The authors have no acknowledgments.

Informed consent was obtained from all participants and the treatment protocol has been approved by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University.
1. Patient selection
<ol>
	<li>Use the following inclusion criteria to include patients who show a clear diagnosis of HPV infection in a common wart, plantar wart, or condyloma acuminatum; the product is indicated for patients who are capable of adhering to medical advice provided by their healthcare practitioners. Ensure that patients can comply with prescribed treatment regimens and adhere to medical directives during therapy to achieve optimal outcomes.
	<ol>
		<li>Pregnancy is not an absolute contraindication for treatment. Prior to therapy, disclose potential risks such as vaginal hemorrhage, spontaneous abortion, fetal demise, and congenital anomalies. Informed consent must be obtained after the patient understands these risks.</li>
	</ol>
	</li>
	<li>Use the following exclusion criteria: Do not apply therapeutic interventions directly to skin lesions in the periocular region. Avoid the management of skin lesions characterized by purulent infections. Do not treat patients who are characterized by a tendency for severe keloid or hypertrophic scar formation. Refrain from treating patients diagnosed with a significant impairment in blood coagulation mechanisms. Do not proceed with treatment for patients exhibiting a documented photosensitivity reaction specifically to red light wavelengths. Do not treat warts that are concomitant with localized skin tumors.</li>
</ol>
2. Target skin lesion selection
<ol>
	<li>For an individual skin lesion, adjust the angle and elevation as needed and apply targeted treatment directly to the lesion (Figure 1).</li>
	<li>For cases involving multiple lesions, select a lesion that is relatively big, planar, and suitable for perpendicular irradiation. The terminology target lesion refers to the lesion chosen for hyperthermia exposure, while lesions not selected for irradiation are referred to as non-target lesions.</li>
	<li>In order to safeguard the patient from potential harm or discomfort during the therapeutic process, avoid sensitive regions. This includes but is not limited to the periocular area. Careful attention to these areas is imperative to ensure patient safety and comfort throughout the treatment.</li>
	<li>Selection of new target points: In cases where the original target point has been resolved but other warts remain, use the criteria described above to select a new target lesion, ensuring consistency in the treatment approach.</li>
</ol>
3. Hyperthermia treatment
<ol>
	<li>Turn on the power switch. Ensure that the device is connected to a power source and flip the switch to the On position. After powering on, the display appears on the machine&#39;s operating screen. The machine allows for the treatment of one patient at a time, and the following are the specific steps for operation.</li>
	<li>Access the registration form: Navigate to the registration module within the machine&#39;s interface. Enter the patient&#39;s basic information by inputting the following details into the corresponding fields: name, gender, age, skin lesion location, skin lesion size, and number of skin lesions.</li>
	<li>The treatment head of this machine is equipped with an integrated camera, enabling photography by simply positioning the treatment head over the affected area. To capture an image of the lesion, click the Capture or Photo button on the screen.</li>
	<li>Level selection: The device offers a range of temperature settings and operational modes to cater to various therapeutic needs. Select from nine temperature levels, starting at 40 &#176;C on Level 1 and increasing to 46 &#176;C on Level 9 (Figure 2A).</li>
	<li>Mode selection: Choose the appropriate treatment mode from the options provided by the machine based on the patient&#39;s condition and treatment plan (Figure 2B).The standard protocol suggests starting at level 5, mode two, but it is essential to adjust the temperature based on the patient&#39;s feedback. 
	NOTE: If a patient experiences a mild, tolerable sensation akin to pinpricks, the treatment may proceed. However, if intense discomfort is felt before reaching the designated temperature, the level should be promptly reduced to prevent injuries such as burns and blisters. On the other hand, if the patient perceives only tolerable, intermittent stinging at the set temperature, it is safe to continue with the treatment.
	<ol>
		<li>Mode one: This mode increments the temperature by 1 &#176;C every 3 min, with each pulse lasting for 10 s.</li>
		<li>Mode two: This is similar to mode one, but each pulse lasts for 20 s, providing a longer exposure to the increased temperature.</li>
		<li>Mode three: This mode accelerates the temperature rise to 2 &#176;C per pulse, with each pulse sustained for 20 s, maintaining a consistent 3 min interval between pulses.</li>
		<li>To initiate the treatment, configure the device settings to Mode two at Level 5 (which corresponds to a temperature of 43 &#176;C). This configuration has been established12,13 as the optimal starting point for patient therapy, ensuring a balance between efficacy and patient comfort. The appropriate treatment level can vary significantly among individuals, with the patient&#39;s tolerance playing a crucial role in its determination.</li>
	</ol>
	</li>
	<li>Set the treatment duration: To ensure optimal treatment efficacy, set the irradiation duration to a minimum of 30 min for each session. This recommended time frame is crucial for achieving the desired therapeutic outcomes.</li>
	<li>Assist the patient in positioning properly. Guide the patient to a comfortable and stable position that allows for effective treatment without discomfort.</li>
	<li>Manually adjust the mechanical arm coarsely. Use manual controls to position the mechanical arm roughly over the treatment area, ensuring it is in the correct general vicinity. 
