Characterization of the Tissue and Strain-Specific Microbiota of Anopheles funestus Giles (Diptera: Culicidae).

The mosquito microbiota is a critical determinant of mosquito life history. It is therefore a target for novel vector control strategies like paratransgenesis. However, the microbiota in Anopheles funestus, a major African malaria vector, is poorly characterized. Thus, the study aimed to investigate the overall bacterial landscape in the salivary glands, ovaries and midguts of three laboratory strains of An. funestus differing in insecticide-resistant phenotype by sequencing the V3-V4 hypervariable region of bacterial 16S rRNA genes. When examining alpha diversity, the salivary glands harbored significantly more bacteria in terms of species richness and evenness compared to ovaries and midguts. On the strain level, the insecticide-susceptible FANG strain had significantly lower bacterial diversity than the insecticide-resistant FUMOZ and FUMOZ-R strains. When looking at beta diversity, the compositions of microbiota between the three tissues as well as between the strains were statistically different. While there were common bacteria across all three tissues and strains of interest, each tissue and strain did exhibit differentially abundant bacterial genera. However, overall, the top five most abundant genera across all tissues and strains were Elizabethkingia, Acinetobacter, Aeromonas, Cedecea and Yersinia. The presence of shared microbiota suggests a core microbiota that could be exploited for paratransgenesis efforts.

Use of Vital Pulp Therapies in Primary Teeth 2024.

Purpose: The purpose of this study was to present an evidence-based guideline for primary teeth with deep caries or trauma requiring vital pulp therapies (VPT). Methods: A systematic review/meta-analysis on vital primary teeth resulting from trauma or caries was conducted using GRADE to assess the certainty of evidence for clinical recommendations. A decision tree was provided for choosing VPTs. Results: No articles on trauma VPT were found. For VPT in primary teeth with deep caries, indirect pulp treatment (IPT) or pulpotomy using the calcium silicate cement (mineral trioxide aggregate [MTA] or Biodentine®) show increased success over using direct pulp capping (DPC) and other pulpotomies. Different liners do not affect IPT success (high certainty) or DPC capping agents' success (very low certainty) after 24 months. It is strongly recommended, with high certainty from 24-month data, that calcium silicate cement pulpotomy is preferred over formocresol, ferric sulfate, zinc oxide eugenol pulpotomy, and other pulpotomies. Using selective caries removal and IPT for deep caries is strongly recommended with moderate certainty over complete and stepwise removal. Statistically, this results in significantly fewer pulp exposures. No caries removal and Hall technique crown may be used when indicated (moderate certainty at 24 months). For vital primary incisors with deep caries, pulpotomy was significantly better statistically than pulpectomy. Teeth diagnosed with/without reversible pulpitis pain showed comparable success after 12 months of treatment by IPT or calcium silicate cement pulpotomy. The following had little or no significant effect on MTA pulpotomy success: coronal pulp removal methods; irrigation solution; method to control hemorrhage; base over MTA; treatment in one or two visits; anterior or posterior teeth. Conclusions: Indirect pulp treatment or calcium silicate cement pulpotomy is likely to increase vital pulp therapy success over other VPTs such as direct pulp capping and other pulpotomies after 24 months (moderate certainty).

Risk indicators for gingival recession in the esthetic zone: A cross-sectional clinical, tomographic, and ultrasonographic study.

