Unfavorable Parameters Research Articles

Puberty progression in girls with Turner syndrome after ovarian tissue cryopreservation.

To study the impact of unilateral ovariectomy for ovarian tissue cryopreservation (OTC) on the function of the remaining ovary in girls with Turner syndrome. A prospective cohort study as follow up of OTC in a research setting (The TurnerFertility trial, NCT03381300). University hospital in Nijmegen, the Netherlands. A total of 28 girls with Turner syndrome with follicles in their cryopreserved ovarian cortex tissue, aged 5-19 years. Of the 28 girls, 21 girls had a 45,X/46,XX mosaic karyotype, five had structural aberrations of the X-chromosome, one girl had a 45,X monosomy, and one girl had a 45,X/47,XXX karyotype. Girls were monitored annually after OTC for pubertal development and levels of anti-Müllerian hormone (AMH), Follicle Stimulating Hormone, Luteinizing Hormone, Estradiol, and Inhibin B. Thelarche, menarche and onset of premature ovarian insufficiency. The girls were monitored for a median duration of 3.4 years (maximum 6.6 years). The pubertal development of five prepubertal girls is still unknown, all were under the age of 10 and had low gonadotropins and estradiol levels at the end of the follow-up. Seven of the eight girls around pubertal age (10-12 years) experienced spontaneous thelarche, while one received medication to induce puberty. Eleven of the fourteen girls between the age of 14-17 years experienced spontaneous menarche, three other girls with thelarche still had ongoing puberty at the end of follow-up with normal gonadotropins and AMH levels above the detection limit. Around six to twelve months after OTC, a decline in AMH concentration was observed in 57% of girls (16/28 girls), followed by an increase in AMH concentration in the following years. Six of the total 28 girls started hormone replacement therapy due to symptoms of premature ovarian insufficiency, and all had AMH levels below 0.50 μg/L before OTC. Pubertal development progressed after unilateral ovariectomy for OTC in most girls with Turner syndrome. Hormone replacement therapy was required within a few years for girls with unfavorable parameters before OTC, such as AMH below 0.50 μg/L. Decisions regarding OTC should be personalized, considering the girl's preferences and specific characteristics.

Determining technological parameters for obtaining ta15 titanium alloy blanks with improved mechanical characteristics using the electron-beam 3D printing method

The object of this study is the process of electron beam 3D printing of articles made of TA15 titanium alloy powder. Peculiarities of the structure and properties formation of alloy blanks, obtained by this method have been described. Influence of process parameters (electron beam power and geometric scanning parameters) on the characteristics of the material were considered. Step of displacement of the beam trajectory changed from 0.1 to 0.25 mm with an interval of 0.05 mm. Specific energy of the electron beam varied from 20 to 70 J/mm3 for every trajectory displacement step. The macrostructure was examined visually while the microstructure was studied by optical microscopy. Mechanical properties were determined by uniaxial tension and impact bending tests. It was established that depending on the 3D printing parameters the macrostructure of most samples is dense but with unfavorable parameters non-fusions or shrinkage porosity defects may form. The microstructure of the dendritic type has an α´+β lamellar-acicular morphology, its dispersity and shape of α´–phase areas vary depending on the process parameters. A scanning step of 0.2 mm and a beam energy of 40 J/mm3 allows obtaining a dispersed microstructure in which there are no non-fusions and shrinkage micropores. The value of the Rm is 27 %, and the R0.2 is 24 % higher than that of the alloy obtained by the conventional technology of electron beam melting. The A5 is 3.2 times higher. However, impact toughness of the sample with dendrite unfavorable orientation to the direction of load applying may be lower compared to conventional technology. The results could be used for devising commercial technology of high strength titanium alloys parts produced by 3D printing

