Category: Statistics

Methods Enzymol. 2024;694:285-301. doi: 10.1016/bs.mie.2023.12.014. Epub 2024 Jan 16.

ABSTRACT

Single-molecule magnetic tweezers have recently been adapted for monitoring the interactions between transmembrane helices of membrane proteins within lipid bilayers. In this chapter, we describe the procedures of conducting studies on membrane protein folding using a robust magnetic tweezer method. This tweezer method is capable of observing thousands of (un)folding transitions over extended periods of several to tens of hours. Using this approach, we can dissect the folding pathways of membrane proteins, determine their folding time scales, and map the folding energy landscapes, with a higher statistical reliability. Our robust magnetic tweezers also allow for estimating the folding speed limit of helical membrane proteins, which serves as a link between the kinetics and barrier energies.

PMID:38492955 | DOI:10.1016/bs.mie.2023.12.014

Fertil Steril. 2024 Mar 14:S0015-0282(24)00173-0. doi: 10.1016/j.fertnstert.2024.03.003. Online ahead of print.

ABSTRACT

The last few decades have witnessed a rise in the global uptake of in vitro fertilization (IVF). To ensure optimal use of this technology, it is important for patients and clinicians to have access to tools which can provide accurate estimates of treatment success and understand the contribution of key clinical and laboratory parameters which influence the chance of conception following IVF. The focus of this review is to identify key predictors of IVF success and assess their impact in terms of live birth rates. We have identified eleven predictors that consistently feature in currently available prediction models, including age, duration of infertility, ethnicity, body mass index (BMI), antral follicle count, previous pregnancy history, cause of infertility, sperm parameters, number of oocytes collected, morphology of transferred embryos, and day of embryo transfer.

PMID:38492930 | DOI:10.1016/j.fertnstert.2024.03.003

J Theor Biol. 2024 Mar 14:111793. doi: 10.1016/j.jtbi.2024.111793. Online ahead of print.

ABSTRACT

The internal behaviour of a population is an important feature to take account of when modelling its dynamics. In line with kin selection theory, many social species tend to cluster into distinct groups in order to enhance their overall population fitness. Temporal interactions between populations are often modelled using classical mathematical models, but these sometimes fail to delve deeper into the, often uncertain, relationships within populations. Here, we introduce a stochastic framework that aims to capture the interactions of animal groups and an auxiliary population over time. We demonstrate the model’s capabilities, from a Bayesian perspective, through simulation studies and by fitting it to predator-prey count time series data. We then derive an approximation to the group correlation structure within such a population, while also taking account of the effect of the auxiliary population. We finally discuss how this approximation can lead to ecologically realistic interpretations in a predator-prey context. This approximation also serves as verification to whether the population in question satisfies our various assumptions. Our modelling approach will be useful for empiricists for monitoring groups within a conservation framework and also theoreticians wanting to quantify interactions, to study cooperation and other phenomena within social populations.

PMID:38492917 | DOI:10.1016/j.jtbi.2024.111793

Ophthalmology. 2024 Mar 14:S0161-6420(24)00186-6. doi: 10.1016/j.ophtha.2024.03.010. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate a commercially available dexamethasone intracanalicular insert to treat dry eye.

DESIGN: Single-center, double-masked, randomized controlled trial.

PARTICIPANTS: Patients with clinically significant aqueous-deficient dry eye [combined ocular surface staining score ≥3 (0-12), corneal fluorescein staining ≥2 (0-6), and Schirmer’s wetting <10 mm at 5 minutes in both eyes] with symptoms (dryness, eye discomfort, or visual fatigue, ≥30 [0-100]) despite treatment with at least one prescription drop and deemed candidate for topical steroid.

METHODS: Seventy-five adult patients were enrolled. A 1:1 randomization sequence was used to determine which eye of each patient would receive the treatment (dexamethasone 0.4 mg intracanalicular insert with 30-day elution time) or the sham (collagen plug). The fellow eye received the opposite treatment. Patients were masked to treatment assignment. Follow-up visits (at weeks 2, 4, and 6) were performed by a masked investigator.

MAIN OUTCOME MEASURES: Dry eye parameters and patient symptoms were used for efficacy and intraocular pressure (IOP) was used for safety assessment.

