Nevin Manimala

Int J Rheum Dis. 2024 Feb;27(2):e15096. doi: 10.1111/1756-185X.15096.

ABSTRACT

AIM: This study aims to evaluate the long-term efficacy, safety, and cumulative retention rate of antitumor necrosis factor-alpha (anti-TNF-α) therapy for patients with Behcet’s uveitis (BU) using meta-analysis.

METHODS: We searched the Web of Science and PubMed databases for eligible studies up to December 1, 2022. The quality of each identified study was assessed using the Joanna Briggs Institute’s case series literature quality assessment tool. Statistical analysis was conducted using Stata 16.0 software with a random-effects model.

RESULTS: Twelve studies comprising 1156 patients with BU were included in our analysis. We found that 85.0% of patients achieved ocular inflammation remission after receiving anti-TNF-α treatment, with a 95% confidence interval (CI) ranging from 78.7% to 90.5%. Additionally, 77.4% (95% CI: 57.5%-92.5%) experienced an improvement in visual acuity (VA). Moreover, the pooled dose reduction of glucocorticoids (GCs) was 11.08 mg (95% CI: -13.34 mg to -8.83 mg). Throughout the follow-up period, the cumulative retention rate of the medication was 67.3% (95% CI: 53.7%-79.6%). Serious adverse events occurred in 5.8% (95% CI: 3.1%-8.9%) of cases, with the three most common types being severe infusion or injection reactions (2.7%; 95% CI: 0.8%-5.4%), tuberculosis (1.3%; 95% CI: 0.0%-3.9%), and bacterial pneumonia (1.3%; 95% CI: 0.1%-3.4%). Subgroup analysis revealed that ocular inflammation remission rates were 89.3% (95% CI: 81.2%-95.5%) for adalimumab treatment and 83.7% (95% CI: 75.3%-90.8%) for infliximab treatment. The drug retention rate after adalimumab therapy was 70.3% (95% CI: 62.0%-78.0%) compared to 66.4% (95% CI: 48.6%-82.2%) for infliximab treatment. Furthermore, the incidence of severe infusion or injection reactions was 2.2% (95% CI: 0.1%-5.8%) following adalimumab treatment and 3.5% (95% CI: 0.7%-7.7%) following infliximab treatment.

CONCLUSIONS: Anti-TNF-α therapy represents an effective treatment for BU patients with favorable safety profile and high drug retention rate and a potential advantage of adalimumab over infliximab in terms of ocular inflammation remission, drug retention, and the incidence of severe infusion or injection reactions.

PMID:38402428 | DOI:10.1111/1756-185X.15096

HGG Adv. 2024 Feb 23:100280. doi: 10.1016/j.xhgg.2024.100280. Online ahead of print.

ABSTRACT

Polygenic scores (PGS) are quantitative metrics for predicting phenotypic values, such as human height or disease status. Some PGS methods require only summary statistics of a relevant genome-wide association study (GWAS) for their score. One such method is Lassosum, which inherits the model selection advantages of Lasso to select a meaningful subset of the GWAS single nucleotide polymorphisms as predictors from their association statistics. However, even efficient scores like Lassosum, when derived from European-based GWAS, are poor predictors of phenotype for subjects of non-European ancestry; that is, they have limited portability to other ancestries. To increase the portability of Lassosum, when GWAS information and estimates of linkage disequilibrium are available for both ancestries, we propose Joint-Lassosum. In the simulation settings we explore, Joint-Lassosum provides more accurate PGS compared with other methods, especially when measured in terms of fairness. In analyses of UK Biobank data, JLS was computationally more efficient but slightly less accurate than a Bayesian comparator, SDPRX. Like all PGS methods, Joint-Lassosum requires selection of predictors, which are determined by data-driven tuning parameters. We describe a new approach to selecting tuning parameters and note its relevance for model selection for any PGS. We also draw connections to the literature on algorithmic fairness and discuss how Joint-Lassosum can help mitigate fairness-related harms that might result from the use of PGS scores in clinical settings. While no PGS method is likely to be universally portable, due to the diversity of human populations and unequal information content of GWAS for different ancestries, Joint-Lassosum is an effective approach for enhancing portability and reducing predictive bias.

