Exploring the role of the built environment and psychosocial mediators on knee function in knee osteoarthritis patients in Singapore: a cross-sectional study.

OBJECTIVES: (1) To examine if a more accessible built environment (BE) is significantly associated with better knee function outcomes in knee osteoarthritis (OA) patients. (2) To assess if the relationship between BE and knee function is mediated by fear of movement and self-efficacy. DESIGN: Cross-sectional study. SETTING: Two tertiary hospitals in Singapore. PARTICIPANTS: 212 knee OA patients (mean: 63.81±8.27 years old), majority female (69.8%). INCLUSION CRITERIA: (i) meets National Institute for Health and Care Excellence criteria for knee OA, (ii) independent community ambulant. EXCLUSION CRITERIA: (i) alternative diagnosis to knee OA, (ii) secondary osteoarthritis, (iii) severe medical and/or cognitive comorbidity impairing activities of daily living, (iv) previous knee arthroplasty, (v) wheelchair bound, or (vi) pregnant. PRIMARY AND SECONDARY OUTCOME MEASURES; STATISTICS: How self-efficacy (Arthritis Self-Efficacy Scale-8 (ASES-8)) and fear of movement (Brief Fear of Movement (BFOM)) mediates impact of overall BE (IPAQ-Environment module: Access to Destinations) and five item-specific domains of BE accessibility on knee function (Knee Injury and Osteoarthritis Outcome Score-12 (KOOS-12)). For variables significantly correlated with BE and KOOS-12 in bivariate Pearson correlation tests, mediation analysis was performed with confounders adjusted. RESULTS: Total BE (r=0.142, p=0.038) and accessibility to transit station (r=0.161, p=0.019) were positively correlated with KOOS-12. Structural barriers (r=-0.138, p=0.045) were negatively correlated with KOOS-12. ASES-8 was a significant mediator in the relationship between accessibility to transit station and KOOS-12 (coeff=0.87, 95% CI=(0.24, 1.69), p=0.005) and between total BE and KOOS-12 (coeff=0.25, 95% CI=(0.10, 0.45), p=0.004). BFOM was a marginally significant mediator between structural barriers and KOOS-12 (coeff=-0.36, 95% CI=(-0.86, -0.02); p=0.054). CONCLUSION: More accessible BE and lesser structural barriers in the BE are associated with better knee function. Self-efficacy mediates the relationship between overall BE accessibility and knee function. Fear of movement mediates the negative association between barriers in the BE and knee function.Applications include assessing BE barriers and psychosocial mediators in clinician consultations, developing multidisciplinary integrated care models and urban designers planning mobility friendly BEs. TRIAL REGISTRATION NUMBER: The study has been registered under clinicaltrials.gov registry (Identifier: NCT04942236).

Comparison of three-dimensional vs. two-dimensional assisted thoracoscopy for recurrent laryngeal nerve lymph nodes dissection in esophagectomy: a retrospective study.

BACKGROUND: This study aimed to explore the clinical value of 3D video-assisted thoracoscopic surgery in dissecting recurrent laryngeal nerve lymph nodes in patients undergoing minimally invasive esophagectomy. METHODS: A retrospective cohort study was conducted on 205 patients, including 120 males, who underwent esophagectomy from May 2018 to May 2020 in the Department of Thoracic Surgery at the Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University. Perioperative parameters, including intraoperative blood loss, operation time, the number of dissected recurrent laryngeal nerve lymph nodes, the incidence and degree of postoperative recurrent laryngeal nerve injury, the volume of postoperative thoracic drainage, and postoperative complications, were compared between the 3D and 2D groups. RESULTS: There were no significant differences in the preoperative baseline data between these two groups (P > 0.05). The number of dissected recurrent laryngeal nerve lymph nodes in the 3D group was significantly higher than in the 2D group (P < 0.05). The operation times were significantly shorter in the 3D group than in the 2D group (P < 0.05). The volume of thoracic drainage in the first 2 days was significantly less in the 3D group than in the 2D group (P < 0.05). CONCLUSIONS: Compared to the 2D system, the application of 3D video-assisted thoracoscopic surgery in minimally invasive esophagectomy can increase the number of dissected recurrent laryngeal nerve lymph nodes and ensure safety. Additionally, it can reduce the duration of the operation, decrease early postoperative thoracic drainage volume, and promote patient recovery.

