Long-term forecasting of a motor outcome following rehabilitation in chronic stroke via a hierarchical bayesian dynamic model.

BACKGROUND: Given the heterogeneity of stroke, it is important to determine the best course of motor therapy for each patient, i.e., to personalize rehabilitation based on predictions of long-term outcomes. Here, we propose a hierarchical Bayesian dynamic (i.e., state-space) model (HBDM) to forecast long-term changes in a motor outcome due to rehabilitation in the chronic phase post-stroke. METHODS: The model incorporates the effects of clinician-supervised training, self-training, and forgetting. In addition, to improve forecasting early in rehabilitation, when data are sparse or unavailable, we use the Bayesian hierarchical modeling technique to incorporate prior information from similar patients. We use HBDM to re-analyze the Motor Activity Log (MAL) data of participants with chronic stroke included in two clinical trials: (1) the DOSE trial, in which participants were assigned to a 0, 15, 30, or 60-h dose condition (data of 40 participants analyzed), and (2) the EXCITE trial, in which participants were assigned a 60-h dose, in either an immediate or a delayed condition (95 participants analyzed). RESULTS: For both datasets, HBDM accounts well for individual dynamics in the MAL during and outside of training: mean RMSE = 0.28 for all 40 DOSE participants (participant-level RMSE 0.26 ± 0.19-95% CI) and mean RMSE = 0.325 for all 95 EXCITE participants (participant-level RMSE 0.32 ± 0.31), which are small compared to the 0-5 range of the MAL. Bayesian leave-one-out cross-validation shows that the model has better predictive accuracy than static regression models and simpler dynamic models that do not account for the effect of supervised training, self-training, or forgetting. We then showcase model's ability to forecast the MAL of "new" participants up to 8 months ahead. The mean RMSE at 6 months post-training was 1.36 using only the baseline MAL and then decreased to 0.91, 0.79, and 0.69 (respectively) with the MAL following the 1st, 2nd, and 3rd bouts of training. In addition, hierarchical modeling improves prediction for a patient early in training. Finally, we verify that this model, despite its simplicity, can reproduce previous findings of the DOSE trial on the efficiency, efficacy, and retention of motor therapy. CONCLUSIONS: In future work, such forecasting models can be used to simulate different stages of recovery, dosages, and training schedules to optimize rehabilitation for each person. Trial registration This study contains a re-analysis of data from the DOSE clinical trial ID NCT01749358 and the EXCITE clinical trial ID NCT00057018.

Performance optimization of multi-plane light conversion (MPLC) mode multiplexer by error tolerance analysis.

The linear polarized (LP) mode multiplexer based on the inverse designed multi-plane light conversion (MPLC) has the advantages of low insertion loss and low mode crosstalk. However, the multiplexer also requires the fabrication and alignment accuracy in experiments, which have not been systematically analyzed. Here, we perform the error tolerance analysis of the MPLC and summarize the design rules for the LP mode multiplexer/demultiplexer. The error tolerances in the fabrication process and experimental demonstration are greatly released with proper parameters of the input/output optical beam waist, the pitch of optical beam array, and the propagation distances between the phase plane. To proof this design rule, we experimentally demonstrate the LP mode multiplexer generating LP01, LP11a, LP11b, LP21 modes and coupling to the few mode fiber, with the insertion loss lower than -5 dB. The LP modes are demultiplexed by MPLC, with the crosstalk of different mode groups lower than -10 dB. LP modes carrying 10 Gbit/s on-off keying signals transmit in a 5 km few mode fiber. The measured bit error rates (BER) curves of the LP01, LP11a, LP21 modes have the power penalties lower than 12 dB.

Polygon Coherent Modes in a Weakly Perturbed Whispering Gallery Microresonator for Efficient Second Harmonic, Optomechanical, and Frequency Comb Generations.

We observe high optical quality factor (Q) polygonal and star coherent optical modes in a lithium niobate microdisk. In contrast to the previous polygon modes achieved by deformed microcavities at lower mechanical and optical Q, we adopt weak perturbation from a tapered fiber for the polygon mode formation. The resulting high intracavity optical power of the polygon modes triggers second harmonic generation at high efficiency. With the combined advantages of a high mechanical Q cavity, we observe optomechanical oscillation in polygon modes for the first time. Finally, we observe frequency microcomb generation from the polygon modes with an ultrastable taper-on-disk coupling mechanism.

[Safety of eight nucleic acid dyeson].

