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Introduction: There is a national trend in increasing cesarean section rates in Greece. The purpose of this study was to determine the frequency of cesarean sections per district of the Greek territory. Materials and Methods: In this retrospective observational study, the records of all births in Greece between 2019-2020 from the official archives of the Hellenic Statistical Authority were processed and analyzed. The NUTS-1 classification according to the EUROSTAT was used for the division of the Greek territory into districts. Based on this classification, Greece is divided into four major districts: Northern Greece, Central Greece, Attica and Aegean Islands-Crete. Results: In total, 169,417 births were recorded in Greece during the two-year period from 1/1/2019 to 31/12/2020. Of these, 55.79% were performed by cesarean section, 40.24% by vaginal delivery, 0.02% by a combination of vaginal delivery and cesarean section, while the mode of procedure was not reported in 3.95% of all deliveries. The highest frequency of cesarean sections was observed in Attica with a rate of 58.86%. The corresponding rates in the other districts were 55.50% (Aegean Islands and Crete), 53.55% (Northern Greece) and 51.49% (Central Greece). Notably, the mode of delivery was not reported in 13.75% of births in Central Greece, while the respective rates in the other districts ranged between 1.02% and 2.1%. Conclusions: The frequency of cesarean sections in Greece was high, with a rate of 55.79% of all births, during the study period. The district with the highest frequency of cesarean section was Attica, with a rate over 58%.

Introduction: The present retrospective study aims to examine the course of ventriculomegaly (VM) during gestation, the association between the degree of VM and the presence of additional sonographic fetal malformations, as well as to inspect the prevalence of VM with reference to fetal gender. Materials and Methods: The databases of two maternal-fetal ultrasound units were reviewed from 2010 to 2021. All cases were classified as either mild (10 to

Starting to resolve the oceanic mesoscale in climate models is a step change in model fidelity. This study examines how certain obstinate biases in the midlatitude North Atlantic respond to increasing resolution (from 1° to 0.25° in the ocean) and how such biases in sea surface temperature (SST) affect the atmosphere. Using a multimodel ensemble of historical climate simulations run at different horizontal resolutions, it is shown that a severe cold SST bias in the central North Atlantic, common to many ocean models, is significantly reduced with increasing resolution. The associated bias in the time-mean meridional SST gradient is shown to relate to a positive bias in low-level baroclinicity, while the cold SST bias causes biases also in static stability and diabatic heating in the interior of the atmosphere. The changes in baroclinicity and diabatic heating brought by increasing resolution lead to improvements in European blocking and eddy-driven jet variability. Across the multimodel ensemble a clear relationship is found between the climatological meridional SST gradients in the broader Gulf Stream Extension area and two aspects of the atmospheric circulation: the frequency of high-latitude blocking and the southern-jet regime. This relationship is thought to reflect the two-way interaction (with a positive feedback) between the respective oceanic and atmospheric anomalies. These North Atlantic SST anomalies are shown to be important in forcing significant responses in the midlatitude atmospheric circulation, including jet variability and the storm track. Further increases in oceanic and atmospheric resolution are expected to lead to additional improvements in the representation of Euro-Atlantic climate.

Apricots are one of the most important fruits in the Mediterranean region for both their nutritional and economic value. They are widely cultivated and consumed fresh or dried or are used in the food industry for the production of jams, juices, etc. In any case, the seeds they contain constitute waste. The kernels are very rich in bioactive compounds such as polyphenols, a fact that makes them very appealing in cosmetology. However, the extraction of the bioactive compounds of apricot kernels is poorly examined. In this study, the preparation of polyphenol-rich extracts from apricot kernel biomass is discussed. To this end, a common extraction procedure with water as a solvent was employed. To enhance the extraction yield, the use of a deep eutectic solvent (DES) was examined. In addition, the use of pulsed electric field (PEF) either as a standalone extraction method or as a complementary step was also examined. According to the results, it was evident that when PEF was applied before the extraction procedure, an increase of 88% in the total polyphenol content (TPC) was recorded. Likewise, the use of a glycerol:choline chloride (2:1, w/w) DES increased the TPC by ~70%. When the two approaches were combined, a 173% increase was recorded. According to the above, it can be concluded that apricot kernel biomass is a very good source of polyphenols, especially using the proposed extraction procedure.

