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BACKGROUND: To compare the effects of proton pump inhibitor (PPI) and histamine-2 receptor antagonist (H2RA) use on the occurrence of acute kidney injury (AKI) in septic patients at high risk for developing stress ulcers. METHODS: Using the Medical Information Mart for Intensive Care IV version 2.2 database, septic patients with high-risk factors for stress ulcers (i.e., shock, coagulopathy, invasive mechanical ventilation, or chronic liver diseases) were included. Exposures included PPIs and H2RAs within 24 h of intensive care unit (ICU) admission or prior to ICU admission. The primary end point was severe sepsis-associated AKI as defined by the Kidney Disease Improving Global Outcomes criteria stage 3 (KDIGO-3). Propensity score matching (PSM) was performed to balance baseline characteristics. Multivariable Cox proportional hazards regression was used to estimate the effect size. RESULTS: 4731 PPI users and 4903 H2RA users were included. After PSM, there were 1785 pairs exposed to PPIs and H2RAs. In the PSM cohort, the cumulative incident KDIGO-3 rate was higher in the PPI group than in the H2RA group (log-rank test, p = 0.009). Regression analyses showed that PPI exposure [adjusted hazard ratio 1.32, 95% confidence interval (CI) 1.11-1.58, p = 0.002] was associated with incident KDIGO-3 compared with H2RA use. This association remained consistent in sensitivity analyses. Additionally, the PPI group had a higher need for kidney replacement therapy compared with the H2RA group (3.6% vs. 2.1%, P = 0.012). CONCLUSIONS: Among septic patients at high risk for developing stress ulcers, PPI exposure was associated with incident KDIGO-3 AKI compared with H2RA use.
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Injúria Renal Aguda , Antagonistas dos Receptores H2 da Histamina , Inibidores da Bomba de Prótons , Sepse , Humanos , Inibidores da Bomba de Prótons/efeitos adversos , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/uso terapêutico , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Antagonistas dos Receptores H2 da Histamina/efeitos adversos , Masculino , Feminino , Sepse/complicações , Pessoa de Meia-Idade , Idoso , Fatores de Risco , Unidades de Terapia Intensiva , Estudos Retrospectivos , Pontuação de Propensão , Úlcera Péptica/complicações , Úlcera Péptica/tratamento farmacológico , Estudos de CoortesRESUMO
Vitamin B5 [D-pantothenic acid (D-PA)] is an essential water-soluble vitamin that is widely used in the food and feed industries. Currently, the relatively low fermentation efficiency limits the industrial application of D-PA. Here, a plasmid-free D-PA hyperproducer was constructed using systematic metabolic engineering strategies. First, pyruvate was enriched by deleting the non-phosphotransferase system, inhibiting pyruvate competitive branches, and dynamically controlling the TCA cycle. Next, the (R)-pantoate pathway was enhanced by screening the rate-limiting enzyme PanBC and regulating the other enzymes of this pathway one by one. Then, to enhance NADPH sustainability, NADPH regeneration was achieved through the novel "PEACES" system by (1) expressing the NAD + kinase gene ppnk from Clostridium glutamicum and the NADP + -dependent gapCcae from Clostridium acetobutyricum and (2) knocking-out the endogenous sthA gene, which interacts with ilvC and panE in the D-PA biosynthesis pathway. Combined with transcriptome analysis, it was found that the membrane proteins OmpC and TolR promoted D-PA efflux by increasing membrane fluidity. Strain PA132 produced a D-PA titer of 83.26 g/L by two-stage fed-batch fermentation, which is the highest D-PA titer reported so far. This work established competitive producers for the industrial production of D-PA and provided an effective strategy for the production of related products.
