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Nevin Manimala Statistics

Monitoring of plant water uptake by measuring root dielectric properties on a fine timescale: diurnal changes and response to leaf excision

Plant Methods. 2024 Jan 9;20(1):5. doi: 10.1186/s13007-023-01133-8.

ABSTRACT

BACKGROUND: The measurement of root dielectric response is a useful non-destructive method to evaluate root growth and function. Previous studies tracked root development throughout the plant growing cycle by single-time electrical measurements taken repeatedly. However, it is known that root conductivity and uptake activity can change rapidly, coupled with the day/night cycles of photosynthetic and transpiration rate. Therefore, the low-frequency dielectric monitoring of intact root-substrate systems at minute-scale temporal resolution was tested using a customized impedance measurement system in a laboratory environment. Electrical capacitance (CR) and conductance (GR) and the dissipation factor (DR) were detected for 144 h in potted maize, cucumber and pea grown under various light/dark and temperature conditions, or subjected to progressive leaf excision or decapitation. Photosynthetic parameters and stomatal conductance were also measured to evaluate the stress response.

RESULTS: The CR and GR data series showed significant 24-h seasonality associated with the light/dark and temperature cycles applied. This was attributed to the diurnal patterns in whole-plant transpiration (detected via stomatal conductance), which is strongly linked to the root water uptake rate. CR and GR decreased during the 6-day dark treatment, and dropped proportionally with increasing defoliation levels, likely due to the loss of canopy transpiration caused by dark-induced senescence or removal of leaves. DR showed a decreasing trend for plants exposed to 6-day darkness, whereas it was increased markedly by decapitation, indicating altered root membrane structure and permeability, and a modified ratio of apoplastic to cell-to-cell water and current pathways.

CONCLUSIONS: Dynamic, in situ impedance measurement of the intact root system was an efficient way of following integrated root water uptake, including diurnal cycles, and stress-induced changes. It was also demonstrated that the dielectric response mainly originated from root tissue polarization and current conduction, and was influenced by the actual physiological activity of the root system. Dielectric measurement on fine timescale, as a diagnostic tool for monitoring root physiological status and environmental response, deserves future attention.

PMID:38195647 | DOI:10.1186/s13007-023-01133-8

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Statistical classification of treatment responses in mouse clinical trials for stratified medicine in oncology drug discovery

Sci Rep. 2024 Jan 9;14(1):934. doi: 10.1038/s41598-023-51055-7.

ABSTRACT

Translational oncology research strives to explore a new aspect: identifying subgroups that exhibit treatment response even during pre-clinical phases. In this study, we focus on PDX models and their implementation in mouse clinical trials (MCT). Our primary objective was to identify subgroups with different treatment responses using Latent Class Mixed Model (LCMM).We used a public dataset and focused on one treatment, encorafenib, and two indications, melanoma and colorectal cancer, for which efficacy depends on a specific mutation BRAF V600E. One LCMM per indication was implemented to classify treatment responses at the PDX level, analyzing the growth kinetics of treated tumors and matched controls within the PDX models. A simulation study was carried out to explore the performance of LCMM in this context. For both applications, LCMM identified classes for which the higher the proportion of mutated BRAF V600E PDX models the greater the treatment effect, which is aligned with encorafenib use recommendations. The simulation study showed that LCMM could identify classes with large differences in treatment effects. LCMM is a suitable tool for MCT to explore treatment response subgroups of PDX. Once these subgroups are defined, characterization of their phenotypes/genotypes could be performed to explore treatment response predictors.

PMID:38195626 | DOI:10.1038/s41598-023-51055-7

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Different risks of early-onset and late-onset Parkinson disease in individuals with mental illness

NPJ Parkinsons Dis. 2024 Jan 9;10(1):17. doi: 10.1038/s41531-023-00621-x.

ABSTRACT

We aimed to investigate the association of various mental illnesses, including depression, bipolar disorder, schizophrenia, insomnia, and anxiety, with the risk of early-onset Parkinson’s disease (EOPD) (age <50 years) and compare it with that of late-onset PD (LOPD) (age ≥50 years). This nationwide cohort study enrolled 9,920,522 people who underwent a national health screening examination in 2009, and followed up until 31 December 2018. There was a significantly increased risk of EOPD and LOPD in individuals with mental illness, and EOPD showed a stronger association than LOPD (EOPD, hazard ratio (HR) = 3.11, 95% CI: 2.61‒3.72; LOPD, HR = 1.70, 95% CI: 1.66‒1.74; p for interaction <0.0001). Our results suggest that people with mental illnesses aged < 50 years are at a higher risk of PD than those aged ≥50 years. Future studies are warranted to elucidate the pathomechanism of EOPD in relation to mental illness.

