Factor V Leiden mutation is commonly associated with venous thromboembolism. Although there are cases reported with prosthetic valve thrombosis, no native valve thrombosis has been reported in the literature. In this case report, we presented the concomitant aortic valve thrombosis and sinus of Valsalva aneurysm in a patient with a Factor V Leiden mutation. To the best of our knowledge, our case is the first in the literature.

A document by Jacqueline Montoya. Click on the document to view its contents.

In this case series, four patients developed or presented with severe infections. In addition to antimicrobial therapy, they were treated with a new matrix therapy technology called CACIPLIQ20®. CACIPLIQ20® markedly improved the outcomes of all cases in terms of healing times and range of motion despite healing by secondary intention.

Comparative studies of genetic diversity and population structure can shed light on the ecological and evolutionary factors governing host–parasite interactions. Even though they are considered of major biological importance, little is known about the adaptation potential of invasive parasites in their new ranges. Here, the genetic diversification of Varroa destructor, a novel parasite of Apis mellifera originating from Asia, was investigated using population genetics to compare how the genetic structure of the parasite changed in response to its interactions with distinct European populations of its new host. To do so, mites infesting two categories of hosts in four European regions were compared: (i) adapted hosts surviving through means of natural selection, thereby expected to impose strong selective pressure on the mites, and (ii) susceptible host populations, surviving because acaricides are applied, therefore characterized by a relaxed selection imposed by the host. Significant genetic divergence was found across regions, reflecting partially the invasion pattern of V. destructor throughout Europe, but also local adaptation of the mite to the host populations. Additionally, varying degrees of genotypic changes were found between mites from adapted and susceptible colonies. Altogether, these results indicate that V. destructor managed to overcome the genetic bottlenecks following its introduction in Europe and that host-mediated selection fostered changes in the genetic structure of this mite at diverse geographical scales. These findings highlight the potential of parasites to adapt to their local host populations and confirm that adaptations developed within co-evolutionary dynamics are a major determinant of population genetic changes.

Soil fungal communities are vital for post-fire ecosystem restoration because of their ability to cycle nutrients and form symbiotic partnerships with regenerating trees. However, understanding is limited about how high-severity wildfires influence the fungal community of ecosystems adapted to low-severity fires. We studied an 11-year-old chronosequence of high-severity burn ponderosa pine (Pinus ponderosa) in eastern Washington, USA. Using Illumina MiSeq of the ITS1 rRNA, we examined changes in soil geochemistry, and drivers of ectomycorrhizal (EcM) and saprobic fungal richness, community shifts, and post-fire fungal succession. High-severity wildfires reduced EcM fungal richness by an average of 45.8% and saprobic richness by 11.7%, leading to significant, long-term alterations to the post-fire fungal communities that did not return to unburned levels even after 11 years. Over time, differences in the post-fire fungal community were driven by the dominance of several pyrophilous fungi, including the EcM Ascomycete genera Pustularia and Wilcoxina, and the saprobic Basidiomycete genus Geminibasidium, which decreased in abundance with time post-fire. EcM fungi and saprobes were intimately linked to the soil environment: total nitrogen, total carbon, and depth of organic matter predicted EcM richness, while total carbon predicted saprobic species richness. We conclude that high-severity wildfires reduced both EcM and saprobic fungal richness and significantly altered the fungal community of this fire-adapted ecosystem, selecting for resilient and fire-adapted species, such as W. rehmii and Geminibasidium sp., thus initiating post-fire succession.

Water resources are crucial for maintaining daily life and healthy ecological environment. In order to gain a harmonious development among water resources and economic development in Chaohu Lake Watershed, it is urgent to quantify the lake-inflow. However, the accurate inflow forecast is severely limited by the lack of information regarding river flow (flow into Chaohu Lake). This paper attempts to overcome these problems through applying the integrated model, which coupled the water balance method and the Xin’anjiang model that the improved single objective particle swarm optimization was added. Meanwhile, the coupled model parameters were calibrated based on the objective function that the maximum weighted average Nash-Sutcliffe efficiency of the flood events with discontinuous time. In addition, the three copula functions (Clayton, Frank and Gumbel-Hougaard method) embodying bivariate probability distribution of annual precipitation and annual highest water level, were performed to select the typical year. According to the results of frequency analysis, Gumbel-Hougaard method is applied to select the typical hydrological years, including high inflow (2016), medium inflow (2007) and low inflow year (1978). Additionally, the calibration and verification results of the coupled model suggest that the simulation results are best in the high inflow year, followed by the media inflow year and the low inflow year. Also, annual lake inflow simulation in normal inflow year is 19.4×108 m3, while the findings of the annual average land surface runoff of the study area is 18.9×108 m3, indicating that the coupled water balance method and Xin’anjiang model have been proved to be robust in determining inflow in ungauged stream. The results of this present provides a basis for determining the appropriate operation and management of water resources systems.