OBJECTIVE: To study the safety of eight nucleic acid dyes: EB, GelGreen, GoldView, GeneGreen, SYBRGreen I, GelRed, SYBRSafe and SYBRGold. METHODS: Salmonell atyphimurium TA97, TA98, TA100 and TA102 involved in the minimum inhibitory concentration(MIC) of the 8 nucleic acid dyes by the Broth dilution, which follows Clinical and Laboratory Standards Institute. The experiment tests the reverse mutation of bacteria with the 8 nucleic acid dyes, which follows GB 15193. 4-2014. RESULTS: EB and its metabolites show significant mutagenicity on TA97, TA98, TA100 and TA102. SYBRGold and its metabolites do not show mutagenicity on TA97, TA98, TA100 and TA102. The other six dyes show varying mutagenicity on TA97, TA98 and TA102, meanwhile show no mutagenicity on TA100. CONCLUSION: This research shows that, except EB, the other dyes show no mutagenicity under working concentration, but show varying mutagenicity under high concentration. SYBRSafe and SYBRGreenI are highly toxic, and the operators must have high precautions when making diluted solution of them.

Efficient electro-optical tuning of an optical frequency microcomb on a monolithically integrated high-Q lithium niobate microdisk.

We demonstrate efficient tuning of a monolithically integrated lithium niobate (LN) microdisk optical frequency microcomb. Utilizing the high optical quality (Q) factor (i.e., Q∼7.1×106) of the microdisk, the microcomb spans over a spectral bandwidth of ∼200nm at a pump power as low as 20.4 mW. Combining the large electro-optic coefficient of LN and the optimum design of the geometry of microelectrodes, we demonstrate electro-optical tuning of the comb with a spectral range of 400 pm and a tuning efficiency of ∼38pm/100V.

Multimode microfiber interferometer for dual-parameters sensing assisted by Fresnel reflection.

A compact and low cost fiber sensor based on single multimode microfiber with Fresnel reflection is proposed and demonstrated for simultaneous measurement of refractive index and temperature. The sensor is fabricated with two simple steps including fiber tapering and then fiber endface cleaving. The reflection spectrum is an intensity modulated interference spectrum, as the tapered fiber generates interference pattern and the cleaved endface provides intensity modulation. By demodulating the fringe power and free spectrum range (FSR) of the spectrum, RI sensitivities of -72.247dB/RIU and 68.122nm/RIU, as well as temperature sensitivities of 0.0283dB/°C and -17pm/°C are obtained. Further, the sensing scheme could also provide the feasibility to construct a more compact sensing probe for dual-paramters measurement, which has great potential in bio/chemical detection.

Refractive index sensitivity characteristics near the dispersion turning point of the multimode microfiber-based Mach-Zehnder interferometer.

The turning point of the refractive index (RI) sensitivity based on the multimode microfiber (MMMF) in-line Mach-Zehnder interferometer (MZI) is observed. By tracking the resonant wavelength shift of the MZI generated between the HE(11) and HE(12) modes in the MMMF, the surrounding RI (SRI) could be detected. Theoretical analysis demonstrates that the RI sensitivity will reach ±∞ on either side of the turning point due to the group effective RI difference (G) approaching zero. Significantly, the positive sensitivity exists in a very wide fiber diameter range, while the negative sensitivity can be achieved in a narrow diameter range of only 0.3 µm. Meanwhile, the experimental sensitivities and variation trend at different diameters exhibit high consistency with the theoretical results. High RI sensitivity of 10777.8 nm/RIU (RI unit) at the fiber diameter of 4.6 µm and the RI around 1.3334 is realized. The discovery of the sensitivity turning points has great significance on trace detection due to the possibility of ultrahigh RI sensitivity.

Simultaneous measurement of refractive index and temperature using multimode microfiber-based dual Mach-Zehnder interferometer.

A multimode microfiber (MMMF)-based dual Mach-Zehnder interferometer (MZI) is proposed and demonstrated for simultaneous measurement of refractive index (RI) and temperature. By inserting a section of MMMF supporting a few modes in the sensing arm of the MZI setup, an inline interference between the fundamental mode and the high-order mode of MMMF, as well as the interference between the high-order mode of MMMF and the reference arm, i.e., the dual MZI, is realized. Due to different interference mechanisms, the former interferometer achieves RI sensitivity of 2576.584 nm/RIU and temperature sensitivity of -0.193 nm/°C, while the latter one achieves RI sensitivity of 1001.864 nm/RIU and temperature sensitivity of 0.239 nm/°C, demonstrating the ability to attain highly accurate multiparameter measurements.

Enumeration and characterization of Salmonella isolates from retail chicken carcasses in Beijing, China.