PMID:38195604 | DOI:10.1038/s41531-023-00621-x

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Prenatal dietary exposure to mixtures of chemicals is associated with allergy or respiratory diseases in children in the ELFE nationwide cohort

Environ Health. 2024 Jan 9;23(1):5. doi: 10.1186/s12940-023-01046-y.

ABSTRACT

INTRODUCTION: Prenatal exposure to environmental chemicals may be associated with allergies later in life. We aimed to examine the association between prenatal dietary exposure to mixtures of chemicals and allergic or respiratory diseases up to age 5.5 y.

METHODS: We included 11,638 mother-child pairs from the French “Étude Longitudinale Française depuis l’Enfance” (ELFE) cohort. Maternal dietary exposure during pregnancy to eight mixtures of chemicals was previously assessed. Allergic and respiratory diseases (eczema, food allergy, wheezing and asthma) were reported by parents between birth and age 5.5 years. Associations were evaluated with adjusted logistic regressions. Results are expressed as odds ratio (OR[95%CI]) for a variation of one SD increase in mixture pattern.

RESULTS: Maternal dietary exposure to a mixture composed mainly of trace elements, furans and polycyclic aromatic hydrocarbons (PAHs) was positively associated with the risk of eczema (1.10 [1.05; 1.15]), this association was consistent across sensitivity analyses. Dietary exposure to one mixture of pesticides was positively associated with the risk of food allergy (1.10 [1.02; 1.18]), whereas the exposure to another mixture of pesticides was positively but slightly related to the risk of wheezing (1.05 [1.01; 1.08]). This last association was not found in all sensitivity analyses. Dietary exposure to a mixture composed by perfluoroalkyl acids, PAHs and trace elements was negatively associated with the risk of asthma (0.89 [0.80; 0.99]), this association was consistent across sensitivity analyses, except the complete-case analysis.

CONCLUSION: Whereas few individual chemicals were related to the risk of allergic and respiratory diseases, some consistent associations were found between prenatal dietary exposure to some mixtures of chemicals and the risk of allergic or respiratory diseases. The positive association between trace elements, furans and PAHs and the risk of eczema, and that between pesticides mixtures and food allergy need to be confirmed in other studies. Conversely, the negative association between perfluoroalkyl acids, PAHs and trace elements and the risk of asthma need to be further explored.

PMID:38195595 | DOI:10.1186/s12940-023-01046-y

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Statistical analysis plan for the multicenter, open, randomized controlled clinical trial to assess the efficacy and safety of intravenous tirofiban vs aspirin in acute ischemic stroke due to tandem lesion, undergoing recanalization therapy by endovascular treatment (ATILA trial)

Trials. 2024 Jan 9;25(1):35. doi: 10.1186/s13063-023-07817-9.

ABSTRACT

RATIONALE: In-stent reocclusion after endovascular therapy has a negative impact on outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Optimal antiplatelet therapy approach in these patients to avoid in-stent reocclusion is yet to be elucidated.

AIMS: To assess efficacy and safety of intravenous tirofiban versus intravenous aspirin in patients undergoing MT plus carotid stenting in the setting of AIS due to TL.

SAMPLE SIZE ESTIMATES: Two hundred forty patients will be enrolled, 120 in every treatment arm.

METHODS AND DESIGN: A multicenter, prospective, randomized, controlled (aspirin group), assessor-blinded clinical trial will be conducted. Patients fulfilling the inclusion criteria will be randomized at MT onset to the experimental or control group (1:1). Intravenous aspirin will be administered at a 500-mg single dose and tirofiban at a 500-mcg bolus followed by a 200-mcg/h infusion during the first 24 h. All patients will be followed for up to 3 months.

STUDY OUTCOMES: Primary efficacy outcome will be the proportion of patients with carotid in-stent thrombosis within the first 24 h after MT. Primary safety outcome will be the rate of symptomatic intracranial hemorrhage.

DISCUSSION: This will be the first clinical trial to assess the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL.

TRIAL REGISTRATION: The trial is registered as NCT05225961. February, 7th, 2022.

PMID:38195586 | DOI:10.1186/s13063-023-07817-9

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Substantial variability exists in the interpretation of survey radiographs among equine veterinarians

Equine Vet J. 2024 Jan 9. doi: 10.1111/evj.14045. Online ahead of print.

ABSTRACT

BACKGROUND: Radiographs are a common diagnostic tool utilised during pre-purchase examinations, yet differences surround their interpretation among equine veterinarians.

OBJECTIVES: (1) To determine veterinarians’ subjective impressions of a spectrum of radiographic abnormalities regarding suitability for purchase; (2) To determine how veterinarians’ years in practice, primary discipline or board certification status influence their subjective impression of radiographic abnormalities, and (3) To determine how horses’ discipline, current level of work (working at intended level vs. future prospect) and buyer intent (sell vs. retain ownership) influence veterinarians’ subsequent recommendation.

