Search

To investigate the outcomes of definitive external-beam radiation therapy (EBRT) plus image-guided brachytherapy (IGBT) in patients with endometrial cancer (EC) unsuitable for surgery.A total of 50 patients with inoperable EC were included. The patients received EBRT in a median dose of 45 Gy to the pelvis over 5 weeks. Thereafter, the patients received brachytherapy using tandem and ovoid applicators. High-risk clinical target volume (HR-CTV) and gross tumor volume in brachytherapy (GTVp) were defined by the assistance of patients' pre-IGBT magnetic resonance imaging.The medical records of the 50 patients were analyzed. The main causes of inoperability were anesthesia contraindications, namely medical comorbidities and obesity. The median cumulative D90s (the minimum dose delivered to 90% of the volume) in EQD2 (equivalent dose in 2-Gy fractions) to the HR-CTV and GTVp were 72.9 Gy10 (range, 64.9 to 80.3) and 166.2 Gy10 (range, 123.0 to 189.8), respectively. Over a median follow-up period of 27 months, 8 of the patients died of cancer. The 2-year overall and cancer-specific survival rates were 75% and 83%, respectively. The cumulative incidences of pelvic and distant failure were 4% (n = 2) and 16% (n = 8), respectively. Gastrointestinal complications of grade 2 or above were noted in 2 patients (4%), and a grade 2 genitourinary complication was noted in one.For patients with inoperable EC, EBRT followed by IGBT is an effective approach for achieving high local control without a high risk of complications.

Self-efficacy (SE) is recognized as a main determinant of successful performance and may mediate the relationship between psychological performance enhancement techniques and sports performance. Identifying the cognitive–motor processes of superior performance can provide crucial information not only for accelerating the motor learning process but also for enhancing motor performance. The frontal midline theta power (Fmθ) reflects the level of top–down attention allocated to achieve a desired cognitive–motor behavior. Thus, this study investigated the effect of SE on the performance and Fmθ of golf players and explored the association between the objective measures of cortical dynamics and SE. Thirty-four skilled golfers were recruited (within-subject design) to perform 60 putts, and their electroencephalographic activity was recorded during the task. The SE score was measured using a visual analog scale ranging from 0 to 10 before each putt. Paired t test results revealed that trials with higher SE scores were associated with a higher putting success rate than trials with lower SE scores (53.3% vs 46.7%). Moreover, trials with higher SE scores were preceded by lower Fmθ than trials with lower SE scores (4.49 vs. 5.18). These findings suggested that higher SE was followed by less top–down attentional control, a characteristic of automatic processing, leading to better putting performance. Our findings support Bandura’s SE theory and elucidate the intermediate processes of SE by investigating the effect of the anticipation of outcomes on sports performance and attentional control before putting.

RationaleCilostazol, an anti-platelet phosphodiesterase-3 inhibitor used for the treatment of intermittent claudication, is known for its pleiotropic effects on platelets, endothelial cells and smooth muscle cells. However, how cilostazol impacts the endocrine system and the injury-induced inflammatory processes remains unclear.MethodsWe used the zebrafish, a simple transparent model that demonstrates rapid development and a strong regenerative ability, to test whether cilostazol influences steroidogenesis, and the temporal and dosage effects of cilostazol on innate immune cells during tissue damage and repair.ResultsWhile dosages of cilostazol from 10 to 100 μM did not induce any noticeable morphological abnormality in the embryonic and larval zebrafish, the heart rate and adrenal/interrenal steroidogenesis in larval zebrafish was increased in a dose-dependent manner. During larval fin amputation and regeneration, cilostazol treatments did not affect the immediate injury-induced recruitment of either neutrophils or macrophages, followed by a subtle yet significant effect on reducing the neutrophil retention at the lesion site.ConclusionsOur results indicate that cilostazol has a significant effect on the growth and endocrine function of steroidogenic tissue; and a limited effect on the neutrophil retention without affecting neutrophil and macrophage recruitment during tissue damage and repair.

