transporters have broad substrate specificity, and their developmental functions remain incompletely understood. Here, we review advances in our understanding of ABC transporters in sea urchin embryos, and methods developed to spatially and temporally map these proteins. These studies reveal that multifunctional transporters are required for signaling, homeostasis, and protection of the embryo, and shed light on how they are integrated into ancestral developmental pathways recapitulated in disease. Mol. Reprod. Dev. 81: 778–793, 2014. © 2014 Wiley Periodicals, Inc.
The Ontology of Determination: From Descartes to Spinoza

Argument This paper argues that Spinoza's notions of “conatus” and “power of acting” are derived by means of generalization from the notions of “force of motion” and “force of determination” that Spinoza discussed in his Principles of Cartesian Philosophy to account for interactions among bodies (impacts) on the basis of their degrees of contrariety. I argue that in the Ethics, Spinoza's ontology entails that interactions must always be accounted for in terms of degrees of “agreement or disagreement in nature” among interacting things. The notion of “power of acting” is used to express the extent to which a thing's conatus is aided or restrained by external causes on the basis of its degree of agreement or disagreement in nature with them. “Power of acting” generalizes the same approach and method of resolution at the basis of the notion of “force of determination” in order to account for causal interactions not only among the simplest bodies but also among more complex individuals.
Spata19 is critical for sperm mitochondrial function and male fertility

Haploid round spermatids undergo differentiation and morphogenesis during spermiogenesis, resulting in mature spermatozoa. The molecular details underlying this transformation, however, remain poorly understood. In this study, we generated and analyzed germ cell‐specific Spata19 knockout mice (Spata19flox/flox; Stra8‐Cre; hereafter termed “Spata19 cKO”) to assess the model that SPATA19 contributes to mitochondrial function in differentiating spermatids. Spata19‐cKO males were infertile, as their sperm exhibited disorganized mitochondrial structure; furthermore, their sperm‐abundance of mitochondrial proteins, activities of mitochondrial respiratory chain complex IV, and ATP levels were significantly reduced. Yet, the infertility of Spata19‐cKO males was rescued by intracytoplasmic sperm injection, so the sperm are capable of initiating development. Collectively, our findings suggest that SPATA19 plays an important role in sperm motility by regulating the organization and function of the mitochondria. Mol. Reprod. Dev. 82: 907–913, 2015. © 2015 Wiley Periodicals, Inc.
An in vitro gastrulation model recapitulates the morphogenetic impact of pharmacological inhibitors of developmental signaling pathways

Certain chemical agents act as teratogens, causing birth defects and fetal deaths when pregnant women are exposed to them. The establishment of in vitro models that recapitulate crucial embryonic events is therefore vital to facilitate screening of potential teratogens. Previously, we created a three‐dimensional culture method for mouse P19C5 embryonal carcinoma stem cells that, when cultured as embryoid bodies, display elongation morphogenesis resembling gastrulation, which is the critical event resulting in the germ layers and major body axes. Determination of how well this in vitro morphogenesis represents in vivo gastrulation is essential to assess its applicability as well as to identify limitations of the model for detecting teratogenic agents. Here, we investigated the morphological and molecular characteristics of P19C5 morphogenesis using pharmacological agents that are known to cause abnormal patterning in the embryo in vivo by inhibiting major developmental signaling—e.g., involving Wnt, Nodal, Bone morphogenic protein (Bmp), Fibroblast growth factor (Fgf), Retinoic acid, Notch, and Hedgehog pathways. Inhibitors of Wnt, Nodal, Bmp, Fgf, and Retinoic acid signaling caused distinct changes in P19C5 morphogenesis that were quantifiable using morphometric parameters. These five inhibitors, plus the Notch inhibitor, also altered temporal expression profiles of developmental regulator genes in a manner consistent with the in vivo roles of the corresponding signaling pathways. In contrast, the Hedgehog inhibitor did not have any impact on the process, suggesting an absence of active Hedgehog signaling in these embryoid bodies. These results indicate that the P19C5 in vitro gastrulation model is a promising tool to screen for teratogenic agents that interfere with many of the key developmental signals. Mol. Reprod. Dev. 82: 1015–1036, 2015. © 2015 Wiley Periodicals, Inc.
Growth alteration and leaf biochemical responses in Phaseolus vulgaris exposed to different doses of ionising radiation.

Ionising radiation may have different effects on plant metabolism, growth and reproduction, depending on radiation dose, plant species, developmental stage and physiological traits. In this study, exposure of dwarf bean plants to different doses of X-rays (0.3, 10, 50, 100 Gy) was investigated with a multidisciplinary approach consisting of morphological, ecophysiological and biochemical analysis. Both mature and young leaves still growing during the X-rays exposure were compared with non-irradiated control leaves. In particular, leaf expansion, leaf anatomy and functional traits, as well as photosynthetic pigment content and Rubisco expression were analysed. Moreover, the activity of poly(ADP-ribose) polymerase (PARP) was also measured as an indicator of radiation-induced DNA damage. Our data showed that leaf growth is affected by high levels of radiation and demonstrate that mature leaves are more radio-resistant than young leaves, which experience severe dose-dependent changes in leaf functional traits. In particular, young leaves exhibited a reduction of area and an increase in specific mass and dry matter content, as well as a decline in Rubisco activity. Moreover, they showed elevated PARP activity and an increase in phenolic compounds in wall cells if compared with mature leaves. Both of these strategies have been interpreted as a way to help developing leaves withstand irradiation.
Komodo as seen from Sumba: Comparative remarks on eastern Indonesian relationship terminology

