Exploring new technologies for the future generation: exploration-exploitation trade-off in an intergenerational framework.

Decision making on exploring or exploiting technology was studied by means of a laboratory experiment with a two-generation framework. In this framework, the design of a virtual tool is transmitted from the first to second generation, and hence, the former can help the latter by frequently exploring better tool designs but at the cost of reduced opportunities to exploit the existing tool to increase its own benefits. We set two experimental conditions ('repaid' and 'unrepaid') as well as a control condition (asocial), in which the second generation is absent. In the 'repaid' experimental condition, participants received an extra payment proportional to the score gained by the second generation, such that they were monetarily incentivized to help the second generation. Such an incentive was not given in the 'unrepaid' condition. An analysis of a formal model and computer simulations predicted that rational participants should increase investment in exploration only in the repaid condition when compared with the asocial control. The prediction was confirmed by the results of the experiment. These findings together suggest that humans may not have a propensity to invest in costly exploration of new technologies solely to help future generations.

Comparison of Postoperative Complications and Outcomes in Anterior Cervical Spine Surgery: Ossification of the Posterior Longitudinal Ligament Versus Cervical Spondylotic Myelopathy.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To compare the frequency of complications and outcomes between patients with ossification of the posterior longitudinal ligament (OPLL) of the cervical spine and those with cervical spondylotic myelopathy (CSM) who underwent anterior surgery. SUMMARY OF BACKGROUND DATA: Anterior cervical spine surgery for OPLL is an effective surgical procedure; however, it is complex and technically demanding compared with the procedure for CSM. Few reports have compared postoperative complications and clinical outcomes after anterior surgeries between the 2 pathologies. METHODS: Among 1434 patients who underwent anterior cervical spine surgery at 3 spine centers within the same spine research group from January 2011 to March 2021, 333 patients with OPLL and 488 patients with CSM were retrospectively evaluated. Demographics, postoperative complications, and outcomes were reviewed by analyzing medical records. In-hospital and postdischarge postoperative complications were investigated. Postoperative outcomes were evaluated 1 year after the surgery using the Japanese Orthopaedic Association score. RESULTS: Patients with OPLL had more comorbid diabetes mellitus preoperatively than patients with CSM ( P <0.001). Anterior cervical corpectomies were more often performed in patients with OPLL than in those with CSM (73.3% and 14.5%). In-hospital complications, such as reoperation, cerebrospinal fluid leak, C5 palsy, graft complications, hoarseness, and upper airway complications, occurred significantly more often in patients with OPLL. Complications after discharge, such as complications of the graft bone/cage and hoarseness, were significantly more common in patients with OPLL. The recovery rate of the Japanese Orthopaedic Association score 1 year postoperatively was similar between patients with OPLL and those with CSM. CONCLUSION: The present study demonstrated that complications, both in-hospital and after discharge following anterior spine surgery, occurred more frequently in patients with OPLL than in those with CSM.

Brain atrophy in normal older adult links tooth loss and diet changes to future cognitive decline.

Several studies have found associations between poor oral health, particularly tooth loss and cognitive decline. However, the specific brain regions affected by tooth loss and the probable causes remain unclear. We conducted a population-based longitudinal cohort study in Nakajima, Nanao City, Japan. Between 2016 and 2018, 2454 residents aged ≥60 participated, covering 92.9% of the local age demographics. This study used comprehensive approach by combining detailed dental examinations, dietary assessments, magnetic resonance imaging (MRI) analysis, and cognitive evaluations. Tooth loss, even in cognitively normal individuals, is associated with parahippocampal gyrus atrophy and increased WMH volume, both of which are characteristics of dementia. Tooth loss was associated with altered dietary patterns, notably a reduction in plant-based food intake and an increase in fatty, processed food intake. This study highlights a possible preventative pathway where oral health may play a significant role in preventing the early neuropathological shifts associated with dementia.

Factors promoting research activities among Japanese pharmacists: a questionnaire survey.

