Category: Statistics

Clin Neurol Neurosurg. 2023 May 5;230:107755. doi: 10.1016/j.clineuro.2023.107755. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the risk factors associated with rebound intracranial pressure (ICP), a phenomenon that occurs when brain swelling reprogresses rapidly during rewarming in patients who have undergone therapeutic hypothermia for traumatic brain injury (TBI).

METHODS: This study analyzed 42 patients who underwent therapeutic hypothermia among 172 patients with severe TBI admitted to a single regional trauma center between January 2017 and December 2020. Forty-two patients were classified into 34.5 °C (mild) and 33 °C (moderate) hypothermia groups according to the therapeutic hypothermia protocol for TBI. Rewarming was initiated post-hypothermia, wherein ICP was maintained at ≤ 20 mmHg and cerebral perfusion pressure was maintained at ≥ 50 mmHg for ≥ 24 h. In the rewarming protocol, the target core temperature was increased to 36.5 °C at 0.1 °C/h.

RESULTS: Of the 42 patients who underwent therapeutic hypothermia, 27 did not survive: 9 in the mild and 18 in the moderate hypothermia groups. The moderate hypothermia group had a significantly higher mortality rate than the mild hypothermia group (p = 0.013). Rebound ICP occurred in 9 of 25 patients: 2 in the mild and 7 in the moderate hypothermia groups. In the risk factor analysis of rebound ICP, only the degree of hypothermia was statistically significant, and rebound ICP was observed more frequently in the moderate than in the mild hypothermia group (p = 0.025).

CONCLUSIONS: In patients who underwent rewarming after therapeutic hypothermia, rebound ICP presented a higher risk at 33 °C than at 34.5 °C. Therefore, more careful rewarming is needed in patients receiving therapeutic hypothermia at 33 °C.

PMID:37207371 | DOI:10.1016/j.clineuro.2023.107755

Toxicol Ind Health. 2023 May 19:7482337231174994. doi: 10.1177/07482337231174994. Online ahead of print.

ABSTRACT

Carbon tetrachloride (CCl₄) is a potent liver toxin. Diclofenac (Dic), leading adverse effects on the liver, is used among the employees of the industries that use CCl₄. The increased use of CCl₄ and Dic in industrial workers has prompted us to investigate their synergistic effect on the liver using male Wistar rats as a model. Male Wistar rats were divided into seven groups (n = 6), and the exposure was by intraperitoneal injection for 14 days as follows. Group 1: Control, 2: Olive oil, 3: CCl₄ (0.8 mL/kg/day (3 times per week)), 4: Normal saline, 5: Dic (1.5 mg/kg/day per day), 6: Olive oil with normal saline, 7: CCl₄ (0.8 mL/kg/day (3 times per week)) and Dic (1.5 mg/kg/day daily). At the end of day 14, the heart blood was collected to measure the liver enzymes, alanine-aminotransferase (ALT), aspartate-aminotransferase (AST), blood alkaline phosphatase (ALP), albumin (ALB), direct bilirubin, and total bilirubin. A pathologist examined the liver tissue. Prism software was used to analyze data using ANOVA and Tukey statistical tests. ALT, AST, ALP, and Total Bilirubin enzymes were increased significantly in the co-administered CCl₄ and Dic group, while the ALB levels decreased (p < 0.05). The histological findings reported liver necrosis, focal hemorrhage, adipose tissue change, and lymphocytic portal hepatitis. In conclusion, using Dic while exposed to CCl₄ may exacerbate hepatotoxicity in rats. Therefore, it is suggested that more severe restrictions and safety regulations be placed on using CCl₄ in the industry, and caution is advised to these industry workers to use Diclofenac.

PMID:37207345 | DOI:10.1177/07482337231174994

J Phys Chem Lett. 2023 May 19:4923-4932. doi: 10.1021/acs.jpclett.3c00839. Online ahead of print.

ABSTRACT

We introduce fluorescence-detected pump-probe microscopy by combining a wavelength-tunable ultrafast laser with a confocal scanning fluorescence microscope, enabling access to the femtosecond time scale on the micrometer spatial scale. In addition, we obtain spectral information from Fourier transformation over excitation pulse-pair time delays. We demonstrate this new approach on a model system of a terrylene bisimide (TBI) dye embedded in a PMMA matrix and acquire the linear excitation spectrum as well as time-dependent pump-probe spectra simultaneously. We then push the technique toward single TBI molecules and analyze the statistical distribution of their excitation spectra. Furthermore, we demonstrate the ultrafast transient evolution of several individual molecules, highlighting their different behavior in contrast to the ensemble due to their individual local environment. By correlating the linear and nonlinear spectra, we assess the effect of the molecular environment on the excited-state energy.

