A case of intraductal papillary neoplasm of the bile duct suspected to be of peribiliary glands origin.

Peribiliary glands are complex lobular structures containing mucus and serous glands, distributed along the extrahepatic and intrahepatic bile ducts. In this report, we describe a case of intraductal papillary neoplasm of the bile duct suspected to be of peribiliary glands origin. The patient was an 80-year-old man who was referred to our hospital for a hepatic mass. On further examination, a 38 × 34 mm cystic lesion with papillary growth was found in S1/4. Because the lesion was extensively bordered by both hepatic ducts and the connection was unclear, it was difficult to determine the extent of hepatic resection. To confirm the location, a peroral cholangioscopy was performed. The connection with the cyst was detected in the right hepatic duct and a villous tumor mucosa protruded through the conduit lumen. Since we found that the lesion communicated with the right hepatic duct, a right hepatectomy was subsequently performed. The postoperative pathological diagnosis was an intraductal papillary neoplasm of the blie duct with associated invasive carcinoma. The postoperative course was good, and the patient experienced no recurrence.

Comprehensive analysis of microRNAs modulated by histone deacetylase inhibitors identifies microRNA-7-5p with anti-myeloma effect.

Basic research to expand treatment options for multiple myeloma is greatly needed due to the refractory nature of the disease. Histone deacetylase (HDAC) inhibitors, which are epigenetic regulators, are attractive but have limited applications. MicroRNAs (miRNAs), which are also epigenetic regulators, are important molecules that may lead to future therapeutic breakthroughs. In this study, we comprehensively searched for miRNAs that are altered by HDAC inhibitors in myeloma cells. We identified miR-7-5p (miR-7) as a miRNA downregulated by HDAC inhibitors. Transfection of myeloma cell lines with miR-7 suppressed cell proliferation, induced apoptosis, and enhanced the effects of the HDAC inhibitor panobinostat. Expression of miR-7 was downregulated by c-Myc inhibition, but upregulated by bortezomib. Comprehensive examination of miR-7 targets revealed four candidates: SLC6A9, LRRC59, EXOSC2, and PSME3. Among these, we focused on PSME3, an oncogene involved in proteasome capacity in myeloma cells. PSME3 knockdown increases myeloma cell death and panobinostat sensitivity. In conclusion, miR-7, which is downregulated by HDAC inhibitors, is a tumor suppressor that targets PSME3. This miR-7 downregulation may be involved in HDAC inhibitor resistance. In addition, combinations of anti-myeloma drugs that complement changes in miRNA expression should be considered.

Titanium nanotopography enhances mechano-response of osteocyte three-dimensional network toward osteoblast activation.

The bone turnover capability influences the acquisition and maintenance of osseointegration. The architectures of osteocyte three-dimensional (3D) networks determine the direction and activity of bone turnover through osteocyte intercellular crosstalk, which exchanges prostaglandins through gap junctions in response to mechanical loading. Titanium nanosurfaces with anisotropically patterned dense nanospikes promote the development of osteocyte lacunar-canalicular networks. We investigated the effects of titanium nanosurfaces on intercellular network development and regulatory capabilities of bone turnover in osteocytes under cyclic compressive loading. MLO-Y4 mouse osteocyte-like cell lines embedded in type I collagen 3D gels on titanium nanosurfaces promoted the formation of intercellular networks and gap junctions even under static culture conditions, in contrast to the poor intercellular connectivity in machined titanium surfaces. The osteocyte 3D network on the titanium nanosurfaces further enhanced gap junction formation after additional culturing under cyclic compressive loading simulating masticatory loading, beyond the degree observed on machined titanium surfaces. A prostaglandin synthesis inhibitor cancelled the dual effects of titanium nanosurfaces and cyclic compressive loading on the upregulation of gap junction-related genes in the osteocyte 3D culture. Supernatants from osteocyte monolayer culture on titanium nanosurfaces promoted osteocyte maturation and intercellular connections with gap junctions. With cyclic loading, titanium nanosurfaces induced expression of the regulatory factors of bone turnover in osteocyte 3D cultures, toward higher osteoblast activation than that observed on machined surfaces. Titanium nanosurfaces with anisotropically patterned dense nanospikes promoted intercellular 3D network development and regulatory function toward osteoblast activation in osteocytes activated by cyclic compressive loading, through intercellular crosstalk by prostaglandin.

Pharmacists' Behavioral Changes after Attending a Multi-Prefectural Palliative Care Education Program.