BACKGROUND: To evaluate the risk indicators associated with midfacial gingival recessions (GR) in the natural dentition esthetic regions. METHODS: Cone-beam computed tomography (CBCT) results of thirty-seven subjects presenting with 268 eligible teeth were included in the cross-sectional study. Clinical measurements included presence/absence of midfacial GR; the depth of the midfacial, mesial, and distal gingival recession; the recession type (RT); keratinized tissue width (KT); and attached gingiva width (AG). Questionnaires were utilized to capture patient-reported esthetics and dental hypersensitivity for each study tooth. Buccal bone dehiscence (cBBD) and buccal bone thickness (cBBT) were measured on the CBCT scans. High-frequency ultrasonography was performed to assess gingival thickness (GT) and buccal bone dehiscence (uBBD). Intraoral optical scanning was obtained to quantify the buccolingual position of each study site (3D profile analysis). Multilevel logistic regression analyses with generalized estimation equations were performed to assess the factors associated with the conditions of interest. RESULTS: The presence of midfacial GR was significantly associated with the history of periodontal treatment for pocket reduction (OR 7.99, p = 0.006), KT (OR 0.62, p < 0.001), cBBD (OR 2.30, p = 0.015), GT 1.5 mm from the gingival margin (OR 0.18, p = 0.04) and 3D profile 1 mm from the gingival margin (OR 1.04, p = 0.001). The depth of midfacial GR was significantly correlated to previous history of periodontal treatment (OR 0.96, p = 0.001), KT (OR -0.18, p < 0.001), presence of bone fenestration (OR 0.24, p = 0.044), and cBBD (OR 0.43, p < 0.001). The depth of midfacial GR was also the only factor associated with patient-reported esthetics (OR -3.38, p = 0.022), while KT (OR 0.77, p = 0.018) and AG (OR 0.82, p = 0.047) were significantly correlated with patient-reported dental hypersensitivity. CONCLUSIONS: Several risk indicators of midfacial and interproximal GR in the esthetic region were identified. The use of imaging technologies allowed for detection of parameters associated with the conditions of interest, and, therefore, their incorporation in future clinical studies is advocated. Ultrasonography could be preferred over CBCT for a noninvasive assessment of periodontal phenotype.

Microscopic in-situ analysis of the mucosal healing around implants treated by protease activated receptor 4-agonist peptide or perpendicularly protruded type I collagen in rats.

Enhanced mucosal sealing around titanium implants can reduce complications such as peri-implantitis. The present study aims to investigate the mucosal healing at the early stage around the protease activated receptor 4-agonist peptide (PAR4-AP)- or perpendicularly protruded type I collagen (pCol)-treated titanium implants. A total of 72 implants were placed in 36 rats in the study. Following extractions, two tissue-level implants among the following three different surfaces, PAR4-AP-coated (PAR4 group, n = 24), pCol-treated (pCol group, n = 24) and non-treated (control group, n = 24) ones, were placed in the maxillae of each rat based on a split-mouth design. The specimens retrieved at 8 h (n = 8 per group), 3 days (n = 8 per group), and 2 weeks (n = 8 per group), were immunostained and tissue-cleared, and the signals of laminin-5 and collagen fibers were observed under multiphoton microscopy. Statistical analyses were performed using linear mixed model with post hoc tests to compare differences between the groups. While there was no intergroup difference at 8 h, the laminin-5 at 3 days was more abundant near the PAR4-group-surface, and its area was significantly larger in the PAR4 group (0.0204 ± 0.0194 mm2 ) than the control (0.0019 ± 0.0025 mm2 , p = .001) and pCol (0.0023 ± 0.0022 mm2 , p < .001) groups. The pCol group showed a significantly larger area of collagen fibers (0.0230 ± 0.0148 mm2 ) compared to the control (0.0035 ± 0.0051 mm2 , p = .002) and PAR4 (0.0031 ± 0.0057 mm2 , p < .001) groups at 3 days. At 3 days and 2 weeks, the collagen fiber orientation of the pCol group showed a more perpendicular manner compared to the control and PAR4 groups. The signal of basal lamina and collagen fibers were stronger around the PAR4-AP- and pCol-treated titanium surfaces, respectively during the early healing stage. This could have implications for improved mucosal sealing around dental implants, potentially reducing complications such as peri-implantitis.

Osseointegration Foundation Charity Overdenture Program Study: Part 2.

This assessment evaluated the clinical feasibility of using narrow-diameter implants to support a mandibular overdenture. Twelve patients presenting with an edentulous mandible were recruited from nine dental offices. Each patient received two to four implants in the mandible. The implants were placed without additional bone augmentation, and a total of 36 implants were placed. All sites achieved satisfactory crestal bone stability and soft tissue maintenance 1 year after the final prosthetic restoration. This investigation was supported by the Osseointegration Foundation, working in conjunction with the Zest Anchors implant company. There are three basic valuable activities that emerge from a professional foundation, which were reflected in this case study. They include disseminating information to practitioners, persuading young clinicians to become research investigators, and reaching out to patients in need of treatment who cannot afford it without a charitable opportunity.

Primary Tooth Vital Pulp Treatment Interventions: Systematic Review and Meta-Analyses.