PMID:37207316 | DOI:10.1021/acs.jpclett.3c00839

J Clin Oncol. 2023 May 19:JCO2202392. doi: 10.1200/JCO.22.02392. Online ahead of print.

ABSTRACT

PURPOSE: Cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) with endocrine therapy (ET) improves progression-free survival (PFS) and overall survival (OS) in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). Although preclinical and clinical data demonstrate a benefit in changing ET and continuing a CDK4/6i at progression, no randomized prospective trials have evaluated this approach.

METHODS: In this investigator-initiated, phase II, double-blind placebo-controlled trial in patients with HR+/HER2- MBC whose cancer progressed during ET and CDK4/6i, participants switched ET (fulvestrant or exemestane) from ET used pre-random assignment and randomly assigned 1:1 to the CDK4/6i ribociclib versus placebo. PFS was the primary end point, defined as time from random assignment to disease progression or death. Assuming a median PFS of 3.8 months with placebo, we had 80% power to detect a hazard ratio (HR) of 0.58 (corresponding to a median PFS of at least 6.5 months with ribociclib) with 120 patients randomly assigned using a one-sided log-rank test and significance level set at 2.5%.

RESULTS: Of the 119 randomly assigned participants, 103 (86.5%) previously received palbociclib and 14 participants received ribociclib (11.7%). There was a statistically significant PFS improvement for patients randomly assigned to switched ET plus ribociclib (median, 5.29 months; 95% CI, 3.02 to 8.12 months) versus switched ET plus placebo (median, 2.76 months; 95% CI, 2.66 to 3.25 months) HR, 0.57 (95% CI, 0.39 to 0.85); P = .006. At 6 and 12 months, the PFS rate was 41.2% and 24.6% with ribociclib, respectively, compared with 23.9% and 7.4% with placebo.

CONCLUSION: In this randomized trial, there was a significant PFS benefit for patients with HR+/HER2- MBC who switched ET and received ribociclib compared with placebo after previous CDK4/6i and different ET.

PMID:37207300 | DOI:10.1200/JCO.22.02392

Chem Res Toxicol. 2023 May 19. doi: 10.1021/acs.chemrestox.2c00368. Online ahead of print.

ABSTRACT

Structural alerts are molecular substructures assumed to be associated with molecular initiating events in various toxic effects and an integral part of in silico toxicology. However, alerts derived using the knowledge of human experts often suffer from a lack of predictivity, specificity, and satisfactory coverage. In this work, we present a method to build hybrid QSAR models by combining expert knowledge-based alerts and statistically mined molecular fragments. Our objective was to find out if the combination is better than the individual systems. Lasso regularization-based variable selection was applied on combined sets of knowledge-based alerts and molecular fragments, but the variable elimination was only allowed to happen on the molecular fragments. We tested the concept on three toxicity end points, i.e., skin sensitization, acute Daphnia toxicity, and Ames mutagenicity, which covered both classification and regression problems. Results showed the predictive performance of such hybrid models is, indeed, better than the models based solely on expert alerts or statistically mined fragments alone. The method also enables the discovery of activating and mitigating/deactivating features for toxicity alerts and the identification of new alerts, thereby reducing false positive and false negative outcomes commonly associated with generic alerts and alerts with poor coverage, respectively.

PMID:37207298 | DOI:10.1021/acs.chemrestox.2c00368

Environ Sci Technol. 2023 May 19. doi: 10.1021/acs.est.3c00253. Online ahead of print.

