DERMATOFIBROSARCOMAPROTUBERANS (DFSP) is a rare recurrent fibrohistiocytic tumor. Given the limitation of available diagnostic modalities in a resource poor setting, diagnosis can be confusing. As most of the tumors recur with time, our case of complete cure was interesting phenomenon observed in our case

This case report displays some of the possible complications of sumatriptan poisoning, including nephritic syndrome.

The Multiple Endocrine Neoplasia type 2 (MEN2) RET proto-oncogene database, originally published in 2008, is a comprehensive repository of all publicly available RET gene variations associated with MEN2 syndromes. The variant-specific genotype/phenotype information, age of earliest reported medullary thyroid carcinoma onset, and relevant references with a brief summary of findings are cataloged. The ACMG/AMP 2015 consensus statement on variant classification was modified specifically for MEN2 syndromes and RET variants using ClinGen sequence variant interpretation working group recommendations and ClinGen expert panel manuscripts, as well as manuscripts from the American Thyroid Association Guidelines Task Force on Medullary Thyroid Carcinoma and other MEN2 RET literature. The classifications for the 166 single unique variants in the MEN2 RET database were reanalyzed using the MEN2 RET specifically modified ACMG/AMP classification guidelines. Applying these guidelines added two new variant classifications to the database (likely benign and likely pathogenic) and resulted in clinically significant classification changes ( e.g. from pathogenic to uncertain) in 16.9% (28/166) of the original variants. Of those clinically significant changes, the highest percentage of changes, 46.4% (13/28), were changes from uncertain to benign or likely benign. The modified ACMG/AMP criteria with MEN2 RET specifications will optimize and standardize RET variant classifications.

Background Household studies are crucial for understanding the transmission of SARS-CoV-2 infection, which may be underestimated from PCR testing of respiratory samples alone. We aim to combine assessment of household mitigation measures; nasopharyngeal, saliva and stool PCR testing; along with mucosal and systemic SARS-CoV-2 specific antibodies, to comprehensively characterise SARS-CoV-2 infection and transmission in households. Methods Between March and September 2020, we obtained samples from 92 participants in 26 households in Melbourne, Australia, in a 4-week period following onset of infection with ancestral SARS-CoV-2 variants. Results The secondary attack rate was 36% (24/66) when using nasopharyngeal swab (NPS) PCR positivity alone. However, when respiratory and non-respiratory samples were combined with antibody responses in blood and saliva, the secondary attack rate was 76% (50/66). SARS-CoV-2 viral load of the index case and household isolation measures were key factors that determine secondary transmission. In 27% (7/26) of households, all family members tested positive by NPS for SARS-CoV-2 and were characterised by lower respiratory Ct-values than low transmission families (Median 22.62 vs 32.91; IQR 17.06 to 28.67 vs 30.37 to 34.24). High transmission families were associated with enhanced plasma antibody responses to multiple SARS-CoV-2 antigens and the presence of neutralising antibodies. Three distinguishing saliva SARS-CoV-2 antibody features were identified according to age (IgA1 to Spike 1, IgA1 to nucleocapsid protein (NP), suggesting that adults and children generate distinct mucosal antibody responses during the acute phase of infection. Conclusion Utilising respiratory and non-respiratory PCR testing, along with measurement of SARS-CoV-2 specific local and systemic antibodies, provides a more accurate assessment of infection within households and highlights some of the immunological differences in response between children and adults.

A 65-year-old male with history of Hashimoto's thyroiditis on Levothyroxine developed Graves' disease with ocular symptoms and was treated with teprotumumab without improvement. Total thyroidectomy was performed to control hyperthyroidism. Surgical pathology revealed multifocal papillary thyroid carcinoma. Rarely a spectrum of thyroid disorders is seen in a single patient.

