Phage display technology has emerged as an indispensable and highly successful platform for the in vitro generation of monoclonal antibodies (mAbs) against a vast spectrum of targets, ranging from disease biomarkers and native biologically important proteins to small molecules. The critical determinant for constructing a high-quality library capable of yielding high-affinity antibodies is the diversity of the source antibody genes. Naïve antibody libraries, the most common type, are typically derived from the IgM repertoire of healthy human donors, using B-cells isolated from peripheral blood mononuclear cells (PBMCs). The preferred format for these displayed antibodies is the single-chain fragment variable (scFv) due to its smaller size and functional suitability for the phage display system. This chapter details the technical workflow for harnessing this power, which involves a robust two-step cloning method for constructing the high-diversity library, followed by the iterative process of biopanning for the efficient selection and isolation of target-specific, high-affinity clones.
The rapid expansion of environmental DNA (eDNA)-based biodiversity monitoring has heightened the need for accurate and well-curated taxonomic reference databases. Although mitochondrial cytochrome oxidase I (COI) is widely used, the mitochondrial 12S ribosomal RNA gene (12S rRNA) has increasingly demonstrated strong taxonomic assignment success in chondrichthyan metabarcoding applications. The South African coastline supports one of the most diverse chondrichthyan faunas globally. However, as in many regions, coverage of 12S rRNA reference databases has remained limited. Well-represented reference libraries are critical for improving the accuracy of eDNA-based species detection. Here, we aimed to expand the regional 12S rRNA reference database for South African chondrichthyans, thereby supporting both local and global eDNA applications for widely distributed species. A total of 36 chondrichthyan species, represented by 69 individuals, were sequenced to expand the 12S rRNA reference library for sharks, rays and chimaeras from South Africa's Indian and Atlantic Ocean coastlines. A newly developed primer set (V05F_898E / teleoR_Elas), designed to overlap with the commonly used Elas02 region, achieved consistent amplification across diverse lineages. The new data increased regional reference coverage from 50.3% to 69.1% and added 18 species globally. Sequence authenticity was confirmed through comparison with GenBank, and Bayesian phylogenetic analyses showed that 97.2% of sequences clustered within their expected family-level lineages, although some uncertainties remained in groups with low mitochondrial divergence or complex taxonomic histories. Percent identity analyses revealed high intraspecific similarity and clear interspecific separation across taxa. However, comparative in silico analyses of the shorter Elas02 fragment demonstrated reduced phylogenetic resolution and less consistent clustering among closely related taxa. While the Elas02 region is suitable for accurate amplicon sequence variant (ASV) matching in eDNA metabarcoding, the longer 12S rRNA fragment generated here provides improved phylogenetic resolution and may aid in the identification of unknown or ambiguous ASVs. The expanded 12S rRNA reference library and associated phylogenetic analyses expanded genetic resources for South African chondrichthyans and support global applications. The newly developed marker can be incorporated in future eDNA studies dealing with elasmobranchs, since it can have the added benefit of providing more phylogenetic resolution than the short Elas02 fragment.
Antibodies, central components of the adaptive immune system, possess the remarkable ability to specifically recognize and bind to foreign substances known as antigens. This recognition occurs through the interaction of the antibody's antigen-binding site, or paratope, with a specific region on the antigen called the epitope. Understanding the precise nature of these interactions, particularly the identification and characterization of epitopes, is of paramount importance for a wide array of biomedical applications. The mapping of antibody epitopes, the process of experimentally identifying the binding site of an antibody on its target antigen, provides critical insights into antibody function and its diverse applications. Peptide phage display provides a convenient and rapid method to identify epitopes of specific monoclonal antibodies. This protocol highlights the use of a peptide phage display library for epitope identification of a recombinant monoclonal antibody.