STUDY DESIGN: Worldwide electronic survey of veterinary professionals.

METHODS: Four radiographic series of navicular bones, tarsi, and stifles, representing varying degrees of pathological change (normal, mild, moderate and marked) were presented. Respondents (n = 211) graded their level of concern from 1 (no concern) to 10 (very concerned) based on the radiographs and case scenarios presented.

RESULTS: Overall, as the grade of pathological change increased for each anatomical location, so did the level of veterinarian concern, but a wide range of answers were submitted for all grades of pathology. Board certified practitioners had a higher level of concern over marked radiographic changes of the navicular bone for both western performance and English sport horses as well as prospect horses (mean = 7.2 vs. 6.1; P = 0.009; 95% CI for difference = [0.3, 2.0]). Board certified respondents had a lower level of concern over marked radiographic changes of the tarsus regardless of the performance status of the horse (mean = 7.1 vs. 8.0; P = 0.008; 95% CI for difference = [-1.5, -0.2]). Western performance horse practitioners had a lower level of concern over mild radiographic changes of the tarsus regardless of the performance status of the horse (mean = 3.3 vs. 4.2; P = 0.009; 95% CI for difference = [-1.6, -0.2]).

MAIN LIMITATIONS: Only one example of each pathological grade per anatomical region was presented.

CONCLUSIONS: On survey radiographs, the perceived clinical relevance of radiographic abnormalities among equine practitioners differs widely, making purchase recommendations highly variable.

PMID:38194693 | DOI:10.1111/evj.14045

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Prediction of outcomes for high-count monoclonal B lymphocytosis using an epigenetic and immunogenetic signature

Blood. 2024 Jan 9:blood.2023022180. doi: 10.1182/blood.2023022180. Online ahead of print.

ABSTRACT

Monoclonal B cell lymphocytosis (MBL) progresses to chronic lymphocytic leukemia (CLL) requiring therapy at 1-5%/year. Improved prediction of progression would greatly benefit individuals with MBL. CLL patients separate into three distinct epigenetic subtypes (epitypes) with high prognostic significance, and recently the intermediate epitype has been shown to be enriched for high-risk IGLV3-21 rearrangements, impacting outcomes for these patients. Here we employed this combined strategy to generate the epigenetic and light chain immunoglobulin (ELCLV3-21) signature to classify 219 individuals with MBL. The ELCLV3-21 high-risk signature distinguished MBL individuals with a high probability of progression (39.9% and 71.1% at 5 and 10 years, respectively). ELCLV3-21 improved the accuracy of predicting time to therapy for MBL individuals compared to other established prognostic indicators, including the CLL international prognostic index (c-statistic 0.767 versus 0.668, respectively). Comparing ELCLV3-21 risk groups in MBL versus a cohort of 226 CLL patients revealed ELCLV3-21 high-risk MBL individuals had significantly shorter time to therapy (P=0.003) and reduced OS (P=0.03) compared to ELCLV3-21 low-risk CLL. These results highlight the power of the ELCLV3-21 approach to identify individuals with a higher likelihood of adverse clinical outcome and may provide a more accurate approach to classify individuals with small B-cell clones.

PMID:38194687 | DOI:10.1182/blood.2023022180

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Association of Designated Pediatric Trauma Center and Outcomes of Severely Injured Children Who Were Mechanically Ventilated and Underwent Tracheostomy: A Propensity-Matched Analysis

Pediatr Emerg Care. 2024 Jan 10. doi: 10.1097/PEC.0000000000003054. Online ahead of print.

ABSTRACT

OBJECTIVES: The purpose of the study is to examine the outcomes of care delivered at the pediatric trauma center (PTC) in severely injured children who were intubated, mechanically ventilated, and underwent tracheostomy.

METHODS: The study data were obtained from the Trauma Quality Improvement Program database for the calendar years 2017 to 2019. All children aged ≤17 years who sustained severe injury, required intubation and mechanical ventilation for more than 96 hours, and underwent tracheostomy were included in the study. Patients’ characteristics, injury severity, and outcomes were compared between the care provided at the PTCs (level I or level II) and nonpediatric trauma centers (NPTCs). The propensity score matching methodology was used to perform the analysis. All P values are 2-sided, and a P value of <0.0.5 is considered statistically significant.

RESULTS: Of 2164 patients who were qualified for the study, 1288 (59%) of the patients were treated at PTCs, and 876 (40.5%) of the patients were treated at NPTCs. Propensity matching created 876 pairs of patients. There were no significant differences found between the 2 groups on patients’ characteristics except for age. Patients who were treated at PTCs had a median age of 14 (10-16) versus 15 (11-17) years (P < 0.001) when compared with care provided at NPTCs. A longer hospital stay was found in the PTC group when compared with the NPTC group (24 [23, 25] vs 22 [21, 24], P = 0.008). Patients who were treated at PTC were found to have significantly less sepsis occurrence (0.9% vs 2.2%), and a higher proportion of patients were discharged home without needing additional support (26.2% vs 18.5%).