Background: Mites represent the second largest group with diverse niches and feeding habits, except for insects. Scabies mites are the causative agents of highly contagious skin disease in humans and more than 100 mammals. Although several versions of Sarcoptes scabiei genome have been published, i.e. var. suis, var. canis and var. hominis, the chromosome-level genome and population divergence is still desired for the community. Besides, the molecular mechanisms that scabies mites adapt to a parasitic lifestyle remains unclear. The taxonomy and ancestral origin of the scabies mite is unknown. Results: Here, we reported the first chromosome-level reference genome of S. scabiei, which was isolated from rabbits. The genome has a contig N50 size of 5.92 Mb, a total assembled length of 57.30 Mb, and ~12.65% of repetitive sequences and 9,333 protein‑coding genes were predicted. Population genetics analysis supported that scabies mites isolated from different hosts can be subdivided by hosts, and humans are likely the primary hosts of scabies mites, followed by pigs, dogs, and rabbits. However, phylogeny results suggested that rabbit was infected with scabies long before they were domesticated by humans, contradicting previous hypothesis that humans transmitted scabies mites to animals through domestication. Comparative genomics between scabies mites and mites of other feeding habits provided clues concerning the mechanisms of adaptation to permanent parasitic life from morphology, detoxification, and metabolism. Conclusions: Together, the first chromosome-level S. scabiei genome and population genetics analysis indicated its genetic subdivisions and within-host species divergence, which also provide evidence for further control of this highly contagious skin disease.

Our study of a patient who experienced a torpid evolution in 9 months incomplete treatment with antimonials and amphotericin B, with the destruction of the eyeball, a large area of necrosis on the face and nasal bone exposure.

For a Life Beyond the CureTissy Lagun Costa11Division of Pedagogical Coordination, Nursery and Pre-kindergarten, Escolinha do Faz-de-Conta, Orlândia, São Paulo, Brasil* Correspondence to:Tissy Lagun Costa, Avenida Dois, 894, Centro, Orlândia, São Paulo, 14620-000, Brasil, Tel.: +55(16)99608-2350, Email: [email protected] word count 1099;Abstract word count: 0;Brief running title: For a life beyond the cureKey words: palliative care, DIPG, brain, tumor, CNS tumorTables: 0Figures: 0I didn’t expect that pregnancy. I really wanted it; but after going through a fertility treatment to have my first son, I couldn’t imagine that the second would come so easily. It was only eighteen months between one birth and the next one. First a boy and then a girl. A girl we called Alice.She was a beautiful baby. Delicate. From the first sight, we knew she would have great hair. She was never bald. When her newborn hair started to fall out, strong thick hair grew immediately covering her cute round head. She had a perfect body. Slender and – believe me! – with a well-defined waist.At three months, the color of her eyes began to change. One eye changed first, followed by the other. Is that normal? I don’t know. But that is how it happened. One eye was already brown, while the other still had shades of light green.She smiled for the first time. She used to grab all the objects surrounding her crib and, several times she watched her own hand moving in awe as if there was magic about it. She sat, crawled and walked all at the proper ages. She spoke her first words and quickly expanded her vocabulary. She admired her chatty brother, and there was no shortage of stimuli.She started to go to school. She was a happy and clever student. Praised by all her teachers. She actively participated in all activities. She rehearsed for presentations and cultural events. My sole contribution was to smile filled with pride – and to sew costumes for her plays and dresses for dancing around.She made bonds. Her friends were dear. They played together all the time. Her gang consisted of two boys, the twin girls, the two other girls who loved to make mischief and her best friend. Alice was the peacemaker of the group; she didn’t like conflict.Her birthdays were celebrated with many guests. When she started to understand what a party was, she made sure to always choose a theme: Little Red Riding Hood, Enchanted Fairies and Doll Tea Party complete with a full set of porcelain tea cups and pots for the stuffed guests.One day, running to get to the door to greet her best friend, she tripped and fell, hitting her mouth on the floor. Her two front teeth blackened. I didn’t worry. They were her baby teeth. After several toothless smiles, new strong teeth would grow. My life was normal, like any other mom.Until in January 2014, when everything changed.“Unfortunately, Alice has a very aggressive tumor called Diffuse Intrinsic Pontine Glioma, a.k.a. DIPG. In ninety-five percent of cases, the child dies after a few months.”; that was her diagnosis.What?! How could a routine medical appointment end up like that? I brought to the doctor a simple question: do we have to do something about her right eye being a bit misaligned? How can a question as simple as that require several appointments, examinations and two MRIs?After a crash course in neuro-oncology, we understood that Alice’s right eye couldn’t move to the right because of the sixth cranial nerve. And that nerve was connected to a time bomb about to explode.Our first reaction was of shock and awe. There must be a mistake. The doctors weren’t considering a second opinion when interpreting the images? Couldn’t it be something else? Maybe some dirt on the lens?When reality finally struck me, I faced a storm. The picture that comes to mind is a dam bursting; my body taking all that chaotic energy to avoid complete devastation. A torrential flow of conflicting emotions compounded each other. It took from me and my family our capacity to breathe, to feel and think – it got into our bones. It made us physically crumble on top of ourselves. But, no matter what, we needed to make the most important decision of our lives, so we didn’t fall apart.And we chose life.It didn’t matter how much time Alice had to live. Her life would be worth it. Each hour, each minute and each second would have meaning.Our first reaction was to avoid medical treatment. To put our plan in motion and to wait for the inevitable outcome. But it is too hard to do nothing. So, we chose the treatment that had the least impact on quality of life. Which until then was perfect. As I said, it was only her eye…What marked that period was the sorrow for the loss of what could be. It was the death of all the dreams we once dreamt for Alice: a long life full of accomplishments. The ending would be a family picture, a big family with grandkids all around and great grandkids on her lap.With our goals reevaluated, our objective was to live intensely in her last months of life. We travel to several places. The kids learned karate. We camped in the forest. We went fishing. We played in the snow. Anything was worthy of celebration. A sunny day. A fun movie. The birth of a puppy at the farm. A shower in the rain. And, against all odds, we celebrated three more birthdays.During those three years, we held our breath and focused on the present. One day, that effort took a toll on us. We were exhausted. After several MRIs that didn’t show any change in the tumor, nobody could tell if it was really dead. But suddenly, the uncertainty became certainty; the tumor started to grow again.Without the same energy we had before, we had to start a new plan. To face the most feared challenges we had avoided until now — the devastating symptoms that would take Alice from us piece by piece.The loss of movement on the right side of her face. The loss of movement of her legs and arms. The loss of her muscular tone. The loss of her ability to swallow. And, in the end… the loss of her heartbeat.Alice left the scene at nine years old.She is deeply missed; it’s painful. It’s a void that establishes itself as a physical being that we learn to live with.Drop by drop, I began to fill this void with memories. Writing helped me to get closer to my daughter. I wrote a book. These memories are dear to me. They are forever etched in paper.And like that, whenever I sit to write, I chat with my daughter Alice.What do we talk about?We talk about the beautiful life she lived.

