Category: Statistics

J Phys Chem Lett. 2023 Aug 14:7469-7476. doi: 10.1021/acs.jpclett.3c00962. Online ahead of print.

ABSTRACT

Metal-organic framework (MOF) glasses have multiple potential applications, as they combine advantages of traditional glasses with those of MOFs. The melt-quenching process used to form MOF glasses typically leads to a significant decrease in porosity, but the structural origin of this thermally induced pore collapse remains largely unknown. Here, we study the melting process of three zeolitic imidazolate frameworks (ZIFs), namely ZIF-4, ZIF-62, and ZIF-76, using ab initio molecular dynamics (MD) simulations. By analyzing the MD data using topological data analysis, we show that while the three ZIF systems exhibit similar short-range order structural changes upon heating, they exhibit significant differences in their medium-range order structure. Specifically, ZIF-76 retains more of its medium-range order structures in the liquid state compared to the other glass-forming ZIF systems, which allows it to remain more porous than ZIF-4 and ZIF-62. As such, our results may aid in understanding the structural features that govern the ability to maintain porosity in the melt-quenched glassy state.

PMID:37579071 | DOI:10.1021/acs.jpclett.3c00962

J Laparoendosc Adv Surg Tech A. 2023 Aug 9. doi: 10.1089/lap.2023.0200. Online ahead of print.

ABSTRACT

Purpose: This study analyzed the safety and effectiveness of laparoscopic sleeve gastrectomy (LSG) in patients over 60 years old, in a long-term follow-up, in a high-volume bariatric center. Methods: We retrospectively analyzed all patients older than 60 years who underwent LSG in our center from January 2009 to December 2018. A prospectively collected database of 4991 consecutive LSG cases was reviewed. Results: One hundred seventy-nine sleeve gastrectomy procedures were performed in patients older than 60 years, 135 were aged 60-65 years (group A) and 44 were older than 65 years (group B). We reported five cases (2.7%) of early complications: three postoperative hemorrhages, one cardial leakage, and one perigastric abscess. No thromboembolic events or mortality rates were reported. The mean follow-up period was 5.5 years (66 months). The follow-up loss rate was about 29%. At last follow-up, the mean body-mass index/body mass/percentage of excess weight loss values were, respectively, 33.7 ± 7/86.1 ± 21/60.4 ± 28.6 in group A and 32.4 ± 6.4/82.6 ± 18/61.8 ± 33 in group B. We reported 5 (4.0%) trocar site hernias, 1 (0.8%) cardial junction stenosis, and 22 (18%) new outbreaks of gastroesophageal reflux (GERD). There were 7 reinterventions (5.7%): 5 for weight regain and 2 for GERD not responding to medical therapy. There were no statistically significant differences between the two age groups. Conclusions: LSG is a safe and effective treatment for severe obesity in people over 60 years old. There are no differences in results of patients over 65 years and between 60 and 65 years old. Scales that include associated medical problems and the patient’s general condition must be considered.

PMID:37579046 | DOI:10.1089/lap.2023.0200

Anal Chem. 2023 Aug 14. doi: 10.1021/acs.analchem.3c02389. Online ahead of print.

ABSTRACT

Mass spectrometry imaging (MSI) has gained increasing popularity for tissue-based diagnostics due to its ability to identify and visualize molecular characteristics unique to different phenotypes within heterogeneous samples. Data from MSI experiments are often assessed and visualized using various supervised and unsupervised statistical approaches. However, these approaches tend to fall short in identifying and concisely visualizing subtle, phenotype-relevant molecular changes. To address these shortcomings, we developed aggregated molecular phenotype (AMP) scores. AMP scores are generated using an ensemble machine learning approach to first select features differentiating phenotypes, weight the features using logistic regression, and combine the weights and feature abundances. AMP scores are then scaled between 0 and 1, with lower values generally corresponding to class 1 phenotypes (typically control) and higher scores relating to class 2 phenotypes. AMP scores, therefore, allow the evaluation of multiple features simultaneously and showcase the degree to which these features correlate with various phenotypes. Due to the ensembled approach, AMP scores are able to overcome limitations associated with individual models, leading to high diagnostic accuracy and interpretability. Here, AMP score performance was evaluated using metabolomic data collected from desorption electrospray ionization MSI. Initial comparisons of cancerous human tissues to their normal or benign counterparts illustrated that AMP scores distinguished phenotypes with high accuracy, sensitivity, and specificity. Furthermore, when combined with spatial coordinates, AMP scores allow visualization of tissue sections in one map with distinguished phenotypic borders, highlighting their diagnostic utility.

