In the hospital settings, performing clinical trials is an intricate process that is generally hampered by several institutional, technical, and record-keeping challenges. Hence, we evaluated the effectiveness and efficiency of our established integrated clinical trial management system (CTMS) in terms of analyzing core functionalities, assessing integration with existing systems, measuring time, and cost efficiency. Our CTMS (version 10.1, August 2024) is integrated into one of the largest teaching hospitals with the human research audit system, biobank management system, biological sample management system, enterprise resource system service, institutional review, and single sign-on system. The total number of trials, subjects enrolled, products developed, investigators, new drug and indication, devices, and new medical technology are found to be 913, 53969, 851, 159, 784, and 98, respectively, with a total budget of 3539846777 New Taiwan Dollar (approx. 106881045 US$). Our CTMS is efficient in updating data, with improved user interface experience, and controlled access according to the defined policy. Integrating CTMS with other components provides effective tracking and monitoring of the clinical study. Conclusively, our integrated CTMS is designed for comprehensive evaluation and supervision of clinical trials, supporting full-process data management and seamless integration with clinical systems of hospitals through a unified interface. The increasing number of trials, subjects enrolled, products developed, investigators, new drugs and indications, devices, and new medical technology indicates its robustness and efficacy.
The article discusses the Clinical Trial
Management System (CTMS), which was established in 2014 through a collaboration
between healthcare researchers and software specialists. Designed for three
major teaching hospitals in Taiwan, the CTMS integrates hospital resources to
streamline clinical trial operations. The core features include real-time
tracking of trial progress and the integration of budget, contract, subject,
and data management within hospital systems. With over 900 supported trials and
more than 53,000 participants, the system has significantly improved data
security, operational efficiency, and cost control. Continued efforts to
integrate electronic health records are essential for future scalability and
trial quality.
In rodents, the whiskers and paws are essential for somatosensory perception, yet their preference for specific textures remains unclear. Here, we examined the preference for rough versus smooth surfaces in rats using a custom open-field paradigm with a water-based motivator to ensure consistent and unbiased movement. We found that rats strongly preferred rough textures with longer interactions and increased dwell time. Notably, this preference persisted in darkness, confirming the tactile, but not visual, influence. These findings highlight the primacy of tactile input in behavioral choices and provide key insights into optimizing rodent environments.
Although tactile sensation is vital for the
survival of rodents, their preference for specific textures is not well
understood. To examine this, the authors developed a novel open-field paradigm
with equally divided rough and smooth surfaces, using a water-based motivator
to encourage unbiased exploration. They demonstrated that rats prefer the rough
texture, as evidenced by longer interaction times. This preference persisted
even in complete darkness, confirming that the choice is driven by tactile
rather than visual cues. Altogether, this work highlights how tactile inputs
guide behavior and offers key insights for creating enriched environments that
align with animals’ innate preferences.
Mechanical hyperalgesia is commonly evaluated using von Frey filaments (vFFs) in the rodent hind paw plantar. However, it is difficult to select the plantar location to stimulate with the vFFs. In the present study, we investigated the effective location of the plantar surface for the evaluation of mechanical hyperalgesia using vFFs in mice treated with paclitaxel (PTX). PTX or vehicle was injected intraperitoneally once daily, 4 times every other day. On Day 14, mechanical hyperalgesia was evaluated using vFFs. The evaluation was performed by stimulation with vFFs on the skin directly under the 3rd and 4th paw pads (base of the index and middle fingers) from closest to the heel on the thumb side, in the central skin surrounded by the pads, and in the plantar skin one-third of the way down from the heel toward the toe. In comparison to vehicle-treated mice, mechanical hyperalgesia was significantly observed in the skin directly under the 3rd and 4th paw pads counted from closest to the heel, and in the plantar skin one-third of the way down from the heel toward the toe. However, this was not significant in the central skin surrounded by the pads. Interestingly, in vehicle-treated mice, the paw withdrawal threshold varied for each location evaluated. In contrast, in PTX-treated mice, the thresholds were similar across all evaluated locations. These results suggest that the selection of the location on the plantar surface to be stimulated is important for pain evaluation using vFFs.
Mechanical hyperalgesia is commonly
evaluated using von Frey filaments (vFFs) in the rodent hind paw plantar.
