Category: Statistics

J Clin Oncol. 2023 Jul 31:JCO2300045. doi: 10.1200/JCO.23.00045. Online ahead of print.

ABSTRACT

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.ARST1321 was a phase II study designed to compare the near complete pathologic response rate after preoperative chemoradiation with/without pazopanib in children and adults with intermediate-/high-risk chemotherapy-sensitive body wall/extremity non-Rhabdomyosarcoma Soft Tissue Sarcoma (ClinicalTrials.gov identifier: NCT02180867). Enrollment was stopped early following a predetermined interim analysis that found the rate of near complete pathologic response to be significantly greater with the addition of pazopanib. As a planned secondary aim of the study, the outcome data for this cohort were analyzed. Eight-five eligible patients were randomly assigned to receive (regimen A) or not receive (regimen B) pazopanib in combination with ifosfamide and doxorubicin + preoperative radiotherapy followed by primary resection at week 13 and then further chemotherapy at week 25. As of December 31, 2021, at a median survivor follow-up of 3.3 years (range, 0.1-5.8 years), the 3-year event-free survival for all patients in the intent-to-treat analysis was 52.5% (95% CI, 34.8 to 70.2) for regimen A and 50.6% (95% CI, 32 to 69.2) for regimen B (P = .8677, log-rank test); the 3-year overall survival was 75.7% (95% CI, 59.7 to 91.7) for regimen A and 65.4% (95% CI, 48.1 to 82.7) for regimen B (P = .1919, log-rank test). Although the rate of near complete pathologic response was significantly greater with the addition of pazopanib, outcomes were not statistically significantly different between the two regimens.

PMID:37523624 | DOI:10.1200/JCO.23.00045

Surg Laparosc Endosc Percutan Tech. 2023 Jul 14. doi: 10.1097/SLE.0000000000001203. Online ahead of print.

ABSTRACT

BACKGROUND: Parastomal hernia repairs (PHRs) are often complex and challenging, even for experienced abdominal wall surgeons. Although the ideal therapeutic option in the setting of a parastomal hernia is to restore intestinal continuity, this is often not feasible, and numerous techniques have been described for PHR. Current guidelines recommend using mesh for elective PHR, but there is a scarcity of evidence comparing different PHR techniques. We aimed to report a meta-analysis comparing the outcomes of the “Sugarbaker” and “Keyhole” mesh configuration in PHR.

METHODS: A literature search of PubMed, Embase, Scopus, and Cochrane Library databases was performed to identify studies comparing Sugarbaker and Keyhole mesh configuration in PHR. Postoperative outcomes were assessed by means of pooled analysis and meta-analysis. Statistical analysis was performed using RevMan 5.4. Heterogeneity was assessed with I2 statistics.

RESULTS: A total of 3247 studies were screened, and 27 were fully reviewed. Ten studies and 632 patients were included in the meta-analysis. Three hundred five patients (48.3%) with Keyhole and 327 patients (51.7%) with Sugarbaker mesh configuration. Four hundred thirty-three patients (68.5%) underwent laparoscopic PHR with intraperitoneal onlay mesh. Sugarbaker mesh configuration was associated with lower hernia recurrence compared with Keyhole (odds ratio: 0.39; 95% CI: 0.19-0.83; P = 0.01; I2 = 46%). No differences were seen in overall complications, reoperations, stoma outlet obstruction, mesh infection, and postoperative bleeding.

CONCLUSION: PHR with Sugarbaker mesh configuration is associated with decreased hernia recurrence compared with Keyhole and had similar rates of overall complications, reoperations, stoma outlet obstruction, mesh infection, and postoperative bleeding.

PMID:37523583 | DOI:10.1097/SLE.0000000000001203

Surg Laparosc Endosc Percutan Tech. 2023 Jul 24. doi: 10.1097/SLE.0000000000001202. Online ahead of print.

ABSTRACT

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is a minimally invasive technique widely used to diagnose and treat pancreatic and biliary diseases; however, it is linked with imminent hyperamylasemia and post-ERCP pancreatitis (PEP). Somatostatin and indomethacin are the classic recommended drugs used for PEP prevention.