Contains fulltext : 290804.pdf (Publisher’s version ) (Closed access) Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder with a major genetic component. Here, we present a genome-wide association study meta-analysis of ADHD comprising 38,691 individuals with ADHD and 186,843 controls. We identified 27 genome-wide significant loci, highlighting 76 potential risk genes enriched among genes expressed particularly in early brain development. Overall, ADHD genetic risk was associated with several brain-specific neuronal subtypes and midbrain dopaminergic neurons. In exome-sequencing data from 17,896 individuals, we identified an increased load of rare protein-truncating variants in ADHD for a set of risk genes enriched with probable causal common variants, potentially implicating SORCS3 in ADHD by both common and rare variants. Bivariate Gaussian mixture modeling estimated that 84-98% of ADHD-influencing variants are shared with other psychiatric disorders. In addition, common-variant ADHD risk was associated with impaired complex cognition such as verbal reasoning and a range of executive functions, including attention. 01 februari 2023

Obesity is one of the most common clinical entities complicating pregnancies and is associated with short- and long-term consequences for both the mother and the offspring.The aim of this study were to review and compare the most recently published influential guidelines on the management of maternal obesity in the preconceptional, antenatal, intrapartum, and postpartum period.A descriptive review of guidelines from the American College of Obstetricians and Gynecologists, the International Federation of Gynecology and Obstetrics, the Society of Obstetricians and Gynecologists of Canada, the Royal College of Obstetricians and Gynecologists, and the Royal Australian and New Zealand College of Obstetricians and Gynecologists on obesity in pregnancy was carried out.There is an overall agreement among the reviewed guidelines regarding the importance of prepregnancy weight loss with behavioral modification, optimization of gestational weight gain, and screening for comorbidities in improving pregnancy outcomes of obese women. Women with previous bariatric surgery should be screened for nutritional deficiencies and have a closer antenatal surveillance, according to all guidelines. In addition, folic acid supplementation is recommended for 1 to 3 months before conception and during the first trimester, but several discrepancies were identified with regard to other vitamins, iodine, calcium, and iron supplementation. All medical societies recommend early screening for gestational diabetes mellitus and early anesthetic assessment in obese women and suggest the use of aspirin for the prevention of preeclampsia when additional risk factors are present, although the optimal dosage is controversial. The International Federation of Gynecology and Obstetrics, Society of Obstetricians and Gynecologists of Canada, Royal College of Obstetricians and Gynecologists, and Royal Australian and New Zealand College of Obstetricians and Gynecologists point out that specific equipment and adequate resources must be readily available in all health care facilities managing obese pregnant women. Moreover, thromboprophylaxis and prophylactic antibiotics are indicated in case of cesarean delivery, and intrapartum fetal monitoring is justified during active labor in obese patients. However, there are no consistent protocols regarding the fetal surveillance, the monitoring of multiple gestations, the timing and mode of delivery, and the postpartum follow-up, although weight loss and breastfeeding are unanimously supported.Obesity in pregnancy is a significant contributor to maternal and perinatal morbidity with a constantly rising global prevalence among reproductive-aged women. Thus, the development of uniform international protocols for the effective management of obese women is of paramount importance to safely guide clinical practice and subsequently improve pregnancy outcomes.

Gastroesophageal reflux disease (GERD) is one of the most common diseases in North America and globally. The aim of this guideline is to provide evidence-based recommendations regarding the most utilized and available endoscopic and surgical treatments for GERD.Systematic literature reviews were conducted for 4 key questions regarding the surgical and endoscopic treatments for GERD in adults: preoperative evaluation, endoscopic vs surgical or medical treatment, complete vs partial fundoplication, and treatment for obesity (body mass index [BMI] ≥ 35 kg/mThe consensus provided 13 recommendations. Through the development of these evidence-based recommendations, an algorithm was proposed for aid in the treatment of GERD. Patients with typical symptoms should undergo upper endoscopy, manometry, and pH-testing; additional testing may be required for patients with atypical or extra-esophageal symptoms. Patients with normal or abnormal findings on manometry should consider undergoing partial fundoplication. Magnetic sphincter augmentation or fundoplication are appropriate surgical procedures for adults with GERD. For patients who wish to avoid surgery, the Stretta procedure and transoral incisionless fundoplication (TIF 2.0) were found to have better outcomes than proton pump inhibitors alone. Patients with concomitant obesity were recommended to undergo either gastric bypass or fundoplication, although patients with severe comorbid disease or BMI 50 should undergo Roux-en-Y gastric bypass for the additional benefits that follow weight loss.Using the recommendations an algorithm was developed by this panel, so that physicians may better counsel their patients with GERD. There are certain patient factors that have been excluded from included studies/trials, and so these recommendations should not replace surgeon-patient decision making. Engaging in the identified research areas may improve future care for GERD patients.

