Reconstructing tumor clonal heterogeneity and evolutionary relationships based on tumor DNA sequencing data.

The heterogeneity of tumor clones drives the selection and evolution of distinct tumor cell populations, resulting in an intricate and dynamic tumor evolution process. While tumor bulk DNA sequencing helps elucidate intratumor heterogeneity, challenges such as the misidentification of mutation multiplicity due to copy number variations and uncertainties in the reconstruction process hinder the accurate inference of tumor evolution. In this study, we introduce a novel approach, REconstructing Tumor Clonal Heterogeneity and Evolutionary Relationships (RETCHER), which characterizes more realistic cancer cell fractions by accurately identifying mutation multiplicity while considering uncertainty during the reconstruction process and the credibility and reasonableness of subclone clustering. This method comprehensively and accurately infers multiple forms of tumor clonal heterogeneity and phylogenetic relationships. RETCHER outperforms existing methods on simulated data and infers clearer subclone structures and evolutionary relationships in real multisample sequencing data from five tumor types. By precisely analysing the complex clonal heterogeneity within tumors, RETCHER provides a new approach to tumor evolution research and offers scientific evidence for developing precise and personalized treatment strategies. This approach is expected to play a significant role in tumor evolution research, clinical diagnosis, and treatment. RETCHER is available for free at https://github.com/zlsys3/RETCHER.

Masking ability of CAD-CAM resin-matrix ceramics with different translucencies and thicknesses combined with four cement shades against varying background colors when facing veneer restorations.

BACKGROUND: To evaluate the comprehensive effect of translucency, thickness, cement shades, and background color on the masking ability of resin-matrix ceramic veneer restorations. METHODS: Resin-matrix ceramic specimens with 2 translucencies (LT, HT) and 3 thicknesses (0.5, 1.0, and 1.5 mm) were made of Upcera Hyramic (A2 shade). Cement specimens were made of Variolink N in 4 shades (yellow, white, transparent, and bleach XL). Five background specimens were made of IPS Natural Die Material in 5 shades (ND1, ND2, ND3, ND4, and ND5). Color coordinates of 120 subgroups (n = 5) of combined specimens composed of different ceramic, cement, and background specimens were obtained using a spectroradiometer. Color difference (ΔE00) compared with a 4-mm thick specimen of LT and HT ceramics was calculated and four-way ANOVA was used for statistical analysis (α = 0.05). RESULTS: Translucency, thickness, cement shade, background color, and their interaction had significant effects on ΔE00 (p < 0.001). ΔE00 values of HT groups were always higher than that of LT groups and were greater than 1.8 against all background colors. ΔE00 values of LT groups could be achieved to be less than 1.8 with appropriate thickness and cement shade. ΔE00 value decreased with increasing ceramic thickness. The effect of cement shade on ΔE00 had no obvious regularity, but ΔE00 values of bleach XL cement shade group were always lower than other cement shade groups under ND3 and ND5 background color. CONCLUSIONS: The masking ability of CAD-CAM resin-matrix ceramics can be simultaneously affected by translucency, thickness, cement shade, and background color. Resin-matrix ceramics with low translucency has a better masking ability than that with high translucency. The masking ability of CAD-CAM resin-matrix ceramics increase with increasing thickness. Cement shade has less impact on the final color of resin-matrix ceramic restorations.

Blastocysts originated from oocytes with smooth endoplasmic reticulum aggregates have a reduced euploidy rate: a retrospective cohort study.

