Nevin Manimala

Gigascience. 2022 Nov 18;11:giac104. doi: 10.1093/gigascience/giac104.

ABSTRACT

BACKGROUND: The alignment of large numbers of protein sequences is a challenging task and its importance grows rapidly along with the size of biological datasets. State-of-the-art algorithms have a tendency to produce less accurate alignments with an increasing number of sequences. This is a fundamental problem since many downstream tasks rely on accurate alignments.

RESULTS: We present learnMSA, a novel statistical learning approach of profile hidden Markov models (pHMMs) based on batch gradient descent. Fundamentally different from popular aligners, we fit a custom recurrent neural network architecture for (p)HMMs to potentially millions of sequences with respect to a maximum a posteriori objective and decode an alignment. We rely on automatic differentiation of the log-likelihood, and thus, our approach is different from existing HMM training algorithms like Baum-Welch. Our method does not involve progressive, regressive, or divide-and-conquer heuristics. We use uniform batch sampling to adapt to large datasets in linear time without the requirement of a tree. When tested on ultra-large protein families with up to 3.5 million sequences, learnMSA is both more accurate and faster than state-of-the-art tools. On the established benchmarks HomFam and BaliFam with smaller sequence sets, it matches state-of-the-art performance. All experiments were done on a standard workstation with a GPU.

CONCLUSIONS: Our results show that learnMSA does not share the counterintuitive drawback of many popular heuristic aligners, which can substantially lose accuracy when many additional homologs are input. LearnMSA is a future-proof framework for large alignments with many opportunities for further improvements.

PMID:36399060 | DOI:10.1093/gigascience/giac104

Phys Chem Chem Phys. 2022 Nov 18. doi: 10.1039/d2cp03823d. Online ahead of print.

ABSTRACT

We examine the current-voltage (I-V) characteristics of different polyacenes, such as anthracene, tetracene, pentacene, etc., under the influence of arbitrarily polarized light. The irradiation effect produces an anisotropy in the system and acenes may therefore be employed as molecular rectifiers. We find that the rectification efficiency can be more than 90% with a specific set of light parameters. The phase of rectification (positive or negative) can suitably be engineered by controlling the light conditions. The effect of light irradiation is incorporated through the Floquet-Bloch ansatz with the minimal coupling scheme. The transport properties are calculated using Green’s function technique following the Landauer-Büttiker formalism. Given the promising rectification results, the present prescription may be useful in designing functional elements, employing several other single/complex molecular structures in digital circuit design with the possibility of immense applications.

PMID:36399012 | DOI:10.1039/d2cp03823d

Orbit. 2022 Nov 18:1-6. doi: 10.1080/01676830.2022.2146727. Online ahead of print.

ABSTRACT

PURPOSE: To our knowledge, there have been no previous reports that investigate trends in ophthalmology residents’ exposure to oculoplastic procedures without Accreditation Council for Graduate Medical Education (ACGME) minimum requirements. To fill this knowledge gap, we investigated publicly available ACGME ophthalmology residency case logs from 2009 to 2021.

METHODS: National resident averages and standard deviations were collected for the following oculoplastic procedures without minimum ACGME requirements: eye removal and implant, lacrimal surgery, other orbital surgery (e.g. orbitotomy), tarsorrhaphy, entropion/ectropion repair, temporal artery biopsy, and other oculoplastic surgery. We also collated average yearly surgical volumes of all oculoplastic procedures, “Total Oculoplastic Surgery,” which includes procedures with minimum requirements and procedures without requirements. Finally, we collected the average yearly volumes of all ophthalmic procedures. Linear regressions were used to characterize trends in resident oculoplastic surgical volume.

RESULTS: We provide evidence that the average yearly volumes of all but one oculoplastic procedure without ACGME minimum requirements have been decreasing. The decreases in volume for these procedures are driven by residents having fewer cases both as primary surgeon and as assistant. In addition, while the total number of ophthalmic procedures logged by residents on average increased (β = 7.519, p = 0.0163), the average volume of total oculoplastic procedures did not demonstrate any statistically significant trends.

CONCLUSIONS: Volumes of oculoplastic procedures without ACGME minimum requirements between 2009 and 2021 have been decreasing among ophthalmology residents.

PMID:36398702 | DOI:10.1080/01676830.2022.2146727

Disabil Rehabil. 2022 Nov 18:1-9. doi: 10.1080/09638288.2022.2146215. Online ahead of print.

ABSTRACT

PURPOSE: To compare the short and medium-term effects of physiotherapy plus corticosteroid injection (combined) with physiotherapy alone on pain intensity, disability, Quality of Life (QoL), and treatment effectiveness in patients with Subacromial Pain Syndrome (SAPS).

