A document by Dr. Gowsic K. Click on the document to view its contents.

A document by Dr. Gowsic K. Click on the document to view its contents.

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: tlaguncosta@gmail.comText 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.

In this paper, a class of second-order Hamiltonian systems is studied. Under the assumption of superquadratic and subquadratic for the nonlinear term, the existence of six periodic solutions and nine periodic solutions are obtained by using the variational method and space decomposition. Finally, two examples are given to verify the feasibility of the new criteria.

Recently, solutions of partial differential equations (PDEs) are under investigation as an effective tool for geometric modeling and shape generation to develop smooth-edge structures. Three-dimensional shape modeling needs the completeness of geometric queries in a design and optimization processes. In this paper, a novel modeling technique using solutions of six-order partial differential equations (PDEs) has been developed to model a 3D shape with a set of boundary conditions. The advantages of using solutions of PDEs for geometry generation over other techniques are PDEs-based solid modeling needs smaller number of parameters and can automatically guarantee some intrinsic smoothness which is not easily achieved in spline-based blending and other conventional techniques. Based on the developed solutions of PDEs, the optimal cell sizes of Body-Centered Cubic (BCC) and Face-Centered Cubic (FCC) lattice structures have been generated which shows smooth structures compared to other conventional techniques. The developed lattice structures have been optimized using fmincon and genetic algorithms. The optimized BCC unit cell width and strut radius are determined to be 0.01 m and 0.0013 m respectively. For the FCC lattice structure, a 0.001 m strut radius and 0.0099 m unit cell width were determined. Finally, these optimal dimensions were used to generate the solid structures and the stresses were evaluated using analytical and ANSYS simulations. The stresses evaluation results indicate that when the aspect ratio becomes 1 the uniform values were obtained.

This paper analyzes the following initial and boundary value problem of fourth-order hyperbolic equations by means of the potential well method utt+Δ2u-▽u-ωΔut+α(t)|ut|m-2ut=|u|p-2u, x∈Ω,t≧0, u(x,0)=u0(x), ut(x,0)=u1(x), x∈Ω u(x,t)=Δu(x,t)=0, x∈∂Ω, t≧0. Firstly, we build up ordinary differential inequalities to show the blow-up of the solution and the upper bounds for lifespan are also given in the case of initial data at different energy level. Subsequently, we discuss some results about lower bounds for lifespan with different critical case. For supercritical case, we invent the techniques which apply the interpolation inequality and energy inequalities to estabilish an inverse Hölder inequality with the correction constant. At last, we study the asymptotic behavior of global solutions in a potential well and obtain some convergence rates by using multiplier method.

A series of di- and polymetal complexes involving closed-shell, heavy main-group atoms and ions shows a selection of special physical properties. These involve short metal-metal contacts, low entropies of formation and, most interestingly, strong Raman bands at low wavenumbers. These results together with the constitution of the coordination compounds, where the majority of electrons are assembled on the highly polarizable metal atoms and ions, experimental results have been interpreted in terms of direct, partial covalent metal-metal bonding. Previous theoretical studies have challenged this view and instead attributed the obvious attractive forces involved to secondary-type of interactions, such as dispersion. The current study utilizes a multitude of theoretical tools, such as NBO, NEDA, NCI, ELF and AIM to characterize the interactions in models comprising closed-shell dimers, as well as experimentally studied ring and cage systems, constituting the main reason for the hypotheses on metal-metal interactions. The results show that all experimental results can be attributed to the covalent interactions between the electron-rich, metal centres and the bridging anions in ring and cage coordination compounds of high symmetry, where the experimentally observed effects can be traced to the combination of covalent interactions between the metal centres and the anions along the edges of the ring and cage systems in combination with the cooperative effects generated by the high symmetry of these ring and cage systems.

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.

