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Background: Prior research has revealed substantial psychological impacts of COVID-19 among the general population. However, there is a noticeable gap in studies addressing the enduring anxiety levels before and during lockdown periods of the COVID-19 pandemic., Objective: The study assessed and compared the psychological impact of the COVID-19 pandemic before and during lockdown periods among the general population in Saudi Arabia., Methods: A validated and reliable General Anxiety Disorder (GAD)-7 instrument was used to quantify stress levels by measuring anxiety. Nonprobability snowball sampling was used to collect data from 516 participants residing in Saudi Arabia. The difference in scores for each of the seven related questions of GAD-7 was determined using a non-parametric Wilcoxon rank test., Results: A mild level of anxiety was consistently observed both before and during the lockdown, as indicated by GAD-7 scores of 6.17 (SD = 5.5) before the lockdown and 6.42 (SD = 5.7) during the lockdown. There were no differences in GAD-7 scores before 6.17 (SD = 5.5) and during 6.42 (SD = 5.7) the lockdown periods. However, levels of moderate anxiety increased by 5% during the lockdown period. Anxiety levels before and during lockdown were significantly associated with gender (χ2 (3, n = 516) =11.23 p = 0.01) and employment status (χ2 (3, n = 516) = 9.41 p = 0.024). Among the GAD-7 questionnaire items, item number 1 ("Feeling nervous, anxious, or on edge") (p= 0.00) and item number 7 ("Feeling afraid as if something awful might happen") (p= 0.025) showed a significant association with anxiety levels before and during the lockdown periods., Conclusion: The enduring prevalence of mild anxiety, persisting both before and during the lockdown periods, underscores the profound impact of COVID-19 on the mental health of the general population in Saudi Arabia., Competing Interests: The authors declare that there is no conflicts of interest in this work., (© 2024 Amin et al.)

Background: Functional health status is increasingly being recognized as a viable endpoint in heart failure (HF) trials. We sought to assess its prognostic impact and relationship with traditional clinical outcomes in patients with HF., Methods: MEDLINE and Cochrane central were searched up to January 2021 for post hoc analyses of trials or observational studies that assessed independent association between baseline health/functional status, and mortality and hospitalization in patients with HF across the range of left ventricular ejection fractions to evaluate the prognostic ability of NYHA class [II, III, IV], KCCQ, MLHFQ, and 6MWD. Hazard ratios (HR) with 95% confidence intervals were pooled., Results: Twenty-two studies were included. Relative to NYHA I, NYHA class II (HR 1.54 [1.16-2.04]; p < 0.01), NYHA class III (HR 2.08 [1.57-2.77]; p < 0.01), and NYHA class IV (HR 2.53 [1.25-5.12]; p = 0.01) were independently associated with increased risk of mortality. 6MWD (per 10 m) was associated with decreased mortality (HR 0.98 [0.98-0.99]; p < 0.01). A 5-point increase in KCCQ-OSS (HR 0.94 [0.91-0.96]; p < 0.01) was associated with decreased mortality. A high MLHFQ score (> 45) was significantly associated with increased mortality (HR 1.30 [1.14-1.47]; p < 0.01). NHYA class, 6MWD (per 10 m), KCCQ-OSS, and MLHFQ all significantly associated with all-cause mortality in patients with HF., Conclusion: Identifying such patients with poor health status using functional health assessment can offer a complementary assessment of disease burden and trajectory which carries a strong prognostic value., (© 2024. The Author(s).)

Non-canonical nucleotides, generated as oxidative metabolic by-products, significantly threaten the genome integrity of Plasmodium falciparum and thereby, their survival, owing to their mutagenic effects. PfHAM1, an evolutionarily conserved inosine/xanthosine triphosphate pyrophosphohydrolase, maintains nucleotide homeostasis in the malaria parasite by removing non-canonical nucleotides, although structure-function intricacies are hitherto poorly reported. Here, we report the X-ray crystal structure of PfHAM1, which revealed a homodimeric structure, additionally validated by size-exclusion chromatography-multi-angle light scattering analysis. The two monomeric units in the dimer were aligned in a parallel fashion, and critical residues associated with substrate and metal binding were identified, wherein a notable structural difference was observed in the β-sheet main frame compared to human inosine triphosphate pyrophosphatase. PfHAM1 exhibited Mg ++ -dependent pyrophosphohydrolase activity and the highest binding affinity to dITP compared to other non-canonical nucleotides as measured by isothermal titration calorimetry. Modifying the pfham1 genomic locus followed by live-cell imaging of expressed mNeonGreen-tagged PfHAM1 demonstrated its ubiquitous presence in the cytoplasm across erythrocytic stages with greater expression in trophozoites and schizonts. Interestingly, CRISPR-Cas9/DiCre recombinase-guided pfham1-null P. falciparum survived in culture under standard growth conditions, indicating its assistive role in non-canonical nucleotide clearance during intra-erythrocytic stages. This is the first comprehensive structural and functional report of PfHAM1, an atypical nucleotide-cleansing enzyme in P. falciparum., (© 2024 Federation of European Biochemical Societies.)

Introduction The unique nature of a lack of good oral health, coupled with the lack of discussion and recognition surrounding the associated stigma, highlights it as a distinct issue. This stigma causes discomfort, devalues individuals, and necessitates urgent care and intervention. In Pakistan, a variety of reasons, including cultural beliefs, socioeconomic gaps, and poor access to dental care services, tend to exacerbate the stigma that is associated with dental care. This study aimed to determine the impact of stigma on oral health-seeking behaviours amongst the population of South Punjab in Pakistan. Methodology The study employed a qualitative design with a phenomenological approach, and the data collection was preceded by the administration of semi-structured interview guides and discussion guides to the patients and the consultant group, respectively. The targeted population was composed of patients who had reported stigmatization and a focus group of 10 dental consultants from various specialisations in dentistry. Data was collected until saturation from 16 patients who were recruited through the purposive convenience sampling technique. Results The study identified three themes, including perceived stigma impact on health-seeking behaviours and coping mechanisms; 10 subthemes emerged. Results showed social attitudes and unhealthy perceptions of oral conditions that lead to shame, loss of self-esteem, and lack of confidence among affected individuals. Behavioural reactions like mockery and discrimination further made it difficult for the participants who sought dental care and treatment. The study highlighted that stigma resulted in the avoidance of dental care, deterioration of oral health, and a tendency towards self-medication. People also used coping strategies such as hiding dental issues by avoiding social gatherings and seeking help from close friends to manage oral health stigma. Dental consultants had the strong opinion that care quality could be enhanced by utilising compassionate communication and patient education campaigns. Conclusions The experiences of patients and consultants related to dental stigma highlighted the complex interplay of sociocultural norms and healthcare practices. The study demonstrated that perceived stigma impacted the health-seeking behaviours of patients. Social support and education about oral health helped patients overcome this stigma. The study revealed that patients avoided dental treatments due to stigmatised behaviour from health professionals, a lack of affordability, and a feeling of shame to show and discuss the condition of their teeth, which got even worse due to self-remedy. The experiences of patients and consultants highlighted the need for increased advocacy, educational campaigns, and policies that can reduce inequalities in oral health and improve health equity. The study recommends specific intervention strategies and policy formulation to address oral health inequalities and contribute to advancing oral health equity in Pakistan., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Review Board of Bakhtawar Amin Dental College and Hospital issued approval COD 341/23. The Institutional Review Board of Bakhtawar Amin Dental College and Hospital, Multan, Pakistan, considered the ethical and technical aspects of the research proposal "Unveiling the Veil of Stigma: Exploring its Impact on Oral Health Seeking Behaviours". After a comprehensive discussion, the members of the committee approved the proposed research project. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Zain Ul Abideen et al.)

Infectious tenosynovitis can involve both flexor and extensor tendons of the extremities. If left untreated, it can lead to high morbidity and mortality. Most emergency providers recognize the signs and symptoms of flexor and extensor tenosynovitis of the hand. However, extensor tenosynovitis of the hallucis longus tendon is a rare condition with a risk of complications similar to infectious tenosynovitis of the hand. This case report describes a presentation of extensor tenosynovitis of the hallucis longus tendon. Clinical suspicion is essential to help the provider not miss this rare condition, which can lead to significant morbidity if not treated promptly or appropriately., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, St Clair et al.)