Pharmacists are expected to demonstrate their expertise in clinical practice and conduct research activities to generate new evidence. However, the factors promoting research activities among pharmacists remain unclear. Therefore, we investigated the research activities of Japanese pharmacists through a questionnaire survey and examined the factors contributing to the promotion of research activities. A web-based questionnaire using Google Forms was disseminated across pharmacists working in community pharmacies, drugstores, hospitals, and clinics. The questionnaire included respondents' backgrounds, research activities, and research environments. Logistic regression analysis was used to examine the factors promoting pharmacists' research activities, with experience in research paper acceptance as the objective variable. In total, 401 responses were included in the analysis. Of the respondents, 54.1% were hospital pharmacists, and 77.1% were pharmacists with > 5 years of pharmacist experience. Furthermore, 50.4% of the pharmacists had presented at conferences, and 22.2% had experience in research paper acceptance. The influential factors were "master's degree or higher," "number of affiliated academic societies," "acquisition of specialists/certified pharmacists," and "daily availability of a consultant for writing research papers." This study revealed the factors contributing to the promotion of research activities among pharmacists. We believe that our findings will help promote research among pharmacists.

Denosumab-induced hypocalcemia in patients with solid tumors and renal dysfunction: a multicenter, retrospective, observational study.

BACKGROUND: Bone metastases are frequently observed in advanced cancer, and bone modifying agents are used to prevent or treat skeletal-related events. Zoledronic acid is contraindicated in patients with severe renal impairment (Ccr < 30 mL/min), but it is not completely known whether denosumab can be used in them. We aimed to determine the association between renal function and hypocalcemia development during denosumab treatment. METHODS: We included patients with solid cancer and bone metastases who started denosumab treatment between April 2017 and March 2019. They were classified into four groups based on creatinine clearance (Ccr; mL/min): normal (Ccr ≥ 80), mild (50 ≤ Ccr ˂80), moderate (30 ≤ Ccr ˂50), and severe (Ccr ˂30). Hypocalcemia was evaluated using the Common Terminology Criteria for Adverse Events (v5.0) based on the albumin-adjusted serum calcium levels; its incidence (stratified by renal function) and risk factors were investigated using a Chi-square test and logistic regression analysis. RESULTS: Of 524 patients (age: 69 ± 11 years; 303 men), 153 had a normal renal function and 222, 117, and 32 had mild, moderate, and severe renal dysfunction. The albumin-adjusted serum calcium level was higher than the measured (total) calcium level in most patients. The incidence of grade ≥ 1 hypocalcemia was 32.0% in the normal group and 37.4%, 29.9%, and 62.5% in the mild, moderate, and severe renal dysfunction groups, respectively. It was, therefore, higher in the severe renal dysfunction groups than in the normal group (P = 0.002). The incidence of grade ≥ 3 hypocalcemia did not differ significantly among the groups. Pre-treatment low serum calcium levels and severe renal dysfunction were risk factors for hypocalcemia. CONCLUSIONS: Evaluating denosumab-induced hypocalcemia required albumin adjustment, and its incidence was high among patients with severe renal dysfunction. Reduced serum calcium levels and severely impaired renal function were associated with an elevated hypocalcemia risk.

Characteristics of deceased subjects transported to a postmortem imaging center due to unusual death related to epilepsy.

OBJECTIVE: Patients with epilepsy have high risk of experiencing uncommon causes of death. This study aimed to evaluate patients who underwent unusual deaths related to epilepsy and identify factors that may contribute to these deaths and may also include sudden unexpected death in epilepsy (SUDEP). METHODS: We analyzed 5291 cases in which a postmortem imaging (PMI) study was performed using plane CT, because of an unexplained death. A rapid troponin T assay was performed using peripheral blood samples. Clinical information including the cause of death suspected by the attending physician, body position, place of death, medical history, and antiseizure medications was evaluated. RESULTS: A total of 132 (2.6%) patients had an obvious history of epilepsy, while 5159 individuals had no history of epilepsy (97.4%). Cerebrovascular disease was the cause of death in 1.6% of patients in the group with epilepsy, and this was significantly lower than that in the non-epilepsy group. However, drowning was significantly higher (9.1% vs. 4.4%). Unspecified cause of death was significantly more frequent in the epilepsy group (78.0% vs. 57.8%). Furthermore, the proportion of patients who demonstrated elevation of troponin T levels without prior cardiac disease was significantly higher in the epilepsy group (37.9% vs. 31.1%). At discovery of death, prone position was dominant (30.3%), with deaths occurring most commonly in the bedroom (49.2%). No antiseizure medication had been prescribed in 12% of cases, while 29.5% of patients were taking multiple antiseizure medications. SIGNIFICANCE: The prevalence of epilepsy in individuals experiencing unusual death was higher than in the general population. Despite PMI studies, no definitive cause of death was identified in a significant proportion of cases. The high troponin T levels may be explained by long intervals between death and examination or by higher incidence of myocardial damage at the time of death. PLAIN LANGUAGE SUMMARY: This study investigated unusual deaths in epilepsy patients, analyzing 5291 postmortem imaging cases. The results showed that 132 cases (2.6%) had a clear history of epilepsy. In these cases, only 22% cases were explained after postmortem examination, which is less than in non-epilepsy group (42.2%). Cerebrovascular disease was less common in the epilepsy group, while drowning was more common. Elevated troponin T levels, which suggest possibility of myocardial damage or long intervals between death and examination, were also more frequent in the epilepsy group compared to non-epilepsy group.