The traditional extraction methods used to recover natural antioxidants from food industry wastes involve significant amounts of hazardous solvents. A viable alternative is the use of non-toxic surfactants to remove organic compounds from wastes at temperatures above the cloud point. Cloud point extraction has only recently begun to be used to recover high-value added compounds from food industry wastes. In the current work, a method for the isolation of high-value added components from liquid tomato wastewater using a cloud point extraction method was developed and optimized. Food-grade lecithin was examined for its potential to be used as a surfactant in the developed procedure. Moreover, parameters affecting the extraction (ionic strength, sample pH, temperature of extraction, and surfactant concentration) were examined and optimized. According to the results, the maximum recovery of carotenoids from the sample could be achieved with the developed procedure, by simply adjusting the pH to 3.5, adding 35.6% (w/v) sodium chloride, and setting the temperature at 45 °C. Moreover, the amount of lecithin used was examined. In order to extract the total amount of carotenoids from a sample, it was found that either three extractions with 1% lecithin are needed, or two extractions with 2% lecithin. In addition, the antioxidant activity of the extract was examined and it was found to scavenge 36.3% of DPPH free radicals. This percentage was 10% lower compared to the initial sample, which suggests that the extracted compounds retain their activity. Overall, the developed procedure can be used to recover carotenoids in a cost-efficient and easy way.

To date, many studies have been published, aiming to extract bioactive compounds from plants. Lately, research focuses on maximizing the extraction yield, using environmentally friendly techniques and solvents. In this study, the extraction of polyphenolic compounds from Cistus creticus is discussed. Extraction of the compounds has been carried out with water and ethanol, employing the most common approach. To further enhance the extraction yield, the usage of four deep eutectic solvents (DESs) has also been examined. In an effort to further enhance the extraction yield, pulsed electric fields have also been employed. According to the results, it was evident that the use of DESs made of glycerol: choline chloride (2:1) increased the extraction yield by 75%, compared to extraction with water. Moreover, the use of pulsed electric fields enhanced the extraction yield of the common approach, by up to 70%. When pulsed electric fields and DESs were combined, the extraction yield increased by 14%, compared to the use of DESs only. Finally, the extract was analyzed for its content in volatile compounds, and it was found that new compounds could be extracted with the use of DESs.

In this study, the use of pulsed electric field (PEF) for the extraction of polyphenols from mature Elaeagnus pungens ‘Limelight’ leaves is discussed. Optimization of the main parameters that affect the extraction process was carried out. More specifically, the composition of the solvent (ethanol, water, and mixtures of the two at a 25% v/v step gradient) and the main PEF-related parameters (i.e., pulse duration, pulse period, and electric field intensity) was optimized. The obtained extracts were examined for their polyphenol content with the Folin–Ciocalteu assay and individual polyphenols were also assessed with high-performance liquid chromatography. The extracts obtained with PEF were compared to the extract compared without PEF, in terms of total polyphenols. According to the results, the optimum extraction parameters were found to be a pulse duration of 10 μs, a pulse period of 1000 μs, and an electric field intensity of 0.85 kV cm−1 after 20 min of extraction. The optimum solvent was found to be the 50% (v/v) ethanol/water mixture. The extract prepared under the optimum conditions was found to contain 58% more polyphenols compared with the extract prepared without PEF. Moreover, an increase of up to 92% was recorded for specific polyphenols. Based on the above, it was evidenced that the examined parameters influenced the recovery of polyphenols, suggesting that such parameters should be also examined in similar studies, in order to maximize the extraction yield of polyphenols.

To review and compare the most recently published recommendations on the investigation and management of abnormal uterine bleeding (AUB).A descriptive review of recommendations from the American College of Obstetricians and Gynaecologists (ACOG), the National Institute for Health and Care Excellence (NICE), the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG), the Society of Obstetricians and Gynaecologists of Canada (SOGC) and the International Federation of Gynaecology and Obstetrics (FIGO) on AUB in reproductive-aged women was carried out.There is a consensus that detailed personal and family history along with physical examination are essential in the investigation of menstrual, intermenstrual or postcoital AUB. All the medical societies recommend transvaginal ultrasound as the first-line imaging modality to determine the AUB cause. Moreover, they agree (except for RANZCOG) that, in women with AUB, endometrial biopsy should only be performed if additional risk factors for endometrial cancer are present. Laboratory tests may be helpful in the AUB investigation; however, there are several discrepancies among the recommendations. Regarding AUB management, NICE, ACOG and SOGC agree that the administration of hormonal or non-hormonal medications should be the first-line treatment modality in bleeding disorders and absent or minor structural pelvic pathology. Surgical management should be preferred in cases of identified polyps, large fibroids or unsuccessful pharmacological treatment.Since AUB affects a significant proportion of reproductive-aged women, the main objective is to improve the quality of life of these patients without missing cases of malignancy.