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Escherichia coli , Engenharia Metabólica , Ácido Pantotênico , Escherichia coli/genética , Escherichia coli/metabolismo , Ácido Pantotênico/biossíntese , Ácido Pantotênico/metabolismoRESUMO
Lung cancer stands as the most prevalent form of cancer globally, posing a significant threat to human well-being. Due to the lack of effective and accurate early diagnostic methods, many patients are diagnosed with advanced lung cancer. Although surgical resection is still a potential means of eradicating lung cancer, patients with advanced lung cancer usually miss the best chance for surgical treatment, and even after surgical resection patients may still experience tumor recurrence. Additionally, chemotherapy, the mainstay of treatment for patients with advanced lung cancer, has the potential to be chemo-resistant, resulting in poor clinical outcomes. The emergence of liquid biopsies has garnered considerable attention owing to their noninvasive nature and the ability for continuous sampling. Technological advancements have propelled circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), extracellular vesicles (EVs), tumor metabolites, tumor-educated platelets (TEPs), and tumor-associated antigens (TAA) to the forefront as key liquid biopsy biomarkers, demonstrating intriguing and encouraging results for early diagnosis and prognostic evaluation of lung cancer. This review provides an overview of molecular biomarkers and assays utilized in liquid biopsies for lung cancer, encompassing CTCs, ctDNA, non-coding RNA (ncRNA), EVs, tumor metabolites, TAAs and TEPs. Furthermore, we expound on the practical applications of liquid biopsies, including early diagnosis, treatment response monitoring, prognostic evaluation, and recurrence monitoring in the context of lung cancer.
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Neoplasias Pulmonares , Células Neoplásicas Circulantes , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Biomarcadores Tumorais/análise , Recidiva Local de Neoplasia , Biópsia Líquida/métodos , Prognóstico , Células Neoplásicas Circulantes/metabolismoRESUMO
Orbital angular momentum (OAM) mode division multiplexing (MDM) systems can support large-capacity and high-speed rate information transmission, in which the OAM mode conversion devices play an important role. In this paper, the mode conversion principle of magneto-optical fiber-based long-period grating (MOF-LPG) is analyzed for further developing new magneto-optical (MO) OAM mode converters, including three types of C P 01 to O A M ±1,1, O A M ±1,1 to O A M ±2,1, and O A M ±1,1 to C P 02. It is shown that the magnetic tunability of the mode converters through the propagation constants of the eigenmodes is useful for compensating for process errors and increasing the operating wavelength range. The implementation of MOF-LPGs is also discussed from the aspect of the prospective experiments.
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We propose a concise hardware architecture supporting efficient exclusive OR (XOR) and exclusive NOR (XNOR) operations, by employing a single photonic spiking neuron based on a passive add-drop microring resonator (ADMRR). The threshold mechanism and inhibitory dynamics of the ADMRR-based spiking neuron are numerically discussed on the basis of the coupled mode theory. It is shown that a precise XOR operation in the ADMRR-based spiking neuron can be implemented by adjusting temporal differences within the inhibitory window. Additionally, within the same framework, the XNOR function can also be carried out by accumulating the input power over time to trigger an excitatory behavior. This work presents a novel, to the best of our knowledge, and pragmatic technique for optical neuromorphic computing and information processing utilizing passive devices.
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BACKGROUND: In view of the lack of attention and predictability in postpartum breastfeeding in primiparas, health education on breastfeeding during pregnancy should be carried out to publicize the benefits of breastfeeding. OBJECTIVE: To investigate how well the primiparas during pregnancy are known of breastfeeding knowledge, and to provide a basis for developing health education measures for them. METHODS: With the adoption of the objective sampling method and the principle of saturation, 10 primiparas in the obstetrics outpatient department of the Hunan Provincial People's Hospital were selected as the study participants. Semi-structured in-depth interviews combined with the observation method were used for data collection. The interview data were analyzed and the theme was refined by Colaizzi's seven-step method. RESULTS: The results of the four themes of the cognition of breastfeeding knowledge among primiparas were as follows: Lack of knowledge and curiosity about breastfeeding in some women, lack of access to correct breastfeeding knowledge, insufficient support from family members for postpartum breastfeeding, and lack of approach to solve problems during breastfeeding among primiparas. CONCLUSION: Due to the current problems of the cognition of breastfeeding knowledge in primiparas, it was imperative to build a health education model suitable for primiparas to improve this knowledge.