	NOTE: The treatment device is designed for ease of use, requiring only that the treatment head be oriented generally towards the vicinity of the lesion. For instance, if the skin lesion is located on the hand, the treatment head should be gently positioned near the general area of the lesion on the hand, followed by precise adjustments for accurate targeting.</li>
	<li>Fine-tune the mechanical arm using the cross switch. Maintain a standard distance of 5 cm between the device head and the lesion.
	<ol>
		<li>The machine is equipped with a cross switch that facilitates the adjustment of the mechanical arm connected to the irradiation head. Initially, the irradiation head emits two light beams at a specific angle, resulting in two separate light spots. Manipulate the cross-switch and these two light spots will gradually merge into a single, circular spot. Once the spots have converged into a single, round point, this indicates that the distance is optimal, and irradiation can begin.</li>
	</ol>
	</li>
	<li>Initiate the irradiation process. Once the mechanical arm is correctly positioned, click the Start button to begin the treatment session.</li>
	<li>Treatment monitoring: During treatment, assess the patient&#39;s comfort every 2-3 min and adjust treatment intensity accordingly.If intolerance is noted, promptly lower the intensity to prevent blisters. Ask the patients to use the bedside call bell for any discomfort; staff should respond swiftly to address needs and ensure safety. 
	NOTE: To guarantee that the temperature reaches the designated set point without surpassing it, the light source&#39;s emission head is equipped with an integrated temperature sensor. This sensor continuously monitors the temperature, compares it with the preset value, and automatically adjusts the output to keep the treatment temperature close to the set point without exceeding it. Additionally, the real-time temperature is displayed promptly on the screen. To ensure optimal treatment outcomes, it is crucial to conduct frequent checks of the light spot position and the distance of the device emission window from the warts.
	<ol>
		<li>In the event of patient movement that affects the treatment focus, the device is designed to automatically trigger an alarm. Upon the alarm, staff should promptly attend to the patient to assist with repositioning without the need to manually pause the treatment. The device will pause automatically upon the alarm trigger.</li>
		<li>Once the patient has been repositioned and the device has successfully reestablished focus, the treatment will automatically continue without manual intervention, ensuring minimal disruption to the therapeutic process.</li>
	</ol>
	</li>
	<li>Treatment termination: The remaining time will be continuously displayed during the treatment process. Upon reaching the set duration, the device&#39;s control panel will automatically revert to the main interface, signaling the end of the treatment. After treatment, reset the mechanical arm to its original position. Ensure it is fully retracted and ready for the next session or storage. Inform the patient of their next treatment appointment.</li>
</ol>
4. Treatment plan
<ol>
	<li>The specific therapeutic protocol is illustrated in Figure 3. Typically, the initial treatment period lasts for 15 &#177; 3 days, during which target and non-target lesions exhibit no particularly significant changes. Ensure that the treatment period is approximately 15 days, with a permissible variation of &#177; 3 days.</li>
	<li>After a 2-week initial phase, commence the intensive treatment phase, with treatments administered once weekly for a total of 10 consecutive weeks. Following this, continue with treatments at the same frequency until clear changes in non-target lesions are observed. Subsequently, reduce treatments to once a month or once every two months until the non-target lesions show noticeable changes, such as the disappearance of some warts, the appearance of characteristic apoptotic necrotic spots in the center of warts, or a significant reduction in wart size, indicating remission.</li>
	<li>Monitor the non-target lesions for significant changes, including partial regression of warts, the emergence of characteristic apoptotic necrotic black spots at the lesion centers, and a notable decrease in wart size. Once these changes are observed, adjust the treatment frequency to once every 1-2 months until full recovery is achieved.</li>
	<li>Following an initial period of 2-3 min to assess the patient&#39;s tolerance, adjust the treatment intensity in accordance with the observed response.</li>
</ol>
5. Precautions
<ol>
	<li>In cases where the patient exhibits hypersensitivity to the initial short-term exposure, immediately reduce the treatment intensity to minimize the risk of blistering.</li>
	<li>Keep each treatment session at 30 min, ensuring consistent perpendicular irradiation directed at the target lesion throughout the entire duration.</li>