Purpose: to update the 2016 systematic review evidence for vital pulp therapy (VPT) for primary teeth affected by caries or trauma. Methods: The population, intervention, comparison, outcomes, and study (PICOS) design inclusion/exclusion was used for multiple databases. Risk of bias, meta-analyses using RevMan, and certainty of evidence was created. Results: A total of 299 studies were included; no trauma was found. Indirect pulp treatment (IPT) resulted in 97 percent success. Two calcium silicate cement (CSC) pulpotomies' success using mineral trioxide aggregate (MTA) and Biodentine® were 94 percent and 90 percent, respectively, greater than for direct pulp capping (DPC; 86 percent) and other pulpotomies (moderate certainty). The success of IPT versus pulpotomy at 24 months showed no significant difference (P=0.31). Different liners or capping agents did not affect the success of IPT (P=0.79) or DPC at 24 months (P=0.24). The two CSC pulpotomies were not significantly different based on 24-month success (P=0.34). The formocresol pulpotomy success at 24 months was significantly lower than for MTA (P=0.02). Ferric sulfate had a significant lower success at 24 months than MTA pulpotomy (69 percent versus 92 percent; P=0.03). Zinc oxide eugenol, as a singular pulpotomy, had low success (65 percent). Selective/stepwise caries removal did significantly better at avoiding pulp exposures than complete excavation (P<0.001). Complete, selective, and no caries removal (Hall technique [HT], steel crown placement with no caries removal) had no significant difference in pulp vitality success for deep caries at 24 months (P=0.29). For deep caries affecting vital incisors, pulpotomy had significantly greater success than pulpectomy (P=0.002). The following had no significant effect on MTA pulpotomy success: coronal pulp removal methods; irrigation solution; method to control hemorrhage; base over MTA; treatment in one or two visits; and anterior or posterior teeth. Conclusions: Vital pulp therapy success of indirect pulp treatment or two calcium silicate cement pulpotomies demonstrated improved success over direct pulp capping and other pulpotomies based on 24-month evidence with moderate certainty. The Hall technique did not significantly reduce pulp vitality success versus caries removal.

Interferon-stimulated gene 15 polymorphisms are associated with spontaneous preterm birth in Taiwanese women.

PROBLEM: Immune and inflammatory responses are known to be major causes of preterm birth (PTB). The maternal genetic background plays an important role in the development of PTB. Interferon-stimulated gene 15 (ISG15) is an interferon-induced protein which can modulate immune cell activation and function. We aim to study if polymorphisms in the ISG15 gene are associated with spontaneous PTB (sPTB) risk in Taiwanese women. METHOD OF STUDY: ISG15 rs4615788 C/G, rs1921 G/A, and rs8997 A/G polymorphisms were genotyped in a hospital-based study of 112 women with sPTB and 1120 term controls. The plasma concentrations of ISG15 were determined by enzyme-linked immunosorbent assay. RESULTS: We found the ISG15 rs1921 G-rs8997 A haplotype was associated with decreased risk for PTB (χ2  = 6.26, p = .01, pc  = .04). The A/G genotype of ISG15 rs8997 polymorphism might have the potential to confer reduced risk of PTB women (χ2  = 4.09, p = .04, pc  = .08). Spontaneous PTB women displayed higher plasma ISG15 levels compared to term controls (p < .001). The plasma ISG15 levels among pregnant women with rs8997 A/G genotype were found significantly lower compared to G/G genotype (p = .03). CONCLUSIONS: Women with the ISG15 rs1921 G-rs8997 A haplotype may associate with spontaneous PTB. These findings provide new insights into the etiology of preterm birth.

Gas Plasma Treatment Improves Titanium Dental Implant Osseointegration-A Preclinical In Vivo Experimental Study.

Recent technological advancements led to the development of various plasma-based technologies for post-packaging modifications. The purpose of the present preclinical in vivo study was to assess the safety and efficacy of a novel chairside nonthermal gas plasma treatment for enhancing osseointegration of titanium implants. Six male mixed foxhounds underwent extraction of mandibular premolars and first molars, and the sockets healed for 42 days. Canine mandibles were randomized to receive either plasma-treated (test) or non-plasma-treated (control) dental implants. A total of 36 implants were placed in six animals, and they were sacrificed at 2 weeks (two animals), 4 weeks (two animals), and 6 weeks (two animals) after the implant surgery. When the radiographic analysis was performed, the changes in bone level were not statistically significant between the two groups at 2 weeks and 4 weeks. The difference became significant at 6 weeks (p = 0.016), indicating more bone loss from baseline to 6 weeks for the control group. The bone-to-implant contact (BIC) appeared to be higher for the test groups at all time points, and the BIC was significantly higher for the test group at 4 weeks (p = 0.046). In conclusion, this study underscored the potential of nonthermal plasma treatment in enhancing implant osseointegration.

