Human sweat contains vast physiological information, which has been a promising resource for on‐body and real‐time health monitoring. Wearable sweat sensors have recently attracted an ever‐increasing ...interest due to their promising capabilities for continuously tracking changes in health status. However, the commercialization of sweat sensors is seriously hindered by drawbacks of materials including high manufacturing and consumables costs, complex integration technology, as well as limited electrochemical signal transduction. In this review, sweat sensing principles are elaborately interpreted, and the latest advances in functional materials for biomarkers sensing in sweat are systematically summarized. Subsequently, the complex structure–activity relationships between various functional materials and sensing capabilities are further elucidated by coupling chemical structures, geometrics, electrochemical properties, and approaches for materials manufacturing. Furthermore, the integration of each component into sensing device for sweat detection and analysis is also discussed. Finally, challenges and opportunities for wearable sweat sensors are delineated in the development of future personalized and predictive healthcare.
Wearable electrochemical sweat sensors have emerged as a type of promising electronic device for continuous monitoring human health. This article reviews the recent progress on various materials for electrochemical sweat sensing. Structure‐activity relationships of sensing materials, approaches for materials manufacturing, and integration of devices are discussed. Challenges and future research directions are also identified.
Current‐induced control of magnetization in ferromagnets using spin–orbit torque (SOT) has drawn attention as a new mechanism for fast and energy efficient magnetic memory devices. Energy‐efficient ...spintronic devices require a spin‐current source with a large SOT efficiency (ξ) and electrical conductivity (σ), and an efficient spin injection across a transparent interface. Herein, single crystals of the van der Waals (vdW) topological semimetal WTe2 and vdW ferromagnet Fe3GeTe2 are used to satisfy the requirements in their all‐vdW‐heterostructure with an atomically sharp interface. The results exhibit values of ξ ≈ 4.6 and σ ≈ 2.25 × 105 Ω‐1 m‐1 for WTe2. Moreover, the significantly reduced switching current density of 3.90 × 106 A cm−2 at 150 K is obtained, which is an order of magnitude smaller than those of conventional heavy‐metal/ferromagnet thin films. These findings highlight that engineering vdW‐type topological materials and magnets offers a promising route to energy‐efficient magnetization control in SOT‐based spintronics.
All‐van der Waals (vdW) heterostructure with an atomically sharp interface based on topological semimetal shows spin–orbit torque (SOT)‐driven magnetization switching. These findings highlight that engineering vdW‐type topological materials and magnets offers a promising route to energy‐efficient magnetization control in SOT‐based spintronics.
The electromechanical brake (EMB) is a key component of the brake-by-wire (BBW) system generating the clamping force between the brake pad and disk through an electric motor and mechanical ...transmission. Control of the clamping force has significant impact on the brake performance. In this paper, an EMB clamping force control system is developed that addresses several major challenges in the practical implementation. Firstly, a nonlinear EMB model including the DC motor, planetary gear set, ball screw, and clamping force model is built. In particular, a novel clamping force model is introduced based on a linear transform of two polynomial functions. For the control system design, a clamping force estimation algorithm is proposed that requires only the existing measurements of motor torque, angular speed, and position. The contact point of the brake pad and the disk is also estimated using an internal model controller and a Rauch-Tung-Striebel smoother. The tracking controller is based on the disturbance observer structure, with a PI feedback controller and a zero-phase error tracking feedforward controller. Furthermore, a unified architecture is proposed such that a smooth transition between gap closing and clamping force tracking is realized. Finally, the performance of the entire control system under various conditions is evaluated based on simulation.