THE RELATIONSHIP BETWEEN NEIGHBORHOOD INFRASTRUCTURE AND RISK FACTORS IN PATIENTS WITH MYOCARDIAL INFARCTION

HighlightsThe analysis of associations between the elements of the neighboughood area infrastructure and cardiovascular risk factors was performed in a high-risk population of patients with myocardial infarction. This analysis has practical importance for the comprehensive optimization of local preventive approaches. Aim. To study the association of the neighborhood infrastructure parameters with cardiovascular risk factors in patients with myocardial infarction (MI).Material and Methods. The study included 150 patients with MI. On the basis of their subjective opinion expressed by the Neighborhood Environmental Walkability Scale questionnaire, the infrastructure of the area of residence was analyzed, and its favorable and unfavorable parameters were identified. Cardiovascular risk factors were identified based on the survey and medical records.Results. Among all patients with MI, the risk of arterial hypertension with MI was reduced by the presence of a dividing dirt strip in the vicinity of OR 0.32 (95% CI 0.12; 0.83) and accessible public transport OR 0.32 (95% CI 0.10; 0.95), dyslipidemia – the remote location of the restaurant OR 0.50 (95% CI 0.26; 0.97) and the place of work OR 0.32 (95% CI 0.12; 0.86), smoking – distance from a public transport stop OR 0.20 (95% CI 0.04; 0.94) and proximity to a restaurant OR 0.50 (95% CI 0.26; 0.97), physical inactivity – distance from work OR 0.08 (95% CI 0.01; 0.76), stress – remote location of a clothing store OR 0.45 (95% CI 0.22; 0.93), alcohol consumption – compliance of the living area with the conditions necessary for raising children OR 0.27 (95% CI 0.07; 0.97), insufficient consumption of fresh fruits and vegetables – remote location of a pharmacy OR 0.18 (95% CI 0.03; 0.97), the lack of dividing ground strip OR 0.10 (95% CI 0.01; 0.91) and the presence of garbage in the vicinity of OR 0.08 (95% CI 0.01; 0.53), patient satisfaction with the compliance of the living area with the conditions necessary for the upbringing of children OR 0.10 (95% CI 0.01; 0.70). Inadequate street lighting at night contributed to an increased risk of dyslipidemia, OR 3.05 (95% CI 1.04; 8.92), alcohol consumption – proximity to a clothing store OR 2.23 (95% CI 1.08; 4.57).In citizens with MI, a decrease in the risk of arterial hypertension was associated with the presence of a dividing dirt strip in the vicinity of OSH 0.17 (95% CI 0.06; 0.49) and accessible public transport OSH 0.19 (95% CI 0.05; 0.65); stress – with the absence of alternative routes in the vicinity of OSH 0.27 (95% CI 0.09; 0.79); the risk of insufficient consumption of fresh fruits and vegetables – with the distance of the pharmacy OR 0.18 (95% CI 0.03; 0.96), the absence of a dividing dirt strip OR 0.07 (95% CI 0.01; 0.63) and sidewalks in the vicinity of OR 0.14 (95% CI 0.02; 0.89). In rural patients with MI, the risk of stress decreased with the presence of sidewalks in the vicinity of OR 0.21 (95% CI 0.05; 0.99) and accessible public transport OR 0.15 (95% CI 0.03; 0.85).Conclusion. The identification of unfavorable parameters of the territory of residence in patients with MI should contribute to the formation of the concept of a health-preserving environment necessary for further reduction of cardiovascular risks of MI in the population.

Isatuximab and Cemiplimab in Relapsed or Refractory Extranodal Natural Killer/T-Cell Lymphoma: A Multi-Center, Open-Labeled Phase II Study (CISL2102/ICING study)

Introduction Extranodal NK/T-cell lymphoma (ENKTL), an Epstein-Barr virus (EBV) associated lymphoid malignancy is a rare but aggressive non-Hodgkin lymphoma (NHL). The prognoses of patients with relapsed or refractory (R/R) ENKTL are still poor because there is limited treatment option for R/R ENKTL. The expression of PD-L1 (Programmed Death Ligand-1) is common in ENKTL because EBV could induce the PD-L1 expression. Thus, PD1 and PD-L1 inhibitors have been tried as salvage treatments, but their single-agent activities in previous studies were not satisfactory. CD38 has been considered as another potential therapeutic target in ENKTL because tumor cells of ENKTL could express CD38. CD38 expression was also reported to be related with the resistance to PD1 inhibitors. Thus, we conducted a phase II study with the combination of cemiplimab (PD1 inhibitor) and isatuximab (monoclonal anti-CD38 antibody) in patients with R/R ENKTL. Methods We aimed to analyze the efficacy of isatuximab (anti-CD38 monoclonal antibody) and cemiplimab (anti-PD1 monoclonal antibody) in patients with R/R ENKTL. Patients eligible for this study had relapsed or refractory disease at least one line of treatment. The induction treatment consisted of cemiplimab 250mg (day 1 and 15) and isatuximab 10mg/kg (day 2 and 16) intravenous administration every 4 weeks for 6 cycles. After that, responders received cemiplimab 250mg and isatuximab 10mg/kg once every 3 weeks up to 24 months or until progression, death, or study withdrawal. The primary end point was complete response (CR) rate and secondary end points were objective response rate (ORR) consisting of CR and partial response (PR), progression-free survival (PFS), and safety. The target CR rate was designated as 40% (P1). Considering 20% (P0) of CR rate after conventional salvage therapies and 10% of drop-out rate, 37 patients were planned to be enrolled. Results Between June 2021 and May 2023, we enrolled 37 patients. At enrollment, 29 (78%) patients had stage IV disease and 26 (70%) belonged to the high-risk of prognostic index of NK lymphoma (PINK-E, Table 1). Prior to the participating in the study, 19 (51%) patients had received ≥ 2 lines of systemic therapy. At the time of enrollment, 10 (27%) patients were refractory to their previous treatments whereas the remaining patients had relapsed diseases. After the first day of first cycle, all patients completed at least one cycle of treatment. The response rate was determined by the best response during treatment. As 16 patients achieved CR, the CR rate was 43% (16/37). Thus, the primary end point was met in the study. The ORR was 65% (24/37) consisting of 16 CR and 8 PR. The responders could maintain their treatments up to 32 cycles, and the median PFS of responders was 21.0 months (95% CI: 7.8-34.2 months, Figure 1). The comparison of characteristics between responders and non-responders showed stage at enrollment was significantly associated with response (P = 0.032, Table 1). Thus, eight patients with stage I/II at enrollment responded to the treatment (100%, 8/8) whereas 55% (16/29) patients in stage III/IV responded to the treatment. The risk of PINK-E and other unfavorable parameters were not related with treatment response. Furthermore, the PD-L1 expression showed an association with response (Table 1), thus, 83% of patients (15/18) achieved CR or PR. Most treatment-emergent adverse events were grade 1-2 in severity. Only one patient with CR withdrew from the study due to neuropathic pain that was related with the patient's previous treatments. The hematologic and non-hematologic grade ≥ 3 events were reported in 12 (32%) patients including pneumonia. However, they were manageable, and there was no treatment-related death. Conclusions The combination of isatuximab with cemiplimab showed durable antitumor activity and manageable safety profiles in R/R ENKTL. Especially, patients with PD-L1 expression showed better outcomes than patients with low PD-L1 expression. Further study with a larger study population should be warranted to confirm our findings.