Sheep and goat pox (SGP) and orf are economically important transboundary animal diseases of small ruminants in India. The current study investigated an outbreak of mixed infection with Goatpox virus (GTPV) and Orf virus (ORFV) that occurred in an extensive system of goat rearing. Based on clinical sings and postmortem findings the disease was preliminary diagnosed as goat pox. The overall morbidity rate of 85.71% (60/70) was reported. The morbidity rate in young animals (100%; 30/30) was higher than adults (75%; 30/40). The overall mortality rate recorded was 40% (28/70), whereas the case fatality rate of 20% and 66.67% in adults and young animals respectively. Preliminary molecular diagnosis revealed presence of capripoxvirus followed by specific confirmation as GTPV by PCR-RFLP and sequencing of major envelope protein gene P32 of CaPV. The ORFV was detected and confirmed by PCR amplification and sequencing of complete B2L gene from the scab samples collected from affected goats. Phylogenetic analysis and multiple sequence analysis of GTPV and ORFV virus isolates from current outbreak showed highest homology to their respective Indian isolates from different parts of country. The present study reported co-infection of GTPV and ORFV in goats, which might have contributed to high morbidity. Therefore, the outbreak is epidemiologically significant and emphasis should be given in future for continuous serological/clinical surveillance of mixed infections in small ruminants’ health management.

Rice husk ash (RHA) has potential as low-cost catalyst support to produce biodiesel. In this study, RHA was used as precursor for heterogeneous silica-based catalyst, Huskcatacid and Huskcatbase for biodiesel production from palm fatty acid distillate (PFAD). The formation of biodiesel from PFAD was performed via esterification using Huskcatacid, followed by transesterification using Huskcatbase. The biodiesel produced was evaluated based on several reaction parameters such as oil to methanol ratio, amount of catalyst, reaction times and temperature and the optimization of parameters was carried out. Results showed that Huskcatacid was efficiently employed in esterification of PFAD to afford 91.6% ester in 1:1 (PFAD:MeOH) and 5 wt% catalyst, followed by transesterification in 1:1 (oil: MeOH) using Huskcatbase (1 wt%) to produce 99.73% biodiesel in 30 min with high percentage of methyl palmitate (34.43%) and methyl oleate (57.86%). Both Huskcatacid and Huskcatbase have high porosity (2.726 x 10-3 cm3/g and 4.985 x 10-3 cm3/g) and surface area (7.362 m2/g and 14.493 m2/g), respectively, which offer efficient esterification and easy glycerol separation. The biodiesel obtained was applied on Megatech®-Mark III engine and demonstrated a proportional increased of torque (ɽ) with the B100 biodiesel loading. Rice husk demonstrated a good potential as solid support heterogeneous catalysts and feedstock for value-added products, which also assists to overcome agricultural waste management issues.

The utility of elevational gradients as tools to test either ecological hypotheses and delineate elevation-associated environmental factors that explain the species diversity patterns is critical for moss species conservation. We examined the elevational patterns of species richness and evaluated the effects of spatial and environmental factors on moss species predicted a priori by alternative hypotheses, including mid-domain effect (MDE), habitat complexity, energy, and environment proposed to explain the variation of diversity. Last, we assessed the contribution of elevation toward explaining the heterogeneity among sampling sites. We observed the hump-shaped distribution pattern of species richness along elevational gradient. The MDE and the habitat complexity hypothesis were supported with MDE being the primary driver for richness patterns, whereas little support was found for the energy, and the environment. Moss species richness pattern in the mountain is driven by ecological and evolutionary effects, whereas evolutionary factors predominately shape the large heterogeneity through dispersal, extinction and speciation processes.