Growth and growth limitation are important indicators of density dependence and environmental limitation of populations. Estimating individual growth trajectories is therefore an important aspect of understanding and predicting the life history and dynamics of a population. Variation in individual growth trajectories arises due to variation in the environmental factors limiting individual growth. This environmental limitation can vary over time, between cohorts and between individuals within a cohort. For a complete and accurate understanding of individual growth in a population, it is important to include all these sources of variation. So far, statistical models only accounted for a subset of these factors or required an extensive growth history of individuals. Here we present a novel model describing the growth curves of cohorts in a population. This model is derived from a stochastic form of the Von Bertalanffy growth equation describing individual growth. The model is specifically tailored for use on length-at-age data in which the growth trajectory of an individual is unknown and every individual is only measured once. The presented method can also be used if growth limitation differs strongly between age or length classes. We demonstrate the use of the model for length-at-age data of North Sea plaice (Pleuronectes platessa) from the last thirty years. Fitting this model to length-at-age data can provide new insights in the dynamics of the environmental factors limiting individual growth and provides a useful tool for ecological research and management.

In studying the stability of B\’{e}nard problem we usually have to solve a variational problem to determine the critical Rayleigh number for linear or nonlinear stability. To solve the variational problem one usually transform it to an eigenvalue problem which is called Euler-Lagrange equations. An operator related to the Euler-Lagrange equations is usually referred to as Euler-Lagrange operator whose spectrum is investigated in this paper. We have shown that the operator possesses only the point spectrum consisting of real number, which forms a countable set. Moreover, it is found that the spectrum of the Euler-Lagrange operator depends on the thickness of the fluid layer.