Complementary-determining regions (CDRs) are the primary factor that determines antibody diversity, while CDR H3 plays a central role in antigen binding. Randomization of this loop within a stable framework provides a powerful strategy for generating synthetic antibody libraries. This chapter outlines an approach that is Kunkel mutagenesis based, for constructing a monoclonal antibody library diversified at CDR H3. The method uses uracilated single-stranded DNA templates and degenerate oligonucleotides to introduce targeted variability while suppressing nonrecombinant background through strategically placed stop codons and restriction sites. The resulting repertoire is directly compatible with phage display for downstream selection. This streamlined protocol enables the generation of antibody libraries suitable for applications in affinity maturation, binder discovery, and antibody development.
Phage display is a powerful high-throughput screening technique used to screen diverse peptide libraries against therapeutically relevant protein targets. Compared to linear peptides, cyclic peptides have improved stability and binding characteristics. There are various methods to construct cyclic peptide phage display libraries, which can be screened against targets to identify cyclic peptide candidates. These peptides can then be optimized to enhance potency and specificity. In this chapter, we outline a strategy to generate cyclic peptide phage display libraries using a bischlooroxime crosslinker.
Tropical areas, particularly Brazil, are home to a significant portion of the world's biodiversity, with the Brazilian Atlantic Forest (BAF) being a crucial biome recognized as a global biodiversity hotspot. However, the BAF has been subject to severe degradation due to anthropogenic activities, resulting in extensive habitat loss and fragmentation. These changes have prompted numerous studies on their effects on biodiversity, focusing on forest fragments and protected areas. Despite this research, there is a notable lack of meta-data on biodiversity in human-modified landscapes within the BAF- where only 31% of the land remains as native forest. Most of the biome has been transformed by human activities, primarily for pasture and agriculture. By recognizing these knowledge gaps, researchers have begun investigating biodiversity in anthropogenically altered landscapes, to better understand species' responses to human-induced changes and inform conservation policies. A comprehensive literature search was conducted to answer the following primary question: "What is the diversity of birds and mammal species in agricultural fields and their adjacent areas of natural vegetation?" We aimed to address this question by creating a systematic map summarizing current knowledge about avian and mammalian species' presence in the BAF's agricultural matrix. This research also aimed (i) to identify common species in agricultural landscapes, (ii) to compare species richness in-crop (inside the agricultural field) and off-crop (non-cultivated areas outside the agricultural field), (iii) to determine crops with high species visitation, and (iv) to highlight areas for future research. We conducted a systematic literature map on bird and mammal biodiversity in agricultural landscapes within the BAF and adjacent natural vegetation areas. The search covered Web of Knowledge, Scopus, the National Library of Medicine, and the "Biblioteca Digital Brasileira" (Brazilian Digital Library) database for grey literature (dissertations and theses). Citation records were surveyed based on predefined criteria through title/abstract screening and full-text analysis. Eligible publications were used for meta-data coding and systematic map construction. Our systematic map identified 207 eligible publications included in the final evidence base. Research effort was distributed across taxonomic groups, with 78 studies focusing on birds, 126 on non-flying mammals (NFM), and 22 on bats. The most frequently studied agricultural systems were pasture and eucalyptus, followed by sugarcane, coffee, cacao, rubber tree, pinus, grape, araucaria, and corn. Extracted meta-data showed that studies reported species occurrences in both agricultural fields and adjacent natural areas. The map revealed significant knowledge clusters and gaps, particularly regarding the distribution of research across different crop types and the inclusion of species with varying conservation statuses. This systematic map identifies 846 species across 48 crop types in BAF agricultural landscapes, potentially indicating their use by wildlife; however, further quantitative synthesis is necessary to assess the relative importance of these areas. By mapping knowledge clusters and gaps-such as underrepresented regions and specific crop-taxa associations-this work provides a foundation for future systematic reviews and informs the development of more targeted environmental risk assessments and conservation policies.
