Neoadjuvant chemotherapy plus camrelizumab for locally advanced cervical cancer (NACI study): a multicentre, single-arm, phase 2 trial.

BACKGROUND: Locally advanced cervical cancer constitutes around 37% of cervical cancer cases globally and has a poor prognosis due to limited therapeutic options. Immune checkpoint inhibitors in the neoadjuvant setting could address these challenges. We aimed to investigate the efficacy and safety of neoadjuvant chemo-immunotherapy for locally advanced cervical cancer. METHODS: In this single-arm, phase 2 trial, which was done across eight tertiary hospitals in China, we enrolled patients aged 18-70 years with untreated cervical cancer (IB3, IIA2, or IIB/IIIC1r with a tumour diameter ≥4 cm [International Federation of Gynecology and Obstetrics, 2018]) and an Eastern Cooperative Oncology Group performance status of 0 or 1. Eligible patients underwent one cycle of priming doublet chemotherapy (75-80 mg/m2 cisplatin, intravenously, plus 260 mg/m2 nab-paclitaxel, intravenously), followed by two cycles of a combination of chemotherapy (cisplatin plus nab-paclitaxel) on day 1 with camrelizumab (200 mg, intravenously) on day 2, with a 3-week interval between treatment cycles. Patients with stable disease or progressive disease received concurrent chemoradiotherapy, and patients with a complete response or partial response proceeded to radical surgery. The primary endpoint was the objective response rate, by independent central reviewer according to Response Evaluation Criteria in Solid Tumours, version 1.1. Activity and safety were analysed in patients who received at least one dose of camrelizumab. This study is registered with ClinicalTrials.gov, NCT04516616, and is ongoing. FINDINGS: Between Dec 1, 2020, and Feb 10, 2023, 85 patients were enrolled and all received at least one dose of camrelizumab. Median age was 51 years (IQR 46-57) and no data on race or ethnicity were collected. At data cutoff (April 30, 2023), median follow-up was 11·0 months (IQR 6·0-14·5). An objective response was noted in 83 (98% [95% CI 92-100]) patients, including 16 (19%) patients who had a complete response and 67 (79%) who had a partial response. The most common grade 3-4 treatment-related adverse events during neoadjuvant chemo-immunotherapy were lymphopenia (21 [25%] of 85), neutropenia (ten [12%]), and leukopenia (seven [8%]). No serious adverse events or treatment-related deaths occurred. INTERPRETATION: Neoadjuvant chemo-immunotherapy showed promising antitumour activity and a manageable adverse event profile in patients with locally advanced cervical cancer. The combination of neoadjuvant chemo-immunotherapy with radical surgery holds potential as a novel therapeutic approach for locally advanced cervical cancer. FUNDING: National Key Technology Research and Development Program of China and the National Clinical Research Center of Obstetrics and Gynecology.

Long-term outcome and risk factors of reintervention after high intensity focused ultrasound ablation for uterine fibroids: a systematic review and meta-analysis.

OBJECTIVES: To quantify the reintervention rate and analyze the risk factors for reintervention after high-intensity focused ultrasound (HIFU) ablation of uterine fibroids. METHODS: Eighteen studies were selected from the seven databases. A meta-analysis was applied to synthesize the reintervention rates for fibroids across various follow-up durations. Subgroup-analysis was conducted based on the year of surgery, sample size, guide methods, and non-perfusion volume ratio (NPVR). Signal intensity of T2-weighted imaging (T2WI) was independently evaluated for reintervention risk. RESULTS: The study enrolled 5216 patients with fibroids treated with HIFU. There were 3247, 1239, 1762, and 2535 women reaching reintervention rates of 1% (95% confidence interval (CI): 1-1), 7% (95% CI: 4-11), 19% (95% CI: 11-27), and 29% (95% CI: 14-44) at 12, 24, 36, and 60-month after HIFU. The reintervention rates of patients treated with US-guided HIFU (USgHIFU) were significantly lower than those of patients treated with MR-guided focused ultrasound surgery (MRgFUS). When the NPVR of fibroids was over 50%, the reintervention rates at 12, 36 and 60-month after HIFU were 1% (95% CI: 0.3-2), 5% (95% CI: 3-8), and 15% (95% CI: 9-20). The reintervention risk for hyper-intensity fibroids on T2WI was 3.45 times higher (95% CI: 2.7-4.39) for hypo-/iso-intensity fibroids. CONCLUSION: This meta-analysis showed that the overall reintervention rates after HIFU were acceptable and provided consultative suggestions regarding treatment alternatives for patients with fibroids. Subgroup-analysis revealed that USgHIFU, NPVR ≥ 50%, and hypo-/iso-intensity of fibroids on T2WI were significant factors in reducing reintervention. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42023456094.