PMID:37579019 | DOI:10.1021/acs.analchem.3c02389

Interact J Med Res. 2023 Aug 14;12:e46900. doi: 10.2196/46900.

ABSTRACT

BACKGROUND: ChatGPT, a dialogue-based artificial intelligence language model, has shown promise in assisting clinical workflows and patient-clinician communication. However, there is a lack of feasibility assessments regarding its use for perioperative patient education in thoracic surgery.

OBJECTIVE: This study aimed to assess the appropriateness and comprehensiveness of using ChatGPT for perioperative patient education in thoracic surgery in both English and Chinese contexts.

METHODS: This pilot study was conducted in February 2023. A total of 37 questions focused on perioperative patient education in thoracic surgery were created based on guidelines and clinical experience. Two sets of inquiries were made to ChatGPT for each question, one in English and the other in Chinese. The responses generated by ChatGPT were evaluated separately by experienced thoracic surgical clinicians for appropriateness and comprehensiveness based on a hypothetical draft response to a patient’s question on the electronic information platform. For a response to be qualified, it required at least 80% of reviewers to deem it appropriate and 50% to deem it comprehensive. Statistical analyses were performed using the unpaired chi-square test or Fisher exact test, with a significance level set at P<.05.

RESULTS: The set of 37 commonly asked questions covered topics such as disease information, diagnostic procedures, perioperative complications, treatment measures, disease prevention, and perioperative care considerations. In both the English and Chinese contexts, 34 (92%) out of 37 responses were qualified in terms of both appropriateness and comprehensiveness. The remaining 3 (8%) responses were unqualified in these 2 contexts. The unqualified responses primarily involved the diagnosis of disease symptoms and surgical-related complications symptoms. The reasons for determining the responses as unqualified were similar in both contexts. There was no statistically significant difference (34/37, 92% vs 34/37, 92%; P=.99) in the qualification rate between the 2 language sets.

CONCLUSIONS: This pilot study demonstrates the potential feasibility of using ChatGPT for perioperative patient education in thoracic surgery in both English and Chinese contexts. ChatGPT is expected to enhance patient satisfaction, reduce anxiety, and improve compliance during the perioperative period. In the future, there will be remarkable potential application for using artificial intelligence, in conjunction with human review, for patient education and health consultation after patients have provided their informed consent.

PMID:37578819 | DOI:10.2196/46900

J Physiol. 2023 Aug 14. doi: 10.1113/JP285003. Online ahead of print.

