The authors thank Professor Mei Jiang for her help in the statistical analysis and Mr. Hammer Tsui in the preparation of the manuscript. This study was supported by the Guangzhou Science and Technology Foundation (201804020043) and the National Natural Science Foundation of China (NSFC 81572063 and NSFC 81802076). The funding groups agreed with the study design, data analysis, manuscript preparation, and decision to publish. No other funding was received for this study.

This study and the use of human serum samples were approved by the Ethics Committee of The First Affiliated Hospital of Guangzhou Medical University (GYYY-2016-73). All participants have given their written consent independently or through their parents (in the case of children).
1. Basic information of the study group
NOTE: The Allergy Information Repository of the State Key Laboratory of Respiratory Disease (AIR-SKLRD) is a large serum bank established inside the Guangzhou Institute of Respiratory Hospital (GIRH). Initiated in the last decade, the AIR-SKLRD has already started to collect and store serum samples from patients with allergic diseases, together with their clinical information (Table 1)4,5. The current study was performed with sera from the AIR-SKLRD.
<ol>
	<li>Search the AIR-SKLRD&#8217;s database for sera collected from January 2015 to June 2018 and select the patients with allergic disease, who were found to be sensitive to the common allergens in the region.</li>
	<li>Ensure that all selected patients have allergic-related diseases, such as allergic rhinitis and or asthma, allergic dermatitis, and/or urticaria, and that the serum of these patients contains multiple serum allergen-specific immunoglobulin E (sIgE) sensitizations of common allergens in this region, detected by the System 1.</li>
	<li>Exclude patients with incomplete medical records, those lost to follow-up, those who refuse to give informed consent regarding the use of their serum samples for scientific purposes, those with an identified immunodeficiency, those currently on immunotherapy or immunomodulatory agents, or those found to have parasitic infections.</li>
	<li>Ensure no treatment or drug prescription was given prior to the serum collection so as to minimize interference to the laboratory findings. All serum samples that do not fulfill the criteria were rejected.</li>
</ol>
2. Study flow and measurements of interest
NOTE: The microfluidic system needs 100 &#181;L of serum for determining 19 allergens. Venous blood (5 mL) was collected from each patient using a vacuum blood vessel containing separating gel. After centrifuging for 10 min at 1,000 x g, the upper layer was collected for testing. Unused serum was stored at -80 &#176;C. Prior to testing, the serum was kept at room temperature for 30 min and was shaken with a vortex mixer. Repeated freeze-and-thaw cycles were avoided.
<ol>
	<li>Primarily test the serum samples for sIgEs to whole allergens of Dermatophagoides pteronyssinus (d1), Dermatophagoides farinae (d2), Blomia tropicalis (d201), cat dander (e1), dog dander (e5), Bermuda grass (g2), timothy grass (g6), cockroaches (i6), Aspergillus fumigatus (m3), Candida albicans (m5), ragweed (w1), egg white (f1), milk (f2), wheat (f4), peanut (f13), soybean (f14), almond (f20), crab (f23), and shrimp (f24). Follow the instructions given in section 3. 
	NOTE: sIgE determination was done with the allergen-specific IgE assay kit (see the Table of Materials) and measured by a chemiluminescence analyzer.</li>
	<li>Randomly select three samples from among the samples with enough serum (at least 900 &#181;L) for a reproducibility study. Keeping all the conditions unchanged, measure the three sera for allergen sIgEs daily for 9 consecutive days (i.e., a total of 100 x 9 = 900 &#181;L of serum).</li>
</ol>
3. Semi-automation test procedure of the microfluidic system
NOTE: The System 2 is the integration of automatic microfluidic technology, protein microarray, cold light analysis, parallel IgE analysis, and image processing technology. The testing protocol is divided into four parts: preparation of the equipment, sample loading, incubation, and measurement.
<ol>