BackgroundCYP2C19 loss-of-function (LOF) alleles reduce the effectiveness of clopidogrel and are associated with high rates of clinical events in patients undergoing percutaneous coronary intervention (PCI) and stenting in Northeast Asians. However, the prevalence and influence of CYP2C19 LOF alleles in Southeast Asians remain unclear.ObjectivesThis study aims to retrospectively investigate the prevalence of CYP2C19 LOF alleles and clinical outcomes in East Asian patients taking clopidogrel and undergoing PCI.MethodsBetween June 2019 and June 2020, volunteer participants in a single medical center were consecutively selected. The genetic data of CYP2C19 were derived from the Taiwan Precision Medicine Initiative (TPMI). Patients receiving clopidogrel while undergoing PCI with stenting were retrospectively analyzed.ResultsA total of 999 patients (62.4 ± 11.1 years old, 83.7% men) were enrolled; 39.3% without the CYP2C19 LOF allele (normal metabolizers + rapid metabolizers, NM + RM); 44.9% with one LOF allele (intermediate metabolizers, IM); 15.7% with two LOF alleles (poor metabolizers, PM). The incidence of stroke was higher in the PM subgroup compared to the NM + RM subgroup or IM subgroup in patients presenting with acute myocardial infarction (AMI). The 1-year major adverse cardiac and cerebrovascular events (MACCE)-free survival rates in all participants were similar among the three groups. However, in the AMI group, the 1-year MACCE-free survival rates were significantly lower in the PM subgroup compared to the NM + RM subgroup or IM subgroup.ConclusionIn East Asians presenting with AMI, CYP2C19 PM was associated with deleterious cardiovascular outcomes and stroke. Our results reinforce the crucial role of preemptive CYP2C19 genotyping in East Asian AMI patients receiving clopidogrel treatment.

Objective To evaluate efficacy of stereotactic body radiotherapy (SBRT) for pelvic boost irradiation in gynecological cancer patients with pelvic recurrence or with intact uterus unsuitable for brachytherapy. Materials and methods We retrospectively reviewed the medical records of 25 gynecological cancer patients who received SBRT boost for pelvic recurrence (salvage group, n = 14), or for local dose escalation instead of intracavitary brachytherapy due to unfavorable medical condition (definitive group, n = 11). The pelvis was irradiated with a median dose of 54 Gy in six weeks, and then SBRT was prescribed with a range of 10–25Gy in two to five fractions. The cumulative radiobiological equivalent dose in 2-Gy fractions (EQD2) to the tumors ranged from 62.5 to 89.5 Gy10 (median, 80.7). Overall survival (OS) and in-field relapse-free survival (IFRFS) were calculated using the Kaplan–Meier method. Results At the initial assessment, eighteen (72%) patients achieved complete or partial remission, and seven (28%) had stable or progressive disease. With a median follow duration of 12 months, the 1-year IFRFS for salvage and definitive group were 64.5% and 90.0%, whereas the 1-year OS for the two groups were 80.8% and 49.1%, respectively. One patient developed entero-vaginal fistula and one had sigmoid perforation. No patient experienced ≧ grade 3 genitourinary complications. Conclusion In gynecological cancer patients with recurrent pelvic tumors or intact uterus unsuitable for brachytherapy, local dose escalation with SBRT resulted in an initial response rate of 72% with acceptable early toxicities. A long-term follow-up is required to assess the impact on local control or survival.

Background Sarcopenia, which is a common risk factor for falls and fractures, affects the functional outcome and mortality in geriatric populations. However, the prevalence of sarcopenia among geriatric Taiwanese patients with a hip fracture is unknown, nor is the effect of sarcopenia on the outcome of hip surgery. Methods From December 2017 to February 2019, geriatric patients who underwent surgery for a hip fracture were prospectively enrolled. Basic demographic data, responses to questionnaires for dementia screening and quality of life (QoL) and daily living activities (ADL) before the injury were analyzed to identify any association with sarcopenia. The QoL and ADL were monitored at six months after the operation to determine the difference between hip fracture patients with or without sarcopenia. Results Of 139 hip fracture patients, 70 (50.36%) were diagnosed with sarcopenia. Accounting for all confounding factors in the multivariate logistic regression, lower body mass index (BMI), male gender and a weaker handgrip are the risk factors that are most strongly associated with a diagnosis of sarcopenia in geriatric patients with a hip fracture. Hip fracture patients with sarcopenia also have poor ADL and a lower QoL than patients without sarcopenia before the injury and six months after the operation. Conclusion A high prevalence of sarcopenia among geriatric hip fracture patients is associated with a poor mid-term outcome following hip surgery. Clinicians must recognize the risk of sarcopenia, especially for male hip fracture patients with a lower BMI and a weaker handgrip.