Aim: To retrospectively characterize real-world therapeutic strategies, clinical outcomes and attrition rates with EGFR tyrosine kinase inhibitors (TKIs), before first-line osimertinib approval, in EGFR-mutated advanced/metastatic non-small-cell lung cancer patients in Greece. Results: Among 160 patients, the discontinuation rate for first-line first- or second-generation EGFR-TKIs was 85%; among these patients, 43% did not receive any second-line therapy and 9.4% died during an 18.7-month follow-up period. Median progression-free and overall survival were 12.1 and 20.9 months, respectively. Osimertinib was offered as second- and third-line treatment in 69.6 and 21.7% of patients with the T790M mutation, respectively. Brain metastases were recorded in 10.6% of patients during treatment, with median overall survival of 4.9 months. Conclusion: Given the high attrition rates and the impact of CNS progression, offering the most appropriate first-line EGFR-TKI treatment with CNS penetration is key to maximize outcomes.

DNA/RNA molecules adopting the left-handed conformation (Z-form) have been attributed with immunogenic properties. However, their biological role and importance has been a topic of debate for many years. The discovery of Z-DNA/RNA binding domains (Zα domains) in varied proteins that are involved in the innate immune response, such as the interferon inducible form of the RNA editing enzyme ADAR1 (p150), Z-DNA binding protein 1 (ZBP1), the fish kinase PKZ and the poxvirus inhibitor of interferon response E3L, indicates important roles of Z-DNA/RNA in immunity and self/non-self-discrimination. Such Zα domain-containing proteins recognise left-handed Z-DNA/RNA in a conformation-specific manner. Recent studies have implicated these domains in virus recognition. Given these important emerging roles for the Zα domains, it is pivotal to understand the mechanism of recognition of the Z-DNA/Z-RNA by these domains. To this end, we assessed the binding thermodynamics of Zα domain from ORF112 and ADAR1 on T(CG)3 and T(CG)6 oligonucleotides which have high propensity to adopt the Z-conformation. Our study highlights important differences in the mode of binding by the two Zα domains originating from different proteins. Site-directed mutagenesis was employed together with isothermal titration calorimetry to tease apart finer details of the binding thermodynamics. Our work advances the understanding on binding thermodynamics of Zα domains to their cognate nucleic acid substrates and contributes to the efforts to gain a complete appreciation of this process.

The direct application of forecasts from seasonal prediction systems (SPSs) in agriculture is limited by their skill, and SPSs are more skilled at El Niño-Southern Oscillation (ENSO) prediction than precipitation prediction. An alternative to the direct application of forecasts from SPSs could be to link the forecast of ENSO conditions with dynamic crop models to evaluate alternate crop management options prior to the start of the actual planting. Although potential benefits of this approach have been tested in many areas of the world, so far limited evidence exists regarding its application in Nepal’s Terai region. The overall goal of this study was to determine the potential relationship between ENSO and summer monsoon precipitation over Nepal’s Terai and ascertain SPSs’ skill in predicting ENSO. This analysis included disentangling the relative contribution of precipitation to interannual variability in rice yield from other factors using a cropping system model, namely, the Crop Environment Resource Synthesis-Rice (CSM-CERES-Rice). The crop model was also employed to explore options for increasing rice yield and minimizing risk by adjusting crop management. This study found that precipitation was the main variable affecting interannual variability in rice yield, that SPSs are good at predicting ENSO, and that the ENSO signal can be used to predict seasonal precipitation anomalies in the study area in all years except ENSO neutral years. Prior knowledge of seasonal precipitation anomalies can then be used to optimize rice yield using a crop model, and ultimately to assist farmers with decision making.

Tzatziki is a deli salad widely consumed in the Eastern Mediterranean and Balkan countries, and it is acknowledged for its health benefits. So far, it is proved to exhibit extreme resistance to microbial spoilage by (pathogenic) microorganisms and microbial self-stabilization, but no research was carried out regarding its oxidative stability despite the fact that it contains a large amount of lipids. In this study, the factor that affects the oxidative stability of tzatziki was exploited. Different samples of tzatziki salad were prepared and stored for 16 or 27 days, depending on the conducted experiment. They varied in the type of yogurt (set yogurt or traditional Greek-style yogurt), the type of oil (olive oil or soybean oil), and the addition or not of preservatives, garlic, and cucumber. Samples were analyzed in terms of oxidative stability (by the Rancimat method), colony-forming units, and tocopherol content throughout the storage period. Among the examined parameters, no correlation between the tocopherol content and oxidative stability was recorded. However, a strong correlation between the microbial population and the oxidative stability was recorded. Therefore, this correlation can be used to prepare tzatziki salads with increased shelf life and decreased flavor deterioration (due to oxidation). Moreover, such correlations should be further exploited for other foods so as to promote their stability.