DNA double-strand break (DSB)-induced mutagenesis is a critical contributor to a variety of human diseases; however, the ability to quantify these mutations is limited by the low sensitivity of current methodologies. Here we describe iMUT-seq, a technique that profiles DSB-induced mutations at high sensitivity and single-nucleotide resolution around endogenous DSBs, by coupling high-depth sequencing to restriction enzyme-inducible DSBs in human cell lines. iMUT-seq uses targeted sequencing to generate high-depth DNA libraries, enabling detection of mutations at incidence rates as low as 1 in 500,000. iMUT-seq can be used to identify novel mutagenic outcomes of DSBs and characterize previously unknown mechanisms of mutagenesis. The technique involves the extraction of genomic DNA from treated cells, followed by a multiplexed polymerase chain reaction and a series of library preparation reactions to generate a DNA library ready for sequencing on Illumina next-generation sequencing platforms. Finally, this novel approach to mutation profiling requires a specific analytical pipeline with careful considerations for the uncommon per-nucleotide nature of the data. Users will need experience in raw next-generation sequencing data analysis, and experience in DNA library preparation is beneficial. Overall, iMUT-seq has the potential to provide advanced insights into DSB mutagenesis, is a powerful tool in the study of novel DNA repair components and can be adapted to other organisms and types of DNA damage.
Prenylated peptides, endowed with hydrophobic prenyl groups, are widely found as secondary metabolites in nature. To develop de novo artificial prenylated peptide ligands with selective affinity for a target protein of choice, a random prenylated peptide library can be constructed through the combination of a custom-made in vitro translation system and a peptide prenyltransferase, which is subsequently applied to mRNA display screening. In this chapter, we describe protocols for constructing a prenylated thioether-closed macrocyclic peptide library and conducting mRNA display screening to identify selective ligands.
Z. Zhu , X. Shi , Z. Zhu , S. Yang , F. Wang , G. Yang , 'Digital pesticide: a comprehensive pesticide information database with dynamic web platform for artificial intelligence applications', Pest Management Science 81, no.9 (2025): 5403-5412. https://doi.org/10.1002/ps.8894 The above article, published online on 28 May 2025 on Wiley Online Library (wileyonlinelibrary.com), has been withdrawn by agreement between the Society of Chemical Industry, the Editors in Chief Yidong Wu, Mithila Jugulam and Ray Hammerschmidt, the authors and John Wiley & Sons Ltd. Uk. The withdrawal has been made due to significant amount of data being included without authorization of the Pesticide Properties Database at the University of Hertfordshire. The authors do not agree with the decision to withdraw the article. © 2026 Society of Chemical Industry.
Approximately 10-20% of patients with gallstones present with concomitant common bile duct stones (CBDS). Although T-tube drainage (TTD) has traditionally been used after bile duct exploration, clinical practice is increasingly shifting toward T-tube-free minimally invasive strategies to enhance postoperative recovery. This study evaluated the effectiveness and safety of these approaches using a network meta-analysis (NMA). PubMed, Web of Science, Embase, and the Cochrane Library were searched from inception to October 2025. Randomized controlled trials (RCTs) and cohort studies were analyzed in parallel using separate frequentist NMAs. Interventions included laparoscopic cholecystectomy (LC) + laparoscopic common bile duct exploration (LCBDE) + TTD, LC + LCBDE + primary suture (PS), LC + laparoscopic transcystic common bile duct exploration (LTCBDE), and LC + endoscopic retrograde cholangiopancreatography (ERCP) performed as either a single-stage or two-stage strategy. Treatment effects were expressed as risk ratios (RRs), odds ratios (ORs), and mean differences (MDs), with treatment rankings estimated using the surface under the cumulative ranking curve (SUCRA). Fifty-two studies including 11,327 patients (19 RCTs and 33 cohort studies) were included. Parallel analyses demonstrated generally consistent findings between randomized and observational evidence. In the RCT network, T-tube-free strategies achieved comparable stone clearance and overall safety compared with TTD. LC + LTCBDE showed the highest SUCRA ranking probabilities for operative time (MD - 47.01 min; SUCRA 96.4%) and length of hospital stay (MD - 5.78 days; SUCRA 86.9%). LC + LCBDE + PS was also associated with shorter operative time (MD - 20.02 min; SUCRA 51.8%) and shorter length of hospital stay (MD - 3.03 days; SUCRA 33.8%). Long-term outcomes and postoperative complication rates were generally comparable across strategies. Differences in SUCRA ranking probabilities were observed for postoperative pancreatitis-related outcomes, with LC + ERCP (two-stage) showing a lower ranking probability (SUCRA 15.8%). T-tube-free minimally invasive strategies achieved stone clearance and overall perioperative safety broadly comparable to those of TTD in patients with gallbladder stones and concomitant common bile duct stones. LC + LTCBDE and LC + LCBDE + PS were associated with shorter operative time and hospital stay in some network comparisons. Overall, treatment selection should remain individualized according to biliary anatomy, stone burden, patient condition, and institutional expertise.