Nonpharmacological Behavior Guidance for the Pediatric Dental Patient.

Purpose: To present evidence-based recommendations on nonpharmacological behavior guidance for the pediatric dental patient. Methods: The work group assessed eight systematic reviews for effectiveness of nonpharmacological behavior guidance techniques in children undergoing preventive care or a dental treatment visit. The key outcomes assessed included cooperative behavior, anxiety, and procedural pain. To formulate the recommendations, the work group used the GRADE framework to obtain consensus on domains such as priority of the problem, certainty of the evidence, balance between desirable and undesirable consequences, patients' values and preferences, acceptability, and feasibility. Results: Overall, the use of basic nonpharmacological behavior guidance techniques resulted in trivial-to-small effect on improvement in behavior or reduction in anxiety. However, for children and adolescents undergoing preventive care, mobile applications and modeling showed large effects in reduction of anxiety. For those undergoing dental treatment, strategies such as modeling, positive reinforcement, biofeedback relaxation, breathing relaxation, animal-assisted therapy, combined tell-show-do, audiovisual distraction, and cognitive behavior therapy showed large reduction in anxiety. For children and adolescents with special health care needs, audiovisual distraction and sensory-adapted dental environment showed large reduction of anxiety. Conclusions: All the formulated recommendations were conditional and were mostly based on very low certainty of evidence. Conditional recommendations imply that different choices or combinations of behavior guidance techniques may be most appropriate for different patients. Clinicians should use techniques consistent with the parent/patient values and preferences. These recommendations are based on the best available evidence to-date and are intended to aid clinical decision making.

Hydrogen-bond-acceptor ligands enable distal C(sp3)-H arylation of free alcohols.

The functionalization of C-H bonds in organic molecules is one of the most direct approaches for chemical synthesis. Recent advances in catalysis have allowed native chemical groups such as carboxylic acids, ketones and amines to control and direct C(sp3)-H activation1-4. However, alcohols, among the most common functionalities in organic chemistry5, have remained intractable because of their low affinity for late transition-metal catalysts6,7. Here we describe ligands that enable alcohol-directed arylation of δ-C(sp3)-H bonds. We use charge balance and a secondary-coordination-sphere hydrogen-bonding interaction-evidenced by structure-activity relationship studies, computational modelling and crystallographic data-to stabilize L-type hydroxyl coordination to palladium, thereby facilitating the assembly of the key C-H cleavage transition state. In contrast to previous studies in C-H activation, in which secondary interactions were used to control selectivity in the context of established reactivity8-13, this report demonstrates the feasibility of using secondary interactions to enable challenging, previously unknown reactivity by enhancing substrate-catalyst affinity.

A model for predicting physical function upon discharge of hospitalized older adults in Taiwan-a machine learning approach based on both electronic health records and comprehensive geriatric assessment.

Background: Predicting physical function upon discharge among hospitalized older adults is important. This study has aimed to develop a prediction model of physical function upon discharge through use of a machine learning algorithm using electronic health records (EHRs) and comprehensive geriatrics assessments (CGAs) among hospitalized older adults in Taiwan. Methods: Data was retrieved from the clinical database of a tertiary medical center in central Taiwan. Older adults admitted to the acute geriatric unit during the period from January 2012 to December 2018 were included for analysis, while those with missing data were excluded. From data of the EHRs and CGAs, a total of 52 clinical features were input for model building. We used 3 different machine learning algorithms, XGBoost, random forest and logistic regression. Results: In total, 1,755 older adults were included in final analysis, with a mean age of 80.68 years. For linear models on physical function upon discharge, the accuracy of prediction was 87% for XGBoost, 85% for random forest, and 32% for logistic regression. For classification models on physical function upon discharge, the accuracy for random forest, logistic regression and XGBoost were 94, 92 and 92%, respectively. The auROC reached 98% for XGBoost and random forest, while logistic regression had an auROC of 97%. The top 3 features of importance were activity of daily living (ADL) at baseline, ADL during admission, and mini nutritional status (MNA) during admission. Conclusion: The results showed that physical function upon discharge among hospitalized older adults can be predicted accurately during admission through use of a machine learning model with data taken from EHRs and CGAs.

