Short-term Response Research Articles

Клинические особенности пограничного личностного расстройства у подростков

Aim. Identification of the features of primary and comorbid signs of borderline personality disorder (BPD) in teenagers. Design. Open-label cohort study. Materials and methods. A pilot clinical evaluation was performed for a full cohort of teenagers admitted to psychiatric in-patient clinic in 2021–2022, the condition of which corresponded to the International Classification of Diseases, revision 11, BPD criteria. The study included 74 teenagers aged 11–17 years old, of which 72 were females. The mean age was 16.6 years old. Results. All 74 patients had comorbid disorders; complex comorbidities were observed in 31 (41.9%) patients. Forty-seven (63.5%) patients had a history of bullying. Anxiety and post-stress disorders preceded clinical manifestations of the BPD symptoms in 64 (86.5%) cases. Self-harm and attempted suicide were recorded in 58 (78.4%) patients; problems with self-identification, including gender preferences, were observed in 56 (75.7%) patients, problems with interpersonal relationships — in 64 (86.5%) patients, and dissociative symptoms — in 41 (55.4%) patients. Multiple personality disorder identification as “we”, “multiple personalities”) was observed in 12 (16.2%) cases. Clinically significant signs of various eating disorders were diagnosed in 16 (21.6%) patients. After being treated in an in-patient clinic, 65 (87.8%) teenagers demonstrated significant improvement. Most challenging was the management of patients with substantial dissociative symptoms, persistent “gender identity disorder” and trends to use abnormal psychological defence mechanisms. Conclusion. Interim data show that manifestation of symptoms and comorbidities, as well as a short-term response to therapy in teenagers differ from those in adults with BPD, favouring BPD with adolescent onset as a relatively separate sub-type and justifying a dimensional approach for the search and optimisation of early therapeutic interventions in teenagers with BPD. Keywords: borderline personality disorder, teenagers, comorbidity, psychiatric disorders, International Classification of Diseases, revision 11 (ICD-11).

ESG performance and organizational resilience ——based on an “extreme heat event”

This study evaluated the organizational resilience of Chinese listed companies under extreme heat events based on the cumulative abnormal return of stocks during severe environmental disturbances. Based on institutional, stakeholder, and risk management theories, the extreme heat event in August 2022 was chosen as the research setting to evaluate the relationships between environmental, social, and governance (ESG) performances and organizational resilience. Results showed that ESG performances significantly improve company resilience in market short-term response. The significantly improved resilience effects were observed in non-state-owned enterprises and companies in low-carbon pilot cities. Further analysis revealed that companies with varying levels of ESG performances demonstrate significant differences in long-term profitability potential. This study has important implications for further research on the effect of ESG performance on company resilience and provides a basis for enhancing company stability and flexibility during frequent extreme weather events.

Short-term response of oat crop yield and soil microbial activity promoted by inorganic fertilization suppression and organic fertilization addition in a periurban agroecosystem

In intensive or long-time agriculture systems, the soil ecological processes are negatively affected, resulting in a loss of regulatory mechanisms that provide stability to plant nutrient supply by microbial metabolism and must be substituted by synthetic fertilization face-off maintain crop production. The change in fertilization practices is a decision for peasants because it represents an economic risk if it is unfavorable, especially in crops that occupy a large area of land as oat crops in periurban agroecosystems of Mexico City. Therefore, this work aimed to evaluate oat crop yield and microbial activity after the change of fertilization regime in a periurban agroecosystem of Mexico City. For this, we substitute inorganic fertilizers with urea and organic amendments (cattle manure and vermicompost), so too, the fertilization suppression in a one-cycle crop field experiment on intensively managed and degraded volcanic soil, classified as Andic Anthrosol at a periurban agroecosystem. We can observe that the addition of cattle manure promotes the oat crop yield increase by 15 % than synthetic fertilization and improves the C use efficiency of the microbial community. In comparison, fertilization suppression decreases by 33 % the crop yield but promotes microbial use efficiency at the same level as cattle manure addition. These findings prove that the highly degraded soils lose resistance to changes in fertilization management. However, this can provide an opportunity to reestablish favorable microbial activity by adding organic amendments or after suppressing the unbalanced nutrient addition represented by synthetic fertilizers or C-poor substrates.

Fifteen years of real-world data on the use of vigabatrin in individuals with infantile epileptic spasms syndrome.