	<li>Preparation of the equipment
	<ol>
		<li>Turn on the PC and the analyzer power. 
		NOTE: The power switch is on the left of the base.</li>
		<li>Start the LabIT program on the PC. If the Dark Frame warning window pops up, click OK to run LEAK Test. Afterward, click the center logo to enter the operation interface. 
		NOTE: The system will remind the user to run LEAK Test if it is idle for more than 24 h.</li>
		<li>Check the Reaction Temp and CCD (charge-coupled device) Temp at the lower right corner of the screen. The Reaction Temp should rise to 37 &#176;C &#177; 1 &#176;C in about 10 min, and the CCD Temp should drop to -15 &#176;C &#177; 1 &#176;C.</li>
		<li>Run the LEAK Test after the CCD Temp has dropped to -15 &#176;C &#177; 1 &#176;C. Before running the LEAK test, make sure there are no other items left inside the instrument and close the door. Click Tools | System Test | LEAK Test. Do not open the door during testing. When the test is finished, the report window will pop up.</li>
	</ol>
	</li>
	<li>Sample loading
	<ol>
		<li>Add 620 &#181;L of wash buffer, 120 &#181;L of blocking buffer, 60 &#181;L of conjugates A and B, 60 &#181;L of substrate A and B, and 100 &#181;L of serum samples to the corresponding reagent tank on the microfluidic cartridge.</li>
	</ol>
	</li>
	<li>Incubation
	<ol>
		<li>Click on Cartridge ID, use the barcode scanner to scan the serial number of the cartridge, enter the sample ID, put the cartridge into the analyzer and close the door, and click Analyzer and Run to start the analysis.</li>
	</ol>
	</li>
	<li>Measurement
	<ol>
		<li>Export the results to statistical software (e.g., Excel) after the measurement. 
		NOTE: After 30 min of incubation, the analyzer automatically performs the measurement and reports the result.</li>
	</ol>
	</li>
	<li>Switching off of the analyzer
	<ol>
		<li>For routine maintenance, after finishing the test, remove the cartridge and wipe the analyzer&#8217;s internal heating iron and electromagnet lightly with 75% alcohol. 
		NOTE: Do not press hard or shake the electromagnet.</li>
		<li>Close the LabIT window. The temperature monitoring window will pop up. It will automatically close when the CCD warms up to the 5 &#176;C protection mode. By then, it will be safe to turn off the power of the analyzer and PC. 
		NOTE: Do not manually close the temperature monitoring window before the CCD Temp has risen to 5 &#176;C, and do not turn off the power of the analyzer nor the PC during the CCD warm-up.</li>
	</ol>
	</li>
</ol>
4. Definition of sIgE reactivity
NOTE: For an undiluted serum specimen, the detection range of the System 2 is 0.21&#8211;100 IU/mL.
<ol>
	<li>Based on the threshold value of 0.35 IU/mL, consider an sIgE level exceeding 0.35 IU/mL to be positive6,7. Rate the reactivity of the sIgE tests as8: class 1 (&#8805;0.35 and &#60;0.70 IU/mL), class 2 (&#8805;0.70 and &#60;3.50 IU/mL), class 3 (&#8805;3.50 and &#60;17.50 IU/mL), class 4 (&#8805;17.50 and &#60;50.00 IU/mL), class 5 (&#8805;50.00 and &#60;100.00 IU/mL), and class 6 (&#8805;100.00 IU/mL).</li>
</ol>
5. Statistical analysis
<ol>
	<li>Use a histogram to show the positive rate of the 19 allergens (Figure 1) and use the Levey-Jennings curve to demonstrate the repeatability of the detection system (Figure 2)9.</li>
	<li>Select the three most common inhalant allergens and food allergens (in total, six allergens) and compare the results to the I System 1 to evaluate its clinical diagnostic performance10,11. Include the concordance rate, sensitivity, specificity, positive and negative predictive values, and the area under the receiver operating characteristic (ROC) curve (AUC) as the evaluation criteria.</li>
	<li>Apply Spearman&#8217;s correlation analysis12 to describe correlations between the two systems and use kappa value for consistency. Categorize the kappa value as almost perfect (0.8&#8211;1.0), substantial (0.6&#8211;0.8), moderate (0.4&#8211;0.6), fair (0.2&#8211;0.4), or poor (&#60;0.2)13. Use SPSS 23.0 and MedCalc 11.0 statistical analysis and define P &#60; 0.05 as statistical significance.</li>
</ol>

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The authors have nothing to disclose.