Objective. Heavy calcifications remain formidable challenges to PCI, even for well-experienced operators. However, rotational atherectomy (RA)-induced coronary perforations (CPs) still could not be obviated. This study was to explore incidence and mechanisms of RA-induced CP in real-world practice. Knowing why CPs occur in RA should help operators avert such mishaps. Method. Patients who received coronary RA from April 2010 to December 2019 with keywords related to perforations were retrieved from database. The procedure details, angiography, and clinical information were reviewed in detail. Results. A total of 479 RAs were performed with 11 perforations in 10 procedures among 9 patients documented. The incidence of RA-induced CP was 2.1%. The RA vessels were distributed in different territories, including first diagonal branch. Most CPs could be treated conservatively, but prolonged profound shock predisposed to poor outcome. CPs caused by rotawire tip occurred in 18.2% of cases, inappropriately sized burrs in 18.2% of cases, and rotawire damage with subsequent transection and perforation in another 18.2% of cases. A total of 5 (45.5%) perforations were caused by unintended and unnoticed bias cutting into noncalcified plaques (4, 36.4%) or through calcified vessel wall (1, 9.1%). The mechanisms for certain CPs were unique and illustrated in diagrams. Conclusion. CPs due to RA occur in certain percentage of patients. The mechanisms for CPs are diverse. Wire damage with subsequent transection could occur due to inappropriately repetitive burr stress on the wire body. A significant portion was due to unintended and unnoticed bias cutting into noncalcified plaque or through calcified vessel wall.

Layout pattern classification, which groups similar layout clips into clusters, underlies a variety of design for manufacturability (DFM) applications, such as hotspot library generation, hierarchical data storage, and yield optimization speedup. The key challenges of layout pattern classification are clip representation and clip clustering. In this paper, we present a fast and general layout pattern classification algorithm considering clip shifting and centroid recreation. Our simple but general clip representation captures both topology and density; we can handle not only rigid area match or edge displacement constraints but also variant edge tolerances and don’t care regions. For achieving a small cluster count, our clip clustering is guided by the natural grouping structure of layout clips. The clustering results are further improved by centroid recreation. Our experiments are conducted on 2016 CAD contest at ICCAD benchmark suite. Our results show that our algorithm outperforms the reference solution and all contest winning teams, delivering the smallest cluster count, fastest runtime, and 100% validity. Moreover, our algorithm with clip shifting and centroid recreation further reduces the cluster count effectively and efficiently. In addition to the good solution quality, the interplay between adopted data structures and our algorithm makes it fast and viable to be incorporated into practical DFM flows.

This study aims to explore lipidic mechanism towards low‐density lipoprotein receptor (LDLR)‐mediated platinum chemotherapy resistance. By using the lipid profiling technology, LDLR knockdown was found to increase lysosomal lipids and decrease membranous lipid levels in EOC cells. LDLR knockdown also down‐regulated ether‐linked phosphatidylethanolamine (PE‐O, lysosomes or peroxisomes) and up‐regulated lysophosphatidylcholine [LPC, lipid droplet (LD)]. This implies that the manner of using Lands cycle (conversion of lysophospholipids) for LDs might affect cisplatin sensitivity. The bioinformatics analyses illustrated that LDLR‐related lipid entry into LD, rather than an endogenous lipid resource (eg Kennedy pathway), controls the EOC prognosis of platinum chemotherapy patients. Moreover, LDLR knockdown increased the number of platinum‐DNA adducts and reduced the LD platinum amount. By using a manufactured LPC‐liposome‐cisplatin (LLC) drug, the number of platinum‐DNA adducts increased significantly in LLC‐treated insensitive cells. Moreover, the cisplatin content in LDs increased upon LLC treatment. Furthermore, lipid profiles of 22 carcinoma cells with differential cisplatin sensitivity (9 sensitive vs 13 insensitive) were acquired. These profiles revealed low storage lipid levels in insensitive cells. This result recommends that LD lipidome might be a common pathway in multiple cancers for platinum sensitivity in EOC. Finally, LLC suppressed both cisplatin‐insensitive human carcinoma cell training and testing sets. Thus, LDLR‐platinum insensitivity can be due to a defective Lands cycle that hinders LPC production in LDs. Using lipidome assessment with the newly formulated LLC can be a promising cancer chemotherapy method.