This study was undertaken to evaluate our treatment algorithm for infantile epileptic spasms syndrome (IESS) used between 2000 and 2018. We initiated vigabatrin (VGB), and steroids were added if the electroclinical response (spasms and electroencephalogram [EEG]) to VGB was not obtained or incomplete. Individuals with IESS treated with VGB were recruited from our hospital clinical data warehouse based on electronic health records (EHRs) generated since 2009 and containing relevant keywords. We confirmed the diagnosis of IESS. Clinical, EEG, imaging, and biological data were extracted from the EHRs. We analyzed factors associated with short-term response, time to response, relapse, time to relapse of spasms, and the presence of spasms at last follow-up. We collected data from 198 individuals (female: 46.5%, IESS onset: 6 [4.5-10.3] months, follow-up: 4.6 [2.5-7.6] years, median [Q1-Q3]) including 129 (65.2%) with identifiable etiology. VGB was started 17 (5-57.5) days after IESS diagnosis. A total of 113 individuals were responders (57.1% of the cohort), 64 with VGB alone and 38 with VGB further combined with steroids (56.6% and 33.6% of responders, respectively). Among responders, 33 (29%) experienced relapses of spasms, mostly those with later onset of spasms (p = .002) and those who received VGB for <24 months after spasms cessation compared to a longer duration on VGB (45% vs. 12.8%, p = .003). At follow-up, 92 individuals were seizure-free (46.5% of the whole cohort), including 26 free of therapy (13.1%). One hundred twelve individuals (56.6%) were still receiving VGB, with a duration of 3.2 (1.75-5.7) years. Our sequential protocol introducing VGB then adding steroids is an effective alternative to a combined VGB-steroids approach in IESS. It avoids steroid-related adverse events, as well as those from VGB-steroid combination. According to our data, a period of 7 days seems sufficient to assess VGB response and enables the addition of steroids rapidly if needed. Continuing VGB for 2 years may balance the risk of relapse and treatment-induced adverse events.

Risk of stroke within 3, 7, 14, 21 and 30 days after influenza vaccination in Alberta, Canada: A population-based study.

Influenza vaccination is associated with a longer-term protective effect against stroke; however, it has a short-term inflammatory response which may increase short-term risk of stroke. The aim was to investigate the association between influenza vaccination and short-term risk of stroke in adults. Administrative data were obtained from the Alberta Health Care Insurance Plan for all adults in Alberta, Canada, from September 2009 to December 2018. The hazard of any stroke (acute ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage and transient ischaemic attack) within 3, 7, 14, 21 and 30 days of influenza vaccination compared to unexposed time was analysed using Andersen-Gill Cox models, with adjustment for age, sex, anticoagulant use, atrial fibrillation, chronic obstructive pulmonary disease, diabetes, hypertension, income quintile, and rural or urban home location. In the entire cohort consisting of 4,141,209 adults (29,687,899 person-years), 1,769,565 (42.7%) individuals received at least one vaccination. In total 38,126 stroke events were recorded with 1309 occurring within 30 days of a vaccination event. Influenza vaccination was associated with a significantly reduced hazard of stroke within 3 days (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.73-0.93), 7 days (HR 0.87, 95% CI 0.80-0.95), 14 days (HR 0.87, 95% CI 0.81-0.93), 21 days (HR 0.85, 95% CI 0.80-0.91) and 30 days (HR 0.66, 95% CI 0.65-0.68). An increased early risk associated with vaccination was not observed. The risk of stroke was reduced at all time points within 30 days after influenza vaccination.

Learning from adversity: Small-scale commercial farming in Nepal amidst COVID-19 pandemic

The COVID-19 pandemic has exposed various shortcomings in Nepal’s small-scale commercial farming system. Farmers who were transitioning from subsistence to a market-dependent model faced significant challenges during the pandemic. This has raised concerns about the well-being of these farmers, the sustainability of their farming practices, and their capacity to withstand future shocks. Our paper aims to assess the current resilience of small commercial farmers and identify factors that can enhance their ability to weather external disruptions like COVID-19. We use the case study in Ravi Opi, a farming village located in Dhulikhel Municipality, Nepal to explore the challenges experienced by the small commercial farmers during the pandemic and the strategic responses adopted at the household and institutional levels. Our analysis reveals that the small-scale commercial farming system demonstrated ‘buffering capabilities’ and ‘adaptability,’ but not ‘transformability.’ This is primarily because farmers adopted short-term responses that are necessary for addressing immediate crises, rather than responses that would facilitate longer-term transformation. We argue that there is a lack of adequate state support for farmers in Nepal, which worsened during the pandemic. As a result, farmers resorted to leveraging their community connections for help, which provided short-term relief, and aided in addressing only immediate but not their long-term needs. Our observations underscore the risks associated with the current approach used by subsistence farmers to transition into commercial farming. Based on our findings, we propose that longer-term initiatives involving the government and other stakeholders are essential to strengthen the supply network and promote community-based agriculture extension services. We posit that these initiatives can potentially enhance farmers’ resilience and their ability to withstand future disruptions, such as the COVID-19 pandemic.

Site matters - Canopy conductance regulation in mature temperate trees diverges at two sites with contrasting soil water availability

Tree-specific canopy conductance (Gc) and its adjustment play a critical role in mitigating excess water loss in changing environmental conditions. However, the change of Gc sensitivity to environmental conditions due to drought remains unclear for European tree species. Here we quantified the environmental operational space of Gc, i.e., the water supply (soil moisture, tree water deficit) and demand conditions (vapor pressure deficit) under which Gc ≥ 50% is possible (Gc50OS), at two sites with different soil water availability for three common European tree species. We collected sap flow and dendrometer measurements for co-occurring Pinus sylvestris, Fagus sylvatica and Quercus petraea growing under different soil hydrological conditions (drier/wetter). These measurements were combined with meteorological variables and soil moisture conditions in five depths. Dendrometer measurements were used to confirm soil water availability patterns. For all analyses, the contrasting soil hydrology between sites was the main driver of Gc response. At the drier sites, F. sylvatica and P. sylvestris reduced their water consumption in response to decreasing soil water supply earlier in the growing season than Q. petraea. However, our analysis on the Gc50OS revealed that at the drier sites, F. sylvatica and Q. petraea reduced the extent of their Gc50OS to a higher degree than P. sylvestris. This indicates a higher level of Gc50OS adjustment to the drier site conditions for the two broadleaved species. These differences were more pronounced when using the dendrometer-derived tree internal water status as proxy for tree water supply. Our results provide preliminary evidence for diverging short-term Gc responses when temperate trees are exposed to prolonged reduction in water availability. These findings suggest that Gc50OS can help to constrain species-specific predictions of water use by mature trees, especially when combined with high-resolution water potential measurements.

Tar pollution event (2021) at the Southeastern Levantine oligotrophic basin, short-term impacts and operational oceanography perspectives

The Levantine basin (LB) in the Southeastern Mediterranean Sea is a high-risk oil pollution hot spot owing to its dense maritime traffic and intense oil and gas exploration and exploitation activities. In February 2021 the Israeli LB shorelines were impacted by an exceptional tar pollution event (~550 tons; average distribution: ~3 kg tar m−1 front beach) of an unknown oil spill source. Here we report on the immediate numerical modelling assessment of the oil spill propagation and tar distribution; operational use of underwater gliders for tracking water column anomalies of dissolved polycyclic aromatic hydrocarbons (PAHs) and turbidity signals; the beached tar composition and amounts and the short-term response of the microbial population along the ~180 km shoreline. This pollution event emphasizes the need for improving the early warning systems for oil spills and implementing continuous operational monitoring at high-risk, ecologically sensitive and valuable resource areas like the Israeli LB waters.

Short-term responses of meat ewes facing an acute nutritional challenge in early-mid lactation.

Simulating a consequence of a climate change event on feed availability, responses of Mediterranean meat ewes facing an acute undernutritional challenge (CHA; i.e., fed only low nutritional value cereal straw) were evaluated at a sensitive physiological stage (i.e., early suckling). Forty Romane ewes were chosen at early-mid pregnancy (around 2 mo) according to parity (20 primiparous, PRIM; 20 multiparous, MULT); feed efficiency genetic line of their sires (residual feed intake [RFI]; efficient, RFI-, n = 10 per parity; inefficient, RFI+, n = 10 per parity); litter size (i.e., bearing twins, diagnosed by ultrasonography); body weight (BW, kg) and body condition score (BCS) (initial BW and BCS [mean ± SD]: 51.6 ± 7.41kg; 2.5 ± 0.20, respectively; representing flock' averages per parity). Effects on dry matter intake (DMI), ewes' BW and BCS, subcutaneous dorsal fat thickness (DFT), energy metabolism (plasma non-esterified fatty acids [NEFA], β-hydroxybutyrate (β-OHB), glucose, urea, triiodothyronine [T3]), and lambs' growth (BW and average daily gain [ADG]; g/d) were examined before, during and after CHA. Individuals' profiles of the response-recovery to CHA were described using a piecewise mixed-effects model. The fixed effect of parity and genetic line and the random effect of individual (ewe) were considered. A linear mixed-effects model was fitted to explore the effects on lambs' growth. The 2-d straw-only CHA had significant effects on most of the recorded parameters. Meaningful drops and recoveries were observed on ewes' DMI, BW, and DFT with effect on postchallenge levels. BW, BCS, DFT, or DMI were also affected by parity (MULT > PRIM) but not by genetic line. Plasma NEFA, β-OHB, glucose, urea, and T3 responded well to CHA with drops in T3, urea, and glucose levels, whereas NEFA and β-OHB significantly increased after CHA. MULT ewes presented sharper β-OHB recovery from CHA than PRIM (P ≤ 0.05). With this study, we provide tangible and necessary data for an emerging field of research. Our results give new insights into how such a short and abrupt CHA affects some key zootechnical and physiological parameters, and to what extent the impacts of CHA and the ewes' response-recovery are influenced. It also revealed potential between-individual differences in the adaptive capacities of ewes, which require further exploration.

Between short-term and medium-to-long-term responses: mapping the impact of COVID-19 on Italian universities

ABSTRACTThis paper presents an empirical analysis that maps the short-term and middle-to-long-term responses of Italian universities to the COVID-19 crisis by focussing on teaching activities. A representative sample of eighteen public universities was analysed to evaluate how they planned their teaching activities for the 2020–21 and 2021/2022 academic years and whether and how the pandemic pushed them to change their strategic plans for the following year. Based on a specific survey, an in-depth analysis of documents, and interviews, the findings reveal very similar short-term responses but three different types of medium-to-long-term responses: rebounding, proactive, and innovative. This empirical evidence indicates that scholars in higher education should heed the ways in which universities react and adapt in turbulent times when they have to make decisions under conditions of high uncertainty and recognize when crises can also become opportunities for change.

An innovative method for measuring the hysteresis effects of soil moisture on meteorological variables at various time scales and climate conditions

ABSTRACTUnderstanding the feedback and reactions of soil moisture to meteorological factors in meteorological-hydrological processes is essential due to the growing importance of soil moisture in energy and water cycles in critical zones. Using soil moisture and meteorological data from 1984 to 2018, based on Mann-Kendall and Sen slope trend, two possible patterns of land–atmosphere interaction were discovered in the Yangtze River Basin (YRB), low soil moisture model with less precipitation and higher evapotranspiration, and high-temperature mode with less soil moisture and less evapotranspiration. To measure the hysteresis between soil moisture and precipitation, temperature, and evapotranspiration, a novel method named Three-Step Method was put out. The lag times were measured at ground stations spread across various climatic zones and timescales. The findings demonstrated that the lag times are generally controlled by the regional climate, with shorter lag times in drier regions. Both long-term and short-term responses were seen in soil moisture to meteorological variables. On a monthly scale, soil moisture correlated positively with precipitation but negatively with temperature and evapotranspiration. On an annual scale, precipitation (temperature, evapotranspiration) lagged by roughly 0 to 2 months in the upper and middle regions and by －2 to －6 months in the lower region of the YRB. The contribution rates of meteorological elements on soil moisture were enhanced by taking lag time into account. This study provides a unique perspective for better understanding climate process forecasts and related drought management by considering the hysteresis of soil moisture on the feedback and responses of climate variables.

Prognostic value of Hematoxylin and eosin staining tumor-infiltrating lymphocytes (H&E-TILs) in patients with esophageal squamous cell carcinoma treated with chemoradiotherapy

BackgroundTumor-infiltrating lymphocytes (TILs) by routine hematoxylin and eosin staining (H&E-TILs) are a robust prognostic biomarker in various cancers. However, the role of H&E-TILs in esophageal squamous cell carcinoma (ESCC) treated with concurrent chemoradiotherapy (CCRT) has not been reported. The purpose of this study was to assess the prognostic value of H&E-TILs in ESCC treated with CCRT.MethodsThe clinical data of 160 patients with ESCC treated with CCRT in our center between Jan. 2014 and Dec. 2021 were collected and retrospectively reviewed, and propensity score matching (PSM) analyses were performed. The H&E-TILs sections before CCRT were reassessed by two experienced pathologists independently. The H&E-TILs sections were classified into a positive group (+, > 10%) and a negative group (-, ≤ 10%) using 10% as the cutoff. The effects of H&E-TILs on overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS) were explored using the Kaplan‒Meier method, and the log-rank test was used to test the differences. Multivariable analysis was performed using the Cox proportion hazards model.ResultsThe short-term response to CCRT and the OS (P < 0.001), DMFS (P = 0.001), and LRFS (P < 0.001) rates were significantly different between the H&E-TILs (+) and H&E-TILs (-) groups. Subgroup analysis showed that H&E-TILs(+) with CR + PR group had a longer survival than H&E-TILs(-) with CR + PR, H&E-TILs(+) with SD + PD and H&E-TILs(-) with SD + PD group, respectively(P < 0.001). Furthermore, based on TCGA data, patients in the high TILs group had a better prognosis than those in the low TILs group. Multivariate analyses indicated that H&E-TILs and the short-term response to CCRT were the only two independent factors affecting OS, PFS, DMFS, and LRFS simultaneously, and H&E-TILs expression was associated with an even better prognosis for those patients with CR + PR.ConclusionsH&E-TILs may be an effective and beneficial prognostic biomarker for ESCC patients treated with CCRT. Patients with H&E-TILs (+) with PR + CR would achieve excellent survival. Further prospective studies are required to validate the conclusions.

Intermittent normobaric hypoxia alters substrate partitioning and muscle oxygenation in individuals with obesity: implications for fat burning.

This single-blind, crossover study aimed to measure and evaluate the short-term metabolic responses to continuous and intermittent hypoxic patterns in individuals with obesity. Indirect calorimetry was used to quantify changes in resting metabolic rate (RMR), carbohydrate (CHOox, %CHO), and fat oxidation (FATox, %FAT) in nine individuals with obesity pre and post: 1) breathing normoxic air [normoxic sham control (NS-control)], 2) breathing continuous hypoxia (CH), or 3) breathing intermittent hypoxia (IH). A mean peripheral oxygen saturation ([Formula: see text]) of 80-85% was achieved over a total of 45 min of hypoxia. Throughout each intervention, pulmonary gas exchanges, oxygen consumption (V̇o2) carbon dioxide production (V̇co2), and deoxyhemoglobin concentration (Δ[HHb]) in the vastus lateralis were measured. Both RMR and CHOox measured pre- and postinterventions were unchanged following each treatment: NS-control, CH, or IH (all P > 0.05). Conversely, a significant increase in FATox was evident between pre- and post-IH (+44%, P = 0.048). Although the mean Δ[HHb] values significantly increased during both IH and CH (P < 0.05), the greatest zenith of Δ[HHb] was achieved in IH compared with CH (P = 0.002). Furthermore, there was a positive correlation between Δ[HHb] and the shift in FATox measured pre- and postintervention. It is suggested that during IH, the increased bouts of muscle hypoxia, revealed by elevated Δ[HHb], coupled with cyclic periods of excess posthypoxia oxygen consumption (EPHOC, inherent to the intermittent pattern) played a significant role in driving the increase in FATox post-IH.

‘It’s about mindset’. How do young migrants in Poland build their resilience?

ABSTRACT The aim of this article is to investigate how young migrants’ resilience manifests in different spheres of their lives. Adapting the Keck and Sakdapolrak's framework, we define resilience as being comprised of coping, adaptive and transformative capacities. While coping capacities are a post-crisis short-term response, adaptive and transformation capacities encompass more proactive and long-term planning. Drawing on interviews with young Third Country Nationals living in Poland, conducted within the framework of H2020 project MIMY, we analyse how the different types of resilience capacities intersect with different areas of integration. We also highlight that resilience is not only the ability to bounce back, but also the power to bounce forward, which implies the capacity to transform individual lives and their environments. Interestingly, in young migrants’ narratives their personal resources, such as a positive mindset, persistence etc. play a crucial role. While community resources (family support and social capital) were mentioned, structural opportunities were largely absent in their narratives on resilience. Therefore, we can talk about a process of (self-)responsibilization of migrants for integration, which relates to the neoliberal discourse on newcomers’ self-reliance.

Short-Term Efficacy of Combination Therapy with Recombinant Human Thrombopoietin (rh-TPO) and Thrombopoietin Receptor Agonists (TPO-Ra) in Patients with Severe Immune Thrombocytopenia

Introduction: Bleeding manifestations in patients with immune thrombocytopenia (ITP) range from mild skin bruises to lifethreatening intracranial hemorrhage. When the risk of bleeding is becoming high or life-threatening bleeding events occurs, we often use a combination of therapies to rapidly raise platelets to the safe range, including platelet transfusions, high-dose glucocorticoid, and intravenous immunoglobulins. Recombinant human thrombopoietin (rh-TPO) and thrombopoietin receptor agonists (TPO-Ra) are two kinds of thrombopoietic drugs commonly used in China. In patients with severe ITP refractory to glucocorticoids, we lack experience with the use of rh-TPO and TPO-Ra in this emergency situation. Patients and methods： We included ITP patients with platelets &amp;lt;10*10 9/L and bleeding symptoms requiring treatment, who were refractory to glucocorticoids and used thrombopoietic drugs. The bleeding score was calculated with reference to the Chinese guidelines for adult ITP. The patients were divided into three groups according to the medication used: rh-TPO group(rh-TPO 30000IU Qd), TPO-Ra group(Eltrombopag 25mg-75mg/d or Avatrombopag 2.5mg-7.5mg/d or Hetrombopagolamine 20mg-60mg/d), and rh-TPO+TPO-Ra group(combination of two drugs at the same dosage). The platelet count should be rechecked every 1-2 days during the treatment. Platelet transfusion and hemostatic drugs can be used as needed. According to the standardized and international criteria, and taking into account the characteristics of this study, platelet counts were classified as short-term Complete Response(sCR), short-term Response(sR), and short-term No Response (sNR), based on the highest value of platelet counts from the start of treatment to the time of hospital discharge, short-term Overall Response(sOR)=sCR+sR. The three groups were compared the effective time(defined as the time to first sCR/sR after treatment) , peak platelet count after treatment, time to peak platelet count after treatment and other short-term efficacy indicators. Results Nineteen patients were include in this study, with 68.4% (13/19) was female. The median age was 58 years [range 17-79]. 15.8%(3/19) were newly diagnosed with ITP, 10.5%(2/19) had persistent ITP, and 73.7%(14/19) had chronic ITP. All patients were treated with glucocorticoids prior to this treatment, but they had a poor response. The median platelet count was 3*10 9/L [range 1-9] and the median bleeding score was 4 [range 2-9] before treatment. The common bleeding sites were skin ecchymosis and oral mucous membrane hemorrhage in 100%(19/19)and 47.3%(9/19), respectively. Severe bleeding symptoms were the manifestation in 3 cases: including 2 heavy menstrual flow and 1 hemoptysis and gastrointestinal. 100%(19/19) achieved a sOR and 31.6%(6/19) achieved a sCR. The median bleeding score was 0[0-2] after treatment and none had active bleeding symptoms. Platelet transfusion and hemostatic drugs were administered to all patients. Further details are provided in Table 1. Among 19 patients, 7(36.8%) used rh-TPO alone, 6(31.6%) TPO-Ra alone and 6(31.6%) used rh-TPO+TPO-Ra. There was no statistically significant difference in Clinical characteristics, including ages, gender, platelet counts and bleeding score among the three groups of patients before treatment (P=0.727, 0.594, 0.719, 0.299). In terms of treatment efficacy, we were unable to perform a statistical analysis of sOR rates because all three groups reached 100%. The sCR and the peak platelet count after treatment of rhTPO+TPO-Ra group was higher than the other two groups, 28.6%(2/7), 16.7%(1/6) and 50%(3/6) of patients achieved sCR respectively, the peak platelet counts after treatment in the three groups were 62*10 9/L, 72*10 9/L, 79.5*10 9/L respectively in this treatment, but there was no statistically significant difference (P=0.425，0.924). In addition, the effective time and time to peak platelet count after treatment of the three group are also no statistically significant difference(p=0.692,0.505). Further details are provided in Table 2. Conclusion This retrospective study suggests that the patients with severe ITP who were refractory to glucocorticoids, the use of rh-TPO and TPO-Ra may rapidly increase to safe ranges, but the combination is not necessary.

The Evolutionary Complexities of DNA Methylation in Animals: From Plasticity to Genetic Evolution.

The importance of DNA methylation in plastic responses to environmental change and evolutionary dynamics is increasingly recognized. Here, we provide a Perspective piece on the diverse roles of DNA methylation on broad evolutionary timescales, including (i) short-term transient acclimation, (ii) stable phenotypic evolution, and (iii) genomic evolution. We show that epigenetic responses vary along a continuum, ranging from short-term acclimatory responses in variable environments within a generation to long-term modifications in populations and species. DNA methylation thus unlocks additional potential for organisms to rapidly acclimate to their environment over short timeframes. If these changes affect fitness, they can circumvent the need for adaptive changes at the genome level. However, methylation has a complex reciprocal relationship with genetic variation as it can be genetically controlled, yet it can also induce point mutations and contribute to genomic evolution. When habitats remain constant over many generations, or populations are separated across habitats, initially plastic phenotypes can become hardwired through epigenetically facilitated mutagenesis. It remains unclear under what circumstances plasticity contributes to evolutionary outcomes, and when plastic changes will become permanently encoded into genotype. We highlight how studies investigating the evolution of epigenetic plasticity need to carefully consider how plasticity in methylation state could evolve among different evolutionary scenarios, the possible phenotypic outcomes, its effects on genomic evolution, and the proximate energetic and ultimate fitness costs of methylation. We argue that accumulating evidence suggests that DNA methylation can contribute toward evolution on various timescales, spanning a continuum from acclimatory plasticity to genomic evolution.

Digital PCR Assay for Evaluation of CD19-CAR-T Cells In Vivo Expansion in Aggressive B-Cell Lymphoma: Impact on Clinical Outcome

Background: Chimeric antigen receptor (CAR)-T cells therapy has revolutionized hematological treatment mainly in non-Hodgkin lymphoma (NHL) demonstrating unprecedented clinical responses when directed against CD19 combining the antigen-binding properties of antibodies with the effector functions of T cells. In particular, CAR-T cell peak concentrations and area under the curve in the first 28 days after Axicabtagene Ciloleucel (Axi-cel) infusion have been associated with long-term efficacy. Based on a digital PCR assay for sensitive CAR-T cells detection, we aimed to detect the CAR-T product in patients (pts) and associate its kinetics with patient outcome. Methods: A retrospective analysis was conducted involving 28 patients diagnosed with NHL treated with Axi-cel CAR-T products (2019-2023) in the Department of Hematology of the Clinical University Hospital of Valencia, Spain according to the Declaration of Helsinki ethical criteria. 97 peripheral blood mononuclear cell (PBMC) DNA samples were extracted from 3-12 ml EDTA tubes. We performed serial measurements of CAR-T-cell blood levels (7,14, 28 days post-infusion) using a newly developed axi-cel-specific dPCR assay (Bio-Rad,USA) with QIAcuity Digital PCR System and QIAcuitySoftware for data analysis (QIAGEN, Germany). The peak CAR-T-cell blood concentrations (CAR-T-Cmax) and the cumulative CAR-T-cell levels over the first 28 days in PB by area under the curve (AUC CAR-T) were calculated based on CAR-T dPCR values (copies/μL). Response assessment was performed per institutional practice and based on Lugano Criteria. Statistical analyses were performed using SPSS Software (IBM, Germany, v.22). Logistic regression was used to evaluate the relationship between covariate and outcome. Kruskal-Wallis and Dunn's tests were used when 3 subgroups were involved. Survival analyses were conducted according to CAR-T dPCR values. Results: A total of 28 pts (16 [57.1%] females) who received CAR-T cell therapy were included [25 (89%) DLBCL; 3 (11%) PMBCL]. The patient's best overall response assignment (partial or complete) were observed in twenty-two (78,4%) named as responders (R), otherwise six (21,4%) nonresponders (NR) around day 30 of evaluation. CAR-T-CMax ranged from 2.30 to 176.10 (median, 40.16) CAR-T copies/μL, 7 days later of majority expansion day post infusion: R pts had a higher peak expansion of 66.38 copies/µL compared to 32.43 copies/µL although this difference did not reach statistical significance ( p=018). Expansión was faster in R pts (median 7.64 days pot-infusion) versus NR pts (median 12.83, p=0,10) . Quantitative 7-d CAR-T copies/μL, and AUC value from days 0 to 7, showed statistical significance differences post-infusion between R and NR (52.08±32.48 vs 15.51±20.51, p&amp;lt;0.005; 3603.88±2520.02 vs 1291.74±1948.77, p&amp;lt;0.037). As for response assessment, 7-d CAR-T values were able to successfully predict the development of NR pts with an area under the curve of 0.841 (CI 95% 0.66-1.00), a sensitivity of 0.950 and a specificity of 0.625 (Fig 1.). Eleven pts (39.3%) died at a median of 3.6 months (1.7-6.1 months) post-infusion. For survival analyses, a cut-off value of 18.35 7-d CAR-T copies/μL that maximized the Log-Rank statistic, was selected to divide pts into R and NR categories. Median overall survival (OS) was 23.9 [16.3-NA, 95% CI] months and 13.2 [3.30-3.96, 95% CI] months for R and NR according to CAR-T copies/μL 7 days, respectively (Fig.2). Conclusions: Digital PCR for CAR-T evaluation shows that quantitative CAR-T copies/μL could be a potential predictor of short-term response and survival at first 7 days post-infusion value in pts with DLBCL or PMBCL treated with CAR-T cell therapy.

Predictors of short-term response and the role of heavy alcohol use in treatment of depression

BackgroundDepression and alcohol use disorders frequently co-occur. However, research on psychosocial interventions for treating this dual pathology is limited. The Ostrobothnian Depression Study (ODS) aimed to increase the systematic use of evidence-based methods, particularly among patients with comorbid depression and substance use in a naturalistic setting. This is a secondary analysis of the ODS study. The aim of the present study was to explore the predictors of a response to treatment during the first six months of the ODS intervention with a specific focus on the role of comorbid heavy alcohol use.MethodsThe study sample (n = 242) comprised psychiatric specialist care patients with depression (Beck Depression Inventory score ≥ 17) at baseline. Patients with a baseline Alcohol Use Disorders Identification Test (AUDIT) score > 10 (n = 99) were assigned to the AUD (Alcohol Use Disorder) group in this study. The ODS intervention comprised behavioral activation (BA) for all and additional motivational interviewing (MI) for those in AUD group. The predictors of response to treatment (minimum of 50% reduction in depressive symptoms) during the first six months were analyzed with logistic regression models.ResultsIn the total sample at six months (n = 150), predictors of response to treatment were more severe depression (OR 1.10, CI 1.02–1.18), larger amounts of alcohol consumed (OR = 1.16, CI 1.03–1.31) and antipsychotic medication “not in use” (OR = 0.17, CI 0.07–0.44). In the non-AUD group (n = 100), more severe depression (OR 1.12, CI 1.01–1.25) and antipsychotics “not in use” (OR 0.20, CI 0.06–0.67) also predicted a positive response. Among AUD group patients (n = 50), larger amounts of alcohol consumed (OR 1.54, CI 1.04–2.27) and antipsychotic medication “not in use” (OR 0.12, CI 0.02–0.60) predicted a response to the treatment intervention.ConclusionsThe severity of symptoms and comorbid disorders were found to predict better treatment response, suggesting that the intervention was more effective in patients with severe symptoms. Patients with depression should be treated effectively regardless of having concomitant AUD. The results of this study suggest that BA combined with MI should be one of the treatment options for this dual pathology.Trial registrationClinicalTrials.gov Identifier NCT02520271 (11/08/2015).

Long-term extreme responses of torsional moments at two-directional hinges for moored very large floating structures

This paper presents an analysis procedure for estimating long-term extreme torsional moments at connections of very large floating structures (VLFS) with two-directional hinges and mooring lines under random waves. This procedure, compared to the common short-term estimation method, can accurately and quickly calculate the extreme response at a certain return period. Applying a coupled frequency-time domain approach, we simulate the hydroelastic response of VLFS with two-directional hinges and vertical mooring lines. In order to validate the proposed approach, numerical simulations are firstly carried out under the action of regular waves. The present approach demonstrates a high level of consistency with experimental data and numerical results from existing studies in terms of vertical displacement, bending moment and shear force. Then, on the basis of the short-term extreme response distribution and environmental model, a procedure for solving long-term extreme responses of the structure is introduced. The long-term extreme response characteristics of the torsional moment at hinges are evaluated and studied in depth using the procedure, providing a reference for the structural design of moored VLFS with two-directional hinges.

A miR-137–Related Biological Pathway of Risk for Schizophrenia Is Associated With Human Brain Emotion Processing

BackgroundmiR-137 is a microRNA involved in brain development, regulating neurogenesis and neuronal maturation. Genome-wide association studies have implicated miR-137 in schizophrenia risk but do not explain its involvement in brain function and underlying biology. Polygenic risk for schizophrenia mediated by miR-137 targets is associated with working memory, although other evidence points to emotion processing. We characterized the functional brain correlates of miR-137 target genes associated with schizophrenia while disentangling previously reported associations of miR-137 targets with working memory and emotion processing. MethodsUsing RNA sequencing data from postmortem prefrontal cortex (N = 522), we identified a coexpression gene set enriched for miR-137 targets and schizophrenia risk genes. We validated the relationship of this set to miR-137 in vitro by manipulating miR-137 expression in neuroblastoma cells. We translated this gene set into polygenic scores of coexpression prediction and associated them with functional magnetic resonance imaging activation in healthy volunteers (n1 = 214; n2 = 136; n3 = 2075; n4 = 1800) and with short-term treatment response in patients with schizophrenia (N = 427). ResultsIn 4652 human participants, we found that 1) schizophrenia risk genes were coexpressed in a biologically validated set enriched for miR-137 targets; 2) increased expression of miR-137 target risk genes was mediated by low prefrontal miR-137 expression; 3) alleles that predict greater gene set coexpression were associated with greater prefrontal activation during emotion processing in 3 independent healthy cohorts (n1, n2, n3) in interaction with age (n4); and 4) these alleles predicted less improvement in negative symptoms following antipsychotic treatment in patients with schizophrenia. ConclusionsThe functional translation of miR-137 target gene expression linked with schizophrenia involves the neural substrates of emotion processing.