With the available solid-liquid equilibrium (SLE) data of six aromatic carboxylic acids (aromatic dicarboxylic acid isomers (terephthalic acid (TPA), isophthalic acid (IPA), phthalic acid (PA)) and methyl benzoic acid isomers (m-toluic acid (m-TA), o-toluic acid (o-TA), p-TA)) in HOAc + H2O solvent mixtures, the relationship between the molecular structure of above aromatic carboxylic acids and the solubility of them in HOAc + H2O solvent mixtures is discussed. Meanwhile, three new groups p-ArCOOH, m-ArCOOH and o-ArCOOH in UNIFAC (Dortmund) model were firstly defined to distinguish the influence of the positions of ArCOOH on thermodynamic properties of aromatic carboxylic acid isomers, which indicate the ArCOOH located in para, meta and ortho positions of the ArCOOH or ArCH3 groups respectively. Then the interaction parameters of the ArCOOH, p-ArCOOH, m-ArCOOH and o-ArCOOH with other involved groups in the solvent systems are firstly obtained by regressing these available SLE data.

Objectives: The current study was carried out to explore the knowledge, attitude, and practices towards Brucellosis in the people of Khyber Pukhtun Khwa Province, Pakistan. Study design: Cross-sectional study Material and methods: Total of 1600 participants belong to different professions, education level, locality and nature of contact with animals were selected by random sample method. The samples were selected from the Khyber Pakhtun Khwa province of Pakistan. Results: The findings of this study documented poor knowledge regarding brucellosis in the selected participants of current study. Although human and animal health professionals had sufficient knowledge about brucellosis, however no serious trends to control brucellosis were noticed even in health professionals. The unhygienic approach was observed in farmers regarding the handling animal and their products. Self medication approach was also documented in many participants which create antibiotic resistance. Conclusions: Based on the findings we noticed a lack of information regarding zoonotic diseases, health facilities and a weak bond between health and non-health professionals in KPK. Proper education and awareness is highly recommended on zoonotic diseases. Keywords: Zoonotic diseases, Brucellosis, Knowledge, Practices, Attitude

The study of mutations that impact fertility has a catch-22. Fertility mutants are often lost since they cannot simply be propagated and maintained. This has hindered progress in understanding the genetics of fertility. In mice, several molecules are found to be required for the interactions between the sperm and egg, with JUNO and IZUMO1 being the only known receptor pair on the egg and sperm surface, respectively. In C. elegans, a total of 12 proteins on the sperm or oocyte have been identified to mediate their interactions. Majority of these genes were identified through mutants isolated from genetic screens. In this review, we summarize the several key screening strategies that led to the identification of fertility mutants in C. elegans and provide a perspective about future research using genetic approaches. Recently, advancements in new technologies such as high-throughput sequencing and Crispr-based genome editing tools have accelerated the molecular, cell biological, and mechanistic analysis of fertility genes. We review how these valuable tools advance our understanding of the molecular underpinnings of C. elegans fertilization and complement fertility research in humans and other species.

This paper presents a low cost, flexible and scalable Smart Home Automation System based on Arduino Technology and Wi-Fi connection, in addition, to apply specific techniques for the reduction of power consumption and load management. The system will be accessible anywhere, anytime for controlling and monitoring. This study relies on Arduino Technology and Node-MCU boards, the electrical appliances are connected to a cloud database that communicates with the user by an android application connected to the internet. A prototype for a specific house has been built, the proposed system is able to control all home electrical units and appliances like lighting, sockets, HVAC units, fire, gas and intruder siren systems, in addition, to monitor the real-time power consumption, the house PV system generation and the current room's temperature and humidity. Furthermore, the system is able to reduce power consumption using predefined algorithms.

Background: Patent ductus arteriosus is an important cause of morbidity and mortality especially in very low birth weight infants.The aim of the present study was to evaluate outcomes of bedside surgical ligation of patent ductus arteriosus via limited upper ministernotomy as an alternative approach to thoracotomy. Material and Method: A total of 23 low birth weight premature infants who underwent bedside ligation of PDA in the neonatal intensive care unit January 2017 to April 2020, were enrolled. The patients were divided into two groups: those with thoracotomy(n=13) and those with limited upper ministernotomy(n=10).These patients were evaluated retrospectively in terms of clinical and preoperative,intraoperative,postoperative parameters between the groups. Results: Mean birth weight was 1059±275 grams in the thoracotomy group and 1035±285 grams in the ministernotomy group. There was no statistically significant difference in the age at surgery,weight at surgery,preoperative MV support,inotropic score onset of surgery and total procedure time between the groups.There was a statistically significant difference in the hospital length of stay,postoperative MV time and complications in the intensive care unit in favor of the ministernotomy group(p=0.04,p=0.03,p=0.034 respectively).The study showed no statistically significant difference in the mortality rate between the two groups (2 patients in the thoracotomy group and 1 patient in the ministernotomy group). Conclusion:The limited upper ministernotomy is anatomically and technically feasible alternative to classical left posterolateral thoracotomy for bedside surgical PDA ligation.

