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Background Cancer-specific adoptive T cell therapy has achieved successful milestones in multiple clinical treatments. However, the commercial production of cancer-specific T cells is often hampered by laborious cell culture procedures, the concern of retrovirus-based gene transfection, or insufficient T cell purity. Methods In this study, we developed a non-genetic engineering technology for rapidly manufacturing a large amount of cancer-specific T cells by utilizing a unique anti-cancer/anti-CD3 bispecific antibody (BsAb) to directly culture human peripheral blood mononuclear cells (PBMCs). The anti-CD3 moiety of the BsAb bound to the T cell surface and stimulated the differentiation and proliferation of T cells in PBMCs. The anti-cancer moiety of the BsAb provided these BsAb-armed T cells with the cancer-targeting ability, which transformed the naïve T cells into cancer-specific BsAb-armed T cells. Results With this technology, a large amount of cancer-specific BsAb-armed T cells can be rapidly generated with a purity of over 90% in 7 days. These BsAb-armed T cells efficiently accumulated at the tumor site both in vitro and in vivo. Cytotoxins (perforin and granzyme) and cytokines (TNF-α and IFN-γ) were dramatically released from the BsAb-armed T cells after engaging cancer cells, resulting in a remarkable anti-cancer efficacy. Notably, the BsAb-armed T cells did not cause obvious cytokine release syndrome or tissue toxicity in SCID mice bearing human tumors. Conclusions Collectively, the BsAb-armed T cell technology represents a simple, time-saving, and highly safe method to generate highly pure cancer-specific effector T cells, thereby providing an affordable T cell immunotherapy to patients.

Background Adequate fluid removal to achieve euvolemic status can be difficult in patients with incident peritoneal dialysis (PD). Limited treatments such as increased high dextrose PD solutions and icodextrin are currently available. We reported four incident PD patients whose’ ultrafiltration volume was increased after sodium-glucose cotransporter-2 inhibitors. Case presentation. The four reported cases were diabetic kidney disease stage 5 (cases 1–3) and IgA nephritis (case 4) patients whostartedt PD because of acute pulmonary edema (case 1 and 3), nausea vomiting (case 2), and hyperkalemia (case 4). They had an ultrafiltration volume of 700-1000 ml per day but hpersistentted peripheral pitting edema or pulmonary edema. Their ultrafiltration volincreased after dapagliflozin 5 mg daily, and the fluid overload symptoms ere improved. No hypotension, or hypoglycemia was found, and the urine was not increased during dapagliflozin treatment. Conclusions SGLT-2 inhibitors may increase ultrafiltration in incident PD patients. More studies are needed to support the safety of SGLT-2 inhibitors in PD patients.

Background The prognostic role of the cardiothoracic ratio (CTR) in chronic kidney disease (CKD) remains undetermined. Methods We conducted a retrospective cohort study of 3117 patients with CKD aged 18–89 years who participated in an Advanced CKD Care Program in Taiwan between 2003 and 2017 with a median follow up of 1.3(0.7–2.5) and 3.3(1.8–5.3) (IQR) years for outcome of end-stage renal disease (ESRD) and overall death, respectively. We developed a machine learning (ML)–based algorithm to calculate the baseline and serial CTRs, which were then used to classify patients into trajectory groups based on latent class mixed modelling. Association and discrimination were evaluated using multivariable Cox proportional hazards regression analyses and C-statistics, respectively. Results The median (interquartile range) age of 3117 patients is 69.5 (59.2–77.4) years. We create 3 CTR trajectory groups (low [30.1%], medium [48.1%], and high [21.8%]) for the 2474 patients with at least 2 CTR measurements. The adjusted hazard ratios for ESRD, cardiovascular mortality, and all-cause mortality in patients with baseline CTRs ≥0.57 (vs CTRs P = 0.04) for cardiovascular mortality and 0.697 (vs 0.693, P Conclusions Our findings support the real-world prognostic value of the CTR, as calculated by a ML annotation tool, in CKD. Our research presents a methodological foundation for using machine learning to improve cardioprotection among patients with CKD.