Introduction Hip fractures can be divided into intra-capsular and extra-capsular fracture based on fracture location; these two types of fracture have different pathogeneses, treatments and prognoses. Many factors influence the patterns of hip fractures, including the injury mechanism, areal bone mineral density and the geometry of the hip. However, the relationship between body composition and hip fracture pattern has not yet been discussed. In this investigation, an analysis of the body compositions of geriatric patients with hip fractures were conducted to identify differences between fat and muscle distributions between patients with intra- and extra-capsular hip fractures. Material and methods From December 2017 to February 2019, 139 patients with a hip fracture were prospectively enrolled in this study. The groups of patients that were diagnosed as having intra- and extra-capsular hip fractures were compared in terms of patient demographics, pre-operative laboratory data, bone mineral density (BMD) and body composition including muscle and fat distributions obtained using dual-energy X-ray absorptiometry (DXA) . Results Eighty-six and 53 patients were diagnosed with intra-capsular and extra-capsular hip fractures, respectively. A significantly higher serum glucose level, a lower hemoglobin level, a lower T-score level in the proximal femur region, a lower T-score of all parts of interest, and a lower percentage fat content on the region of bilateral proximal hips (gynoid region) and in the lower limb region, were observed in patients with an extra-capsular hip fracture than in those with an intra-capsular hip fracture. However, with all confounding factors controlled for, only the T-score at the proximal femur, percentage fat content in the region of bilateral proximal hips and the ratio of android fat content to gynoid fat content (A/G ratio) are the most relevant factors in predicting the patterns of hip fracture in geriatric patients after falling. Conclusion This work demonstrates that lower fat content in the region of bilateral proximal hips and a lower BMD on the proximal femur may predict greater vulnerability of geriatric patients to extra-capsular rather than intra-capsular hip fracture after a falling accident.

Platinum-based therapy remains the cornerstone for cancer therapy; however, its efficacy varies. The role of lipoprotein receptor-mediated lipid entry for cancer development has been reported. Yet, the roles and mechanism of the low-density lipoprotein receptor (LDLR) in chemo-sensitivities are unknown. In the current report, we used epithelial ovarian cancer (EOC), composed of various cellularities, to study this issue. Using public cDNA microarray database and single cohort study, LDLR expressions were positively associated with epithelial ovarian carcinomas (EOCs) platinum-based chemotherapy patients’ disease prognosis. In vitro and in vivo add-in/silencing LDLR was introduced to determine cisplatin sensitivity and cancer growth. Results revealed that knocked-down LDLR could sensitize while overexpressed LDLR could insensitize EOC cells to the cytotoxic effects of cisplatin. Moreover, the trans-omics approaches depicted an LDLR→LPC (Lyso-phosphatidylcholine)→FAM83B (phospholipase-related)→FGFRs (cisplatin sensitivity and phospholipase-related) regulatory axis. Finally, the manipulation of LDLR expression in EOC cells was found to determine the efficacy of cisplatin therapy in terms of tumor suppression. In conclusion, the LDLR→LPC→FAM83B→FGFRs axis is an example of tumor macroenvironmental regulation of therapy outcomes. Relatedly, LDLR expression could serve as a biomarker of chemotherapy sensitivity in EOCs. Significance: this study describes the role of LDLR in the development of insensitivity to platinum-based chemotherapy in epithelial ovarian cancer. The lipidome (e.g., LPC) and transcriptome (e.g., FAM38B) interactions revealed using trans-omics approaches an LDLR→LPC→FAM83B→FGFRs regulatory axis in cancer cells, in an animal model, and in patients.

BackgroundRotational atherectomy (RA) is an indispensable tool used for calcified lesion preparation in percutaneous coronary intervention (PCI). However, use of RA in the setting of acute myocardial infarction (AMI) is challenged with limited clinical data.ObjectivesThis study aims to retrospectively investigate the procedural results, periprocedural complications, and clinical outcomes of RA in patients with AMI.MethodsAll possible consecutive patients who received RA in AMI from January 2009 to March 2018 in a single tertiary center were analyzed retrospectively. Patients without AMI during the study period were also enrolled for comparison.ResultsA total of 121 patients with AMI (76.0 ± 10.8 years, 63.6% males) and 290 patients without AMI were recruited. Among the AMI group, 81% of patients had non-ST-elevation myocardial infarction (NSTEMI) and 14% presented with cardiogenic shock. RA could be completed in 98.8% of patients in the AMI group and 98.3% in the non-AMI group (p = 1.00). The periprocedural complication rates were comparable between the AMI and non-AMI groups. The risks of in-hospital, 30-day, 90-day, and 1-year cardiovascular major adverse cardiac events (CV MACE) were significantly higher in the AMI group compared with the non-AMI group (in-hospital 13.2 vs. 2.8%, p < 0.001; 30-day 14.2 vs. 4.5%, p < 0.001; 90-day 20.8 vs. 6.9%, p < 0.001; 1-year 30.8 vs. 19.1%, p = 0.01). AMI at initial presentation and cardiogenic shock were predictors for both in-hospital CV MACE and 1-year CV MACE in multivariable binary logistic regression analysis. Other predictors for 1-year CV MACE included serum creatinine level and triple vessel disease.ConclusionRA in patients with AMI is feasible with a high procedural completion rate and acceptable periprocedural complications. Given unstable hemodynamics and complex coronary anatomy, the in-hospital and 1-year MACE rates remained higher in patients with AMI compared with patients without AMI.