The purpose of these notes is to record several observations regarding the terminology of relationship found on the eastern Indonesian island of Komodo as described by Father J. A. J. Verheijen in his valuable linguistic and ethnographic monograph (1982). The occasion for doing so is provided by Professor Needham's recent, mostly formal analysis of Verheijen's data (1986), and more particularly by a notable omission from the comparative evidence which Needham adduces in this context. Here I refer to eastern Sumbanese mamu, FZ, FZH, as compared with Komodo mamo, FZ, FZH, HP. After discussing what the evident con nection between these two words might imply for an understanding of the Komodo terminology, I shall consider several more general features of the classification, especially as these bear upon the issues of symmetry/asymmetry and prescription in the comparative analysis of eastern Indonesian relationship terminologies. In an earlier essay, Needham, on the basis of an unpublished version of the Komodo terminology provided by Father Verheijen, character izes the terminology with a 'structural formula' written as 'A(S)A' (1984:226). What this means is, quite simply, that the classification exhibits asymmetric features in the first ascending genealogical level, predominantly symmetric features in ego's level, and asymmetric features again in the first descending level. The purposes of Needham's more recent remarks on the Komodo terminology, as the author himself states, are to justify this 'structural formula' and 'to bring out from the new evidence', by which he refers to the Komodo terminological data published in Verheijen's monograph, 'some of the singular interest of
Dependency of seed dormancy types on embryo traits and environmental conditions in Ribes species.

The hypothesis that seed dormancy may be dependent on environmental conditions and seed morphological traits was tested for six Ribes species, across an altitudinal gradient of 1300 m and a longitudinal separation of 120°. Embryo measurements and seed germination experiments were conducted for R. alpinum L. , R. hudsonianum Richardson var. petiolare (Douglas) Jancz. , R. nevadaense Kellogg, R. roezlii Regel var. cruentum (Greene) Rehder and R. speciosum Pursh, and data taken from the literature for R. multiflorum Kit. ex Schult. ssp. sandalioticum Arrigoni. Germination was compared with seed viability to reveal proportional seed dormancy, which was then correlated to seed/embryo morphological traits and these traits related to the seed provenance environment. The embryos of all the investigated species are linear underdeveloped and all had a morphological component of seed dormancy (MD). Seeds of R. roezlii, R. hudsonianum and R. nevadaense required a temperature and/or hormone pre-treatment in order to germinate, highlighting morphophysiological seed dormancy (MPD). Seed dormancy was found to be strongly negatively correlated with embryo length, but not with embryo to seed (E:S) ratio or seed mass. Initial embryo length was positively related to mean annual temperature. Seed dormancy in the investigated Ribes species could be quantified and predicted by the interaction of embryo traits and environmental conditions. This approach may be helpful in assessing and predicting seed dormancy in the Ribes genus and in other genera and families with underdeveloped embryos.
Children's interpretation of disjunction in the scope of ‘before’: a comparison of English and Mandarin

ABSTRACT This study investigates three- to five-year-old children's interpretation of disjunction in sentences like ‘The dog reached the finish line before the turtle or the bunny’. English disjunction has a conjunctive interpretation in such sentences (‘The dog reached the finish line before the turtle and before the bunny’). This interpretation conforms with classical logic. Mandarin disjunction (‘huozhe’) can take scope over ‘before’ (‘zai … zhiqian’), so the same sentence can mean ‘The dog reached the finish line before the turtle or before the bunny (I don't know which)’. If children are guided by adult input in the acquisition of sentence meanings, English- and Mandarin-speaking children should assign different interpretations to such sentences. If children are guided by logical principles, then children acquiring either language should initially assign the conjunctive interpretation of disjunction. A truth-value judgment task was used to test this prediction and English- and Mandarin-speaking children were found to behave similarly.
Floral biology of two Vanilloideae (Orchidaceae) primarily adapted to pollination by euglossine bees.

Vanilloideae comprises 15 genera distributed worldwide, among which are Vanilla and Epistephium (tribe Vanilleae). Based on field and laboratory investigations, the pollination biology of V. dubia and E. sclerophyllum was analysed. The former was surveyed in a semi-deciduous mesophytic forest at the biological reserve of Serra do Japi and in a marshy forest at the city of Pradópolis, southeastern Brazil. The latter was examined in rocky outcrop vegetation in the Chapada Diamantina, northeastern Brazil. In the studied populations, the tubular flowers of V. dubia and E. sclerophyllum were pollinated by bees. Pollen was deposited on either their scutellum (V. dubia) or scutum (E. sclerophyllum). The mentum region of V. dubia is dry, whereas that of E. sclerophyllum presents a small quantity of dilute nectar. Flowers of E. sclerophyllum are scentless, while those of V. dubia are odoriferous. Although V. dubia is self-compatible, it needs a pollinator to produce fruit. In contrast, E. sclerophyllum sets fruit through spontaneous self-pollination, but biotic pollination also occurs. Both species are primarily adapted to pollination by euglossine bees. Pollination by Euglossina seems to have occurred at least twice during the evolution of Vanilleae. Furthermore, shifts between rewarding and reward-free flowers and between autogamous and allogamous species have been reported among vanillas.
Effect of foster care on language learning at eight years: Findings from the Bucharest Early Intervention Project*

ABSTRACT This study reports on language outcomes at eight years from the Bucharest Early Intervention Project, a randomized controlled study of foster care. We previously have shown that children placed in foster care by age two have substantially stronger preschool language outcomes than children placed later and children remaining in institutional care. One hundred and five children participated in the current study, fifty-four originally assigned to foster care and fifty-one to continued institutional care. Even though current placements varied, children originally in foster care had longer sentences and stronger sentence repetition and written word identification. Children placed in foster care by age two had significant advantages in word identification and nonword repetition; children placed by age 1 ; 3 performed equivalently to community peers. The results show the continuing adverse effects of early poor institutional care on later language development and the key importance of age of placement in a more optimal environment.