Objectives The purpose of this study was to determine the onset of fetal movements’ perception and to identify parameters that affect this timing. Methods This was a prospective cohort study including singleton pregnancies that attended routine prenatal care, in a tertiary care center, in northern Greece, between January 2020 and July 2021. We collected data on medical and obstetric history, and invited women to record the time that they perceived the fetal movements for the first time, that being the primary outcome of the study. Furthermore, we studied the associations between this timing and several obstetric and sociodemographic parameters. Results In total, 2,009 women participated in the study. The mean gestational age at first perception of fetal movements was 19 weeks (±1.5). This ranged from as early as 14+0–14+6 weeks (0.1%) to 24+0–24+6 weeks (0.1%). The majority of women (73.3%) reported initial perception of fetal movements between 18+0 and 20+6 weeks. Following multivariate logistic regression analysis, we found that nulliparity (OR: 2.607; 95% CI: 1.876–3.622; p Conclusions The onset of maternal perception of fetal movements is around 19 weeks and this timing may be delayed by higher maternal age, higher body mass index, nulliparity and anterior placental position.

Introduction: Migrant pregnant women may require antenatal hospitalization due to complications of pregnancy. The aim of this study was to investigate the indications for admission, the baseline and the obstetric characteristics of migrant women hospitalized in a high-risk pregnancy unit (HRPU) and compare them with the native-Greek individuals. Materials and Methods: A retrospective cohort study was conducted during the period 2005-2019. All pregnant women at ≥ 24 gestational weeks admitted in a University hospital HRPU were eligible for the study. Epidemiological characteristics, along with the indications for admission were studied and comparisons of several parameters between native-Greek and migrant pregnant women were conducted. Results: Overall, 3,823 women were included in the study, of which 838 (21.9%) were migrant women. The main indication for hospital admission was threatened preterm labor (38.0%). When we compared the two groups in terms of indications for admission, we found that maternal indications were more common in migrants than Greek pregnant women (32.8% vs 26.8%; p=0.001; OR:1.332; 95% CI:1.129-1.571). Compared to native women, migrants were younger (28.7±6.1 vs 30.9±6.4 years, p

Introduction We assessed students' perception of the impact of the pandemic on their well-being, education, academic achievement, and whether grit and resilience alter students’ ability to mitigate the stress associated with disruptions in education. We hypothesized that students would report a negative impact, and those with higher grit and resilience scores would be less impacted. Methods A multidisciplinary team of educators created and distributed a survey to medical students. Survey results were analyzed using descriptive statistics, ANOVA, and multivariate linear regressions. A p-value

Dysphagia post head and neck cancer (HNC) multimodality treatment is attributed to reduced pharyngeal strength. We hypothesized that pharyngeal tongue base augmentation for dysphagia (PAD therapy) would increase pharyngeal pressures during swallowing thereby improving swallow symptoms.Adults with moderate-severe dysphagia post-HNC treatment had PAD therapy using a temporary filler (hyaluronic acid [HA]), with follow-up long-lasting lipofilling. Swallowing preprocedure and postprocedure was assessed with the Sydney Swallow Questionnaire (SSQ), High-Resolution Pharyngeal Manometry (HRPM), and Videofluoroscopic Swallowing Study (VFSS). Statistical comparison utilized paired tests.Six participants (all male; median age 64 years [IQR 56, 71]) underwent PAD therapy at a median of 47 [IQR 8, 95] months post-treatment. SSQ scores reduced from baseline (mean 1069 [95%CI 703, 1434]) to post-HA (mean 579 [76, 1081], p 0.05), and post-lipofilling (491 [95%CI 913, 789], p = 0.003, n = 4). Individual participants demonstrated reduced Swallow Risk Index, Bolus Presence Time, and increased Upper Esophageal Sphincter opening, but mesopharyngeal contractile pressures were unchanged. VFSS measures of aspiration, residue, and severity were unchanged.Novel PAD therapy is safe and improves dysphagia symptoms. Biomechanical swallowing changes are suggestive of more efficacious bolus propulsion with conservative filler volume, but this was unable to resolve residue or aspiration measures.

ChromaX is a Python library that enables the simulation of genetic recombination, genomic estimated breeding value calculations, and selection processes. By utilizing GPU processing, it can perform these simulations up to two orders of magnitude faster than existing tools with standard hardware. This offers breeders and scientists new opportunities to simulate genetic gain and optimize breeding schemes.

Accurate predictions of climate variations at the decadal timescale are of great interest for decision-making, planning and adaptation strategies for different socio-economic sectors. Notably, decadal predictions have rapidly evolved during the last 15 years and are now produced operationally worldwide. The majority of the studies assessing the skill of decadal prediction systems focus on time-mean anomalies of standard meteorological variables, such as annual mean near-surface air temperature and precipitation. However, the predictability of extreme events frequency may differ substantially from the predictability of multi-year annual or seasonal means. Predicting the frequency of extreme events at different timescales is of major importance, since they are associated with severe impacts on various natural and human systems. In the current study we evaluate the capability of state-of-the-art decadal prediction systems to predict the frequency of temperature extremes in Europe. More specifically, we assess the skill of a multi-model ensemble from the Decadal Climate Prediction Project (DCPP, 163 ensemble members from 12 models in total) to forecast the number of days belonging to heatwaves episodes during summer (June–August). We find statistically significant predictive skill over Europe, except for the United Kingdom and a large part of the Scandinavian Peninsula, most of which is associated with the long-term warming trend. We are progressing with the evaluation of other statistical aspects of extreme events, including warm and cold episodes during winter, and we are also investigating whether there is predictive skill beyond that stemming from the external forcing.