Allele frequencies and haplotype frequencies of HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, -DPA1, and -DPB1 have been rarely reported in South Koreans using unambiguous, phase-resolved next ...generation DNA sequencing. In this study, HLA typing of 11 loci in 173 healthy South Koreans were performed using next generation DNA sequencing with long-range PCR, TruSight.sup.® HLA v2 kit, Illumina MiSeqDx platform system, and Assign.sup.TM for TruSight.sup.TM HLA software. Haplotype frequencies were calculated using the PyPop software. Direct counting methods were used to investigate the association with DRB1 for samples with only one copy of a particular secondary DRB locus. We compared these allele types with the ambiguous allele combinations of the IPD-IMGT/HLA database. We identified 20, 40, 26, 31, 19, 16, 4, and 16 alleles of HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQA1, HLA-DQB1, HLA-DPA1, and HLA-DPB1, respectively. The number of HLA-DRB3/4/5 alleles was 4, 5, and 3, respectively. The haplotype frequencies of most common haplotypes were as follows: A*33:03:01-B*44:03:01-C*14:03-DRB1*13:02:01-DQB1*06:04:01-DPB1*04:01:01 (2.89%), A*33:03:01-B*44:03:01-C*14:03 (4.91%), DRB1*08:03:02-DQA1*01:03:01-DQB1*06:01:01-DPA1*02:02:02-DPB1*05:01:01 (5.41%), DRB1*04:05:01-DRB4*01:03:01 (12.72%), DQA1*01:03:01-DQB1*06:01:01 (13.01%), and DPA1*02:02:02-DPB1*05:01:01 (30.83%). In samples with only one copy of a specific secondary DRB locus, we examined its association with DRB1. We, thus, resolved 10 allele ambiguities in HLA-B, -C (each exon 2+3), -DRB1, -DQB1, -DQA1, and -DPB1 (each exon 2) of the IPD-IMGT/HLA database. Korean population was geographically close to Japanese and Han Chinese populations in the genetic distances by multidimensional scaling (MDS) plots. The information obtained by HLA typing of the 11 extended loci by next generation sequencing may be useful for more exact diagnostic tests on various transplantations and the genetic population relationship studies in South Koreans.
The major histocompatibility complex region has been suggested to play an important role in the development of autoimmune thyroid disease (AITD). In this study, we investigated the associations of ...human leukocyte antigen (HLA) alleles and amino acid variants of HLA with early-onset AITD. HLA class I and class II genes were analyzed in 116 Korean children with AITDs (Graves' disease GD: 71, Hashimoto's disease HD: 45) and 142 healthy controls. HLA-B*46:01 (OR = 3.96, Pc = 0.008), -C*01:02 (OR = 2.51 Pc = 0.04), -DPB1*02:02 (OR = 3.99, Pc = 0.04), and -DPB1*05:01 (OR = 4.6, Pc = 0.003) were significantly associated with GD, and HLA-A*02:07 (OR = 4.68, Pc = 0.045) and -DPB1*02:02 (OR = 6.57, Pc = 0.0001) with HD. The frequency of HLA-DPB1*05:01 was significantly higher in GD patients than in HD patients (Pc = 0.0005). Furthermore, differences were found between patients with Thyroid associated ophthalmopathy (TAO) and those without TAO in the distribution of HLA-B*54:01 (8.6% vs. 30.6%, P = 0.04) and -C*03:03 (37.1% vs. 11.1%, P = 0.02). In the analysis of amino acid variants of HLA molecules, both Leu35 (OR = 23.38, P = 0.0002) and Glu55 (OR = 23.38, P = 0.0002) of HLA-DPB1 were strongly associated with GD and showed different distributions between GD and HD (P = 0.001). Our results suggest that HLA alleles, especially amino-acid signatures of the HLA-DP β chain, might contribute to the molecular pathogenesis of early-onset AITD.