Central to the pharmacist's role in palliative care is symptom management through direct participation in patient care and the provision of optimal pharmacotherapy to support patient outcomes. Consequently, palliative care requires extensive knowledge and action for patients with cancer. Therefore, this study aimed to evaluate how pharmacists' behavior changed after attending a palliative care educational program. We conducted a web-based questionnaire survey examining the behavior of pharmacists regarding palliative care before participating in the program, two months after participating in the program, and eight months after participating in the program to determine their behavior and changes over time. For all questions, scores were higher at two and eight months after attending the program than before attending the program (p < 0.05). In addition, no significant difference was observed between two and eight months after attending the program for any question (p = 0.504-1.000). The knowledge gained from the educational program was used to repeatedly intervene with patients with cancer in order to address the various symptoms they experienced and maintain their behavior. The proven effectiveness of this program serves as a stepping stone for nationwide rollout across Japan's 47 prefectures.

The Effect of Motor Imagery Practice on an Aiming Task with Attentional Focus Cues.

When one directs their attention to an intended effect (external focus of attention, EFOA), motor performance is generally better than when one directs their attention to their own body movements (internal focus of attention, IFOA). However, the effect of attentional focus is unclear when a skill is practiced through motor imagery (MI) in the absence of physical trials. Participants (N = 30, M = 22.33 yrs, SD = 2.69) in the present study completed three physical trials of a reciprocal aiming task before and (24-h) after MI practice. During MI practice, the EFOA (n = 15) and IFOA (n = 15) groups mentally practiced the task with no physical practice with EFOA-MI or IFOA-MI, respectively, for three consecutive days. Our results showed that both groups significantly improved in accuracy (F1,28 = 6.49, p = .017), supporting the benefit of MI in motor skill acquisition. However, a significant effect of attentional focus was not observed (F1.,28 = 0.445, p = 0.51). We discussed two potential explanations: EFOA/IFOA requires physical trials to affect performance, or individuals must use both EFOA and IFOA in the process of creating imagery of the environment and movements, which may obscure the effect of EFOA and IFOA.

Risk of severe COVID-19 in unvaccinated patients during the period from wild-type to Omicron variant: real-world evidence from Japan.

BACKGROUND: Many studies have reported that the Omicron variant is less pathogenic than the Delta variant and the wild-type. Epidemiological evidence regarding the risk of severe COVID-19 from the wild-type to the Omicron variant has been lacking. METHODS: Study participants were COVID-19 patients aged 18 and older without previous COVID-19 infection who were notified to the Nara Prefecture Chuwa Public Health Center from January 2020 to March 2023, during the periods from the wild-type to the Omicron variant. The outcome variable was severe COVID-19 (i.e., ICU admission or COVID-19-related death). The explanatory variable was SARS-CoV-2 variant type or the number of COVID-19 vaccinations. Covariates included gender, age, risk factors for aggravation, and the number of general hospital beds per population. The generalized estimating equations of negative binomial regression models were used to estimate the adjusted incidence proportion (AIP) with 95% confidence interval (CI) for severe COVID-19. RESULTS: Among 77,044 patients included in the analysis, 14,556 (18.9%) were unvaccinated and 520 (0.7%) developed severe COVID-19. Among unvaccinated patients, the risk of severe COVID-19 increased in the Alpha/Delta variants and decreased in the Omicron variant compared to the wild-type (AIP [95% CI] was 1.55 [1.06-2.27] in Alpha/Delta and 0.25 [0.15-0.40] in Omicron), but differed by age. Especially in patients aged ≥80, there was no significant difference in the risk of severe COVID-19 between the wild-type and the Omicron variant (AIP [95% CI] = 0.59 [0.27-1.29]). Regarding the preventive effect of vaccines, among all study participants, the number of vaccinations was significantly associated with the prevention of severe COVID-19, regardless of variant type. After stratified analyses by age, patients aged ≥80 remained a significant association for all variant types. On the other hand, the number of vaccinations had no association in Omicron BA.5 of patients aged 18-64. CONCLUSIONS: Patients aged ≥80 had less reduction in risk of severe COVID-19 during the Omicron variant period, and a greater preventive effect of vaccines against severe COVID-19, compared to younger people. Our findings suggest that booster vaccination is effective and necessary for older people, especially aged ≥80.

Innate immune regulation in dental implant osseointegration.