PMID:38402414 | DOI:10.1016/j.xhgg.2024.100280

Microb Cell Fact. 2024 Feb 24;23(1):67. doi: 10.1186/s12934-024-02319-y.

ABSTRACT

BACKGROUND: In recent years, the production of inclusion bodies that retain substantial catalytic activity was demonstrated. These catalytically active inclusion bodies (CatIBs) are formed by genetic fusion of an aggregation-inducing tag to a gene of interest via short linker polypeptides. The resulting CatIBs are known for their easy and cost-efficient production, recyclability as well as their improved stability. Recent studies have outlined the cooperative effects of linker and aggregation-inducing tag on CatIB activities. However, no a priori prediction is possible so far to indicate the best combination thereof. Consequently, extensive screening is required to find the best performing CatIB variant.

RESULTS: In this work, a semi-automated cloning workflow was implemented and used for fast generation of 63 CatIB variants with glucose dehydrogenase of Bacillus subtilis (BsGDH). Furthermore, the variant BsGDH-PT-CBDCell was used to develop, optimize and validate an automated CatIB screening workflow, enhancing the analysis of many CatIB candidates in parallel. Compared to previous studies with CatIBs, important optimization steps include the exclusion of plate position effects in the BioLector by changing the cultivation temperature. For the overall workflow including strain construction, the manual workload could be reduced from 59 to 7 h for 48 variants (88%). After demonstration of high reproducibility with 1.9% relative standard deviation across 42 biological replicates, the workflow was performed in combination with a Bayesian process model and Thompson sampling. While the process model is crucial to derive key performance indicators of CatIBs, Thompson sampling serves as a strategy to balance exploitation and exploration in screening procedures. Our methodology allowed analysis of 63 BsGDH-CatIB variants within only three batch experiments. Because of the high likelihood of TDoT-PT-BsGDH being the best CatIB performer, it was selected in 50 biological replicates during the three screening rounds, much more than other, low-performing variants.

CONCLUSIONS: At the current state of knowledge, every new enzyme requires screening for different linker/aggregation-inducing tag combinations. For this purpose, the presented CatIB toolbox facilitates fast and simplified construction and screening procedures. The methodology thus assists in finding the best CatIB producer from large libraries in short time, rendering possible automated Design-Build-Test-Learn cycles to generate structure/function learnings.

PMID:38402403 | DOI:10.1186/s12934-024-02319-y

Clin Proteomics. 2024 Feb 24;21(1):15. doi: 10.1186/s12014-024-09458-9.

ABSTRACT

BACKGROUND: Hypertension is an important public health priority with a high prevalence in Africa. It is also an independent risk factor for kidney outcomes. We aimed to identify potential proteins and pathways involved in hypertension-associated albuminuria by assessing urinary proteomic profiles in black South African participants with combined hypertension and albuminuria compared to those who have neither condition.

METHODS: The study included 24 South African cases with both hypertension and albuminuria and 49 control participants who had neither condition. Protein was extracted from urine samples and analysed using ultra-high-performance liquid chromatography coupled with mass spectrometry. Data were generated using data-independent acquisition (DIA) and processed using Spectronaut™ 15. Statistical and functional data annotation were performed on Perseus and Cytoscape to identify and annotate differentially abundant proteins. Machine learning was applied to the dataset using the OmicLearn platform.

