Use of consecutive transcutaneous oxygen measurement when assessing the need for revascularization and association with the outcomes of ischemic diabetic ulcers.

This study compared the ankle-brachial index (ABI) with transcutaneous oxygen pressure (TcPO2 ) in assessing peripheral vascular disease (PVD) prevalence in 100 diabetic foot ulcer (DFU) patients. Patients were categorized into vascular or nonvascular reconstruction groups and underwent both ABI and TcPO2 measurements four times over 6 months. Predictive validity for PVD diagnosis was analysed using the area under the receiver-operating characteristic curve (AUC). The study found TcPO2 to be a superior predictor of PVD than ABI. Among the DFU patients, 51 with abnormal TcPO2 values underwent vascular reconstruction. Only TcPO2 values showed significant pretreatment differences between the groups and increased post-reconstruction. These values declined over a 6-month follow-up, whereas ABI values rose. For those with end-stage renal disease (ESRD), TcPO2 values saw a sharp decrease within 3 months. Pre-reconstruction TcPO2 was notably lower in amputation patients versus limb salvage surgery patients. In conclusion, TcPO2 is more effective than ABI for evaluating ischemic limb perfusion and revascularization necessity. It should be prioritized as the primary follow-up tool, especially for ESRD patients.

Early identification of delayed wound healing in complex diabetic foot ulcers treated with a dermal regeneration template: a novel clinical target and its risk factors.

BACKGROUND: The dermal regeneration template (DRT), a tissue-engineered skin substitute composing a permanent dermal matrix and an upper temporary silicone layer that serves as the epidermis, has demonstrated efficacy in treating uncomplicated diabetic foot ulcers (DFUs). Our institution has obtained good outcomes with DRT in patients with more complicated DFUs. Because of its chronicity, the authors are working to identify a clinical target that anticipates delayed healing early in the treatment in addition to determining the risk factors linked to this endpoint to increase prevention. MATERIALS AND METHODS: This retrospective single-center study analyzed patients with DFUs who underwent wound reconstruction using DRT between 2016 and 2021. The patients were categorized into poor or good graft-take groups based on their DRT status on the 21st day after the application. Their relationship with complete healing (CH) rate at day 180 was analyzed. Variables were collected for risk factors for poor graft take at day 21. Independent risk factors were identified after multivariable analysis. The causes of poor graft take were also reported. RESULTS: This study examined 80 patients (38 and 42 patients in the poor and good graft-take groups, respectively). On day 180, the CH rate was 86.3% overall, but the poor graft-take group had a significantly lower CH rate (76.3 vs. 95.2%, P =0.021) than the good graft-take group. Our analysis identified four independent risk factors: transcutaneous oxygen pressure less than 30 mmHg (odds ratio, 154.14), off-loading device usage (0.03), diabetic neuropathy (6.51), and toe wound (0.20). The most frequent cause of poor graft take was infection (44.7%), followed by vascular compromise (21.1%) and hematoma (15.8%). CONCLUSION: Our study introduces the novel concept of poor graft take at day 21 associated with delayed wound healing. Four independent risk factors were identified, which allows physicians to arrange interventions to mitigate their effects or select patients more precisely. DRT represents a viable alternative to address DFUs, even in complicated wounds. A subsequent split-thickness skin graft is not always necessary to achieve CH.

Synthesis and Evaluation of Alginate-Based Nanogels as Sustained Drug Carriers for Caffeine.

The objective of this study is to design a polymeric network of nanogels for sustained release of caffeine. Therefore, alginate-based nanogels were fabricated by a free-radical polymerization technique for the sustained delivery of caffeine. Polymer alginate was crosslinked with monomer 2-acrylamido-2-methylpropanesulfonic acid by crosslinker N',N'-methylene bisacrylamide. The prepared nanogels were subjected to sol-gel fraction, polymer volume fraction, swelling, drug loading, and drug release studies. A high gel fraction was seen with the increasing feed ratio of polymer, monomer, and crosslinker. Greater swelling and drug release were observed at pH 4.6 and 7.4 as compared to pH 1.2 due to the deprotonation and protonation of functional groups of alginate and 2-acrylamido-2-methylpropanesulfonic acid. An increase was observed in swelling, loading, and release of the drug with the incorporation of a high feed ratio of polymer and monomer, while a reduction was seen with the increase in crosslinker feed ratio. Similarly, an HET-CAM test was used to evaluate the safety of the prepared nanogels, which showed that the prepared nanogels have no toxic effect on the chorioallantoic membrane of fertilized chicken eggs. Similarly, different characterizations techniques such as FTIR, DSC, SEM, and particle size analysis were carried out to determine the development, thermal stability, surface morphology, and particle size of the synthesized nanogels, respectively. Thus, we can conclude that the prepared nanogels can be used as a suitable agent for the sustained release of caffeine.