Similar to the results from many other studies15,16,17, the results from the microfluidic system based on sera from 293 allergic patients showed that house dust mites (including D. pteronyssinus, D. farinae, and B. tropicalis) are the main inhalant allergens leading to allergic diseases in southern China, whereas for food, milk, peanut, shrimp, and crab are the commonest allergens that cause allergic s...

The prevalence of allergies has increased steadily in the past decades and is affecting 20%-30% of the global population1. Identification of the causative allergens has important significance in managing the diseases. In China, since registered in vivo skin prick tests are not available in the country, in vitro determination of serum-specific IgE is the most important and commonly used tool for type I allergy diagnoses2. This is similar to practices in the Western world, but although ImmunoCAP system (System 1), a fluorescence enzyme-linked immunosorbent base system, is perceived as the gold standard for in vitro allergy diagnosis3, its usage in China is very limited due to its high equipment and reagent price. Hence a new alternative allergy diagnosis system with a high price-performance ratio is badly needed.
The BioIC System (System 2) is a microfluidic cartridge-based system based on the chemiluminescence principle for multiplexed assays of serum-specific IgE. With a size of 7 cm x 4 cm, the microfluidic cartridge is composed of three layers of injection-molded plastic. The upper part is 3 mm-thick transparent polycarbonate which carries good stability during thermal assembly processes. Together with the 3 mm-thick bottom layer constructed from a copolymer of acrylonitrile, butadiene, and styrene (ABS), it sandwiches the 0.5 mm-thick middle layer made of silicone rubber. Being black in color, the middle layer offers lower background during chemiluminescence detection. On top of the silica gel, a thin layer of nitrocellulose membrane (NC membrane) is sprayed at the position corresponding to the reaction zone, which allows the spotting of different allergenic proteins. The purpose of this study is to evaluate the clinical performance of the microfluidic system for the multiplexed determination of allergen-specific IgE in serum.

<table>
	<tbody>
		<tr>
			<td>Agnitio BioIC Analyzer</td>
			<td>Agnitio Science &#38; Technology(Taiwan, China)</td>
			<td>BA-G2000</td>
			<td></td>
		</tr>
		<tr>
			<td>BioIC Allergen specific-IgE Detection Kit</td>
			<td>Agnitio Science &#38; Technology(Taiwan, China)</td>
			<td>DR17A12</td>
			<td></td>
		</tr>
		<tr>
			<td>BioIC Cartrideg Placement plate</td>
			<td>Agnitio Science &#38; Technology(Taiwan, China)</td>
			<td>T20SET</td>
			<td></td>
		</tr>
		<tr>
			<td>BioIC Reagent Dispenser</td>
			<td>Agnitio Science &#38; Technology(Taiwan, China)</td>
			<td>DS-1</td>
			<td></td>
		</tr>
		<tr>
			<td>Image two-dimensional barcode machine</td>
			<td>Agnitio Science &#38; Technology(Taiwan, China)</td>
			<td>NLS-HR200</td>
			<td></td>
		</tr>
		<tr>
			<td>Software Package, LabIT</td>
			<td>Agnitio Science &#38; Technology(Taiwan, China)</td>
			<td>Version 2.4.12</td>
			<td></td>
		</tr>
		<tr>
			<td>VORTEX-5 Vortex Mixer</td>
			<td>Haimen Kylinbell Lab Lastruments Co., Ltd.</td>
			<td>VORTEX-5</td>
			<td></td>
		</tr>
	</tbody>
</table>

application of biochip microfluidic technology to detect serum allergen-specific immunoglobulin e (sige)