Purpose: Tarsal tunnel syndrome is well documented following lateralizing calcaneal osteotomy to manage varus hindfoot deformity. Traditionally, calcaneal osteotomy is performed with an oscillating saw. No studies have investigated the effect of alternative surgical techniques on postoperative tarsal tunnel pressure. The purpose of this study was to investigate the difference in tarsal tunnel pressures following lateralizing calcaneal osteotomy performed using a high-torque, low-speed "minimally invasive surgery" (MIS) Shannon burr versus an oscillating saw., Methods: Lateralizing calcaneal osteotomy was performed on 10 below-knee cadaveric specimens. This was conducted on 5 specimens each using an oscillating saw (Saw group) or MIS burr (Burr group). The calcaneal tuberosity was translated 1 cm laterally and transfixed using 2 Kirschner wires. Tarsal tunnel pressure was measured before and after osteotomy via ultrasound-guided percutaneous needle barometer. Mean pre/post-osteotomy pressures were compared between groups. Differences were analyzed using Student's t test., Results: The mean pre-procedure tarsal tunnel pressure was 25.8 ± 5.1 mm Hg in the Saw group and 26.4 ± 4.3 mm Hg in the Burr group (p = 0.85). The mean post-procedure pressure was 63.4 ± 5.1 in the Saw group and 47.8 ± 4.3 in the Burr group (p = 0.01). Change in tarsal tunnel pressure was significantly lower in the Burr group (21.4 ± 4.5) compared to the Saw group (37.6 ± 12.5) (p = 0.03). The increase in tarsal tunnel pressure was 43% lower in the Burr group., Conclusion: In this cadaveric study, tarsal tunnel pressure increase after lateralizing calcaneal osteotomy was significantly lower when using a burr versus a saw. This is likely because the increased width ("kerf") of the 3 mm MIS burr, compared to the submillimeter saw blade width, causes calcaneal shortening. Given the smaller increase in tarsal tunnel pressure, using the MIS burr for lateralizing calcaneal osteotomy may decrease the risk of postoperative tarsal tunnel syndrome. Future research in vivo should explore this., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Introduction: The purpose of this study was to investigate whether the use of a dedicated early morning orthopaedic trauma operating room (OR) resulted in shorter wait times, decreased surgical times, decreased length of stay (LOS), and decreased complications in children treated with urgent surgical intervention for supracondylar humerus fractures., Methods: This retrospective comparative cohort study at a level I pediatric trauma center included patients younger than 12 years with supracondylar humerus fractures urgently treated with closed or open reduction and percutaneous pinning. Index surgical cases from April 28, 2013, to February 26, 2020, were included. Patients with prior humerus fracture, concomitant injuries, open fracture, pulseless supracondylar fracture, or missing data were excluded. Patients were analyzed based on the type of OR: dedicated early morning orthopaedic trauma OR or typical daytime orthopaedic OR. The primary outcome was time from presentation to surgery. Secondary outcomes included surgical time, complications, and LOS., Results: A total of 401 patients with a mean age of 5 ± 2 (range: 1 to 11) years and a mean follow-up of 2.0 ± 2.1 (range: 0.5 to 25.0) months were included, of whom 137 patients (34%) underwent surgery in the early morning dedicated orthopaedic trauma OR. The dedicated early morning orthopaedic OR group had significantly less time from presentation to surgery (7.5 versus 9.4 hours; P = 0.0002) and shorter LOS (21.0 versus 24.0 hours; P = 0.004) compared with children treated in the typical daytime orthopaedic OR. Surgical time (31.1 versus 32.6 minutes; P = 0.40) and complication rates (5.8% versus 4.9%; P = 0.65) were similar between the groups. No revision surgery was required in either group., Discussion: Surgical wait times were diminished with use of the dedicated early morning OR, as was LOS. Surgical times and complication rates were similar between groups. Institutions may consider adopting a dedicated early morning orthopaedic trauma OR to improve surgical wait times and decrease LOS., Level of Evidence: III., (Copyright © 2023 by the American Academy of Orthopaedic Surgeons.)

Aim: The efficacy and safety of bivalirudin when used concurrently with glycoprotein IIb/IIIa inhibitors (GPI) is uncertain. In this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of bivalirudin versus heparin in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) and to explore the impact of differential use (greater and balanced) of GPI., Methods: Online databases were queried from inception to March 2023 to identify eight randomized controlled trials (n = 22,483) for inclusion. The primary outcomes included all-cause mortality, major bleeding, major adverse cardiovascular events (MACE), and net adverse clinical events (NACE). Secondary efficacy endpoints included cardiac death, reinfarction, stent thrombosis (ST), and stroke. Data were pooled using a random-effects model to derive risk ratios (RRs) and 95% confidence intervals (CIs)., Results: When compared to heparin, bivalirudin was associated with a significant reduction in all-cause mortality (RR 0.83; 95% CI 0.72-0.97; P = 0.02), major bleeding (RR 0.73; 95% CI 0.57-0.93; P = 0.01), cardiac death (RR 0.79; 95% CI 0.66-0.94; P = 0.01), and NACE (RR 0.80; 95% CI 0.72-0.89; P < 0.0001). However, while the bivalirudin arm showed an increased likelihood of ST in the greater GPI subgroup (RR 1.70; 95% CI 1.13-2.56; P = 0.01), it was associated with a decreased likelihood of ST in the balanced GPI subgroup (RR 0.40; 95% CI 0.24-0.65; P = 0.0003)., Conclusion: Overall, our findings suggest that bivalirudin may be a more efficacious intervention than heparin for reducing certain adverse events in patients with STEMI undergoing primary PCI., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: The study aimed to develop international consensus recommendations on the safe use of lumen-apposing metal stents (LAMSs) for on- and off-label indications., Methods: Based on the available literature, statements were formulated and grouped into the following categories: general safety measures, peripancreatic fluid collections, endoscopic ultrasound (EUS)-biliary drainage, EUS-gallbladder drainage, EUS-gastroenterostomy, and gastric access temporary for endoscopy. The evidence level of each statement was determined using the Grading of Recommendations Assessment, Development, and Evaluation methodology.International LAMS experts were invited to participate in a modified Delphi process. When no 80% consensus was reached, the statement was modified based on expert feedback. Statements were rejected if no consensus was reached after the third Delphi round., Results: Fifty-six (93.3%) of 60 formulated statements were accepted, of which 35 (58.3%) in the first round. Consensus was reached on the optimal learning path, preprocedural imaging, the need for airway protection and essential safety measures during the procedure, such as the use of Doppler, and measurement of the distance between the gastrointestinal lumen and the target structure. Specific consensus recommendations were generated for the different LAMS indications, covering, among others, careful patient selection, the preferred size of the LAMS, the need for antibiotics, the preferred anatomic location of the LAMS, the need for coaxial pigtail placement, and the appropriate management of LAMS-related adverse events., Discussion: Through a modified international Delphi process, we developed general and indication-specific experience- and evidence-based recommendations on the safe use of LAMS., (Copyright © 2023 by The American College of Gastroenterology.)