Introduction: Mavacamten (MAVA), Blebbistatin (BLEB), and Omecamtiv mecarbil (OM) are promising drugs directly targeting sarcomere dynamics, with demonstrated efficacy against hypertrophic cardiomyopathy (HCM) in clinical trials. However, the molecular mechanism affecting cardiac contractility regulation, and the diseased cell mechano-energetics are not fully understood yet. Methods: We present a new metabolic-sensitive computational model of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) electromechanics to investigate the pathology of R403Q HCM mutation and the effect of MAVA, BLEB, and OM on the cell mechano-energetics. Results: We offer a mechano-energetic HCM calibration of the model, capturing the prolonged contractile relaxation due to R403Q mutation (~33%), without assuming any further modifications such as an additional Ca2+ flux to the thin filaments. The HCM model variant correctly predicts the negligible alteration in ATPase activity in R403Q HCM condition compared to normal hiPSC-CMs. The simulated inotropic effects of MAVA, OM, and BLEB, along with the ATPase activities in the control and HCM model variant agree with in vitro results from different labs. The proposed model recapitulates the tension-Ca2+ relationship and action potential duration change due to 1uM OM and 5uM BLEB, consistently with in vitro data. Finally, our model replicates the experimental dose-dependent effect of OM and BLEB on the normalized isometric tension. Conclusion: This work is a step toward deep-phenotyping the mutation-specific HCM pathophysiology, manifesting as altered interfilament kinetics. Accordingly, the modeling efforts lend original insights into the MAVA, BLEB, and OM contributions to a new interfilament balance resulting in a cardioprotective effect.

Acute respiratory distress syndrome (ARDS) is an acute respiratory disease which is characterized by non-cardiogenic pulmonary oedema. It has a high mortality rate and lacks effective pharmacotherapy. As the outbreak of COVID worldwide, the mortality of ARDS has increased correspondingly, which makes it urgent to find effective targets and strategies for the treatment of ARDS. Recent clinical trials of Janus kinase (JAK) inhibitors in treating COVID induced ARDS have shown a positive outcome, which makes the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway a potential therapeutic target for treating ARDS. Here, we review the complex cause of ARDS, the molecular pathway of JAK/STAT involved in ARDS pathology, and the progress that has been made in strategies of targeting JAK/STAT to treat ARDS Specially, JAK/STAT signaling directly participates in the progression of ARDS or collude with other pathways to aggravate ARDS. We summarize JAK and STAT inhibitors with ARDS treatment benefits, including inhibitors in clinical trials and pre-clinical studies and natural products, and discuss the side effects of the current JAK inhibitors to reveal the future trends in designing of JAK inhibitors, which will help to develop effective treatment strategies for ARDS in the future.

Introduction: the role of vaccines in preventing diseases is well-established. However, the evolving techniques and types of vaccine necessitate the search for its safety more than ever. While cases of takotsubo cardiomyopathy and COVID-19 vaccine have been described, a comprehensive study to investigate the role of vaccination with cardiomyopathy and heart failure is lacking. The aim of this study is to investigate the link between the current vaccines and heart failure. Method: we utilized vaccine adverse event reporting system (VAERS) to search for cardiomyopathy, cardiac failure or ventricular dysfunction. Disproportionality signal analysis was conducted by measuring reporting odds ratio (ROR) with 95% confidence interval (CI). Results: VAERS reported over 1,300,000 adverse events between 1990-2021. Heart failure was reported over 2000 times in association with multiple vaccines. 56% of vaccine-related heart failure reported in males; 88% were serious; 19% mortality rate. The majority of reported heart failure was related to COVID-19 vaccines with ROR of 21.6 (CI: 18.3 to 25.4, P<0.0001). Smallpox was also significant with ROR 7.2 (CI 5.5-9.6, P<0.0001) On the other hand, heart failure was minimally described to be associated with other vaccines (influenza, zoster, tetanus, human papillomavirus (PPV)). Conclusions: Our study showed for the first time that vaccines maybe associated with heart failure. In particular, we show that covid-19 and smallpox vaccines are associated with increased risk of heart failure. Vaccines against Influenza, zoster, tetanus and (PPV) are associated with reduced heart failure. These data warrant longitudinal studies to delineate the association between heart failure and vaccines.