Early mortality of emergency surgery for acute type A aortic dissection in octogenarians and nonagenarians: A multi-center retrospective study.

OBJECTIVES: The clinical data on postoperative mortality and central nervous system (CNS) complications in older adults who underwent acute type A aortic dissection are limited. Thus, in this study we aimed to evaluate the association between age and early postoperative mortality and occurrence of CNS complications. METHODS: This multicentric retrospective cohort study included 5 tertiary hospitals in Japan. All patients who underwent emergency surgery for acute type A aortic dissection between October 1998 and December 2019 were enrolled. The multilevel Cox proportional hazards model, which considered years as level 1, institutions as level 2, and surgeons as level 3, was used to evaluate the association between age and early postoperative hospital mortality and occurrence of CNS complications. RESULTS: Of the 1037 patients, 227 (21.9%) were ≥80 years old and 810 (78.1%) were <80 years old. Overall, 134 patients (12.9%) died within 30 days postoperatively; among them, 42/227 (18.5%) and 92/810 (11.4%) were aged ≥80 and <80 years, respectively (hazard ratio [HR], 1.63; P = .0046). CNS complications within 30 days postoperatively occurred in 140/1037 (13.5%) patients; among them, 42/227 (18.5%) and 98/810 (12.1%) were aged ≥80 and <80 years, respectively (HR, 1.63; P = .011). In multivariate analysis, age ≥80 years was associated with mortality within 30 days postoperatively (adjusted HR, 2.37; 95% CI, 1.23-4.57; P = .01) but not with CNS complications (adjusted HR, 1.58; 95% CI, 0.93-2.69; P = .091). CONCLUSIONS: The early postoperative mortality in older patients was approximately 50% higher than in the younger population. A thorough discussion regarding the surgical indications should be done.

Three-dimensional micro-X-ray topography using focused sheet-shaped X-ray beam.

X-ray topography is a powerful method for analyzing crystal defects and strain in crystalline materials non-destructively. However, conventional X-ray topography uses simple X-ray diffraction images, which means depth information on defects and dislocations cannot be obtained. We have therefor developed a novel three-dimensional micro-X-ray topography technique (3D µ-XRT) that combines Bragg-case section topography with focused sheet-shaped X-rays. The depth resolution of the 3D µ-XRT depends mainly on the focused X-ray beam size and enables non-destructive observation of internal defects and dislocations with an accuracy on the order of 1 µm. The demonstrative observation of SiC power device chips showed that stacking faults, threading screw, threading edge, and basal plane dislocations were clearly visualized three-dimensionally with a depth accuracy of 1.3 µm. 3D µ-XRT is a promising new approach for highly sensitive and non-destructive analysis of material crystallinity in a three-dimensional manner.

Regulation of Osteoblast to Osteocyte Differentiation by Cyclin-Dependent Kinase-1.