Photocatalytic water splitting is attracting considerable interest because it enables the conversion of solar energy into hydrogen for use as a zero-emission fuel or chemical feedstock. Herein, we present a universal approach for inserting hydrophilic non-conjugated segments into the main-chain of conjugated polymers to produce a series of discontinuously conjugated polymer photocatalysts. Water can effectively be brought into the interior through these hydrophilic non-conjugated segments, resulting in effective water/polymer interfaces inside the bulk discontinuously conjugated polymers in both thin-film and solution. Discontinuously conjugated polymer with 10 mol% hexaethylene glycol-based hydrophilic segments achieves an apparent quantum yield of 17.82% under 460 nm monochromatic light irradiation in solution and a hydrogen evolution rate of 16.8 mmol m−2 h−1 in thin-film. Molecular dynamics simulations show a trend similar to that in experiments, corroborating that main-chain engineering increases the possibility of a water/polymer interaction. By introducing non-conjugated hydrophilic segments, the effective conjugation length is not altered, allowing discontinuously conjugated polymers to remain efficient photocatalysis.

Primary hyperparathyroidism has deleterious effects on health and causes nephrolithiasis and osteoporosis. However, it remains unclear whether parathyroidectomy benefits kidney function among patients with primary hyperparathyroidism. In this retrospective study, patients with primary hyperparathyroidism receiving parathyroidectomy in a tertiary medical center between 2003 and 2017 were followed up until December 31 2017, death, or requiring renal replacement therapy. Impact of parathyroidectomy on kidney function was examined using longitudinal estimated glomerular filtration rate (eGFR) change scales: single, average, absolute difference, percent change, annual decline rate, and slope. We applied linear mixed-effect model to determine the effect of parathyroidectomy on kidney function. During study period, 167 patients with primary hyperparathyroidism were identified from 498 parathyroidectomized patients, and finally, 27 patients fulfilled our stringent criteria. Median follow-up duration was 1.50 years (interquartile range 1.05–1.81) before surgery and 2.47 years (1.37–6.43) after surgery. Although parathyroidectomy did not affect amount of proteinuria and distribution of eGFR, parathyroidectomy significantly slowed decline rate of eGFR compared with that before surgery (− 1.67 versus − 2.73 mL/min/1.73 m2/year, p

Recently, researchers have focused on optoelectronics based on two-dimensional van der Waals materials to realize multifunctional memory and neuron applications. Layered indium selenide (InSe) semiconductors satisfy various requirements as photosensitive channel materials, and enable the realization of intriguing optoelectronic applications. Herein, we demonstrate InSe photonic devices with different trends of output currents rooted in the carrier capture/release events under various gate voltages. Furthermore, we reported an increasing/flattening/decreasing synaptic weight change index (∆Wn) via a modulated gate electric field, which we use to imitate medicine-acting metaplasticity with effective/stable/ineffective features analogous to the synaptic weight change in the nervous system of the human brain. Finally, we take advantage of the low-frequency noise (LFN) measurements and the energy-band explanation to verify the rationality of carrier capture-assisted optoelectronics applied to neural simulation at the device level. Utilizing optoelectronics to simulate essential biomedical neurobehaviors, we experimentally demonstrate the feasibility and meaningfulness of combining electronic engineering with biomedical neurology.

Background Bacterial cultures allow the identification of infectious disease pathogens. However, obtaining the results of conventional culture methods is time-consuming, taking at least two days. A more efficient alternative is the use of concentrated bacterial samples to accelerate culture growth. Our study focuses on the development of a high-yield sample concentrating technique. Results A total of 71 paired samples were obtained from patients on peritoneal dialysis (PD). The peritoneal dialysates were repeat-centrifuged and then washed with saline, namely the centrifuging and washing method (C&W method). The concentrated samples were Gram-stained and inoculated into culture plates. The equivalent unprocessed dialysates were cultured as the reference method. The times until culture results for the two methods were compared. The reference method yielded no positive Gram stain results, but the C&W method immediately gave positive Gram stain results for 28 samples (p p = 0.044). The average time for bacterial identification achieved with the C&W method (22.0 h) was shorter compared to using the reference method (72.5 h) (p Conclusions The C&W method successfully concentrated bacterial samples and superseded blood culture bottles for developing adequate bacterial cultures. The C&W method may decrease the culture report time, thus improving the treatment of infectious diseases.