Research question: Does the presence of smooth endoplasmic reticulum aggregates (SERa) in oocytes adversely impact the euploidy rate of subsequent blastocysts? Design: We performed a retrospective cohort study with 671 young patients (< 38 years) undergoing their first preimplantation genetic testing for aneuploidy (PGT-A) between January 2019 and October 2022 at a reproductive medical center of university affiliated teaching hospitals in China. Cycles were categorized as either SERa(+) cycles (containing at least one SERa(+) oocyte) or SERa(-) cycles (all oocytes without SERa). In SERa(+) cycles, oocytes were further subdivided into the SERa(+) oocyte group and the sibling SERa(-) oocyte group, comprising oocytes with normal morphology. Results: No significant differences were observed in the normal fertilization rate (72.9% vs. 75.4% vs. 72.6%, P=0.343), and cleavage rate (96.8% vs. 97.1% vs. 96.4%, P=0.839) among the SERa(-) cycle group, the SERa(-) oocyte group, and the SERa(+) oocyte group. Additionally, there were no statistically significant differences in the rates of good quality embryos (44.7% vs. 48.8% vs. 46.2%, P=0.177) or blastocyst formation (60.1% vs. 60.9% vs. 60.5%, P=0.893) among the groups. However, the euploidy rate of blastocysts derived from SERa(+) oocytes was significantly lower compared to those from SERa(-) oocytes in SERa(+) cycles and normal oocytes in SERa(-) cycles (39.3% vs. 51.2% vs. 54.5%, P=0.005). Despite this, there were no significant differences in pregnancy and neonatal outcomes after euploid embryo transfer among the three groups. Conclusions: Blastocysts derived from SERa(+) oocytes have a lower euploidy rate than those derived from SERa(-) oocytes. Nevertheless, comparable reproductive outcomes were achieved following euploid embryo transfer from both SERa(+) and SERa(-) oocytes.

A predictive risk-scoring model for survival prognosis of multiple myeloma based on gain/amplification of 1q21: Experience in a tertiary hospital in South-Western China.

BACKGROUND: Chromosomal 1q gains and amplifications (+1q21) are frequently observed in patients with newly diagnosed multiple myeloma (NDMM). However, the interpretation of the high-risk (HR) prognostic implications stemming from 1q21 abnormalities remain challenging to implement effectively. METHODS: In a comprehensive analysis of 367 consecutive patients with symptomatic MM, we assessed the prognostic significance of +1q21 using FISH with a threshold of 7.4%. The patient cohort was randomly divided into a training set (66.5%, n = 244) and a validation set (33.5%, n = 133). A multivariate Cox regression analysis was conducted to identify significant prognostic factors associated with PFS. Weight scores were assigned to each risk factor based on the ß-value of the corresponding regression coefficient. A predictive risk-scoring model involving +1q21 was then developed, utilizing the total score derived from these weight scores. The model's discriminative ability was evaluated using the AUC in both the training and validation sets. Finally, we compared the performance of the +1q21-involved risk with the established R-ISS and R2-ISS models. RESULTS: Upon initial diagnosis, 159 patients (43.32%) exhibited +1q21, with 94 (59.11%) having three copies, referred to as Gain(1q21), and 65 (40.89%) possessing four or more copies, referred to as Amp (1q21). Both were significantly linked to a reduced PFS in myeloma (p < 0.05), which could be effectively mitigated by ASCT. The +1q21-involved risk model, with an AUC of 0.697 in the training set and 0.725 in the validation set, was constructed including Gain(1q21), Amp(1q21), no-ASCT, and TP53 deletion. This model, termed the ultra-high-risk (UHR) model, demonstrated superior performance in predicting shorter PFS compared to the R-ISS stage 3 and R2-ISS stage 4. CONCLUSION: The UHR model, which integrates the presence of +1q21 with no-ASCT and TP53 deletion, is designed to identify the early relapse subgroup among patients with +1q21 in NDMM.

DMF-ChIP-seq for Highly Sensitive and Integrated Epigenomic Profiling of Low-Input Cells.

Mapping genome-wide DNA-protein interactions (DPIs) provides insights into the epigenetic landscape of complex biological systems and elucidates the mechanisms of epigenetic regulation in biological progress. However, current technologies in DPI profiling still suffer from high cell demands, low detection sensitivity, and large reagent consumption. To address these problems, we developed DMF-ChIP-seq that builds on digital microfluidic (DMF) technology to profile genome-wide DPIs in a highly efficient, cost-effective, and user-friendly way. The entire workflow including cell pretreatment, antibody recognition, pA-Tn5 tagmentation, fragment enrichment, and PCR amplification is programmatically manipulated on a single chip. Leveraging closed submicroliter reaction volumes and a superhydrophobic interface, DMF-ChIP-seq presented higher sensitivity in peak enrichment than other current methods, with high accuracy (Pearson Correlation Coefficient (PCC) > 0.86) and high repeatability (PCC > 0.92). Furthermore, DMF-ChIP-seq was capable of processing the samples with as few as 8 cells while maintaining a high signal-to-noise ratio. By applying DMF-ChIP-seq, H3K27ac histone modification of early embryonic cells during differentiation was profiled for the investigation of epigenomic landscape dynamics. With the benefits of high efficiency and sensitivity in DPI analysis, the system provides great promise in studying epigenetic regulation during various biological processes.