Imidazole derivatives are the foundation of different types of drugs with a wide range of biological activities. In this study, the genetic algorithm multiple linear regression (GA- MLR), and backpropagation-artificial artificial neural network (BP-ANN) were applied to design QSPR models to predict the quantum chemical properties like the entropy(S) and enthalpy of formation(∆Hf) of imidazole derivatives. In order to draw molecular structure of 84 derivative compounds Gauss View 05 program was used. These structures were optimized at DFT-B3LYP / 6-311G* level with Gaussian09W. The Dragon software was used to calculate a set of different molecular descriptors, and the genetic algorithm procedure and backward stepwise regression were applied for the selection of descriptors. The resulting quantitative GA-MLR model of ∆Hf, showed that there is good linear correlation between the selected descriptors and ∆Hf of compounds. Also the results show that the BP-ANN model appeared to be superior to GA-MLR model for prediction of entropy. Different internal and external validation metrics were adopted to verify the predictive performance of QSPR models. The predictive powers of the models were found to be acceptable. Thus, these QSPR models may be useful for designing new series of imidazole derivatives and prediction of their properties.

Raman spectroscopy has gained popularity to monitor multiple process indicators simultaneously in biopharmaceutical processes. However, robust and specific model calibration remains a challenge due to insufficient analyte variability to train the models and high cross-correlation of various media components and artefacts throughout the process. Therefore, a systematic Raman calibration workflow for perfusion processes enabling highly specific and fast model calibration was developed. A harvest library consisting of frozen harvest samples from multiple CHO cell culture bioreactors collected at different process times was established, capturing process variability as widely as possible. Model calibration was subsequently performed in an offline setup using a flow cell by spiking process harvest with various sugars known to modulate glycosylation patterns of monoclonal antibodies. In a screening phase, Raman spectroscopy was proven capable not only to distinguish glucose, raffinose, galactose, mannose, and fructose in perfusion harvest, but also to quantify them independently in process relevant concentrations. In a second phase, a robust and highly specific calibration model for simultaneous glucose (RMSEP = 0.32 g/L) and raffinose (RMSEP = 0.17 g/L) real-time monitoring was generated and verified in a third phase during a perfusion process. The proposed offline calibration workflow allowed proper Raman peak decoupling, reduced calibration time from months down to days and can potentially be applied to other analytes of interest including lactate, ammonia, amino acids, or product titer.

We present ultra-fast quantum chemical methods for the calculation of infrared and ultraviolet-visible spectra designed to provide fingerprint information during autonomous and interactive explorations of molecular structures. Characteristic spectral signals can serve as diagnostic probes for the identification and characterization of molecular structures. These features often do not require ultimate accuracy with respect to peak position and intensity, which alleviates the accuracy--time dilemma in ultra-fast electronic structure methods. If approximate ultra-fast algorithms are supplemented with an uncertainty quantification scheme for the detection of potentially large prediction errors in signal position and intensity, an offline refinement will always be possible to confirm or discard the predictions of the ultra-fast approach. Here, we present ultra-fast electronic structure methods for such a protocol in order to obtain ground- and excited-state electronic energies, dipole moments, and their derivatives for real-time applications in vibrational spectroscopy and photophysics. As part of this endeavor, we devise an information-inheritance partial Hessian approach for vibrational spectroscopy, a tailored subspace diagonalization approach and a determinant-selection scheme for excited-state calculations.