Gastric cancer (GCa) is a malignancy with few effective treatments. Ursolic acid (UA), a bioactive triterpenoid enriched in Hedyotis diffusa Willd, known to suppress GCa without identified target. CYP19A1 (cytochrome P450 family 19A1; also known as aromatase, Ar) was correlated to GCa prognosis. Relatedly, Ar silencers, which halt the expression of Ar exhibited anti-GCa effects in experimental models, are currently being investigated.The docking simulation score of UA was compared with Ar inhibitors, e.g., letrozole, exemestane, in Ar protein crystallization. Hedyotis diffusa Willd ethanol extract, UA, or 5-fluracil were applied onto AGS, SC-M1, MKN45 GCa cells for cancer inhibition tests. Immunoblot for measuring gene expressions upon drug treatments, or gene knockdown/overexpression. Treatments were also applied in a MKN45 implantation tumor model. A web-based GCa cohort for Ar expression association with prognosis was performed.The ethanol extracts of Hedyotis diffusa Willd, enrich with UA, exhibited cytotoxic activity against GCa cells. Molecular docking simulations with the 3D Ar structure revealed an excellent fitting score for UA. UA increase cytotoxic, and suppressed colony, in addition to its Ar silencing capacity. Moreover, UA synergistically facilitated 5-FU, (a standard GCa treatment) regimen in vitro. Consistent with those results, adding estradiol did not reverse the cancer-suppressing effects of UA, which confirmed UA acts as an Ar silencer. Furthermore, UA exhibited tumor-suppressing index (TSI) score of 90% over a 6-week treatment term when used for single dosing in xenograft tumor model. In the clinical setting, Ar expression was found to be higher in GCa tumors than normal parental tissue from the TCGA (The Cancer Genome Atlas) cohort, while high Ar expression associated with poor prognosis. Together, the results indicate UA could be used to treat GCa by silencing Ar expression in GCa. Hedyotis diffusa Willd ethanol extract could be an functional food supplements.

Platinum-based therapy remains the cornerstone for cancer therapy; however, its efficacy varies. The role of lipoprotein receptor-mediated lipid entry for cancer development has been reported. Yet, the roles and mechanism of the low-density lipoprotein receptor (LDLR) in chemo-sensitivities are unknown. In the current report, we used epithelial ovarian cancer (EOC), composed of various cellularities, to study this issue. Using public cDNA microarray database and single cohort study, LDLR expressions were positively associated with epithelial ovarian carcinomas (EOCs) platinum-based chemotherapy patients' disease prognosis. In vitro and in vivo add-in/silencing LDLR was introduced to determine cisplatin sensitivity and cancer growth. Results revealed that knocked-down LDLR could sensitize while overexpressed LDLR could insensitize EOC cells to the cytotoxic effects of cisplatin. Moreover, the trans-omics approaches depicted an LDLR→LPC (Lyso-phosphatidylcholine)→FAM83B (phospholipase-related)→FGFRs (cisplatin sensitivity and phospholipase-related) regulatory axis. Finally, the manipulation of LDLR expression in EOC cells was found to determine the efficacy of cisplatin therapy in terms of tumor suppression. In conclusion, the LDLR→LPC→FAM83B→FGFRs axis is an example of tumor macroenvironmental regulation of therapy outcomes. Relatedly, LDLR expression could serve as a biomarker of chemotherapy sensitivity in EOCs. Significance: this study describes the role of LDLR in the development of insensitivity to platinum-based chemotherapy in epithelial ovarian cancer. The lipidome (e.g., LPC) and transcriptome (e.g., FAM38B) interactions revealed using trans-omics approaches an LDLR→LPC→FAM83B→FGFRs regulatory axis in cancer cells, in an animal model, and in patients.