Generation of a hiPSC line (TONGJIi001-A) from a 46,XX,ins(1;15)(p13.3; q22.31q26.1),inv(2)(p22.1p16.3),t(2;14)(q34;q12) infertility patient.

We have successfully derived a hiPSC line from PBMCs obtained from a 41-year-old infertile female. The patient's karyotype, as determined by Bionano OGM, revealed complex chromosomal rearrangements, including 46,XX,ins(1;15)(p13.3;q22.31q26.1),inv(2)(p22.1p16.3),t(2;14)(q34;q12). Specifically, the episomal plasmids encoding key reprogramming factors OCT4, sh-p53, SOX2, KLF4, L-MYC, and LIN28 were applied to generate the integration-free hiPSC line, which was designated as TONGJIi001-A. This line exhibits typical hiPSC morphology, expresses core pluripotency markers and presents the ability to differentiate into all three germ layers in vitro. Collectively, hiPSC TONGJIi001-A provides a valuable resource for investigating the mechanisms underlying chromosomal structural abnormalities associated with infertility.

Atypical POEMS syndrome: Report of a patient.

BACKGROUND: The order of clinical symptoms of POEMS syndrome is different, and the first diagnosis department is different accordingly, which is easy to cause misdiagnosis by clinicians. METHODS: A retrospective study was conducted between 2019 and 2023 in West China Hospital. Demographic, clinical and laboratory test indicators data were collected. RESULTS: Out of a total of 48 patients, 32 patients were from outpatient clinics and 16 were inpatients. The median age was 51 years old, and 30 were male. The most prevalent initial symptom is polyneuropathy (77.1%). 22 out of the 48 patients had an elevated VEGF. The most prevalent serum M protein was lgA λ(54.2%), and one patient had no M protein which could be regarded as the atypical POEMS syndrome. CONCLUSIONS: At present, the diagnosis of POEMS syndrome is based on the combination of clinical manifestations and laboratory tests. Emphasizing pluralism is of great significance for the diagnosis of this disease.

Novel Loss-of-Function SYCP2 Variants in Infertile Males Upgrade the Gene-Disease Clinical Validity Classification for SYCP2 and Male Infertility to Strong.

Male infertility affects approximately 7% of the male population, and about 15% of these cases are predicted to have a genetic etiology. One gene implicated in autosomal dominant male infertility, SYCP2, encodes a protein critical for the synapsis of homologous chromosomes during meiosis I, resulting in impaired spermatogenesis. However, the clinical validity of the gene-disease pair was previously categorized as on the border of limited and moderate due to few reported cases. This study investigates the genetic cause of infertility for three unrelated Chinese patients with oligoasthenozoospermia. Whole exome sequencing (WES) and subsequent Sanger sequencing revealed novel heterozygous loss-of-function (LOF) variants in SYCP2 (c.89dup, c.946_947del, and c.4378_4379del). These cases, combined with the previously reported cases, provide strong genetic evidence supporting an autosomal dominant inheritance pattern. The experimental evidence also demonstrates a critical role for SYCP2 in spermatogenesis. Collectively, this updated assessment of the genetic and experimental evidence upgrades the gene-disease association strength of SYCP2 and autosomal dominant male infertility from on the border of limited and moderate to strong. The reclassification improves SYCP2 variant interpretation and qualifies it for the inclusion on diagnostic male infertility gene panels and prioritization in whole exome or genome studies for related phenotypes. These findings therefore improve the clinical interpretation of SYCP2 LOF variants.

Spurious dyslipidemia due to paraprotein in a patient with Waldenström macroglobulinemia.