Ceramide d18:1/24:1 as a potential biomarker to differentiate obesity subtypes with unfavorable health outcomes

BackgroundThe criteria for metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) remain controversial. This research aimed to identify a potential biomarker to differentiate the subtypes of obesity.MethodsThe study conducted a lipidomic evaluation of ceramide in the serum of 77 Chinese adults who had undergone hyperinsulinemic-euglycemic clamps. These adults were divided into three groups according to the clinical data: normal weight control group (N = 21), MHO (N = 20), and MUO (N = 36).ResultsThe serum Cer d18:1/24:1 level in the MHO group was lower than that in the MUO group. As the Cer d18:1/24:1 level increased, insulin sensitivity decreased, and the unfavorable parameters increased in parallel. Multivariate logistic regression analysis revealed that serum Cer d18:1/24:1 levels were independently correlated with MUO in obesity. Individuals with higher levels of Cer d18:1/24:1 also had an elevated risk of cardiovascular disease. Most ceramide subtype levels increased in obesity compared to normal-weight individuals, but the levels of serum Cer d18:0/18:0 and Cer d18:1/16:0 decreased in obesity.ConclusionsThe relationships between ceramide subtypes and metabolic profiles might be heterogeneous in populations with different body weights. Cer d18:1/24:1 could be a biomarker that can be used to differentiate MUO from MHO, and to better predict who will develop unfavorable health outcomes among obese individuals.Trial registrationThe First Affiliated Hospital of Nanjing Medical University’s Institutional Review Board authorized this study protocol, and all participants provided written informed consent (2014-SR-003) prior to study entry.

Novel MCDM Methods and Similarity Measures for Extended Fuzzy Parameterized Possibility Fuzzy Soft Information with Their Applications

Complicated uncertainties arising in the multicriteria decision-making (MCDM) problems that show distinct possible satisfaction of the subjects to favorable and equally unfavorable parameters with varying preferences require reliable decision-making under comprehensive mathematical tools. For such complications, this work aims to develop a novel fuzzy parameterized possibility fuzzy bipolar soft set model as a fuzzy parameterized bipolar soft extension of possibility fuzzy sets. The proposed model efficiently depicts the possibility of fuzzy belongingness of alternatives under fuzzy parameterized bipolar parameters (or attributes). The respective operations and properties such as subset, complement, union, and intersection are presented along with their numerical illustrations. Two logical operations namely “AND” and “OR” operations followed by two corresponding MCDM algorithms have been developed and implemented. Furthermore, similarity measures between fuzzy parameterized possibility fuzzy bipolar soft sets are proposed and applied to an agricultural land selection scenario. Finally, a comparative analysis of current work with existing ones is discussed in detail to show the eminent quality of the proposed work over them.