Methadone maintenance treatment (MMT) remains the cornerstone for the management of opiate abuse. However, MMT can be associated with complex factors, including complications during the tolerance phase, the inability of some patients to maintain treatment effects during the tapering or abstinence phases, and the development of methadone dependence. Previous studies have revealed a sex disparity in MMT efficacy, showing that women undergoing MMT experiencing an increase in psychological symptoms compared with men and suggesting a link between disparate responses and the effects of estrogen signaling on methadone metabolism. More specifically, estradiol levels are positively associated with MMT dosing, and the expression of a single-nucleotide polymorphism (SNP) associated with estrogen receptor (ER) regulation is also associated with MMT dosing. In addition to performing mechanistic dissections of estrogen signaling in the presence of methadone, past studies have also proposed the targeting of estrogen signaling during MMT. The present report provides an overview of the relevant literature regarding sex effects, including differences in sex hormones and their potential impacts on MMT regimens. Moreover, this article provides a pharmacological perspective on the targeting of estrogen signals through the use of selective ER modulators (SERMs) during MMT. Preliminary preclinical experiments were also performed to evaluate the potential effects of targeting estrogen signaling with tamoxifen on methadone metabolism.

Ovarian cancer (OVCA) arises from three cellular origins, namely surface epithelial cells, germ cells, and stromal cells. More than 85% of OVCAs are EOCs (epithelial ovarian carcinomas), which are the most lethal gynecological malignancies. Cancer stem/progenitor cells (CSPCs) are considered to be cancer promoters due to their capacity for unlimited self-renewal and drug resistance. Androgen receptor (AR) belongs to the nuclear receptor superfamily and can be activated through binding to its ligand androgens. Studies have reported an association between AR expression and EOC carcinogenesis, and AR is suggested to be involved in proliferation, migration/invasion, and stemness. In addition, alternative AR activating signals, including both ligand-dependent and ligand-independent, are involved in OVCA progression. Although some clinical trials have previously been conducted to evaluate the effects of anti-androgens in EOC, no significant results have been reported. In contrast, experimental studies evaluating the effects of anti-androgen or anti-AR reagents in AR-expressing EOC models have demonstrated positive results for suppressing disease progression. Since AR is involved in complex signaling pathways and may be expressed at various levels in OVCA, the aim of this article was to provide an overview of current studies and perspectives regarding the relevance of androgen/AR roles in OVCA.

The world's population is aging, and the prevalence of hip fracture is rising. Vitamin D deficiency is a risk factor for hip fracture and predicts functional recovery and survival following hip fracture surgery. This cross-sectional study identified the prevalence of vitamin D deficiency in Taiwanese older patients with hip fracture and potential risk factors for vitamin D deficiency. Data from older adults with hip fracture admitted to a single medical center in Taipei, Taiwan were prospectively collected. The preoperative serum 25-hydroxyvitamin D [25(OH)D] concentration and comprehensive clinical history of each patient were examined. A multinomial logistic regression model was used to compare the clinical characteristics of deficient, insufficient, and sufficient 25(OH)D concentration groups. The cohort comprised 310 older adults with hip fracture. The mean age was 80±10 y. The deficient, insufficient, and sufficient groups comprised 180, 84, and 46 patients (58.1%, 27.1%, and 14.8%), respectively. Univariate analysis revealed significant intergroup differences in serum albumin level and body fat percentage and marginally significant differences in serum albumin, estimated glomerular filtration rate, body mass index, and comorbidities of affective or psychotic disorders. In the multinomial logistic regression model, albumin level was the only factor significantly correlated with higher 25(OH)D concentrations in the sufficient and insufficient groups compared with the deficient group. No variable, including preinjury functional status, was significantly correlated with vitamin D deficiency except malnutrition. Our findings may aid the establishment of a robust screening and treatment program for vitamin D deficiency.

Background: Hip fractures are a major public health concern among elderly individuals. This study aimed to investigate potential perioperative factors that predict 1-year functional outcome, quality of life (QoL), care demands, and mortality in geriatric patients with a hip fracture. Methods: We prospectively enrolled geriatric patients who had undergone hip fracture surgery in one medical center from December 2017 to December 2019. Basic demographic data, handgrip strength, and responses to questionnaires for QoL and activities of daily living (ADL) before the injury were collected at baseline. QoL, ADL, additional care demands other than family support, and mortality events were monitored at 1 year after the operation. Results: Among 281 patients with a hip fracture, 39 (13.9%) died within 1 year of the index operation. The mean follow-up interval for the survivors was 403.3 (range: 358–480) days. Among the 242 survivors, ADL and QoL considerably decreased at approximately 1 year following hip surgery. Up to 33.9% of the participants became severely dependent and needed additional care at 1-year follow up. Prefracture ADL status was the crucial predictor for functional outcome, QoL, and additional care demand at 1-year follow up. Cox regression models indicated that male sex, low preoperative serum creatinine, handgrip strength, long surgical delay after a falling accident, and high Charlson Comorbidity Index were considerably associated with a high 1-year mortality risk in the geriatric hip fracture population. Conclusion: Hip fracture has long-lasting effects (e.g. functional loss, decline in QoL, increased care demands, and high postoperative mortality rate) on the geriatric population. A robust screening method must be developed for identifying potential prognostic factors, and a stratified care approach must be used that accounts for personalized risks to improve functional outcomes and reduce mortality after hip fracture in geriatric patients, especially in Taiwan.