ABSTRACT

A central question in sensory neuroscience is how neurons represent complex natural stimuli. This process involves multiple steps of feature extraction to obtain a condensed, categorical representation useful for classification and behaviour. It has previously been shown that central auditory neurons in the starling have composite receptive fields composed of multiple features. Whether this property is an idiosyncratic characteristic of songbirds, a group of highly specialized vocal learners or a generic property of sensory processing is unknown. To address this question, we have recorded responses from auditory cortical neurons in mice, and characterized their receptive fields using mouse ultrasonic vocalizations (USVs) as a natural and ethologically relevant stimulus and pitch-shifted starling songs as a natural but ethologically irrelevant control stimulus. We have found that these neurons display composite receptive fields with multiple excitatory and inhibitory subunits. Moreover, this was the case with either the conspecific or the heterospecific vocalizations. We then trained the sparse filtering algorithm on both classes of natural stimuli to obtain statistically optimal features, and compared the natural and artificial features using UMAP, a dimensionality-reduction algorithm previously used to analyse mouse USVs and birdsongs. We have found that the receptive-field features obtained with both types of the natural stimuli clustered together, as did the sparse-filtering features. However, the natural and artificial receptive-field features clustered mostly separately. Based on these results, our general conclusion is that composite receptive fields are not a unique characteristic of specialized vocal learners but are likely a generic property of central auditory systems. KEY POINTS: Auditory cortical neurons in the mouse have composite receptive fields with several excitatory and inhibitory features. Receptive-field features capture temporal and spectral modulations of natural stimuli. Ethological relevance of the stimulus affects the estimation of receptive-field dimensionality.

PMID:37578817 | DOI:10.1113/JP285003

JAMA Neurol. 2023 Aug 14. doi: 10.1001/jamaneurol.2023.2679. Online ahead of print.

ABSTRACT

IMPORTANCE: Levodopa has a short half-life and a limited window of opportunity for absorption in the proximal small intestine. IPX203 is an oral, extended-release formulation of carbidopa-levodopa developed to address these limitations.

OBJECTIVE: To assess the efficacy and safety of IPX203 vs immediate-release carbidopa-levodopa in patients with Parkinson disease who are experiencing motor fluctuations.

DESIGN, SETTING, AND PARTICIPANTS: RISE-PD was a 20-week, randomized, double-blind, double-dummy, active-controlled, phase 3 clinical trial. The study was conducted between November 6, 2018, and June 15, 2021, at 105 academic and clinical centers in the US and Europe. Patients with Parkinson disease taking a total daily dose of 400 mg or more of levodopa and experiencing an average of 2.5 hours or more daily off-time were included in the study. A total of 770 patients were screened, 140 were excluded (those taking controlled-release carbidopa-levodopa apart from a single daily bedtime dose, Rytary (Amneal Pharmaceuticals), additional carbidopa or benserazide, or catechol O-methyl transferase inhibitors or who had a history of psychosis within the past 10 years), and 630 were enrolled in the trial.

INTERVENTIONS: Following open-label immediate-release carbidopa-levodopa dose adjustment (3 weeks) and conversion to IPX203 (4 weeks), patients were randomized in a 1:1 ratio to double-blind, double-dummy treatment with immediate-release carbidopa-levodopa or IPX203 for 13 weeks.

MAIN OUTCOME AND MEASURES: The primary end point was mean change in daily good on-time (ie, on-time without troublesome dyskinesia) from baseline to the end of the double-blind treatment period.

RESULTS: A total of 630 patients (mean [SD] age, 66.5 [8.95] years; 396 [62.9%] men) were enrolled, and 506 patients were randomly assigned to receive IPX203 (n = 256) or immediate-release carbidopa-levodopa (n = 250). The study met its primary end point, demonstrating statistically significant improvement in daily good on-time for IPX203 compared to immediate-release carbidopa-levodopa (least squares mean, 0.53 hours; 95% CI, 0.09-0.97; P = .02), with IPX203 dosed a mean 3 times per day vs 5 times per day for immediate-release carbidopa-levodopa. Good on-time per dose increased by 1.55 hours with IPX203 compared to immediate-release carbidopa-levodopa (95% CI, 1.37-1.73; P < .001). IPX203 was well tolerated. The most common adverse events in the double-blind phase (IPX203 vs immediate-release carbidopa-levodopa) were nausea (4.3% vs 0.8%) and anxiety (2.7% vs 0.0%).

CONCLUSIONS AND RELEVANCE: In this study, IPX203 provided more hours of good on-time per day than immediate-release carbidopa-levodopa, even as IPX203 was dosed less frequently.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03670953.