INTRODUCTION: Serum lipid profiles play a crucial role in diagnosing and evaluating cardiovascular diseases. However, the presence of paraprotein can lead to inaccurate dyslipidemia results on automated analyzers. CASE REPORT: A 65-year-old woman whose combined concentrations of HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) consistently surpassed her total serum cholesterol levels over a period of three months presented with unusual lipid component detection. Further analysis revealed the presence of a monoclonal paraprotein, identified as an IgMλ band, with a concentration of 28.0 g/L. The patient was subsequently diagnosed with Waldenström macroglobulinemia. The use of abnormal reaction kinetic curves and the ß quantification method, along with an alternative method that did not suffer from interference, revealed that the monoclonal paraprotein interfered with the measurements of HDL-C, LDL-C, apolipoprotein A-I (apoA-I), and apolipoprotein B (apoB) when using the Roche detection system. This interference led to spurious elevated HDL-C concentrations and falsely decreased apoA-I and apoB concentrations, while the LDL-C results were minimally affected. Although diluting the sample normalized the HDL-C and LDL-C measurements, the interference with the apoA-I and apoB assays persisted. No other common biochemical tests were interfered with this paraprotein. CONCLUSION: Caution is advised when using a homogenous method for direct measurement of HDL-C and LDL-C in patients with monoclonal paraprotein. Techniques to recognize and eliminate this interference are available. However, immunoturbidimetric detection of apoA-I and apoB levels is also susceptible to this interference, which is not readily removable.

Comparison of case-based and lecture-based learning in dental fluorosis diagnostic ability with visual analog scale assessment.

OBJECTIVE: This study aimed to compare the impact of case-based learning (CBL) versus lecture-based learning (LBL) on dental students' clinical decision-making regarding DF severity using Visual Analog Scale (VAS) scoring. METHODS: Eighty first-year graduate dental students were randomly assigned to either the CBL (n = 38) or LBL (n = 42) groups. Both groups received instruction on DF diagnosis, with CBL involving small group sessions analyzing real cases and LBL involving traditional lectures. Effectiveness was assessed by presenting 32 dental fluorosis cases with Thylstrup-Fejerskov Index (TSIF) scores ranging from 0 to 7 through slide presentations to both groups for VAS assessment. Five evaluators of each group randomly selected were asked to repeat the rating 2 weeks later. Statistical analysis included two-way ANOVA for group and gender differences, intra-class correlation coefficient (ICC) for reliability, and Spearman correlation coefficients for validity. RESULTS: Variations in VAS scores were observed between CBL and LBL groups, with no significant gender impact. Excellent inter- and intra-evaluator agreement was found for VAS scoring in both groups, indicating its reliability. Validation against established indices (such as DI and TSIF) demonstrated strong correlations, with CBL students exhibiting higher correlations. CONCLUSIONS: CBL enhances students' clinical decision-making and proficiency in DF diagnosis, as evidenced by more consistent and accurate VAS scoring compared to LBL. These findings highlight the importance of innovative educational strategies in dental curricula, with implications for improving training quality and clinical outcomes. TRIAL REGISTRATION: The study was registered at the Clinical Research Center, Hospital of Stomatology, Wuhan University (Registration code: HGGC-036).

Unexpected Self-Assembly of Nanographene Oxide Membranes upon Electron Beam Irradiation for Ultrafast Ion Sieving.

Nanographene oxide (nGO) flakes-graphene oxide with a lateral size of ≈100 nm or less-hold great promise for superior flux and energy-efficient nanofiltration membranes for desalination and precise ionic sieving owing to their unique high-density water channels with less tortuousness. However, their potential usage is currently limited by several challenges, including the tricky self-assembly of nano-sized flakes on substrates with micron-sized pores, severe swelling in aqueous solutions, and mechanical instability. Herein, the successful fabrication of a robust membrane stacked with nGO flakes on a substrate with a pore size of 0.22 µm by vacuum filtration is reported. This membrane achieved an unprecedented water permeance above 819.1 LMH bar-1, with a high rejection rate of 99.7% for multivalent metal ions. The nGO flakes prepared using an electron beam irradiation method, have uniquely pure hydroxyl groups and abundant aromatic regions. The calculations revealed the strong hydrogen bonds between two nGO flakes, which arise from hydroxyl groups, coupled with hydrophobic aromatic regions, greatly enhance the stability of stacked flakes in aqueous solutions and increase their effective lateral size. The research presents a simple yet effective approach toward the fabrication of advanced 2D nanographene membranes with superior performance for ion sieving applications.