The long-term success of periodontal regeneration: a 10-year follow-up case report.

OBJECTIVE: The predictability and long-term success of periodontal regeneration begins with oral hygiene education, disease management, and an individually tailored periodontal maintenance protocol. The treatment outcomes could be enhanced when biologics and bone grafts are combined. The aim of this report was to describe the outcome of two complex infrabony defects in the same patient treated with recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and freeze-dried bone allograft (FDBA) over 10 years. CASE PRESENTATION: Two complex infrabony defects were treated following guided tissue regeneration principles and procedures. Full-thickness flaps were raised to allow visualization of the defects. The areas were debrided, and exposed root surfaces were planed. FDBA and rhPDGF-BB were combined to fill both defects. A collagen membrane was used over the bone graft in one case. The flaps were reapproximated to achieve primary closure. The patient was seen for regular periodontal maintenance visits and clinical and radiographic follow-ups over 10 years. Throughout the examination periods, the probing depths improved without bleeding on probing, and there was radiographic evidence of bone regeneration. CONCLUSION: The growth factor-infused bone graft was successfully utilized for periodontal regeneration in complex bony defects.

The Guided Bone Regeneration of a Large, Non-Contained, Perforated Maxillary Anterior Perforation Defect: A Case Report.

The reconstruction of alveolar ridge defects can be challenging, especially when the lesion is large, non-contained, and located in the esthetic region. The present report describes the guided bone regeneration (GBR) procedure and prosthetic rehabilitation of a severe perforation defect in the anterior maxilla. Clinical and radiographic evaluation of the lesion indicated an endodontic-periodontal origin, and biopsy results confirmed the absence of malignancy. GBR was performed with the use of cortical mineralized freeze-dried bone allograft (FDBA) combined with recombinant human platelet derived growth factor BB (rhPDGF-BB) and a resorbable collagen membrane without the use of tenting or fixation screws. At six months post-GBR, cone beam computed tomography (CBCT) revealed adequate bone fill for the placement of 4.1 x 10 mm or 4.1 x 12 mm dental implants. The implant surgery was fully guided with a two-stage approach. After a ten-month of healing phase, the implants were loaded with a screw-retained porcelain bridge. The staged GBR approach using a combination of FDBA, rhPDGF-BB, and a resorbable membrane without the use of tenting or fixation screws resulted in significant bone fill, successful implant placement, and a functional and esthetic implant-supported prosthesis.

Survival and Its Correlates in Multiple Sclerosis Patients under a Universal Health Insurance Program in Taiwan: An 18-Year Nationwide Cohort Study.

Despite the global decline in the standardized mortality rate of multiple sclerosis (MS), recent research on MS patient survival, especially in Taiwan, remains limited. This study aimed to investigate survival, mortality causes, and associated factors among MS patients in Taiwan. The Taiwan National Health Insurance Research Database was used as the primary data source, and a Cox proportional hazard model was employed to estimate and analyze factors related to survival. We analyzed data from 1444 MS patients diagnosed between 2000 and 2018. Age at diagnosis was positively correlated with the risk of death. Among the 190 patients who died, the leading causes of disease-related deaths were nervous system diseases (n = 83, 43.68%), followed by respiratory system diseases and certain infectious and parasitic diseases. The 8-, 13-, and 18-year survival rates for MS patients were 0.97, 0.91, and 0.81, respectively. This study highlights that the MS patient's socioeconomic status, environmental factors, comorbidity severity, and related medical variables were not significantly associated with survival.

Nonpharmacological Behavior Guidance For Children During Dental Treatment Visits: A Systematic Review and Meta-Analysis-Part 2.