Alba domain proteins, owing to their functional plasticity, play a significant role in organisms. Here, we report an intrinsic DNase activity of PfAlba6 from Plasmodium falciparum , an etiological agent responsible for human malignant malaria. We identified that tyrosine28 plays a critical role in the Mg 2+ driven 5'-3' DNase activity of PfAlba6. PfAlba6 cleaves both dsDNA as well as ssDNA. We also characterized PfAlba6-DNA interaction and observed concentration-dependent oligomerization in the presence of DNA, which is evident from size exclusion chromatography and single molecule AFM-imaging. PfAlba6 mRNA expression level is up-regulated several folds following heat stress and treatment with artemisinin, indicating a possible role in stress response. PfAlba6 has no human orthologs and is expressed in all intra-erythrocytic stages; thus, this protein can potentially be a new anti-malarial drug target., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Background: When high thromboembolic and bleeding risks coexist, the former tends to influence physicians' decision making for anti-coagulation therapy. However, the ideal is to weigh the risk of major bleeding and stroke together to ensure effective anti-coagulation treatment, which is a limitation of traditional guideline recommended CHA2DS2-VASc and HAS-BLED. This meta-analysis assesses the performance of the two new scores - ABC and GARFIELD-AF compared to CHA2DS2-VASc and HAS-BLED for major bleeding and stroke outcomes in patients with atrial fibrillation (AF) on anticoagulation therapy., Methods: MEDLINE and Cochrane central were searched from 2010 to February 2023 that compared GARFIELD-AF and/or ABC with CHA2DS2-VASc and/or HAS-BLED scores using C-statistics to assess their discriminative ability., Results: 12 studies were included in this meta-analysis. When assessing stroke risk prediction, GARFIELD-AF stroke (C-Statistic: 0.71; 95 % CI: 0.70-0.72; I 2  = 0 %, p < 0.05) was found to be significantly better than ABC-stroke (C-Statistic: 0.67; 95 % CI: 0.65-0.68; I 2  = 0 %, p < 0.05), and CHA2DS2-VASc (C-Statistic: 0.64; 95 % CI: 0.60-0.67; I 2  = 92 %, p < 0.05). Additionally, when assessing bleeding risk prediction, ABC-bleeding (C-Statistic: 0.66; 95 % CI: 0.61-0.70; I 2  = 84 %, p < 0.05), GARFIELD-AF (C-Statistic: 0.64; 95 % CI: 0.60-0.68; I 2  = 95 %, p < 0.05), and HAS-BLED (C-Statistic: 0.64; 95 % CI: 0.62-0.66; I 2  = 85 %, p < 0.05) all showed equivalent performances., Conclusion: The GARFIELD-AF stroke score showed superior performance to the well-established CHA2DS2-VASc score as well as the ABC-stroke score. Therefore, new guidelines should favor GARFIELD-AF use in clinical practice., Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Aims: EUS-guided gallbladder drainage using lumen-apposing metal stents (EUS-GBD-LAMSs) and percutaneous cholecystostomy for gallbladder drainage (PTGBD) are the alternative treatment modalities in high-risk surgical patients with acute cholecystitis (AC). The aim of this study was to compare the safety of these procedures for AC in surgically suboptimal candidates., Methods: Six studies compared the 2 groups' early, delayed, and overall adverse events; they also compared length of hospital stay, re-interventions, and re-admissions rate. A random effect model calculated odds ratios (ORs) with a 95% confidence interval (CI)., Results: The 2 groups had similar early adverse events; however, EUS-GBD-LAMS was associated with a lower rate of delayed (OR, .21; 95% CI, .07-.61; P ≤ .01) and overall (OR, .43; 95% CI, .30-.61; P ≤ .01) adverse events. Patients with EUS-GBD-LAMSs had a shorter hospital stay than PTGBD., Conclusions: EUS-GBD-LAMS is a safer option than PTGBD and is associated with a shorter hospital stay in nonsurgical candidates with AC., Competing Interests: Disclosure The following author disclosed financial relationships: D. G. Adler: consultant for Boston Scientific. All other authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Objective: This metanalysis aims to assess the efficacy and safety of biliary stenting along with radiofrequency ablation compared with stents alone to treat malignant biliary obstruction (MBO) due to extrahepatic biliary strictures secondary to cholangiocarcinoma, pancreatic cancer, and metastatic cancer., Methods: A systemic search of major databases through April 2022 was done. All original studies were included comparing radiofrequency ablation with stenting versus stenting alone for treating malignant biliary strictures. The primary outcomes of interest were the difference in the mean stent patency and overall survival (OS) days between the 2 groups. The secondary outcome was to compare the adverse events of the 2 groups. The mean difference in the stent patency and OS days was pooled by using a random-effect model. We calculated the odds ratio to compare the adverse events between the 2 groups., Results: A total of 13 studies with 1339 patients were identified. The pooled weighted mean difference in stent patency was 43.50 days (95% CI, 25.60-61.41), favoring the RFA plus stenting. Moreover, the pooled weighted mean difference in OS was 90.53 days (95% CI, 49.00-132.07), showing improved survival in the RFA group. Our analysis showed no statistically significant difference in adverse events between the 2 groups OR 1.13 (95% CI, 0.90-1.42)., Conclusion: Our analysis showed that RFA, along with stent, is safe and is associated with improved stent patency and overall patient survival in malignant biliary strictures. More robust prospective studies should assess this association further., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To assess the refractive accuracy of eight intraocular lens (IOL) formulas in eyes that underwent combined phacovitrectomy., Methods: A retrospective chart review of 59 eyes that underwent uncomplicated phacovitrectomy between 2017 and 2020 at the Johns Hopkins Wilmer Eye Institute. Inclusion criteria were postoperative best corrected visual acuity of 20/40 or better within 6 months of surgery and IOL implantation in the capsular bag. The Barrett Universal II (BUII), Emmetropia Verifying Optical (EVOv2.0), Hill-Radial Basis Function (Hill-RBFv3.0), Hoffer Q, Holladay I, Kane, Ladas Super Formula (LSF), and SRK/T formulas were compared for accuracy in predicting postoperative spherical equivalents (SE) using Wilcoxon rank sum tests. Pearson's correlation coefficients were used to assess correlations between biometric parameters and errors for all formulas., Results: Prediction errors of SE ranged from - 1.69 to 1.43 diopters (D), mean absolute errors (MAE) ranged from 0.39 to 0.47 D, and median absolute errors (MedAE) ranged from 0.23 to 0.37 D among all formulas. The BUII had the lowest mean error (- 0.043), MAE (0.39) and MedAE (0.23). The BUII also had the highest percentage of eyes with predicted error within ± 0.25 D (51%) and ± 0.50 D (83%). Based on MedAE however, no pairwise comparisons resulted in statistically significant differences. Axial length (AL) was positively correlated with the error from the Hoffer Q and Holladay I formulas (correlation coefficients = 0.34, 0.30, p values < 0.01, 0.02 respectively)., Conclusion: While all eight IOL formulas had comparable accuracy in predicting refractive outcomes in eyes undergoing combined phacovitrectomy, the BUII and Kane formulas had a tendency to greater accuracy., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

During the COVID-19 pandemic, educational institutions confronted the possibility of complete closure and took countermeasures by adapting e-learning platforms. The present cross-sectional study quantified the impact of the pandemic on medical education using a validated and reliable tool. The tool was used to explore the perceptions of 270 healthcare students about e-learning in comparison to traditional learning systems. Inferential statistics were employed using Pearson's chi-squared test. It was found that e-learning was advantageous because of its location flexibility (46.1%) and the ease of access to study materials (46.5%). However, in-person learning was found to lead to an increase in knowledge (44.9%), clinical skills (52.7%), and social competencies (52.7%). The study concluded that while e-learning offers flexibility, traditional face-to-face teaching is deemed more effective for skill development and social interaction. Hence, e-learning should complement rather than replace traditional methods due to limitations in replicating clinical environments., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Siddiqui et al.)

Recombinase enzymes are extremely efficient at integrating very large DNA fragments into target genomes. However, intrinsic sequence specificities curtail their use to DNA sequences with sufficient homology to endogenous target motifs. Extensive engineering is therefore required to broaden applicability and robustness. Here, we describe the directed evolution of novel lambda integrase variants capable of editing exogenous target sequences identified in the diatom Phaeodactylum tricornutum and the algae Nannochloropsis oceanica. These microorganisms hold great promise as conduits for green biomanufacturing and carbon sequestration. The evolved enzyme variants show >1000-fold switch in specificity towards the non-natural target sites when assayed in vitro. A single-copy target motif in the human genome with homology to the Nannochloropsis oceanica site can also be efficiently targeted using an engineered integrase, both in vitro and in human cells. The developed integrase variants represent useful additions to the DNA editing toolbox, with particular application for targeted genomic insertion of large DNA cargos., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Peter Droge is a co-founder and share holder of LambdaGen. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Siau et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Myofascial pain (MFP) is characterized by localized pain in the maxillofacial region attributed to the presence of hypersensitive spots known as trigger points (TrPs). This condition is particularly prevalent in the maxillofacial area, warranting a comprehensive examination of evidence-based management techniques. This review aims to equip healthcare professionals with a more profound insight into evidence-based MFP management techniques, facilitating improved patient care and treatment outcomes. In this review, we conducted a thorough literature search using Google Scholar, Scopus, Web of Science (WOS), and MEDLINE, with the keywords "Myofascial pain syndrome," "Pain," and "Orofacial pain." Articles were selected based on their relevance to the study's objective. Pharmacological interventions, such as analgesics and muscle relaxants, are frequently prescribed. Additionally, a range of non-pharmacological modalities, including transcutaneous electrical nerve stimulation (TENS), ultrasound therapy, topical applications, dry needling, TrP injections, oral myofunctional therapy, and stretching exercises, have demonstrated efficacy in MFP management. The authors hope to give clinicians a more thorough understanding of the therapies for MFP by conducting a rigorous evidence-based evaluation of pharmacologic and non-pharmacological treatments. Our findings support the use of a combined approach that integrates both pharmacological and non-pharmacological strategies for the holistic management of TrPs., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Alshammari et al.)