Purpose To systemically evaluate current evidence on the association between non-invasively monitored atherosclerosis progression and adverse cardiovascular outcomes, assessing its potential as a surrogate endpoint for clinical trials. Methods PubMed, Embase, and Cochrane Library were searched from 1988 to 2024 to locate studies. Bias was assessed using the Newcastle-Ottawa Scale. Multivariable-adjusted hazard ratios (aHR) were included in a random-effects meta-analysis with modality-specific estimates. Between-study heterogeneity was quantified using I2. Results Thirty-four observational studies were included with an aggregate sample size of 56,189 participants (mean age: 60 ± 10 years; females: 44%). Carotid ultrasound plaque progression (n = 4,727) showed a consistent association with outcome (aHR: 1.38 (95% CI: 1.08-1.77), P = 0.009); however, heterogeneity was high (I2 = 95.7%). Conversely, conflicting results were found between carotid intima-media thickness progression and outcome. Non-contrast computed tomography of coronary calcification progression (n = 27,067; aHR: 1.61 (95% CI: 1.30-1.99), P < 0.001; I2 = 83.9%) and aortic calcification progression (n = 10,916; aHR: 1.50 (95% CI: 1.02-2.23), P = 0.042; I2 = 66.1%) were independently associated with outcome, despite high heterogeneity. Evidence on coronary plaque progression on computed tomography angiography was inconclusive due to low-quality studies. Conclusion Atherosclerosis progression, assessed by ultrasound or computed tomography, in the carotids, coronaries, and aorta was independently associated with cardiovascular outcomes, despite substantial between-study heterogeneity. Highest-quality evidence was found for carotid ultrasound plaque progression and coronary and aortic calcification progression on non-contrast computed tomography. Still, large-scale studies are warranted to identify the optimal surrogate for clinical trials.
Oral squamous cell carcinoma (OSCC) refers to a prevalent cancer in the neck and head region, with poor prognosis and a high risk of recurrence after surgery. Surgical margin (SM) and the margin to depth of invasion ratio (MDR) are critical factors influencing survival outcomes. Currently, the impact of SM width and MDR on prognosis remains controversial. This study seeks to systematically compare the predictive value of SM width and MDR for OSCC prognosis, providing evidence for optimizing SM evaluation standards. We systematically searched PubMed, Web of Science, Embase, and Cochrane Library for relevant studies from database inception to April 1, 2026. Two researchers separately reviewed the included studies and extracted the data. The quality of the included studies was assessed using the Quality In Prognosis Studies (QUIPS) tool. Meta-analysis was carried out via STATA 18.0 software, and the related summary plots were generated. A total of 41 studies involving 61,863 individuals were included. A poor SM was significantly associated with unfavorable overall survival (OS) (HR = 1.56, 95% CI 1.37-1.77, p < 0.001), disease-free survival (DFS) (HR = 1.72, 95% CI 1.29-2.28, p < 0.001), and recurrence-free survival (RFS) (HR = 1.99, 95%CI 1.53-2.58, p < 0.001). A low margin to depth of invasion ratio (MDR) was significantly associated with worse OS (HR = 1.36, 95% CI 1.21-1.54, p < 0.001) and DFS (HR = 1.40, 95% CI 1.12-1.74, p = 0.003). Subgroup analysis demonstrated that these associations might be influenced by different cutoff values, data analysis sources, and geographical factors. This study revealed significant associations between SM, MDR, and the OSCC prognosis. Nevertheless, the clinical value of these indicators may be affected by variability in cutoff values across studies. Future large-scale, multicenter prospective studies are required to validate these findings and further investigate the prognostic impact of varying cutoff values.