Correcting force error-induced underestimation of lattice thermal conductivity in machine learning molecular dynamics.

Machine learned potentials (MLPs) have been widely employed in molecular dynamics simulations to study thermal transport. However, the literature results indicate that MLPs generally underestimate the lattice thermal conductivity (LTC) of typical solids. Here, we quantitatively analyze this underestimation in the context of the neuroevolution potential (NEP), which is a representative MLP that balances efficiency and accuracy. Taking crystalline silicon, gallium arsenide, graphene, and lead telluride as examples, we reveal that the fitting errors in the machine-learned forces against the reference ones are responsible for the underestimated LTC as they constitute external perturbations to the interatomic forces. Since the force errors of a NEP model and the random forces in the Langevin thermostat both follow a Gaussian distribution, we propose an approach to correcting the LTC by intentionally introducing different levels of force noises via the Langevin thermostat and then extrapolating to the limit of zero force error. Excellent agreement with experiments is obtained by using this correction for all the prototypical materials over a wide range of temperatures. Based on spectral analyses, we find that the LTC underestimation mainly arises from increased phonon scatterings in the low-frequency region caused by the random force errors.

A Retrospective Cohort Study of vNOTES Extraperitoneal Versus Laparoscopic Sacral Hysteropexy With Uterine Preserving Regarding Surgical Outcomes and 2 Year Follow-up Results.

STUDY OBJECTIVE: To explore the effectiveness of transvaginal natural orifice transluminal endoscopic surgery extraperitoneal sacral hysteropexy (vNOTES-ESH) in women with symptomatic uterine prolapse over a 2 year follow-up. DESIGN: Retrospective cohort study. SETTING: Gynecological minimally invasive center. PATIENTS: Women undergoing sacral hysteropexy either by vNOTES (n = 25) or laparoscopic (n = 74) between November 2016 and December 2020. INTERVENTIONS: Both vNOTES-ESH and laparoscopic sacral hysteropexy (LAP-SH) were used for uterine prolapse. Demographic data, operative characteristics, perioperative outcomes, and follow-up information 2 years postsurgery in the 2 groups were retrospectively evaluated. RESULTS: Both procedures showed similar operation time, estimated blood loss, hospital stays, and pain scores (p >0.05). During a median follow-up of 59 (24-72) months, the surgical success rate was 96% for vNOTES-ESH and 97.3% for LAP-SH (p >0.05), with no differences in anatomical position or pelvic organ function after the operation. Women in the LAP-SH group experienced more bothersome symptoms of constipation compared to those in the vNOTES-ESH group (5.41% vs 0, p <0.05). Lastly, 1 case in the vNOTES-ESH group had a mesh exposed area of less than 1 cm2, and 1 patient in the LAP-SH group experienced stress incontinence. CONCLUSIONS: In this retrospective study, vNOTES-ESH met our patients' preference for uterine preservation and was a successful and effective treatment for uterine prolapse, providing good functional improvement in our follow-up. This procedure should be considered as an option for patients with pelvic organ prolapse.

Integrated microRNA and whole-transcriptome sequencing reveals the involvement of small and long non-coding RNAs in the fiber growth of ramie plant.

BACKGROUND: MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are the two main types of non-coding RNAs that play crucial roles in plant growth and development. However, their specific roles in the fiber growth of ramie plant (Boehmeria nivea L. Gaud) remain largely unknown. METHODS: In this study, we performed miRNA and whole-transcriptome sequencing of two stem bark sections exhibiting different fiber growth stages to determine the expression profiles of miRNAs, lncRNAs, and protein-encoding genes. RESULTS: Among the identified 378 miRNAs and 6,839 lncRNAs, 88 miRNAs and 1,288 lncRNAs exhibited differential expression. Bioinformatics analysis revealed that 29 and 228 differentially expressed protein-encoding genes were targeted by differentially expressed miRNAs and lncRNAs, respectively, constituting eight putative competing endogenous RNA networks. lncR00022274 exhibited downregulated expression in barks with growing fibers. It also had an antisense overlap with the MYB gene, BntWG10016451, whose overexpression drastically increased the xylem fiber number and secondary wall thickness of fibers in the stems of transgenic Arabidopsis, suggesting the potential association of lncR00022274-BntWG10016451 expression with fiber growth. CONCLUSIONS: These findings provide insights into the roles of ncRNAs in the regulation of fiber growth in ramie, which can be used for the biotechnological improvement of its fiber yield and quality in the future.