RESULTS: Overall, a mean of 1,225 and 915 proteins were quantified in the control and case groups, respectively. Three hundred and thirty-two differentially abundant proteins were constructed into a network. Pathways associated with these differentially abundant proteins included the immune system (q-value [false discovery rate] = 1.4 × 10^{– 45}), innate immune system (q = 1.1 × 10^{– 32}), extracellular matrix (ECM) organisation (q = 0.03) and activation of matrix metalloproteinases (q = 0.04). Proteins with high disease scores (76-100% confidence) for both hypertension and chronic kidney disease included angiotensinogen (AGT), albumin (ALB), apolipoprotein L1 (APOL1), and uromodulin (UMOD). A machine learning approach was able to identify a set of 20 proteins, differentiating between cases and controls.

CONCLUSIONS: The urinary proteomic data combined with the machine learning approach was able to classify disease status and identify proteins and pathways associated with hypertension-associated albuminuria.

PMID:38402394 | DOI:10.1186/s12014-024-09458-9

BMC Cancer. 2024 Feb 24;24(1):263. doi: 10.1186/s12885-024-11990-8.

ABSTRACT

BACKGROUND: Whether Transanal drainage tubes (TDTs) placement reduces the occurrence of anastomotic leakage (AL) after rectal cancer (RC) surgery remains controversial. Most existing meta-analyses rely on retrospective studies, while the prospective studies present an inadequate level of evidence.

METHODS: A systematic review and meta-analysis of prospective studies on TDTs placement in RC patients after surgery was conducted. The main analysis index was the incidence of AL, Grade B AL, and Grade C AL, while secondary analysis index was the incidence of anastomotic bleeding, incision infection, and anastomotic stenosis. A comprehensive literature search was performed utilizing the databases Cochrane Library, Embase, PubMed, and Web of Science. We recorded Risk ratios (RRs) and 95% confidence intervals (CI) for each included study, and a fixed-effect model or random-effect model was used to investigate the correlation between TDTs placement and four outcomes after RC surgery.

RESULTS: Seven studies (1774 participants, TDT 890 vs non-TDT 884) were considered eligible for quantitative synthesis and meta-analysis. The meta-analysis revealed that the incidence of AL was 9.3% (83/890) in the TDT group and 10.2% (90/884) in the non-TDT group. These disparities were found to lack statistical significance (P = 0.58). A comprehensive meta-analysis, comprising four studies involving a cumulative sample size of 1259 participants, revealed no discernible disparity in the occurrence of Grade B AL or Grade C AL between the TDT group and the non-TDT group (Grade B AL: TDT 34/631 vs non-TDT 26/628, P = 0.30; Grade C AL: TDT 11/631 vs non-TDT 27/628, P = 0.30). Similarly, the incidences of anastomotic bleeding (4 studies, 876 participants), incision infection (3studies, 713 participants), and anastomotic stenosis (2studies, 561 participants) were 5.5% (24/440), 8.1% (29/360), and 2.9% (8/280), respectively, in the TDT group, and 3.0% (13/436), 6.5% (23/353), and 3.9% (11/281), respectively, in the non-TDT group. These differences were also determined to lack statistical significance (P = 0.08, P = 0.43, P = 0.48, respectively).

CONCLUSION: The placement of TDTs does not significantly affect the occurrence of AL, Grade B AL, and Grade C AL following surgery for rectal cancer. Additionally, TDTs placement does not be associated with increased complications such as anastomotic bleeding, incision infection, or anastomotic stenosis.

TRIAL REGISTRATION: PROSPERO: CRD42023427914.

PMID:38402391 | DOI:10.1186/s12885-024-11990-8

BMC Oral Health. 2024 Feb 24;24(1):271. doi: 10.1186/s12903-024-04037-8.

ABSTRACT

BACKGROUND: In recent era, digitalization in the dental sciences has been observed in wide ranges. This cross-sectional study aimed to assess knowledge and practice of additive manufacturing (AM) in dentistry among university teaching faculty in Saudi Arabia.

METHODS: A questionnaire was prepared and validated to distribute to the different dental colleges in Saudi Arabia. The questionnaire was divided into three parts: demographic information, knowledge and practices of AM among the dental teaching faculty. After receiving all the responses, descriptive statistics were used for the frequency distribution of all the responses.