Osteocytes have recently been identified as a new regulator of bone remodeling, but the detailed mechanism of their differentiation from osteoblasts remains unclear. The purpose of this study is to identify cell cycle regulators involved in the differentiation of osteoblasts into osteocytes and determine their physiological significance. The study uses IDG-SW3 cells as a model for the differentiation from osteoblasts to osteocytes. Among the major cyclin-dependent kinases (Cdks), Cdk1 is most abundantly expressed in IDG-SW3 cells, and its expression is down-regulated during differentiation into osteocytes. Inhibition of CDK1 activity reduces IDG-SW3 cell proliferation and differentiation into osteocytes. Osteocyte and Osteoblast-specific Cdk1 knockout in mice (Dmp1-Cdk1KO ) results in trabecular bone loss. Pthlh expression increases during differentiation, but inhibiting CDK1 activity reduces Pthlh expression. Parathyroid hormone-related protein concentration is reduced in the bone marrow of Dmp1-Cdk1KO mice. Four weeks of Parathyroid hormone administration partially recovers the trabecular bone loss in Dmp1-Cdk1KO mice. These results demonstrate that Cdk1 plays an essential role in the differentiation from osteoblast to osteocyte and the acquisition and maintenance of bone mass. The findings contribute to a better understanding of the mechanisms of bone mass regulation and can help develop efficient therapeutic strategies for osteoporosis treatment.

[Effect of Landiolol for Atrial Fibrillation after Open Heart Surgery].

PURPOSE: Postoperative atrial fibrillation (POAF) after open heart surgery is common complication. POAF is reported to prolong hospital stay and increase long-term mortality, therefore prevention of POAF is important. It is widely known that beta blocker decrease POAF, and we had used oral beta blocker after open heart surgery. We examined the effect of intraoperative and postoperative administration of intravenous beta blocker( landiolol) for POAF. METHOD: We evaluated 291 consecutive patients who underwent open heart surgery from November 2016 to November 2018. Those who underwent open heart surgery after November 2017 were 145, and 100 of the patients( group A) had intraoperative and postoperative landiolol administration. Those who underwent open heart surgery before November 2017 were 146, and 100 of the patients (group B) did not have landiolol administration. The primary endpoint was incidence of POAF within 7 days after surgery. RESULT: There was no significant difference in preoperative character between the groups, other than the ratio of males to females( group A:54 males, 46 females;group B:68 males, 32 females;p<0.05). The incidences of POAF were 20% and 36% in group A and group B, respectively( p<0.05). CONCLUSION: Intraoperative and postoperative administration of landiolol is effective for preventing POAF after open heart surgery.

Augmented Reality Support for Anterior Decompression and Fusion Using Floating Method for Cervical Ossification of the Posterior Longitudinal Ligament.

Anterior decompression and fusion (ADF) using the floating method for cervical ossification of the posterior longitudinal ligament (OPLL) is an ideal surgical technique, but it has a specific risk of insufficient decompression caused by the impingement of residual ossification. Augmented reality (AR) support is a novel technology that enables the superimposition of images onto the view of a surgical field. AR technology was applied to ADF for cervical OPLL to facilitate intraoperative anatomical orientation and OPLL identification. In total, 14 patients with cervical OPLL underwent ADF with microscopic AR support. The outline of the OPLL and the bilateral vertebral arteries was marked after intraoperative CT, and the reconstructed 3D image data were transferred and linked to the microscope. The AR microscopic view enabled us to visualize the ossification outline, which could not be seen directly in the surgical field, and allowed sufficient decompression of the ossification. Neurological disturbances were improved in all patients. No cases of serious complications, such as major intraoperative bleeding or reoperation due to the postoperative impingement of the floating OPLL, were registered. To our knowledge, this is the first report of the introduction of microscopic AR into ADF using the floating method for cervical OPLL with favorable clinical results.

Prospective Comparative Study of Dysphagia after Subaxial Cervical Spine Surgery: Cervical Spondylotic Myelopathy and Posterior Longitudinal Ligament Ossification.

We prospectively investigated the postoperative dysphagia in cervical posterior longitudinal ligament ossification (C-OPLL) and cervical spondylotic myelopathy (CSM) to identify the risk factors of each disease and the incidence. A series of 55 cases with C-OPLL: 13 anterior decompression with fusion (ADF), 16 posterior decompression with fusion (PDF), and 26 laminoplasty (LAMP), and a series of 123 cases with CSM: 61 ADF, 5 PDF, and 57 LAMP, were included. Vertebral level, number of segments, approach, and with or without fusion, and pre and postoperative values of Bazaz dysphagia score, C2-7 lordotic angle (∠C2-7), cervical range of motion, O-C2 lordotic angle, cervical Japanese Orthopedic Association score, and visual analog scale for neck pain were investigated. New dysphagia was defined as an increase in the Bazaz dysphagia score by one grade or more than one year after surgery. New dysphagia occurred in 12 cases with C-OPLL; 6 with ADF (46.2%), 4 with PDF (25%), 2 with LAMP (7.7%), and in 19 cases with CSM; 15 with ADF (24.6%), 1 with PDF (20%), and 3 with LAMP (1.8%). There was no significant difference in the incidence between the two diseases. Multivariate analysis demonstrated that increased ∠C2-7 was a risk factor for both diseases.