Failure to achieve reduction on developmental dysplasia of hip: an ultrasound evaluation.

BACKGROUND: Ultrasound examination of the medial side of the hip joint has been rarely used to evaluate the status of developmental dysplasia of the hip (DDH) in Pavlik harness treatment according to the literature. PURPOSE: To analyze the effects of cartilaginous acetabulum, hip joint labrum, and acetabular tissue on the reduction of DDH. MATERIAL AND METHODS: A total of 50 cases (100 hips) were detected by the Graf method with a high-frequency linear transducer (L 5-12), and there were 59 dislocated hips and 41 non-dislocated hips. Patients were treated with a Pavlik harness. Ultrasound examination of the medial side of the hip joint was performed for follow-up. The hip joints were divided into three groups: the non-dislocated group; the reducible group; and the non-reducible group. RESULTS: The success rate of reduction was significantly higher when the acetabulum cartilage was located on the cephalic side (chi-square = 28.12, P < 0.001). The success rate was also significantly higher when the hip joint labrum was located on the cephalic side (chi-square = 17.21, P < 0.001). Type III and D had a higher success rate of reduction than type IV (P < 0.001). The pairwise comparison of the measurements of acetabular tissue between the non-dislocated group, the reducible group, and the non-reducible group showed statistical differences (P < 0.001). CONCLUSION: The present study confirmed that the location of acetabulum cartilage and hip joint labrum affected the outcome of treatment. The degree of dislocation and the amount of acetabular tissue were correlated with the success rate of treatment.

Genomic analyses provide comprehensive insights into the domestication of bast fiber crop ramie (Boehmeria nivea).

Ramie (Boehmeria nivea) is an economically important natural fiber-producing crop that has been cultivated for thousands of years in China; however, the evolution of this crop remains largely unknown. Here, we report a ramie domestication analysis based on genome assembly and resequencing of cultivated and wild accessions. Two chromosome-level genomes representing wild and cultivated ramie were assembled de novo. Numerous structural variations between two assemblies, together with the genetic variations from population resequencing, constituted a comprehensive genomic variation map for ramie. Domestication analysis identified 71 high-confidence selective sweeps comprising 320 predicted genes, and 29 genes from sweeps were associated with fiber growth in the expression. In addition, we identified seven genetic loci associated with the fiber yield trait in the segregated population derived from the crossing of two assembled accessions, and two of which showed an overlap with the selective sweeps. These findings indicated that bast fiber traits were focused on during the domestication history of ramie. This study sheds light on the domestication of ramie and provides a valuable resource for biological and breeding studies of this important crop.

Resequencing of 301 ramie accessions identifies genetic loci and breeding selection for fibre yield traits.

Ramie is an important fibre-producing crop in China; however, the genetic basis of its agronomic traits remains poorly understood. We produced a comprehensive map of genomic variation in ramie based on resequencing of 301 landraces and cultivars. Genetic analysis produced 129 signals significantly associated with six fibre yield-related traits, and several genes were identified as candidate genes for respective traits. Furthermore, we found that natural variations in the promoter region of Bnt14G019616 were associated with extremely low fibre abundance, providing the first evidence for the role of pectin methylesterase in fibre growth of plants. Additionally, nucleotide diversity analysis revealed that breeding selection has been markedly focussed on chromosome 9 in which ~ 39.6% sequence underwent selection, where one gibberellin-signalling-repressed DELLA gene showed distinct selection signatures in the cultivars. This study provides insights into the genetic architecture and breeding history of fibre yield traits in ramie. Moreover, the identification of fibre yield-related genetic loci and large-scale genomic variation represent valuable resources for genomics-assisted breeding of this crop.