Silicone Elastomer: Encapsulating Materials for Flexible Thermoelectric Generator

The flexibility of thermoelectric generators (TEG) is an encouraging factor to apprehend self-powered wearable applications as we move on in the demand of energy harvesting and compactness of electronic devices. Conventional rigid thermoelectric modules are not capable to cover irregular surfaces of the human body including unfavourable parameters like bulkiness, heaviness, fragile, and are expensive. In this study, we propose silicone elastomer as an obedient filling material for flexible thermoelectric generators matrix with conductive fabric as electrodes interconnect bismuth-telluride based thermoelectric legs which permit TEGs to adapt curved surfaces. This article presents the use of texture profile analysis (TPA) to mechanically characterize the hardness, adhesiveness, springiness, resilience, cohesion ratio, and chewiness of silicone elastomer. The ability to resist environmental effects such as water, moisture, heat, acid, alkali, corrosion, and weather aging are important for considering the filling material. In addition to these the statistically decreased adhesiveness and increased hardness, springiness, and chewiness identify silicone elastomer as a filling material for wearable thermoelectric devices. An output voltage of TEG for a temperature gradient of ~2°C shows it is highly sensitive to human body temperature.

Intelligent safety assessment method for demolition construction of closure segment of long-span continuous rigid frame bridges

In order to clarify the risk of demolition construction of large-span continuous rigid structure bridge and put forward an intelligent safety assessment method to ensure the safety of demolition construction of the closure segment. Taking a concrete continuous rigid bridge as an example, this paper uses the combination of finite element analysis, theoretical calculation and actual measurement verification to study the influencing parameters and construction safety assessment methods of the long-span continuous rigid bridge in the demolition construction stage of the closure segment. The results show that the parameters that have a great influence on the stress state of box girder and pier during the demolition stage of the closure segment are mainly the self-weight of the structure, tendon prestress state and construction temperature difference. Through the influence envelope analysis of each parameter, it is clear that the ultimate failure mode caused by the most unfavorable parameter combination in the demolition stage of the closure segment is the crushing of the bottom plate of the box girder in the middle span, and the cracking of the piers on the side span at the top and the variable section. In order to further accurately evaluate the construction safety in the demolition stage of the closure segment, based on the long-term down-warping state inversion analysis of the box girder, the identification method of cross-section damage and prestress loss of the box girder and the calculation results of engineering examples are given. Finally, a safety assessment method of the most unfavorable section based on the principle of influence matrix is proposed. Through the analysis of an example, the safety of the closure segment demolition construction is clarified, and the correctness of the analysis is verified by intelligent monitoring means.

Self-Regulatory Neuronal Mechanisms and Long-Term Challenges in Schizophrenia Treatment.

Schizophrenia is a chronic and relapsing disorder that is characterized not only by delusions and hallucinations but also mainly by the progressive development of cognitive and social deficits. These deficits are related to impaired synaptic plasticity and impaired neurotransmission in the nervous system. Currently, technological innovations and medical advances make it possible to use various self-regulatory methods to improve impaired synaptic plasticity. To evaluate the therapeutic effect of various rehabilitation methods, we reviewed methods that modify synaptic plasticity and improve the cognitive and executive processes of patients with a diagnosis of schizophrenia. PubMed, Scopus, and Google Scholar bibliographic databases were searched with the keywords mentioned below. A total of 555 records were identified. Modern methods of schizophrenia therapy with neuroplastic potential, including neurofeedback, transcranial magnetic stimulation, transcranial direct current stimulation, vagus nerve stimulation, virtual reality therapy, and cognitive remediation therapy, were reviewed and analyzed. Since randomized controlled studies of long-term schizophrenia treatment do not exceed 2-3 years, and the pharmacological treatment itself has an incompletely estimated benefit-risk ratio, treatment methods based on other paradigms, including neuronal self-regulatory and neural plasticity mechanisms, should be considered. Methods available for monitoring neuroplastic effects in vivo (e.g., fMRI, neuropeptides in serum), as well as unfavorable parameters (e.g., features of the metabolic syndrome), enable individualized monitoring of the effectiveness of long-term treatment of schizophrenia.

Determination of Exploitable Coefficient of Coral Island Freshwater Lens Considering the Integrated Effects of Lens Growth and Contraction

Groundwater on small coral islands (so-called freshwater lens) is an important water resource for residents and local ecosystems. However, an overexploitation of it may induce a contamination by saltwater. In this paper, we strive to determine the exploitable coefficient of the freshwater lens considering the integrated effects of lens growth and contraction and examine the impacts of well layout schemes on the evolution of the freshwater lens. For this purpose, a numerical model is setup to simulate the saltwater upconing and recovery process under pumping conditions during different evolution stages. Our results show that long-term and higher intensity pumping activities are suggested to be conducted at the latter stage of the lens evolution. Meanwhile, the seasonal contraction of the freshwater lens caused by the seasonal variation in rainfall is characterized by a quicker response of center thickness than maximum thickness of the lens, which further impacts the pumping intensity. The results also indicate that the exploitable coefficient (ρ) of the freshwater lens in small coral island is generally smaller than that in inland areas, ranging from 0.09 to 0.37 under different well layout schemes. Additionally, it is also affected by the uncertainty of hydrogeological parameters. Finally, a safe exploitable coefficient is proposed under the most unfavorable parameter combination for the studied island. The study has important implications for the protection and sustainable exploitation of subsurface freshwater resources on island.