The simulated North Atlantic atmosphere­–ocean variability is assessed in a subset of models from HighResMIP that have either low-resolution (LR) or high-resolution (HR) in their atmosphere and ocean model components. In general, the LR models overestimate the low-frequency variability of subpolar sea-surface temperature (SST) anomalies and underestimate their correlation with the NAO compared to ERA5 reanalysis. These biases are substantially reduced in the HR models, and it is shown that the improvements are related to a reduction of intrinsic (non-NAO-driven) variability of the subpolar ocean circulation.To understand the mechanisms behind the overestimated intrinsic subpolar ocean variability in the LR models, a link is demonstrated between the biases in subpolar ocean variability and known biases in the mean state of the Labrador-Irminger seas. Supporting previous studies, the Labrador-Irminger seas are found to be too cold and too fresh in the LR models compared to observations from EN4 and the HR models. This causes upper-ocean density and hence convection anomalies in this region to be more salinity-controlled in the LR models versus more temperature-controlled in the HR models. It is hypothesized that this may cause the excessive subpolar ocean variability in the LR models by 1) promoting a positive feedback between subpolar upper-ocean salinity, convection and Atlantic Meridional Overturning Circulation (AMOC) anomalies, and 2) weakening the negative feedback between subpolar upper-ocean temperature, convection and AMOC anomalies that is apparent in the HR models. The results overall suggest that mean ocean biases play an important role in the simulation of the variability of the extratropical ocean.

A solid understanding of the global water cycle and how land surface processes respond to both changes in climate and pressure due to water use is essential for society. Although Land Surface Models (LSM) and Global Hydrological Models (GHM) are able to simulate the spatiotemporal variability of the water balance relatively reliably, intercomparison studies have indicated considerable differences between the models. Each LSM and GHM present a unique set of equations, parameters and configurations that contribute to the spread of simulated hydrological responses to meteorological forcings. In order to improve our understanding of modeling uncertainties, we propose a variable importance assessment for 5 LSM/GHM (JULES, HTESSEL, PCR-GLOBWB, SURFEX and ORCHIDEE) from the EartH2Observe (E2O) project. The output of the models and the meteorological forcings were collected from the Water Resources Reanalysis Tier 2 of the E2O project, which consists of a global dataset with spatial resolution of 0.25ox0.25o. We used soil texture and land cover datasets that most resemble the inputs used by each LSM/GHM during the E2O project. The models’ outputs were used to estimate 6 hydrological indices for every land cell: Evaporation-Precipitation ratio; Runoff-Precipitation ratio; Surface Runoff-Total Runoff ratio; median Soil Moisture variation caused by a Rainfall event; median Surface Runoff caused by a Rainfall event; and Soil Moisture temporal autocorrelation. Then, we evaluate the input features (meteorological, land cover, and soil texture) importance to the hydrological indices of each model using machine learning. With the analysis we aim to examine a) How much the models differ and why? b) To what extent are the output differences related to the input features or/and to the models formulation? and c) How significant is each feature to the respective hydrological index?

Supplementary Figure from Functional Testing to Characterize and Stratify PI3K Inhibitor Responses in Chronic Lymphocytic Leukemia

Supplementary Table from Functional Testing to Characterize and Stratify PI3K Inhibitor Responses in Chronic Lymphocytic Leukemia

Purpose:PI3K inhibitors (PI3Ki) are approved for relapsed chronic lymphocytic leukemia (CLL). Although patients may show an initial response to these therapies, development of treatment intolerance or resistance remain clinical challenges. To overcome these, prediction of individual treatment responses based on actionable biomarkers is needed. Here, we characterized the activity and cellular effects of 10 PI3Ki and investigated whether functional analyses can identify treatment vulnerabilities in PI3Ki-refractory/intolerant CLL and stratify responders to PI3Ki.Experimental Design:Peripheral blood mononuclear cell samples (n = 51 in total) from treatment-naïve and PI3Ki-treated patients with CLL were studied. Cells were profiled against 10 PI3Ki and the Bcl-2 antagonist venetoclax. Cell signaling and immune phenotypes were analyzed by flow cytometry. Cell viability was monitored by detection of cleaved caspase-3 and the CellTiter-Glo assay.Results:pan-PI3Kis were most effective at inhibiting PI3K signaling and cell viability, and showed activity in CLL cells from both treatment-naïve and idelalisib-refractory/intolerant patients. CLL cells from idelalisib-refractory/intolerant patients showed overall reduced protein phosphorylation levels. The pan-PI3Ki copanlisib, but not the p110δ inhibitor idelalisib, inhibited PI3K signaling in CD4+ and CD8+ T cells in addition to CD19+ B cells, but did not significantly affect T-cell numbers. Combination treatment with a PI3Ki and venetoclax resulted in synergistic induction of apoptosis. Analysis of drug sensitivities to 73 drug combinations and profiling of 31 proteins stratified responders to idelalisib and umbralisib, respectively.Conclusions:Our findings suggest novel treatment vulnerabilities in idelalisib-refractory/intolerant CLL, and indicate that ex vivo functional profiling may stratify PI3Ki responders.