PURPOSE: Dental implant osseointegration comprises two types of bone formation-contact and distance osteogenesis-which result in bone formation originating from the implant surface or bone edges, respectively. The physicochemical properties of the implant surface regulate initial contact osteogenesis by directly tuning the osteoprogenitor cells in the peri-implant environment. However, whether these implant surface properties can regulate osteoprogenitor cells distant from the implant remains unclear. Innate immune cells, including neutrophils and macrophages, govern bone metabolism, suggesting their involvement in osseointegration and distance osteogenesis. This narrative review discusses the role of innate immunity in osseointegration and the effects of implant surface properties on distant osteogenesis, focusing on innate immune regulation. STUDY SELECTION: The role of innate immunity in bone formation and the effects of implant surface properties on innate immune function were reviewed based on clinical, animal, and in vitro studies. RESULTS: Neutrophils and macrophages are responsible for bone formation during osseointegration, via inflammatory mediators. The microroughness and hydrophilic status of titanium implants have the potential to alleviate this inflammatory response of neutrophils, and induce an anti-inflammatory response in macrophages, to tune both contact and distance osteogenesis through the activation of osteoblasts. Thus, the surface micro-roughness and hydrophilicity of implants can regulate the function of distant osteoprogenitor cells through innate immune cells. CONCLUSIONS: Surface modification of implants aimed at regulating innate immunity may be useful in promoting further osteogenesis and overcoming the limitations encountered in severe situations, such as early loading protocol application.

Prognostic impact of peripheral blood WT1 mRNA dynamics in patients with acute myeloid leukemia treated with venetoclax combination therapy.

BACKGROUND: Wilms' tumor gene 1 (WT1) mRNA quantification is a useful marker of measurable residual disease in acute myeloid leukemia (AML). However, whether monitoring the WT1 mRNA levels may predict the outcome of venetoclax (VEN) combination therapy in AML is not reported. This study aims to elucidate whether WT1 mRNA dynamics could predict long-term prognosis. METHODS: 33 patients with untreated or relapsed/refractory AML evaluated for peripheral blood WT1 dynamics in VEN combination therapy were analyzed. RESULTS: The median age was 73 years (range 39-87). Azacitidine was combined with VEN in 91% of patients. Overall, the median overall survival (OS) was 334 days (95% CI 210-482), and the complete remission (CR) plus CR with incomplete hematologic recovery rate was 59%. A 1-log reduction of WT1 mRNA values by the end of cycle 2 of treatment was associated with significantly better OS and event-free survival (EFS) (median OS 482 days vs. 237 days, p = 0.049; median EFS 270 days vs. 125 days, p = 0.02). The negativity of post-treatment WT1 mRNA value during the treatment was associated with significantly better OS and EFS (median OS 482 days vs. 256 days, p = 0.02; median EFS not reached vs. 150 days, p = 0.005). Multivariate analysis confirmed the significance of these two parameters as strong EFS predictors (HR 0.26, p = 0.024 and HR 0.15, p = 0.013, respectively). The increase in WT1 mRNA values was correlated with relapse. CONCLUSION: This study demonstrates that WT1 mRNA dynamics can be a useful marker for assessing long-term prognosis of VEN combination therapy for AML.

Goal conceptualization has distinct effects on spatial and temporal bimanual coordination after left- and right- hemisphere stroke.

Perception of task goal influences motor performance and coordination. In bimanual actions, it is unclear how one's perception of task goals influences bimanual coordination and performance in individuals with unilateral stroke. We characterized inter-limb coordination differences in individuals with chronic right- and left-hemisphere damaged (RCVA: n = 24, LCVA: n = 24) stroke and age-matched neurotypical controls (n = 24) as they completed bimanual reaching tasks under distinct goal conditions. In the dual-goal condition, participants reached to move two virtual bricks (cursors) assigned to each hand toward independent targets. In the common-goal condition, they moved a central common virtual brick representing both hands to a single, central target. Spatial and temporal coordination (cross-correlation coefficients of hand velocity and their time-lag), the redundant axis deviations (the hand deviations in the axis orthogonal to the axis along the cursor-target direction), and the contribution ratio of the paretic hand were measured. Compared to the dual-goal condition, reaching actions to the common-goal demonstrated better spatial bimanual coordination in all three participant groups. Temporal coordination was better during common-goal than dual-goal actions only for the LCVA group. Additionally, and novel to this field, sex, as a biological variable, differently influenced movement time and redundant axis deviation in participants with stroke under the common-goal condition. Specifically, female stroke survivors showed larger movements in the redundant axes and, consequently, longer movement times, which was more prominent in the LCVA group. Our results indicate that perception of task goals influences bimanual coordination, with common goal improving spatial coordination in neurotypical individuals and individuals with unilateral stroke and providing additional advantage for temporal coordination in those with LCVA. Sex influences bimanual performance in stroke survivors and needs to be considered in future investigations.