In the present study, we aim to help improve the design of van der Waals stacking, i.e., vertical 2D electronics, by probing charge transport differences in both parallel and vertical conducting channels of layered molybdenum disulfide (MoS2), with thin graphite acting as source and drain electrodes. To avoid systematic errors and variable contact contributions to the MoS2 channel, parallel and vertical electronics are all fabricated and measured on the same conducting material. Large differences in the on/off current ratio, mobility, and charge fluctuations, between parallel and vertical electronics are evident in electrical performance as well as in charge transport mechanisms. Further insights are drawn from a well-constrained analysis of both temperature-dependent current-voltage characteristics and low-frequency (LF) current fluctuations. This work offers significant insight into the fundamental understanding of charge transport and the development of future layered-materials-based integration technology.

Urothelial cancer (UC) is a common kidney cancer in Taiwan and patients with chronic kidney disease (CKD) are more at risk for UC than the general population. The diagnostic value of urine analysis and urine cytology is limited, especially in CKD patients. The aim of the study is to develop a nomogram to predict the risk of UC in CKD patients. We enrolled 169 UC patients and 1383 CKD patients from 9 hospitals in Taiwan between 2012 and 2015. CA125, HE4, clinical characteristics, and medical history were analyzed using multivariable logistic regression for its association with UC. A nomogram was developed to predict the risk of UC and was validated using Bootstrap. CA125 was associated with UC in CKD patients (OR: 5.91, 95% CI: 3.24–10.77) but HE4 was not (OR: 1.29, 95% CI: 0.67–2.35). A nomogram based on patients’ age, estimated glomerular filtration rate, CA125 (log transformed), smoking, exposure of environmental toxin, use of nonsteroid anti-inflammatory drugs, and use of traditional Chinese medicine was conducted. The AUC of the nomogram was 0.90 (95% CI: 0.86–0.92, p

Background Abdominal aortic calcification (AAC) has been known to be associated with cardiovascular mortality in hemodialysis. However, the association between AAC and future coronary artery disease (CAD) occurrence is not clear. We aimed to clarify the association of AAC severity and the occurrence of future CAD events in hemodialysis patients. Methods Hemodialysis (HD) patients were recruited in this prospective cohort study. AAC severity was quantified by AAC score, which was measured by lateral lumbar radiography. We used receiver operation curve (ROC) analysis to find the cutoff AAC value for CAD prediction. CAD-free survival was analyzed by Kaplan-Meier study. Results There were 303 patients recruited for study with a median (interquartile range) follow-up of 95 (65–146) months. The AAC score in patients with occurrence of new CAD [9 (3–15.25), n = 114] was higher than in patients without new CAD occurrence [5 (1–9) n = 189], p