Deep sequencing of human tumours has uncovered a previously unappreciated role for epigenetic regulators in tumorigenesis. H3K4 methyltransferase KMT2C/MLL3 is mutated in several solid malignancies, including more than 10% of breast tumours. To study the tumour suppressor role of KMT2C in breast cancer, we generated mouse models of Erbb2/Neu, Myc or PIK3CA-driven tumorigenesis, in which the Kmt2c locus is knocked out specifically in the luminal lineage of mouse mammary glands using the Cre recombinase. Kmt2c knock out mice develop tumours earlier, irrespective of the oncogene, assigning a bona fide tumour suppressor role for KMT2C in mammary tumorigenesis. Loss of Kmt2c induces extensive epigenetic and transcriptional changes, which lead to increased ERK1/2 activity, extracellular matrix re-organization, epithelial-to-mesenchymal transition and mitochondrial dysfunction, the latter associated with increased reactive oxygen species production. Loss of Kmt2c renders the Erbb2/Neu-driven tumours more responsive to lapatinib. Publicly available clinical datasets revealed an association of low Kmt2c gene expression and better long-term outcome. Collectively, our findings solidify the role of KMT2C as a tumour suppressor in breast cancer and identify dependencies that could be therapeutically amenable.

Background: ‘ALARM’ is a systematic review of available literature aiming to provide updated information on the prevalence of Human Papillomavirus (HPV) in locally-regionally advanced (LA) and recurrent/metastatic (RM) head and neck cancer (HNC) worldwide. Methods: Electronic searches were conducted on clinicaltrials.gov, MEDLINE (via Pubmed), Embase and ASCO/ESMO journals of congresses for interventional studies (IS; phase I-III trials) as well as MEDLINE and Embase for non-interventional studies (NIS) of LA/RM HNC published between 01Jan2010 and 31Dec2020. Criteria for study selection included: availability of HPV prevalence data for patients with LA/RM HNC, patient enrollment from 01Jan2010 onwards, and oropharyngeal cancer (OPC) included among HNC types. HPV prevalence per study was calculated as proportion of HPV-positive (HPV+) over total number of HNC enrolled patients. For overall HPV prevalence across studies, mean of reported HPV prevalence rates across studies and pooled estimate, i.e., sum of all HPV+ patients over sum of all HNC patients enrolled, were assessed. Results: Eighty-one studies (62 IS; 19 NIS) were included in this evidence synthesis, representing 9607 LA/RM HNC cases, with an overall mean (pooled) HPV prevalence of 32.6% (25.1%). HPV prevalence was 44.7% (44.0%) in LA and 24.3% (18.6%) in RM. Among 2714 LA/RM OPC patients from 52 studies with available data, the mean (pooled) value was 55.8% (50.7%). The majority of published HPV prevalence data were derived from countries in Northern America and Europe, with overall HPV prevalence of 46.0% (42.1%) and 24.7% (25.3%) across studies conducted exclusively in these geographic regions, respectively. Mean (pooled) HPV prevalence in Northern Europe was 31.9% (63.1%), numerically higher than the European average. A “p16-based” assay was the most frequently reported HPV detection methodology (58.0%). Conclusion: Over the last decade, at least one quarter of LA/RM HNC and half of OPC cases studied in IS and NIS were HPV+, with variation across disease stages and geographic regions. This alarming burden is consistent with a potential implication of HPV in the pathogenesis of at least a subgroup of HNC. The observed rates underscore the relevance of HPV testing and prophylaxis to the prevention and management of these cancers. PROSPERO Number: CRD42021256876