Multifocal intraoral ductal ectasia with metaplasia and focal epithelial proliferation: A case report.

Ductal ectasia with metaplasia and focal epithelial proliferation in the oral cavity does not correspond to any existing salivary gland lesion. A 72-year-old man presented with a mass in the buccal mucosa, which was excised and initially diagnosed as a cystadenoma. An upper lip mass on the right side, which developed later, was also excised. The lesions were histologically similar, and since they were multifocal and in non-contiguous and independent sites with multiple dilated cystic structures that did not destroy the lobar architecture, the final diagnosis was confirmed as ductal ectasia with metaplasia and focal epithelial proliferation. This condition may mimic various neoplastic lesions.

Mutational analysis of DNMT3A improves the prognostic stratification of patients with acute myeloid leukemia.

Nucleophosmin1 (NPM1) mutations are the most frequently detected gene mutations in acute myeloid leukemia (AML) and are considered a favorable prognostic factor. We retrospectively analyzed the prognosis of 605 Japanese patients with de novo AML, including 174 patients with NPM1-mutated AML. Although patients with NPM1-mutated AML showed a high remission rate, this was not a favorable prognostic factor for overall survival (OS); this is contrary to generally accepted guidelines. Comprehensive gene mutation analysis showed that mutations in codon R882 of DNA methyltransferase 3A (DNMT3AR882 mutations) were a strong predicative factor indicating poor prognosis in all AML (p < 0.0001) and NPM1-mutated AML cases (p = 0.0020). Furthermore, multivariate analysis of all AML cases showed that DNMT3AR882 mutations and the co-occurrence of internal tandem duplication in FMS-like tyrosine kinase 3 (FLT3-ITD), NPM1 mutations, and DNMT3AR882 mutations (triple mutations) were independent factors predicting a poor prognosis related to OS, with NPM1 mutations being an independent factor for a favorable prognosis (hazard ratios: DNMT3AR882 mutations, 1.946; triple mutations, 1.992, NPM1 mutations, 0.548). Considering the effects of DNMT3AR882 mutations and triple mutations on prognosis and according to the classification of NPM1-mutated AML into three risk groups based on DNMT3AR882 /FLT3-ITD genotypes, we achieved the improved stratification of prognosis (p < 0.0001). We showed that DNMT3AR882 mutations are an independent factor for poor prognosis; moreover, when confounding factors that include DNMT3AR882 mutations were excluded, NPM1 mutations were a favorable prognostic factor. This revealed that ethnological prognostic discrepancies in NPM1 mutations might be corrected through prognostic stratification based on the DNMT3A status.

Risk factors for recurrence and regrowth of spinal schwannoma.

BACKGROUND: Spinal schwannoma recurs after initial surgery at a rate of 4%-6%, with known risk factors including subtotal resection, multilevel involvement, large tumor size, and malignant histopathology. This study examined risk factors for schwannoma recurrence and residual tumor regrowth. METHODS: Sixty-five patients who underwent resection of spinal schwannoma in our department between July 2010 and December 2018 and were followed up for more than 1 year were retrospectively analyzed for age, sex, follow-up duration, imaging and surgical data, recurrence, reoperation, and Japanese Orthopaedic Association scores before and 1 year after surgery. Patients with postoperative recurrence or residual tumor regrowth of >10% at the final visit (R+ group) were compared with patients without recurrence or regrowth (R- group). Multivariate logistic regression analysis was performed to analyze concurrent effects of risk factors on recurrence and regrowth. RESULTS: The 65 patients (mean age 52.4 years at surgery) had schwannomas involving cervical (n = 14), thoracic (n = 25), and lumbar (n = 26) spinal levels. Mean follow-up duration was 58 months. Location was intradural in 65%, extradural in 17%, and both intradural and extradural in 18%. There were 4 recurrences (6.2%), and the mean interval between surgery and recurrence was 18.8 months. Seven patients (10.8%) experienced regrowth. Comparing group R+ (n = 11) and group R- (n = 54), univariate analysis showed significant differences in Sridhar tumor classification, giant tumor (Sridhar classification II, IVb, and V), left-right and cranial-caudal tumor size, largest diameter, operative time, blood loss, subtotal resection, reoperation, fusion surgery, and follow-up duration. Multivariate logistic regression analysis revealed giant tumor (Sridhar classification types II, IVb, and V) as an independent risk factor for recurrence and regrowth. CONCLUSIONS: This retrospective review of 65 consecutive patients with spinal schwannoma in a single institution demonstrated that 16.9% had recurrence or regrowth, demonstrating that this potential risk should be kept in mind.