1. Thermal performance curves (TPCs) are commonly used to forecast species’ responses to temperature change. Recent work has demonstrated that the breadth and shape of a consumer’s TPC change with resource densities, highlighting the potential for inaccurate forecasts if resource densities are not static. In particular, if resource densities decline, the optimal temperature and breadth of thermal performance also declines leading to an enhanced risk of warming, particularly among species that may incur additional costs of behavioral thermoregulation. 2. Here, we investigate the relationship between resource density and temperature (warming) on the persistence of a consumer population which exerts top-down control on its resource via trophic interaction. Trophic coupling generally reduces the potential for resource declines to exacerbate the negative effects of warming on consumers; when warming has negative effects on the consumer, resource densities tend to increase due to a reduction in top-down control. However, if resources are more sensitive to warming (e.g. due to an asymmetry amongst their thermal performance curves), the negative effects of warming on consumers can be exacerbated by declining resources. 3. Our work elucidates the importance of jointly considering temperature and resource limitation when utilizing assessing the thermal performance of species. We demonstrate how knowledge of the thermal performance of a resource population can be used to generate realized consumer thermal performance curves.

【Abstract】Aim To construct a prediction model based on functional mitral regurgitation (FMR) in patients with paroxysmal atrial fibrillation (PAF) for predicting atrial fibrillation recurrence after the post-circular pulmonary vein radiofrequency ablation (CPVA). Methods We retrospectively analyzed 289 patients with PAF who underwent CPVA for the first time . The patients were randomly divided into modeling group and verification group at the ratio of 75:25. In the modeling group, the multivariate logistic regression was used to analyze and construct a prediction model for post-CPVA recurrence in PAF patients, which was then validated in the verification group. Results (1) After 3-6 months of follow-up, the patients were divided into sinus rhythm group (252 cases) and recurrence group (24 cases); (2) In the modeling group, the age, LAD(left atrial diameter) and degree of MR (mild, moderate, severe) were higher in recurrence group than that of the sinus rhythm group, and the left atrial appendage emptying velocity (LAAV) was lower in recurrence group (all P<0.05). (3) A model for predicting the recurrence of PAF after radiofrequency ablation was constructed in the modeling group. The equation was: Logit(P) = -3.253 + 0.092 × age + 1.263 × mild MR + 2.325 × moderate MR + 5.111 ×severe MR - 0.113 × LAAV. The area under the curve (AUC) of the model was 0.889 in modeling group and 0.866 in verification group, and the difference was not statistically significant ( P>0.05). Conclusion: The prediction model of atrial fibrillation (AF) recurrence after CPVA in PAF patients has good predictive efficacy, high specificity and accuracy.

Fibrosis is a common process of tissue repair response to multiple injuries in all chronic progressive diseases, which featured with excessive deposition of extracellular matrix. Actually fibrosis can occur in all organs and tends to be nonreversible with the progresses of the diseases. Different cells types in different organs are involved in the occurrence and development of fibrosis, i.e. hepatic stellate cell, pancreatic stellate cell, fibroblasts, myofibroblasts. Present studies have shown that several programmed cell deaths including apoptosis, autophagy, ferroptosis, and necroptosis were closely related to organ fibrosis. Among these programmed cell deathes type, necroptosis, an emerging regulated cell death type were regard as a huge potential target to ameliorate organ fibrosis. In this review, we summarized the role of necroptosis signaling in organ fibrosis, and collected the present small molecule compounds targeting necroptosis. In addition, we have discussed the potential challenges, opportunities and open questions in using necroptosis signaling as a potential target for antifibrotic therapies.

Fetal atrioventricular block (AVB) is a failure of conduction from atria to ventricles. Immune- and non-immune-mediated forms occur, especially in association with congenital heart disease. Second-degree (2°) AVB may be reversible with dexamethasone and IVIG in immune-mediated disease. However, once third-degree AVB develops, it is deemed irreversible with need for a pacemaker and risk for cardiomyopathy. Rarely, 2° AVB is a transient, benign phenomenon in the immature conduction system. Few case series of transient AVB have been reported, but a management approach has not been defined. We report four patients with self-resolving, non-immune fetal AVB and outline a management strategy.

The literature has identified continued needs for children with cystic fibrosis. The profession of occupational therapy is uniquely equipped and trained to address a variety of needs that children with cystic fibrosis experience during daily life engagement, potentially filling this gap in services. Despite this, occupational therapists are rarely consulted or included in patient care plans. It is the goal of this letter that professionals working in the field of cystic fibrosis will gain an understanding and appreciation for the profession of occupational therapy when considering care plans for their patients.