Characteristics of macrophage aggregates prepared by rotation culture and their response to polymeric materials.

Understanding the interaction between macrophages and biomaterials is important for the creation of new biomaterials and the development of technologies to control macrophage function. Since macrophages are strongly adhesive, caution is required when performing in vitro evaluations. Similarly, when THP-1 cells, macrophage precursor cells, are differentiated into macrophages using phorbol-12-myristate-13-acetate (PMA), it becomes difficult to detach them from the adherent substrate, which has been a problem on investigation of immunological responses to biomaterials. In this study, the interaction of THP-1 cell-differentiated macrophages with biomaterials was analyzed based on a new method of seeding THP-1 cells. THP-1 cells were cultured in static and rotation culture without and with PMA. In undifferentiated THP-1 cells, there was no change in cellular function between static and rotation cultures. In rotation culture with PMA, THP-1 cells differentiated and formed macrophage aggregates. IL-1ß and MRC1 expression in macrophage aggregates was examined after differentiation and M1/M2 polarization. Macrophage aggregates in rotation culture tended to be polarized toward M2 macrophages compared with those in static culture. In the evaluation of the responses of macrophage aggregates to several kinds of polymeric materials, macrophage aggregates showed different changes in MRC1 expression over time at 30, 50, and 70 rpm. Rotation speed of 30 rpm was considered most appropriate condition in that it gave stable results with the same trend as obtained with static culture. The use of macrophage aggregates obtained by rotational culture is expected to provide new insights into the evaluation of inflammatory properties of biomaterials.

Immunomodulators after the discontinuation of anti-tumor necrosis factor-alpha antibody treatment and relapse in ulcerative colitis: A multicenter cohort study.

BACKGROUND AND AIM: Strategies to reduce relapse using immunomodulators (IMs) after discontinuing anti-tumor necrosis factor-alpha (TNF-α) antibody treatment are controversial in patients with ulcerative colitis (UC). In this study, we assessed the association between IMs after discontinuing anti-TNF-α antibody treatment and relapse in patients with UC. METHODS: This retrospective, multicenter cohort study included 257 patients with UC in clinical remission. These patients discontinued anti-TNF-α antibody treatment between June 2010 and March 2019 and were followed up until March 2020. We evaluated the differences in relapse rates between patients with IMs (IM group) and those without IMs (non-IM group) after discontinuing the treatment. Relapse was defined as further undergoing an induction treatment or colectomy. Cox proportional hazards models adjusted for confounders were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for relapse. Exploratory analyses were performed to identify other factors that could predict relapse. RESULTS: During the median follow-up period of 22 months (interquartile range: 10-41), 114 relapses occurred: 42/100 (42.0%) in the IM group and 72/157 (45.9%) in the non-IM group. In the multivariable analysis, IMs were not associated with relapse (HR, 0.95 [95% CI, 0.64-1.41]). In the exploratory analyses, discontinuation due to side effects (HR, 1.83 [95% CI, 1.18-2.82]) and younger age (HR, 0.99 [95% CI, 0.98-1.00]) predicted relapse. CONCLUSION: Immunomodulators were not associated with relapse after discontinuing anti-TNF-α antibody treatment in patients with UC. Careful patient follow-up is needed when discontinuing due to side effects or when the patient is of a younger age at the time of discontinuation.

Impact of the coronavirus disease 2019 pandemic on gastric and colorectal cancer surgeries: a multicenter epidemiologic study from the Kinki region of Japan.

The coronavirus disease 2019 pandemic affected cancer surgeries and advanced cancer diagnoses; however, the trends in patient characteristics in medical institutions during this time, and the surgical approaches used are unclear. We investigated the impact of the pandemic on gastric and colorectal cancer surgeries in the Kinki region of Japan. We grouped 1688 gastric and 3493 colorectal cancer surgeries into three periods: "pre-pandemic" (April 2019-March 2020), "pandemic 1" (April 2020-March 2021), and "pandemic 2" (April 2021-September 2021), to investigate changes in the number of surgeries, patient characteristics, surgical approaches, and cancer progression after surgery. Gastric and colorectal cancer surgeries decreased from the pre-pandemic levels, by 20% and 4%, respectively, in pandemic 1, and by 31% and 19%, respectively, in pandemic 2. This decrease had not recovered to pre-pandemic levels by September, 2021. Patient characteristics, surgical approaches, and cancer progression of gastric and colorectal surgeries did not change remarkably as a result of the coronavirus disease 2019 pandemic.