Evaluation and Prediction of Healing Morphology After Closed Reduction for Unilateral Mandibular Condyle Fractures.

Although closed reduction is common for condylar fractures, bone fragments may heal improperly. This study aimed to investigate the healing morphology of unilateral condylar fractures. We retrospectively investigated 70 patients with unilateral condylar fractures. Clinico-statistical analyses were performed on the whole-condylar fracture, closed reduction, and observation/functional therapy groups. Among these patients, 52 patients aged older than 16 years underwent closed reduction. The extent of maximum mouth opening, the incidence of malocclusion, and the relationship between healing morphology and Arbeitsgemeinschaft für Osteosynthesefragen classification or trismus were analyzed in the closed reduction group. There were significant differences in age ( P= 0.008) and sex ( P =0.025) between the closed reduction and observation/functional therapy groups. However, there were no significant differences in trauma etiologies and concomitant fractures between the 2 groups. The average maximum mouth opening extent for unilateral fractures after closed reduction was 42.6±6.1 mm. Only 1 case (2.1%) of post-treatment malocclusion was observed. In all the MacLennan classification of deviation or more, regardless of the classification, upper fractures (head and upper neck) tended to heal through a spherical ( P <0.001) morphology, whereas lower fractures (lower neck and subcondylar) tended to heal through an L-shaped and lateral fusion ( P <0.001). There was no significant difference in the incidence of trismus between the healing morphology of unchanged type and others ( P =0.690). Our results elucidated the etiology, dysfunction, and healing morphology classification of unilateral mandibular condyle fractures treated with closed reduction.

Simultaneous detection of JAK2, CALR, and MPL mutations and quantitation of JAK2 V617F allele burden in myeloproliferative neoplasms using the quenching probe-Tm method in i-densy IS-5320.

INTRODUCTION: Accurate detection of myeloproliferative neoplasms (MPN)-associated gene mutations is necessary to correctly diagnose MPN. However, conventional gene testing has various limitations, including the requirement of skilled technicians, cumbersome experimental procedures, and turnaround time of several days. The gene analyzer i-densy IS-5320 allows gene testing using the quenching probe-Tm method. Specifically, pretreatment of samples including DNA extraction, amplification and detection of genes, and analysis of results are performed in a fully automatic manner after samples and test reagents are added into this system, which is compact and can be easily installed in a laboratory. The aim of this study is to investigate the sensitivity and specificity associated with the simultaneous detection of MPN-associated gene mutations. METHODS: We conducted an analysis of MPN-associated genes using i-densy IS-5320. We analyzed 384 samples (171 JAK2 V617F mutations, 10 JAK2 exon12 mutations, 104 CALR mutations, and 26 MPL mutations) that had been examined using conventional approaches such as allele-specific polymerase chain reaction (PCR), droplet digital PCR, and the direct sequencing method. RESULTS: The detection accuracy of JAK2 V617F, JAK2 exon 12, CALR, and MPL was 100.0% (383/383), 99.7% (383/384), 100.0% (370/370), and 99.7% (377/378), respectively. There was a strong positive correlation between the JAK2 V617F allele burden measured using conventional methods and i-densy IS-5320 (r = .989). CONCLUSION: Overall, i-densy IS-5320 exhibited good accuracy in terms of analyzing MPN-associated genes; thus, it can serve as a replacement for conventional methods of MPN-associated gene testing.

Rheological Behavior and Dynamic Mechanical Properties for Interpretation of Layer Adhesion in FDM 3D Printing.