METHODS: In this double-blind, parallel Randomized Controlled Trial (RCT), 50 patients with SAPS were randomly assigned into combined (N = 25, a single injection 3-6 days before physiotherapy) and physiotherapy alone group (N = 25). Pain, disability, QoL, and treatment-effectiveness were measured at pre-intervention, post-intervention, and 3 and 6-month follow-up with Visual Analog Scale (VAS), Shortened Disability of the Arm, Shoulder, and Hand (Quick-DASH), Shoulder Pain and Disability Index (SPADI) (primary outcome measure), Western Ontario Rotator Cuff (WORC), and Global Rating of Change (GRC) respectively. A 2 × 4 (group × time) mixed model analysis of variance (ANOVA) was applied for analysis.

RESULTS: The ANOVA revealed statistically significant group-in-time interaction for all outcome measures (p-value < 0.05). The independent t-test showed more effectiveness in the combined group at medium-term, as the mean scores of almost all outcome measures were substantially lesser (p < 0.01). Moreover, in short-time, despite a greater number of patients stating “completely recovered” in the combined group, there was no statistically significant difference between groups.

CONCLUSIONS: Effects of physiotherapy plus corticosteroid injection could be more long-lasting than physiotherapy alone in improving pain intensity, disability, QoL, and treatment effectiveness in patients with SAPS.

TRIAL REGISTRATION NUMBER: IRCT20201010048980N1.IMPLICATIONS FOR REHABILITATIONShoulder pain is common, persistent, and predominantly results from subacromial pain syndrome (SAPS).Physiotherapy and corticosteroid injections are effective interventions for this condition.Comprehensive physiotherapy alone can be as effective as corticosteroid injection combined with physiotherapy in the short term.A combined approach versus physiotherapy alone may have more medium-term effects on SAPS patients’ pain, disability, quality of life, and treatment effectiveness.

PMID:36398695 | DOI:10.1080/09638288.2022.2146215

Int J Lang Commun Disord. 2022 Nov;57(6):1244-1254. doi: 10.1111/1460-6984.12749. Epub 2022 Jun 15.

ABSTRACT

BACKGROUND: Texture-modified foods (TMF) is a common intervention for improving swallowing safety and efficiency for people with dysphagia. Non-standardized texture classification (NSTC) of foods is used worldwide. However, as this study documents, it can introduce a lack of clarity and confusion over definitions that can potentially harm patients’ safety. The International Dysphagia Diet Standardisation Initiative (IDDSI) framework offers international terminology and standardized methods for texture testing that can address this issue AIMS: To document differences between NSTC and standardized texture classification (STC) of the IDDSI, to document changes in the STC in the 30 min following meal delivery, and to explore the relationship between food intake and texture level.

METHODS & PROCEDURES: In this observational study, data were collected from 24 long-term care departments during five meals served to 624 residents, including at least one breakfast, lunch and dinner. To document differences between NSTC and STC, all NSTC food textures used in the LTC facilities were reclassified to match the IDDSI texture level at the time food left the kitchen (n = 1276). To document time-related changes in texture, the STC texture as food left the kitchen was compared with texture 30 min later (n = 1276). Finally, to explore the relationship between texture and consumption, estimates were made of single-item food consumption (n = 3820) using a subjective evaluation of consumption percentage OUTCOMES & RESULTS: A total of 1276 food items were classified over the course of five meal services (with at least one each from breakfast, lunch and dinner). Statistically significant differences in NSTC and STC texture levels were found that revealed that residents were consuming food that was more difficult to eat than intended by the TMF prescription. In addition, significant changes in food texture were found over time, with texture levels significantly increasing 30 min after food left the kitchen. Finally, greater consumption was found for softer textures in comparison with regular foods; moreover, food consumption was greatest during breakfast and lowest during lunch.

CONCLUSIONS & IMPLICATIONS: Residents requiring TMF received harder textures than intended which required complex swallowing ability, thus introducing a choking risk. Using the STC as proposed by the IDDSI could improve patient safety, oral intake and nutritional status. Time-related changes should also be considered in circumstances where patients do not consume food soon after service. Lastly, reduced food consumption during lunch might negatively impact overall nutrient intake, particularly in cultures where lunch is the main meal of the day.

WHAT THIS PAPER ADDS: What is already known on the subject Despite widespread agreement on the importance of STC, institutional care providers widely use NSTC. The IDDSI framework offers international terminology and standardized methods for texture testing. The clinical importance of using STC is not well understood. What this paper adds to existing knowledge This study found that residents who required texture-modified foods were eating food textures that were more challenging to swallow than intended. Differences were found in food texture between when it left the kitchen compared with texture 30 min later. Pureed texture had greater consumption than regular textured food. Food consumption was found to be the highest during breakfast, and reduced during lunch, which might negatively impact overall nutrient intake. What are the potential or actual clinical implications of this work? Accurate food texture prescription is the first step towards increasing patients’ safety. However, food preparation and handling are also very important steps, not to be disregarded. Time-related changes in food texture are remarkable and should be considered in circumstances where patients do not consume food soon after service, as these can compromise patients’ safety.