Temporal development of unfavourable urodynamic parameters during the first year after spinal cord injury.

To describe the temporal development of and risk factors for the occurrence of unfavourable urodynamic parameters during the first year after spinal cord injury (SCI). This population-based longitudinal study used data from 97 adult patients with a single-event traumatic or ischaemic SCI who underwent video-urodynamic investigation (UDI) at a university SCI centre. The first occurrences of unfavourable urodynamic parameters (detrusor overactivity combined with detrusor sphincter dyssynergia [DO-DSD], maximum storage detrusor pressure ≥40 cmH2 O, bladder compliance <20 mL/cmH2 O, vesico-ureteric reflux [VUR] and any unfavourable parameter [composite outcome]) were evaluated using time-to-event analysis. The majority of the population (87/97 [90%]) had at least one unfavourable urodynamic parameter. Most unfavourable urodynamic parameters were initially identified during the 1- or 3-month UDI, including 92% of the DO-DSD (78/85), 82% of the maximum storage pressure ≥40 cmH2 O (31/38), and 100% of the VUR (seven of seven) observations. No low bladder compliance was observed. The risk of DO-DSD was elevated in patients with thoracic SCI compared to those with lumbar SCI (adjusted hazard ratio [aHR] 2.38, 95% confidence interval [CI] 1.16-4.89). Risk of maximum storage detrusor pressure ≥40 cmH2 O was higher in males than females (aHR 8.33, 95% CI 2.51-27.66), in patients with a cervical SCI compared to those with lumbar SCI (aHR 14.89, 95% CI 3.28-67.55), and in patients with AIS Grade B or C compared to AIS Grade D SCI (aHR 6.17, 95% CI 1.78-21.39). No risk factors were identified for the composite outcome of any unfavourable urodynamic parameter. The first UDI should take place within 3 months after SCI as to facilitate early diagnosis of unfavourable urodynamic parameters and timely treatment. Neuro-urological guidelines and individualised management strategies for patients with SCI may be strengthened by considering sex and SCI characteristics in the scheduling of UDIs.

Neurogenic Lower Urinary Tract Dysfunction in the First Year After Spinal Cord Injury: A Descriptive Study of Urodynamic Findings.

We aimed to provide a real-world description of neurogenic lower urinary tract dysfunction within the first year after spinal cord injury with a focus on unfavorable urodynamic parameters that are associated with urological morbidity. Urodynamic investigations from 97 patients with traumatic or ischemic acute spinal cord injury and managed according to the European Association of Urology Guidelines on Neuro-Urology were analyzed at a single university spinal cord injury center at 1 month, 3 months, 6 months, and 12 months after injury. Unfavorable urodynamic parameters were defined as detrusor overactivity in combination with detrusor sphincter dyssynergia, maximum storage detrusor pressure of 40 cm H2O or higher, bladder compliance less than 20 mL/cm H2O, and vesicoureteral reflux of any grade. One or more unfavorable urodynamic parameter was observed in 87 out of 97 patients (90%) within the first year after spinal cord injury. Eighty-eight percent of the patients showed detrusor overactivity with detrusor sphincter dyssynergia, 39% a maximum storage detrusor pressure of 40 cm H2O or higher, and 7% vesicoureteral reflux. No patient developed a low-compliance bladder. Using a standardized urodynamic follow-up schedule, we found unfavorable urodynamic parameters in a majority of the population within the first year after spinal cord injury. As early treatment based on urodynamic findings might reduce the risk of deterioration of upper and lower urinary tract function, thereby improving long-term outcomes, there is need for further research regarding recommendations for a urodynamic follow-up schedule during the first year after spinal cord injury.

Off-design operation of a proton conducting solid oxide fuel cell

• The off-design performance of H + SOFC is examined. • The design point of H + SOFC is optimized. • The operational characteristics of H + SOFC are developed. The aim of this research is to examine the off-design performance of H + SOFC based on numerical simulations. The model used in the study was discussed in our previous papers thus the study focuses only on the characteristics generated by the model. In the first part of our study, we selected the design point of the cell where the highest possible effectiveness is achieved in view of key parameters: efficiency, power density, operating temperature, and electrolyte thickness. The next stage was to develop off-design maps of the cell where we marked the ranges of fuel cell operation i.e. ranges in which there are no unfavorable parameters – mainly temperature and voltage. The results of the study will be useful for selecting the operational strategy for micro-CHP units based on H + SOFC.