OBJECTIVE: To elucidate the effects of somatostatin and indomethacin mono or in combination to prevent hyperamylasemia and PEP in high-risk individuals.

METHODS: Altogether 1458 patients who underwent ERCP in our hospital from January 2016 to May 2022 were included in this investigation and categorized into 4 groups based on the treatment regimen: placebo, indomethacin, somatostatin, and indomethacin + somatostatin. The pre operation and post operation (at 6, 12, and 24 h) hospitalization cost, length of stay, the occurrence of hyperamylasemia and PEP, levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-8, and VAS pain score were determined in the 4 groups. In all the groups, VAS and IL-6, TNF-α, and IL-8 levels substantially increased in the pretreatment and decreased sequentially from 6 to 24 h post operation. The individuals in the indomethacin revealed substantially reduced hyperamylasemia, VAS, and levels of IL-6, TNF-α, and IL-8, 6 h post operation, whereas the hospitalization fee, length of stay, PEP incidence, VAS, levels of IL-6, TNF-α, and IL-8, 12 and 24 h post operation were not statistically important in comparison with the individuals who received placebo therapy. The somatostatin and the indomethacin + somatostatin groups indicated markedly alleviated hospitalization fee, length of stay, the occurrence of hyperamylasemia and PEP, VAS, and the levels of IL-6, TNF-α, and IL-8 at 6, 12, and 24 h post operation compared with the placebo cohort. Furthermore, compared with the indomethacin group, the above-determined factors notably reduced at 6, 12, and 24 h post operation in somatostatin and indomethacin + somatostatin groups. It was also observed that the indomethacin + somatostatin group has substantially decreased the occurrence of hyperamylasemia, VAS score, and levels of IL-6, TNF-α, and IL-8, 6 hours post operation, while at 12 and 24 h post operation, the hospitalization fee, length of stay and incidence of PEP, VAS, levels of IL-6, TNF-α, and IL-8 were not statistically important compared with the somatostatin group. It is also worth noting that the side effects of both drugs are rare and mild.

RESULTS: For high-risk PEP patients, indomethacin and somatostatin can efficiently alleviate post-operative hyperamylasemia and improve their life standard within 6 hours and 24 hours, respectively. Indomethacin is suitable for individuals who underwent simple, short-duration ERCP with expected mild post-operative abdominal pain, whereas somatostatin is given to patients with complicated, long-duration ERCP and expected severe post-operative abdominal pain. Their combinational therapy produces a synergistic effect and can reduce the incidence of hyperamylasemia, thereby improving patients’ quality of life within 6 h and is also effective against individuals who received a more complicated, longer-duration ERCP and were expected to have severer and longer post-operative abdominal pain.

PMID:37523580 | DOI:10.1097/SLE.0000000000001202

Proc Natl Acad Sci U S A. 2023 Aug 8;120(32):e2308935120. doi: 10.1073/pnas.2308935120. Epub 2023 Jul 31.

ABSTRACT

The instability of Stokes waves, steady propagating waves on the surface of an ideal fluid of infinite depth, is a fundamental problem in the field of nonlinear science. The dominant instability of these waves depends on their steepness. For small amplitude waves, it is well known that the Benjamin-Feir or modulational instability dominates the dynamics of a wave train. We demonstrate that for steeper waves, an instability caused by disturbances localized at the wave crest vastly surpasses the growth rate of the modulational instability. These dominant localized disturbances are either coperiodic with the Stokes wave or have twice its period. In either case, the nonlinear evolution of the instability leads to the formation of plunging breakers. This phenomenon explains why long propagating ocean swell consists of small-amplitude waves.

PMID:37523557 | DOI:10.1073/pnas.2308935120

Proc Natl Acad Sci U S A. 2023 Aug 8;120(32):e2300828120. doi: 10.1073/pnas.2300828120. Epub 2023 Jul 31.