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Aleitamento Materno , Cognição , Gravidez , Feminino , Humanos , Pesquisa QualitativaRESUMO
Auxiliary laser heating has become a widely adopted method for Kerr soliton frequency comb generation in optical microcavities, thanks to its reliable and easy-to-achieve merits for solving the thermal instability during the formation of dissipative Kerr solitons. Here, we conduct optimization of auxiliary laser heating by leveraging the distinct loss and absorption characteristics of different longitudinal and polarization cavity modes. We show that even if the auxiliary and pump lasers enter orthogonal polarization modes, their mutual photothermal balance can be efficient enough to maintain a cavity thermal equilibrium as the pump laser enters the red-detuning soliton regime, and by choosing the most suitable resonance for the auxiliary and pump lasers, the auxiliary laser power can be reduced to 20% of the pump laser and still be capable of warranting soliton generation. Moreover, we demonstrate soliton comb generation using integrated laser modules with a few milliwatt on-chip pump and auxiliary powers, showcasing the potential for further chip integration of the auxiliary laser heating method.
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In this paper, we propose a feed-forward equalizer (FFE)-assisted simplified soft-output MLSE (sMLSE) by collaborating the maximum likelihood sequence estimation (MLSE) with soft-decision low-density-parity-check (LDPC) decoding. The simplified sMLSE results in undetermined log-likelihood ratio (LLR) magnitudes when the reserved level is less than or equal to the half of modulation order. This severely degrades the performance of soft-decision forward error correction (SD-FEC) decoding. In the FFE-assisted simplified sMLSE, we use the LLRs calculated from pre-set FFE to replace these undetermined LLRs of simplified sMLSE. Thus, the proposed method eliminates the SD-FEC decoding performance degradation resulted from simplification. We conduct experiments to transmit 184-Gb/s PAM-4 or 255-Gb/s PAM-8 signal in IM-DD system at C-band to evaluate the performance of the proposed sMLSE. The results show that the proposed sMLSE can effectively compensate for the degradation of LLR quality. For 255-Gb/s PAM-8 signal transmissions, the FFE-assisted simplified sMLSE achieves almost the same SD-FEC decoding performance as the conventional sMLSE but with 85% complexity reduction.
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The network traffic of data centers (DCs) has increased unprecedentedly with the rapid development of digital economy. However, the data transmission faces security threats in the distributed optical interconnection and intensive interaction of DC networks. In this paper, we propose a chaotic phase noise-like encryption algorithm using geometric shaping (GS) for coherent DC interconnections (DCIs). A GS constellation is used to improve transmission performance, and it is combined with coherent equalization algorithms to improve security performance. Then, a chaotic encryption is designed based on phase noise-like transformation (PNLT). The data are effectively scrambled, and the confusion level of phase can be increased. Finally, 216 Gb/s 8-quadrature amplitude modulation (8-QAM) encrypted data are successfully verified on a 240â km transmission link of DCIs. The results show that this scheme can achieve a bit error rate (BER) performance gain of 1.1â dB and provide a highly compatible solution for realizing security enhanced DCIs.
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Refractive index perturbation caused by erbium-doped fiber (EDF) bending is inevitable in the fabrication of erbium-doped fiber amplifiers (EDFAs). The resulting mode coupling might bring about the deviation of theoretical results from experimental data. We present a theoretical model of FM-EDFAs with mode coupling due to fiber bending and carry out a proof-of-concept experiment by a 3.2-m-long EDF stretcher. Our experiments show that the fluctuation of modal gain due to fiber bending is about 1.5 dB for L P 01 and L P 11e modes, and about 2.5 dB for L P 11o mode, and the theoretical model is more useful for the FM-EDFA design in the presence of fiber bending.