PMID:37578800 | DOI:10.1001/jamaneurol.2023.2679

JAMA Netw Open. 2023 Aug 1;6(8):e2328810. doi: 10.1001/jamanetworkopen.2023.28810.

ABSTRACT

IMPORTANCE: Pharmacy deserts have increased, potentially affecting patient access and care. Historically, telepharmacies have been used to reduce pharmacy deserts to restore access, but states frequently restrict their operation.

OBJECTIVE: To analyze whether telepharmacy policy is associated with pharmacy deserts and access to pharmacy services.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed pharmacy location and census data from 2016 through 2019 for US states with new telepharmacy policies. Nearby control states were used for comparison in a pretest-posttest nonequivalent group design. Statistical analysis was performed from January 2022 to July 2023.

EXPOSURE: Intervention states were selected if a change in telepharmacy policy was adopted in 2017 or 2018.

MAIN OUTCOMES AND MEASURES: Pharmacy deserts were defined as any geographic area located at least 10 miles from the nearest pharmacy. Primary outcomes included the change in number of telepharmacies, pharmacy deserts, and population in pharmacy deserts. Secondary outcomes included the percentage of telepharmacies located in medically underserved areas or populations (MUA/Ps), and the association between a telepharmacy opening nearby and the transition of a pharmacy desert into a nonpharmacy desert.

RESULTS: Twelve US states were included in the study (8 intervention states, 4 control states). Intervention states experienced an increase in the mean number of telepharmacies to 7.25 with a range of 4 (Arizona, Indiana) to 14 (Iowa), but control states remained at a mean of 0.25 telepharmacies with a range of 0 to 1 (Kansas). Compared with controls, intervention states experienced a 4.5% (95% CI, 1.6% to 7.4%) decrease in the percentage of places defined as pharmacy deserts (P = .001) and an 11.1% (95% CI, 2.4% to 22.6%) decrease in the population in a pharmacy desert (P = .03). Telepharmacies were more likely to be located in a MUA/P than traditional pharmacies (preperiod in MUA/P: 63.2% of telepharmacies [12 of 19] vs 33.9% of traditional pharmacies [5984 of 17 511]; P = .01; postperiod in MUA/P: 62.7% of telepharmacies [37 of 59] vs 33.7% of traditional pharmacies [5998 of 17 800]; P < .001). When a telepharmacy was established in pharmacy deserts, 37.5% (30 of 80) no longer met the study’s definition of a pharmacy desert the following year. In contrast, only 1.8% of places (68 of 3892) where a nearby telepharmacy did not open experienced this change (χ21=416.4; P < .001).

CONCLUSIONS AND RELEVANCE: In this cohort study, intervention states experienced a reduced population in pharmacy deserts, suggesting an association with new telepharmacy openings. States aiming to improve pharmacy access might consider less restrictive telepharmacy policies to potentially elicit greater patient outcomes.

PMID:37578793 | DOI:10.1001/jamanetworkopen.2023.28810

JAMA Netw Open. 2023 Aug 1;6(8):e2328828. doi: 10.1001/jamanetworkopen.2023.28828.

ABSTRACT

IMPORTANCE: Ginkgo diterpene lactone meglumine (GDLM) has attracted much attention because of its potential neuroprotective properties in ischemic stroke. The efficacy of GDLM in patients with acute ischemic stroke (AIS) needs to be verified by well-designed randomized clinical trials.

OBJECTIVE: To assess the efficacy and safety of GDLM in patients with AIS.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group trial involved 3448 patients who had AIS, were aged 18 to 80 years, had a clinically diagnosed AIS symptom within 48 hours of onset, had a modified Rankin Scale (mRS) score of 0 or 1 prior to onset, and had a National Institutes of Health Stroke Scale score ranging from 4 to 24. The trial took place at 100 centers in China from February 1, 2016, to May 1, 2018. The mRS is a global stroke disability scale with scores ranging from 0 (no symptoms or completely recovered) to 6 (death). The National Institutes of Health Stroke Scale is a tool used by clinicians to quantify impairment caused by stroke (range, 0-42, with higher scores indicating greater severity). Data were analyzed from January 2019 to December 2022.