PMID:36398686 | DOI:10.1111/1460-6984.12749

Health Commun. 2022 Nov 18:1-12. doi: 10.1080/10410236.2022.2145781. Online ahead of print.

ABSTRACT

Pre-exposure prophylaxis (PrEP) is a highly effective daily pill that decreases the likelihood of HIV acquisition by up to 92% among individuals at risk for HIV. PrEP can be discretely used, autonomously controlled, and in place at the time of risk exposure, making it an especially promising method for HIV prevention for cisgender women (CGW). But, PrEP is underutilized by CGW relative to the demonstrable need. We apply the Integrative Model of Behavioral Prediction to identify the critical psychosocial factors that shape CGW’s intentions to use PrEP and their relevant underlying beliefs. We surveyed (N = 294) community- and clinic-recruited PrEP eligible CGW to understand the relative importance of attitudes, norms, and efficacy in shaping PrEP intentions. We utilized structural equation modeling to identify the relevant paths. We inspected the summary statistics in relation to three message three selection criteria. We identified beliefs that demonstrated (1) an association with intention, (2) substantial room to move the population, (3) practicality as a target for change through communication intervention. Results show that PrEP awareness was low. When women learned about PrEP, they voiced positive intentions to use it. There were significant and positive direct effects of SE (0.316***), attitudes (0.201**), and subjective norms (0.249***) on intention to initiate PrEP. We illustrate the strategic identification of beliefs within the relevant paths using the 3 belief selection criteria. We also discuss implications for social and structural communication interventions to support women’s HIV prevention.

PMID:36398676 | DOI:10.1080/10410236.2022.2145781

Ann Surg. 2022 Nov 18. doi: 10.1097/SLA.0000000000005758. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to compare the short-term outcomes between laparoscopic and open distal pancreatectomy for lesions of the distal pancreas from a real-world database.

SUMMARY BACKGROUND DATA: Reports on the benefits of laparoscopic distal pancreatectomy include two randomized controlled trials; however, large-scale, real-world data are scarce.

METHODS: We analyzed the data of patients undergoing laparoscopic or open distal pancreatectomy for benign or malignant pancreatic tumors from April 2008 to May 2020 from a Japanese nationwide inpatient database. We performed propensity score analyses to compare the in-hospital mortality, morbidity, readmission rate, reoperation rate, length of postoperative stay, and medical cost between the two groups.

RESULTS: From 5,502 eligible patients, we created a pseudo-population of patients undergoing laparoscopic and open distal pancreatectomy using inverse probability of treatment weighting. Laparoscopic distal pancreatectomy was associated with lower in-hospital mortality during the period of admission (0.0% vs. 0.7%, P<0.001) and within 30 days (0.0% vs. 0.2%, P=0.001), incidence of reoperation during the period of admission (0.7% vs. 1.7%, P=0.018), post-pancreatectomy hemorrhage (0.4% vs. 2.0%, P<0.001), ileus (1.1% vs. 2.8%, P=0.007), and shorter postoperative length of stay (17 vs. 20 d, P<0.001).

CONCLUSIONS: The propensity score analysis revealed that laparoscopic distal pancreatectomy was associated with better outcomes than open surgery in terms of in-hospital mortality, reoperation rate, postoperative length of stay, and incidence of postoperative complications such as post pancreatectomy hemorrhage and ileus.

PMID:36398656 | DOI:10.1097/SLA.0000000000005758

Biostatistics. 2022 Nov 18:kxac044. doi: 10.1093/biostatistics/kxac044. Online ahead of print.

ABSTRACT

With the ongoing development of treatments and the resulting increase in survival in oncology, clinical trials based on endpoints such as overall survival may require long follow-up periods to observe sufficient events and ensure adequate statistical power. This increase in follow-up time may compromise the feasibility of the study. The use of surrogate endpoints instead of final endpoints may be attractive for these studies. However, before a surrogate can be used in a clinical trial, it must be statistically validated. In this article, we propose an approach to validate surrogates when both the surrogate and final endpoints are censored event times. This approach is developed for meta-analytic data and uses a mediation analysis to decompose the total effect of the treatment on the final endpoint as a direct effect and an indirect effect through the surrogate. The meta-analytic nature of the data is accounted for in a joint model with random effects at the trial level. The proportion of the indirect effect over the total effect of the treatment on the final endpoint can be computed from the parameters of the model and used as a measure of surrogacy. We applied this method to investigate time-to-relapse as a surrogate endpoint for overall survival in resectable gastric cancer.

PMID:36398615 | DOI:10.1093/biostatistics/kxac044

Cochrane Database Syst Rev. 2022 Nov 18;11:CD013760. doi: 10.1002/14651858.CD013760.pub2.