RESULTS: The severity of dry eye was comparable between the treatment arms (fellow eyes) at baseline. Eyes that received the dexamethasone insert had significantly less corneal staining at week 4 (mean difference [MD] -0.55, 95% confidence interval [CI] = -0.91, -0.19) and conjunctival staining at week 4 (MD -0.68, 95% CI = -1.05, -0.30) and week 6 (MD -0.34, 95% CI = -0.65, -0.02). Schirmer’s wetting was comparable between the two treatment arms. Although the patients reported less dryness in eyes that received the insert at week 4 (MD -5.5, 95% CI = -11.4, 0.4), there were no statistically significant differences in any patient-reported symptoms. At week 4, dexamethasone-treated eyes were more likely to experience an IOP increase (by 5-10 mm Hg) (9 eyes vs. 1 eye; relative risk [RR] = 9.00, 95% CI = 1.14, 71.0; due to sparse events, the CI was very wide). All cases of increased IOP were managed with short-term topical beta blockers and subsided.

CONCLUSIONS: Dexamethasone intracanalicular insert may be considered a dropless dual treatment for clinically significant aqueous-deficient dry eye when topical steroid treatment is deemed appropriate.

PMID:38492864 | DOI:10.1016/j.ophtha.2024.03.010

J ISAKOS. 2024 Mar 14:S2059-7754(24)00052-X. doi: 10.1016/j.jisako.2024.03.007. Online ahead of print.

ABSTRACT

IMPORTANCE: Bibliometric research is a statistical analysis of publications to measure the scientific output in a specific field in order to highlight medical developments or knowledge gaps and to direct future scientific research. The quantity of orthopedic papers on the internet is astounding and is steadily growing as a result of recent advancements in technology and medicine. This is why choosing the right information is essential AIM: The purpose of this study was to analyze the current literature for trends in publications regarding quadriceps tendon grafting of the anterior cruciate ligament (ACL).

EVIDENCE REVIEW: PubMed was searched on 8/28/2023. References were collected from PubMed, and trends were analyzed using this information. This search retrieved 405 articles regarding human and animal studies. We analyzed the top 10 authors and journals in terms of publication numbers, citation numbers, and citations per year. The PubMed-by-year feature was used to compare the number of publications regarding ACL reconstruction by quadriceps grafting with all publications in PubMed.

FINDINGS: The number of yearly publications averaged 10 or less up to 2018, starting from 1982 when the first paper on the quadriceps tendon was published. However, the number of publications increased from 2018. While the total number of publications on this topic was 405, 260 were published from 2018 alone. The number of citations was 8262 in total over all years. It is expected that the last five years’ publications, especially those for the last year, will be low in number, as it takes time for citations to accrue. The journal Arthroscopy published the most articles on this topic, with 57 papers and 1884 citations, followed by the American Journal of Sports Medicine, with 39 articles and 1576 citations. The top three journals on this topic were Arthroscopy, AJSM and KSSTA. The most published author was Musahl V (with 24 articles), and the most cited author was Xerogeanes JW (with 570 citations).

CONCLUSIONS AND RELEVANCE: Global trend analysis suggests that research on anterior cruciate ligament reconstruction with the quadriceps has significantly increased in the last 5 years and that the number of papers on this topic is increasing steadily. We found that the publications and citations are exhibiting a rising trend, Arthroscopy is the most impactful journal, and Musahl V is the most impactful author on the topic. Xerogeanes JW is the author with the most citations on the topic. The promising clinical results of anterior cruciate ligament reconstruction with the quadriceps tendon have attracted the most research interest.

LEVEL OF EVIDENCE: Level IV.

PMID:38492850 | DOI:10.1016/j.jisako.2024.03.007

J ISAKOS. 2024 Mar 14:S2059-7754(24)00055-5. doi: 10.1016/j.jisako.2024.03.010. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess for clinically important differences in patient reported outcome measures (PROMs) at one- and two-years post anterior cruciate ligament reconstruction (ACLR).