ABSTRACT

Plankton are widely distributed in the aquatic environment and serve as an indicator of water quality. Monitoring the spatiotemporal variation in plankton is an efficient approach to forewarning environmental risks. However, conventional microscopy counting is time-consuming and laborious, hindering the application of plankton statistics for environmental monitoring. In this work, an automated video-oriented plankton tracking workflow (AVPTW) based on deep learning is proposed for continuous monitoring of living plankton abundance in aquatic environments. With automatic video acquisition, background calibration, detection, tracking, correction, and statistics, various types of moving zooplankton and phytoplankton were counted at a time scale. The accuracy of AVPTW was validated with conventional counting via microscopy. Since AVPTW is only sensitive to mobile plankton, the temperature- and wastewater-discharge-induced plankton population variations were monitored online, demonstrating the sensitivity of AVPTW to environmental changes. The robustness of AVPTW was also confirmed with natural water samples from a contaminated river and an uncontaminated lake. Notably, automated workflows are essential for generating large amounts of data, which are a prerequisite for available data set construction and subsequent data mining. Furthermore, data-driven approaches based on deep learning pave a novel way for long-term online environmental monitoring and elucidating the correlation underlying environmental indicators. This work provides a replicable paradigm to combine imaging devices with deep-learning algorithms for environmental monitoring.

PMID:37207295 | DOI:10.1021/acs.est.3c00253

J Phys Chem A. 2023 May 19. doi: 10.1021/acs.jpca.2c08662. Online ahead of print.

ABSTRACT

The reaction between the ground-state hydroxyl radical, OH(²Π), and ethylene, C₂H₄, has been investigated under single-collision conditions by the crossed molecular beam scattering technique with mass-spectrometric detection and time-of-flight analysis at the collision energy of 50.4 kJ/mol. Electronic structure calculations of the underlying potential energy surface (PES) and statistical Rice-Ramsperger-Kassel-Marcus (RRKM) calculations of product branching fractions on the derived PES for the addition pathway have been performed. The theoretical results indicate a temperature-dependent competition between the anti-/syn-CH₂CHOH (vinyl alcohol) + H, CH₃CHO (acetaldehyde) + H, and H₂CO (formaldehyde) + CH₃ product channels. The yield of the H-abstraction channel could not be quantified with the employed methods. The RRKM results predict that under our experimental conditions, the anti– and syn-CH₂CHOH + H product channels account for 38% (in similar amounts) of the addition mechanism yield, the H₂CO + CH₃ channel for ∼58%, while the CH₃CHO + H channel is formed in negligible amount (<4%). The implications for combustion and astrochemical environments are discussed.

PMID:37207281 | DOI:10.1021/acs.jpca.2c08662

Am J Med Open. 2023 Jun;9:100040. doi: 10.1016/j.ajmo.2023.100040. Epub 2023 Mar 22.

ABSTRACT

BACKGROUND: The use of statins, angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs), and anticoagulants may be associated with fewer adverse outcomes in COVID-19 patients.

METHODS: Nested within a cohort of 800,913 patients diagnosed with COVID-19 between April 1, 2020 and June 24, 2021 from the Optum COVID-19 database, three case-control studies were conducted. Cases-defined as persons who: (1) were hospitalized within 30 days of COVID-19 diagnosis (n = 88,405); (2) were admitted to the intensive care unit (ICU)/received mechanical ventilation during COVID-19 hospitalization (n = 22,147); and (3) died during COVID-19 hospitalization (n = 2300)-were matched 1:1 using demographic/clinical factors with controls randomly selected from a pool of patients who did not experience the case definition/event. Medication use was based on prescription ≤90 days before COVID-19 diagnosis.

RESULTS: Statin use was associated with decreased risk of hospitalization (adjusted odds ratio [aOR], 0.72; 95% confidence interval [95% CI], 0.69, 0.75) and ICU admission/mechanical ventilation (aOR, 0.90; 95% CI, 0.84, 0.97). ACEI/ARB use was associated with decreased risk of hospitalization (aOR, 0.67; 95% CI, 0.65, 0.70), ICU admission/mechanical ventilation (aOR, 0.92; 95% CI, 0.86, 0.99), and death (aOR, 0.60; 95% CI, 0.47, 0.78). Anticoagulant use was associated with decreased risk of hospitalization (aOR, 0.94; 95% CI, 0.89, 0.99) and death (aOR, 0.56; 95% CI, 0.41, 0.77). Interaction effects-in the model predicting hospitalization-were statistically significant for statins and ACEI/ARBs (P < .0001), statins and anticoagulants (P = .003), ACEI/ARBs and anticoagulants (P < .0001). An interaction effect-in the model predicting ventilator use/ICU-was statistically significant for statins and ACEI/ARBs (P = .002).

CONCLUSIONS: Statins, ACEI/ARBs, and anticoagulants were associated with decreased risks of the adverse outcomes under study. These findings may provide clinically relevant information regarding potential treatment for patients with COVID-19.