ABSTRACT

Traditionally, nuclear spin is not considered to affect biological processes. Recently, this has changed as isotopic fractionation that deviates from classical mass dependence was reported both in vitro and in vivo. In these cases, the isotopic effect correlates with the nuclear magnetic spin. Here, we show nuclear spin effects using stable oxygen isotopes (¹⁶O, ¹⁷O, and ¹⁸O) in two separate setups: an artificial dioxygen production system and biological aquaporin channels in cells. We observe that oxygen dynamics in chiral environments (in particular its transport) depend on nuclear spin, suggesting future applications for controlled isotope separation to be used, for instance, in NMR. To demonstrate the mechanism behind our findings, we formulate theoretical models based on a nuclear-spin-enhanced switch between electronic spin states. Accounting for the role of nuclear spin in biology can provide insights into the role of quantum effects in living systems and help inspire the development of future biotechnology solutions.

PMID:37523549 | DOI:10.1073/pnas.2300828120

Proc Natl Acad Sci U S A. 2023 Aug 8;120(32):e2303402120. doi: 10.1073/pnas.2303402120. Epub 2023 Jul 31.

ABSTRACT

The endoplasmic reticulum (ER) and mitochondria form a unique subcellular compartment called mitochondria-associated ER membranes (MAMs). Disruption of MAMs impairs Ca²⁺ homeostasis, triggering pleiotropic effects in the neuronal system. Genome-wide kinase-MAM interactome screening identifies casein kinase 2 alpha 1 (CK2A1) as a regulator of composition and Ca²⁺ transport of MAMs. CK2A1-mediated phosphorylation of PACS2 at Ser207/208/213 facilitates MAM localization of the CK2A1-PACS2-PKD2 complex, regulating PKD2-dependent mitochondrial Ca²⁺ influx. We further reveal that mutations of PACS2 (E209K and E211K) associated with developmental and epileptic encephalopathy-66 (DEE66) impair MAM integrity through the disturbance of PACS2 phosphorylation at Ser207/208/213. This, in turn, causes the reduction of mitochondrial Ca²⁺ uptake and the dramatic increase of the cytosolic Ca²⁺ level, thereby, inducing neurotransmitter release at the axon boutons of glutamatergic neurons. In conclusion, our findings suggest a molecular mechanism that MAM alterations induced by pathological PACS2 mutations modulate Ca²⁺-dependent neurotransmitter release.

PMID:37523531 | DOI:10.1073/pnas.2303402120

Proc Natl Acad Sci U S A. 2023 Aug 8;120(32):e2303647120. doi: 10.1073/pnas.2303647120. Epub 2023 Jul 31.

ABSTRACT

Multimodal single-cell technologies profile multiple modalities for each cell simultaneously, enabling a more thorough characterization of cell populations. Existing dimension-reduction methods for multimodal data capture the “union of information,” producing a lower-dimensional embedding that combines the information across modalities. While these tools are useful, we focus on a fundamentally different task of separating and quantifying the information among cells that is shared between the two modalities as well as unique to only one modality. Hence, we develop Tilted Canonical Correlation Analysis (Tilted-CCA), a method that decomposes a paired multimodal dataset into three lower-dimensional embeddings-one embedding captures the “intersection of information,” representing the geometric relations among the cells that is common to both modalities, while the remaining two embeddings capture the “distinct information for a modality,” representing the modality-specific geometric relations. We analyze single-cell multimodal datasets sequencing RNA along surface antibodies (i.e., CITE-seq) as well as RNA alongside chromatin accessibility (i.e., 10x) for blood cells and developing neurons via Tilted-CCA. These analyses show that Tilted-CCA enables meaningful visualization and quantification of the cross-modal information. Finally, Tilted-CCA’s framework allows us to perform two specific downstream analyses. First, for single-cell datasets that simultaneously profile transcriptome and surface antibody markers, we show that Tilted-CCA helps design the target antibody panel to complement the transcriptome best. Second, for developmental single-cell datasets that simultaneously profile transcriptome and chromatin accessibility, we show that Tilted-CCA helps identify development-informative genes and distinguish between transient versus terminal cell types.

PMID:37523521 | DOI:10.1073/pnas.2303647120

Vascular. 2023 Jul 31:17085381231192377. doi: 10.1177/17085381231192377. Online ahead of print.

ABSTRACT

INTRODUCTION: Iliac aneurysms occur in 10% of patients with abdominal aortic aneurysms (AAA). There are three different endovascular approaches to their treatment in the context of infrarenal Endovascular Aortic Aneurysm Repair (EVAR): occlusion by coiling the internal iliac, incorporation using an iliac branch device, and delaying repair using a bell bottom limb. We sought to determine outcomes associated with these three strategies in our practice.