Allergic disease is common in both adults and children. Identification of the causative allergens is significant in disease management and prevention. However, a specific immunoglobulin E (IgE) measurement system with a high price-performance ratio is lacking in mainland China, especially in the primary care hospitals. This paper describes the principle and operation procedures of using a microfluidic cartridge-based chemiluminescence system to detect allergen-specific IgE in serum. The results were compared with those from ImmunoCAP (System 1), the industrial standard, and the reproducibility of the system to detect patients sensitized to common allergens is evaluated. The results showed that in comparison with ImmunoCAP (System 1), the BioIC System (System 2) has good precision and sensitivity in detecting serum-specific IgE against various inhalant and food allergens but with a significantly lower cost. It can serve as a good alternative to System 1 in primary care hospitals in mainland China who have lower financial affordability.

Positive rates for 19 common allergens 
The results on 293 sera are shown in Figure 3. Among all the inhalant allergens, D. farinae had the highest positive rate (80.89%, 273/293), followed by D. pteronyssinus (78.84%, 231/293). Among the food allergens, crab has the highest positive rate (20.48%, 60/293), followed by 13.65% (40/293) for shrimp. The total positive rate for inhalant allergens was higher than tha...

Watch this Scientific Journal Video about Application of Biochip Microfluidic Technology to Detect Serum Allergen-specific Immunoglobulin E sIgE at JoVE.com

Application of Biochip Microfluidic Technology to Detect Serum Allergen-specific Immunoglobulin E sIgE

This paper presents a protocol for detecting serum-specific immunoglobulin E with a microfluidic cartridge-based chemiluminescence system and the evaluation of its usefulness in allergy diagnoses.

Application of Biochip Microfluidic Technology to Detect Serum Allergen-specific Immunoglobulin E (sIgE)

Allergic disease is common in both adults and children. Identification of the causative allergens is significant in disease management and prevention. ...

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16.3K Views.  First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University. This paper presents a protocol for detecting serum-specific immunoglobulin E with a microfluidic cartridge-based chemiluminescence system and the evaluation of its usefulness in allergy diagnoses.

Video: Application of Biochip Microfluidic Technology to Detect Serum Allergen-specific Immunoglobulin E sIgE

The Use of Thermal Infra-Red Imaging to Detect Delayed Onset Muscle Soreness

Delayed onset muscle soreness (DOMS), also known as exercise induced muscle damage (EIMD), is commonly experienced in individuals who have been physically inactive for prolonged periods of time, and begin with an unexpected bout of exercise1-4, but can also occur in athletes who exercise beyond their normal limits of training5. The symptoms associated with this painful phenomenon can range from slight muscle tenderness, to severe debilitating pain1,3,5. The intensity of these symptoms and the related discomfort increases within the first 24 hours following the termination of the exercise, and peaks between 24 to 72 hours post exercise1,3. For this reason, DOMS is one of the most common recurrent forms of sports injury that can affect an individual&#x2019;s performance, and become intimidating for many1,4.
For the last 3 decades, the DOMS phenomenon has gained a considerable amount of interest amongst researchers and specialists in exercise physiology, sports, and rehabilitation fields6. There has been a variety of published studies investigating this painful occurrence in regards to its underlying mechanisms, treatment interventions, and preventive strategies1-5,7-12. However, it is evident from the literature that DOMS is not an easy pathology to quantify, as there is a wide amount of variability between the measurement tools and methods used to quantify this condition6. It is obvious that no agreement has been made on one best evaluation measure for DOMS, which makes it difficult to verify whether a specific intervention really helps in decreasing the symptoms associated with this type of soreness or not. Thus, DOMS can be seen as somewhat ambiguous, because many studies depend on measuring soreness using a visual analog scale (VAS)10,13-15, which is a subjective rather than an objective measure. Even though needle biopsies of the muscle, and blood levels of myofibre proteins might be considered a gold standard to some6, large variations in some of these blood proteins have been documented 6,16, in addition to the high risks sometimes associated with invasive techniques. 
Therefore, in the current investigation, we tested a thermal infra-red (IR) imaging technique of the skin above the exercised muscle to detect the associated muscle soreness. Infra-red thermography has been used, and found to be successful in detecting different types of diseases and infections since the 1950&#x2019;s17. But surprisingly, near to nothing has been done on DOMS and changes in skin temperature. The main purpose of this investigation was to examine changes in DOMS using this safe and non-invasive technique.