NeuroSeg-III: efficient neuron segmentation in two-photon Ca2+ imaging data using self-supervised learning.

Two-photon Ca2+ imaging technology increasingly plays an essential role in neuroscience research. However, the requirement for extensive professional annotation poses a significant challenge to improving the performance of neuron segmentation models. Here, we present NeuroSeg-III, an innovative self-supervised learning approach specifically designed to achieve fast and precise segmentation of neurons in imaging data. This approach consists of two modules: a self-supervised pre-training network and a segmentation network. After pre-training the encoder of the segmentation network via a self-supervised learning method without any annotated data, we only need to fine-tune the segmentation network with a small amount of annotated data. The segmentation network is designed with YOLOv8s, FasterNet, efficient multi-scale attention mechanism (EMA), and bi-directional feature pyramid network (BiFPN), which enhanced the model's segmentation accuracy while reducing the computational cost and parameters. The generalization of our approach was validated across different Ca2+ indicators and scales of imaging data. Significantly, the proposed neuron segmentation approach exhibits exceptional speed and accuracy, surpassing the current state-of-the-art benchmarks when evaluated using a publicly available dataset. The results underscore the effectiveness of NeuroSeg-III, with employing an efficient training strategy tailored for two-photon Ca2+ imaging data and delivering remarkable precision in neuron segmentation.

Network meta-analysis of probiotics, prebiotics, and synbiotics for the treatment of chronic constipation in adults.

OBJECTIVE: To compare the outcomes associated with the use of probiotics, prebiotics, and synbiotics for the treatment of chronic constipation in adults. METHODS: We searched eight electronic databases from database inception to July 11, 2023, to identify randomized controlled trials (RCTs) that report efficacy and safety for the treatment of chronic constipation. The risk of bias in the included RCTs was evaluated according to the Cochrane tool, and the certainty of the evidence was assessed using the Confidence in Network Meta-Analysis framework. The analysis was conducted using R version 4.3.0. RESULTS: Out of the 37 RCTs, a total of 21 different types of interventions were reported, involving 3,903 patients. This NMA demonstrated that both prebiotics and synbiotics resulted in an increase in frequency of stool movements per week. Compared to placebo, lactulose (Mean difference [MD] = 3.39, 95% Confdence interval [CI] [1.13, 5.65], moderate certainty), mix2 (consisting of Lactulose and Bacillus coagulans) (MD = 3.63, 95% CI [1.37, 5.89], moderate certainty), mix6 (consisting of Lactulose and Bifidobacterium coagulans) (MD = 4.30, 95% CI [1.04, 7.54], low certainty), and mix7 (consisting of Lactulose, Bifidobacterium subtilis, and Enterococcus faecium) (MD = 4.58, 95% CI [1.35, 7.78], moderate certainty) exhibited a significant effect. Notably, mix7 demonstrated the highest probability of being the most effective intervention (94.8%). Furthermore, when compared to L. plantarum, four probiotics and two synbiotics showed significant advantages in the Patient Assessment of Constipation Symptoms (PAC-SYM) score. L. reuteri (MD = -13.74, 95% CI [-22.20, -4.66], very low certainty) exhibited a significant effect in improving the Patient Assessment of Constipation Quality of Life (PAC-QoL) score. In terms of safety, there were no statistically significant differences between the intervention and control groups in all adverse event analyses. CONCLUSIONS: Moderate to very low evidence supports the use of lactulose and synbiotics to increase the number of weekly stool movements in patients, particularly highlighting the significant impact of synbiotics in increasing the number of weekly stool movements in patients with constipation. The use of L. paracasei showed improvements in PAC-SYM scores, while L. reuteri demonstrated enhancements in PAC-QoL scores.