Efficacy and Safety of Hepatic Arterial Infusion Chemotherapy(HAIC) Combined with PD-1 Inhibitors for Advanced Hepatocellular Carcinoma with Macrovascular Invasion: A Multicenter Propensity Score Matching Analysis.

Aim: To investigate the efficacy and safety of HAIC combined with programmed cell death protein-1 (PD1) inhibitors in MVI-positive advanced hepatocellular carcinoma(HCC). Methods: From September 2017 to May 2019, we retrospectively collected the clinical data from three medical centers in China pertaining to patients diagnosed with BCLC C stage HCC with MVI and receiving treatment with a combination of HAIC and PD-1 inhibitors treatment or HAIC alone, and we compared the efficacy of HAIC combined with PD-1 inhibitors and HAIC monotherapy. Propensity score matching(PSM) was utilized to adjust for baseline differences between groups. Survival outcomes and tumor response rate were used to assess survival benefits, while the incidence of adverse events was used to evaluate safety. Results: After screening for eligibility, 489 patients diagnosed with HCC and concomitant MVI were enrolled. Of these, 173 patients received treatment combining HAIC with PD-1 inhibitors, while 316 patients underwent HAIC monotherapy. After PSM adjustment, the combination therapy group demonstrate superior survival outcomes. Median overall survival(OS) and progression free survival(PFS) were 31.8 months and 10.8 months, respectively, significantly higher than those in the monotherapy group (OS: 10.0 months; PFS: 6.1 months; both P<0.0001). Moreover, ORR and DCR remained significantly elevated in the combination therapy group (ORR: 44.3% vs 20.4%, P<0.0001; DCR: 89.8% vs 82.0%, P=0.041). Safety profiles indicated no significant differences in adverse event rates between the two treatment groups, encompassing both overall and grade-specific assessments. Conclusion: Compared to HAIC alone, the combination of HAIC with PD-1 inhibitors represents a more promising and effective approach for patients with HCC complicated by macrovascular invasion.

Perceptions and experiences of a multi-domain preventive health programme: a qualitative study informing future community-based health interventions in singapore.

BACKGROUND: Despite global popularity, Community-based Health Intervention (CBHI) programmes have yet to be fully incorporated into Singapore's public healthcare systems, with most initiatives focusing on specific diseases. This qualitative study aimed to evaluate older adults' perceptions of the "Get Well, Live Well" multi-domain preventive health programme, explore the effectiveness of Community Health Workers (CHWs) in promoting health literacy and modifying health behaviours, and examine participants' experiences in the CHW-delivered CBHI programme. METHODS: Purposeful sampling was used to recruit study subjects from participants in the "Get Well, Live Well" programme until data saturation was achieved. In-depth, semi-structured, one-to-one telephone interviews were conducted in English or Chinese with participants aged ≥ 40 years. Audio recordings were translated into English as needed and transcribed in full. The collected data were anonymised, and thematic analysis was performed by three trained evaluators using a structured process. RESULTS: The final study sample included 19 subjects (median age of 64 years; 84% women; and 95% Chinese). Three key themes emerged regarding the programme's value, interactions with CHW, also known as Care Connectors, and their facilitation of health services/behaviours. Participants acknowledged that the "Get Well, Live Well" programme provided physical/emotional support, improved health literacy, and enhanced social interaction. The programme's effectiveness may depend on Care Connector's personal qualities, service quality beyond expectation, connection with participants, and their proactive and authoritative roles in facilitating health services/behaviours. CONCLUSION: The findings suggest that future Community-based Health Interventions could benefit from deploying CHWs with strong people skills to enhance the programme's success.

Preclinical characterization of a water-soluble low-impact ampakine prodrug, CX1942 and its active moiety, CX1763.

Aim: AMPA-glutamate receptor (AMPAR) dysfunction mediates multiple neurological/neuropsychiatric disorders. Ampakines bind AMPARs and allosterically enhance glutamate-elicited currents. This report describes the activity of the water-soluble ampakine CX1942 prodrug and the active moiety CX1763.Results: CX1763 and CX1942 enhance synaptic transmission in hippocampi of rats. CX1763 increases attention in the 5CSRTT in rats and reduces amphetamine-induced hyperactivity in mice. CX1942 potently reverses opioid-induced respiratory depression in rats. CX1942/CX1763 was effective at 2.5-10 mg/kg. CX1763 lacked epileptogenicity up to 1500 mg/kg in rats.Conclusion: These data document that CX1942 and CX1763 are active and without prominent side effects in multiple pre-clinical assays. CX1942 could serve as a prodrug for CX1763 with the advantage of high water solubility as in an intravenous formulation.