Acute Myeloid Leukemia Harboring the t(16;21)(p11;q22) Translocation Treated With Venetoclax Plus Azacitidine After Cord Blood Transplantation.

A 62-year-old female was diagnosed with acute myeloid leukemia (AML) with t(16;21)(p11;q22). She achieved complete hematological remission after induction therapy and underwent umbilical cord blood stem cell transplantation (CBT). At 150 days after the CBT, a bone marrow examination revealed relapse. We treated the patient with venetoclax plus azacitidine as salvage therapy. After five cycles of venetoclax and azacitidine therapy, the patient died due to disease progression. The prognosis of AML with t(16;21)(p11;q22) is very poor owing to the high rate of early relapse even after hematopoietic stem cell transplantation. Therefore, a novel therapeutic approach is required to improve patient outcomes.

Association between vaccination status and severe health consequences among community-dwelling COVID-19 patients during Omicron BA.1/BA.2 and BA.5-predominant periods in Japan.

BACKGROUND: Many previous studies have reported that COVID-19 vaccine effectiveness decreased over time and declined with newly emerging variants. However, there are few such studies in Japan. Using data from a community-based retrospective study, we aimed to assess the association between vaccination status and severe COVID-19 outcomes caused by the Omicron variant, considering the length of time since the last vaccination dose. METHODS: We included all persons aged ≥12 diagnosed with COVID-19 by a doctor and notified to the Chuwa Public Health Center of Nara Prefectural Government during the Omicron BA.1/BA.2 and BA.5-predominant periods in Japan (January 1 to September 25, 2022). The outcome variable was severe health consequences (SHC) (i.e., COVID-19-related hospitalization or death). The explanatory variable was vaccination status of the individuals (i.e., the number of vaccinations and length of time since last dose). Covariates included gender, age, risk factors for aggravation, and the number of hospital beds per population. Using the generalized estimating equations of the multivariable Poisson regression models, we estimated the cumulative incidence ratio (CIR) and 95% confidence interval (CI) for SHC, with stratified analyses by period (BA.1/BA.2 or BA.5) and age (65 and older or 12-64 years). RESULTS: Of the 69,827 participants, 2,224 (3.2%) had SHC, 12,154 (17.4%) were unvaccinated, and 29,032 (41.6%) received ≥3 vaccine doses. Regardless of period or age, there was a significant dose-response relationship in which adjusted CIR for SHC decreased with an increased number of vaccinations and a longer time since the last vaccination. On the one hand, in the BA.5 period, those with ≥175 days after the third dose had no significant difference in people aged 65 and older (CIR 0.77; 95% CI, 0.53-1.12), but significantly lower CIR for SHC in people aged 12-64 (CIR 0.47; 95% CI, 0.26-0.84), compared with those with ≥14 days after the second dose. CONCLUSION: A higher number of vaccinations were associated with lower risk of SHC against both BA.1/BA.2 and BA.5 sublineages. Our findings suggest that increasing the number of doses of COVID-19 vaccine can prevent severe COVID-19 outcomes, and that a biannual vaccination is recommended for older people.

Mechanoregulation of Osteoclastogenesis-Inducing Potentials of Fibrosarcoma Cell Line by Substrate Stiffness.

A micro-physiological system is generally fabricated using soft materials, such as polydimethylsiloxane silicone (PDMS), and seeks an inflammatory osteolysis model for osteoimmunological research as one of the development needs. Microenvironmental stiffness regulates various cellular functions via mechanotransduction. Controlling culture substrate stiffness may help spatially coordinate the supply of osteoclastogenesis-inducing factors from immortalized cell lines, such as mouse fibrosarcoma L929 cells, within the system. Herein, we aimed to determine the effects of substrate stiffness on the osteoclastogenesis-inducing potential of L929 cells via cellular mechanotransduction. L929 cells showed increased expression of osteoclastogenesis-inducing factors when cultured on type I collagen-coated PDMS substrates with soft stiffness, approximating that of soft tissue sarcomas, regardless of the addition of lipopolysaccharide to augment proinflammatory reactions. Supernatants of L929 cells cultured on soft PDMS substrates promoted osteoclast differentiation of the mouse osteoclast precursor RAW 264.7 by stimulating the expression of osteoclastogenesis-related gene markers and tartrate-resistant acid phosphatase activity. The soft PDMS substrate inhibited the nuclear translocation of YES-associated proteins in L929 cells without reducing cell attachment. However, the hard PDMS substrate hardly affected the cellular response of the L929 cells. Our results showed that PDMS substrate stiffness tuned the osteoclastogenesis-inducing potential of L929 cells via cellular mechanotransduction.