METHODS: A retrospective comparison of prospectively collected PROMs for a single cohort who underwent a primary ACLR with or without associated meniscal surgery from 2016 to 2020 was assessed. Six externally validated PROMs were collected pre-operatively and at standardized times post-operatively. Descriptive statistics and paired equivalence testing of PROMs at one- and two-years after surgery was completed using previously published or calculated minimal clinically important differences as upper and lower equivalence limits. A repeated measures analysis of PROMs that were not clinically equivalent at one- and two-years after surgery was completed to assess for a clinically significant difference. Subgroup analyses based on sex, age and associated meniscal injury were completed.

RESULTS: One-hundred and forty-five participants with a mean age of 28.7 years (standard deviation: 9.9 years) were included in the final analysis. All PROMs were clinically equivalent at two- compared to one-year after ACLR except the Quality of Life and Sport and Recreation domains of the Knee Injury and Osteoarthritis Outcome Score (KOOS). The Quality of Life (mean difference (MD):12.3, P < 0.01, effect size (η²): 0.65) and Sport and Recreation (MD: 8.78, P < 0.01, η²: 0.50) domains of the KOOS were clinically different at two- compared to one-year post-operatively. No major differences were found in the subgroup analyses compared to the entire included sample.

CONCLUSION: While most PROMs were equivalent at two- compared to one-year after ACLR, the Quality of Life and Sport and Recreation domains of the KOOS, which reflect knee performance during higher demand activities exhibited a clinically significant difference.

LEVEL OF EVIDENCE: IV.

PMID:38492849 | DOI:10.1016/j.jisako.2024.03.010

Brain Res. 2024 Mar 14:148863. doi: 10.1016/j.brainres.2024.148863. Online ahead of print.

ABSTRACT

BACKGROUND: Parkinson’s disease (PD) is a debilitating neurodegenerative condition characterized by the loss of dopaminergic neurons and neuroinflammation. Previous research has identified the involvement of Poly (rC)-binding protein 1 (PCBP1) in certain degenerative diseases; however, its specific mechanisms in PD remain incompletely understood.

METHODS: In this study, 6-OHDA-induced neurotoxicity in the cell lines SH-SY5Y, BV-2 and HA, was used to evaluate the protective effects of PCBP1. We assessed alterations in BDNF levels in SY5Y cells, changes in GDNF expression in glial cells, as well as variations in HSP70 and NF-κB activation. Additionally, glial cells were used as the in vitro model for neuroinflammation mechanisms.

RESULTS: The results indicate that the overexpression of PCBP1 significantly enhances cell growth compared to the control plasmid pEGFP/N1 group. Overexpression of PCBP1 leads to a substantial reduction in early apoptosis rates in SH-SY5Y, HA, and BV-2 cells, with statistically significant differences (p < 0.05). Furthermore, the overexpression of PCBP1 in cells results in a marked increase in the expression of HSP70, GDNF, and BDNF, while reducing NF-κB expression. Additionally, in SH-SY5Y, HA, and BV-2 cells overexpressing PCBP1, there is a decrease in the inflammatory factor IL-6 compared to the control plasmid pEGFP/N1 group, while BV-2 cells exhibit a significant increase in the anti-inflammatory factor IL-10.

CONCLUSION: Our findings suggest that PCBP1 plays a substantial role in promoting cell growth and modulating the balance of neuroprotective and inflammatory factors. These results offer valuable insights into the potential therapeutic utility of PCBP1 in mitigating neuroinflammation and enhancing neuronal survival in PD.

PMID:38492841 | DOI:10.1016/j.brainres.2024.148863

Int J Radiat Oncol Biol Phys. 2024 Mar 14:S0360-3016(24)00429-2. doi: 10.1016/j.ijrobp.2024.03.013. Online ahead of print.

ABSTRACT

BACKGROUND: Alliance A021501 is the first randomized trial to evaluate stereotactic body radiation therapy (SBRT) for borderline resectable pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant chemotherapy. In this post hoc study, we reviewed the quality of radiation therapy (RT) delivered.

METHODS: SBRT (6.6 Gy x 5) was intended, although hypofractionated RT (5 Gy x 5) (HIGRT) was permitted if SBRT specifications could not be met. Institutional credentialing through the National Cancer Institute-funded Imaging and Radiation Oncology Core (IROC) was required. Rigorous RT quality assurance (RT QA) was mandated, including pretreatment review by a radiation oncologist. Revisions were required for unacceptable deviations. Additionally, we performed a post hoc RT QA analysis in which contours and plans were reviewed by 3 radiation oncologists and assigned a score (1, 2, 3) based on adequacy. A score of 1 indicated no deviation, a 2 indicated minor deviation, and a 3 indicated a major deviation that could be clinically significant. Clinical outcomes were compared by treatment modality and by case score.