ABSTRACT

BACKGROUND: Endophthalmitis is a sight-threatening emergency that requires prompt diagnosis and treatment. The condition is characterised by purulent inflammation of the intraocular fluids caused by an infective agent. In exogenous endophthalmitis, the infective agent is foreign and typically introduced into the eye through intraocular surgery or open globe trauma.

OBJECTIVES: To assess the potential role of combined pars plana vitrectomy and intravitreal antibiotics in the acute management of exogenous endophthalmitis, versus the standard of care, defined as vitreous tap and intravitreal antibiotics.

SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2022, Issue 5); Ovid MEDLINE; Ovid Embase; the International Standard Randomised Controlled Trial Number registry; ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform. There were no restrictions to language or year of publication. The date of the search was 5 May 2022.

SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared pars plana vitrectomy and intravitreal injection of antibiotics versus intravitreal injection of antibiotics alone, for the immediate management of exogenous endophthalmitis.

DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane. Two review authors independently screened search results and extracted data. We considered the following outcomes: visual acuity improvement and change in visual acuity at three and six months; additional surgical procedures, including vitrectomy and cataract surgery, at any time during follow-up; quality of life and adverse effects. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We identified a single RCT that met our inclusion criteria. The included RCT enrolled a total of 420 participants with clinical evidence of endophthalmitis, within six weeks of cataract surgery or secondary intraocular lens implantation. Participants were randomly assigned according to a 2 x 2 factorial design to either treatment with vitrectomy (VIT) or vitreous tap biopsy (TAP) and to treatment with or without systemic antibiotics. Twenty-four participants did not have a final follow-up: 12 died, five withdrew consent to be followed up, and seven were not willing to return for the visit. The study did not report visual acuity according to the review’s predefined outcomes. At three months, 41% of all participants achieved 20/40 or better visual acuity and 69% had 20/100 or better acuity. The study authors reported that there was no statistically significant difference in visual acuity between treatment groups (very low-certainty evidence). There was low-certainty evidence of a similar requirement for additional surgical procedures (risk ratio RR 0.90, 95% confidence interval 0.66 to 1.21). Adverse effects included: VIT group: dislocated intraocular lens (n = 2), macular infarction (n = 1). TAP group: expulsive haemorrhage (n = 1). Quality of life and mean change in visual acuity were not reported. AUTHORS’ CONCLUSIONS: We identified a single RCT (published 27 years ago) for the role of early vitrectomy in exogenous endophthalmitis, which suggests that there may be no difference between groups (VIT vs TAP) for visual acuity at three or nine months’ follow-up. We are of the opinion that there is a clear need for more randomised studies comparing the role of primary vitrectomy in exogenous endophthalmitis. Moreover, since the original RCT study, there have been incremental changes in the surgical techniques with which vitrectomy is performed. Such advances are likely to influence the outcome of early vitrectomy in exogenous endophthalmitis.

PMID:36398614 | DOI:10.1002/14651858.CD013760.pub2

Am J Reprod Immunol. 2022 Nov 18. doi: 10.1111/aji.13654. Online ahead of print.

ABSTRACT

PROBLEM: Dysregulation of factors vital to the survival B cells and/or plasma cells, such as BAFF and APRIL, could be detrimental to a pregnancy.

METHOD OF STUDY: Serially collected first-, second-, and third-trimester serum samples were measured for BAFF and APRIL by ELISA from 150 pregnant women (71 healthy + 79 with a chronic medical disease) at a single medical center. Postpartum serum samples were also collected from the majority of these women. Matched third-trimester and cord blood samples were collected from 168 women (86 healthy + 82 with a chronic medical disease). Data were analyzed by chi-square statistic, unpaired t test, paired t test, Mann-Whitney rank sum test, Wilcoxon signed rank test, Spearman rank order correlation, and receiver operator characteristic (ROC) curve analyses as appropriate.

RESULTS: Maternal serum BAFF levels declined as the pregnancies progressed and rebounded postpartum, whereas serum APRIL levels remained relatively flat throughout pregnancy and postpartum. Cord BAFF and APRIL levels correlated positively with gestation age and were considerably greater than the corresponding maternal third-trimester serum BAFF and APRIL levels, respectively. In women who developed preeclampsia, third-trimester BAFF levels were greater, rather than lower, than their corresponding second-trimester BAFF levels. ROC curve analysis suggested a potential role for third-trimester serum BAFF level as a biomarker of preeclampsia.

CONCLUSIONS: BAFF and APRIL are differentially regulated in the mother during and following pregnancy, whereas each is upregulated in the developing fetus. An increase in third-trimester serum BAFF level may portend development of preeclampsia. This article is protected by copyright. All rights reserved.

PMID:36398594 | DOI:10.1111/aji.13654