Cellular senescence is a fundamental mechanism of ageing, characterised by stable cell cycle arrest and the acquisition of a pro-inflammatory secretory phenotype. Nutritional interventions are widely proposed to modulate ageing biology, but their effects on cellular senescence in humans remain unclear. We systematically synthesised evidence from interventional human studies assessing the impact of nutritional strategies on biomarkers of cellular senescence. We searched MEDLINE, Embase, Cochrane Library, and Web of Science from inception to September 10, 2024. We included interventional studies in humans reporting biomarkers of cellular senescence, including markers of cell cycle arrest, DNA damage, telomere length, transcriptomic signatures, and factors of the senescence-associated secretory phenotype (SASP). Twenty-nine articles (27 trials; 3,811 participants) were included. Across studies, nutritional interventions modulated multiple senescence biomarkers to varying extents, with calorie restriction producing the most recurrent reductions in circulating inflammatory and secretory factors commonly included in SASP panels as well as senescence-associated transcriptomic signatures. Classical markers of cell cycle arrest (e.g., CDKN2A/p16, CDKN1A/p21) and telomere length were largely unchanged or highly variable. Calorie restriction mimetics, particularly metformin and rapamycin, showed context-dependent effects, most evident under conditions of metabolic or physiological stress. Among dietary supplements, n-3 polyunsaturated fatty acids may modulate selected inflammatory/SASP-related circulating markers, although the evidence for dietary supplements remains limited and heterogeneous. In humans, available evidence suggests that nutritional interventions may preferentially affect senescence-associated inflammatory and secretory biomarker profiles, particularly SASP-related mediators, rather than markers more directly related to senescent cell abundance. However, because SASP factors and circulating cytokines are heterogeneous and not specific to senescent cells, these findings should be interpreted as evidence for possible modulation of senescence-associated markers rather than definitive effects on senescence burden. These observations support the use of multi-marker and functionally relevant endpoints in future clinical studies targeting biological ageing and cellular senescence.
Women undergo progressive musculoskeletal, cardiovascular, and metabolic changes during menopause that usually end up in less functional capacity, compensatory balance impairment, and reduced quality of lives. The further decrease of estrogen levels heightens the risk of osteoporosis, sarcopenia, and cardiovascular disease, rendering them more vulnerable to functional deterioration because they will all occur after menopause. Recently, rehabilitation and physical exercise-based approaches are recommended as nonpharmacological solutions to fix these health problems. Nevertheless, evidence appears to be inconsistent across studies. The natural evolution of musculoskeletal, cardiovascular, and metabolic changes during the menopause in women is associated with poor functional ability, poor balance, and poor quality of life. This further reduction in the hormone estrogen increases the risk for osteoporosis, sarcopenia, and cardiovascular disease, putting females in a postmenopausal state at higher threat levels for functional decline. Rehabilitation and exercise-based intervention strategies are commonly prescribed as nonpharmacological ways of combating these health issues. The research evidence seems conflicting among different studies, though. This systematic review was aimed to detect the effect in the study about rehabilitation and exercise-based interventions on functional performance, musculoskeletal health, cardiovascular outcomes, balance, the health and quality of life of postmenopausal women. Systematic review and Meta-Analysis based on randomised controlled trials. Randomised controlled trials published between 2015 and 2025 were found by searching electronic resources such as PubMed, Scopus, PEDro, the Cochrane Library, and Google Scholar. The Cochrane Risk of Bias-2 tool was used to assess bias risk, and the PEDro scale was used to evaluate methodological quality. In total, 20 randomized controlled trials have been included for quantitative synthesis, with particular studies pooling to contribute to each meta-analysis. The exercise-based rehabilitation interventions showed considerable improvements in vasomotor symptoms. The meta-analysis indicated a large pooled effect favouring exercise interventions under a random-effects model (SMD = -0.862; 95% CI -1.154 to -0.570; p < 0.001; I2 = 0.34%), suggesting a high level of consistency across studies. However, exercise did not show any significant pooled effect concerning the following variables: body mass index (SMD = -0.729; 95% CI -1.754 to 0.297; p = 0.163; I2 = 94.68%), blood pressure (SMD = 0.186; 95% CI -0.204 to 0.577; p = 0.347; I2 = 25.16%), or physical performance outcomes (SMD = -0.483; 95% CI -1.238 to 0.272; p = 0.209; I2 = 90.24%). Heterogeneity was substantial for BMI and physical performance outcomes and, thus, varied by intervention type, intervention duration, and outcome measures between studies. Generally, exercise and rehabilitation interventions showed the most consistent and clinically relevant outcomes in terms of reducing vasomotor symptoms in postmenopausal women, while effects on metrics such as anthropometry, cardiovascularity, and physical performance varied across interventions. Postmenopausal women can benefit from rehabilitation and exercise therapy; these are evidence-based nonpharmacological approaches for improved physical functioning, cardiovascular health, and quality of life.