Aberrant protein aggregation jeopardizes cellular functionality and underlies the development of a myriad of late-onset maladies including Alzheimer's disease (AD) and Huntington's disease (HD). Accordingly, molecules that mitigate the toxicity of hazardous protein aggregates are of great interest as potential future therapeutics. Here we asked whether a small peptide, composed of five amino acids (5MER peptide) that was derived from the human pro-inflammatory CD44 protein, could protect model nematodes from the toxicity of aggregative proteins that underlie the development of neurodegenerative disorders in humans. We found that the 5MER peptide mitigates the toxicity that stems from both; the AD-causing Aβ peptide and a stretch of poly-glutamine that is accountable for the development of several disorders including HD, while minimally affecting lifespan. This protection was dependent on the activity of aging-regulating transcription factors and associated with enhanced Aβ and polyQ35-YFP aggregation. A transcriptomic analysis unveiled that the peptide modifies signaling pathways, thereby modulating the expression of various genes, including these, which are known as protein homeostasis (proteostasis) regulators such as txt-13 and modifiers of proteasome activity. The knockdown of txt-13 protects worms from proteotoxicity to the same extent as the 5MER peptide, suggesting that the peptide activates the transcellular chaperone signaling to promote proteostasis. Together, our results propose that the 5MER peptide should be considered as a component of future therapeutic cocktails for the treatment of neurodegenerative maladies., (© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Background: The aim of the study was to determine the facial divergence and lip position combinations that are most and least preferred, and to investigate whether age or gender has an impact on these preferences., Methods: The current investigation was carried out on a sample of 1077 individuals who were not experts in the field (253 men and 824 females). The research employed black silhouette photographs of profiles featuring different lip locations and profile divergences. The recruitment of participants was conducted in order to assess the attractiveness of the profiles, employing a Likert scale. The various positions of the lips and variations in facial profiles were thoroughly categorized. Results were analyzed using the Chi-square test., Results: The findings of the research demonstrated that aesthetic perceptions displayed diversity when considering different lip locations and profile divergences. It was shown that neutral lip positions were predominantly favored, accounting for approximately 40.2% of the total frequencies in the anterior diverging group. It is noteworthy to highlight the aesthetically pleasing features exhibited by those with the most prominent lip position, occurring at a frequency of 10.9% in straight-diverging group. In the posterior divergent group, the most protruded lip position, showed very attractive aesthetics with frequency (7.1%). Gender, age, region, and level of education had significant influence on aesthetic perception., Conclusions: The variety of aesthetic preferences is influenced by the location of the lips and the divergence of the facial profile, resulting in different outcomes within the categories of anterior, straight, and posterior divergence. Clinicians are advised to customize the treatment regimen in order to correspond with the unique desires and preferences of the patient., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction The most significant element in halting the coronavirus disease 2019 (COVID-19) epidemic was the availability of reliable and efficient vaccines. Vaccine acceptability is influenced by many factors, including perceptions of the vaccine's safety and side effects. Adverse reactions to vaccines can vary with regard to the type, although they are frequently mild, localized, temporary, and self-limiting. Therefore, this study aimed to assess the prevalence of side effects experienced by postmenopausal women after receiving the Sinovac vaccine. Methods This multicenter, prospective cross-sectional study was carried out at multiple centers in Karachi, Pakistan. In this study, the non-probability sampling method was used. The study continued from August 1, 2022, to January 31, 2023, for six months. The study comprised 600 postmenopausal women over the age of 50 years who received two doses of Sinovac COVID-19 vaccination. Demographic parameters such as gender, the existence of comorbidities, and local and systemic side effects in postmenopausal women were documented as frequencies and percentages. Age, weight, and duration of comorbidities are expressed as means and standard deviations. Results The study findings showed that the mean age of study participants was 63.93 ± 8.24 years. There were related comorbidities with hypertension and diabetes mellitus in 181 (30.2%) and 40 (6.7%) women, respectively. Fever was the most often reported side effect, with 349 (58.2%) participants reporting it and 198 (56.7%) participants reporting it as mild. After the second dose, 234 (39.5%) participants reported fever as their most frequent adverse effect, and 158 (67.5%) of them reported it was mild. Conclusion This study concluded that the most commonly reported side effects among postmenopausal women were fever, pain, and swelling at the injection site after getting either dose of Sinovac vaccine. These overall side effects were generally mild to moderate in intensity, not life-threatening, and did not require hospitalization, although fever was reported in severe intensity in some cases, particularly after the first dose., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Syed et al.)

Introduction The most efficient method of combating the coronavirus disease 2019 (COVID-19) pandemic would be to use effective, safe, and proven vaccines; however, their widespread use has been hampered partly by concerns over possible adverse effects. Therefore, this study aimed to assess the prevalence of Oxford/AstraZeneca vaccine side effects among participants. Methods This was a multicenter, cross-sectional study conducted using a non-probability sampling technique. The duration of the study was nine months, from February 1, 2022, to October 31, 2022. The study included 900 participants who provided informed consent and had received two doses of the AstraZeneca vaccine. Demographic characteristics of participants, such as gender, age, comorbidities, AstraZeneca vaccine with both doses along with booster dose, previous exposure to COVID-19 infection, and the prevalence of any local and systemic side effects following the first and second doses of vaccine, were documented. Results The study findings showed that of the 900 participants, 414 (46.0%) were males and 486 (54.0%) were females; their mean age was 40.72 ± 13.47 years. Among them, 198 (22.0%) had hypertension and 144 (16.0%) had diabetes mellitus. Following the first dose of the AstraZeneca vaccine, pain at the injection site was the most commonly reported side effect in 594 (66.0%) participants. Moreover, swelling at the injection site was the most commonly reported side effect in 522 (58.0%) participants after receiving the second dose of the vaccine. The level of satisfaction showed that the majority of the 648 participants (72.0%) were satisfied with their vaccination. Conclusion This study concluded that pain at the injection site was the most commonly reported side effect, followed by swelling and fever after the first dose of the vaccine. Following the second dose of the vaccine, adverse effects included headache, swelling, and burning at the injection site., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Haider et al.)

Introduction It has been discovered that low levels of thiamine reserves in the body are related to diabetes mellitus (DM) because thiamine directly influences carbohydrate metabolism. Therefore, the purpose of this study was to assess several metabolic variables and blood thiamine levels in patients with type 1 and type 2 DM and compare them with those in a control group of healthy individuals. Methods This case-control study was conducted at multiple diabetic outpatient centers in Karachi. A total of 90 participants, who were divided into three groups, each containing 30 individuals, were chosen using a convenient non-probability sampling technique. Group A served as the control group and consisted of healthy, non-diabetic individuals. Groups B and C contained subjects with type 1 and type 2 DM, respectively. Descriptive analysis was reported as mean standard deviation, whereas gender and comorbidities were expressed as frequencies and percentages. The chi-square test and Pearson's correlation coefficient were used to determine the associations of the variables with type 1 DM, type 2 DM, and controls. Results The study results revealed statistically significant differences between controls, type 1 and type 2 DM, in the means of blood glucose levels and all lipid profiles, such as glycated hemoglobin (HbA1c), fasting blood sugar (FBS), random blood sugar (RBS), serum thiamine, triglycerides (p < 0.001), high-density lipoprotein (HDL) (p = 0.014), and total cholesterol (p = 0.013). Furthermore, it was shown that among the control group, type 1 and type 2 DM, HbA1c, and FBS were insignificantly correlated with thiamine levels, whereas the HbA1c and FBS of the combined diabetic groups were significantly correlated with the thiamine level (r = 0.465, p < 0.001) and (r = 0.360, p = 0.005), respectively, where 'r' is the Pearson correlation coefficient. Additionally, HbA1c and FBS in the combined three groups were significantly correlated with the thiamine level (r = -0.626, p < 0.001) and (r = -0.561, p < 0.001), respectively. Conclusion This study concluded that patients with type 1 and type 2 DM had significantly higher levels of FBS, RBS, HbA1c, triglycerides, and total cholesterol than controls. Furthermore, both type 1 and type 2 DM patients' serum thiamine and HDL levels were observed to be considerably lower than those of controls. Additionally, among both types of DM and controls, there was a strong correlation between FBS and HbA1c. Therefore, we recommend that serum thiamine levels be routinely monitored in diabetic patients, and thiamine supplementation should be considered to avoid complications, especially vascular complications of DM., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Khan et al.)

Aim: To evaluate the effect of facial clefts on the dental health quality of life of affected individuals, and to determine whether age and gender affect the oral health quality of life differently., Materials and Methods: The cross-sectional survey included 50 participants (32 females and 18 males) from the northern region of Saudi Arabia, using a reliable and validated questionnaire, the Child Oral Health Impact Profile (COHIP), which measured self-reported oral health-related quality of life (OHRQoL) in children and adults using a five-point Likert scale. Statistical analysis was performed, and results were considered significant if the p -value was less than 0.05., Results: The highest scores in the oral health domain were related to bad breath and reluctance in speaking or reading aloud in class within the school environment domain, with mean scores of 3.44 ± 1.3 and 3.52 ± 1.2, respectively. Most patients showed apprehension regarding necessary dental treatments (mean = 1.44 ± 0.07). The study found a non-statistically significant difference in tooth discomfort between age groups ( p = 0.092), with individuals aged from 20 to 29 experiencing higher levels of discomfort than other age groups surveyed., Conclusion: The two topics with the highest mean scores in the oral health domain and the school environment domain were bad breath and not wanting to speak or read aloud in class. Females reported more discomfort, and there was a substantial association between gender and tooth pain/sensitivity., Clinical Significance: Understanding the difficulties cleft patients face is crucial, as doing so will enable dentists to encourage and handle these issues more effectively.