[Box: see text].

Developing large language models to detect adverse drug events in posts on x.

Adverse drug events (ADEs) are one of the major causes of hospital admissions and are associated with increased morbidity and mortality. Post-marketing ADE identification is one of the most important phases of drug safety surveillance. Traditionally, data sources for post-marketing surveillance mainly come from spontaneous reporting system such as the Food and Drug Administration Adverse Event Reporting System (FAERS). Social media data such as posts on X (formerly Twitter) contain rich patient and medication information and could potentially accelerate drug surveillance research. However, ADE information in social media data is usually locked in the text, making it difficult to be employed by traditional statistical approaches. In recent years, large language models (LLMs) have shown promise in many natural language processing tasks. In this study, we developed several LLMs to perform ADE classification on X data. We fine-tuned various LLMs including BERT-base, Bio_ClinicalBERT, RoBERTa, and RoBERTa-large. We also experimented ChatGPT few-shot prompting and ChatGPT fine-tuned on the whole training data. We then evaluated the model performance based on sensitivity, specificity, negative predictive value, positive predictive value, accuracy, F1-measure, and area under the ROC curve. Our results showed that RoBERTa-large achieved the best F1-measure (0.8) among all models followed by ChatGPT fine-tuned model with F1-measure of 0.75. Our feature importance analysis based on 1200 random samples and RoBERTa-Large showed the most important features are as follows: "withdrawals"/"withdrawal", "dry", "dealing", "mouth", and "paralysis". The good model performance and clinically relevant features show the potential of LLMs in augmenting ADE detection for post-marketing drug safety surveillance.

Genome-Wide Mapping of RNA-Protein Associations via Sequencing.

RNA-protein interactions are crucial for regulating gene expression and cellular functions, with their dysregulation potentially impacting disease progression. Systematically mapping these interactions is resource-intensive due to the vast number of potential RNA and protein interactions. Here, we introduce PRIM-seq (Protein-RNA Interaction Mapping by sequencing), a method for the concurrent de novo identification of RNA-binding proteins (RBPs) and the elucidation of their associated RNAs. PRIM-seq works by converting each RNA-protein pair into a unique chimeric DNA sequence, which is then decoded through DNA sequencing. Applied to two human cell types, PRIM-seq generated a comprehensive human RNA-protein association network (HuRPA), consisting of more than 350,000 RNA-proteins pairs involving approximately 7,000 RNAs and 11,000 proteins. The data revealed an enrichment of previously reported RBPs and RNA-protein interactions within HuRPA. We also identified LINC00339 as a protein-associating non-coding RNA and PHGDH as an RNA-associating protein. Notably, PHGDH interacts with BECN1 and ATF4 mRNAs, suppressing their protein expression and consequently inhibiting autophagy, apoptosis, and neurite outgrowth while promoting cell proliferation. PRIM-seq offers a powerful tool for discovering RBPs and RNA-protein associations, contributing to more comprehensive functional genome annotations.

High Impact AMPAkines Induce a Gq-Protein Coupled Endoplasmic Calcium Release in Cortical Neurons: A Possible Mechanism for Explaining the Toxicity of High Impact AMPAkines.