Nanoplastics exposure disrupts circadian rhythm associated with dysfunction of the endolysosomal pathway and autophagy in Caenorhabditis elegans.

Nanoplastics (NPs), an emerging pollutant, have raised great safety concerns due to their widespread applications and continuous release into the environment, which lead to potential human and environmental risks. Recently, polystyrene NPs (100 nm; 100 mg/L) exposure has been reported to disrupt circadian rhythms under five days temperature entrainment and be associated with stress resistance decline in Caenorhabditis elegans. This study explored the possible relationship between circadian rhythm disruption and endocytosis and autophagy under polystyrene NPs exposure in C. elegans. We show that the disrupted circadian rhythm induced by NPs exposure reduced stress resistance via endocytosis and autophagy impairment. Furthermore, we found that most NPs taken up by intestinal cells were localized to early endosomes, late endosomes, and lysosomes and delivered to autophagosomes. In addition, the disruption of circadian rhythm inhibited NPs localization to these organelles. These findings indicate that NPs exposure disrupts circadian rhythm and alters its subcellular trafficking, leading to enhanced toxicity in C. elegans. Our results shed light on the prominent role of NPs exposure in circadian rhythm disruption associated with endocytosis and autophagy impairments, which may be conserved in higher animals such as humans.

Multidisciplinary Strategies With Real-Time Fluorescence Images and Negative Pressure Wound Therapy to Manage Organ/Space Surgical Site Infection in Transplanted Kidneys.

BACKGROUND: Surgical site infection (SSI) after kidney transplantation can severely compromise graft function and prolong hospital stay. Organ/space SSI (osSSI) is a severe type of SSI associated with a significantly higher mortality rate. AIMS AND OBJECTIVES: This study aims to provide new strategies of managing (osSSI) after kidney transplant and other high-risk wound infections. METHOD: This is a single-center, retrospective study that analyzed the treatment outcomes of 4 patients who developed osSSI after kidney transplant at Shuang-Ho Hospital. The management strategy included real-time fluorescence imaging with MolecuLight, negative-pressure wound therapy (NPWT) with Si-Mesh, and incisional NPWT (iNPWT). RESULT: The average length of hospital stay was 18 days (range, 12-23 days). During hospitalization, all patients obtained high-quality debridement under real-time fluorescence image confirmation. The average duration of NPWT was 11.8 days (range, 7-17 days) and iNPWT was 7 days. All transplanted kidneys were preserved with normal function after 6 months of follow-up. CONCLUSIONS: Our strategies with real-time fluorescence imaging provide a novel and effective method that can be used in adjunct with the standard of care for managing osSSI after kidney transplantation. More studies are warranted to validate the efficacy of our approach.

Multiomic characterization and drug testing establish circulating tumor cells as an ex vivo tool for personalized medicine.

Matching the treatment to an individual patient's tumor state can increase therapeutic efficacy and reduce tumor recurrence. Circulating tumor cells (CTCs) derived from solid tumors are promising subjects for theragnostic analysis. To analyze how CTCs represent tumor states, we established cell lines from CTCs, primary and metastatic tumors from a mouse model and provided phenotypic and multiomic analyses of these cells. CTCs and metastatic cells, but not primary tumor cells, shared stochastic mutations and similar hypomethylation levels at transcription start sites. CTCs and metastatic tumor cells shared a hybrid epithelial/mesenchymal transcriptome state with reduced adhesive and enhanced mobilization characteristics. We tested anti-cancer drugs on tumor cells from a metastatic breast cancer patient. CTC responses mirrored the impact of drugs on metastatic rather than primary tumors. Our multiomic and clinical anti-cancer drug response results reveal that CTCs resemble metastatic tumors and establish CTCs as an ex vivo tool for personalized medicine.

C. elegans BLMP-1 controls apical epidermal cell morphology by repressing expression of mannosyltransferase bus-8 and molting signal mlt-8.