Muscle development and lipid accumulation in muscle critically affect meat quality of livestock. However, the genetic factors underlying myofiber-type specification and intramuscular fat (IMF) ...accumulation remain to be elucidated. Using two independent intercrosses between Western commercial breeds and Korean native pigs (KNPs) and a joint linkage-linkage disequilibrium analysis, we identified a 488.1-kb region on porcine chromosome 12 that affects both reddish meat color (a*) and IMF. In this critical region, only the MYH3 gene, encoding myosin heavy chain 3, was found to be preferentially overexpressed in the skeletal muscle of KNPs. Subsequently, MYH3-transgenic mice demonstrated that this gene controls both myofiber-type specification and adipogenesis in skeletal muscle. We discovered a structural variant in the promotor/regulatory region of MYH3 for which Q allele carriers exhibited significantly higher values of a* and IMF than q allele carriers. Furthermore, chromatin immunoprecipitation and cotransfection assays showed that the structural variant in the 5'-flanking region of MYH3 abrogated the binding of the myogenic regulatory factors (MYF5, MYOD, MYOG, and MRF4). The allele distribution of MYH3 among pig populations worldwide indicated that the MYH3 Q allele is of Asian origin and likely predates domestication. In conclusion, we identified a functional regulatory sequence variant in porcine MYH3 that provides novel insights into the genetic basis of the regulation of myofiber type ratios and associated changes in IMF in pigs. The MYH3 variant can play an important role in improving pork quality in current breeding programs.
We investigated the effects of nilotinib plus multiagent chemotherapy, followed by consolidation/maintenance or allogeneic hematopoietic cell transplantation (allo-HCT) for adult patients with newly ...diagnosed Philadelphia-positive (Ph-pos) acute lymphoblastic leukemia (ALL). Study subjects received induction treatment that comprised concurrent vincristine, daunorubicin, prednisolone, and nilotinib. After achieving complete hematologic remission (HCR), subjects received either 5 courses of consolidation, followed by 2-year maintenance with nilotinib, or allo-HCT. Minimal residual disease (MRD) was assessed at HCR, and every 3 months thereafter. The molecular responses (MRs) were defined as MR3 for BCR-ABL1/G6PDH ratios ≤10−3 and MR5 for ratios <10−5. Ninety evaluable subjects, ages 17 to 71 years, were enrolled in 17 centers. The HCR rate was 91%; 57 subjects received allo-HCT. The cumulative MR5 rate was 94%; the 2-year hematologic relapse-free survival (HRFS) rate was 72% for 82 subjects that achieved HCR, and the 2-year overall survival rate was 72%. Subjects that failed to achieve MR3 or MR5 were 9.1 times (P = .004) or 6.3 times (P = .001) more prone to hematologic relapse, respectively, than those that achieved MR3 or MR5. MRD statuses just before allo-HCT and at 3 months after allo-HCT were predictive of 2-year HRFS. Adverse events occurred mainly during induction, and most were reversible with dose reduction or transient interruption of nilotinib. The combination of nilotinib with high-dose cytotoxic drugs was feasible, and it effectively achieved high cumulative complete molecular remission and HRFS rates. The MRD status at early postremission time was predictive of the HRFS. This trial was registered at www.clinicaltrials.gov as #NCT00844298.
•Nilotinib plus multiagent chemotherapy was feasible and showed a comparable outcome to previous results with imatinib for Ph-pos ALL.•The achievement of deep MR with nilotinib at postremission correlated well with the clinical outcomes for Ph-pos ALL.
Background
Several important changes were made to the 8th edition of the American Joint Committee on Cancer (AJCC) tumor staging system for intrahepatic cholangiocarcinoma (ICC). We assessed the ...prognostic impact of this new tumor staging system compared to the 7th edition.
Methods
A retrospective single‐institution study was performed with 626 patients who underwent R0 resection for ICC over 20‐year period.
Results
Anatomical resection and concurrent bile duct resection were performed in 571 (91.2%) and 62 (9.9%) patients, respectively. Cumulative tumor recurrence and patient survival rates were 40.6% and 73.3% at 1 year; 66.7% and 43.8% at 3 years; 73.6% and 30.4% at 5 years; and 74.4% and 20.3% at 10 years, respectively. Independent prognostic factors for tumor recurrence and patient survival were multiple tumors, carbohydrate antigen 19‐9 >200 U/ml, tumor size >5 cm, direct invasion to extrahepatic structure, and lymph node metastasis. For tumor‐node‐metastasis stages in the 7th versus the 8th editions, concordance index was 0.615 and 0.625 for tumor recurrence and 0.626 and 0.628 for patient survival, respectively.