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The digital subcarrier multiplexing (DSCM) transmission scheme is expected for future ultra-large baud rate transmission. However, the phase noise and transmitter (Tx) IQ skew tolerance are decreased due to the narrow sub-band transmission and conjugated interference from symmetric subcarrier. In this paper, we propose a paired-subcarrier equalization scheme to jointly mitigate the phase noise and Tx IQ skew. We use a phase locking loop (PLL) embedded 4 × 4 MIMO equalizer to simultaneously realize polarization demultiplexing, phase noise and Tx IQ skew compensation. The 4 × 4 MIMO can deal with the paired-subcarrier interference in the DSCM transmission. Besides, since the inner subcarrier suffers smaller interference from its symmetric subcarrier, we estimate the phase noise by inner subcarriers and share the phase noise information with other subcarriers to reduce the overall complexity. Through simulations of 100-GBaud 64-QAM DSCM coherent optical fiber transmission consisting of eight 12.5-Gbaud subcarriers and experiment of 10-GBaud four-subcarriers PM-16QAM transmission, we find that the PLL embedded equalizer for DSCM scheme exhibits better skew and phase noise compensation ability compared with other equalizers. Additionally, we compare the performance of single-carrier and DSCM schemes with the proposed equalizers in simulation. The influence of phase noise and Tx IQ skew on DSCM transmission can be largely relaxed.
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Space-division multiplexing (SDM) has been expected to support the continuous growth of transmission capacity. However, it suffers from high computation complexity that limits its physical implementations. In this paper, we propose and experimentally demonstrate a low-complexity MIMO equalization method to leverage the sparsity of weights and reduce the complexity by L1&L2-regularization in long-haul space-division multiplexing (SDM) systems. The L1-regularization finds the sparse solution of equalizer filters and substitutes it for optimal solution, reducing the complexity with performance degradation. On the other hand, the L2-regularization tends to produce a smoother estimation than L1 regularization and is therefore more robust to large variance. We conduct a 39.87-GBaud QPSK coherent optical transmission experiment based on a 4-core coupled-core fiber with the transmission distance from 1206-km to 7236-km. Comparisons on the equalization performance and computational complexity show that the sparse equalizer using L1&L2-regularization achieves a 30% reduction in complexity at the similar system performance, compared with the traditional time-domain MIMO.
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Alamouti space-time block code (STBC) combined with a simple heterodyne coherent receiver can realize polarization-insensitive phase-diversity detection to reduce the cost. In the receiver, a joint equalizer has been used for STBC's polarization demultiplexing and phase tracking. However, the joint equalizer requires two different step size parameters to update the tap weight coefficients for polarization demultiplexing and the phase noise estimation. This leads to the search process being complex so requiring more iterations for convergence. In this paper, we propose a partially decoupled equalizer that consists of a polarization and phase decoupled equalizer (PPDE) and a pilot-aided blind phase search (P-BPS) algorithm to accelerate the convergence and improve the phase noise tolerance. By theoretically calculating the phase noise, the PPDE can achieve polarization demultiplexing with only one single step size parameter, thus suppressing the searching space and greatly reducing the iterations required for convergence. In the carrier phase recovery stage, the P-BPS algorithm can effectively improve the phase noise tolerance and solve the cyclic slip problem of BPS. We conduct numerical simulations and an experiment to transmit a quadrature phase-shift keying (QPSK) signal. The results demonstrate that the number of iterations required for PPDE convergence is only half of that of the joint equalizer while maintaining polarization-insensitive characteristics in large phase noise. Meanwhile, the achievable linewidth tolerance of P-BPS is increased by three times compared with DD-LMS.
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Microresonator soliton frequency combs offer unique flexibility in synthesizing microwaves over a wide range of frequencies. Therefore, it is very important to study the time jitter of soliton microcombs. Here, we fabricate optical microresonators with perfect transmission spectrum that characterizes highly uniform extinction ratio and absence of mode interactions by laser machining high-purity silica fiber preforms. Based on such perfect whispering-gallery-mode cavity, We demonstrate that K-band microwave with ultra-low phase noise (-83 dBc/Hz@100â Hz; -112 dBc/Hz@1kHz; -133 dBc/Hz@10kHz) can be generated by photo-detecting the repetition rate of a soliton microcomb. Also, with the Raman scattering and dispersive wave emission largely restricted, we show that ultra-low time jitter soliton has a wide existence range. Our work illuminates a pathway toward low-noise photonic microwave generation as well as the quantum regime of soliton microcombs.