Objective: To evaluate the effect of transferring a poor quality embryo (PQE) with a good quality embryo (GQE) on the outcomes in poor prognosis patients. Design: Retrospective cohort study. Setting: University-affiliated hospital. Population: A total of 5,037 FBT cycles between January 2012 and May 2019. Methods: Single FBT with GQE were defined as group G and double FBT with GQE plus PQE were defined as group GP. Propensity score matching was applied to control for potential confounders. Multivariate generalized estimating equations (GEE) models were used to identify the association between the effect of an additional PQE and outcomes. Main Outcome Measures: Live births and multiple pregnancies. Results: Group GP resulted in a significantly higher live birth rate (LBR) than group G in women aged 35 and over and in women who received over 3 cycles of embryo transfer (ET) (48.1% vs 27.2%, OR:2.56, 95% CI: 1.3-5.03 and 46.6% vs 35.4%, OR:1.6, 95% CI: 1.09-2.35), while LBR were statistically similar between two groups in women under 35 and in women who received less than 3 cycles of ET (48.7% vs 43.9%, OR:1.22, 95% CI: 0.93-1.59 and 48.3% vs 41.4%, OR:1.33, 95% CI: 0.96-1.85). Notably, group GP were found a consistent significantly higher multiple pregnancy rate than group G. Conclusions: The transfer of an additional PQE with a GQE increases live births in poor prognosis patients. Funding：None. Keywords: poor quality embryo, good quality embryo, LBR, poor prognosis patients

The main causes of death in hemodialysis patients (HD) are cardiovascular diseases (CVD) and infections both of which are linked to impaired immune function. In patients with end stage renal disease, immunodeficiency and immune activation co-exist. Changes in the immune system are complex, but to some extent result from malnutrition or insufficiency in essential vitamins or trace elements. Based on the link between high mortality, immune system dysregulation, vitamins and trace elements insufficiency, it emphasizes the potential role of nutritional counseling and supplementation.

Objective: The impact of thyroid hormones within normal range on muscle mass remains unknown. We examined the association between new onset of low muscle mass (LMM) and thyroid hormones among euthyroid men and women with three different definitions of LMM in prospective cohort study. Methods: We performed a cohort study of 198,069 Korean adults (mean age of 39.2 years), free of LMM at baseline, who participated in a repeated screening examination and were followed-up annually or biennially for up to 6.3 years. Thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxin (FT4) levels were measured by an electrochemiluminescent immunoassay. Muscle mass was assessed using a bioelectrical impedance analyzer. LMM was defined as the appendicular skeletal muscle mass (ASM) by body weight (ASM/weight, LMM-W), height squared (ASM/height2, LMM-H) and BMI (ASM/BMI, LMM-B) of one standard deviation below the sex-specific mean for young reference group. Results: During a median follow-up of 3.1 years (interquartile range, 2.0-4.1 years), new-onset LMM-W, LMM-H, and LMM-B occurred in 17,856 (incident rate, 27.8 per 1,000 person-years), 8,307 (incident rate, 13.4 per 1,000 person-years), and 13,990 participants (incident rate, 24.5 per 1,000 person-years) in each. In euthyroid men, FT4 was inversely and FT3 positively associated with incident LMM-W in a dose-response manner. TSH and FT4 had inverse dose-response relationship with incident LMM-B. Incident LMM-H of euthyroid men has no apparent associations with any thyroid hormones. Euthyroid women had no dose-response relationship between thyroid hormones and any definition of LMM. Conclusions: Among euthyroid men, FT4 had inverse dose-response association with new onset of LMM defined with weight (LMM-W) and BMI (LMM-B). Height squared LMM (LMM-H) had no apparent relationship with any thyroid hormones. Euthyroid women had no dose-responsive association between thyroid hormones and incident LMM. Key words: appendicular skeletal muscle mass, low muscle mass, thyroid hormones, Cohort study