What can surgeons do to prevent job leave soon after cancer diagnosis? A brief report on colorectal cancer survivors in Japan.

PURPOSE: Colorectal cancer is one of the most diagnosed cancers in Japan and the number of cancer survivors has increased. Work-related issues of cancer survivors have been investigated in relation to occupational health, and sufficient evidence in clinical practice is needed to support this. This study aimed to obtain the relevant information, intending to support the employment of patients with colorectal cancer for clinical settings. METHODS: We conducted a prospective, multicenter cohort study, which included patients who underwent surgery with clinical stage I-III colorectal cancer. An electronic survey was used at the time of hospital admission to collect the patients' occupational information, including job resignation soon after cancer diagnosis. A cross-sectional analysis was performed to evaluate the patients' employment situations. RESULTS: Of 129 eligible patients, 46 (36%) were female. Thirty-nine (30%) were self-employed and 72 (56%) worked at small-sized workplaces, which are not obliged to have occupational physicians. Most patients (89%) expressed their desire to return to work, but eight patients (6%) left their jobs soon after being diagnosed with colorectal cancer before undergoing surgery for several reasons stemming from worries about future treatment and its consequences. Multivariable analyses indicated that nonregular employees and the self-employed might be at a disadvantage in keeping their job at diagnosis. CONCLUSION: Surgeons should address work-related issues for survivorship, which begins at cancer diagnosis and, when available, collaborate with occupational physicians while being mindful that patients working at smaller companies do not have immediate access to occupational physicians.

Stiffness-Tunable Hydrogel-Sandwich Culture Modulates the YAP-Mediated Mechanoresponse in Induced-Pluripotent Stem Cell Embryoid Bodies and Augments Cardiomyocyte Differentiation.

Microenvironmental factors, including substrate stiffness, regulate stem cell behavior and differentiation. However, the effects of substrate stiffness on the behavior of induced pluripotent stem cell (iPSC)- derived embryoid bodies (EB) remain unclear. To investigate the effects of mechanical cues on iPSC-EB differentiation, a 3D hydrogel-sandwich culture (HGSC) system is developed that controls the microenvironment surrounding iPSC-EBs using a stiffness-tunable polyacrylamide hydrogel assembly. Mouse iPSC-EBs are seeded between upper and lower polyacrylamide hydrogels of differing stiffness (Young's modulus [E'] = 54.3 ± 7.1 kPa [hard], 28.1 ± 2.3 kPa [moderate], and 5.1 ± 0.1 kPa [soft]) and cultured for 2 days. HGSC induces stiffness-dependent activation of the yes-associated protein (YAP) mechanotransducer and actin cytoskeleton rearrangement in the iPSC-EBs. Moreover, moderate-stiffness HGSC specifically upregulates the mRNA and protein expression of ectoderm and mesoderm lineage differentiation markers in iPSC-EBs via YAP-mediated mechanotransduction. Pretreatment of mouse iPSC-EBs with moderate-stiffness HGSC promotes cardiomyocyte (CM) differentiation and structural maturation of myofibrils. The proposed HGSC system provides a viable platform for investigating the role of mechanical cues on the pluripotency and differentiation of iPSCs that can be beneficial for research into tissue regeneration and engineering.

Identification of Senescent Cells in Peri-Implantitis and Prevention of Mini-Implant Loss Using Senolytics.

Peri-implantitis is a disease that causes the detachment of orthodontic mini-implants. Recently, stress-induced senescent cells have been reported to be involved in various inflammatory diseases. Senescent cell-eliminating drugs, termed "senolytics", can improve the symptoms of such diseases. However, the relationship between peri-implantitis and senescent cells remains unclear. In this study, we evaluated the presence of senescent cells in a rat peri-implantitis model developed with a gum ring. The effect on bone resorption and implant loss was also investigated with and without senolytics (Dasatinib and Quercetin). The number of senescence markers (p19, p21, and p16) was found to increase, and implant detachment occurred in 24 days. After the administration of senolytics, the number of senescence markers decreased and implant detachment was inhibited. This study suggests that senescent cells aggravate peri-implantitis and senolytic administration latently reduces implant loss by inhibiting senescence-related mechanisms.