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Background: It is known that ETV6-RUNX1 is usually related to favorable prognosis, but MLL aberration has been associated with poor prognosis among pediatric acute lymphoblastic leukemia (ALL). However, the outcome of coexistence of ETV6-RUNX1 and MLL aberration in pediatric ALL patients is unknown. Herein, we report 4 cases of the coexistence of ETV6-RUNX1 and MLL-partial tandem duplications (MLL-PTD) in pediatric ALL patients and show the favorable outcome, which was never reported before. Case Description: The frequency of coexistence of ETV6-RUNX1 and MLL aberration at our children's medical center was calculated as 0.98% (4/410). All of them were ETV6/RUNX1-positive cases that exhibited MLL-PTD, and the 10-year event-free survival (EFS) and overall survival (OS) were both 75%. With the following keywords of "ETV6-RUNX1", "MLL", "children" and "acute lymphoblastic leukemia", a literature search of coexistence of ETV6-RUNX1 and MLL aberration was conducted in the database of PubMed, and 4 articles were retrieved finally, involving 16 cases of children. Among the 16 cases of pediatric ALL, the age ranged from 2 to 7 years old, including 9 males and 7 females and the white blood cell (WBC) count was (2.66-68.6)×109/L. In terms of fusion genes, they all had positive ETV6/RUNX1. Among them, MLL deletion was exhibited among 8 ETV6/RUNX1-positive patients, and 2 cases of der(21) duplication. MLL allelic deletions were shown among the remaining ETV6/RUNX1-positive patients. All patients showed a favorable outcome. Conclusions: The results of our analysis primarily provide compelling evidence that cases with an MLL-PTD or other types of MLL aberration are in fact a distinct subentry among ETV6-RUNX1 B-cell ALL (B-ALL).
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We propose a time-delayed photonic reservoir computing (RC) architecture utilizing a reflective semiconductor optical amplifier (RSOA) as an active mirror. The performance of the proposed RC structure is investigated by two benchmark tasks, namely the Santa Fe time-series prediction task and the nonlinear channel equalization task. The simulation results show that both the prediction and equalization performance of the proposed system are significantly improved with the contribution of RSOA, with respect to the traditional RC system using a mirror. By increasing the drive current of the RSOA, the greater nonlinearity of the RSOA gain saturation is achieved, as such the prediction and equalization performance are enhanced. It is also shown that the proposed RC architecture shows a wider consistency interval and superior robustness than the traditional RC structure for most of the measured parameters such as coupling strength, injection strength, and frequency detuning. This work provides a performance-enhanced time-delayed RC structure by making use of the nonlinear transformation of the RSOA feedback.
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All-optical phase regeneration aims at restoring the phase information of coherently encoded data signals directly in the optical domain so as to compensate for phase distortions caused by transceiver imperfections and nonlinear impairments along the transmission link. Although it was proposed two decades ago, all-optical phase regeneration has not been seen in realistic networks to date, mainly because this technique entails complex bulk modules and relies on high-precision phase sensitive nonlinear dynamics, both of which are adverse to field deployment. Here, we demonstrate a new, to the best of our knowledge, architecture to implement all-optical phase regeneration using integrated photonic devices. In particular, we realize quadrature phase quantization by exploring the phase-sensitive parametric wave mixing within on-chip silicon waveguides, while multiple coherent pump laser tones are provided by a chip-scale micro-cavity Kerr frequency comb. Multi-channel all-optical phase regeneration is experimentally demonstrated for 40 Gbps QPSK data, achieving the best SNR improvement of more than 6â dB. Our study showcases a promising avenue to enable the practical implementation of all-optical phase regeneration in realistic long-distance fiber transmission networks.