Parallel imaging is ubiquitous in MRI, enabling higher spatial and/or temporal resolution. However, successful unfolding is contingent on robust and accurate estimation of relative coil sensitivities, which often involves computation times that preclude online deployment. We present a computationally efficient method of robustly estimating coil sensitivities, and reconstructing under-sampled images using a data-driven regularised SENSE formalism that is commensurate with online deployment for Cartesian k-space acquisitions. The proposed image reconstruction method via Multiple Orthogonal Reference Sensitivity Encoding (MORSE) estimates multiple sensitivities per voxel to address issues, such as rapidly varying sensitivities, chemical shift artefact, or insufficient fields of view. It simultaneously provides a data-driven regularisation term for noise control providing inherent adaptability to diverse imaging contexts. MORSE has been successfully deployed in multiple neuroimaging studies at both 3T and 7T, including functional studies of autobiographical memory processing, visual and auditory perception, and quantitative MRI studies of neurodegenerative diseases including Huntington's, Alzheimer's and Parkinson's. Exemplar image reconstructions are presented and compared with GRAPPA, ENLIVE, ESPIRiT and LORAKS. We also showcase application of MORSE outside of the brain via application in liver and knee imaging. MORSE consistently produced high-quality, artefact-free images with reconstruction times feasible for online deployment. The proposed method of sensitivity estimation and unfolding regularisation is flexible and robust. It is made available to the community in open-source as a library of functions within the vendor-agnostic Gadgetron image reconstruction framework.
Depression affects up to 30% of older adults and is associated with increased morbidity and mortality. Animal-assisted interventions (AAIs) - usually known as "pet therapy" - have emerged as promising complementary approaches, yet evidence synthesis remains fragmented. To comprehensively evaluate the effectiveness of AAI in reducing depressive symptoms among older adults through an umbrella review of systematic reviews and meta-analyses, incorporating trial sequential analysis. We systematically searched PubMed, Embase, and Cochrane Library through September 2025 for systematic reviews and meta-analyses examining AAIs for depression in older adults. Quality assessment was performed using AMSTAR-2. We calculated the Corrected Covered Area to assess overlap between meta-analyses, re-analyzed primary study data to avoid double-counting, and conducted trial sequential analysis to evaluate evidence sufficiency. Five systematic reviews encompassing 27 unique primary studies with 2,156 participants were included. The pooled random-effects meta-analysis demonstrated a significant reduction in depressive symptoms (SMD = 0.73; 95% CI: 0.57-0.89; p < 0.001) with moderate heterogeneity (I² = 43.4%). Trial sequential analysis revealed that the cumulative Z-curve crossed monitoring boundaries at 75% of the required information size, confirming evidence sufficiency. The Corrected Covered Area was 20.4%, indicating moderate overlap between meta-analyses. AAIs are associated with clinically meaningful reductions in depressive symptoms among older adults. Trial sequential analysis confirms that sufficient evidence exists to support this conclusion. AAIs represent a valuable, low-risk, patient-centered complement to conventional depression treatments in geriatric care. PROSPERO REGISTRATION: [CRD420251250448].