Background and Purpose: Mitochondrial oxidative stress, inflammation and apoptosis primarily underlie gastric mucosal injury caused by the widely used non-steroidal anti-inflammatory drugs (NSAIDs). Alternative gastroprotective strategies are therefore needed. Sirtuin-3 pivotally maintains mitochondrial structural integrity and metabolism while preventing oxidative stress; however, its relevance to gastric injury was never explored. Here, we have investigated whether and how sirtuin-3 stimulation by the phytochemical, honokiol, could rescue NSAID-induced gastric injury., Experimental Approach: Gastric injury in rats induced by indomethacin was used to assess the effects of honokiol. Next-generation sequencing-based transcriptomics followed by functional validation identified the gastroprotective function of sirtuin-3. Flow cytometry, immunoblotting, qRT-PCR and immunohistochemistry were used measure effects on oxidative stress, mitochondrial dynamics, electron transport chain function, and markers of inflammation and apoptosis. Sirtuin-3 deacetylase activity was also estimated and gastric luminal pH was measured., Key Results: Indomethacin down-regulated sirtuin-3 to induce oxidative stress, mitochondrial hyperacetylation, 8-oxoguanine DNA glycosylase 1 depletion, mitochondrial DNA damage, respiratory chain defect and mitochondrial fragmentation leading to severe mucosal injury. Indomethacin dose-dependently inhibited sirtuin-3 deacetylase activity. Honokiol prevented mitochondrial oxidative damage and inflammatory tissue injury by attenuating indomethacin-induced depletion of both sirtuin-3 and its transcriptional regulators PGC1α and ERRα. Honokiol also accelerated gastric wound healing but did not alter gastric acid secretion, unlike lansoprazole., Conclusions and Implications: Sirtuin-3 stimulation by honokiol prevented and reversed NSAID-induced gastric injury through maintaining mitochondrial integrity. Honokiol did not affect gastric acid secretion. Sirtuin-3 stimulation by honokiol may be utilized as a mitochondria-based, acid-independent novel gastroprotective strategy against NSAIDs., (© 2023 British Pharmacological Society.)

A simple, rapid, sensitive and specific gas chromatography-tandem mass spectrometry (GC-MS/MS) method was developed for quantitation of salbutamol in human urine using salbutamol-d3 as the internal standard. The processing of urines samples includes deconjugation with enzymatic hydrolysis, solid phase extraction procedure utilizing XAD2 column and liquid-liquid extraction accompanied by the derivatization by means of MSTFA/IODO-TMS/DTE mixture. The GC column was a HP Ultra-1 (17 m × 0.22 mm × 0.11 μm) used to separate the peak of interest. The data for GC-MS/MS were acquired and processed utilizing GC Labs Solution and Insight GCMS Software. The detection of spectra was performed on TQ 8050. This method included a chromatographic run of 13.67 min and the linearity was found over the concentration range of 250-2000 ng/mL with a regression coefficient (r2) of 0.99. The coefficient of variation for intra and interday assay precision was between 1.85 and 2.85% and the accuracy was between 95.50 and 107.04% for low quality control (QC), medium QC and high QC. The recovery was adequate to reliable detect the analyte at or below the level recommended by the World Anti-Doping Agency i.e., threshold 1000 ng/mL. The limit of detection and limit of quantification were found to be 10 and 100 ng/mL, respectively. The expanded measurement uncertainty (Uexp%) was found to be 8.28%., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Control of schistosomiasis depends on a single drug, praziquantel, with variable cure rates, high reinfection rates, and risk of drug resistance. A vaccine could transform schistosomiasis control. Preclinical data show that vaccine development is possible, but conventional vaccine efficacy trials require high incidence, long-term follow-up, and large sample size. Controlled human infection studies (CHI) can provide early efficacy data, allowing the selection of optimal candidates for further trials. A Schistosoma CHI has been established in the Netherlands but responses to infection and vaccines differ in target populations in endemic countries. We aim to develop a CHI for Schistosoma mansoni in Uganda to test candidate vaccines in an endemic setting. This is an open-label, dose-escalation trial in two populations: minimal, or intense, prior Schistosoma exposure. In each population, participants will be enrolled in sequential dose-escalating groups. Initially, three volunteers will be exposed to 10 cercariae. If all show infection, seven more will be exposed to the same dose. If not, three volunteers in subsequent groups will be exposed to higher doses (20 or 30 cercariae) following the same algorithm, until all 10 volunteers receiving a particular dose become infected, at which point the study will be stopped for that population. Volunteers will be followed weekly after infection until CAA positivity or to 12 weeks. Once positive, they will be treated with praziquantel and followed for one year. The trial registry number is ISRCTN14033813 and all approvals have been obtained. The trial will be subjected to monitoring, inspection, and/or audits., Competing Interests: The authors declare that the research was conceptualized and protocol written in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology.)

Introduction: The aim of this study was to compare the peri-operative outcomes, especially intraoperative surgeon workload and early post-operative pain, following midline ventral hernia repair by laparoscopic enhanced-view totally extraperitoneal (eTEP) approach and laparoscopic intraperitoneal onlay mesh plus (IPOM plus) approach., Patients and Methods: This single-centre randomised control trial study was conducted from January 2020 to June 2022. A total of 60 adult patients undergoing elective ventral hernia surgery with small- and medium-sized midline defects were included. Intraoperative surgeon workload and early post-operative pain were systematically recorded and analysed for each procedure., Results: Out of 30 patients assigned to each group, 29 patients underwent eTEP mesh repair and 27 patients underwent successful IPOM plus repair. The intraoperative surgeon's workload, especially mental demand, physical demand, task complexity and degree of difficulty as reported and felt by the operating surgeon, was significantly higher in the eTEP mesh repair group compared to IPOM plus group (P < 0.001) with comparable operating room distractions (P = 0.039). The mean overall post-operative pain score on post-operative day 1 was slightly less in eTEP mesh repair (4.28 ± 1.12) group compared to IPOM plus group (4.93 ± 1.17), which was statistically insignificant (P = 0.042). The eTEP group had significantly longer operative time and length of hospital stay compared to the IPOM plus group., Conclusion: Our study revealed significantly longer operative time, higher surgical workload and increased length of hospital stay in the eTEP group with comparable early post-operative pain in both groups, thus making eTEP mesh repair a more difficult and challenging procedure., Competing Interests: None

The review discusses the diagnostic application of biosensors as point-of-care devices in the COVID-19 pandemic. Biosensors are important analytical tools that can be used for the robust and effective detection of infectious diseases in real-time. In this current scenario, the utilization of smart, efficient biosensors for COVID-19 detection is increasing and we have included a few smart biosensors such as smart and intelligent based biosensors, plasmonic biosensors, field effect transistor (FET) biosensors, smart optical biosensors, surface enhanced Raman scattering (SERS) biosensor, screen printed electrode (SPE)-based biosensor, molecular imprinted polymer (MIP)-based biosensor, MXene-based biosensor and metal-organic frame smart sensor. Their significance as well as the benefits and drawbacks of each kind of smart sensor are mentioned in depth. Furthermore, we have compiled a list of various biosensors which have been developed across the globe for COVID-19 and have shown promise as commercial detection devices. Significant challenges in the development of effective diagnostic methods are discussed and recommendations have been made for better diagnostic outcomes to manage the ongoing pandemic effectively., (© 2022 John Wiley & Sons Ltd.)

Purpose: The purpose of this study is to investigate the effect of the deformity angular ratio (DAR) on intra-operative neuromonitoring (IONM) signal changes during posterior spinal fusion (PSF) without vertebral column resection (VCR)., Methods: Retrospective review of severe pediatric spinal deformity patients treated with PSF without VCR or three-column osteotomy from 2008 to 2018. Exclusion criteria were prior instrumentation, lack of IONM, and incomplete radiographic data. Coronal DAR (C-DAR), sagittal DAR (S-DAR), and total DAR (T-DAR) were calculated and compared between patients with IONM signal loss and those without., Results: Two hundred and fifty-three patients met inclusion criteria. Forty-seven of two hundred and fifty-three (19%) patients had IONM signal loss. Intra-operative wake-up test was performed in seven cases; three of seven (43%) had a neurological deficit on wake-up test. All neurological deficits resolved at a mean of 41 days postop. IONM loss was associated with increased kyphosis (p = 0.003) and was not associated with Cobb angle (p = 0.16). S-DAR (p = 0.03) and T-DAR (p = 0.005) were associated with IONM signal loss but C-DAR was not (p = 0.06). Increased incidence of IONM signal loss was seen with S-DAR > 7 (p = 0.02) or T-DAR > 27 (p = 0.02). Twenty-four of ninety-two (26%) patients with S-DAR > 7 had IONM signal loss compared to twenty-three of one hundred and sixty-one (14%) with S-DAR ≤ 7 (OR, 2.1; 95% CI, 1.1-4.0). Seven of sixteen (44%) patients with T-DAR > 27 had signal loss compared to forty of two hundred and thirty-seven (17%) patients with T-DAR ≤ 27 (OR, 3.8; 95% CI, 1.3-10.9)., Conclusion: Patients with S-DAR > 7 or T-DAR > 27 have a higher risk of IONM loss during pediatric PSF even in the absence of a VCR or three-column osteotomies., (© 2023. The Author(s).)