Skin epidermis secretes apical extracellular matrix (aECM) as a protective barrier from the external environment. The aECM is highly dynamic and constantly undergoes remodeling during animal development. How aECM dynamics is temporally regulated during development, and whether and how its mis-regulation may impact epidermal cell morphology or function remains to be fully elucidated. Here, we report that the conserved Zn-finger transcription factor BLMP-1/Blimp1, which regulates epidermal development in C. elegans, controls apical cell shape of the epidermis by downregulation of aECM remodeling. Loss of blmp-1 causes upregulation of genes essential for molting, including bus-8 and mlt-8, in adult, leading to an abnormal shape in the apical region of adult epidermal cells. The apical epidermal morphological defect is suppressed by reduction of bus-8 or mlt-8. BUS-8 is a key mannosyltransferase, which functions in glycosylation of N-linked glycoproteins; MLT-8 has a ganglioside GM2 lipid-binding domain and is implicated in signaling during molting, a process where the old cuticle is shed and synthesized anew. Overexpression of bus-8 or mlt-8 induces an apical epidermal cell defect as observed in blmp-1 mutants. MLT-8::GFP fusion protein is localized to lysosomes and secreted to aECM. BUS-8 is important for MLT-8 stability and lysosomal targeting, which may be regulated by BUS-8-mediated glycosylation of MLT-8 and function as a molting signaling cue in aECM remodeling. We propose that BLMP-1 represses MLT-8 expression and glycosylation in the epidermis to prevent inappropriate aECM remodeling, which is essential for maintenance of apical epidermal cell morphology during larva-to-adult transition.

Early developmental nanoplastics exposure disturbs circadian rhythms associated with stress resistance decline and modulated by DAF-16 and PRDX-2 in C. elegans.

Plastics pollution is an emerging environmental problem and nanoplastics (NPs) toxicity has received great concern. This study investigated whether early developmental exposure to polystyrene NPs influence the circadian rhythms and the possible underlying mechanisms in C. elegans. We show that early developmental NPs exposure disturbs circadian rhythms in C. elegans and ASH neurons and G protein-coupled receptor kinase (GRK-2) are involved in the level of chemotaxis response. A higher bioconcentration factor in entrained worms was observed, suggesting that circadian interference results in increased NPs bioaccumulation in C. elegans. In addition, we show that reactive oxygen species produced by NPs exposure and peroxiredoxin-2 (PRDX-2) are related to the disturbed circadian rhythms. We further show that the NPs-induced circadian rhythms disruption is associated with stress resistance decline and modulated by transcription DAF-16/FOXO signaling. Because circadian rhythms are found in most living organisms and the fact that DAF-16 and PRDX-2 are evolutionarily conserved, our findings suggest a possible negative impact of NPs on circadian rhythms and stress resistance in higher organisms including humans.

Development of a water refractive index-matched microneedle integrated into a light sheet microscopy system for continuous embryonic cell imaging.

In this study, microneedle-integrated light sheet microscopy (LSM) was developed for trapping and continuously imaging embryos of Caenorhabditis elegans with subcellular resolution. To reduce aberrations when the light sheet was propagated into the device, a microneedle was fabricated using a transparent, water refractive index-matched polymer. It was proven that when the light sheet emerged from the water-immersed objective and penetrated through the microneedle with a circular surface, even with a non-perpendicular incident angle, fewer aberrations were found. An embryo was injected into and trapped at the tip of the microneedle, which was positioned at the interrogation window of the LSM apparatus with the image plane perpendicular to the light sheet, and this setup was used to sequentially acquire embryo images. By applying the light sheet, higher-resolution, higher-contrast images were obtained. The system also showed low photobleaching and low phototoxicity to embryos of C. elegans. Furthermore, three-dimensional embryo images with a whole field of view of the microneedle could be achieved by stitching together images and reconstructing sequential two-dimensional embryo images.

Ultrasensitive Detection of Alzheimer's Amyloids on a Plasmonic-Gold Platform.