We systematically explored PEG alternatives by synthesizing a combinatorial library of nine copolymers composed of three hydrophilic monomers including oligo(ethylene glycol) methyl ether methacrylate and 2-(methylsulfinyl)ethyl methacrylate and three hydrophobic monomers. These copolymers were evaluated for their hydrophobicity by reversed-phase chromatography and LCST behavior, and for their biodistribution. Extended hydrophilic brushes enhanced blood retention and tumor accumulation. For copolymers with the longest brushes, hydrophobic side chains minimally influenced kidney accumulation, whereas kidney accumulation of copolymers with medium-length brushes was strongly influenced. Liver accumulation of the copolymers was hardly affected by the hydrophobic side chain, except for the copolymer with the longest brushes and the most hydrophobic side chains, which showed increased liver accumulation. This study highlights the critical role of hydrophilic brushes and hydrophobic side chains in modulating biodistribution of polymeric carriers and provides a foundation for rational design of drug delivery systems.
The direct anterior approach (DAA) and the posterolateral approach (PLA) are commonly used surgical techniques in total hip arthroplasty (THA). However, whether DAA is associated with different wound complication rates compared with PLA remains controversial. This meta-analysis aimed to compare wound complications and clinical outcomes between DAA and PLA in THA based on randomized controlled trials. A comprehensive search was conducted across six major electronic databases: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and Chongqing VIP Information (CQVIP). The search strategy encompassed studies indexed from database inception to 31 December 2025. The primary outcomes were wound complications, including incisional infection, hematoma, and delayed wound healing. Predefined eligibility criteria were applied during study screening. The risk of bias of the included studies was assessed using the revised Cochrane Risk of Bias tool for randomized trials (RoB 2). The PLA group was used as the control group. Data were extracted from the included randomized controlled trials (RCTs). A pooled statistical analysis was performed to estimate the rate of wound complications and to compare the clinical effects of DAA and PLA. The meta-analysis was conducted with Review Manager 5.3 and Stata 15. A total of 18 eligible RCTs, comprising 1,485 patients, were included. Compared with PLA, DAA was associated with decreased rates of incisional infection (RR = 0.48, P = 0.03, I2 = 0%) and a lower overall rate of wound complications (RR = 0.58, P = 0.04, I2 = 0%). No evidence of a significant difference between groups was observed for hematoma incidence, poor wound healing, or overall surgical complications. Regarding perioperative indicators, DAA demonstrated several advantages. DAA was associated with a shorter incision length (MD = -3.44, P < 0.001, I2 = 97%), less intraoperative blood loss (MD = -76.74, P < 0.001, I2 = 97%), and a shorter hospital stay (MD = -2.15, P < 0.001, I2 = 95%). In terms of functional recovery, DAA demonstrated better early postoperative function. The DAA group had higher HHS at 1 month (MD = 5.87, P < 0.001, I2 = 15%), 3 months (MD = 5.10, P < 0.001, I2 = 95%), and 6 months (MD = 2.94, P < 0.001, I2 = 92%). No significant difference was observed at 12 months. For pain outcomes, DAA was associated with lower VAS scores in the postoperative period, including at 1 day (MD = -0.84, P < 0.001, I2 = 59%), 3 days (MD = -0.77, P < 0.001, I2 = 76%), 7 days (MD = -0.85, P < 0.001, I2 = 88%), 1 month (MD = -0.49, P = 0.002, I2 = 90%), 3 month (MD = -0.67, P = 0.02, I2 = 96%), and 6 month (MD = -0.12, P = 0.04, I2 = 75%). Compared with the PLA, the DAA is associated with improved perioperative outcomes following THA. Specifically, the DAA demonstrates a lower incidence of incision infection, fewer overall wound complications, shorter incision length, reduced intraoperative blood loss, and a shorter length of hospital stay. Early postoperative functional outcomes and pain, assessed by HHS and VAS, are also superior with the DAA. However, owing to heterogeneity and limited robustness of certain outcomes, these findings should be interpreted with caution. Further high-quality randomized controlled trials are warranted to confirm these results.