CONCLUSIONS: Care at the PTC was associated with a lower occurrence of sepsis complications. A higher number of patients were discharged home without additional services when the care was provided at PTC.

PMID:38194684 | DOI:10.1097/PEC.0000000000003054

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The effect of internal limiting membrane peeling on the inner retinal layers in patients without macular pathology

Retina. 2024 Jan 8. doi: 10.1097/IAE.0000000000004042. Online ahead of print.

ABSTRACT

BACKGROUND: To examine the effect of internal limiting membrane (ILM) peeling on the inner retinal layers in patients without macular pathology.

METHODS: A prospective nonrandomized trial of patients undergoing pars plana vitrectomy with ILM peeling for pathology outside of the macula was performed. Optical coherence tomography (OCT) including macular ganglion cell layer (GCL), inner plexiform layer (IPL) and peripapillary retinal nerve fiber layer imaging was performed prior to surgery, 1,3 and 6 months post-operatively and at the end of follow up (ranges between 4-17 months). Patients with any macular pathology on OCT prior to surgery were excluded. The main outcome measure was change in thickness of the GCL and IPL.

RESULTS: Ten patients who underwent pars plana vitrectomy with ILM peeling for macula-on retinal detachment were included in the analysis. The mean age was 55 years and the mean follow up was 10.8 months. All patients completed at least 2 post-operative follow up visits that included an OCT as per the protocol (range 2-6 months). There was an immediate reduction in the global (G), infero-temporal (IT), supero-temporal (ST) and superior (S) GCL thickness at the first follow up as compared to the pre-operative state (P=0.028, P=0.027, P=0.026 and P=0.027 respectively). From the first follow up visit onward until the final follow up the thinning persisted, though there was no further statistically significant thinning.

CONCLUSION: Peeling of the ILM causes significant GCL thinning in maculae without pathology prior to surgery. At up to 17 months of follow up, this effect seems to be immediate and non-progressive.

PMID:38194675 | DOI:10.1097/IAE.0000000000004042

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Mental Health Effects on the Minimal Clinically Important Difference in Total Joint Arthroplasty

J Am Acad Orthop Surg. 2024 Jan 9. doi: 10.5435/JAAOS-D-23-00538. Online ahead of print.

ABSTRACT

INTRODUCTION: The effect of mental health on patient-reported outcome measures is not fully understood in total joint arthroplasty (TJA). Thus, we investigated the relationship between mental health diagnoses (MHDs) and the Minimal Clinically Important Difference for Improvement (MCID-I) and Worsening (MCID-W) in primary TJA and revision TJA (rTJA).

METHODS: Retrospective data were collected using relevant Current Procedural Terminology and MHDs International Classification of Diseases, 10th Revision, codes with completed Hip Disability and Osteoarthritis Outcome Score-Physical Function Short Form, Knee Injury and Osteoarthritis Outcome Score-Physical Function Short Form, Patient-reported Outcomes Measurement Information System (PROMIS)-Physical Function Short Form 10a, PROMIS Global-Mental, or PROMIS Global-Physical questionnaires. Logistic regressions and statistical analyses were used to determine the effect of a MHD on MCID-I/MCID-W rates.

RESULTS: Data included 4,562 patients (4,190 primary TJAs/372 rTJAs). In primary total hip arthroplasty (pTHA), MHD-affected outcomes for Hip Disability and Osteoarthritis Outcome Score-Physical Function Short Form (MCID-I: 81% versus 86%, P = 0.007; MCID-W: 6.0% versus 3.2%, P = 0.008), Physical Function Short Form 10a (MCID-I: 68% versus 77%, P < 0.001), PROMIS Global-Mental (MCID-I: 38% versus 44%, P = 0.009), and PROMIS Global-Physical (MCID-I: 61% versus 73%, P < 0.001; MCID-W: 14% versus 7.9%, P < 0.001) versus pTHA patients without MHD. A MHD led to lower rates of MCID-I for PROMIS Global-Physical (MCID-I: 56% versus 63%, P = 0.003) in primary total knee arthroplasty patients. No effects from a MHD were observed in rTJA patients.

DISCUSSION: The presence of a MHD had a prominent negative influence on pTHA patients. Patients who underwent rTJA had lower MCID-I rates, higher MCID-W rates, and lower patient-reported outcome measure scores despite less influence from a MHD.

LEVEL OF EVIDENCE: Level III, retrospective comparative study.

PMID:38194673 | DOI:10.5435/JAAOS-D-23-00538