Objective: To evaluate whether a particular group of women with intrahepatic cholestasis of pregnancy would benefit from treatment with ursodeoxycholic acid. Design: Secondary analysis of the PITCHES trial (ISRCTN91918806). Setting: United Kingdom. Population or Sample: Women with intrahepatic cholestasis of pregnancy. Methods: Subgroup analyses were performed to determine whether baseline bile acid concentrations or baseline itch scores moderated a woman’s response to treatment with ursodeoxycholic acid. Main Outcome Measures: Bile acid concentration and itch score. Results: In women with baseline bile acid concentrations less than 40 μmol/L, treatment with UDCA resulted in increased post-randomisation bile acid concentrations (geometric mean ratio 1.19, 95% CI 1.99 to 1.41, p = 0.048). A test of interaction showed no significance (p = 0.647). A small, clinically insignificant difference was seen in itch response in women with a high baseline itch score (–6.0 mm, 95% CI –11.80 to –0.21, p = 0.042), with a test of interaction not showing significance (p = 0.640). Further subgroup analyses showed no significance. Across all women there was a weak relationship between bile acid concentrations and itch severity. Conclusions: There was no subgroup of women with intrahepatic cholestasis of pregnancy in whom a beneficial effect of treatment with ursodeoxycholic acid on bile acid concentration or itch score could be identified. This confirms that its routine use in women with this condition for improvement of bile acid concentration or itch score should be reconsidered. Funding: NIHR Efficacy and Mechanism Evaluation Programme 12/164/16. Keywords: Cholestasis, Pregnancy, Ursodeoxycholic acid, Perinatal, Stillbirth.

Background: Structural remodeling in chronic systolic heart failure (HF) is associated with neurohormonal and hemodynamic perturbations among HF patients presenting with cardiogenic shock (CS) and HF. Objectives: To test the hypothesis was that atrial remodeling marked by an increased right atrial volume index (RAVI) to left atrial volume index (LAVI) ratio is associated with adverse clinical outcomes in CS. Methods: Patients included were admitted to the intensive care unit with evidence of congestion (pulmonary capillary wedge pressure >15) and cardiogenic shock (cardiac index <2.2, systolic blood pressure <90 mmHg, and clinical evidence supporting CS) and had an admission echocardiogram. LAVI and RAVI were measured using the biplane disc summation method by two independent observers. Cox proportional hazards regression analysis was used to assess the association of RAVI-LAVI with the combined outcome of death or left ventricular assist device (LVAD). Results: Among 113 patients (mean age 59 ± 14.9 years, 29.2% female), median RAVI/LAVI was 0.84. During a median follow-up of 12 months, 43 patients died, and 65 patients had the combined outcomes of death or LVAD.Patients with RAVI/LAVI ratio above the median had a greater incidence of death or LVAD (Log-rank p=<0.001), and increasing RAVI/LAVI was significantly associated with the outcomes of death or LVAD (HR 1.71 95% CI 1.11-2.64, chi square 5.91, p=0.010) even after adjustment for patient characteristics and hemodynamic variables. Conclusion: RAVI/LAVI is an easily assessed novel echocardiographic parameter with strong associations with the survival or the need for mechanical circulatory support in patients with CS.

Postpartum unscarred uterine ruptures are exceedingly rare. A 29-year-old multipara with a retained placenta presented hypovolemic shock. An emergency laparotomy revealed that her uterus was ruptured where the placenta adhered to. Pathological examination confirmed the placental accreta that could be a risk factor for postpartum unscarred uterine rupture.

An 84 year old male presented to the Emergency Department with an acutely painful inguinoscrotal swelling. CT revealed complete herniation of the bladder and prostate and urinary retention. He was catheterised and discharged home. He re-presented with upper tract obstruction and urosepsis. Nephrostomies were inserted and emergency hernia repair performed.

An impressive percentage of biomedical knowledge and advances were achieved through animal research and cell culture investigations. For drug testing and disease researches, both animal models and preclinical trials with cell cultures are extremely important, but they present some limitations, such as ethical concern and lack of representatively of human tissues and organs. Most cells are currently cultured using two-dimensional (2D) methods, but new and improved methods that implement three-dimensional (3D) cell culture techniques suggest convincing evidence that much more advanced experiments can be performed with more complex information. The environment and cell types in 3D culture can be manipulated to mimic tissue in vivo and provide more accurate data on cell-to-cell interactions; the cultivation techniques are based on a scaffold, which can be based on hydrogel or polymeric material, in addition there are techniques without using scaffold, such as suspended microplates, magnetic levitation and microplates for spheroids with ultra-low fixation coating. Even though 3D culturing is clearly incapable of replacing other current research types, they might continue to replace some unnecessary animal experimentation, as well as improve monolayer cultures. It is not even recommended or expected that 3D models substitute all other research types, but in regard to animal testing, they come in hand for the 3 Rs: Reduction, Refinement, Replacement. In this aspect, 3D culture emerges as valuable alternatives to the investigation of functional, biochemical and molecular aspects of human pathologies.