Conclusions
The 8th edition of the AJCC staging system appears to provide high prognostic contrast for T stage categories, except for T3. However, overall prognostic performance of the 8th edition was not markedly improved over the 7th edition.
Highlight
In this high‐volume single‐center study, Kang and colleagues compared the prognostic impact of the 7th and 8th editions of the AJCC tumor staging system for intrahepatic cholangiocarcinoma. The 8th edition appears to provide high prognostic contrast for most tumor stage categories, but no marked improvement in overall prognostic performance.
What is known and objective
Although patients may have received vancomycin therapy with therapeutic drug monitoring (TDM), those treated with high‐strength and long‐term vancomycin therapy might have ...unstable and time‐varying renal function. The methods used to estimate renal function should not be considered interchangeable with pharmacokinetic (PK) modeling and model‐based estimation of vancomycin pharmacokinetics. While Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) for renal function estimation has been widely integrated into clinical practice, a population PK model including CKD‐EPI has not been established. The study was aimed at developing a new population PK model for optimal vancomycin prediction in patients with time‐varying and variable renal function to evaluate the interchangeability of estimation methods.
Methods
The most suitable population PK model was explored and evaluated using non‐linear mixed‐effect modelling for the best fit of vancomycin concentrations from patients who needed to maintain high trough vancomycin concentrations of >10 mg/L or >15 mg/L. Renal function was estimated using the Cockcroft‐Gault (CG), Modification of Diet in Renal Disease (MDRD) and CKD‐EPI equations. NONMEM 7.4 was used to develop the population PK model.
Results
A total of 328 vancomycin concentrations in 99 patients were used to develop the population PK model. Vancomycin pharmacokinetics was best described by a two‐compartment model. The CKD‐EPI equation for vancomycin clearance was included in the final model among the estimation methods of renal function. A new covariate model, including extended covariate parameters that explain changes in renal function from the population‐predicted value and individual dosing time, provided the best explanation for vancomycin pharmacokinetics among the various models tested.
What is new and conclusion
A new extended covariate model for vancomycin using the CKD‐EPI method may afford suitable dose adjustment for high‐strength and long‐term vancomycin therapy that results in unstable renal function.
Combined hepatocellular carcinoma–cholangiocarcinoma (cHCC‐CC) is a rare disease. We investigated the clinicopathological features of cHCC‐CC and compared the longterm outcomes following liver ...transplantation (LT) and hepatic resection (HR). We identified 32 LT patients with cHCC‐CC through an institutional database search. The HR control group (n = 100) was selected through propensity score‐matching. The incidence of cHCC‐CC among all adult LT patients was 1.0%. Mean patient age was 53.4 ± 6.7 years, and 26 patients were male. Thirty patients had hepatitis B virus infection. All patients of cHCC‐CC were diagnosed incidentally in the explanted livers. Mean tumor diameter was 2.5 ± 1.3 cm, and 28 patients had single tumors. Tumor stage was stage I in 23 and II in 9. Concurrent hepatocellular carcinoma (HCC) was detected in 12 patients with stage I in 5 and II in 7. Mean tumor diameter was 1.9 ± 1.2 cm, and 5 had single tumors. Tumor recurrence and survival rates were 15.6% and 84.4% at 1 year and 32.2% and 65.8% at 5 years, respectively. Patients with very early stage cHCC‐CC (1 or 2 tumors ≤ 2.0 cm) showed 13.3% tumor recurrence and 93.3% patient survival rates at 5 years, which were significantly improved than those with advanced tumors (P = 0.002). Tumor recurrence and survival rates did not differ significantly between the LT and HR control groups (P = 0.22 and P = 0.91, respectively); however, postrecurrence patient survival did (P = 0.016). In conclusion, cHCC‐CC is rarely diagnosed following LT, and one‐third of such patients have concurrent HCC. The longterm posttransplant prognosis was similar following LT and HR. Very early cHCC‐CC resulted in favorable posttransplant prognosis, thus this selection condition can be prudently considered for LT indication. Liver Transplantation 23 330–341 2017 AASLD.
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