Introduction: Although surgery has been proven to improve the long-term survival of older adults with hip fracture, in-hospital mortality directly resulting from repair of hip fracture is undesirable. This study aimed to identify potential prognostic factors that predict in-hospital mortality risk in elderly patients following hip fracture surgery. Materials and Methods: This case–control study comprehensively collected data from older adults with hip fracture admitted to a single medical centre. Age was selected as the cross-matching factor. Univariate and binary multivariate logistic regression models were used to estimate the odds ratios with 95% confidence intervals. A receiver operating characteristic curve was constructed to quantify the discrimination power of the model. Results: Among a total of 841 older adults who received hip fracture surgery, 17 died during hospitalisation, yielding a 2.0% in-hospital mortality rate. Using a binary multivariate logistic regression model to perform a comparison with 51 age-matched patients in survival groups, the model revealed that estimated glomerular filtration rate (eGFR) and malignant cancer history were the only 2 factors significantly correlated with in-hospital mortality. The prognostic values for the eGFR and malignant cancer history were acceptable, with areas under the curve of .76 and .67, respectively. Conclusion: The prevalence of in-hospital mortality following hip fracture is low. After adjustment for age, eGFR and malignant cancer history were identified as factors significantly correlated with in-hospital mortality. The findings of this study could assist in the early screening and detection of patients with high in-hospital mortality risks.

Placental mesenchymal dysplasia (PMD) and partial hydatidiform mole (PHM) placentas share similar characteristics, such as placental overgrowth and grape-like placental tissues. Distinguishing PMD from PHM is critical because the former can result in normal birth, while the latter diagnosis will lead to artificial abortion. Aneuploidy and altered dosage of imprinted gene expression are implicated in the pathogenesis of PHM and also some of the PMD cases. Diandric triploidy is the main cause of PHM, whereas mosaic diploid androgenetic cells in the placental tissue have been associated with the formation of PMD. Here, we report a very special PMD case also presenting with trophoblast hyperplasia phenotype, which is a hallmark of PHM. This PMD placenta has a normal biparental diploid karyotype and is functionally sufficient to support normal fetal growth. We took advantage of this unique case to further dissected the potential common etiology between these two diseases. We show that the differentially methylated region (DMR) at NESP55, a secondary DMR residing in the GNAS locus, is significantly hypermethylated in the PMD placenta. Furthermore, we found heterozygous mutations in NLRP2 and homozygous variants in NLRP7 in the mother’s genome. NLRP2 and NLRP7 are known maternal effect genes, and their mutation in pregnant females affects fetal development. The variants/mutations in both genes have been associated with imprinting defects in mole formation and potentially contributed to the mild abnormal imprinting observed in this case. Finally, we identified heterozygous mutations in the X-linked ATRX gene, a known maternal–zygotic imprinting regulator in the patient. Overall, our study demonstrates that PMD and PHM may share overlapping etiologies with the defective/relaxed dosage control of imprinted genes, representing two extreme ends of a spectrum.

CYP19A1/aromatase (Ar) is a prognostic biomarker of gastric cancer (GCa). Ar is a critical enzyme for converting androstenedione to oestradiol in the steroidogenesis cascade. For decades, Ar has been targeted with Ar inhibitors (ARIs) in gynaecologic malignancies; however, it is unexplored in GCa. A single‐cohort tissue microarray examination was conducted to study the association between Ar expression and disease outcome in Asian patients with GCa. The results revealed that Ar was a prognostic promoter. Bioinformatics analyses conducted on a Caucasian‐based cDNA microarray databank showed Ar to be positively associated with GCa prognosis for multiple clinical modalities, including surgery, 5‐Fluorouracil (5‐FU) for adjuvant chemotherapy, or HER2 positivity. These findings imply that targeting Ar expression exhibits a potential for fulfilling unmet medical needs. Hence, Ar‐targeting compounds were tested, and the results showed that exemestane exhibited superior cancer‐suppressing efficacy to other ARIs. In addition, exemestane down‐regulated Ar expression. Ablating Ar abundance with short hairpin (sh)Ar could also suppress GCa cell growth, and adding 5‐FU could facilitate this effect. Notably, adding oestradiol could not prevent exemestane or shAr effects, implicating a nonenzymatic mechanism of Ar in cancer growth. Regarding translational research, treatment with exemestane alone exhibited tumour suppression efficacy in a dose‐dependent manner. Combining subminimal doses of 5‐FU and exemestane exerted an excellent tumour suppression effect without influencing bodyweight. This study validated the therapeutic potentials of exemestane in GCa. Combination of metronomic 5‐FU and exemestane for GCa therapy is recommended.