The practice of hormone therapy (HT) witnessed a widespread application in the 1980s to control menopausal symptoms. In the 1990s, the speculation about HT’s cardiovascular protective effect and bone loss prevention potential in the postmenopausal period increased its use. The lack of evidence about the risks and benefits of HT has led the Women’s Health Initiative (WHI) group to conduct a series of randomized clinical trials aiming to answer some of these questions. The WHI Hormone Therapy trials included 27,347 women who were followed during the treatment. The subjects were randomized to take oral estrogen plus progestin or placebo, and women with prior hysterectomy were randomized to receive oral estrogen alone or placebo 1The outcomes of this randomized clinical trial published by the WHI abruptly changed the prescription of HT. The study aimed to evaluate the risks and benefits of HT; however, it was interrupted precociously due to the adverse effects. The study showed an increased relative risk of breast cancer (BC) development after an average use of combined HT for five years. The BC risk rate was 1.26 (CI 1.00–1.59) after an average of 5.2 years, and the risk raised to 2.3 (CI 1.12–3.94) when the use was extended to ten years. Thus, the WHI study indicated that the risks exceeded the benefits of combined HT usage after an average time of 5.2 years, despite the all-cause mortality being not affected in the study. One limitation of the study was the evaluation of only one combined hormonal therapy regimen, i.e., the conjugated equine estrogen 0.625 mg/d associated with 2.5 mg/d medroxyprogesterone acetate1. Nevertheless, despite this limitation of the study and the lack of specific mortality information, there was an unquestionable change-over after the WIH study. The 13 years of cumulative follow-up just corroborate these findings1.Another WHI publication assessed the use of estrogen alone in postmenopausal women who had undergone a hysterectomy. The primary outcome found was also the incidence of invasive BC; however, there was a decrease in the hazard ratio (HR) value to 0.77 (CI 0.59–1.01), suggesting a reduction in the risk of BC. Unfortunately, the study had to be interrupted due to an increased risk of cerebral vascular disease. The reduction in BC risk had no statistical significance according to this data. However, further investigation is warranted.1These publications encouraged discussions regarding the risks and benefits of the use of HT, a topic that has been widely studied since then. It raised new questions, such as which type and duration of therapy and age of onset were related to the increased risk of BC. A recent meta-analysis answered some of these questions. The use of combined HT for five years in postmenopausal women, regardless of the age of onset, showed an increase in the risk of BC. Further, while evaluating the different types of therapies, no statistically significant differences between the estrogen therapies were observed. All HTs, except those given via vaginal route, increased the relative risk of BC.2Remarkable data were presented at the ”San Antonio Breast Cancer Symposium 2019” on the WHI Hormone Therapy trials. This 20-year follow-up of combined therapy group(>=5years) in postmenopausal women confirmed the increased BC incidence and associated mortality (incidence BC HR: 1.29; CI 1.14 - 1.47; p< 0.001 and mortality after BC HR:1.29; CI 1.02-1.63, p 0.03). Mortality related to BC development in HT users was not assessed in previous literature, probably, due to shorter follow-ups. The second group of hysterectomized women using estrogen alone showed new data that resulted in a reduced incidence (HR: 0.77; CI 0.65-0.92; p=0.005) and mortality for BC (HR: 0.56; CI 0.34-0.92; p=0.005). Further studies are still needed to clarify this evidence, although, these impactful data on mortality come from a randomized clinical trial. 