PMID:37207280 | PMC:PMC10032048 | DOI:10.1016/j.ajmo.2023.100040

Osteoarthr Cartil Open. 2023 Apr 28;5(3):100365. doi: 10.1016/j.ocarto.2023.100365. eCollection 2023 Sep.

ABSTRACT

OBJECTIVE: Therapy for osteoarthritis ideally aims at preserving structure before radiographic change occurs. This study tests: a) whether longitudinal deterioration in cartilage thickness and composition (transverse relaxation-time T2) are greater in radiographically normal knees “at risk” of incident osteoarthritis than in those without risk factors; and b) which risk factors may be associated with these deteriorations.

DESIGN: 755 knees from the Osteoarthritis Initiative were studied; all were bilaterally Kellgren Lawrence grade [KLG] 0 initially, and had magnetic resonance images available at 12- and 48-month follow-up. 678 knees were “at risk”, whereas 77 were not (i.e., non-exposed reference). Cartilage thickness and composition change was determined in 16 femorotibial subregions, with deep and superficial T2 being analyzed in a subset (n ​= ​59/52). Subregion values were used to compute location-independent change scores.

RESULTS: In KLG0 knees “at risk”, the femorotibial cartilage thinning score (-634 ​± ​516 ​μm) over 3 years exceeded the thickening score by approximately 20%, and was 27% greater (p ​< ​0.01; Cohen D -0.27) than the thinning score in “non-exposed” knees (-501 ​± ​319 ​μm). Superficial and deep cartilage T2 change, however, did not differ significantly between both groups (p ​≥ ​0.38). Age, sex, body mass index, knee trauma/surgery history, family history of joint replacement, presence of Heberden’s nodes, repetitive knee bending were not significantly associated with cartilage thinning (r²<1%), with only knee pain reaching statistical significance.

CONCLUSIONS: Knees “at risk” of incident knee OA displayed greater cartilage thinning scores than those “non-exposed”. Except for knee pain, the greater cartilage loss was not significantly associated with demographic or clinical risk factors.

PMID:37207279 | PMC:PMC10188628 | DOI:10.1016/j.ocarto.2023.100365

Continence (Amst). 2022 Mar;1:100014. doi: 10.1016/j.cont.2022.100014. Epub 2022 Mar 18.

ABSTRACT

PURPOSE OR THE RESEARCH: Nearly 300,000 people are affected by spinal cord injury (SCI) with approximately 18,000 new cases annually, according to the National SCI Statistics Center. SCI affects physical mobility and impairs the function of multiple internal organs to cause lower urinary tract (LUT) dysfunctions manifesting as detrusor sphincter dyssynergia (DSD) and neurogenic detrusor overactivity (NDO) with detrimental consequences to the quality of life and increased morbidity. Multiple lines of evidence now support time dependent evolution of the complex SCI pathology which requires a multipronged treatment approach of immediate, specialized care after spinal cord trauma bookended by physical rehabilitation to improve the clinical outcomes. Instead of one size fits all treatment approach, we propose adaptive drug treatment to counter the time dependent evolution of SCI pathology, with three small molecule drugs with distinctive sites of action for the recovery of multiple functions.

PRINCIPAL RESULTS: Our findings demonstrate the improvement in the recovery of hindlimb mobility and bladder function of spinal cord contused mice following administration of small molecules targeting neurotrophin receptors, LM11A-31 and LM22B-10. While LM11A-31 reduced the cell death in the spinal cord, LM22B-10 promoted cell survival and axonal growth. Moreover, the soluble guanylate cyclase (sGC) activator, cinaciguat, enhanced the revascularization of the SCI injury site to promote vessel formation, dilation, and increased perfusion.

MAJOR CONCLUSIONS: Our adaptive three drug cocktail targets different stages of SCI and LUTD pathology: neuroprotective effect of LM11A-31 retards the cell death that occurs in the early stages of SCI; and LM22B-10 and cinaciguat promote neural remodeling and reperfusion at later stages to repair spinal cord scarring, DSD and NDO. LM11A-31 and cinaciguat have passed phase I and IIa clinical trials and possess significant potential for accelerated clinical testing in SCI/LUTD patients.

PMID:37207253 | PMC:PMC10194419 | DOI:10.1016/j.cont.2022.100014