AIM To compare the advantage of image-guided brachytherapy (IGBT) over conventional two-dimensional brachytherapy (2DBT) in patients with advanced cervical squamous cell carcinoma. PATIENTS AND METHODS This study included 253 patients with stage IB2-IVA diseases treated with two schemes of brachytherapy. One hundred and thirty-six patients received 2DBT, whereas 117 patients received IGBT. Tumor stage, age, and tumor diameter were matched between the two groups. Local relapse-free survival, overall survival, and cumulative incidences of gastrointestinal and genitourinary complications were compared between the two groups. RESULTS The overall and local relapse-free survival rates were similar between the two groups. The cumulative rate of grade 2 and higher gastrointestinal complication was 21.3% for the 2DBT group, and 8.5% for the IGBT group (p=0.007), whereas that of grade 2 and higher genitourinary injury was 11.8% for the 2DBT group, and 1.7% for the IGBT group (p=0.002). CONCLUSION In patients with advanced cervical squamous cell carcinoma, IGBT achieves a higher therapeutic ratio compared to 2DBT technique by minimizing the late toxicities.

We designed a deep learning model for assessing 18F-FDG PET/CT for early prediction of local and distant failures for patients with locally advanced cervical cancer. All 142 patients with cervical cancer underwent 18F-FDG PET/CT for pretreatment staging and received allocated treatment. To augment the amount of image data, each tumor was represented as 11 slice sets each of which contains 3 2D orthogonal slices to acquire a total of 1562 slice sets. In each round of k-fold cross-validation, a well-trained proposed model and a slice-based optimal threshold were derived from a training set and used to classify each slice set in the test set into the categories of with or without local or distant failure. The classification results of each tumor were aggregated to summarize a tumor-based prediction result. In total, 21 and 26 patients experienced local and distant failures, respectively. Regarding local recurrence, the tumor-based prediction result summarized from all test sets demonstrated that the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 71%, 93%, 63%, 95%, and 89%, respectively. The corresponding values for distant metastasis were 77%, 90%, 63%, 95%, and 87%, respectively. This is the first study to use deep learning model for assessing 18F-FDG PET/CT images which is capable of predicting treatment outcomes in cervical cancer patients. • This is the first study to use deep learning model for assessing 18 F-FDG PET/CT images which is capable of predicting treatment outcomes in cervical cancer patients. • All 142 patients with cervical cancer underwent 18 F-FDG PET/CT for pretreatment staging and received allocated treatment. To augment the amount of image data, each tumor was represented as 11 slice sets each of which contains 3 2D orthogonal slices to acquire a total of 1562 slice sets. • For local recurrence, all test sets demonstrated that the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 71%, 93%, 63%, 95%, and 89%, respectively. The corresponding values for distant metastasis were 77%, 90%, 63%, 95%, and 87%, respectively.

Use of chimeric antigen receptors (CARs) as the basis of targeted adoptive T cell therapies has enabled dramatic efficacy against multiple hematopoietic malignancies, but potency against bulky and solid tumors has lagged, potentially due to insufficient CAR-T cell expansion and persistence. To improve CAR-T cell efficacy, we utilized a potent activation switch based on rimiducid-inducible MyD88 and CD40 (iMC)-signaling elements. To offset potential toxicity risks by this enhanced CAR, an orthogonally regulated, rapamycin-induced, caspase-9-based safety switch (iRC9) was developed to allow in vivo elimination of CAR-T cells. iMC costimulation induced by systemic rimiducid administration enhanced CAR-T cell proliferation, cytokine secretion, and antitumor efficacy in both in vitro assays and xenograft tumor models. Conversely, rapamycin-mediated iRC9 dimerization rapidly induced apoptosis in a dose-dependent fashion as an approach to mitigate therapy-related toxicity. This novel, regulatable dual-switch system may promote greater CAR-T cell expansion and prolonged persistence in a drug-dependent manner while providing a safety switch to mitigate toxicity concerns. Keywords: CAR-T, dimerizer, cell therapy, costimulation switch, apoptosis, rapamycin, rimiducid, iMC, iRC9, safety switch