RESULTS: A total of 367 responses were received from the different faculty members. Most of the participants were male (67.30%), holding assistant professor (52.50%) positions in the field of prosthodontics (23.40%). In terms of knowledge, even though most of the participants were aware of AM (64.30%); however, do not understand the AM techniques (33.50). Moreover, 71.90% of the participants had no experience working with AM and only 13.60% of participants used AM in their respective dental colleges.

CONCLUSION: AM techniques are not commonly used in the field of dentistry in Saudi Arabia; therefore, more platforms should have created to enhance the knowledge and practice of AM in the current population.

PMID:38402388 | DOI:10.1186/s12903-024-04037-8

BMC Med Res Methodol. 2024 Feb 24;24(1):48. doi: 10.1186/s12874-024-02180-y.

ABSTRACT

BACKGROUND: In recent years, the use of non- and semi-parametric models which estimate hazard ratios for analysing time-to-event outcomes is continuously criticized in terms of interpretation, technical implementation, and flexibility. Hazard ratios in particular are critically discussed for their misleading interpretation as relative risks and their non-collapsibility. Additive hazard models do not have these drawbacks but are rarely used because they assume a non- or semi-parametric additive hazard which renders computation and interpretation complicated.

METHODS: As a remedy, we propose a new parametric additive hazard model that allows results to be reported on the original time rather than on the hazard scale. Being an essentially parametric model, survival, hazard and probability density functions are directly available. Parameter estimation is straightforward by maximizing the log-likelihood function.

RESULTS: Applying the model to different parametric distributions in a simulation study and in an exemplary application using data from a study investigating medical care to lung cancer patients, we show that the approach works well in practice.

CONCLUSIONS: Our proposed parametric additive hazard model can serve as a powerful tool to analyze time-to-event outcomes due to its simple interpretation, flexibility and facilitated parameter estimation.

PMID:38402386 | DOI:10.1186/s12874-024-02180-y

BMC Musculoskelet Disord. 2024 Feb 24;25(1):173. doi: 10.1186/s12891-024-07286-4.

ABSTRACT

BACKGROUND: Identification of knee osteoarthritis (OA) pain phenotypes, their transition patterns, and risk factors for worse phenotypes, may guide prognosis and targeted treatment; however, few studies have described them. We aimed to investigate different pain phenotypes, their transition patterns, and potential risk factors for worse pain phenotypes.

METHODS: Utilizing data from the Osteoarthritis Initiative (OAI), pain severity was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. We identified the activity-related pain phenotypes and estimated the transition probabilities of pain phenotypes from baseline to the 24-month using latent transition analysis. We examined the risk factors at baseline with the 24-month pain phenotypes and the transition of pain phenotypes.

RESULTS: In 4796 participants, we identified four distinct knee pain phenotypes at both baseline and 24-month follow-up: no pain, mild pain during activity (Mild P-A), mild pain during both rest and activity (Mild P-R-A), and moderate pain during both rest and activity (Mod P-R-A). 82.9% knees with no pain at baseline stayed the same at 24-month follow-up, 17.1% progressed to worse pain phenotypes. Among “Mild P-A” at baseline, 32.0% converted to no-pain, 12.8% progressed to “Mild P-R-A”, and 53.2% remained. Approximately 46.1% of “Mild P-R-A” and 54.5% of “Mod P-R-A” at baseline experienced remission by 24-month. Female, non-whites, participants with higher depression score, higher body mass index (BMI), higher Kellgren and Lawrence (KL) grade, and knee injury history were more likely to be in the worse pain phenotypes, while participants aged 65 years or older and with higher education were less likely to be in worse pain phenotypes at 24-month follow-up visit. Risk factors for greater transition probability to worse pain phenotypes at 24-month included being female, non-whites, participants with higher depression score, higher BMI, and higher KL grade.