INTERVENTIONS: Patients were randomized to receive GDLM or placebo once daily via intravenous infusion in a 1:1 ratio. The treatment was dispensed within 48 hours after symptoms and continued for 14 days. Interventions of thrombolysis and thrombectomy were not permitted during the treatment.

MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients with an mRS of 0 or 1 on day 90 after randomization. Safety outcomes included adverse events and serious adverse events.

RESULTS: A total of 3448 patients were randomized, with 1725 patients assigned to the GDLM group and 1723 patients assigned to the placebo group. The median (IQR) age of the patients was 63 (55-71) years, and 1232 (35.7%) were women. The primary outcome on day 90 occurred in 877 patients (50.8%) in the GDLM group, and 759 patients (44.1%) in the placebo group (risk difference, 6.79%; 95% CI, 3.46%-10.10%; odds ratio, 1.31; 95% CI, 1.15-1.50; relative risk, 1.15; 95% CI, 1.08-1.24; P < .001). Adverse events occurred relatively equally between the 2 groups (303 [17.6%] vs 298 [17.3%]; risk difference, 0.27%; 95% CI, -2.26% to 2.80%; odds ratio, 1.02; 95% CI, 0.85-1.21; relative risk, 1.02; 95% CI, 0.88-1.17; P = .83).

CONCLUSIONS AND RELEVANCE: Among patients with AIS in this randomized clinical trial, GDLM improved the proportion of patients achieving favorable clinical outcomes at 90 days compared with placebo.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02526225.

PMID:37578791 | DOI:10.1001/jamanetworkopen.2023.28828

JAMA Neurol. 2023 Aug 14. doi: 10.1001/jamaneurol.2023.2560. Online ahead of print.

ABSTRACT

IMPORTANCE: An increased tau positron emission tomography (PET) signal in the medial temporal lobe (MTL) has been observed in older individuals in the absence of amyloid-β (Aβ) pathology. Little is known about the longitudinal course of this condition, and its association with Alzheimer disease (AD) remains unclear.

OBJECTIVE: To study the pathologic and clinical course of older individuals with PET-evidenced MTL tau deposition (TMTL+) in the absence of Aβ pathology (A-), and the association of this condition with the AD continuum.

DESIGN, SETTING, AND PARTICIPANTS: A multicentric, observational, longitudinal cohort study was conducted using pooled data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), Harvard Aging Brain Study (HABS), and the AVID-A05 study, collected between July 2, 2015, and August 23, 2021. Participants in the ADNI, HABS, and AVID-A05 studies (N = 1093) with varying degrees of cognitive performance were deemed eligible if they had available tau PET, Aβ PET, and magnetic resonance imaging scans at baseline. Of these, 128 participants did not meet inclusion criteria based on Aβ PET and tau PET biomarker profiles (A+ TMTL-).

EXPOSURES: Tau and Aβ PET, magnetic resonance imaging, cerebrospinal fluid biomarkers, and cognitive assessments.

MAIN OUTCOMES AND MEASURES: Cross-sectional and longitudinal measures for tau and Aβ PET, cortical atrophy, cognitive scores, and core AD cerebrospinal fluid biomarkers (Aβ42/40 and tau phosphorylated at threonine 181 p-tau181 available in a subset).