The purpose of this investigation was to assess whether using an infra-red thermal camera is a valid tool for detecting and quantifying the muscle soreness after exercising.

Delayed onset muscle soreness (DOMS), also known as exercise induced muscle damage (EIMD), is commonly experienced in individuals who have been physically ...

Visualization and Analysis of Blood Flow and Oxygen Consumption in Hepatic Microcirculation: Application to an Acute Hepatitis Model

There is a considerable discrepancy between oxygen supply and demand in the liver because hepatic oxygen consumption is relatively high but about 70% of the hepatic blood supply is poorly oxygenated portal vein blood derived from the gastrointestinal tract and spleen. Oxygen is delivered to hepatocytes by blood flowing from a terminal branch of the portal vein to a central venule via sinusoids, and this makes an oxygen gradient in hepatic lobules. The oxygen gradient is an important physical parameter that involves the expression of enzymes upstream and downstream in hepatic microcirculation, but the lack of techniques for measuring oxygen consumption in the hepatic microcirculation has delayed the elucidation of mechanisms relating to oxygen metabolism in liver. We therefore used FITC-labeled erythrocytes to visualize the hepatic microcirculation and used laser-assisted phosphorimetry to measure the partial pressure of oxygen in the microvessels there. Noncontact and continuous optical measurement can quantify blood flow velocities, vessel diameters, and oxygen gradients related to oxygen consumption in the liver. In an acute hepatitis model we made by administering acetaminophen to mice we observed increased oxygen pressure in both portal and central venules but a decreased oxygen gradient in the sinusoids, indicating that hepatocyte necrosis in the pericentral zone could shift the oxygen pressure up and affect enzyme expression in the periportal zone. In conclusion, our optical methods for measuring hepatic hemodynamics and oxygen consumption can reveal mechanisms related to hepatic disease.

An optical system was developed to visualize hepatic microcirculation with FITC-labeled erythrocytes and to measure the partial pressure of oxygen in the microvessels with laser-assisted phosphorimetry. This method can be used to investigate physiological and pathological mechanisms by analyzing microvascular structure, diameter, blood flow velocity, and oxygen tension.

There is a considerable discrepancy between oxygen supply and demand in the liver because hepatic oxygen consumption is relatively high but about 70% of ...

Using Continuous Data Tracking Technology to Study Exercise Adherence in Pulmonary Rehabilitation

Pulmonary rehabilitation (PR) is an important component in the management of respiratory diseases. The effectiveness of PR is dependent upon adherence to exercise training recommendations. The study of exercise adherence is thus a key step towards the optimization of PR programs. To date, mostly indirect measures, such as rates of participation, completion, and attendance, have been used to determine adherence to PR. The purpose of the present protocol is to describe how continuous data tracking technology can be used to measure adherence to a prescribed aerobic training intensity on a second-by-second basis.
In our investigations, adherence has been defined as the percent time spent within a specified target heart rate range. As such, using a combination of hardware and software, heart rate is measured, tracked, and recorded during cycling second-by-second for each participant, for each exercise session. Using statistical software, the data is subsequently extracted and analyzed. The same protocol can be applied to determine adherence to other measures of exercise intensity, such as time spent at a specified wattage, level, or speed on the cycle ergometer. Furthermore, the hardware and software is also available to measure adherence to other modes of training, such as the treadmill, elliptical, stepper, and arm ergometer. The present protocol, therefore, has a vast applicability to directly measure adherence to aerobic exercise.