CONCLUSIONS: We identified four distinct knee pain phenotypes. While the pain phenotypes remained stable in the majority of knees over 24 months period, substantial proportion of knees switched to different pain phenotypes. Several socio-demographics as well as radiographic lesions at baseline are associated with worse pain phenotypes at 24-month follow-up visit and transition of pain phenotypes.

PMID:38402384 | DOI:10.1186/s12891-024-07286-4

BMC Nurs. 2024 Feb 24;23(1):139. doi: 10.1186/s12912-024-01816-0.

ABSTRACT

AIM: This study aimed to assess inclusive leadership and presenteeism among clinical nurses and to examine the moderating effect of perceived organizational support on presenteeism related to the inclusive leadership among nurses.

BACKGROUND: Nurses’ presenteeism has become common. In hospitals, inclusive leadership is an acknowledged leadership style that has a positive influence on nurses. However, little emphasis has been paid to research on their relationships and moderating effect.

METHODS: A cross-sectional study was undertaken to assess 2222 nurses using a general information questionnaire, Stanford Presenteeism Scale (SPS-6), Perceived Organisational Support Scale, and Inclusive Leadership Scale. Study variables were analyzed using descriptive statistics, correlation, and structural equation modelling (SEM).

RESULTS: Presenteeism was relatively severe among clinical nurses. There were correlations between inclusive leadership, perceived organizational support and presenteeism. Perceived organizational support moderated the relationship between inclusive leadership and presenteeism.

DISCUSSION AND CONCLUSION: Nursing managers should actively adopt an inclusive leadership style and improve nurses’ sense of perceived organizational support to improve clinical nurses’ presenteeism behaviors.

IMPLICATIONS FOR NURSING POLICY AND PRACTICE: Healthcare organizations and nursing managers should pay attention to the psychological needs of their nurses, provide complete understanding and support, encourage staff to actively participate in their work and contribute new ideas and opinions, reduce the incidence of presenteeism, and improve nurses’ sense of well-being at work.

PMID:38402383 | DOI:10.1186/s12912-024-01816-0

Respir Res. 2024 Feb 24;25(1):99. doi: 10.1186/s12931-024-02701-9.

ABSTRACT

BACKGROUND: Intra-breath oscillometry has been proposed as a sensitive means of detecting airway obstruction in young children. We aimed to assess the impact of early life wheezing and lower respiratory tract illness on lung function, using both standard and intra-breath oscillometry in 3 year old children.

METHODS: History of doctor-diagnosed asthma, wheezing, bronchiolitis and bronchitis and hospitalisation for respiratory problems were assessed by questionnaires in 384 population-based children. Association of respiratory history with standard and intra-breath oscillometry parameters, including resistance at 7 Hz (R₇), frequency-dependence of resistance (R_{7 – 19}), reactance at 7 Hz (X₇), area of the reactance curve (AX), end-inspiratory and end-expiratory R (R_eI, R_eE) and X (X_eI, X_eE), and volume-dependence of resistance (ΔR = R_eE-R_eI) was estimated by linear regression adjusted on confounders.

RESULTS: Among the 320 children who accepted the oscillometry test, 281 (88%) performed 3 technically acceptable and reproducible standard oscillometry measurements and 251 children also performed one intra-breath oscillometry measurement. Asthma was associated with higher R_eI, R_eE, ΔR and R₇ and wheezing was associated with higher ΔR. Bronchiolitis was associated with higher R₇ and AX and lower X_eI and bronchitis with higher R_eI. No statistically significant association was observed for hospitalisation.

CONCLUSIONS: Our findings confirm the good success rate of oscillometry in 3-year-old children and indicate an association between a history of early-life wheezing and lower respiratory tract illness and lower lung function as assessed by both standard and intra-breath oscillometry. Our study supports the relevance of using intra-breath oscillometry parameters as sensitive outcome measures in preschool children in epidemiological cohorts.

PMID:38402379 | DOI:10.1186/s12931-024-02701-9