Reliable cell-based platforms to test and/or produce biologics in a sustainable manner are important for the biotech industry. Utilizing enhanced λ integrase, a sequence-specific DNA recombinase, we developed a novel transgenesis platform involving a fully characterized single genomic locus as an artificial landing pad for transgene insertion in human Expi293F cells. Importantly, transgene instability and variation in expression were not observed in the absence of selection pressure, thus enabling reliable long-term biotherapeutics testing or production. The artificial landing pad for λ integrase can be targeted with multi-transgene constructs and offers future modularity involving additional genome manipulation tools to generate sequential or nearly seamless insertions. We demonstrated broad utility with expression constructs for anti PD-1 monoclonal antibodies and showed that the orientation of heavy and light chain transcription units profoundly affected antibody expression levels. In addition, we demonstrated encapsulation of our PD-1 platform cells into bio-compatible mini-bioreactors and the continued secretion of antibodies, thus providing a basis for future cell-based applications for more effective and affordable therapies., Competing Interests: Authors SN, JD, and WG were employed by Austrianova Singapore Pte. Ltd.; Authors HM and PD are the co-founders and shareholders of LambdaGen Pte. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Siddiqui, Peter, Ngoh, Wang, Ng, Dangerfield, Gunzburg, Dröge and Makhija.)

Plasmodium falciparum Alba domain-containing protein Alba3 (PfAlba3) is ubiquitously expressed in intra-erythrocytic stages of Plasmodium falciparum, but the function of this protein is not yet established. Here, we report an apurinic/apyrimidinic site-driven intrinsic nuclease activity of PfAlba3 assisted by divalent metal ions. Surface plasmon resonance and atomic force microscopy confirm sequence non-specific DNA binding by PfAlba3. Upon binding, PfAlba3 cleaves double-stranded DNA (dsDNA) hydrolytically. Mutational studies coupled with mass spectrometric analysis indicate that K23 is the essential residue in modulating the binding to DNA through acetylation-deacetylation. We further demonstrate that PfSir2a interacts and deacetylates K23-acetylated PfAlba3 in favoring DNA binding. Hence, K23 serves as a putative molecular switch regulating the nuclease activity of PfAlba3. Thus, the nuclease activity of PfAlba3, along with its apurinic/apyrimidinic (AP) endonuclease feature identified in this study, indicates a role of PfAlba3 in DNA-damage response that may have a far-reaching consequence in Plasmodium pathogenicity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Pediatric hip disorders represent a broad range of pathology and remain a significant source of morbidity for children and young adults. Surgical intervention is often required for joint preservation, but when salvage is not possible, joint replacement may be indicated to eliminate pain and preserve function. Although there have been significant updates in the management of both pediatric hip disease and the field of total hip arthroplasty (THA), there is a paucity of literature reflecting advancements in the area of pediatric and young adult (PYA) arthroplasty. No study has investigated the impact of approach on outcomes after PYA THA. The purpose of this study is to describe the indications, techniques, and early outcomes of THA in the PYA population in a modern practice setting., Methods: We performed a retrospective descriptive analysis of all patients undergoing primary THA performed at a tertiary care children's hospital from 2004 to 2019. Ninety-three hips in 76 patients were evaluated. Demographics, intraoperative variables, postoperative pain and function ratings, and complication and revision rates were collected., Results: Eighty-five hips in 69 patients were included. Patients were aged 12 to 23 years old, with males and females represented equally (33 vs. 36, respectively). The most common cause of hip pain was avascular necrosis (AVN, 56/85, 66%), most commonly due to slipped capital femoral epiphysis (13/56, 23%) idiopathic AVN (12/56, 21%), and chemotherapy (12/56, 21%). Half of all hips had been previously operated before THA (43/85). Thirty-six procedures were performed via the posterolateral approach (36/85, 42%), 33 were performed via direct anterior approach (33/85, 39%), and 16 were performed via the lateral approach (LAT, 16/85, 19%). At final follow-up, 98% (83/85) of patients had complete resolution of pain, 82% (70/85) had no notable limp, and 95% (81/85) had returned to all activities. There were 6 complications and 1 early revision. Average Hip disability and Osteoarthritis Outcomes Score for Joint Replacement scores increased by 37 points from 56 to 93. The overall revision-free survival rate for PYA THA was 98.8% (at average 19-mo follow-up)., Conclusions: Modern PYA THA is dissimilar in indications and surgical techniques to historic cohorts, and conclusions from prior studies should not be generalized to modern practice. In our practice, PYA patients most commonly carry a diagnosis of AVN, and THA can be performed with modern cementless fixation with large cup and head sizes and ceramic-on-cross-linked polyethylene bearings utilizing any approach. Further study is required to better characterize middle-term and long-term results and patient-reported outcomes., Level of Evidence: Therapeutic Level IV-retrospective case series., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The last decade's developments in sensor technologies and artificial intelligence applications have received extensive attention for daily life activity recognition. Autism spectrum disorder (ASD) in children is a neurological development disorder that causes significant impairments in social interaction, communication, and sensory action deficiency. Children with ASD have deficits in memory, emotion, cognition, and social skills. ASD affects children's communication skills and speaking abilities. ASD children have restricted interests and repetitive behavior. They can communicate in sign language but have difficulties communicating with others as not everyone knows sign language. This paper proposes a body-worn multi-sensor-based Internet of Things (IoT) platform using machine learning to recognize the complex sign language of speech-impaired children. Optimal sensor location is essential in extracting the features, as variations in placement result in an interpretation of recognition accuracy. We acquire the time-series data of sensors, extract various time-domain and frequency-domain features, and evaluate different classifiers for recognizing ASD children's gestures. We compare in terms of accuracy the decision tree (DT), random forest, artificial neural network (ANN), and k-nearest neighbour (KNN) classifiers to recognize ASD children's gestures, and the results showed more than 96% recognition accuracy.

An intelligent transportation system (ITS) aims to improve traffic efficiency by integrating innovative sensing, control, and communications technologies. The industrial Internet of things (IIoT) and Industrial Revolution 4.0 recently merged to design the industrial Internet of things-intelligent transportation system (IIoT-ITS). IIoT sensing technologies play a significant role in acquiring raw data. The application continuously performs the complex task of managing traffic flows effectively based on several parameters, including the number of vehicles in the system, their location, and time. Traffic density estimation (TDE) is another important derived parameter desirable to keep track of the dynamic state of traffic volume. The expanding number of vehicles based on wireless connectivity provides new potential to predict traffic density more accurately and in real time as previously used methodologies. We explore the topic of assessing traffic density by using only a few simple metrics, such as the number of surrounding vehicles and disseminating beacons to roadside units and vice versa. This research paper investigates TDE techniques and presents a novel Markov model-based TDE technique for ITS. Finally, an OMNET++-based approach with an implementation of a significant modification of a traffic model combined with mathematical modeling of the Markov model is presented. It is intended for the study of real-world traffic traces, the identification of model parameters, and the development of simulated traffic.

Fatty liver disease is characterized as nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). Fatty liver disease is one of the most common causes of chronic liver disease worldwide among adults and children. It is characterized by excessive fat accumulation in the liver cells. It has a genetically heterogenous background with complex pathogenesis and progressions and is accompanied by significant morbidity, mortality, and healthcare costs. NAFLD's risk factors include metabolic syndrome, abdominal obesity, type 2 diabetes, and atherogenic dyslipidemia. ALD is associated with the excessive consumption of alcohol. Here, we describe the functions of various proteins encoded by gene variants contributing to the pathogenesis of nonalcoholic fatty liver disease and alcoholic fatty liver disease. Advancements in genome engineering technology have generated various in vivo and in vitro fatty liver disease models reflecting the genetic abnormalities contributing toward fatty liver disease. We will discuss currently developed different ALD and NAFLD models using the clustered regularly interspaced short palindromic repeats (CRISPR/Cas9) genome editing tool.Furthermore, we will also discuss the salient features of CRISPR/Cas9 editing technology and Cas9 variants such as prime and base editors to replicate genetic topographies linked specifically to ALD and NAFLD. The advantages and limitations of currently available genome delivery methods necessary for optimal gene editing will also be discussed in this review. This review will provide the essential guidance for appropriate genome editing tool selection and proper gene delivery approaches for the effective development of ALD and NAFLD models, leading to the development of clinical therapeutics for fatty liver disease., (© 2023. The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.)