Pulmonary rehabilitation is widely recognized in the management of respiratory diseases. A key component to successful pulmonary rehabilitation is adherence to the recommended exercise training. The purpose of the present protocol is to describe how continuous data tracking technology can be used to precisely measure adherence to a prescribed aerobic training intensity.

Pulmonary rehabilitation (PR) is an important component in the management of respiratory diseases. The effectiveness of PR is dependent upon adherence to ...

High-throughput Flow Cytometry Cell-based Assay to Detect Antibodies to N-Methyl-D-aspartate Receptor or Dopamine-2 Receptor in Human Serum

Over the recent years, antibodies against surface and conformational proteins involved in neurotransmission have been detected in autoimmune CNS diseases in children and adults. These antibodies have been used to guide diagnosis and treatment. Cell-based assays have improved the detection of antibodies in patient serum. They are based on the surface expression of brain antigens on eukaryotic cells, which are then incubated with diluted patient sera followed by fluorochrome-conjugated secondary antibodies. After washing, secondary antibody binding is then analyzed by flow cytometry. Our group has developed a high-throughput flow cytometry live cell-based assay to reliably detect antibodies against specific neurotransmitter receptors. This flow cytometry method is straight forward, quantitative, efficient, and the use of a high-throughput sampler system allows for large patient cohorts to be easily assayed in a short space of time. Additionally, this cell-based assay can be easily adapted to detect antibodies to many different antigenic targets, both from the central nervous system and periphery. Discovering additional novel antibody biomarkers will enable prompt and accurate diagnosis and improve treatment of immune-mediated disorders.

Over the recent years, live cell-based assays have been used successfully to detect antibodies against surface and conformational antigens. Here, we describe a method using high-throughput flow cytometry enabling the analysis of large cohorts of patients. Detection of novel antibodies will improve diagnosis and treatment of immune-mediated disorders.

Over the recent years, antibodies against surface and conformational proteins involved in neurotransmission have been detected in autoimmune CNS diseases ...

Adapting Human Videofluoroscopic Swallow Study Methods to Detect and Characterize Dysphagia in Murine Disease Models

This study adapted human videofluoroscopic swallowing study (VFSS) methods for use with murine disease models for the purpose of facilitating translational dysphagia research. Successful outcomes are dependent upon three critical components: test chambers that permit self-feeding while standing unrestrained in a confined space, recipes that mask the aversive taste/odor of commercially-available oral contrast agents, and a step-by-step test protocol that permits quantification of swallow physiology. Elimination of one or more of these components will have a detrimental impact on the study results. Moreover, the energy level capability of the fluoroscopy system will determine which swallow parameters can be investigated. Most research centers have high energy fluoroscopes designed for use with people and larger animals, which results in exceptionally poor image quality when testing mice and other small rodents. Despite this limitation, we have identified seven VFSS parameters that are consistently quantifiable in mice when using a high energy fluoroscope in combination with the new murine VFSS protocol. We recently obtained a low energy fluoroscopy system with exceptionally high imaging resolution and magnification capabilities that was designed for use with mice and other small rodents. Preliminary work using this new system, in combination with the new murine VFSS protocol, has identified 13 swallow parameters that are consistently quantifiable in mice, which is nearly double the number obtained using conventional (i.e., high energy) fluoroscopes. Identification of additional swallow parameters is expected as we optimize the capabilities of this new system. Results thus far demonstrate the utility of using a low energy fluoroscopy system to detect and quantify subtle changes in swallow physiology that may otherwise be overlooked when using high energy fluoroscopes to investigate murine disease models.

This study successfully adapted human videofluoroscopic swallowing study (VFSS) methods for use with murine disease models for the purpose of facilitating translational dysphagia research.

This study adapted human videofluoroscopic swallowing study (VFSS) methods for use with murine disease models for the purpose of facilitating ...