However, it is difficult to select the plantar location to stimulate with the
vFFs. This study showed the effective location of the plantar surface for the
evaluation of mechanical hyperalgesia using vFFs in mice treated with
paclitaxel, which elicits peripheral neuropathy in a stocking-glove
distribution in human patients. The authors’ results suggest that the selection
of the location on the plantar surface to be stimulated is important for pain
evaluation using vFFs.
Circadian rhythms regulate essential physiological functions, including body temperature and hormone secretion, in a 24-h cycle. These rhythms are synchronized with environmental cues, primarily light, through the suprachiasmatic nucleus. Disruptions, such as jet lag, misalign internal rhythms with external time, leading to fatigue and insomnia. This study explores the potential of dietary sweetening agents as non-pharmacological interventions to facilitate circadian re-entrainment in a mouse jet lag model. Male C57BL/6 mice, maintained on a 12-h light/dark cycle, underwent a 6-h phase advance to simulate jet lag. Mice received drinking water with or without sweeteners (sucrose, sucralose, xylitol, maltitol), and locomotor activity was assessed using wheel-running behavior and intraperitoneally implanted nanotags measuring 3dimensional acceleration and body temperature. Sucrose and sucralose significantly accelerated re-entrainment, with phase-shifting rates of 0.93 and 1.28 h/d, respectively, compared to 0.76 h/d in controls. Both sweeteners also enhanced post-shift activity, whereas xylitol had a minor effect and maltitol showed no significant impact. Sweeteners did not affect rest duration during the jet lag period. These findings indicate that sweet taste can facilitate circadian adaptation, offering a potential dietary approach to mitigate jet lag symptoms. This study provides insights into how taste perception influences circadian regulation, with implications for managing circadian misalignment in frequent travelers and shift workers.
[Highlighted Paper selected by Editor-in-Chief]
The authors investigated the effects of sweet-tasting
substances on the re-entrainment of circadian rhythms in a mouse model of jet
lag. Using behavioral activity monitoring, they demonstrated that intake of
both sucrose and the artificial sweetener sucralose facilitated adaptation to
shifted light-dark cycles. These findings suggest that sweet taste may aid in
recovery from circadian misalignment and serve as a basis for
non-pharmacological strategies to manage jet lag. Additionally, the results may
open new avenues for research on chrononutrition and lifestyle-based circadian
health interventions.
Small interfering RNAs (siRNAs) hold great therapeutic promise due to their ability to selectively silence disease-associated genes. Although chemically modified siRNAs have demonstrated clinical efficacy, their development remains hindered by challenges such as stability and delivery under physiological conditions. Furthermore, in vitro screening of chemically modified siRNAs using cultured cells is cost-effective but often fails to recapitulate in vivo complexity, limiting predictive accuracy. To address this, we have developed a transfection-free siRNA evaluation platform using Gryllus bimaculatus (Gb), an insect model with natural RNA uptake capacity. We first demonstrated that 21-nucleotide siRNAs induced RNA interference upon abdominal injection under conditions of free uptake. We then generated transgenic lines harboring an EGFP reporter fused to the therapeutic siRNA target sequence and integrated into the β-actin locus via clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated protein 9-mediated knock-in. Two transgenic strains (s1 and d1) were established and validated. We compared unmodified and chemically modified siRNAs designed using enhanced stabilization chemistry (ESC), a clinically validated modification pattern incorporating 2′-O-methyl, 2′-fluoro, and phosphorothioate modifications. While ESC-modified siRNAs showed reduced activity compared to unmodified natural siRNAs in conventional cell-based assays requiring transfection reagents, they exhibited consistent gene silencing in Gb, reflecting their enhanced biochemical stability under free uptake conditions at picomole-scale doses. These results establish Gb as a scalable, cost-effective, and biologically relevant platform for evaluating therapeutic siRNAs, particularly those incorporating chemical modifications.
In the development of
siRNA therapeutics, chemical modifications are crucial
for enhancing their potency and biochemical stability. However, optimizing the
design of chemically modified siRNAs remains challenging due to differences in
assay volume and delivery methods between in vitro and in vivo screening.
To address this, Inoue et al. have established a novel evaluation platform
using the model insect, Gryllus bimaculatus (Gb). In Gb, RNAi
efficacy of chemically modified siRNAs can be evaluated in a transfection-free
manner using small assay amounts comparable to those used in cultured cell
experiments. This assay platform has the potential to serve as a practical and
scalable method for bridging the gap between in vitro and in vivo
evaluation.
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