P-453 No major changes in ovarian function after unilateral ovariectomy in the context of ovarian tissue cryopreservation in girls with Turner syndrome

Abstract Study question What is the impact of unilateral ovariectomy on the ovarian function in girls with Turner syndrome (TS) undergoing ovarian tissue cryopreservation (OTC)? Summary answer In most girls with TS, ovarian markers remained stable up to three years after unilateral ovariectomy. What is known already Girls with TS have a complete or partial loss of one of the sex-chromosomes causing premature ovarian insufficiency which reduces the chances of a spontaneous pregnancy. OTC may be an option to preserve fertility at an early age to increase the chance on genetic offspring. However, this requires a unilateral ovariectomy for young girls with TS who are already subjected to an accelerated loss of ovarian reserve. Previous research in women without TS undergoing a unilateral ovariectomy has shown that the remaining ovary compensate for the function of the removed ovary with no effect on pubertal development and fertility outcome. Study design, size, duration This is a descriptive study of 28 girls with TS (age 5-19 years). Girls were monitored for up to three years after unilateral ovariectomy on pubertal development, and level of follicle stimulating hormone (FSH), luteinizing hormone (LH), oestrogen, Anti-Mullerian hormone (AMH) and inhibin B. Participants/materials, setting, methods The cohort was recruited from girls with TS undergoing OTC as part of the ongoing TurnerFertility study at a university medical centre. Follicles were found in the ovarian cortex fragments in 28 of the 86 cases. These cases were considered to have functional ovaries and were included in the study. Main results and the role of chance Follow-up data are not yet available for three girls because they had surgery only three months ago. Of the other 25 girls, two girls had a monosomic karyotype (45,X), fourteen were mosaic (45,X/46,XX), four had a mosaic with triple X-chromosome (45,X/47,XXX) and five girls had structural aberrations of the X chromosome. Ten girls were prepubertal at time of unilateral ovariectomy, twelve girls had a spontaneous thelarche and three girl had induced puberty. After unilateral ovariectomy, one of the 10 prepubertal girls entered puberty spontaneously and one of the prepubertal girls needed puberty induction. It is still unknown what the impact of a unilateral ovariectomy will be on the pubertal development of the other girls, due to their young age but AMH levels remained stable. 8/12 girls with spontaneous thelarche maintained a measurable AMH and FSH &amp;lt;20 IE/L during the median follow-up of 20 months (IQR 13-30). 4/12 girls with spontaneous thelarche before OTC needed hormone supplementation because of signs of premature ovarian insufficiency, e.g. irregular menstruations (n = 2), flushes (n = 1) and high FSH (84 IE/L; n = 1). However, these girls had unfavourable hormonal parameters before unilateral ovariectomy (e.g. AMH &amp;lt; 0.5 ug/L or FSH &amp;gt; 20 IE/L). Limitations, reasons for caution These results should be interpreted with caution because of the highly heterogeneous population of girls with TS. Moreover, the results should ideally be compared with age- and karyotype-matched controls to determine the natural course of ovarian function of girls with TS. Wider implications of the findings This cohort will be monitored for a longer period of time to observe the consequences on pubertal development, need for hormone supplementation, and eventually fertility outcome. If OTC becomes part of routine care for girls with TS, our results will be of great value in the counselling for future parenthood. Trial registration number NCT03381300

Avoiding Barren Plateaus Using Classical Shadows

Variational quantum algorithms are augmented by an additional subroutine that efficiently detects signatures of barren plateaus -- unfavorable parameter regions that prevent optimization due to vanishing gradients.

Гідрохімічні показники ставів ДП ДГ «Нивка» ІРГ НААН України в контексті вимог до водного середовища великоротого окуня (Micropterus salmoides Lacepede, 1802)