Does an incomplete ferrule affect the fracture of endodontically treated teeth? A systematic review of in vitro studies.

OBJECTIVE: The purpose of this systematic review was to assess the impact of the incomplete ferrule on the fracture of endodontically treated teeth (ETT). DATA: The keywords such as "incomplete ferrule," "ferrule," "ferrule effect," "residual dentin," "remaining dentin," or "remaining coronal dentin" were used for searching, and only in vitro studies investigating the incomplete ferrule effect on natural teeth were included. SOURCES: PubMed, Medline, Embase, Cochrane Library, and Science Direct databases, and manual-searching. STUDY SELECTION: The search strategy yielded 1633 hits, and a total of 19 in vitro studies closely related to the effect of incomplete ferrule on ETT were included. CONCLUSION: The presence of an incomplete ferrule may significantly increase the fracture resistance of restored ETT, compared with restored ETT without ferrule. The number of residual axial walls of the incomplete ferrule may have an impact on the fracture resistance and fracture mode. The location of residual axial walls of the incomplete ferrule may affect the fracture resistance but not the fracture mode. CLINICAL IMPLICATIONS: Limited data suggest that the presence of incomplete ferrule has a positive effect on the fracture resistance of restored ETT. An incomplete ferrule can be an alternative for restoring ETT when a complete ferrule is not present. Nevertheless, further high-quality studies are still needed to offer more robust evidence and to take potential confounding factors into account.

A digital guide device to facilitate CAD-CAM veneer cementation for mandibular incisors: A dental technique.

The novel design of a digital guide to facilitate the cementation of computer-aided design and computer-aided manufacturing (CAD-CAM) veneers for mandibular incisors by using a polymer infiltrated ceramic network (PICN) material is described. This guide provided an efficient, reliable, and accurate approach to facilitating multiple veneers with minimally invasive preparation during cementation, reducing the technique sensitivity of freehand practice and chairside time.

Patient-derived organoid elucidates the identical clonal origin of bilateral breast cancer with diverse molecular subtypes.

Bilateral breast cancer (BBC), an infrequent breast cancer subtype, has primarily been studied in terms of incidence, prognosis, and through comparative analysis of synchronous (SBBC) and metachronous (MBBC) manifestations. The advent and application of organoid technology hold profound implications for tumor research and clinical management. This study represents the pioneering use of organoid models in BBC research. We established organoid lines from two surgical tumor specimens of a BBC patient, with one line undergoing detailed pathological and genomic analysis. The BBC organoid from the right breast demonstrated a marker expression profile of ER (-), PR (-), HER-2 (0), and Ki67 index 10%, indicating that it may derived from the TNBC tissue. Whole Exome Sequencing (WES) displayed consistent set of Top10 cancer driver genes affected by missense mutations, frameshift mutation, or splice site mutations in three tumor tissues and the organoid samples. The organoids' single nucleotide polymorphisms (SNPs) were more closely aligned with the TNBC tissue than other tumor tissues. Evolutionary analysis suggested that different tumor regions might evolve from a common ancestral layer. In this case, the development of BBC organoids indicated that simultaneous lesions with diverse molecular profiles shared a high degree of consistency in key tumor-driving mutations. These findings suggest the feasibility of generating BBC organoids representing various molecular types, accurately replicating significant markers and driver mutations of the originating tumor. Consequently, organoids serve as a valuable in vitro model for exploring treatment strategies and elucidating the underlying mechanisms of BBC.

Chemical characterisation of essential oil from Sambucus williamsii Hance leaves and its hepatoprotective effects.

This study is the first to examine the effect of leaves of Sambucus williamsii Hance essential oil on acute liver injury. According to gas chromatography-mass spectrometry analysis, the major constituents of S. williamsii essential oil (SEO)were (S)-falcarinol (62.66%), 17-pentatriacontene (7.78%) and tetrapentacontane (8.64%). Mice were pre-treated with SEO for 6 days followed by inducing liver injury with CCl4. The results indicated that SEO protected the liver against CCl4-induced injuries. Elevated levels of alanine-aminotransferase (ALT), aspartate amino-transferase (AST), alkaline phosphatase (ALP) in serum were significantly reduced on SEO pre-treatment. SEO pre-treatment significantly inhibited the oxidative stress and inflammation. Furthermore, toll-like receptor-4 (TLR4)/nuclear factor kappa-B (NF-κB) signalling pathways were significantly modulated by SEO in the liver tissue. The findings demonstrate that the essential oil of S. williamsii has enhancing the resistance to CCl4-induced liver injury.