More than 55 million people live with dementia worldwide in 2021, and there are nearly 10 million new cases every year. Alzheimer's disease (AD) is the most common cause of dementia. Despite urgent need, early detection of AD and long-term monitoring of AD progression have been challenging. This is due to the limited availability of brain imaging facilities and the highly invasive procedure with the cerebrospinal fluid assay to assess the level of AD biomarkers, such as beta-amyloid (Aß). Reliable measurements of AD biomarkers in blood samples are still difficult because of their very low abundance. Here, we develop a rapid, specific, and ultrasensitive immunoassay using plasmonic-gold nanoisland (pGOLD) chips with near-infrared fluorescence-enhanced detection for Aß1-40 and Aß1-42. We show step-by-step processes and results during the platform establishment, including antibody specificity and sensitivity tests, antibody pair examination, condition optimization, and procedure refinement. Finally, we demonstrate the platform performance with detection sensitivity at the subpicogram per milliliter level. This platform, therefore, has a great application potential for early detection of AD using blood samples.

BLMP-1 promotes developmental cell death in C. elegans by timely repression of ced-9 transcription.

Programmed cell death (PCD) is a common cell fate in metazoan development. PCD effectors are extensively studied, but how they are temporally regulated is less understood. Here, we report a mechanism controlling tail-spike cell death onset during Caenorhabditis elegans development. We show that the zinc-finger transcription factor BLMP-1, which controls larval development timing, also regulates embryonic tail-spike cell death initiation. BLMP-1 functions upstream of CED-9 and in parallel to DRE-1, another CED-9 and tail-spike cell death regulator. BLMP-1 expression is detected in the tail-spike cell shortly after the cell is born, and blmp-1 mutations promote ced-9-dependent tail-spike cell survival. BLMP-1 binds ced-9 gene regulatory sequences, and inhibits ced-9 transcription just before cell-death onset. BLMP-1 and DRE-1 function together to regulate developmental timing, and their mammalian homologs regulate B-lymphocyte fate. Our results, therefore, identify roles for developmental timing genes in cell-death initiation, and suggest conservation of these functions.

Effect of A-scan rate and interscan interval on optical coherence angiography.

Optical coherence tomography angiography (OCTA) can provide rapid, volumetric, and noninvasive imaging of tissue microvasculature without the requirement of exogenous contrast agents. To investigate how A-scan rate and interscan time affected the contrast and dynamic range of OCTA, we developed a 1.06-µm swept-source OCT system enabling 100-kHz or 200-kHz OCT using two light sources. After system settings were carefully adjusted, almost the same detection sensitivity was achieved between the 100-kHz and 200-kHz modalities. OCTA of ear skin was performed on five mice. We used the variable interscan time analysis algorithm (VISTA) and the designated scanning protocol with OCTA images reconstructed through the correlation mapping method. With a relatively long interscan time (e.g., 12.5 ms vs. 6.25 ms for 200-kHz OCT), OCTA can identify more intricate microvascular networks. OCTA image sets with the same interscan time (e.g., 12.5 ms) were compared. OCTA images acquired with a 100-kHz A-scan rate showed finer microvasculature than did other imaging modalities. We performed quantitative analysis on the contrast from OCTA images reconstructed with different A-scan rates and interscan time intervals in terms of vessel area, total vessel length, and junction density.

Blood sugar control among type 2 diabetic patients who travel abroad: A cross sectional study.

The dose adjustment of anti-diabetic drugs during traveling abroad remains an important issue for the diabetic patients. However, there are few studies exploring the changes in blood sugar in patients with type 2 diabetes mellitus (T2DM) when traveling abroad. The study aimed to investigate the hypoglycemic episodes, sugar control, and associated factors during travel among patients with T2DM.A questionnaire was administrated to T2DM patients visiting the family medicine clinic in a medical center from September 2016 to April 2017. The Chi-square test was used to examine the differences in risk factors of hypoglycemia between hypoglycemic group and non-hypoglycemic group. Multivariate logistic regression models were used to examine the risk factors for the hypoglycemia.A total of 65 males and 74 females completed the questionnaire. The mean age was 59.3 ±â€Š12.1 year olds, the mean BMI was 28.1 ±â€Š5.9 kg/m, and the mean HbA1C was 7.4 ±â€Š1.1%. There was 8.6% of diabetic patients reporting hypoglycemic episodes during travel. The hypoglycemic episodes were significantly related to the numbers of crossing time zones after adjusting for possible confounders. Only 21.6% of subjects told physicians their travel plan whereas two third of the physicians did not provide pre-travel consultation.The hypoglycemic episodes sometimes occurred and were related to the numbers of crossing time zones in diabetic travelers. The proportion of pre-travel consultation was low in patients with T2DM. Besides, most of the physicians did not offer pre-travel education when patients mentioned their traveling plan. The willing and ability of physicians to offer the pre-travel diabetic education deserved further investigation.