Purpose. Largemouth bass (Micropterus salmoides), a fish native to freshwaters of North America, is adapted within its natural and introduced ranges to freshwater biotopes with temperate climatic conditions. Considering the fact that biotopes in temperate climatic conditions are usually characterized by a significant diversity of physicochemical parameters, it can be concluded that largemouth bass is adapted to a broad range of hydrochemical parameters of the aquatic environment. However, such an adaptive range has its own limiting values, and a long stay of fish in an aquatic environment, the hydrochemical parameters of which approach the upper or lower limit of the adaptive range, can make negatively affect their growth, development, activity, ability to withstand stress factors, as well as inhibit reproductive function. This work examines favorable and unfavorable parameters of the aquatic environment, that have the greatest impact in the process of growing of largemouth bass, as well as an analysis of hydrochemical parameters of ponds of the State Enterprise «Experimental Fish Farm «Nyvka»» of the Institute of Fisheries of the National Academy of Agrarian Sciences of Ukraine for the possibility of growing this species. Findings. This paper contains brief information about main hydrochemical parameters that can have a negative impact on largemouth bass within natural or aquaculture water bodies as well as a comparison of their values ​​with some parameters of the aquatic environment of ponds of the State enterprise «Experimental Fish Farm «Nyvka» of the Institute of Fisheries of the National Academy of Agrarian Sciences of Ukraine obtained during hydrochemical studies in 2018-2019. Practical value. The information from this review can be used in further cultivation of largemouth bass in full-system warm-water pond fish farms with water supply from rivers with the drainage basin located in areas with a high level of urbanization. Keywords: largemouth bass, Micropterus salmoides, hydrochemical parameters, pond farming, aquaculture, adaptation, mineralization, pH, general hardness.

Exploring synthetic biology for the development of a sensor cell line for automated bioprocess control

Unfavorable process conditions lead to adverse cultivation states, limited cell growth and thus hamper biotherapeutic protein production. Oxygen deficiency or hyperosmolality are among the most critical process conditions and therefore require continuous monitoring. We established a novel sensor CHO cell line with the ability to automatically sense and report unwanted process conditions by the expression of destabilized fluorescent proteins. To this end, an inducible real-time system to detect hypoxia by hypoxia response elements (HREs) of vascular endothelial growth factor (VEGF) origin reporting limitations by the expression of destabilized green fluorescent protein (GFP) was created. Additionally, we established a technique for observing hyperosmolality by exploiting osmotic response elements (OREs) for the expression of unstable blue fluorescent protein (BFP, FKBP-BFP), enabling the simultaneous automated supervision of two bioprocess parameters by using a dual sensor CHO cell line transfected with a multiplexable monitoring system. We finally also provided a fully automated in-line fluorescence microscopy-based setup to observe CHO cells and their response to varying culture conditions. In summary, we created the first CHO cell line, reporting unfavorable process parameters to the operator, and provided a novel and promising sensor technology accelerating the implementation of the process analytical technology (PAT) initiative by innovative solutions.

Use of Proton-Pump Inhibitor Is Not Associated with Adverse Clinical Outcomes in COVID-19 Patients: A Territory-Wide Cohort Study

Background. Evidence regarding the use of proton-pump inhibitors (PPIs) in COVID-19 patients remains elusive. Aim. To examine the potential effects of PPI use on the clinical outcomes of COVID-19 patients in a territory-wide cohort. Methods. A retrospective cohort study was performed using data from a territory-wide database in Hong Kong. Patients diagnosed with COVID-19 from 23 January 2020 to 1 January 2021 were identified by virological results. The primary endpoint was a composite of intensive care unit admission, use of invasive mechanical ventilation, and/or death. PPI users were identified by PPI use within 12 months prior to their diagnosis of COVID-19. Results. We identified 8,675 COVID-19 patients (mean age 46 years, 49% male, 97.6% of all reported cases in Hong Kong), of which 579 (6.7%) patients had used PPI. PPI users were found to be older, more likely to have comorbidities, concomitant medications and unfavourable laboratory parameters than nonusers. Of the 8,675 COVID-19 patients, 500 (5.8%) developed the primary endpoint. After propensity score (PS) balancing for patients’ demographics, comorbidities, laboratory parameters, and use of medications, PPI use was not found to be associated with the development of primary endpoint in PS weighting (weighted hazard ratio (HR) 1.10, 95% confidence interval (CI) 0.82–1.46, P = 0.529 ), and PS matching analysis (weighted HR 0.79, 95% CI 0.56–1.13, P = 0.198 ). Consistent nonassociation was observed after multivariable adjustment (adjusted HR 0.84, 95% CI 0.67–1.06, P = 0.142 ), and in subgroups of current and past PPI users. Conclusion. PPI use is not found to be associated with adverse clinical outcomes in COVID-19 patients. The result remains robust after PS weighting, PS matching, and multivariable adjustment.