Variability of the North Atlantic Oscillation (NAO) drives wintertime temperature anomalies in the Northern Hemisphere. Dynamical seasonal prediction systems can skilfully predict the winter NAO. However, prediction of the NAO‐dependent air temperature anomalies remains elusive, partially due to the low variability of predicted NAO. Here, we demonstrate a hidden potential of a multi‐model ensemble of operational seasonal prediction systems for predicting wintertime temperature by increasing the variability of predicted NAO. We identify and subsample those ensemble members which are close to NAO index statistically estimated from initial autumn conditions. In our novel multi‐model approach, the correlation prediction skill for wintertime Central Europe temperature is improved from 0.25 to 0.66, accompanied by an increased winter NAO prediction skill of 0.9. Thereby, temperature anomalies can be skilfully predicted for the upcoming winter over a large part of the Northern Hemisphere through increased variability and skill of predicted NAO., Plain Language Summary: Wintertime temperature in the Northern Hemisphere is regulated by the variations of atmospheric pressure, represented by the so‐called North Atlantic Oscillation (NAO). The NAO's phase—negative or positive—is associated with the pathways of cold and warm air masses leading to cold or warm winters in Europe. While the NAO phase can be predicted well, predictions of the NAO‐dependent air temperature remain elusive. Specifically, it is challenging to predict the strength of the NAO, the most important requirement for the accurate prediction of wintertime temperature. Here, we improve wintertime temperature prediction by increasing the strength of the predicted NAO. We use observation based autumn Northern Hemisphere ocean and air temperature, as well as ice and snow cover for statistical estimation of the first guess NAO for the upcoming winter. Then, we sub‐select only those simulations from the multi‐model ensemble, which are consistent with our first guess NAO. As a result, based on these selected members, the wintertime temperature prediction is substantially improved over a large part of the Northern Hemisphere., Key Points: Amplitude and skill of predicted North Atlantic Oscillation (NAO) improve significantly by subsampling of ensemble of existing seasonal prediction systems. Amplified NAO variability leads to significant improvement in predicting the upcoming winter temperature anomalies in the Northern Hemisphere., Deutsche Forschungsgemeinschaft, Climate, Climatic Change, and Society, Marine Institute grant, European Union's Horizon 2020 research and innovation programme, https://cds.climate.copernicus.eu/cdsapp#!/dataset/seasonal-original-single-levels?tab=overview, http://www.ecmwf.int/en/forecasts/datasets

Preterm labor (PTL) is one of the most common and serious pregnancy complications associated with significant perinatal morbidity and mortality, as well as long-term neurologic impairment in the offspring.The aim of this study was to review and compare the most recently published major guidelines on diagnosis, management, prediction, and prevention of this severe complication of pregnancy.A descriptive review of guidelines from the National Institute for Health and Care Excellence (NICE), the World Health Organization, the American College of Obstetricians and Gynecologists, the New South Wales Government, and the European Association of Perinatal Medicine (EAPM) on PTL was carried out.There is a consensus among the reviewed guidelines that the diagnosis of PTL is based on clinical criteria, physical examination, measurement of cervical length (CL) with transvaginal ultrasound (TVUS) and use of biomarkers, although there is disagreement on the first-line diagnostic test. The NICE and the EAPM are in favor of TVUS CL measurement, whereas the New South Wales Government mentions that fetal fibronectin testing is the mainstay for PTL diagnosis. Moreover, there is consistency among the guidelines regarding the importance of treating PTL up to 34 weeks of gestation, to delay delivery for 48 hours, for the administration of antenatal corticosteroids, magnesium sulfate, and in utero transfer to higher care facility, although several discrepancies exist regarding the tocolytic drugs of choice and the administration of corticosteroids and magnesium sulfate after 34 and 30 gestational weeks, respectively. Routine cesarean delivery in case of PTL is unanimously not recommended. Finally, the NICE, the American College of Obstetricians and Gynecologists, and the EAPM highlight the significance of screening for PTL by TVUS CL measurement between 16 and 24 weeks of gestation and suggest the use of either vaginal progesterone or cervical cerclage for the prevention of PTL, based on specific indications. Cervical pessary is not recommended as a preventive measure.Preterm labor is a significant contributor of perinatal morbidity and mortality with a substantial impact on health care systems. Thus, it seems of paramount importance to develop consistent international practice protocols for timely diagnosis and effective management of this major obstetric complication and subsequently improve pregnancy outcomes.

Polyphenols are an important class of compounds, due to their excellent antioxidant properties. Lately, much effort has been placed into developing new extraction techniques and optimizing them, so that polyphenols can be retrieved more efficiently from the plant materials. One of the most recent advances in extraction techniques is pulsed electric field extraction (PEF). This new technique is environmentally friendly and has the potential to maximize the recovery of compounds from plant tissues. Although the efficiency of PEF depends, among others, on the nature of the solvent used, up to date, there are no reports on the optimization of the PEF extraction of polyphenols, using hydroethanolic solutions of varying content in ethanol. In this study, three hydroethanolic solutions, water, and ethanol were used for the PEF-based extraction of total polyphenols from Sideritis raiseri. Results were conclusive that the 1:1 mixture of ethanol and water can increase by up to 146% the yield of polyphenols in the extract, highlighting the need to study more extensively, in the future, mixtures of solvents and not just plain water.