Tuberculosis among migrant workers in Taiwan.

BACKGROUND: Although the worldwide incidence of tuberculosis (TB) has been slowly decreasing, the migrant workers remains an important gap for regional TB control. In Taiwan, the numbers of the migrant workers from countries with high TB incidence increase significantly in past decades and the impact on public health remains unknown. This study aimed to explore the difference of TB incidence between Taiwanese and the migrant workers. METHODS: The migrant workers are obligated to receive pre-arrival, post-arrival and regular chest X-ray screening during their stay in Taiwan. We retrospectively collected these data extracted from the Alien Workers Health Database in Centers for Disease Control, Taiwan from Jan. 1, 2004 to Dec. 31, 2013. Poisson regression models were used to compare the hazard ratios of TB between Taiwanese and the migrant workers after adjusting gender and age groups. RESULTS: The total migrant workers in Taiwan reached 314,034 persons in 2004 and 489,134 persons in 2013, accounting for 2% of Taiwan population. The TB incidence of migrant workers was similar to Taiwanese (53-73.7 per 105 vs 45.5-76.8 per 105). Comparing with Taiwanese, the TB risk was significantly lower in male migrant workers (HR: 0.76; 95% CI: 0.70-0.83, P < 0.001), but higher in female migrant workers (HR: 1.40; 95% CI: 1.35-1.46, P < 0.001). Besides, we found that the TB risk in migrant workers was 5.30-fold (95% CI: 4.83-5.83, P < 0.001) in youngest group (≤24 year-old) comparing with Taiwanese. CONCLUSIONS: Migrant workers in Taiwan have higher TB incidence than Taiwanese in young groups, especially in females. The mainstay young laborers with latent tuberculosis infection risk is an important vulnerability for public health. Further investigation and health screening are warranted.

Engulfing cells promote neuronal regeneration and remove neuronal debris through distinct biochemical functions of CED-1.

Two important biological events happen coincidently soon after nerve injury in the peripheral nervous system in C. elegans: removal of axon debris and initiation of axon regeneration. But, it is not known how these two events are co-regulated. Mutants of ced-1, a homolog of Draper and MEGF10, display defects in both events. One model is that those events could be related. But our data suggest that they are actually separable. CED-1 functions in the muscle-type engulfing cells in both events and is enriched in muscle protrusions in close contact with axon debris and regenerating axons. Its two functions occur through distinct biochemical mechanisms; extracellular domain-mediated adhesion for regeneration and extracellular domain binding-induced intracellular domain signaling for debris removal. These studies identify CED-1 in engulfing cells as a receptor in debris removal but as an adhesion molecule in neuronal regeneration, and have important implications for understanding neural circuit repair after injury.

Attitudes and awareness of medical assistance while traveling abroad.

BACKGROUND: With globalization, more and more people travel to countries where they are at risk of injuries and travel-related diseases. To protect travelers' health, it is crucial to understand whether travelers accurately perceive medical assistance resources before and during their trips. This study investigated the need, awareness, and previous usage of overseas emergency medical assistance services (EMAS) among people traveling abroad. METHODS: Anonymous questionnaires were distributed to patients (n = 500) at a travel clinic in Taipei, Taiwan. RESULTS: The results showed that EMAS were important, especially in the following categories: 24-h telephone medical consultation (91.8%), emergent medical repatriation (87.6%), and assistance with arranging hospital admission (87.4%). Patients were less aware of the following services: arrangement of appointments with doctors (70.7%) and monitoring of medical conditions during hospitalization (73.0%). Less than 5% of respondents had a previous experience with EMAS. CONCLUSIONS: EMAS are considered important to people who are traveling abroad. However, approximately 20-30% of travelers lack an awareness of EMAS, and the percentage of travelers who have previously received medical assistance through these services is extremely low. The discrepancy between the need and usage of EMAS emphasizes the necessity to adapt EMAS materials in pre-travel consultations to meet the needs of international travelers.

Functional characterization of the meiosis-specific DNA double-strand break inducing factor SPO-11 from C. elegans.