Application of End-to-end Anastomosis in Robotic Central Pancreatectomy

Central pancreatectomy is carried out for the treatment of benign or low-malignant potential tumors located in the pancreatic neck or proximal part of pancreatic body. With technological development, the robotic surgical system has shown its advantage in minimally invasive surgery and been increasingly applied in central pancreatectomy. However, reconstruction of the continuity of pancreas with end-to-end anastomosis after robotic central pancreatectomy has not been applied. In this study, we report surgical techniques for robotic central pancreatectomy with end-to-end anastomosis. The pancreas is reconstructed by duct-to-duct anastomosis of the pancreatic duct with a pancreatic stent inserted in the two stumps of pancreatic duct, and by end-to-end anastomosis of the pancreatic parenchyma. Compared with traditional central pancreatectomy with pancreaticoenteric anastomosis, this approach decreases the operative injury to the patient, and also conserves the integrity and continuity of the digestive duct and pancreatic duct. The robotic surgical system integrated with multiple instruments with flexible and precise movement is particularly suitable for the dissection and reconstruction of the pancreatic duct. We found that robotic central pancreatectomy with end-to-end anastomosis is safe and feasible, and we need more experience to evaluate its best indications and long-term outcomes.

The robotic central pancreatectomy with end-to-end anastomosis is feasible and safe for tumor in the pancreatic neck and proximal portion of pancreatic body. The operative techniques of this operation are presented.

Central pancreatectomy is carried out for the treatment of benign or low-malignant potential tumors located in the pancreatic neck or proximal part of ...

Proton Therapy Delivery and Its Clinical Application in Select Solid Tumor Malignancies

Radiation therapy is a frequently used modality for the treatment of solid cancers. Although the mechanisms of cell kill are similar for all forms of radiation, the in vivo properties of photon and proton beams differ greatly and maybe exploited to optimize clinical outcomes. In particular, proton particles lose energy in a predictable manner as they pass through the body. This property is used clinically to control the depth at which the proton beam is terminated, and to limit radiation dose beyond the target region. This strategy can allow for substantial reductions in radiation dose to normal tissues located just beyond a tumor target. However, the degradation of proton energy in the body remains highly sensitive to tissue density. As a consequence, any changes in tissue density during the course of treatment may significantly alter proton dosimetry. Such changes may occur through alterations in body weight, respiration, or bowel filling/gas, and may result in unfavorable dose deposition. In this manuscript, we provide a detailed method for the delivery of proton therapy using both passive scatter and pencil beam scanning techniques for prostate cancer. Although the described procedure directly pertains to prostate cancer patients, the method may be adapted and applied for the treatment of virtually all solid tumors. Our aim is to equip readers with a better understanding of proton therapy delivery and outcomes in order to facilitate the appropriate integration of this modality during cancer therapy.

The fundamentals of radiation planning and delivery for proton therapy using prostate cancer as a model are presented. The application of these principles to other selected disease sites highlights how proton radiotherapy may enhance clinical outcomes for cancer patients.

Radiation therapy is a frequently used modality for the treatment of solid cancers. Although the mechanisms of cell kill are similar for all forms of ...

Analyzing Long-Term Electrocardiography Recordings to Detect Arrhythmias in Mice

Arrhythmias are common, affecting millions of patients worldwide. Current treatment strategies are associated with significant side effects and remain ineffective in many patients. To improve patient care, novel and innovative therapeutic concepts causally targeting arrhythmia mechanisms are needed. To study the complex pathophysiology of arrhythmias, suitable animal models are necessary, and mice have been proven to be ideal model species to evaluate the genetic impact on arrhythmias, to investigate fundamental molecular and cellular mechanisms, and to identify potential therapeutic targets.
Implantable telemetry devices are among the most powerful tools available to study electrophysiology in mice, allowing continuous ECG recording over a period of several months in freely moving, awake mice. However, due to the huge number of data points (&gt;1 million QRS complexes per day), analysis of telemetry data remains challenging. This article describes a step-by-step approach to analyze ECGs and to detect arrhythmias in long-term telemetry recordings using the software, Ponemah, with its analysis modules, ECG Pro and Data Insights, developed by Data Sciences International (DSI). To analyze basic ECG parameters, such as heart rate, P wave duration, PR interval, QRS interval, or QT duration, an automated attribute analysis was performed using Ponemah to identify P, Q, and T waves within individually adjusted windows around detected R waves. 
Results were then manually reviewed, allowing adjustment of individual annotations. The output from the attribute-based analysis and the pattern recognition analysis was then used by the Data Insights module to detect arrhythmias. This module allows an automatic screening for individually defined arrhythmias within the recording, followed by a manual review of suspected arrhythmia episodes. The article briefly discusses challenges in recording and detecting ECG signals, suggests strategies to improve data quality, and provides representative recordings of arrhythmias detected in mice using the approach described above.