Background Although vertebrates are bilaterally symmetric organisms, their internal organs are distributed asymmetrically along a left-right axis. Disruption of left-right axis asymmetric patterning often occurs in human genetic disorders. In zebrafish embryos, Kupffer’s vesicle, like the mouse node, breaks symmetry by inducing asymmetric expression of the Nodal-related gene, spaw, in the left lateral plate mesoderm (LPM). Spaw then stimulates transcription of itself and downstream genes, including lft1, lft2, and pitx2, specifically in the left side of the diencephalon, heart and LPM. This developmental step is essential to establish subsequent asymmetric organ positioning. In this study, we evaluated the role of krüppel-like factor 8 (klf8) in regulating left-right asymmetric patterning in zebrafish embryos. Methods Zebrafish klf8 expression was disrupted by both morpholino antisense oligomer-mediated knockdown and a CRISPR-Cas9 system. Whole-mount in situ hybridization was conducted to evaluate gene expression patterns of Nodal signalling components and the positions of heart and visceral organs. Dorsal forerunner cell number was evaluated in Tg(sox17:gfp) embryos and the length and number of cilia in Kupffer’s vesicle were analyzed by immunocytochemistry using an acetylated tubulin antibody. Results Heart jogging, looping and visceral organ positioning were all defective in zebrafish klf8 morphants. At the 18–22 s stages, klf8 morphants showed reduced expression of genes encoding Nodal signalling components (spaw, lft1, lft2, and pitx2) in the left LPM, diencephalon, and heart. Co-injection of klf8 mRNA with klf8 morpholino partially rescued spaw expression. Furthermore, klf8 but not klf8△zf overexpressing embryos showed dysregulated bilateral expression of Nodal signalling components at late somite stages. At the 10s stage, klf8 morphants exhibited reductions in length and number of cilia in Kupffer’s vesicle, while at 75% epiboly, fewer dorsal forerunner cells were observed. Interestingly, klf8 mutant embryos, generated by a CRISPR-Cas9 system, showed bilateral spaw expression in the LPM at late somite stages. This observation may be partly attributed to compensatory upregulation of klf12b, because klf12b knockdown reduced the percentage of klf8 mutants exhibiting bilateral spaw expression. Conclusions Our results demonstrate that zebrafish Klf8 regulates left-right asymmetric patterning by modulating both Kupffer’s vesicle morphogenesis and spaw expression in the left LPM. Electronic supplementary material The online version of this article (doi:10.1186/s12929-017-0351-y) contains supplementary material, which is available to authorized users.

Early detection of neck lymph node (LN) recurrence is paramount in improving the prognosis of treated head and neck cancer patients. Ultrasound (US) with US-guided fine needle aspiration (FNA) and core needle biopsy (CNB) have been shown to have great accuracy for LN diagnoses in the untreated neck. However, in the treated neck with fibrosis, their roles are not clarified. Here, we retrospectively review 153 treated head and neck cancer patients who had received US and US-guided FNA/CNB. In multivariate logistic regression analyses, size (short-axis diameter >0.8 cm) (odds ratio (OR) 4.19, P = 0.007), round shape (short/long axis ratio >0.5) (OR 3.44, P = 0.03), heterogeneous internal echo (OR 3.92, P = 0.009) and irregular margin (OR 7.32, P

Asthma is an inflammatory disease and interleukin 12 (IL-12) may play a regulatory role in allergen-induced inflammation. The aim of this study was to investigate the association of polymorphisms in IL-12A/IL-12B with asthma. The asthma group included 198 adult patients and the control group included 453 individuals without asthma that were frequency-matched by gender and age. The distribution of genotypic and allelic frequencies of IL-12A rs568408 demonstrated significant differences between case and control groups. Specifically, the percentages of AA genotype of IL-12A rs568408 was significantly higher among asthmatic patients in Taiwan than healthy controls, compared to GG genotype. No significant difference was observed among the IL-12A rs2243115 and IL-12B rs3212227 genotypes between case and control groups. In addition, the A allele at IL-12A rs568408 was associated with more severe symptoms (P = 0.0085) among asthmatic patients. These results suggest that IL-12A rs568408 may contribute to the etiology and symptoms severity of asthma, indicating its usefulness as a predictive and diagnostic biomarker of asthma.