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) positive allosteric modulators (AMPAkines) have a multitude of promising therapeutic properties. The pharmaceutical development of high impact AMPAkines has, however, been limited by the appearance of calcium-dependent neuronal toxicity and convulsions in vivo. Such toxicity is not observed at exceptionally high concentrations of low impact AMPAkines. Because most AMPAR are somewhat impermeable to calcium, the current study sought to examine the extent to which different mechanisms contribute to the rise in intracellular calcium in the presence of high impact ampakines. In the presence of AMPA alone, cytosolic calcium elevation is shown to be sodium-dependent. In the presence of high impact AMPAkines such as cyclothiazide (CTZ) or CX614, however, AMPAR potentiation also activates an additional mechanism that induces calcium release from endoplasmic reticular (ER) stores. The pathway that connects AMPAR to the ER system involves a Gq-protein, phospholipase Cß-mediated inositol triphosphate (InsP3) formation, and ultimately stimulation of InsP3-receptors located on the ER. The same linkage was not observed using high concentrations of the low impact AMPAkines, CX516 (Ampalex), and CX717. We also demonstrate that CX614 produces neuronal hyper-excitability at therapeutic doses, whereas the newer generation low impact AMPAkine CX1739 is safe at exceedingly high doses. Although earlier studies have demonstrated a functional linkage between AMPAR and G-proteins, this report demonstrates that in the presence of high impact AMPAkines, AMPAR also couple to a Gq-protein, which triggers a secondary calcium release from the ER and provides insight into the disparate actions of high and low impact AMPAkines.

Palladium-Catalyzed Branch-Selective Allylic C-H Amination Enabled by Nucleophile Coordination.

Regiochemical control is a central subject in the field of synthetic chemistry. Here we unveil an innovative approach for the branch-selective allylic C-H amination of α-alkenes with amine nucleophiles facilitated by phosphoramidite-palladium catalysis. A diverse array of α-alkenes has been effectively utilized to produce a variety of structurally distinct allylamines with moderate to excellent regioselectivity. Furthermore, the asymmetric version of this reaction is feasible through the use of chiral phosphoramidite ligands, albeit with currently modest enantioselectivity.

Polyetheretherketone split post and core for restoration of multirooted molar with insufficient dental tissue remnants by digital techniques: a case report and 3-year follow up.

BACKGROUND: Multi-rooted teeth with extensive dental defects often face challenges in stability and biomechanical failure. High-performance polymer PEEK materials, with properties closer to dentin, show promise in reducing stress concentration and preserving tooth structure. This report aimed to explore the use of a highly retentive polyetheretherketone (PEEK) for manufacturing custom-made split post and core for the restoration of grossly destroyed endodontically treated molars. CLINICAL CONSIDERATIONS: A 40-year-old female patient presented with complaints of loss of tooth substance in the posterior mandibular tooth. This case involved the digital design and fabrication of PEEK split post and core to restore multirooted molar with insufficient dental tissue remnants. The restorations were evaluated over a 3-year follow-up using the World Federation criteria (FDI). The restoration was clinically evaluated through intraoral examination, radiographic assessment, and subjective patient satisfaction, and was deemed clinically good according to FDI criteria. CONCLUSION: The outstanding mechanical properties of PEEK, coupled with the structure of the split post, provide an effective treatment option for weakened multirooted teeth. Simultaneously, the restoration configuration effectively addressed the challenge of varying postinsertion directions, and the interlocking mechanism between the primary and auxiliary posts enhanced the stability of the post and core.

Giant viruses as reservoirs of antibiotic resistance genes.

Nucleocytoplasmic large DNA viruses (NCLDVs; also called giant viruses), constituting the phylum Nucleocytoviricota, can infect a wide range of eukaryotes and exchange genetic material with not only their hosts but also prokaryotes and phages. A few NCLDVs were reported to encode genes conferring resistance to beta­lactam, trimethoprim, or pyrimethamine, suggesting that they are potential vehicles for the transmission of antibiotic resistance genes (ARGs) in the biome. However, the incidence of ARGs across the phylum Nucleocytoviricota, their evolutionary characteristics, their dissemination potential, and their association with virulence factors remain unexplored. Here, we systematically investigated ARGs of 1416 NCLDV genomes including those of almost all currently available cultured isolates and high-quality metagenome-assembled genomes from diverse habitats across the globe. We reveal that 39.5% of them carry ARGs, which is approximately 37 times higher than that for phage genomes. A total of 12 ARG types are encoded by NCLDVs. Phylogenies of the three most abundant NCLDV-encoded ARGs hint that NCLDVs acquire ARGs from not only eukaryotes but also prokaryotes and phages. Two NCLDV-encoded trimethoprim resistance genes are demonstrated to confer trimethoprim resistance in Escherichia coli. The presence of ARGs in NCLDV genomes is significantly correlated with mobile genetic elements and virulence factors.

Relationship between serum iron, zinc, calcium, and HIF-1a-comparative analysis of 2 regions and 4 ethnic groups in China.