Background: Although constipation is a common syndrome and a worldwide health problem, the mechanism of underlying remission remains poorly understood. Patients with constipation are becoming younger with a 29.6% overall prevalence in the children, which has captured great attention of scientists because of its epigenetic rejuvenation and recurrent episodes. Despite the usage of rhubarb torelieveconstipation, novel targets and genes involved in target-relevant pathways with remarkable functionalities should still be sought after. Materials and methods: We established a reliable constipation model in C57B/6N male mice using intragastric administration diphenoxylate and the eligible subjects received rhubarb extraction at a dose of 600mg/25g for three days to ameliorate constipation. Resultant constipation was morphological and genetically compared to the different group’s specimen. Results: The constipation mice exhibited thicker muscle layers, improved content of cytokines, including IL-17 and IL-23, and lower content of IL-22. Afterward, the bacterial abundance and diversity varied tremendously. Additionally, SCFA and MLCFA were significantly influenced by the constipation condition accompanied by the enhanced expressions of SCFA receptors, GPR41 and GPR43. Nevertheless, the alterations were reversed to the normal level when constipation mice were treated with rhubarb. Conclusion: This thesis has provided a deeper insight into the confirmation that rhubarb promoted the flexibility of collagen fiber, reduced pro-inflammatory cytokines and enhanced anti-inflammatory cytokines to relieve inflammation, improved intestinal barrier function and maintained intestinal microflora balance, with potential effects on intestinal microenvironment such as affecting the metabolism of fatty acids and polyamines.

Background and Purpose: Irritable bowel syndrome (IBS) is usually associated with chronic gastrointestinal disorders. Its most common subtype is accompanied with diarrhea (IBS-D). The enteric nervous system (ENS) modulates major gastrointestinal motility and functions whose aberration may induce IBS-D. The enteric neurons are susceptible to long-term neurotransmitter level alterations. The patchouli alcohol (PA), extracted from Pogostemonis Herba, has been reported to regulate neurotransmitter release in the ENS, while its effectiveness against IBS-D and the underlying mechanism remain unknown. Experimental Approach: In this study, we established an IBS-D model in rats through chronic restraint stress. We administered the rats with 5, 10, and 20 mg/kg of PA for intestinal and visceral examinations. The longitudinal muscle myenteric plexus (LMMP) neurons were further immunohistochemically stained for quantitative, morphological, and neurotransmitters analyses. Key Results: We found that PA decreased visceral sensitivity, diarrhea symptoms and intestinal transit in the IBS-D rats. Meanwhile, 10 and 20 mg/kg of PA significantly reduced the proportion of excitatory LMMP neurons in the distal colon, decreased the number of acetylcholine (Ach)- and substance P (SP)-positive neurons in the distal colon and restored the levels of Ach and SP in the IBS-D rats. Conclusion and Implications: These findings indicated that PA modulated LMMP excitatory neuron activities, improved intestinal motility and alleviated IBS-induced diarrheal symptoms, suggesting the potential therapeutic efficacy of PA against IBS-D.