GPUMD: A package for constructing accurate machine-learned potentials and performing highly efficient atomistic simulations.

We present our latest advancements of machine-learned potentials (MLPs) based on the neuroevolution potential (NEP) framework introduced in Fan et al. [Phys. Rev. B 104, 104309 (2021)] and their implementation in the open-source package gpumd. We increase the accuracy of NEP models both by improving the radial functions in the atomic-environment descriptor using a linear combination of Chebyshev basis functions and by extending the angular descriptor with some four-body and five-body contributions as in the atomic cluster expansion approach. We also detail our efficient implementation of the NEP approach in graphics processing units as well as our workflow for the construction of NEP models and demonstrate their application in large-scale atomistic simulations. By comparing to state-of-the-art MLPs, we show that the NEP approach not only achieves above-average accuracy but also is far more computationally efficient. These results demonstrate that the gpumd package is a promising tool for solving challenging problems requiring highly accurate, large-scale atomistic simulations. To enable the construction of MLPs using a minimal training set, we propose an active-learning scheme based on the latent space of a pre-trained NEP model. Finally, we introduce three separate Python packages, viz., gpyumd, calorine, and pynep, that enable the integration of gpumd into Python workflows.

Genotype-Phenotype Relationship and Follow-up Analysis of a Chinese Cohort With Osteogenesis Imperfecta.

OBJECTIVE: To evaluate the genotype-phenotype relationship and the effect of treatment on the clinical course of osteogenesis imperfecta (OI). METHODS: We established a Chinese hospitalized cohort with OI and followed them up for an average of 6 years. All patients were confirmed as having OI using whole-exome sequencing. We analyzed the genotype-phenotype relationship based on different types, pathogenic mechanisms, and gene inheritance patterns of OI. Additionally, we assessed whether there was a difference in treatment efficacy based on genotype. RESULTS: One hundred sixteen mutations in 6 pathogenic genes (COL1A1, COL1A2, IFITM5, SERPINF1, FKBP10, and WNT1) were identified in 116 patients with type I, III, IV, V, VI, XI, or XV OI. Compared with patients with COL1A1 mutations, patients with COL1A2 mutations were younger at the time of the first fracture, whereas other phenotypes were similar. When 3 groups (helical, haploinsufficiency, and non-collagen I gene mutations) were compared, patients with helical mutations were the shortest and most prone to dentinogenesis imperfecta. Patients with haploinsufficiency mutations were the oldest at the time of the first fracture. Moreover, patients with non-collagen I gene mutations were least susceptible to blue sclerae and had the highest fracture frequency. Furthermore, there were some minor phenotypic differences among non-collagen I gene mutations. Interestingly, pamidronate achieved excellent results in the treatment of patients with OI, and the treatment effect appeared to be unrelated to their genotypes. CONCLUSION: Our findings indicated a genotype-phenotype relationship and a similar effect of pamidronate treatment in patients with OI, which could provide a basis for guiding clinical treatment and predicting OI prognosis.

Synergetic effects of a front ITO nanocylinder array and a back square Al array to enhance light absorption for organic solar cells.

Efficient light management is critical to obtain high performance for organic solar cells (OSCs), which aims to solve the contradiction between limited carrier extraction and light absorption for the normally employed photoactive layers generally having both short exciton diffusion lengths and low extinction coefficients. In this study, we introduce a simple and efficient light management structure consisting of a front indium tin oxide nanocylinder (ITO-NC) array and a back square Al array. Thanks to the synergetic effects of antireflection and light scattering induced by the ITO-NC array, together with the secondary scattering and localized surface plasmon resonance because of the square Al array, remarkably enhanced light absorption in a broad spectral range can be achieved. Taking the most investigated photoactive layer of the P3HT:PC61BM blend as an example, simulation results reveal that, compared with the planar control device of the ITO/PEDOT:PSS/P3HT:PC61BM(80nm)/ZnO/Al, the short-circuit current density and power conversion efficiency can be enhanced by 36.58% and 38.38% after incorporating the light management structure with the optimal structural parameters. Furthermore, good omnidirectional light management can be achieved for the proposed device structure. Given the excellent performance and simple structure, we believe that this study would provide a meaningful exploration of developing light management structures applicable for thin film-based optoelectronic devices.

Use of ultrasonography to evaluate early outcomes of reduction in developmental dysplasia of the hip.