RESULTS: Forty patients were registered to receive RT (1 planned but not treated) at 27 centers (18 academic, 9 community). Twenty-three centers were appropriately credentialed for moving lung/liver targets, while 4 were approved for static head and neck only. Thirty-two of 39 patients (82.1%) were treated with SBRT, and 7 (17.9%) with HIGRT. Five cases (13%) required revision prior to treatment. On post hoc review, 23 patients (59.0%) were noted to have suboptimal contours or plan coverage, 12 (30.8%) were scored a 2 and 11 cases (28.2%) were scored a 3. There were no apparent differences in failure patterns or surgical outcomes based on treatment technique or post hoc case score. Details related to on-treatment imaging were not recorded.

CONCLUSION: Despite rigorous QA, we encountered variability in simulation, contouring, plan coverage, and dose on trial. While clinical outcomes did not appear to be impacted, findings from this analysis serve to inform subsequent PDAC SBRT trial designs and QA requirements.

PMID:38492812 | DOI:10.1016/j.ijrobp.2024.03.013

J Endod. 2024 Mar 14:S0099-2399(24)00164-X. doi: 10.1016/j.joen.2024.03.005. Online ahead of print.

ABSTRACT

INTRODUCTION: The aims were to investigate 1) the frequency of nonsurgical retreatment, root-end surgery, extraction, and further restorative treatment during a follow-up of 10 to 11 years after root filling and compare the frequencies according to tooth group and type of coronal restoration, and 2) the timing of nonsurgical retreatment, root-end surgery, and extraction.

METHODS: Data were collected from the Swedish Social Insurance Agency’s register. A search for treatment codes identified teeth root filled in 2009 and the type of coronal restoration (direct, indirect, unspecified) registered within 6 months of root filling. The root-filled teeth were followed 10-11 years, and further interventions were recorded. Descriptive statistics and Chi-square tests were used for statistical analysis.

RESULTS: In 2009, root fillings were registered for 215,611 individuals/teeth. Nonsurgical retreatment, root-end surgery, and extraction were undertaken in 3.5%, 1.4%, and 20% teeth, respectively. The frequency of further interventions varied with respect to tooth group and type of coronal restoration, but only slightly for endodontic retreatments. Further interventions, except for root-end surgery, were registered more often for molars and directly restored teeth (P < 0.001). The majority of endodontic retreatments were undertaken within 4 years, while extractions were evenly distributed over 10-11 years.

CONCLUSIONS: The frequency numbers of nonsurgical retreatment and root-end surgery were low, despite one in five root-filled teeth registered as extracted. Further interventions were most common in molars and directly restored teeth. Endodontic retreatments were performed more often during the first 4 years.

PMID:38492798 | DOI:10.1016/j.joen.2024.03.005

Am Surg. 2024 Mar 15:31348241239926. doi: 10.1177/00031348241239926. Online ahead of print.

ABSTRACT

This study examines the safety and efficacy of using peak anti-Xa levels to achieve prophylactic enoxaparin (Lovenox, Sanofi-Aventis) levels in patients who underwent hepatic surgery. Prospectively enrolled patients undergoing major and minor hepatic procedures received postoperative enoxaparin dosing. The enoxaparin dose was adjusted to attain a peak anti-Xa level ≥ 0.20 U/ml. This group was compared to a historical cohort of patients who underwent similar procedures and received standard postoperative VTE chemoprophylaxis dosing. Inpatient postoperative VTE rates were higher in the control group when compared to the experimental group (0 patients [0.00%] vs 4 patients [8.16%]; P = .035). There was no statistically significant difference in number of postoperative blood transfusions, discharge hemoglobin, or in-hospital bleeding events. Adjusting enoxaparin dosing to achieve prophylactic peak anti-Xa levels of ≥0.20 IU/ml was associated with a reduced incidence of symptomatic inpatient postoperative VTE in patients who underwent hepatic surgery without increasing postoperative bleeding events.

PMID:38490954 | DOI:10.1177/00031348241239926