METHODOLOGY: The study was a combined prospective cohort study with a retrospective arm: prospective patient recruitment was done for 1 year from September 2019 and ended by September 2020, and retrospective data was collected from 2017 to 2019. Demographic, procedural, and imaging data was collected. SPSS was used to analyze data as patients were classified by limbs in four groups: iliac branched, bell bottom, coil and cover technique, and standard treated limbs.

RESULTS: There were 65 male and 4 female patients included in this study incorporating 137 limbs with a mean age of 78 years (SD ± 8 years). Two patients died after discharge (at 3 and 21 months postoperatively, without hospital admission) and five patients were lost to long-term follow-up. Three patients had operations that deviated from the plan: one was an IBD converted to bell bottom, one was an IBD that was converted to coil and cover, and one was a bell bottom that did not seal. Follow-up revealed late type IB endoleak in three bell bottom limbs and one limb treated with coil and cover. Common iliac occlusion occurred in one IBD, three bell bottom limbs, and two limbs treated with coil/cover technique. There were four additional ischemic events (buttock claudication in three and intestinal ischemia in one): all ischemic events occurred in the coil and cover group (p = .001).

CONCLUSIONS: Given the small population size examined in this study, there is no statistical difference between treatment groups; however, there was a trend toward bell bottom technique being associated with higher incidence of type IB endoleak. Coil and cover technique was associated with decreased IB endoleak; however, Buttock claudication and intestinal ischemia occurred more significantly in this group. Using IBD may be the best strategy to improve short- and long-term outcomes in patients with iliac aneurysms.

PMID:37523224 | DOI:10.1177/17085381231192377

J Comput Biol. 2023 Jul 31. doi: 10.1089/cmb.2023.0096. Online ahead of print.

ABSTRACT

International Classification of Diseases (ICD) serves as the foundation for generating comparable global disease statistics across regions and over time. The process of ICD coding involves assigning codes to diseases based on clinical notes, which can describe a patient’s condition in a standard way. However, this process is complicated by the vast number of codes and the intricate taxonomy of ICD codes, which are hierarchically organized into various levels, including chapter, category, subcategory, and its subdivisions. Many existing studies focus solely on predicting subcategory codes, ignoring the hierarchical relationships among codes. To address this limitation, we propose a multitask learning model that trains multiple classifiers for different code levels, while also capturing the relations between coarser and finer-grained labels through a reinforcement mechanism. Our approach is evaluated on both English and Chinese benchmark dataset, and we demonstrate that our method achieves competitive performance with baseline models, particularly in terms of macro-F1 results. These findings suggest that our approach effectively leverages the hierarchical structure of ICD codes to improve disease code prediction accuracy. Analysis of attention mechanism shows that multigranularity attention of our model captures crucial feature of input text on different granularity levels, which can provide reasonable explanations for the prediction results.

PMID:37523219 | DOI:10.1089/cmb.2023.0096

Ergonomics. 2023 Jul 31:1-21. doi: 10.1080/00140139.2023.2240048. Online ahead of print.

ABSTRACT

Accident analysis methods are used to model the multifactorial cause of adverse incidents. Methods such as AcciMap, STAMP-CAST and recently AcciNet, are systemic approaches that support the identification of safety interventions across sociotechnical system levels. Despite their growing popularity, little is known about how reliable systems-based methods are when used to describe, model and classify contributory factors and relationships. Here, we conducted an intra-rater and inter-rater reliability assessment of AcciMap, STAMP-CAST and AcciNet using the Signal Detection Theory (SDT) paradigm. A total of 180 hours’ worth of analyses across 360 comparisons were performed by 30 expert analysts. Findings revealed that all three methods produced a weak to moderate positive correlation coefficient, however the inter-rater reliability of STAMP-CAST was significantly higher compared to AcciMap and AcciNet. No statistically significant or practically meaningful differences were found between methods in the overall intra-rater reliability analyses. Implications and future research directions are discussed.

PMID:37523211 | DOI:10.1080/00140139.2023.2240048