Using radial basis function network to model the heat transfer and pressure drop of water based nanofluids containing MgO nanoparticles

Present study is focused on feasibility of predicting the thermal and fluid properties of MgO/water nanofluid using radial based function (RBF) type artificial neural networks (ANNs). To design the ANN, Reynolds number and volume fraction of nanoparticles (ϕ) were considered as ANN inputs and in principle independent parameters and on the other hand, the parameters of relative pressure drop and relative heat transfer coefficient were considered as the outputs of this ANN. One of the important innovations in the present study is the attempt to simultaneously predict the relative pressure drop as undesirable and the relative heat transfer coefficient as undesirable parameters. The designed ANN using the radial basis function (RBF) was able to predict the laboratory parameters of relative pressure drop and relative heat transfer coefficient (RHTC) with 99.3% and 99.5% accuracy, respectively. It can drastically reduce the time and financial costs of laboratory methods. Based on the obtained results in ϕ = 0.125%, the unfavorable parameter (relative pressure drop) has a significant supremacy over the optimal parameter (RHTC) and therefore the ϕ is not suitable for use in thermal cycles. But on the other hand, with ϕ = 0.5%, the optimal parameter (RHTC) has a significant supremacy over the undesirable parameter (relative pressure drop), and therefore for MgO/water nanofluid, ϕ>0.5% are suitable for using in thermal cycles.

P–660 Impact of elevated late-follicular phase serum estrogen and progesterone levels on blastocyst utilization and cumulative live birth rates in freeze-all cycles

Abstract Study question Does elevated late-follicular phase estrogen and progesterone levels have an impact on blastocyst utilization and/or cumulative live birth rates in freeze-all cycles? Summary answer High estrogen or progesterone on the day of ovulation trigger is associated with poor blastocyst utilization but comparable cumulative live birth rates in freeze-all cycles. What is known already Several studies suggest impaired clinical outcome in cycles with high estrogen (&amp;gt;3500 pg/ml) or progesterone (&amp;gt;1.5 ng/ml) levels. However, these data were derived from cycles where top-quality embryo(s) were transferred in the fresh cycle and surplus embryos were frozen. These findings might be confounded by alterations in endometrial receptivity. Freeze-all cycles might provide a better model to assess the impact of high late-follicular estrogen or progesterone levels on laboratory and clinical outcome. Study design, size, duration We performed a retrospective cohort study of all IVF cycles (n = 712) between 2016 and 2018 where the entire cohort of embryos was cryopreserved at the blastocyst stage. After excluding cases with &amp;lt;4 oocytes or preimplantation genetic test, the study group comprised 459 women who had 699 frozen-thawed embryo transfer cycles. Participants/materials, setting, methods Women were classified into four groups by the indication for freeze-all strategy as elevated progesterone (high P, n = 61), high estrogen (high E, n = 224), elective freezing (elective, n = 114) and tubal-endometrial pathologies (TEP, n = 60). The primary outcome was the cumulative live birth rate in subsequent thaw-transfer cycles and the secondary outcome was the blastocyst utilization rate. Groups were compared using ANOVA and Cox regression analyses to adjust for confounding variables. Main results and the role of chance The mean age of the study group was 32.8 ± 5.3 years, total number of oocytes and cryopreserved blastocysts were 15.0±7.6 and 4.2±3.0, respectively. The high-E group was younger (31.5 ± 5.2 years) and had higher peak E2 levels (4078.9 ± 588.4 pg/ml), number of oocytes (19.7 ± 7.0), cryopreserved embryos (5.3 ± 3.3) and transfer cycles (2.3 ± 1.4) than the other groups. Blastocyst utilization rate was significantly lower (40.4%) compared to elective freezing (53.6%) and TEP groups (55.7%) (both p = 0.001). The high-P group had higher peak progesterone levels (2.1 ± 0.5 ng/ml, p = 0.001), number of oocytes (14.0 ± 5.2) and frozen embryos (4.1 ± 3.5) compared to elective and TEP groups (both p = 0.04). Blastocyst utilization rate was lower (45.7%) than elective freezing and TEP groups but the difference lacked statistical significance (p = 0.33 and p = 0.21, respectively). Cumulative live birth rates were 42.6% in high-P, 59.8% in high-E, 44.7% in elective freezing and 46.7% in TEP groups. Significant predictors of cumulative live birth were female age (aHR: 0.97, 95%CI:0.95–0.99, p = 0.02) and number of frozen blastocysts (aHR:1.05, 95%CI:1.01–1.10), p = 0.02). When adjusted for these confounders, the cumulative live birth rate was not associated with high-E (aHR: 0.86, 95%CI:0.56–1.31) or high-P (aHR: 0.76,95%CI:0.44–1.32). Limitations, reasons for caution This was a retrospective study with small sample size performed at a single fertility center, which may limit the generalizability of our findings. Wider implications of the findings: While lower blastocyst utilization rates are observed in women high late-follicular estradiol or progesterone levels, cumulative live birth rates in subsequent thaw-transfer cycles were not impaired. However, unfavorable outcome parameters observed in women with elevated progesterone deserve further research. Trial registration number Not applicable