'Purpose: To assess the effectiveness of nonpharmacological behavior guidance interventions used for children undergoing dental treatment visits. METHODS: Databases: Ovid MEDLINE, PsycINFO (EBSCOhost), Embase, and Cochrane Library, were searched from 1946 to February 2022, for randomized clinical trials (RCTs) comparing effectiveness of basic and advanced nonpharmacological techniques rendered during a dental treatment visit including sealants, restorative care, dental local anesthesia, and simple surgical procedures. The primary outcome measures were reduction in anxiety, fear, pain, and improvement in cooperative behavior. Eight authors determined the included RCTs, performed data extraction, and assessed the risk of bias (ROB). Standardized Mean Difference calculation and assignment of quality of evidence by Grading of Recommenda- tions Assessment, Development and Evaluation approach were done. RESULTS: Forty articles qualified for analysis from 219 screened articles. Included studies evaluated the effectiveness of pre-visit preparation and in office strategies rendered pre-/post- or during treatment such as positive imagery, direct observation/modeling, desensitization, tell-show-do and its modifications, voice control, positive reinforcement, memory restructuring, bio- feedback and breathing relaxation, animal assisted therapy, combined therapies, and cognitive behavior therapy. The certainty of evidence ranged from Very low to high and the magnitude of effect varied from trivial to large change in the desired outcomes. CONCLUSIONS: Most of the basic non- pharmacological behavior guidance techniques showed trivial to small reduction in self-reported anxiety and/or improvement in behavior, with modeling, positive reinforcement, biofeedback relaxation, breathing relaxation, animal assisted therapy, combined tell-show-do and audiovisual distraction, and cognitive behavior therapy showing large effects in reduction of anxiety based on some scales.

Nonpharmacological Behavior Guidance for Children with Special Health Care Needs During Preventive and Treatment Dental Visits: A Systematic Review-Part 3.

PURPOSE: To assess the effectiveness of nonpharmacological behavior guidance interventions used for children and youth with special health care needs (CYSHCN) during preventive and dental treatment visits. METHODS: Databases: Ovid MEDLINE, PsycINFO (EBSCOhost), Embase, and Cochrane Library, were searched from 1946 to February 2022, for randomized clinical trials (RCTs) comparing effectiveness of basic and advanced nonpharmacological techniques rendered during a preventive visit (exam, fluoride application, radiographs, and prophylaxis) or a treat- ment visit (simple surgical treatment, sealants, restorative care with or with local anesthesia) with control or other interventions. The primary outcome measures for the studied interventions were reduction in anxiety, fear, pain, and improvement in cooperative behavior. Eight authors determined the included Randomized Controlled Trials (RCTs), performed data extraction, and assessed the risk of bias (ROB). Standardized Mean Difference calculation and assignment of quality of evidence by Grading of Recommendations Assessment, Development and Evaluation approach were done. RESULTS: Eleven articles qualified for analysis from 219 screened articles. Included studies evaluate the effectiveness of in office strategies such as modeling, audio-visual distraction, sensory adapted dental environment, and picture exchange communication system. The certainty of evidence ranged from Very low to Low and the magnitude of effect varied from trivial to large change in the desired outcomes. CONCLUSIONS: Most basic non-pharmacological behavior guidance techniques showed some trivial to small reduction in self-reported anxiety and/ or improvement in behavior, with audiovisual distraction, Sensory Adapted Dental Environment, and Picture Exchange Communication System showing large reduction in anxiety based on some rating scales. Systematic Review Registration Number: PROSPERO: CRD42022314723.

Nonpharmacological Behavior Guidance for Children During Preventive Dental Visits: A Systematic Review-Part 1.

PURPOSE: To assess the effectiveness of nonpharmacological behavior guidance interventions used for a child undergoing preventive dental visits. METHODS: Databases: Ovid MEDLINE, PsycINFO (EBSCOhost), Embase, and Cochrane Library, were searched from 1946 to February 2022, for randomized clinical trials (RCTs) comparing effectiveness of basic and advanced nonpharmacological techniques rendered during a pre- ventive visit including examination, prophylaxis, fluoride application and radiographs. Workgroup (WG) identified moderate-to-high quality system- atic reviews (SRs) published on hypnosis, audiovisual distraction, and parental presence/ absence; and decided to exclude these interventions from current SR to avoid duplication. The primary outcome measures for the studied interventions included reduction in anxiety, fear, pain, and improve- ment in cooperative behavior. Eight authors determined the included RCTs, performed data extraction, and assessed the risk of bias. Standardized Mean Difference calculation and assignment of quality of evidence by Grading of Recommendations Assessment, Development and Evaluation approach were done. RESULTS: Fifteen articles qualified for analysis from 219 screened articles. WG found studies evaluating effectiveness of pre- visit preparation and in-office strategies rendered pre- or during treatment such as positive imagery, communication, modeling, tell-show-do, magic tricks, mobile applications, positive reinforcement, and sensory adapted dental environment. The certainty of evidence ranged from Very low to Moderate and the magnitude of effect varied from trivial to a large change in the desired outcomes. CONCLUSIONS: Most basic nonpharmacological behavior guidance techniques showed trivial to small reduction in self-reported anxiety and/or improvement in behavior, with mobile application and modeling showing large effects in reduction of anxiety based on some rating scales. Systematic Review Registration Number: PROSPERO: CRD42022314723.