3The decreased risk of BC using estrogen alone in postmenopausal women might be due to an increase in estrogen-induced apoptosis in the breast cells 4. The key point for estrogen-induced apoptosis is the selection of cell populations that can survive prolonged estrogen deprivation, comparable to long-standing menopause, and become sensitive to this apoptotic mechanism. These cells survive estrogen deprivation due to the activation of different types of receptors, and estradiol can bind to the receptors and trigger apoptosis 4. The WHI hormone therapy trial selected women aged 50 – 79 years at baseline, many of whom probably have been in menopause for more than five years1. Therefore, we can hypothesize that this trial may have selected patients with long-standing menopause (with cells sensitive to this apoptotic mechanism) who were being benefited from the estrogen-induced apoptotic death of breast cells, thereby reducing the risk of BC.The complexity of estrogen and BC is not completely understood. Another important randomized placebo-controlled trial, the International Breast Cancer Intervention Study I ( IBIS I), showed an extended protection period of tamoxifen for BC risk in women deemed to be at an increased risk of developing BC with a hazard ratio of 0.69 (CI 0.53–0.91). The five-year use of 20 mg tamoxifen, a selective estrogen receptor modulator with antiestrogenic effects in the breast, reduced the incidence of BC in high-risk women5. So, there are trials that show that estrogen can protect from BC in some cases; however, medication with antiestrogenic effect has also demonstrated efficacy in BC prevention 3,5.An interesting fact related to the effect of estrogen on breast cancer is the pathophysiology of HT in transgenders. Studies have demonstrated that testosterone therapy decreases the risk of BC in female to male transgenders, regardless of mastectomy. This probably is due to a decrease in estradiol-induced tissue proliferation resulting from a decrease in the expression of estrogen receptors and increase in the induction of epithelial breast cells apoptosis. All these alterations might prevent the effects of estradiol on inducing BC development6. It can be hypothesized that the basis for BC prevention lies on the estrogen receptors. Consequently, the decrease in estrogen receptors in breast induced by testosterone may lead to a reduction in BC cases in transgenders. The role of progesterone in this topic is still unknown. Despite these encouraging findings, further studies are required to assess the real effect of the therapy on this population and to understand the pathophysiology.The rational use of HT is strongly based on evidence from randomized clinical studies related to the topic. Therefore, the gynecologist should provide information to their patients individually about benefits and adverse events, especially the risk of BC. It is important to note that the well-established time for safely using HT is five years. There is no evidence for the use of estrogen alone just for the prevention of BC in healthy postmenopausal hysterectomy patients. Therefore, the gynecologists must be updated regarding the use of HT unless these topics are fully understood. There is no doubt that the risk of BC should be individually discussed with the patients before initiation of HT, considering other individual risk factors for BC and other pathologies.Acknowledgments: We thank all the doctors and students that were involved inthis commentary.Disclosure of interest: The authors have no financial conflicts of interest to disclose. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Contribution to authorship:Gustavo dos Santos Raupp - Substantial contributions to conception and design*.Alessandra Borba Anton de Souza - Substantial contributions to conception and design; critical review of the intellectual content; final approval of the version to be published*.Martina Lichtenfels - Critical review of the intellectual contentAntonio Luiz Frasson - Critical review of the intellectual content; final approval of theversion to be published.* both authors contributed equally to the paperReferences1. About WHI - WHI Findings [Internet]. Whi.org. 2020 [cited 9 July 2020]. Available from: https://www.whi.org/about/SitePages/WHI%20Findings.aspx2. Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence. The Lancet. 2019;394(10204):1159-1168.3. Chlebowski RT, et al. Menoupasal Hormone Therapy and Breast Cancer: Long Term Findings from the Women’s Health Initiative Randomized Clinical Trials. San Antonio Breast Cancer Symposium 20194. Vaz-Luis I, Partridge A. Exogenous reproductive hormone use in breast cancer survivors and previvors. Nature Reviews Clinical Oncology. 2018;15(4):249-261.5. Cuzick J, Sestak I, Cawthorn S, Hamed H, Holli K, Howell A et al. Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial. The Lancet Oncology. 2015;16(1):67-75.6. Patel H, Arruarana V, Yao L, Cui X, Ray E. Effects of hormones and hormone therapy on breast tissue in transgender patients: a concise review. Endocrine. 2020;68(1):6-15.