OBJECTIVE: To compare pubo-femoral distance (PFD) in normal hips and those treated for developmental dysplasia of the hip (DDH) and to investigate the value of ultrasonography from the medial hip in early follow-up of dislocated DDH after reduction. MATERIALS AND METHODS: This study included 58 infants (49 females) with DDH who presented with 65 dislocated hips (51 unilateral and 7 bilateral). Dislocation was treated by closed reduction for 53 and open reduction for 12 hips. Ultrasonography on the medial side of the hip was performed within 1-2 weeks and 4 weeks after reduction. The distance from the pubic bone to the femoral head (PFD) was measured to assess the reduction and stability of the femoral head and compared to that on the contralateral side (control) in cases of unilateral DDH. RESULTS: The PFD value for the normal group (2.9 ± 0.4 mm) was significantly less than that for the closed reduction group (4.9 ± 2.8 mm, P<0.001) and that for the open reduction group (4.4 ± 1.6 mm; P=0.02), but no difference in the PFD was observed between the closed reduction and the open reduction groups (P=0.73). Despite successful reduction, the PFD values in the successful reduction group remained higher than those of the normal hips. CONCLUSION: PFD measurement by ultrasonography of the medial hip can be used to evaluate the effectiveness of reduction procedures in DDH. The clinical implications of post-reduction ultrasound evaluation in the diagnosis and long-term follow-up of outcomes require further research.

Identification of proteins associated with bast fiber growth of ramie by differential proteomic analysis.

BACKGROUND: Ramie is an important fiber-producing crop in China, and its fibers are widely used as textile materials. Fibers contain specialized secondary cellular walls that are mainly composed of cellulose, hemicelluloses, and lignin. Understanding the mechanism underlying the secondary wall biosynthesis of fibers will benefit the improvement of fiber yield and quality in ramie. RESULTS: Here, we performed a proteomic analysis of the bark from the top and middle parts of the stem, where fiber growth is at different stages. We identified 6971 non-redundant proteins from bast bark. Proteomic comparison revealed 983 proteins with differential expression between the two bark types. Of these 983 proteins, 46 were identified as the homolog of known secondary wall biosynthetic proteins of Arabidopsis, indicating that they were potentially associated with fiber growth. Then, we proposed a molecular model for the secondary wall biosynthesis of ramie fiber. Furthermore, interaction analysis of 46 candidate proteins revealed two interacting networks that consisted of eight cellulose biosynthetic enzymes and seven lignin biosynthetic proteins, respectively. CONCLUSION: This study sheds light on the proteomic basis underlying bast fiber growth in ramie, and the identification of many candidates associated with fiber growth provides important basis for understanding the fiber growth in this crop.

Phosphoproteome analysis reveals an extensive phosphorylation of proteins associated with bast fiber growth in ramie.

BACKGROUND: Phosphorylation modification, one of the most common post-translational modifications of proteins, widely participates in the regulation of plant growth and development. Fibers extracted from the stem bark of ramie are important natural textile fibers; however, the role of phosphorylation modification in the growth of ramie fibers is largely unknown. RESULTS: Here, we report a phosphoproteome analysis for the barks from the top and middle section of ramie stems, in which the fiber grows at different stages. A total of 10,320 phosphorylation sites from 9,170 unique phosphopeptides that were assigned to 3,506 proteins was identified, and 458 differentially phosphorylated sites from 323 proteins were detected in the fiber developmental barks. Twelve differentially phosphorylated proteins were the homologs of Arabidopsis fiber growth-related proteins. We further focused on the function of the differentially phosphorylated KNOX protein whole_GLEAN_10029667, and found that this protein dramatically repressed the fiber formation in Arabidopsis. Additionally, using a yeast two-hybridization assay, we identified a kinase and a phosphatase that interact with whole_GLEAN_10029667, indicating that they potentially target this KNOX protein to regulate its phosphorylation level. CONCLUSION: The finding of this study provided insights into the involvement of phosphorylation modification in ramie fiber growth, and our functional characterization of whole_GLEAN_10029667 provide the first evidence to indicate the involvement of phosphorylation modification in the regulation of KNOX protein function in plants.

Ubiquitylome analysis reveals the involvement of ubiquitination in the bast fiber growth of ramie.