LongDat: an R package for covariate-sensitive longitudinal analysis of high-dimensional data.

Summary: We introduce LongDat, an R package that analyzes longitudinal multivariable (cohort) data while simultaneously accounting for a potentially large number of covariates. The primary use case is to differentiate direct from indirect effects of an intervention (or treatment) and to identify covariates (potential mechanistic intermediates) in longitudinal data. LongDat focuses on analyzing longitudinal microbiome data, but its usage can be expanded to other data types, such as binary, categorical and continuous data. We tested and compared LongDat with other tools (i.e. MaAsLin2, ANCOM, lgpr and ZIBR) on both simulated and real data. We showed that LongDat outperformed these tools in accuracy, runtime and memory cost, especially when there were multiple covariates. The results indicate that the LongDat R package is a computationally efficient and low-memory-cost tool for longitudinal data with multiple covariates and facilitates robust biomarker searches in high-dimensional datasets. Availability and implementation: The R package LongDat is available on CRAN (https://cran.r-project.org/web/packages/LongDat/) and GitHub (https://github.com/CCY-dev/LongDat). Supplementary information: Supplementary data are available at Bioinformatics Advances online.

Transannular C-H functionalization of cycloalkane carboxylic acids.

Cyclic organic molecules are common among natural products and pharmaceuticals1,2. In fact, the overwhelming majority of small-molecule pharmaceuticals contain at least one ring system, as they provide control over molecular shape, often increasing oral bioavailability while providing enhanced control over the activity, specificity and physical properties of drug candidates3-5. Consequently, new methods for the direct site and diastereoselective synthesis of functionalized carbocycles are highly desirable. In principle, molecular editing by C-H activation offers an ideal route to these compounds. However, the site-selective C-H functionalization of cycloalkanes remains challenging because of the strain encountered in transannular C-H palladation. Here we report that two classes of ligands-quinuclidine-pyridones (L1, L2) and sulfonamide-pyridones (L3)-enable transannular γ-methylene C-H arylation of small- to medium-sized cycloalkane carboxylic acids, with ring sizes ranging from cyclobutane to cyclooctane. Excellent γ-regioselectivity was observed in the presence of multiple ß-C-H bonds. This advance marks a major step towards achieving molecular editing of saturated carbocycles: a class of scaffolds that are important in synthetic and medicinal chemistry3-5. The utility of this protocol is demonstrated by two-step formal syntheses of a series of patented biologically active small molecules, prior syntheses of which required up to 11 steps6.

Comparison of Cervical Cancer Screening Used between Individuals with Disabilities and Individuals without Disabilities.

OBJECTIVE: Cervical cancer is the fourth most prevalent cancer in women worldwide. It is vital to achieve a high cervical cancer screening rate among women. We compared the Pap smear test (PST) used between individuals with disabilities and those without disabilities in Taiwan. METHODS: Individuals registered in the Taiwan Disability Registration File and the National Health Insurance Research Database (NHIRD) were screened for this nationally representative retrospective cohort study. Women aged 30 and above in 2016 and who were still alive in 2016 were matched in a 1:1 ratio via propensity score matching (PSM); 186,717 individuals with disabilities and 186,717 individuals without disabilities were included. Controlling for relevant variables, the odds of receiving PST were compared using conditional logistic regression analysis. RESULTS: A lower percentage of individuals with disabilities (16.93%) received PST than those without disabilities (21.82%). The odds of individuals with disabilities receiving PST were 0.74 times that of individuals without disabilities (OR = 0.74, 95% CI = 0.73-0.76). Compared to individuals without disabilities, individuals with intellectual and developmental disabilities had the lower odds of receiving PST (OR = 0.38, 95% CI = 0.36-0.40), followed by individuals with dementia (OR = 0.40, 95% CI = 0.33-0.48) or multiple disabilities (OR = 0.52, 95% CI = 0.49-0.54). CONCLUSIONS: We highly recommend that healthcare practitioners recognize the unique needs of individuals with different types of disabilities, especially those with cognitive impairments.