Background: Altitude illness has serious effects on individuals who are not adequately acclimatized to high-altitude areas and may even lead to death. However, the individualized mechanisms of onset and preventive measures are not fully elucidated at present, especially the relationship between altitude illness and elements, which requires further in-depth research. Methods: Fresh serum samples were collected from individuals who underwent health examinations at the two hospitals in Xining and Sanya between November 2021 and December 2021. The blood zinc (Zn), iron (Fe), and calcium (Ca) concentrations, as well as hypoxia-inducible factor 1-alpha (HIF-1α) concentrations, were measured. This study conducted effective sample size estimation, repeated experiments, and used GraphPad Prism 9.0 and IBM SPSS version 19.0 software for comparative analysis of differences in the expression of elements and HIF-1α among different ethnic groups, altitudes, and concentration groups. Linear regression and multiple linear regression were employed to explore the relationships among elements and their correlation with HIF-1α. Results: This study included a total of 400 participants. The results from the repeated measurements indicated that the consistency of the laboratory test results was satisfactory. In terms of altitude differences, except for Fe (p = 0.767), which did not show significant variance between low and high altitude regions, Zn, Ca, and HIF-1α elements all exhibited notable differences between these areas (p < 0.0001, p = 0.004, and p < 0.0001). When grouping by the concentrations of elements and HIF-1α, the results revealed significant variations in the distribution of zinc among different levels of iron and HIF-1α (p < 0.05). The outcomes of the linear regression analysis demonstrated that calcium and zinc, iron and HIF-1α, calcium and HIF-1α, and zinc and HIF-1α displayed substantial overall explanatory power across different subgroups (p < 0.05). Finally, the results of the multiple linear regression analysis indicated that within the high-altitude population, the Li ethnic group in Sanya, and the Han ethnic group in Sanya, the multiple linear regression model with HIF-1αas the dependent variable and elements as the independent variables exhibited noteworthy overall explanatory power (p < 0.05). Conclusion: The levels of typical elements and HIF-1α in the blood differ among various altitudes and ethnic groups, and these distinctions may be linked to the occurrence and progression of high-altitude illness.

Soil keystone viruses are regulators of ecosystem multifunctionality.

Ecosystem multifunctionality reflects the capacity of ecosystems to simultaneously maintain multiple functions which are essential bases for human sustainable development. Whereas viruses are a major component of the soil microbiome that drive ecosystem functions across biomes, the relationships between soil viral diversity and ecosystem multifunctionality remain under-studied. To address this critical knowledge gap, we employed a combination of amplicon and metagenomic sequencing to assess prokaryotic, fungal and viral diversity, and to link viruses to putative hosts. We described the features of viruses and their potential hosts in 154 soil samples from 29 farmlands and 25 forests distributed across China. Although 4,460 and 5,207 viral populations (vOTUs) were found in the farmlands and forests respectively, the diversity of specific vOTUs rather than overall soil viral diversity was positively correlated with ecosystem multifunctionality in both ecosystem types. Furthermore, the diversity of these keystone vOTUs, despite being 10-100 times lower than prokaryotic or fungal diversity, was a better predictor of ecosystem multifunctionality and more strongly associated with the relative abundances of prokaryotic genes related to soil nutrient cycling. Gemmatimonadota and Actinobacteria dominated the host community of soil keystone viruses in the farmlands and forests respectively, but were either absent or showed a significantly lower relative abundance in that of soil non-keystone viruses. These findings provide novel insights into the regulators of ecosystem multifunctionality and have important implications for the management of ecosystem functioning.

IARS2 mutations lead to Leigh syndrome with a combined oxidative phosphorylation deficiency.