The purpose of this meta-analysis was to strengthen the credibility of primary research results by combining open-source scientific material, namely a comparison of craniofacial features (Cfc) between Crouzon's syndrome (CS) patients and non-CS populations. All articles published up to October 7, 2021, were included in the search of PubMed, Google Scholar, Scopus, Medline, and Web of Science. The PRISMA guidelines were followed to conduct this study. PECO framework was applied in the following ways: Those who have CS are denoted by the letter P, those who have been diagnosed with CS via clinical or genetic means by the letter E, those who do not have CS by the letter C, and those who have a Cfc of CS by the letter O. Independent reviewers collected the data and ranked the publications based on their adherence to the Newcastle-Ottawa Quality Assessment Scale. A total of six case-control studies were reviewed for this meta-analysis. Due to the large variation in cephalometric measures, only those published in at least two previous studies were included. This analysis found that CS patients had a smaller skull and mandible volumes than those without CS.in terms of SNA° (MD = -2.33, p  = <0.001, I 2  = 83.6%) and ANB°(MD = -1.89, p  = <0.005, I 2  = 93.1%)), as well as ANS (MD = -1.87, p  = 0.001, I 2  = 96.5%)) and SN/PP (MD = -1.99, p  = 0.036, I 2  = 77.3%)). In comparison to the general population, people with CS tend to have shorter and flatter cranial bases, smaller orbital volumes, and cleft palates. They differ from the general population in having a shorter skull base and more V-shaped maxillary arches.

Background: Modern medical education has flourished with an emergent interest in a variety of assessment approaches that entails direct observation of performance and provision of feedback. Workplace-based assessment (WPBA) has been embraced into specialty training in the United Kingdom (UK) within National Health Service (NHS). In Pakistan, this educational framework is incorporated to gauge the clinical proficiency of trainees at the postgraduate and undergraduate levels. The present study was done to identify how WPBA is perceived by dental field postgraduate trainees in Pakistan., Objective: The study explored and ascertained trainees' perceptions, attitudes, and preferences considering their experiences with the systematic organization and execution of WPBA in dental educational settings., Methods: This cross-sectional study design involved the clinical trainees of various cadres in a tertiary care hospital in Multan. A structured and validated questionnaire previously used for another analysis was administered among 90 trainees at the institute. The results were analyzed and tabulated using SPSS-21. Influential statistics (Pearson's Chi-Square Test) was performed and the confidence interval was set at 95% (P≤0.05)., Results: The response rate was 88%. Opinions were more positive compared to the former surveys. The majority of the respondents (65.8%) have shown a positive attitude towards WPBA and preferred it to be a valuable assessment system as it fosters reflective practices in educational settings. In addition, it was shown that WPBA has the potential to improve clinical training (72.2%) and aid in the effective implementation of clinical practice (68.4%). As the system of digital education has been introduced ever since the pandemic, the highest percentage of participants (56%) preferred a combination of on-paper and online assessment systems., Conclusion: The study reported that WPBA proposes the opportunity to associate teaching, learning, and assessment. The faculty training program is a significant input to upholding the quality of WPBA. Empirical research on WPBA is essential to be carried out to overcome the inadequacies thus endorsing its application universally.

Laser feedback-based self-mixing interferometry (SMI) is a promising technique for displacement sensing. However, commercial deployment of such sensors is being held back due to reduced performance in case of variable optical feedback which invariably happens due to optical speckle encountered when sensing the motion of non-cooperative remote target surfaces. In this work, deep neural networks have been trained under variable optical feedback conditions so that interferometric fringe detection and corresponding displacement measurement can be achieved. We have also proposed a method for automatic labelling of SMI fringes under variable optical feedback to facilitate the generation of a large training dataset. Specifically, we have trained two deep neural network models, namely Yolov5 and EfficientDet, and analysed the performance of these networks on various experimental SMI signals acquired by using different laser-diode-based sensors operating under different noise and speckle conditions. The performance has been quantified in terms of fringe detection accuracy, signal to noise ratio, depth of modulation, and execution time parameters. The impact of network architecture on real-time sensing is also discussed.

Patients’ decisions regarding orthodontic treatment are influenced by a variety of factors, such as their subjective opinions of how their oral cavity looks, age, gender, educational level, and income. The present study aimed to measure the orthodontic treatments needs for the Saudi Arabian population, and also to report potential barriers towards it. It is an observational study with cross sectional design. Data was collected from nationals and residents living in Saudi Arabia and who are at least 18 years old. A total of 1184 adult patients (880 females and 304 males) were included in this study. The population for the study was reached and chosen using a non-probability snowball sampling method. A validated and reliable questionnaire was distributed to the participants electronically through google form. Inferential statistics was applied using Pearson Chi Square test. p value < 0.05 was considered significant. The majority of the sample (73.2%) exhibited a favorable attitude toward orthodontic treatment. Most participants including male and female gender wanted orthodontic treatment primarily to have their protruding teeth fixed. The proportion of persons who cited chewing difficulty as the reason they needed orthodontic treatment was strongly influenced by the monthly income variable (p = 0.005). Cost and time of orthodontic therapy were the biggest obstacles to undergoing treatment, accounting for 34.5% and 19.5%, respectively. There was highly significant difference between the underlying medical conditions and the age and monthly income variables (p = 0.000). Based on the findings of the present study, it can be concluded that protruding teeth are the most important treatment needs perceived by the Saudi population, followed by spacing in between teeth, crowding of teeth, and unaesthetic smile. Cost of the orthodontic treatment was identified as the most significant barrier to the treatment needs, followed by long duration of orthodontic treatment, and pain.

With an astounding five million fatal cases every year, lung cancer is among the leading causes of mortality worldwide for both men and women. The diagnosis of lung illnesses can benefit from the information a computed tomography (CT) scan can offer. The major goals of this study are to diagnose lung cancer and its seriousness and to identify malignant lung nodules from the provided input lung picture. This paper applies unique deep learning techniques to identify the exact location of the malignant lung nodules. Using a DenseNet model, mixed ground glass is analyzed in low-dose, low-resolution CT scan images of nodules (mGGNs) with a slice thickness of 5 mm in this study. This was done to categorize and identify many histological subtypes of lung cancer. Low-resolution CT scans are used to pathologically classify invasive adenocarcinoma (IAC) and minimally invasive adenocarcinoma (MIA). 105 low-resolution CT images with 5 mm thick slices from 105 patients at Lishui Central Hospital were selected. To detect and distinguish, IAC and MIA, extend and enhance deep learning two- and three-dimensional DenseNet models are used. The two-dimensional DenseNet model was shown to perform much better than the three-dimensional DenseNet model in terms of classification accuracy (76.67%), sensitivity (63.3%), specificity (100%), and area under the receiver operating characteristic curve (0.88). Finding the histological subtypes of persons with lung cancer should aid doctors in making a more precise diagnosis, even if the image quality is not outstanding., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Shanmugasundaram Marappan et al.)

Telerehabilitation offers an alternative healthcare delivery remotely in a patient's environment at a lower cost, better accessibility, and equivalent quality to the standard approach. Several studies had examined the effectiveness of telerehabilitation inpatients with musculoskeletal disorders, and although there is evidence that it is at least equally effective as the standard care, the patient and rehabilitation professional satisfaction with the delivery method is not conclusive. A systematic review was conducted to study the patients' and rehabilitation professionals' satisfaction with telerehabilitation for musculoskeletal disorders. A search for relevant studies on 29 April 2021 was carried out in Medline/PubMed, Scopus, and Web of Science (WOS). The search terms included "telerehabilitation," AND "satisfaction" AND "musculoskeletal disorders," "telehealth," "telemedicine," "patient experience," and "pain". Fifteen eligible studies with 12,341 patients were included in this systematic review. A report was included if it (a) assessed the satisfaction of patients or professionals or both as one of the outcomes of a telerehabilitation intervention, (b) included adults 18 years and above with musculoskeletal disorders, and (c) is an intervention study using a quantitative approach. The quality of studies was assessed using the critical appraisal checklist tool developed by Joanna Briggs Institute (JBI). Most of the studies reported that patients were satisfied with both telerehabilitation and face-to-face intervention. However, few studies reported that patients were more satisfied with telerehabilitation compared to face-to-face of intervention. Patients in one study had preferred the incorporation of telerehabilitation and face-to-face sessions. Two of three studies had reported overall satisfaction with telerehabilitation by the professionals. Overall, there is evidence that patients and rehabilitation professional are satisfied with telerehabilitation compared to face-to-face consultation., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Junaid Amin et al.)

Introduction: Metabolic-associated fatty liver disease (MAFLD) is a hepatic manifestation of metabolic syndrome (MS). MAFLD patients have a higher prevalence of COVID-19. MAFLD also is associated with worse clinical outcomes of COVID-19, such as disease severity, intensive care unit (ICU) admission rate, and higher mortality rates. However, this evidence has not been well characterized in the literature. This meta-analysis aimed to determine the clinical outcomes of COVID-19 among MAFLD patients compared to the non-MAFLD group., Methods: A comprehensive search was conducted in the Cumulative Index of Nursing and Allied Health (CINAHL), PubMed/Medline, and Embase for studies reporting MAFLD prevalence among COVID-19 patients and comparing clinical outcomes such as severity, ICU admission, and mortality among patients with and without MAFLD. The pooled prevalence of MAFLD among COVID-19 patients and the pooled odds ratios (OR) with 95% confidence intervals (CI) for clinical outcomes of COVID-19 were calculated., Results: Sixteen observational studies met inclusion criteria involving a total of 11,484 overall study participants, including 1,746 MAFLD patients. The prevalence of COVID-19 among MAFLD patients was 0.29 (95% CI: 0.19-0.40). MAFLD was associated with the COVID-19 disease severity OR 3.07 (95% CI: 2.30-4.09). Similarly, MAFLD was associated with an increased risk of ICU admission compared to the non-MAFLD group OR 1.46 (95% CI: 1.12-1.91). Lastly, the association between MAFLD and COVID-19 mortality was not statistically significant OR 1.45 (95% CI: 0.74-2.84)., Conclusions: In this study, a high percentage of COVID-19 patients had MAFLD. Moreover, MAFLD patients had an increased risk of COVID-19 disease severity and ICU admission rate., (© 2022 The University of Kansas Medical Center.)