Here we present a step-by-step protocol for a semiautomated approach to analyze murine long-term electrocardiography (ECG) data for basic ECG parameters and common arrhythmias. Data are obtained by implantable telemetry transmitters in living and awake mice and analyzed using Ponemah and its analysis modules.

Arrhythmias are common, affecting millions of patients worldwide. Current treatment strategies are associated with significant side effects and remain ...

Nerve Ultrasound Protocol to Detect Dysimmune Neuropathies

Nerve ultrasound is increasingly used in the differential diagnosis of polyneuropathy as a complementary tool to nerve conduction studies. Morphological alterations of the peripheral nerves, such as increasing the cross-sectional area (CSA), have been described in various immune-mediated polyneuropathies. The most prominent morphological changes in nerve ultrasound have been described for the chronic inflammatory demyelinating polyneuropathy (CIDP)-spectrum disease. CIDP may be distinguished from hereditary and other polyneuropathies by measuring the extent and pattern of nerve swellings (CSA increase). Typical findings in demyelinating inflammatory neuropathies are multifocal nerve swellings with inhomogeneous fascicular structure, while CSA increase in demyelinating hereditary neuropathies occurs in a more generalized and homogenous manner. In other non-inflammatory axonal neuropathies, nerves can appear with normal or slight CSA increases, especially in typical entrapment sites. This article presents technical requirements for nerve ultrasound, an examination procedure using a standardized examination protocol, current reference values for the CSA, and typical sonographic pathological findings in patients with inflammatory neuropathies.

This article presents a protocol for nerve ultrasound in polyneuropathies to aid the diagnosis of inflammatory neuropathies.

Nerve ultrasound is increasingly used in the differential diagnosis of polyneuropathy as a complementary tool to nerve conduction studies. Morphological ...

Bridging the Technology Divide in the COVID-19 Era: Using Virtual Outreach to Expose Middle and High School Students to Imaging Technology

Increasing the diversity of students choosing careers in science, technology, engineering, and mathematics (STEM) fields is an area of intense focus across the USA, especially in kindergarten through 12th grade (K-12)-focused pipeline programs in medical schools. A diverse STEM workforce contributes to better problem-solving and equity in health care. Two of the many major barriers for rural students are the lack of sufficient STEM role models and limited access to technology in the classroom. Medical schools often serve as an important resource for students in the local community who can easily gain access to STEM professionals and modern technology through on-campus, sponsored events and STEM outreach to the local classrooms. However, underrepresented minority (URM) students often live in socioeconomically distressed parts of rural states such as Arkansas, where access to STEM role models and technology is limited. Virtual learning in the COVID-19 era has proven that the imaging technology resources of a medical school can be harnessed to reach a wider audience, especially students living in rural areas far from the medical school campus.

This article presents an overview of how synchronous web-based virtual outreach can be used to expose 6th-12th grade students to advanced imaging technologies such as ultrasound, computerized tomography, and electroencephalography. The paper discusses the methods and equipment needed to livestream integrated educational sessions for effective student engagement in STEM.

Increasing the diversity of students choosing careers in science, technology, engineering, and mathematics (STEM) fields is an area of intense focus ...