RESULTS: Among the 965 individuals included in the study, 503 were women (52.1%) and the mean (SD) age was 73.9 (8.1) years. A total of 51% of A- individuals and 78% of A+ participants had increased tau PET signal in the entorhinal cortex (TMTL+) compared with healthy younger (aged <39 years) controls. Compared with A- TMTL-, A- TMTL+ participants showed statistically significant, albeit moderate, longitudinal (mean [SD], 1.83 [0.84] years) tau PET increases that were largely limited to the temporal lobe, whereas those with A+ TMTL+ showed faster and more cortically widespread tau PET increases. In contrast to participants with A+ TMTL+, those with A- TMTL+ did not show any noticeable Aβ accumulation over follow-up (mean [SD], 2.36 [0.76] years). Complementary cerebrospinal fluid analysis confirmed longitudinal p-tau181 increases in A- TMTL+ in the absence of increased Aβ accumulation. Participants with A- TMTL+ had accelerated MTL atrophy, whereas those with A+ TMTL+ showed accelerated atrophy in widespread temporoparietal brain regions. Increased MTL tau PET uptake in A- individuals was associated with cognitive decline, but at a significantly slower rate compared with A+ TMTL+.

CONCLUSIONS AND RELEVANCE: In this study, individuals with A- TMTL+ exhibited progressive tau accumulation and neurodegeneration, but these processes were comparably slow, remained largely restricted to the MTL, were associated with only subtle changes in global cognitive performance, and were not accompanied by detectable accumulation of Aβ biomarkers. These data suggest that individuals with A- TMTL+ are not on a pathologic trajectory toward AD.

PMID:37578787 | DOI:10.1001/jamaneurol.2023.2560

Updates Surg. 2023 Aug 14. doi: 10.1007/s13304-023-01628-y. Online ahead of print.

ABSTRACT

Neoadjuvant therapy (NAT) + surgical resection for pancreatic cancer (PC) has gained consensus in recent years. Pathological response (PR) is generally assessed according to the College of American Pathologists grading system, ranging from 0 (complete response) to 3 (no response). The aim of our study is to evaluate the PR in a series of resections for PC after NAT and its prognostic implication. 112 patients undergone NAT and resection for PC between 2011 and 2020 were retrospectively evaluated. PR was 0/1, 2 and 3 in 18 (15%), 79 (61%) and 29 (24%) cases, respectively. Chemotherapy regimens different from FOLFIRINOX and gemcitabine + nab-paclitaxel (OR 11.61 (2.53-53.36), p = 0.002) and lymphovascular invasion (OR 11.28 (1.89-67.23), p = 0.008) were associated to PR-3. Median follow-up was 25.8 (3.6-130.5) months. For PR-0/1, PR-2 and PR-3, median DFS was 45.8, 11.5, 4.6 months (p < 0.0001), respectively, while median OS was not reached, 27.1 and 17.5 months (p = 0.0006), respectively. At univariate analysis, PR-0/1 was significantly associated to better DFS and OS (HR 0.33 (0.17-0.67), p = 0.002; HR 0.20 (0.07-0.54), p = 0.002, respectively). At multivariate analysis, pancreaticoduodenectomy (HR 0.50 (0.30-0.84), p = 0.009), LNR (HR 27.14 (1.21-608.9), p = 0.038) and lymphovascular invasion (HR 1.99 (1.06-3.76), p = 0.033) were independently associated to DFS; pre-treatment CA 19.9 value (HR 1.00 (1.00-1.00), p = 0.025), post-treatment resectability status (HR 0.51 (0.28-0.95), p = 0.035), pancreaticoduodenectomy (HR 0.56 (0.32-0.99), p = 0.050), severe morbidity (2.99 (1.22-7.55), p = 0.017), LNR (HR 56.8 (2.08-1548.3), p = 0.017), lymphovascular invasion (HR 2.18 (1.08-4.37), p = 0.029) were independently associated to OS. PR did not reach statistical significance at multivariate analysis. A favorable PR is observed only in a limited number of cases. The prognostic role of PR, despite being promising, remains unclear and further multicentric studies are needed.

PMID:37578734 | DOI:10.1007/s13304-023-01628-y