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Background: The childhood patients with mixed-lineage leukemia rearrangement (MLL-r) gene have worse outcome than non-MLL, and thus often treated with high-risk chemotherapy regimens, so targeted therapy is important for this type of leukemia. This purpose of study was to explore the effects of ruxolitinib on the proliferation, apoptosis, and cell cycle of Nalm-6 cells. Methods: In this study, human acute lymphoblastic leukemia (ALL) cell line Nalm-6 was used as the research object. By constructing an MLL overexpression vector to transfect Nalm-6 cells, exogenous JAK2/STAT3 signal pathway inhibitor ruxolitinib was applied to observe the proliferation, apoptosis, and cell cycle changes of the transfected Nalm-6 cells. Western blot was performed to determine the proteins (MLL-BP, JAK, STAT) involved in the mechanism of action of MLL-r leukemia. CCK8 assay and flow cytometry (FCM) were used for testing the proliferation and apoptosis among MLL-BP transfected Nalm-6 cells. Results: Firstly, we determine the IC50 of ruxolitinib on Nalm-6 cells. Secondly, FCM and CCK8 showed that ruxolitinib dosedependentlyinhibits proliferation of Nalm-6 cells by blocking the cell cycle at G0/G1 phase. In addition, FCM showed that ruxolitinib promoted the apoptosis of MLL-BP transfected Nalm-6 cells. Mechanistically, ruxolitinib inactivated JAK/STAT signaling pathway in MLL-BP transfected Nalm-6 cells, mediating ruxolitinib's inhibition of cell proliferation, and inducing apoptosis. Finally, ruxolitinib significantly inhibited the proliferation of MLL-r ALL cells and promoted their apoptosis. Conclusions: These data provide compelling evidence that ruxolitinib is a promising agent against MLL-r leukemia cell line. However, it needs going through multiple more steps to confirm before it can be an option in clinical practice.
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Optical signal processing (OSP) technology is a crucial part of the optical switching node in the modern optical-fiber communication system, especially when advanced modulation formats, e.g., quadrature amplitude modulation (QAM), are applied. However, the conventional on-off keying (OOK) signal is still widely used in access or metro transmission systems, which leads to the compatibility requirement of OSP for incoherent and coherent signals. In this paper, we propose a reservoir computing (RC)-OSP scheme based on nonlinear mapping behavior through a semiconductor optical amplifier (SOA) to deal with the non-return-to-zero (NRZ) signals and the differential quadrature phase-shift keying (DQPSK) signals in the nonlinear dense wavelength-division multiplexing (DWDM) channel. We optimized the key parameters of SOA-based RC to improve compensation performance. Based on the simulation investigation, we observed a significant improvement in signal quality over 10 dB compared to the distorted signals on each DWDM channel for both the NRZ and DQPSK transmission cases. The compatible OSP achieved by the proposed SOA-based RC could be a potential application of the optical switching node in the complex optical fiber communication system, where incoherent and coherent signals meet.
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Semicondutores , Processamento de Sinais Assistido por Computador , Desenho de Equipamento , Análise de Falha de Equipamento , Fibras ÓpticasRESUMO
Maximum likelihood sequence estimation (MLSE) is the optimal signal sequence detection that can remove the inter-symbol interference (ISI). However, we find that the MLSE causes burst consecutive errors alternating between +2 and -2 in M-ary pulse amplitude modulation (PAM-M) IM/DD systems with large ISI. In this paper, we propose to use precoding to suppress the burst consecutive errors resulted from MLSE. A 2 M modulo operation is employed to guarantee that the probability distribution as well as the peak-to-average power ratio (PAPR) of encoded signal remain unchanged. After the receiver-side MLSE, the decoding process that involves adding the current MLSE output to the previous one and applying a 2 M modulo is implemented to break the burst consecutive errors. We conduct experiments to transmit 112/150-Gb/s PAM-4 or beyond 200-Gb/s PAM-8 signals at C-band to investigate the performance of the proposed MLSE integrated with precoding. The results show that the precoding can break burst errors effectively. For 201-Gb/s PAM-8 signal transmission, the precoding MLSE can achieve 1.4-dB receiver sensitivity gain and reduce the maximum length of burst consecutive errors from 16 to 3.