Background Pruritus is a common and frustrating symptom in hemodialysis (HD) patients and 5-D itch scale is proposed as a reliable measurement of pruritus. However, information regarding 5-D itch scale categories is currently unavailable. We explored optimal cut-offs 5-D itching scale based on numerical rating scale (NRS) categories in HD patients. Methods Four hundred and nine HD patients in China Medical University Hospital in December 2014 were included and severity of pruritus was estimated using NRS and 5-D itch scale. The association of NRS and 5-D itch scale was analyzed by linear regression. The optimal cut-offs for 5-D itch scale based on NRS categories were generated. Results The average NRS was 3.4 ± 3.0 and the average 5-D itch scale was 10.9 ± 4.8. The 5-D score was strongly correlated with the NRS: r = 0.831 (p

Matrix metalloproteinase-9 (MMP-9) plays a crucial role in tumor metastasis. Previous studies showed that polyunsaturated fatty acids exhibit an anti-cancer effect in various human carcinoma cells, but the effect of docosahexaenoic acid (DHA) and linoleic acid (LA) on metastasis of breast cancer cells is not fully clarified. We studied the anti-metastasis potential of DHA and LA in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MCF-7 cells. We found that TPA (100 ng/ml) induced MMP-9 enzyme activity both dose- and time-dependently, and 200 μM DHA and LA significantly inhibited MMP-9 mRNA and protein expression, enzyme activity, cell migration, and invasion. Treatment with PD98059 (10 μM), wortmannin (10 μM), and GF109203X (0.5 μM) decreased TPA-induced MMP-9 protein expression and enzyme activity. TPA-induced activation of ERK1, Akt, and PKCδ was attenuated by DHA, whereas LA attenuated only ERK1 activation. GF109203X also suppressed ERK1 activation. EMSA showed that DHA, LA, PD98059, and wortmannin decreased TPA-induced NF-κB and AP-1 DNA-binding activity. Furthermore, DHA rather than LA dose-dependently increased HO-1 expression. HO-1 siRNA alleviated the inhibition by DHA of TPA-induced MMP-9 protein expression and enzyme activity in MCF-7 cells, and HO-1 knockdown reversed the DHA inhibition of cell migration. These results suggest that DHA and LA have both similar and divergent signaling pathways in the suppression of TPA-induced MCF-7 metastasis.

The suitability of the Levy-stable distribution for geophysical data from a sedimentary environment has been investigated. Four types of geophysical well logging measurements from the Choshuichi alluvial fan in central Taiwan were analyzed—long-normal electrical resistivity, short-normal electrical resistivity, natural gamma-ray logging, and spontaneous potential. The results demonstrate that the Levy-stable distribution describes the geophysical data better than a Gaussian distribution. Because the Levy-stable distribution is flexible in fitting data from strongly heterogeneous fields and the traditional Gaussian distribution is only its special case, the Levy-stable distribution should be considered when analyzing geophysical data.

Orientation relationships between the growth direction of carbon nanotubes and encapsulated residual iron-containing particles have been determined using transmission electron microscopy. The nanotubes that are prepared by Fe-catalysed chemical vapour deposition on sol–gel Fe(NO3)3-tetraethyl orthosilicate substrates are the helical multiwall type. Nanoscale particles of both the low-temperature α-Fe (ferrite) and high-temperature γ-Fe (austenite) were found in the cavity of the carbon nanotubes with $$ {\left\langle {001} \right\rangle }_{\alpha } $$ , $$ {\left\langle {011} \right\rangle }_{\alpha } $$ and $$ {\left\langle {110} \right\rangle }_{\gamma } $$ parallel to the tube growth direction, respectively. Cementite Fe3C, the most abundant Fe-containing phase in present samples was also found to be entrapped in nanotubes with $$ {\text{[100]}}_{{{\text{Fe}}_{{\text{3}}} {\text{C}}}} $$ or $$ {\text{[101]}}_{{{\text{Fe}}_{{\text{3}}} {\text{C}}}} $$ parallel to the tube axis. The metastable retention of γ-Fe particles at room temperature is ascribed to the strain energy induced at the particle-nanotube interface due to volume expansion upon the γ- → α-Fe phase transformation. The decomposition of initially high aspect-ratio, rod-shape particles into a string of ovulation, while encapsulated in carbon nanotubes is accounted for by the Rayleigh instability. Ovulation leading to reduced particle size has also contributed to increase the surface energy term that counterbalances the total free energy change of phase transformation from γ- to α-Fe and further aids to the metastable retention of γ-Fe.