Globally, land degradation disproportionally affects women more than men and, to close the gender gap, several landscape restoration projects promote gender inclusiveness. However, empirical evidence based on gender-disaggregated data is a major research gap. Using a gender-inclusive restoration case of Amhara and SNNP (Southern Nations, Nationalities and Peoples) regions in Ethiopia in the last 6-10 years, we collected data from 59 wife-husband paired households and six gender-disaggregated focus groups. The study revealed large gender differences in perceptions of landscape scenic beauty and habitat quality in terms of wildlife, pollinators, beneficial plants, weeds, and pests and diseases as indicators of ecological health. Despite that, the paired husbands and wives live together and share resources, their perceptions and valuation of degradation and restoration were divergent. Men largely attributed degradation to external and natural forces while women considered the lack of appropriate restoration strategies as a precursor for accelerated land degradation. Women noted that in areas that receive heavy rainfall and have sleep slopes, cultivation without management measures exacerbates degradation. Gendered experiences on impacts of degradation were captured: women indicated to be greatly impacted in terms of water scarcity for livestock whilst men were impacted on the water for irrigation. On restoration impacts, women display increased concern and knowledge of regulatory services while men are knowledgeable of provision services. Women attribute a moderate impact of land degradation on habitat quality than men and attribute restoration to the enhancement of biodiversity and pollinators. These results are key in understanding the divergence between men’s and women’s valuation of impacts of degradation and restoration that underpins their involvement in ecosystem restoration and can be a basis for gender equity discourse and policy.

Objective: To determine whether preterm twins who receive antenatal corticosteroid (ACS) are at increased risk for developing neonatal hypoglycemia. Design: A retrospective cohort study Setting: Single university-affiliated tertiary referral center Population: Indicated and spontaneous preterm births (24+0-36+6 weeks) at a single center between 2011-2018. The study population included 3 groups matched for gestational age at delivery and birth weight: 1. Twin neonates who received a course of ACS 1-7 days before birth (n=266); 2. Twins who did not receive ACS at that time interval (n=266); and 3. Singletons receiving ACS 1-7 days before birth (n=266). Methods: The rate of neonatal hypoglycemia was determined. Parametric, non-parametric statistical methods, and regression analysis, were employed. Main outcome measures: Neonatal hypoglycemia (<40 mg/dL) within the first 24-h and 48-h of life. Results: The rate of neonatal hypoglycemia during the first 24-h of life was significantly higher in singletons exposed to ACS compared to twins not exposed to ACS (p=0.019) and in twins exposed to ACS compared to twins not exposed to ACS (p=0.047). The rate of neonatal hypoglycemia was almost identical between twins and singletons exposed to ACS (40.6% vs. 42.1%,p=0.72). Regression analysis revealed that exposure to ACS (p=0.027) and birth weight (p=0.009) were independently associated with neonatal hypoglycemia after adjustment for maternal age, maternal BMI, gravidity, GDM diagnosis, and GA at delivery. The rate of neonatal hypoglycemia between 24-48 hours after birth did not differ significantly among groups (p=0.068). Conclusions: Exposure to ACS, rather than plurality, is associated with short-lived neonatal hypoglycemia

Isothermal and thermomechanical fatigue crack growth tests up to and above the maximum usage temperature for Inconel 718, nominally, 650°C, were executed to characterize the impact of time spent at elevated temperature on the fatigue crack growth rate. Various spectra were tested which showed tensile holds executed at a spectrum’s maximum load or immediately following an increase in load increased the fatigue crack growth rate. Additionally, a series of tests were executed to evaluate the impact of the stress intensity, duration, and temperature of a tensile hold on fatigue crack growth rate. The concept of a thermally affected zone to describe an area ahead of the crack tip weakened by the tensile hold that accelerates crack propagation is presented. As the stress intensity, duration, or temperature of a tensile hold increase, the temperature affected zone increases in size leading to an increase in fatigue crack growth rate for subsequent cycling.