No genetic causality between obesity and benign paroxysmal vertigo: A two-sample Mendelian randomization study.

Objective: We applied Mendelian randomization to explore the causal relationship between obesity and benign paroxysmal vertigo (BPV). Methods: We chose two types of obesity diseases. Obesity due to excessive calories and other or unspecified obesity from the FinnGen database. We used genomic significance (p < 5 × 10-8) to obtain independent single nucleotide polymorphisms (SNPs) as instrumental variables. Similarly, genome-wide association study data for the disease BPV were selected from the FinnGen database. R was then used to test the data for multiplicity and heterogeneity, as well as to detect the effect of individual SNPs on the results. Random effects inverse variance weighting was used as the main statistical analysis. Results: First, by analyzing, we found an outlier in obesity due to excessive calories (rs12956821). Outliers were then removed, and the statistical results were analyzed without heterogeneity (p > 0.05) and horizontal pleiotropy (p > 0.05), as well as individual SNPs having no effect on the results. Meanwhile, random-effects IVW results showed obesity due to excessive calories (p = 0.481; OR = 0.941), and other or unspecified obesity (p = 0.640; OR = 0.964). Conclusions: The present study did not find a causal relationship between the above two obesity types and BPV at the genetic level.

A WeChat-based nursing intervention program improves the postoperative rehabilitation of breast cancer patients: results from a randomized controlled trial.

Background: In postoperative setting, breast cancer (BC) patients can experience adverse effects, including fatigue, sleep disorders, and pain, which substantially affect their health-related quality of life (HRQoL). This study sought to assess the effectiveness of a WeChat-based multimodal nursing program (WCBMNP) that was specifically designed for the rehabilitation of women following BC surgery. Methods: BC patients were randomly, single-blinded allocated to either the intervention (n=62) or control (n=63) cohorts. Over a period of 6 months (24 weeks), the intervention cohort received a WCBMNP in addition to routine nursing care, while the control cohort received routine nursing care only. To evaluate patients' fear of cancer recurrence (FCR), their overall fear score was assessed using the Japanese version of the Concerns About Recurrence Scale (CARS-J) for primary outcome. The initial outcome (HRQoL) and secondary results, such as fatigue, sleep, and pain, were examined using the Functional Assessment of Cancer Therapy-Breast (FACT-B, version 4.0) and Nursing Rating Scale (NRS), respectively. Results: Two hundred and ten participants, 85 participants were excluded. Compared to the controls (n=63), the intervention cohort (n=62) showed statistically significant improvements in their CARS-J scores. The intervention cohort aggregate scores on the FACT-B improved significantly but were affected by the compounding influences of cohort dynamics, temporal progression, and their interaction. Similar improvements were observed in the social/family and functional well-being domains. Emotional well-being was improved based on the effects of time and group-time interaction. In the intervention cohort, the "BC-specific subscale for additional concerns" was affected by group and time, whereas physical well-being was only affected by time. Conversely, there were no statistically significant changes in the variables of fatigue, sleep, and pain. Conclusions: The WCBMNP reduced FCR and significantly increased the HRQoL of female patients with BC postoperatively. The WCBMNP could be implemented as a postoperative rehabilitation intervention in this patient population to improve outcomes. Trial Registration: Chinese Clinical Trial Registry (ChiCTR2400081557).

Combining a CAD-CAM composite resin palatal wall with a direct composite resin layering technique for the restoration of a large Class IV fracture: A clinical report.

This clinical report presents combining a computer-aided design and computer-aided manufacturing (CAD-CAM) composite resin palatal wall with a direct composite resin layering technique for the esthetic and functional restoration of a large Class IV fracture of a maxillary central incisor to achieve optimal esthetic and functional outcomes.