MAIN CONCLUSION: A total of 249 sites from 197 proteins showed a differential ubiquitination level in the fiber development of ramie barks. The function of two differentially ubiquitinated proteins for fiber growth was demonstrated. Ubiquitination is one of the most common post-translational modifications of proteins, and it plays essential roles in plant growth and development. However, the involvement of ubiquitination in the growth of plant fibers remains largely unknown. We compared the ubiquitylome of the top and middle stems of ramie bark, with different fiber growth stages. We identified 249 differentially ubiquitinated sites in 197 proteins in fiber-developing barks in the stems and found that seven were homologs of Arabidopsis proteins associated with fiber growth. Overexpression of the differentially ubiquitinated proteins, RWA3 homolog whole_GLEAN_10024150 and MYB protein whole_GLEAN_10015497, significantly promoted fiber growth in transgenic Arabidopsis, indicating their involvement in this process. We also found that the abundance of these proteins decreased when their ubiquitination levels increased and vice versa in the fiber-developing bark. These results indicated that the abundance of these two proteins was adjusted through ubiquitin-dependent degradation. Collectively, our findings provide important insights into the involvement of ubiquitination in the growth of ramie fibers.

vNOTES Hysterectomy with Sentinel Lymph Node Mapping for Endometrial Cancer: Description of Technique and Perioperative Outcomes.

STUDY OBJECTIVE: To explore the technique and clinical value of transvaginal natural orifice transluminal endoscopic surgery (vNOTES) in hysterectomy and sentinel lymph node (SLN) mapping for endometrial cancer by comparing its perioperative outcomes with those of laparoscopic staging. DESIGN: Retrospective cohort study. SETTING: Department of gynecology at a tertiary medical center. PATIENTS: All women diagnosed with endometrial cancer who underwent minimally invasive surgery at our center between August 2017 and May 2020. INTERVENTIONS: Both vNOTES and laparoscopic approaches were used for hysterectomy and SLN mapping. The success of SLN detection as well as perioperative outcomes were subsequently analyzed. MEASUREMENTS AND MAIN RESULTS: This study included 74 patients; 23 patients underwent vNOTES surgery, whereas 51 underwent standard laparoscopic surgery. The total successful SLN detection was 95.7% in the vNOTES group and 92.2% in the laparoscopy group (p >.05), whereas the bilateral success rates were 87.0% and 90.2%, respectively. No difference in SLN detection was observed between the 2 groups in terms of the side-specific mapping efficacy quotient (91.3% vs 91.2%, p = .47). The number of harvested SLNs, operative time, estimated blood loss, and intraoperative complications in the 2 groups were similar. One (4.3%) postoperative complication occurred in the vNOTES group vs 4 (7.9%) in the laparoscopy group (p = .029), and the median postoperative hospital stay was 3 days vs 4 days (p = .003). CONCLUSION: This study suggests that the vNOTES procedure is feasible, with a potentially decreased postoperative hospital stay, faster recovery, and better cosmetic results. However, prospective research is needed to validate its broader clinical application.

Establishing reference values for the pubofemoral distance in normal infant medial hips by ultrasound.

BACKGROUND: Measuring the pubofemoral distance (PFD) is important for evaluating the effectiveness of hip reduction in the treatment of developmental dysplasia of the hip (DDH). However, reference PFD values have not been established in normal infants. PURPOSE: To investigate variations in PFD values measured in normal infant medial hips stratified by age, laterality, and gender. MATERIAL AND METHODS: A total of 240 infants diagnosed with Graf type Ia and/or Graf type Ib hips by ultrasonography were stratified into eight age groups: 0-1 month; 1-2 months; 2-3 months; 3-4 months; 4-5 months; 5-6 months; 6-7 months; and 7-12 months. The bilateral medial hips were scanned with transinguinal ultrasound. The PFD was defined as the distance between the lateral edge of the superior ramus of pubic bone and the medial edge of the femoral head. Inter-observer reproducibility was assessed. RESULTS: Among the 240 infants, there were 371 Graf type Ia hips and 109 Graf type Ib hips. Mean ± SD bilateral PFD values of eight groups were measured separately. There were no significant differences in mean PFD values for left or right hips (t = 0.946, P = 0.345) or mean bilateral PFD values in male and female infants (t = 1.445, P = 0.149). Mean PFD values increased linearly with age (left: r = 0.680, P < 0.0001; right: r = 0.682, P < 0.0001). Inter-observer reproducibility was excellent. CONCLUSION: This study established reference PFD values from the medial hip in infants aged 0-12 months. PFD values increased with age, but were not significantly influenced by laterality or gender. These data provide detailed information that can support follow-up of infants treated for DDH.