Epidemiological reports have implicated contaminated raw or undercooked chicken as primary vehicles of Salmonella transmission to human beings. Risk assessments relating to Salmonella contamination of poultry products in China are frequently hampered by the lack of quantitative data. In this study, whole chicken carcasses (n=395) were collected from the retail markets of Beijing, and the level of Salmonella contamination was enumerated by most probable number (MPN) analysis and all Salmonella isolates were further characterized for their serotypes and antimicrobial resistance. Overall, 49.9% (197/395) of the retail whole chicken carcasses were contaminated by Salmonella and the MPN values ranged from 1.5 to >550 MPN/100 g. The 50% percentile of Salmonella MPN value was 7.5 MPN/100 g in chicken carcass. The predominant serotypes isolated were Salmonella Enteritidis (n=309, 94 samples), Salmonella Indiana (n=205, 54 samples) and Salmonella Infantis (n=89, 23 samples). Multidrug-resistant Salmonella isolates were recovered from 100 chicken carcass samples; 102 isolates (from 41 chicken carcasses) even showed resistance to both ciprofloxacin and cefotaxime. Our findings showed a high prevalence of Salmonella contamination in retail chicken carcasses, which could be a source of exposure for consumers to multidrug-resistant isolates. This study provided baseline enumeration data for the risk assessment and evaluation of new control measures of Salmonella contamination in retail chicken products.

Slow rupture in a fluid-rich fault zone initiated the 2024 Mw 7.5 Noto earthquake.

The 2024 moment magnitude (Mw) 7.5 Noto Peninsula (Japan) earthquake caused devastation to communities and was generated by a complex rupture process. Using space geodetic and seismic observations, we show that the event deformed the peninsula with a peak uplift reaching 5 m at the west coast. Shallow slip exceeded 10 m on an offshore fault. Peak stress drop was greater than 10 MPa. This devastating event began with a slow rupture propagation lasting 15-20 s near its hypocenter, where seismic swarms had surged since 2020 due to lower-crust fluid supply. The slow start was accompanied by intense high-frequency seismic radiation. These observations suggest a distinct coseismic slip mode reflecting high heterogeneity in fault properties within a fluid-rich fault zone.

Block copolymer@ZIF-8 nanocomposites as a pH-responsive multi-steps release system for controlled drug delivery.

Developing the hybrid nanosystems for controlled drug release is still a challenging task. In this work, pH-responsive core-shell nanocomposites have been prepared by the growth of zeolitic imidazolate framework-8 (ZIF-8) on the surface of polymeric aggregates self-assembled from poly(ε-caprolactone)-block-poly (quaternized vinylbenzyl chloride/bipyridine) (PCL-b-q(PVBC/BPy), BCP for short) in water. The core of the micelles or the inner cavity of vesicles serves as the drug storage reservoir for the doxorubicin hydrochloride (DOX) and the ZIF-8 shells act as the gatekeepers to prevent drug premature release at physiological environment. Upon pH stimulus, the core-shell nanocomposites (BCP@ZIF-8) show a retarded drug release behavior compared with DOX-loaded polymeric aggregates counterparts (without the shell of ZIF-8). Moreover, the as-prepared nanocomposites perform good biocompatibility towards MCF-7 cell. Meanwhile, the DOX-loaded BCP@ZIF-8 nanocomposites present lower cytotoxicity compared with DOX-loaded BCP and free DOX. The confocal microscopy study shows the core-shell nanocomposites could be efficiently internalized by cancer cells, and the loaded DOX could be successfully released under acidic intracellular environment. The above result shows that the core-shell nanocomposite could be a promising candidate for pH-responsive drug delivery system in the cancer therapy.

Characterization of an Oxacillin-Susceptible mecA-Positive Staphylococcus aureus Isolate from an Imported Meat Product.