BACKGROUND: Leigh syndrome (LS) is a common mitochondrial disease caused by mutations in both mitochondrial and nuclear genes. Isoleucyl-tRNA synthetase 2 (IARS2) encodes mitochondrial isoleucine-tRNA synthetase, and variants in IARS2 have been reported to cause LS. However, the pathogenic mechanism of IARS2 variants is still unclear. METHODS: Two unrelated patients, a 4-year-old boy and a 5-year-old boy diagnosed with LS, were recruited, and detailed clinical data were collected. The DNA of the patients and their parents was isolated from the peripheral blood for the identification of pathogenic variants using next-generation sequencing and Sanger sequencing. The ClustalW program, allele frequency analysis databases (gnomAD and ExAc), and pathogenicity prediction databases (Clinvar, Mutation Taster and PolyPhen2) were used to predict the conservation and pathogenicity of the variants. The gene expression level, oxygen consumption rate (OCR), respiratory chain complex activity, cellular adenosine triphosphate (ATP) production, mitochondrial membrane potential (MMP) and mitochondrial reactive oxygen species (ROS) levels were measured in patient-derived lymphocytes and IARS2-knockdown HEK293T cells to evaluate the pathogenicity of the variants. RESULTS: We reported 2 unrelated Chinese patients manifested with LS who carried biallelic IARS2 variants (c.1_390del and c.2450G > A from a 4-year-old boy, and c.2090G > A and c.2122G > A from a 5-year-old boy), of which c.1_390del and c.2090G > A were novel. Functional studies revealed that the patient-derived lymphocytes carrying c.1_390del and c.2450G > A variants exhibited impaired mitochondrial function due to severe mitochondrial complexes I and III deficiencies, which was also found in IARS2-knockdown HEK293T cells. The compensatory experiments in vitro cell models confirmed the pathogenicity of IARS2 variants since re-expression of wild-type IARS2 rather than mutant IARS2 could rescue complexes I and III deficiency, oxygen consumption, and cellular ATP content in IARS2 knockdown cells. CONCLUSION: Our results not only expand the gene mutation spectrum of LS, but also reveal for the first time the pathogenic mechanism of IARS2 variants due to a combined deficiency of mitochondrial complexes I and III, which is helpful for the clinical diagnosis of IARS2 mutation-related diseases.

Deep Eutectic Solvent-Assisted Corrosion Boosting Bulk FeCoNiCrMo High-Entropy Alloys as Highly Efficient Oxygen Evolution Reaction Catalyst.

The key to enhancing water electrolysis efficiency lies in selecting highly efficient catalysts. Currently, high-entropy alloys (HEAs) are utilized in electrocatalysis applications owing to their diverse elemental composition, disordered elemental distribution, and the high solubility of each element, endowing them with excellent catalytic performance. The experiments were conducted using isoatomic FeNiCrMo HEA as a precursor, with a high-activity three-dimensional nanoporous structure rapidly synthesized via electrochemical one-step dealloying in a choline chloride-thiourea (ChCl-TU) deep eutectic solvent (DES). The results indicate that the dealloyed Fe20Co20Ni20Cr20Mo20 HEA mainly consists of two phases: face-centered cubic and σ phases. The imbalance in the distribution of elements in these two phases leads to quite different corrosion speeds with the FCC phase being preferentially corroded. Furthermore, synergistic electron coupling between surface atoms in the three-dimensional nanoporous structure strengthens the behavior of the oxygen evolution reaction (OER). At a current density of 40 mA cm-2, the overpotential after dealloying decreased to 370 mV, demonstrating excellent stability. The technique demonstrated in this work provides a novel approach to improve the catalytic activity of OER.

Comparison of the efficacy and safety of MAKO robot-assisted total knee arthroplasty versus conventional manual total knee arthroplasty in uncomplicated unilateral total knee arthroplasty a single-centre retrospective analysis.

PURPOSE: To compare the efficacy and safety of MAKO robot-assisted total knee arthroplasty (MA-TKA) with conventional manual total knee arthroplasty (CM-TKA) in patients with end-stage knee osteoarthritis (KOA) during the early postoperative period. METHOD: A retrospective analysis was conducted on 22 patients with KOA who underwent MA-TKA and 26 patients who underwent CM-TKA from April 2023 to July 2023. Hip-knee-ankle angle (HKA), lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), American Knee Society Score (AKSS), Forgotten Joint Score-12 (FJS-12), visual analogue scale (VAS), and postoperative complications were recorded and compared between the two groups. RESULT: Both groups successfully completed the surgeries. In terms of radiographic parameters, postoperative one month LDFA and HKA in the MA-TKA group were significantly lower than those in the CM-TKA group (P < 0.05). At the one month follow-up, 19 patients (86.4%) in the MA-TKA group had an HKA less than 3°, compared to 20 patients (76.9%) in the CM-TKA group. Clinically, VAS scores at 24 h, 48 h, and 72 h postoperatively were lower in the MA-TKA group both at rest and during activity. At one month and three months postoperatively, AKSS Function Scores and FJS-12 scores in the MA-TKA group were significantly higher than those in the CM-TKA group (P < 0.05). Regarding postoperative complications, no complications occurred in the MA-TKA group, while one patient in the CM-TKA group experienced postoperative knee stiffness, which resolved after physical therapy, with no statistically significant difference (P > 0.05). CONCLUSION: Compared with conventional manual total knee arthroplasty, MAKO robot-assisted TKA demonstrates better short-term clinical efficacy, achieves better alignment planning, and maintains good safety.