Background: To analyse the functional outcome of primary cemented bipolar hemi arthroplasty (PCBH) for unstable osteoporotic intertrochanteric femur fractures in elderly patients., Methods: : It was a multicentre prospective study conducted at Institute of Orthopaedics & Surgery, Medicare Cardiac & General Hospital and Dr Ruth K M Pfau Civil Hospital Karachi, Pakistan from February 2015 to July 2020. Thirty-eight patients of 60-90 years of either gender diagnosed as close UIF, severe osteoporosis as per Singh index grade ≤3, time since injury <2 weeks, ASA status II & III and pre-injury independent walking were enrolled in this study. All patients with UIF underwent PCBH. The radiographs were performed before surgery and at intervals postoperatively. All patients were requested to come for follow up visits at 2 weeks, 4 weeks, 3 months, 6 months 1 year and then at 3 years to assess the functional outcome of patients. At first postoperative day check X-rays taken and rehabilitation started as per institutional rehabilitation protocol, at 2-week stiches removed, at 4 weeks' x-ray was done and all the patients were followed for 3 years. The primary outcomes were noted using Harris Hip Score (HHS) for the functional outcome assessed at the end of 1 year and at final follow up., Results: The mean age of the study participants was 68.29±8.04 years. One male (2.6%) died at 6th month, then 2 females (5.2%) patients died at 1 year and 2 females (5.2%) patients died at the end of 3 years due to multiple comorbid conditions. During 1st year 3 patients (7.4%) developed DVT and 4 patients (10.5%) having diabetes and hypertension developed superficial wound infection. The mean Harris Hip Score between time points which indicated that the mean Harris Hip Score significantly improve over the period of time (p=0.001). Post hoc tests revealed that there were statistically significant differences between each time points (p<0.05). The functional outcome at 3 years, shown, one patient had excellent outcome, 24 patients had good outcome and 8 had fair outcome, respectively., Conclusion: The Primary Cemented Bipolar Hemiarthoplasty is a good choice of treatment in terms of reasonable functional outcome such as early mobilization and associated with less post-operative complications in elderly patients of UIF.

Background: The proximal femur is a common location for pathologic fractures in children, yet there is little published information regarding this injury. The purpose of this study was to investigate the outcomes of pediatric pathologic proximal femur fractures due to benign bone tumors., Methods: A retrospective review of patients treated for pathologic proximal femur fractures from 2004 to 2018 was conducted. Inclusion criteria were age below 18 years and pathologic proximal femur fracture secondary to a benign bone tumor. Patients were excluded if they had <1 year of follow-up. Medical charts and serial radiographs were reviewed for fracture classification, underlying pathology, treatment, complications, and time to fracture healing., Results: A total of 14 patients were included. Mean age was 6±3 (3 to 11) years, and mean follow-up was 44±21 (22 to 86) months. Index treatment was spica casting in 9/14 (68%) patients, while 5/14 (32%) were treated with internal fixation. Of the 9 patients initially treated with casting, 22% (2/9) required repeat spica casting at a mean of 0.6 months after index treatment, 67% (6/9) required internal fixation at a mean of 20.3 months after index treatment, and 11% (1/9) did not require revision treatment. Eighty-eight percent (8/9) of patients treated with casting required revision treatment compared with 40% (2/5) of those treated with internal fixation (P=0.05). Nonunion occurred after 1 refracture, malunion with coxa vara occurred in 2 fractures, and the remaining 11/14 (84%) fractures had a union at a mean of 4.9±3.0 months All cases of malunion occurred in patients initially treated nonoperatively. There were 19 distinct complications in 10/14 (71%) patients. The incidence of any revision surgery was 64% (9/14)., Conclusions: In this series, pediatric pathologic proximal femur fractures demonstrated prolonged time to union, high incidence of revision surgery (64%), and substantial complication rate (71%). In children with pathologic proximal femur fractures, treatment with internal fixation is recommended as this series showed a 78% failure rate of initial conservative management., Level of Evidence: Level IV., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: This study will aid in determining the prevalence and risk factors for dental trauma. This will assist in developing a treatment budget plan, thereby, fend off complications., Materials and Methods: This study was an observational study, having a cross-sectional design, in which information was obtained from 555 participants. Data were obtained using a non-probability convenient sampling technique. A validated questionnaire was used as a study tool. Data were analyzed using the statistical package for the social sciences (SPSS, version 20). Descriptive and inferential statistics were used. Data were displayed as numbers and percentages, and the Chi-squared test was used to measure the association., Results: Dental trauma was found to be 44% prevalent. Most of the injuries occurred in the 6-9-years age-group (19.1%) and were more common in boys (54.13%) than in girls. The majority of respondents (61%) identified "falls" as the most common cause of dental trauma, and the frequent location for the occurrence of dental injuries was found to be "home" (64.44%). Only 18% of parents reported that their kid's experienced nail-biting concerns, with the majority claimed that their kids never developed oral habits. Most dental injuries occurred during the summer season (48%)., Conclusion: Young aged group and male gender group were more prone to dental injuries; dental injuries along with fall were found as the most common cause of dental trauma, whereas most of the dental traumas were reported to have occurred at home., Clinical Significance: The study evaluated risk factors and the prevalence of dental trauma in the population of Ha'il, Saudi Arabia. It will be an effective tool for determining the need for treatment facilities.

Introduction: Due to the COVID-19 pandemic, many countries imposed lockdowns on their citizens in an attempt to contain the disease. Pakistan is one of these countries. A government mandated lockdown can have mitigating psychological effects on young adults, out of which a large fraction is made up of students. This study aims to investigate the correlations between changes in sleep pattern, perception of time, and digital media usage. Furthermore, it explores the impact of these changes on the mental health of students of different educational levels., Methods: This cross-sectional study was conducted via a web-based questionnaire, from March 24 to April 26, 2020. The survey was targeted at students and 251 responses were obtained. It was a 5-section long questionnaire. The first section inquired about demographics of participants. Each of the other 4 sections was devoted to changes in sleep pattern, perception of time flow, digital media usage and mental health status of students. Close-ended questions with multiple choice responses, dichotomous, interval and 4-point Likert scales were used in the construction of the survey questionnaire. Chi 2 T-tests multinomial and binary logistic regression were used as primary statistical tests. All data were analysed using Statistical Package for Social Science (SPSS) version 23.0 (IBM Corp., Armonk, NY)., Results: Out of 251 adolescents that participated in our study, the majority (70.2%) were females. The mean age of the participants was 19.40 ± 1.62 years. Two-thirds of the respondents did not have much trouble falling asleep (66.5%). The analysis found no significant association between longer sleep periods and procrastination level ( P  = 0.054). Nearly three-fourths (72.9%) of our participants felt that getting through quarantine would have been more difficult if they did not have any electronic gadgets. Of these, a majority (85.8%) had a general feeling of tiredness and lacked motivation ( P  = 0.023). Additionally, a large number of students (69.7%) had reported that time is seemingly moving faster. A significant relationship between increased usage of electronic items and longer sleep periods was also noted ( P  = 0.005). With respect to the level of education, statistically significant values were noted for alarm use both before and after quarantine began ( P  = 0.021 and P  = 0.004, respectively). Further analysis showed that there was a significant difference in the median difference of time spent on social media before the outbreak (3.0 ± 32.46) and time spent on social media after the outbreak (6.0 ± 3.52) in a single day ( P  = 0.000)., Conclusions: Our research has revealed that due to the lockdown imposed by the government in response to COVID-19, the sleeping patterns of the students was affected the most. Our findings show that the increase in use of social media applications led to a widespread increase in the length of sleep, worsening of sleep habits (people sleeping at much later hours than usual), and a general feeling of tiredness. A general lack of recollection regarding what day of the week it was, as well as a change in the perceived flow of time were also notable. All these findings indicate the decline in mental health of students due to the lockdown. Promoting better sleep routines, minimising the use of digital media, and encouragement of students to take up more hobbies could collectively improve the health and mood of students in self-quarantine., (© 2021 Elsevier Masson SAS. All rights reserved.)