Parte 11. ¿Que son few shot learners? ¿One shot learners?En problemas de categorización en los modelos de aprendizaje, los “one-shot learners” tienen como objetivo aprender información sobre categorías de objetos de una, o solo unas pocas, muestras/imágenes durante el entrenamiento. En el paper usan el término “meta-learning” para demostrar la estructura del bucle interno / bucle externo del método general, y el término “in context-learning” para referirse al bucle interno del “meta-learning”. Por lo que los autores describen a “zero-shot”, “one-shot”, o “few-shot” dependiendo de cuántas demostraciones se brinden en el momento de la inferencia.2. Comente el modelo GPT-3 que utilizan, ¿Cómo es?El modelo de Pre-entrenamiento Generativo (GPT-3) utiliza modelado de lenguaje de probabilidad condicional con una arquitectura de red neuronal transformadora que se basa en mecanismos de auto atención (inspirados en mecanismos de atención de tareas de procesamiento de imágenes) en lugar de recurrencia o convolución. Según los autores este es un modelo de lenguaje autorregresivo de 175 mil millones de parámetros. 3. Comente alguna de las aplicaciones para la que lo utilizaronUtilizaron el modelo GPT-3 para evaluarlo en más de dos docenas de conjuntos de datos NLP, así como en varias tareas diseñadas para probar la adaptación rápida a tareas que probablemente no estén contenidas directamente en el conjunto de entrenamiento.Compararon el modelo GPT-3 con configuraciones de “one-shot” y “few-shot” con resultados de F1 en conjuntos de datos: CoQA DROP QuACSQuADv2 RACE-h RACE-m, LAMBADA y otros con datos limpios y sucios.Probaron el modelo en varias medidas GPT-3 Small (con 125M de parámetros), GPT-3 Medium (con 350M de parámetros), GPT-3 Large (con 760M de parámetros), así hasta llegar al “GPT-3” (con 175.0B de parámetros).Parte 2 La Siguiente Gran Revolución: NLPEl aprendizaje profundo o “Deep learning” es un conjunto de algoritmos de aprendizaje automático que intenta modelar abstracciones de alto nivel en datos usando arquitecturas computacionales que admiten transformaciones no lineales múltiples e iterativas de datos expresados en forma matricial o tensorial. A lo largo de 10 años se ha visto un crecimiento sustancial en el campo de la Inteligencia Artificial, aunque desde muy temprano se acuñaban los términos de red neuronal artificial. Todo esto ha desarrollado un revolución tecnológica que el día de hoy nos ha cambiado la vida. En el Deep learning viéndolo desde una perspectiva general y en función de las tareas que queramos resolver y los tipos de datos que analicemos nos moveremos en diferentes campos como la robótica, visión artificial “computer visión” o el procesamiento del lenguaje natural “Natural Language Processing”. En setiembre de 2012, AlexNet compitió en el Desafío de reconocimiento visual a gran escala ImageNet. La red logró un error de top 5 del 15.3%, más de 10.8 puntos porcentuales menos que el del segundo lugar. Lo que hizo que se valorará el uso de redes neuronales para las tareas basadas en imágenes. En 2014, los modelos generativos obtuvieron un gran impacto para la evolución generativa artificial.GPT-3 tiene 175 mil millones de parámetros. Un parámetro es un cálculo en una red neuronal que aplica una ponderación mayor o menor a algún aspecto de los datos, para darle mayor o menor importancia a ese aspecto en el cálculo general de los datos. Son estos pesos los que dan forma a los datos y le dan a la red neuronal una perspectiva aprendida sobre los datos, es decir este modelo se usa para predecir la siguiente palabra a partir de palabras anteriores. Lo sorprendente de GPT-3 es que es capaz de generar texto muy realista sobre poesía, diálogo, juegos de palabras, parodias literarias y narración de cuentos.Es impresionante cómo se publican cada vez más artículos y experimentos sobre IA, como el ChatBot Blender de Facebook, un chatbot que aprende a combinar varias habilidades de conversación, incluidas: la capacidad de asumir una personalidad, discutir casi cualquier tema y mostrar empatía. Como diría el locutor: ¡Es brutal!.Es impresionante lo que se puede lograr con el procesamiento del lenguaje natural, desde consolas con programación inteligente hasta traductores de código. En Junio de 2020, Facebook AI Research anunció el lanzamiento de TransCoder, un sistema que utiliza el aprendizaje profundo sin supervisión para convertir el código de un lenguaje de programación a otro. TransCoder recibió un entrenamiento en más de 2.8 millones de proyectos de código abierto y supera los sistemas de traducción de código existentes que utilizan métodos basados en reglas. Lo que es un poco preocupante son las noticias como las de Microsoft que despidió a sus colaboradores para reemplazarlos por máquinas entrenadas. Lo que parece curioso también es cómo hacen los seres humanos para aprender y saber que con tener un panorama visual poco detallado y algunos inputs puedan concluir con resultados coherentes. Por esto es importante profundizar en estos temas, e aprender más sobre la teoría. Parte 4Para las siguientes secciones es importante saber la máquina sobre la que se corrieron los problemas: