Variation In Response Research Articles

Help, Teach, Counsel: How Terminology Changes in the ProQOL-5 Impact Score Reliability

Objective: This study evaluated score reliability of the Professional Quality of Life Scale (ProQoL) when contextualizing help to a relevant derivative. Method: The researchers evaluated score reliability across three datasets among school-based professionals (n = 122), teachers (n = 216), and mental health professionals (n = 543) using Cronbach’s alpha, McDonald’s omega, inter-item correlations and visual analysis. Results: Score reliability was acceptable across samples. However, item analysis indicated variability in responses indicating participants’ extracting different meaning or relevance to the items. Terminology changes may extract different meaning based on profession resulting in measurement error. Conclusions: Findings highlight use of one-word derivative changes to items may impact score reliability based on the professional activities represented. Researchers should adjust item terminology for clarity and relevance to all the professions represented in the sample. Evidence of the nature of professional activities with client or student trauma to secondary traumatic stress is presented.

Highly heterogenous humoral immune response in Lyme disease patients revealed by broad machine learning-assisted antibody binding profiling with random peptide arrays.

Lyme disease (LD), a rapidly growing public health problem in the US, represents a formidable challenge due to the lack of detailed understanding about how the human immune system responds to its pathogen, the Borrelia burgdorferi bacterium. Despite significant advances in gaining deeper insight into mechanisms the pathogen uses to evade immune response, substantial gaps remain. As a result, molecular tools for the disease diagnosis are lacking with the currently available tests showing poor performance. High interpersonal variability in immune response combined with the ability of the pathogen to use a number of immune evasive tactics have been implicated as underlying factors for the limited test performance. This study was designed to perform a broad profiling of the entire repertoire of circulating antibodies in human sera at the single-individual level using planar arrays of short linear peptides with random sequences. The peptides sample sparsely, but uniformly the entire combinatorial sequence space of the same length peptides for profiling the humoral immune response to a B.burg. infection and compare them with other diseases with etiology similar to LD and healthy controls. The study revealed substantial variability in antibody binding profiles between individual LD patients even to the same antigen (VlsE protein) and strong similarity between individuals diagnosed with Lyme disease and healthy controls from the areas endemic to LD suggesting a high prevalence of seropositivity in endemic healthy control. This work demonstrates the utility of the approach as a valuable analytical tool for agnostic profiling of humoral immune response to a pathogen.

Diabetic Macular Edema Management: A Review of Anti-Vascular Endothelial Growth Factor (VEGF) Therapies.

Diabetic macular edema (DME) is a major cause of vision impairment in diabetic individuals, characterized by fluid accumulation in the macula due to a breakdown of the blood-retinal barrier (BRB). This review article explores the role of anti-vascular endothelial growth factor (anti-VEGF) therapies in the management of DME. Anti-VEGF treatments, including ranibizumab, bevacizumab, and aflibercept, have revolutionized DME management by targeting VEGF, a key mediator in DME pathogenesis. We critically examined the efficacy of these therapies in reducing macular edema and improving visual acuity, assessed their safety and tolerability, and explored the variability in treatment response. The review highlights the latest advancements and future directions in anti-VEGF therapy, including novel drug delivery systems and emerging treatment paradigms. By providing a comprehensive overview of current anti-VEGF therapies, this review seeks to inform clinical practice, guide future research, and contribute to improved patient outcomes in DME management.

Tumoral microbial and pathway alterations associated with young-onset rectal cancer and its response to therapy.

160 Background: Given the increasing incidence of young onset rectal cancer (YORC) in recent decades, we examined the potential of tumor and fecal microbiome pathways in YORCs as compared to late-onset rectal cancers (LORCs) while also exploring markers of response to neoadjuvant therapy (NAT). We hypothesize microbial markers reflect unique and potentially causative biology in YORC, and variability in response to NAT. Methods: Treatment-naïve patients with YO- (<50 years old) or LO- ≥50 years old) rectal cancers were prospectively enrolled. Tumor and tumor-adjacent normal tissues (TANs) were collected via endoscopic biopsy, as well as stool at baseline. After whole genome sequencing, metagenomic analysis was performed using MetaPhlAn4, VirMAP and HUMAnN3 for taxonomical and metabolomic profiling. Association of microbial and immune signatures were examined comparing tumors vs. TANs, and YO- vs. LORC tumors. Differential abundance analyses were performed using paired Wilcoxon test and MaAsLin2. Molecular subtype defined for tissues with whole transcriptomic sequencing available. Results: 162 tumors and paired normal tissues, 73 (45.1%) YO- and 89 (54.9%) LORC were analyzed. Additional whole transcriptomic sequencing was available for 88 patients. The majority 145 (89.5%) of patients received neoadjuvant therapy. Observed bacterial diversity was higher in tumors as compared to tumor associated normal (TAN) tissue (p<0.001). Moreover, bacterial diversity also increased linearly with age of diagnosis in tumors (p=0.01), but not TAN (p=NS). Oral bacteria previously associated with colorectal cancer were noted in these rectal cancers including Fusobacterium nucleatum (q<0.001) and Parvimonas micra (q<0.001). Escherichia coli, previously associated with colorectal cancer and development of metastatic disease was associated with YORC (q<0.001) but not LORC. For NAT treated patients, major pathologic response in YORC was associated with higher bacterial diversity (p=0.03) but not in LORC (p=NS). Similarly, no significant bacterial marker of response to neoadjuvant therapy was noted in LORC. While Butyricimonas virosa (q<0.001), Alistipes shahi (q=0.01), and Parabacteroides merdae (q=0.01) were all associated with a diminished pathologic response. Conclusions: Oral bacterial signatures previously associated with colorectal cancer were noted in both YORC and LORC when comparing matched tumor and TAN. Importantly, several unique bacterial associations were identified with YORC, including Escherichia Coli – previously associated with development of metastases in CRC. We also noted distinct microbial associations related to response to therapy in YORC suggesting the unique biology of these tumors. Functional bacterial pathway associations with response suggest a potential to augment NAT with existing or next-generation microbial modulation strategies.

Molecular and genetic predictors of ovarian response in vitro fertilization programs

The most effective method of treating infertility is in vitro fertilization, the key element of which is ovarian stimulation. Ovarian response in IVF protocols has varying variability among patients. The ovarian response depends on many factors, but none of these factors has sufficient prognostic ability, and therefore the question of the individual ovarian response during stimulation in IVF programs still remains open, and the association of the ovarian response with polymorphisms of certain genes is being actively studied. The most effective IVF programs are observed among patients of young reproductive age. A decrease in the effectiveness of IVF programs and the appearance of complications is observed in patients of advanced reproductive age. Several types of ovarian response have been identified: poor (it is possible to obtain 3 oocytes), normal (from 4 to 15 oocytes), suboptimal response (less than 7 oocytes) and hyperergic response (more than 15 oocytes). Also, there is a group of patients of various age groups with a paradoxical ovarian response to stimulation. The response of oocytes to hormones can be regulated depending on the expression of receptor genes. FSH receptor (FSHR) polymorphism may explain interindividual variability in ovarian response to stimulation. Genetic screening is determined once and does not depend on endogenous and exogenous factors, while allowing you to adjust the dose of gonadotropins in ovarian stimulation protocols. This review presents current data on the polymorphism of the main genes that regulate the ovarian response in stimulating superovulation in in vitro fertilization programs.

Life-cycle performance of aluminium cladding panels in resisting hailstorms

This paper delves into cumulative damage on aluminium cladding panels attributed to hailstorms throughout the lifespan of the installations. 40 gas gun tests subjecting the cladding panel to repeated impact were undertaken for the purpose of studying cumulative damage behaviour. Insights from these tests were integrated into a hail size distribution model to characterise the probabilistic distribution of permanent indentation resulted from multiple hailstorm events. A life-cycle analysis framework was subsequently introduced, incorporating the natural variability of hailstone sizes and dynamic response of claddings to repeated ice impact. Intervention criterion can be established based on knowledge of the accumulation of permanent indentation into the cladding panels. Proactive actions are recommended should the indentations become visible to prevent worsening damage. Randomness of hailstorm occurrences was considered using hazard function which can be inferred from historical observations. Practical application of the proposed model is illustrated through case studies of two Australian states, coupled with comparative analyses highlighting key factors influencing cladding performance. The ability to account for stochasticity distinguishes the presented framework from existing deterministic approaches.

Impact of soil and water conservation structures on the spatial variability of topsoil moisture content and crop productivity in semi-arid Ethiopia

Plant available soil moisture and its spatial variability is among the most important limiting factors for crop and livestock productivity in semi-arid Ethiopia. The objectives of this study were therefore: 1) to measure the effects of land use and slope gradient on spatial variability of topsoil moisture content. 2) to analyze the variability of topsoil moisture content and crop responses under different soil and water conservation (SWC) structures and 3) to analyze whether topsoil moisture content, grain and biomass yields vary in relation to SWC structures. In total, 21 large runoff plots (600–1000 m2) were installed and treated with stone bunds, trenches, stone bunds with trenches and a control plot at each site. Plot sites were located on gentle (5%), medium (12%) and steep (16%) slopes of cropland and rangeland. Topsoil (0–15 cm) moisture content for plots were monitored daily using soil moisture probes (Theta-Probes) and weekly using manual sampling over two growing seasons. Crop performance was monitored during two growing seasons and grain and biomass yield were measured at harvest. Results show that average gravimetric moisture content of the topsoil during growing seasons is remarkably higher for cropland (33–25 g/100 g) compared to rangelands (24–20 g/100 g). This is due to tillage-induced runoff retention and infiltration. Soil moisture content decreases with increasing slope gradients, owing to increased drainage. Considering the effects of SWC structures, average topsoil moisture contents at accumulation and erosion zones are generally higher as compared to middle zone between two successive SWC structures. Average seasonal volumetric soil moisture content of 38.2 (cm3/100 cm3) in 2011 and 39.4 (cm3/100 cm3) in 2012 for accumulation zone of plots with stone bunds with trenchers are significantly higher than at other sampling locations. Crop growth performance, grain and biomass yield varied among plots and depended on slope gradients and SWC structures. Grain yields of wheat in 2011 and barley in 2012 were significantly higher for plots with SWC structures as compared to control plots and are highly correlated to topsoil moisture content (r = 0.64; p < 0.04 in 2011 and r = 0.59, p < 0.01 in 2012). Even when taking into account the cropland area occupied by SWC structures, grain yield increased by (4.2%−33%) for plots with SWC structures as compared to control plots. Overall, our results show that implemented measures may not only reduce runoff and soil loss, but also increase crop productivity by enhancing soil moisture and thus can significantly contribute to sustainability of agro-ecosystems in semi-arid environments.

SMART use of medications for the treatment of adolescent severe obesity: A sequential multiple assignment randomized trial protocol

BackgroundSevere obesity is a complex, chronic disease affecting nearly 9% of adolescents in the U.S. Although the current mainstay of treatment is lifestyle therapy, pediatric clinical practice guidelines recommend the addition of adjunct anti-obesity medication (AOM), such as phentermine and topiramate. However, guidance regarding when adjunct AOM should be started and how AOM should be used is unclear. Furthermore, an inherent limitation of current treatment guidelines is their “one-size-fits-all” approach, which does not account for the heterogeneous nature of obesity and high degree of patient variability in response to all interventions. MethodsThis paper describes the study design and methods of a sequential multiple assignment randomized trial (SMART), “SMART Use of Medications for the Treatment of Adolescent Severe Obesity.” The trial will examine 1) when to start AOM (specifically phentermine) in adolescents who are not responding to lifestyle therapy and 2) how to modify AOM when there is a sub-optimal response to the initial pharmacological intervention (specifically, for phentermine non-responders, is it better to add topiramate to phentermine or switch to topiramate monotherapy). Critically, participant characteristics that may differentially affect response to treatment will be assessed and evaluated as potential moderators of intervention efficacy. ConclusionData from this study will be used to inform the development of an adaptive intervention for the treatment of adolescent severe obesity that includes empirically-derived decision rules regarding when and how to use AOM. Future research will test this adaptive intervention against standard “one-size-fits-all” treatments.

Understanding risk and causal mechanisms for developing obesity in infants and young children: A National Institutes of Health workshop.

Obesity in children remains a major public health problem, with the current prevalence in youth ages 2-19 years estimated to be 19.7%. Despite progress in identifying risk factors, current models do not accurately predict development of obesity in early childhood. There is also substantial individual variability in response to a given intervention that is not well understood. On April 29-30, 2021, the National Institutes of Health convened a virtual workshop on "Understanding Risk and Causal Mechanisms for Developing Obesity in Infants and Young Children." The workshop brought together scientists from diverse disciplines to discuss (1) what is known regarding epidemiology and underlying biological and behavioral mechanisms for rapid weight gain and development of obesity and (2) what new approaches can improve risk prediction and gain novel insights into causes of obesity in early life. Participants identified gaps and opportunities for future research to advance understanding of risk and underlying mechanisms for development of obesity in early life. It was emphasized that future studies will require multi-disciplinary efforts across basic, behavioral, and clinical sciences. An exposome framework is needed to elucidate how behavioral, biological, and environmental risk factors interact. Use of novel statistical methods may provide greater insights into causal mechanisms.

Polymorphisms and Pharmacogenomics of NQO2: The Past and the Future.

The flavoenzyme N-ribosyldihydronicotinamide (NRH):quinone oxidoreductase 2 (NQO2) catalyzes two-electron reductions of quinones. NQO2 contributes to the metabolism of biogenic and xenobiotic quinones, including a wide range of antitumor drugs, with both toxifying and detoxifying functions. Moreover, NQO2 activity can be inhibited by several compounds, including drugs and phytochemicals such as flavonoids. NQO2 may play important roles that go beyond quinone metabolism and include the regulation of oxidative stress, inflammation, and autophagy, with implications in carcinogenesis and neurodegeneration. NQO2 is a highly polymorphic gene with several allelic variants, including insertions (I), deletions (D) and single-nucleotide (SNP) polymorphisms located mainly in the promoter, but also in other regulatory regions and exons. This is the first systematic review of the literature reporting on NQO2 gene variants as risk factors in degenerative diseases or drug adverse effects. In particular, hypomorphic 29 bp I alleles have been linked to breast and other solid cancer susceptibility as well as to interindividual variability in response to chemotherapy. On the other hand, hypermorphic polymorphisms were associated with Parkinson's and Alzheimer's disease. The I and D promoter variants and other NQO2 polymorphisms may impact cognitive decline, alcoholism and toxicity of several nervous system drugs. Future studies are required to fill several gaps in NQO2 research.

Novel Treatment of Laryngomalacia: A Case Series

Background: Laryngomalacia is a prevalent neonatal condition characterized by the increased pliability of laryngeal tissues, leading to airway obstruction and associated respiratory complications. It necessitates a nuanced approach to diagnosis and management, given its variable clinical presentation and potential for significant morbidity. Objective: This study aims to investigate the clinical presentation, management, and outcomes of neonates with laryngomalacia, focusing on the efficacy of individualized treatment approaches including bronchoscopy, laser ablation, and various ventilation strategies. Methods: This retrospective case series analyzed data from two neonates treated for laryngomalacia at Children Center Hospital Tehran between 2021 and 2022. Inclusion criteria were neonates beyond 28 weeks gestation without congenital abnormalities and with an RDS score ≥8. Exclusion criteria included preterm neonates (&lt;28 weeks), an RDS score &lt;8, and congenital abnormalities. Data collection involved measures such as respiratory assistance, stridor, feeding issues, oxygen requirement, hospital stay duration, ventilation days, gestational age, RDS score, retraction severity, and amniotic blood gas values. Ethical considerations were observed throughout the study. Results: The first neonate, a 29-day-old female with a gestational age of 36 weeks and 5 days, required HFNC and laser ablation, leading to the resolution of stridor and feeding difficulties. Her hospital stay was 46 days. The second neonate, a 16-day-old male born at 38 weeks gestation, experienced complications including VAP and required a more extended treatment course, including intubation, NIV, CPAP, and HFNC, culminating in an 80-day hospital stay. Conclusion: The study highlights the importance of personalized and adaptable treatment strategies in managing laryngomalacia in neonates. The variability in clinical presentations and responses to treatment underscores the need for ongoing research and the development of refined management protocols. A multidisciplinary approach, incorporating timely diagnosis and flexible intervention, is crucial for optimal patient outcomes.

Assessment of inter-individual variability in hamstring muscle recovery after a sport-specific sprint training in women and men.

Background: Hamstring muscles are most affected by multiple sprint-based sports as a result of muscle strain during sprinting, leading to reduced performance and increased risk of injury. Therefore, the purpose of the study was to assess inter-individual variability in hamstrings recovery after a sport-specific repeated-sprint training (RST), through sprint-specific markers of muscle recovery and associated muscle damage biomarkers in women and men. Methods: Healthy females (n = 14) and males (n = 15) underwent 10 repeated 40-m sprints with a 3-min rest pause between each repetition. Force-generating capacity (FGC) by the 90° hip :20° knee test and range of motion Jurdan test, together with serum biomarkers [sarcomeric mitochondrial creatine kinase (sMtCK), oxidative stress, irisin] were tested at baseline and 24-, 48- and 72-h post-exercise through a repeated measures design. Participants were classified according to FGC loss into high responders (HR) and low responders (LR). Results: 21 individuals (10 females, 11 males) were classified as HR (FGC loss >20% and recovery >48h), while 8 individuals (4 females, 4 males) were classified as LR. HR individuals showed unrecovered maximal voluntary isometric contraction (MVIC) torque until 72h post-training (p = 0.003, np 2 = 0.170), whereas only HR males showed decreased range of motion (p = 0.026, np 2 = 0.116). HR individuals also showed increased sMtCK (p = 0.016, np 2 = 0.128), oxidative stress (p = 0.038, np 2 = 0.106) and irisin (p = 0.019, np 2 = 0.123). Conclusion: There is inter-individual variability in the muscular response to a sport-specific RST, identifiable by MVIC torque assessment. The findings support that the 90° hip :20° knee test is a powerful indirect test to screen hamstrings recovery in both women and men, in a cost-effective way. However, the Jurdan test might not be able to monitor hamstrings recovery in sportswomen after RST. Decreases in muscle capacity are linked to damage to muscle sarcolemma and mitochondria until 72h post-exercise. Overall, 72h will not be adequate time to restore hamstrings structure and function after a sport-specific RST in both female and male responders.

Effects of Individualized Exercise on Risk Factors of Metabolic Syndrome: A Scoping Review.

Exercise intervention is effective in alleviating the severity of metabolic syndrome (MetS). However, the results of previous studies on the effect of exercise on MetS have demonstrated considerable individual variability in response to a specific dose of exercise, which was attributed to the lack of a personalized approach to exercise prescription. It is essential to consider individual factors to enhance the effectiveness of exercise in addressing MetS. This scoping review assesses the effectiveness of individualized exercise on the risk factors associated with MetS. Various databases and articles were examined based on eligibility criteria and nine studies were chosen for this review. Personal and adjusted factors were predominantly analyzed to tailor exercise prescriptions to individual needs. This review proposes that personal factors can be classified into three categories: fixed factors, adaptation factors, and response factors, considering both clinical and exercise science perspectives. It also suggests that a two-way communication approach between specialists and individuals is more effective for prescribing exercise to address MetS compared to a one-way method. A one-way communication approach relies solely on an expert's decision, even whether or not he or she fully considers a client's lifestyle and preferences. If the individualized selection of exercise prescriptions is achieved through two-way communication between specialists and subjects, significant improvements can be expected in terms of both MetS severity and exercise adherence.

Extreme drought impacts have been underestimated in grasslands and shrublands globally.

Climate change is increasing the frequency and severity of short-term (~1 y) drought events-the most common duration of drought-globally. Yet the impact of this intensification of drought on ecosystem functioning remains poorly resolved. This is due in part to the widely disparate approaches ecologists have employed to study drought, variation in the severity and duration of drought studied, and differences among ecosystems in vegetation, edaphic and climatic attributes that can mediate drought impacts. To overcome these problems and better identify the factors that modulate drought responses, we used a coordinated distributed experiment to quantify the impact of short-term drought on grassland and shrubland ecosystems. With a standardized approach, we imposed ~a single year of drought at 100 sites on six continents. Here we show that loss of a foundational ecosystem function-aboveground net primary production (ANPP)-was 60% greater at sites that experienced statistically extreme drought (1-in-100-y event) vs. those sites where drought was nominal (historically more common) in magnitude (35% vs. 21%, respectively). This reduction in a key carbon cycle process with a single year of extreme drought greatly exceeds previously reported losses for grasslands and shrublands. Our global experiment also revealed high variability in drought response but that relative reductions in ANPP were greater in drier ecosystems and those with fewer plant species. Overall, our results demonstrate with unprecedented rigor that the global impacts of projected increases in drought severity have been significantly underestimated and that drier and less diverse sites are likely to be most vulnerable to extreme drought.

Development of anti-PEG IgG/IgM/IgE ELISA assays for profiling anti-PEG immunoglobulin response in PEG-sensitized individuals and patients with alpha-gal allergy

Polyethylene glycol (PEG) is frequently used in various protein and nanomedicine therapeutics. However, various studies have shown that select PEGylated therapeutics can induce production of anti-PEG antibodies (APA), potentially culminating in rapid clearance from the systemic circulation, loss of efficacy and possibly increased risks of allergic reactions. Although IgE is a frequent cause of immediate hypersensitivity reactions (IHR), the role of IgE APA in PEG-related IHR is not well understood, due in part to a lack of standardized assays for measuring IgE APA. Here, we developed a rigorous competitive ELISA method to measure the concentrations of various APA isotypes, including IgE, with picomolar sensitivities. In a small number of serum samples from patients with known PEG allergy, the assay allowed us to detect a strong correlation between IgG and IgE APA in individuals with history of allergic reactions to PEG or PEGylated drugs, but not between IgM and IgE APA. We detected appreciable levels of IgG and IgM APA in individuals with history of alpha-gal allergy, however, they were not elevated relative to those detected in other healthy controls, and we found no pre-existing IgE APA. While preliminary and should be further investigated, these results suggest that differences in the route and mechanism of PEG exposure may drive variability in APA response.

Modeling Variability in Seismic Analysis of Concrete Gravity Dams: A Parametric Analysis of Koyna and Pine Flat Dams

This study addresses the vital issue of the variability associated with modeling decisions in dam seismic analysis. Traditionally, structural modeling and simulations employ a progressive approach, where more complex models are gradually incorporated. For example, if previous levels indicate insufficient seismic safety margins, a more advanced analysis is then undertaken. Recognizing the constraints and evaluating the influence of various methods is essential for improving the comprehension and effectiveness of dam safety assessments. To this end, an extensive parametric study is carried out to evaluate the seismic response variability of the Koyna and Pine Flat dams using various solution approaches and model complexities. Numerical simulations are conducted in a 2D framework across three software programs, encompassing different dam system configurations. Additional complexity is introduced by simulating reservoir dynamics with Westergaard-added mass or acoustic elements. Linear and nonlinear analyses are performed, incorporating pertinent material properties, employing the concrete damage plasticity model in the latter. Modal parameters and crest displacement time histories are used to highlight variability among the selected solution procedures and model complexities. Finally, recommendations are made regarding the adequacy and robustness of each method, specifying the scenarios in which they are most effectively applied.

NK cell-triggered CCL5/IFNγ-CXCL9/10 axis underlies the clinical efficacy of neoadjuvant anti-HER2 antibodies in breast cancer

BackgroundThe variability in responses to neoadjuvant treatment with anti-HER2 antibodies prompts to personalized clinical management and the development of innovative treatment strategies. Tumor-infiltrating Natural Killer (TI-NK) cells can predict the efficacy of HER2-targeted antibodies independently from clinicopathological factors in primary HER2-positive breast cancer patients. Understanding the mechanism/s underlying this association would contribute to optimizing patient stratification and provide the rationale for combinatorial approaches with immunotherapy.MethodsWe sought to uncover processes enriched in NK cell-infiltrated tumors as compared to NK cell-desert tumors by microarray analysis. Findings were validated in clinical trial-derived transcriptomic data. In vitro and in vivo preclinical models were used for mechanistic studies. Findings were analysed in clinical samples (tumor and serum) from breast cancer patients.ResultsNK cell-infiltrated tumors were enriched in CCL5/IFNG-CXCL9/10 transcripts. In multivariate logistic regression analysis, IFNG levels underlie the association between TI-NK cells and pathological complete response to neoadjuvant treatment with trastuzumab. Mechanistically, the production of IFN-ɣ by CD16+ NK cells triggered the secretion of CXCL9/10 from cancer cells. This effect was associated to tumor growth control and the conversion of CD16 into CD16-CD103+ NK cells in humanized in vivo models. In human breast tumors, the CD16 and CD103 markers identified lineage-related NK cell subpopulations capable of producing CCL5 and IFN-ɣ, which correlated with tissue-resident CD8+ T cells. Finally, an early increase in serum CCL5/CXCL9 levels identified patients with NK cell-rich tumors showing good responses to anti-HER2 antibody-based neoadjuvant treatment.ConclusionsThis study identifies specialized NK cell subsets as the source of IFN-ɣ influencing the clinical efficacy of anti-HER2 antibodies. It also reveals the potential of serum CCL5/CXCL9 as biomarkers for identifying patients with NK cell-rich tumors and favorable responses to anti-HER2 antibody-based neoadjuvant treatment.

Refined innate plasma signature after rVSVΔG-ZEBOV-GP immunization is shared among adult cohorts in Europe and North America.

During the last decade Ebola virus has caused several outbreaks in Africa. The recombinant vesicular stomatitis virus-vectored Zaire Ebola (rVSVΔG-ZEBOV-GP) vaccine has proved safe and immunogenic but is reactogenic. We previously identified the first innate plasma signature response after vaccination in Geneva as composed of five monocyte-related biomarkers peaking at day 1 post-immunization that correlates with adverse events, biological outcomes (haematological changes and viremia) and antibody titers. In this follow-up study, we sought to identify additional biomarkers in the same Geneva cohort and validate those identified markers in a US cohort. Additional biomarkers were identified using multiplexed protein biomarker platform O-link and confirmed by Luminex. Principal component analysis (PCA) evaluated if these markers could explain a higher variability of the vaccine response (and thereby refined the initial signature). Multivariable and linear regression models evaluated the correlations of the main components with adverse events, biological outcomes, and antibody titers. External validation of the refined signature was conducted in a second cohort of US vaccinees (n=142). Eleven additional biomarkers peaked at day 1 post-immunization: MCP2, MCP3, MCP4, CXCL10, OSM, CX3CL1, MCSF, CXCL11, TRAIL, RANKL and IL15. PCA analysis retained three principal components (PC) that accounted for 79% of the vaccine response variability. PC1 and PC2 were very robust and had different biomarkers that contributed to their variability. PC1 better discriminated different doses, better defined the risk of fever and myalgia, while PC2 better defined the risk of headache. We also found new biomarkers that correlated with reactogenicity, including transient arthritis (MCP-2, CXCL10, CXCL11, CX3CL1, MCSF, IL-15, OSM). Several innate biomarkers are associated with antibody levels one and six months after vaccination. Refined PC1 correlated strongly in both data sets (Geneva: r = 0.97, P < 0.001; US: r = 0.99, P< 0.001). Eleven additional biomarkers refined the previously found 5-biomarker Geneva signature. The refined signature better discriminated between different doses, was strongly associated with the risk of adverse events and with antibody responses and was validated in a separate cohort.

Acute dissociation as part of the defense cascade: Associations with behavioral, autonomic, and experiential threat responses in posttraumatic stress disorder.

Dissociative symptoms, such as depersonalization and derealization, are experienced by about half of individuals with posttraumatic stress disorder (PTSD). Theoretical models propose that acute dissociation is accompanied by specific behavioral, physiological, and experiential alterations and contributes to unfavorable PTSD symptom course. Yet, empirical evidence is scarce. Here, we explored associations between dissociative and behavioral, physiological, and experiential threat responses as well as effects of dissociative responding on PTSD symptom course. Individuals with PTSD (N = 71) participated in a preregistered script-driven imagery study including exposure to standardized, detail-enriched trauma, and neutral scripts. Stabilometry, eye-tracking, facial electromyography, autonomic psychophysiology, and self-report data were collected. Moreover, PTSD symptoms were assessed before and 3 months after testing. Analyses did not link acute dissociation to bodily and facial immobility or staring in response to trauma scripts. However, dissociation displayed an inverted U-shaped relationship with heart rate and was linked to higher nonspecific skin conductance fluctuation and higher high-frequency heart rate variability in response to trauma scripts. Moreover, acute dissociation was linked to higher self-reported negative affect responses to trauma scripts and displayed a U-shaped relationship with unfavorable PTSD symptom course. While results did not confirm hypothesized behavioral markers of dissociation, they do support defense-cascade model assumptions of an inverted U-shaped relationship between dissociation and psychophysiological arousal resulting from a progression of parasympathetic versus sympathetic dominance with increasing dissociation. On an experiential level, results did not confirm posttraumatic dissociation-induced emotional numbing, questioning theoretical notions. The observed nonlinear associations may help explain the heterogeneity of prior findings and might inform an updated conceptualization of posttraumatic dissociation. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Forecasting Crop Yield Variability in Response to Weather Information Using Quantile Random Forest Regression --- An Application in Non-Irrigated Upland Cotton

Forecasting Crop Yield Variability in Response to Weather Information Using Quantile Random Forest Regression --- An Application in Non-Irrigated Upland Cotton