Objective To compare the effect of levonorgestrel-intrauterine system (LNG-IUS) with or without oral megestrol acetate (MA) versus MA alone on fertility preserving treatment in patients with atypical endometrial hyperplasia (AEH). Design Single-center phase II study with open-label, randomized and controlled trial conducted between July 2017 and June 2020. Setting Obstetrics & Gynecology Hospital of Fudan University, Shanghai, China Population A total of 180 patients (18-45 years) with primary AEH were randomly assigned (1:1:1) to MA group (N=60), LNG-IUS group (N=60), or MA+LNG-IUS group (N=60). Methods Patients received MA (160 mg orally daily), LNG-IUS, or MA+LNG-IUS (MA 160 mg orally daily plus LNG-IUS), respectively. Main outcomes and measures The primary endpoint was the complete response (CR) rate at 16 weeks of treatment. The secondary endpoints were the CR rate at 32 weeks of treatment, adverse events, recurrent rate, and pregnancy rate. Results LNG-IUS group yielded a higher 16-week CR rate than MA group (P=0.049; Odds ratio [OR], 2.44; 95% confidence interval [95%CI], 1.00-6.00). However, MA+LNG-IUS group did not yield better 16-week or 32-week CR rates than MA group (P=0.245; P=0.915) or LNG-IUS group (P=0.419; P=0.653). Meanwhile, less side-effects were found in LNG-IUS group compared with the other two groups. No significant difference was seen in recurrence rates and pregnancy rates among all three groups. Conclusions LNG-IUS might be considered as the first-line choice of fertility-sparing treatment in AEH patients with proper size of uterine cavity. LNG-IUS combined with MA might not provide better treatment effect than MA or LNG-IUS alone.

This study aimed to investigate the acclimation responses of crop hydraulic traits to future climate scenarios and quantify the potential hydraulic risks. Potted maize was acclimated to varying [CO 2] levels (400, 700, and 1,000 ppm in 2018; 400 and 700 ppm in 2020), while under water deficit (WS) or soil salinity (SS) treatments. Plant growth and hydraulic traits following the acclimation were comprehensively assessed. WS or SS inhibited growth and showed remarkable impacts on maize hydraulic traits. Especially, the water potential that leads to 50% loss of conductivity (P 50) decreased by 1 MPa. When subjected to elevated [CO 2], the WS and SS plants improved their growth by 7-23%. Meanwhile, elevated [CO 2] significantly increased xylem vulnerability, resulting in smaller hydraulic safety margins. According to the t crit plant desiccation model, the critical desiccation degree (time*VPD) plants can tolerate under drought was 43-64% reduced at elevated [CO 2]. In addition, the sensitivity analysis showed that the P 50 is the most important trait in determining the critical desiccation degree. Our findings demonstrated that while elevated [CO 2] was beneficial to plant productivity under WS or SS, it interfered with the plant hydraulic acclimation, potentially placing them at a higher risk of hydraulic failure and mortality.

Light can be used to regulate protein interactions with a high degree of spatial and temporal precision. Photo-switchable systems therefore allow the development of controllable protein complexes that can influence various cellular and molecular processes. Here we describe a plant virus-based nanoparticle shuttle for the distribution of proteins that can be released when exposed to light. Potato virus X (PVX) is often used as a presentation system for heterologous proteins and epitopes, and has ideal properties for biomedical applications such as good tissue penetration and the ability to form hydrogels that present signaling molecules and promote cell adhesion. We describe three different systems attached to the surface of PVX particles: LOVTRAP, BphP1/QPAS1 and Dronpa145N. We demonstrated the functionality of all three photo-switchable protein complexes in vitro and the successful loading and unloading of PVX particles. The new systems provide the basis for promising applications in the biomedical and biomaterial sciences.

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.

Although natural populations are typically subjected to multiple stressors, most past research has focused on single stressors and two-stressor interactions, with little attention paid to higher-order interactions among three or more stressors. However, higher-order interactions increasingly appear to be widespread. Consequently, we used a recently introduced and improved framework to re-analyze higher-order ecological interactions. We conducted a literature review of the last 100 years (1920-2020) and reanalyzed 151 ecological three-stressor interactions from 45 published papers. We found that 89% (n=134) of the three-stressor combinations resulted in new or different interactions than previously reported. We also found substantial levels of emergent properties—interactions that are only revealed when all three stressors are present. Antagonism was the most prevalent net interaction whereas synergy was the most prevalent emergent interaction. Understanding multiple stressor interactions is crucial for fundamental questions in ecology and also has implications for conservation biology and population management.