Anthropogenic-driven changes in concentrations and sources of winter volatile organic compounds in an urban environment in the Yangtze River Delta of China between 2013 and 2021.

Volatile organic compounds (VOCs) serve as crucial precursors to surface ozone and secondary organic aerosols (SOA). In response to severe air pollution challenges, China has implemented key air quality control policies from 2013 to 2021. Despite these efforts, a comprehensive understanding of the chemical composition and sources of urban atmospheric VOCs and their responses to emission reduction measures remains limited. Our study focuses on analyzing VOCs composition and concentrations during the winters of 2013 and 2021 through online field observations in urban Nanjing, a typical city in the Yangtze River Delta region of China. Using a machine learning approach, we found a notable reduction in total VOCs concentration from 52.4 ± 30.4 ppb to 33.9 ± 21.6 ppb between the two years, with dominant contributions (approximately 94.3 %) associated with anthropogenic emission control. Furthermore, alkanes emerged as the major contributors (48.6 %) to such anthropogenic-driven decline. The total SOA formation potential decreased by approximately 27.4 %, with aromatics identified as the major contributing species. Positive matrix factorization analysis identified six sources. In 2013, prominent contributors were solid fuel combustion (43.6 %), vehicle emission (16.7 %), and paint and solvent use (12.8 %). By 2021, major sources shifted to solid fuel combustion (31.9 %), liquefied petroleum gas and natural gas (26.8 %), and vehicle emission (25.5 %). Solid fuel combustion emerged as the primary driver for total VOCs reduction. The lifetime carcinogenic risk in 2021 decreased by 72.6 % relative to 2013, emphasizing the need to address liquefied petroleum gas and natural gas source, and vehicle emissions for improved human health. Our findings contribute critical insights for policymakers working on effective air quality management.

A machine learning case study to predict rare clinical event of interest: imbalanced data, interpretability, and practical considerations.

Accurate prediction of a rare and clinically important event following study treatment has been crucial in drug development. For instance, the rarity of an adverse event is often commensurate with the seriousness of medical consequences, and delayed detection of the rare adverse event can pose significant or even life-threatening health risks to patients. In this machine learning case study, we demonstrate with an example originated from a real clinical trial setting how to define and solve the rare clinical event prediction problem using machine learning in pharmaceutical industry. The unique contributions of this work include the proposal of a six-step investigation framework that facilitates the communication with non-technical stakeholders and the interpretation of the model performance in terms of practical consequences in the context of patient screenings for conducting a future clinical trial. In terms of machine learning methodology, for data splitting into the training and test sets, we adapt the rare-event stratified split approach (from scikit-learn) to further account for group splitting for multiple records of a patient simultaneously. To handle imbalanced data due to rare events in model training, the cost-sensitive learning approach is employed to give more weights to the minor class and the metrics precision together with recall are used to capture prediction performance instead of the raw accuracy rate. Finally, we demonstrate how to apply the state-of-the-art SHAP values to identify important risk factors to improve model interpretability.

Fully integrated additive manufacturing of an obturator prosthesis for an edentulous patient with a maxillectomy defect.

Maxillary defects pose challenges for prosthodontists, especially when patients have no remaining teeth. This clinical report describes rehabilitation with a complete denture obturator fabricated in 2 visits for an edentulous patient after a maxillectomy. The obturator base and artificial teeth were digitally designed and merged into a 1-piece prosthesis. Following a virtual reduction, the integrated prosthesis and a gingival veneer were calculated and then printed and bonded together to complete the fabrication. Balanced occlusion was achieved with the assistance of a digital occlusion analyzer at the insertion visit. This approach avoided base-tooth assembly deviations and provided a prosthesis with good patient-reported outcomes at the 6-month follow-up.