The mechanical effects of screw modifications, including coating and surface treatment, and the tightening conditions, including lubrication or contamination, on implant prosthetic screws remain unclear. This systematic review and meta-analysis aimed to evaluate the effects on screw-related mechanical outcomes of screw modifications, including coating and surface treatment, and the tightening conditions, including lubrication or contamination. A systematic search was conducted in the PubMed, Embase, Scopus, Web of Science, and Cochrane Library databases up to July 2025. In vitro studies assessing screw-related interventions were included. Outcomes were synthesized as weighted mean differences (WMDs) using random-effects meta-analysis. Heterogeneity (Cochrane Q, I²), subgroup and meta-regression analyses, publication bias (Egger, trim-and-fill), and risk of bias were assessed (α=.05). Twenty-six studies were included. Across screw-related interventions, detorque (WMD=0.997 Ncm; P=.011) and preload (WMD=16.072 N; P<.001) increased, while vertical gap and friction were unchanged. Screw coating increased detorque (WMD=1.73 Ncm; P<.001) and preload (WMD=78.59 N; P<.001) and reduced friction (P<.001) but did not affect vertical gap, fracture load, elastic modulus, or hardness. Surface treatment did not affect detorque. Contamination had no overall detorque effect, although blood with or without hemostatic agents reduced it. Lubrication increased preload (WMD=3.963 N; P=.001) without affecting detorque. Heterogeneity was substantial in most analyses. Selected screw coatings increased detorque and preload and reduced friction, whereas surface treatment had no significant effect. Contamination and lubrication showed protocol- and torque-dependent effects. Substantial heterogeneity limited certainty regarding effect magnitude.
The combination of doravirine and islatravir (DOR/ISL) is a novel two-drug regimen for HIV-1. Early development faced challenges due to dose-dependent immunological signals. We aimed to synthesize the evidence on the efficacy and safety of DOR/ISL across all treatment-experience categories, specifically evaluating the impact of islatravir dosage (0.25 mg vs 0.75 mg) on clinical and immunological outcomes. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) following PRISMA guidelines. We searched PubMed, Embase, Cochrane Library, and Google Scholar from inception through April 2026. Primary outcomes were virological suppression (<50 copies/mL) and mean change in CD4+ T-cell count at week 48. Data were pooled using random-effects models. Islatravir dose was evaluated as a pre-specified moderator. Quality was assessed using Cochrane RoB 2.0 and certainty of evidence was graded using the GRADE approach. Seven RCTs (n = 3,600 participants) were included. At Week 48, DOR/ISL showed non-inferior suppression rates (RR 1.01 [95% CI 0.99-1.02]; p = 0.516; moderate-certainty evidence) and a statistically significant reduction in virological failure risk (RR 0.55 [0.33-0.92]; p = 0.022) compared to active control. Overall CD4+ gain was lower with DOR/ISL (MD -34.55 cells/μL; low-certainty evidence); however, a profound moderator effect of dose was observed (p < 0.0001). The 0.75 mg dose was associated with significant CD4+ and lymphocyte declines, whereas the approved 0.25 mg dose was immunologically neutral. DOR/ISL was weight-neutral compared to bictegravir/emtricitabine/tenofovir alafenamide (MD -0.25 kg [-0.66 to 0.16]; low-certainty evidence). DOR/ISL 100/0.25 mg once daily achieved virological suppression comparable to standard-of-care ART regimens and was associated with lower rates of virological failure compared with active comparators. The immunological safety concerns observed in early trials were successfully resolved by dose optimization. These findings support the use of DOR/ISL (IDVYNSO) as a potential treatment option for both treatment-naïve and virologically suppressed adults while emphasizing long-term safety surveillance.