Methicillin-resistant Staphylococcus aureus (MRSA) isolates that carry mecA but are oxacillin susceptible (OS-MRSA; oxacillin minimum inhibitory concentration [MIC] ≤2 µg/mL) are increasingly reported worldwide in the past decade. In this study, an OS-MRSA isolate FC1102921 from an imported meat sample was characterized and the oxacillin resistance mutation frequency and mutant prevention concentration (MPC) to oxacillin was determined. Isolate FC1102921 was pvl negative and contained SCCmec V (5C2&5), the sequence type and spa type were identified as ST398-t034. The MPCs of isolate FC1102921 to oxacillin was 16 µg/mL. The resistance mutation frequency of isolate FC1102921 to oxacillin was 0.036%. The expression of mecA in isolate FC1102921 was detectable, but the mecA expression in the mutant isolate FC1102921m increased 13.8-folds. Our data indicated that S. aureus FC1102921 was not a hypermutator, and the high-resistance mutation frequency of S. aureus FC1102921 was specific to oxacillin and penicillin. SCCmec V region of isolate FC1102921 and FC1102921m was identical, functional blaI and blaR1 were identified in SCCmec region of both isolates, and no plasmid loss was identified in mutant isolate FC1102921m. To the best of our knowledge, this is the first report of the resistance mutation frequency and MPC study of an OS-MRSA ST398-t034 isolate. The high oxacillin MPC value and high oxacillin resistance mutation frequency was not related to a curable plasmid as previously reported, which further highlighted that an in-depth study should be carried out to clarify the mechanism and role of the OS-MRSA isolates in the emergence and transmission of MRSA ST398-t034.

Identification and Quantification of Nonviable Lactobacillus pentosus Cells in a Health Food Product.

BACKGROUND: The lack of formal protocol to verify the nonviable cell probiotic product authenticity blocks its registration and supervision process. OBJECTIVE: To develop a protocol for identification, enumeration, and purity determination of a Lactobacillus pentosus nonviable cell product. METHODS: The 16S ribosomal RNA (rRNA) sequencing, 16S rRNA metagenomic analysis, whole-genome sequencing, matrix-assisted laser desorption ionization-time of flight MS (MALDI-TOF-MS), and FACSMicroCount™ system were applied to establish a protocol of identification, enumeration and purity determination of a Lactobacillus pentosus nonviable cell product. RESULTS: The 1530 bp of 16S rRNA sequence could only identify the bacteria at genus level, but the MALDI-TOF-MS could identify both the nonviable cell and fresh culture to species level with high confidence. Metagenomic analysis of the 16S rRNA amplicon could recognize Lactobacillus as the dominant genus in the nonviable cell product. The total number of matching k-mers between the nonviable cell product and the L. pentosus BGM48 in the GenBank was the highest. The 95% confidence interval of the nonviable cell concentration in the product was determined as 4.31-4.68 × 1010 cells/g through the BD FACSMicroCount system. CONCLUSIONS: This validation protocol offers an executable approach that can verify microbial contents in nonviable cell products and ensure the compliance with label claims. HIGHLIGHTS: The established validation protocol could determine the nonviable cell species through MALDI-TOF-MS, the concentration through FACSMicroCount system, and the purity and strain level identification through metagenomic analysis of 16S rRNA and the genomic deoxyribonucleic acid.

Upper critical solution temperature polymer-grafted hollow mesoporous silica nanoparticles for near-infrared-irradiated drug release.

Near-infrared (NIR) irradiation responsive drug delivery systems have many advantages, which have attracted extensive interest from researchers. In this study, a NIR-triggered drug release system was established by grafting upper critical solution temperature (UCST) polymers on the surface of hollow mesoporous silica nanoparticles (HMSNs) followed by treatment with the photothermal conversion agent indocyanine green (ICG). The as-prepared UCST polymers showed the clearing temperature of 45 °C, which were advantageous to serve as gatekeepers in the physiological environment (37 °C). Under NIR irradiation, the temperature of the solution was elevated above the clearing point due to the presence of ICG; consequently, the collapsed UCST polymer chains became more hydrophilic; this resulted in the exposure of the mesoporous channels of the HMSNs and achievement of a burst drug release. Moreover, this NIR-responsive delivery system showed good biocompatibility and high anticancer efficiency towards the MCF-7 cancer cells upon exposure to NIR irradiation. In addition, a synergistic effect of thermal and chemo treatment has been achieved by the application of NIR irradiation since cancer cells are more vulnerable to high temperatures than normal cells.

Reactive Oxygen Species Synergistic pH/H2O2-Responsive Poly(l-lactic acid)-block-poly(sodium 4-styrenesulfonate)/Citrate-Fe(III)@ZIF-8 Hybrid Nanocomposites for Controlled Drug Release.