Commercial filaments of poly(lactic acid) (PLA) composites with particulate filler, carbon fiber, and copper powder with different contents were fabricated by FDM 3D printing in XZ-direction at bed temperatures of 45 °C and 60 °C. The effects of additives and bed temperatures on layer adhesion, fracture behavior, and mechanical performance of the PLA composites 3D printing were evaluated. Rheological properties informed viscous nature of all filaments and interface bonding in the PLA composites, which improved printability and dimensional stability of the 3D printing. Crystallinity of the PLA composites 3D printing increased with increasing bed temperature resulting in an improvement of storage modulus, tensile, and flexural properties. On the contrary, the ductility of the 3D printing was raised when printed at low bed temperature. Dynamic mechanical properties, the degree of entanglement, the adhesion factor, the effectiveness coefficient, the reinforcing efficiency factor, and the Cole-Cole analysis were used to understand the layer adhesion, and the interfacial interaction of the composites as compared to the compression molded sheets. SEM images revealed good adhesion between the additives and the PLA matrix. However, the additives induced faster solidification and showed larger voids in the 3D printing, which indicated lower layer adhesion as compared to neat PLA. It can be noted that the combination of the additives and the optimized 3D printing conditions would be obtain superior mechanical performance even layer adhesion has been restricted.

Differences in the stemness characteristics and molecular markers of distinct human oral tissue neural crest-derived multilineage cells.

OBJECTIVES: Although multilineage cells derived from oral tissues, especially the dental pulp, apical papilla, periodontal ligament, and oral mucosa, have neural crest-derived stem cell (NCSC)-like properties, the differences in the characteristics of these progenitor cell compartments remain unknown. The current study aimed to elucidate these differences. MATERIAL AND METHODS: Sphere-forming apical papilla-derived cells (APDCs), periodontal ligament-derived cells (PDLDCs), and oral mucosa stroma-derived cells (OMSDCs) from the same individuals were isolated from impacted developing teeth. All sphere-forming cells were characterized through biological analyses of stem cells. RESULTS: All sphere-forming cells expressed neural crest-related markers. The expression of certain tissue-specific markers such as CD24 and CD56 (NCAM1) differed among tissue-derived cells. Surprisingly, the expression of only CD24 and CD56 could be discriminated in human tissues. Although APDCs and PDLDCs exhibited greater mineralized cell differentiation than OMSDCs, they exhibited poorer differentiation into adipocytes in vitro. In immunocompromised mice, APDCs formed hard tissues better than PDLDCs and OMSDCs. CONCLUSIONS: Although cells with NCSC-like properties present the same phenotype, they differ in the expression of certain markers and differentiation abilities. This study is the first to demonstrate the differences in the differentiation ability and molecular markers among multilineage human APDCs, PDLDCs, and OMSDCs obtained from the same patients, and to identify tissue-specific markers that distinguish tissues in the developing stage of the human tooth with immature apex.

Foxf2 represses bone formation via Wnt2b/ß-catenin signaling.

Differentiation of mesenchymal stem cells (MSCs) into osteoblasts is a critical process for proper skeletal development and acquisition/maintenance of bone mass. However, since this regulatory mechanism has not yet been fully elucidated, the treatment of severe osteoporosis and fractures is a challenge. Here, through a comprehensive analysis of gene expression during the differentiation of MSCs into osteoblasts, we show that the forkhead transcription factor Foxf2 is a crucial regulator of this process. Foxf2 expression transiently increased during MSC osteoblastic differentiation. Overexpression of Foxf2 in MSCs inhibited osteoblastic differentiation, and conversely, knockdown of Foxf2 expression promoted this process. Osteoprogenitor-specific Foxf2 knockout mice developed a high bone mass phenotype due to increased bone formation. RNA-seq analysis and molecular experiments revealed that Foxf2 regulation of bone formation is mediated by Wnt2b. Knockdown of Foxf2 in mouse femurs enhanced bone regeneration in vivo. FOXF2 expression was correlated with hip bone mineral density in postmenopausal women with low bone mass. Finally, inhibition of FOXF2 promoted osteoblastic differentiation of human MSCs. This study uncovers a critical role of Foxf2 in the differentiation of MSCs into osteoblasts and provides insight into the pathogenesis associated with bone-related diseases such as osteoporosis and nonunion after fracture.