Comprehensive genomic variation profiling of cervical intraepithelial neoplasia and cervical cancer identifies potential targets for cervical cancer early warning.

BACKGROUND: To better understand the pathogenesis of cervical cancer (CC), we systematically analysed the genomic variation and human papillomavirus (HPV) integration profiles of cervical intraepithelial neoplasia (CIN) and CC. METHODS: We performed whole-genome sequencing or whole-exome sequencing of 102 tumour-normal pairs and human papillomavirus probe capture sequencing of 45 CCs, 44 CIN samples and 25 normal cervical samples, and constructed strict integrated workflow of genomic analysis. RESULTS: Mutational analysis identified eight significantly mutated genes in CC including four genes (FAT1, MLL3, MLL2 and FADD), which have not previously been reported in CC. Targetable alterations were identified in 55.9% of patients. In addition, HPV integration breakpoints occurred in 97.8% of the CC samples, 70.5% of the CIN samples and 42.8% of the normal cervical samples with HPV infection. Integrations of high-risk HPV strains in CCs, including HPV16, 18, 33 and 58, also occurred in the CIN samples. Moreover, gene mutations were detected in 52% of the CIN specimens, and 54.8% of these mutations occurred in genes that also mutated in CCs. CONCLUSION: Our results lay the foundation for a deep understanding of the molecular mechanisms and finding new diagnostic and therapeutic targets of CC.

Genotypic and phenotypic characterization of Chinese patients with osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a rare hereditary skeletal dysplasia, characterized by recurrent fractures and bone deformity. This study presents a clinical characterization and mutation analysis of 668 patients, aiming to establish the mutation spectrum and to elucidate genotype-phenotype correlations in Chinese OI patients. We identified 274 sequence variants (230 in type I collagen encoding genes and 44 in noncollagen genes), including 102 novel variants, in 340 probands with a detection rate of 90%. Compared with 47 loss-of-function variants detected in COL1A1, neither nonsense nor frameshift variants were found in COL1A2 (p < 0.0001). The major cause of autosomal recessive OI was biallelic variants in WNT1 (56%, 20/36). It is noteworthy that three genomic rearrangements, including one gross deletion and one gross duplication in COL1A1 as well as one gross deletion in FKBP10, were detected in this study. Of ten individuals with glycine substitutions that lie towards the N-terminal end of the triple-helical region of the α1(I) chain, none exhibited hearing loss, suggesting a potential genotype-phenotype correlation. The findings in this study expanded the mutation spectrum and identified novel correlations between genotype and phenotype in Chinese OI patients.

A genomic resource derived from the integration of genome sequences, expressed transcripts and genetic markers in ramie.

BACKGROUND: The redundancy of genomic resources, including transcript and molecular markers, and their uncertain position in the genome have dramatically hindered the study of traits in ramie, an important natural fiber crop. RESULTS: We obtained a high-quality transcriptome consisting of 30,591 non-redundant transcripts using single-molecule long-read sequencing and proposed it as a universal ramie transcriptome. Additionally, 55,882 single nucleotide polymorphisms (SNPs) were identified and a high-density genetic map was developed. Based on this genetic map, 181.7 Mb ramie genome sequences were assembled into 14 chromosomes. For the convenient use of these resources, 29,286 (~ 95.7%) of the transcripts and all 55,882 SNPs, along with 1827 previously reported sequence repeat markers (SSRs), were mapped into the ramie genome, and 22,343 (~ 73.0%) transcripts, 50,154 (~ 89.7%) SNPs, and 1466 (~ 80.3%) SSRs were assigned to a specific location in the corresponding chromosome. CONCLUSION: This is the first study to characterize the ramie transcriptome by long-read sequencing, and the substantial number of transcripts of significant length obtained will accelerate our understanding of ramie growth and development. This integration of genome sequences, expressed transcripts, and genetic markers will provide an extremely useful resource for genetic, molecular, and breeding studies of ramie.