Combination of photodynamic therapy and chemotherapeutic drugs is a promising strategy to achieve enhanced anticancer effect. In this study, a novel reactive oxygen species (ROS) synergistic pH/H2O2-responsive nanocomposite has been prepared from the self-assembly of poly(l-lactic acid)-block-poly(sodium 4-styrenesulfonate) in aqueous solution, followed by addition of ferric citrate (Cit-Fe(III)) through electrostatic interaction and growing ZIF-8 among the surface of the particles. Upon H2O2 and visible light stimuli, efficient ROS such as hydroxyl radicals (•OH) and sulfate radicals (SO4•-) can be generated through the catalyst of Cit-Fe(III). Meanwhile, sulfonate-containing polymeric vesicles are disassembled through oxidization by ROS, and the encapsulated doxorubicin (DOX) will gradually diffuse into the ZIF-8 (one type of metal-organic framework, MOF) channels. The gatekeepers, ZIF-8, will collapse only under low pH condition, and a burst drug release is achieved. In the presence of H2O2 and pH stimuli upon visible light exposure, the prepared DOX-loaded nanocomposite exhibits good selectivity for both generating ROS and releasing drug in tumor cell instead of normal cell. The merits of nanocomposites such as good biocompatibility and especially the synergistic effect of chemo-photodynamic therapy make the material a highly promising candidate for drug delivery system in chemo-photodynamic therapy.

Redox and pH responsive polymeric vesicles constructed from a water-soluble pillar[5]arene and a paraquat-containing block copolymer for rate-tunable controlled release.

Herein, for rate-tunable controlled release, pH and redox dual responsive polymeric vesicles were constructed based on host-guest interaction between a water soluble pillar[5]arene (WP5) and a paraquat-containing block copolymer (BCP) in water. The yielding polymeric vesicles can be further applied in the controlled release of a hydrophilic model drug, doxorubicin hydrochloride (DOX). The drug release rate is regulated depending on the type of single stimulus or the combination of two stimuli. Meanwhile, DOX-loaded polymeric vesicles present anticancer activity in vitro comparable to free DOX under the studied conditions, which may be important for applications in the therapy of cancers as a controlled-release drug carrier.

Characterization of Carbapenem-Resistant Escherichia coli Isolates Through the Whole-Genome Sequencing Analysis.

Limited studies have characterized multiple carbapenem-resistant Escherichia coli isolates and compared their genetic characteristics through whole-genome sequencing (WGS) because of the scarcity of these isolates. In this study, we determined the prevalence of carbapenem resistance in 2,993 E. coli isolates collected from three Chinese hospitals. The carbapenem-resistant isolates were further characterized by WGS, and the molecular epidemiological characters and resistance mechanisms were explored through the publicly available platforms from the Center for Genomic Epidemiology. Twenty-four carbapenem-resistant E. coli isolates were screened out from 2,993 E. coli clinical isolates and all carbapenem-resistant isolates showed multiple drug-resistant phenotypes. The main serotypes identified among carbapenem-resistant isolates through WGS included E. coli O8:H21 (n = 6), E. coli O102:H6 (n = 6), and E. coli O25:H4 (n = 3), and the dominant sequence types (ST) were ST410 (n = 8), ST405 (n = 6), and ST131 (n = 3). Carbapenemase encoding genes, including blaIMP-4 (n = 3), blaKPC-2 (n = 2), blaNDM-5 (n = 1), and blaIMP-1 (n = 1) were identified in seven isolates. WGS analysis could provide a vast amount of molecular epidemiological data of the resistant isolates all at once, such as serotypes, multilocus sequence typing (MLST) types, plasmid replicons, and resistant determinants. Since carbapenem is the last resort to treat life-threatening E. coli infections, it is urgent to characterize the transmission routes and develop risk management strategies to block or slow down the transmission of resistance mechanisms and save carbapenems.

Glucose- and H2O2-Responsive Polymeric Vesicles Integrated with Microneedle Patches for Glucose-Sensitive Transcutaneous Delivery of Insulin in Diabetic Rats.

Herein, a dual-responsive insulin delivery device by integrating glucose- and H2O2-responsive polymeric vesicles (PVs) with transcutaneous microneedles (MNs) has been designed. This novel microneedle delivery device achieves a goal of fast response, excellent biocompatibility, and painless administration. The PVs are self-assembled from a triblock copolymer including poly(ethylene glycol), poly(phenylboronic acid) (glucose-sensitive block), and poly(phenylboronic acid pinacol ester) (H2O2-sensitive block). After loading with insulin and glucose oxidase (GO x), the drug-loaded PVs display a basal insulin release as well as a promoted insulin release in response to hyperglycemic states. The insulin release rate responds quickly to elevated glucose and can be further promoted by the incorporated GO x, which will generate the H2O2 at high glucose levels and further break the chemical links of phenylboronic acid pinacol ester group. Finally, the transdermal delivery of insulin to the diabetic rats ((insulin + GO x)-loaded MNs) presents an effective hypoglycemic effect compared to that of subcutaneous injection or only insulin-loaded MNs, which indicates the as-prepared MNs insulin delivery system could be of great importance for the applications in the therapy of diabetes.