The programmed induction of meiotic DNA double-strand breaks (DSBs) by the evolutionarily conserved SPO-11 protein, which is structurally related to archaeal Topo VIA topoisomerases, triggers meiotic recombination. Identification of several meiosis-specific factors that are required for SPO-11-mediated DSB formation raises the question whether SPO-11 alone can cleave DNA. Here, we have developed procedures to express and purify C. elegans SPO-11 in a soluble, untagged, and monodispersed form. Our biochemical and biophysical analyses demonstrate that SPO-11 is monomeric and binds DNA, double-stranded DNA in particular. Importantly, SPO-11 does not exhibit DNA cleavage activity under a wide range of reaction conditions, suggesting that co-factors are needed for DSB induction activity. Our SPO-11 purification system and the findings reported herein should facilitate future mechanistic studies directed at delineating the mechanism of action of the SPO-11 ensemble in meiotic DSB formation.

Taiwan's Travel and Border Health Measures in Response to Zika.

Zika virus has recently emerged as a worldwide public health concern. Travel and border health measures stand as one of the main strategies and frontline defenses in responding to international epidemics. As of October 31, 2016, Taiwan has reported 13 imported cases, 5 of which were detected through routine entry screening and active monitoring at international airports. This article shares Taiwan's disease surveillance activities at designated points of entry and travel and border health measures in response to Zika. The Taiwan government collaborates with its tourism industry to disseminate information about precautionary measures and encourages tour guides to report suspected individuals or events to activate early response measures. Taiwan also engages in vector control activities at points of entry, including targeting aircraft from countries where vector-borne diseases are endemic, implementing mosquito sweep measures, and collecting vector surveillance data. In future emerging and reemerging disease events, entry surveillance at designated points of entry may enable early detection of diseases of international origin and more rapid activation of public health preparedness activities and international collaboration. Taiwan will continue to maximize border and travel health measures in compliance with IHR (2005) requirements, which rely on continued risk assessment, practical implementation activities, and engagement with all stakeholders.

Programmed Cell Death During Caenorhabditis elegans Development.

Programmed cell death is an integral component of Caenorhabditis elegans development. Genetic and reverse genetic studies in C. elegans have led to the identification of many genes and conserved cell death pathways that are important for the specification of which cells should live or die, the activation of the suicide program, and the dismantling and removal of dying cells. Molecular, cell biological, and biochemical studies have revealed the underlying mechanisms that control these three phases of programmed cell death. In particular, the interplay of transcriptional regulatory cascades and networks involving multiple transcriptional regulators is crucial in activating the expression of the key death-inducing gene egl-1 and, in some cases, the ced-3 gene in cells destined to die. A protein interaction cascade involving EGL-1, CED-9, CED-4, and CED-3 results in the activation of the key cell death protease CED-3, which is tightly controlled by multiple positive and negative regulators. The activation of the CED-3 caspase then initiates the cell disassembly process by cleaving and activating or inactivating crucial CED-3 substrates; leading to activation of multiple cell death execution events, including nuclear DNA fragmentation, mitochondrial elimination, phosphatidylserine externalization, inactivation of survival signals, and clearance of apoptotic cells. Further studies of programmed cell death in C. elegans will continue to advance our understanding of how programmed cell death is regulated, activated, and executed in general.

Noise propagation with interlinked feed-forward pathways.

Functionally similar pathways are often seen in biological systems, forming feed-forward controls. The robustness in network motifs such as feed-forward loops (FFLs) has been reported previously. In this work, we studied noise propagation in a development network that has multiple interlinked FFLs. A FFL has the potential of asymmetric noise-filtering (i.e., it works at either the "ON" or the "OFF" state in the target gene). With multiple, interlinked FFLs, we show that the propagated noises are largely filtered regardless of the states in the input genes. The noise-filtering property of an interlinked FFL can be largely derived from that of the individual FFLs, and with interlinked FFLs, it is possible to filter noises in both "ON" and "OFF" states in the output. We demonstrated the noise filtering effect in the developmental regulatory network of Caenorhabditis elegans that controls the timing of distal tip cell (DTC) migration. The roles of positive feedback loops involving blmp-1 and the degradation regulation of DRE-1 also studied. Our analyses allow for better inference from network structures to noise-filtering properties, and provide insights into the mechanisms behind the precise DTC migration controls in space and time.