	<li>To ensure the induction of an immune response, predicate the choice of modality and intensity on the patient perceiving a mild pricking sensation.</li>
	<li>If a blister does form, manage it appropriately and resume treatment once the blisters have fully resolved.</li>
	<li>The application of hyperthermia is contraindicated for skin areas with open wounds.</li>
	<li>Start with hyperthermia, and if necessary, provide medication treatment. If the initial therapeutic outcome is unsatisfactory, augment local hyperthermia with additional treatments, including topical antiviral medications like imiquimod. This combination may improve cure rates and may reduce the treatment duration for topical medications.</li>
	<li>Ensure the selection of warts for hyperthermia treatment targets areas that are relatively flat and facilitate perpendicular irradiation.</li>
</ol>

Effective Wart Treatment with Local Hyperthermia: A Minimally Invasive Approach

<ol>
	<li>White, E. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Manipulation+of+epithelial+differentiation+by+HPV+oncoproteins.">Manipulation of epithelial differentiation by HPV oncoproteins.</a> Viruses. 11 (4), 369 (2019).</li><li>Witchey, D. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Plantar+warts:+Epidemiology,+pathophysiology,+and+clinical+management.">Plantar warts: Epidemiology, pathophysiology, and clinical management.</a> J Osteo Med. 118 (2), 92-105 (2018).</li><li>Burli, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=HPV+vaccination+status+and+resolution+of+warts+in+pediatric+patients.">HPV vaccination status and resolution of warts in pediatric patients.</a> Indian J Dermatol. 66 (6), 604-608 (2021).</li><li>Lofty, A. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intralesional+combined+furosemide+and+digoxin+in+cutaneous+warts+treatment:+A+randomized+controlled+clinical+trial.">Intralesional combined furosemide and digoxin in cutaneous warts treatment: A randomized controlled clinical trial.</a> Derma Ther. 35 (12), e15935 (2022).</li><li>Garc&#237;a-Oreja, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Topical+treatment+for+plantar+warts:+A+systematic+review.">Topical treatment for plantar warts: A systematic review.</a> Derma Ther. 34 (1), e14621 (2021).</li><li>Fields, J. R., Saikaly, S. K., Schoch, J. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intralesional+immunotherapy+for+pediatric+warts:+A+review.">Intralesional immunotherapy for pediatric warts: A review.</a> Pedia Derma. 37 (2), 265-271 (2020).</li><li>Zhang, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Amplifying+cancer+treatment:+advances+in+tumor+immunotherapy+and+nanoparticle-based+hyperthermia.">Amplifying cancer treatment: advances in tumor immunotherapy and nanoparticle-based hyperthermia.</a> Front Immunol. 14, 1258786 (2023).</li><li>Chen, J. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Successful+treatment+of+extensive+flat+warts+with+local+hyperthermia:+A+case+report.">Successful treatment of extensive flat warts with local hyperthermia: A case report.</a> Derma Ther. 33 (6), e14525 (2020).</li><li>De Planell-Mas, E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Human+papillomaviruses+genotyping+in+plantar+warts.">Human papillomaviruses genotyping in plantar warts.</a> J Med Virol. 4689 (5), 902-907 (2017).</li><li>Li, X., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Local+hyperthermia+could+induce+migrational+maturation+of+Langerhans+cells+in+condyloma+acuminatum.">Local hyperthermia could induce migrational maturation of Langerhans cells in condyloma acuminatum.</a> J Dermatol Sci. 54, 121-123 (2009).</li><li>Huo, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clearance+of+genital+warts+in+pregnant+women+by+mild+local+hyperthermia:+a+pilot+report.">Clearance of genital warts in pregnant women by mild local hyperthermia: a pilot report.</a> Dermatol Ther. 27, 109-112 (2014).</li><li>Hildebrandt, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+cellular+and+molecular+basis+of+hyperthermia.">The cellular and molecular basis of hyperthermia.</a> Crit Rev Oncol Hematol. 43, 33-56 (2002).</li><li>Huo, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Local+hyperthermia+at+44+&#176;C+for+the+treatment+of+plantar+warts:+a+randomized,+patient-blinded,+placebo-controlled+trial.">Local hyperthermia at 44 &#176;C for the treatment of plantar warts: a randomized, patient-blinded, placebo-controlled trial.</a> J Infect Dis. 201 (8), 1169-1172 (2010).</li><li>Chen, X., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+observation+and+study+of+local+hyperthermia+for+treating+plantar+warts:+A+pilot+study+with+38+patients.">Clinical observation and study of local hyperthermia for treating plantar warts: A pilot study with 38 patients.</a> Front Medi. 10, 1087659 (2023).</li><li>Qi, R. Q., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clearance+of+multiple+cutaneous+warts+by+targeting+a+single+lesion:+A+randomized+comparative+evaluation+of+mild+local+hyperthermia+versus+cryotherapy.">Clearance of multiple cutaneous warts by targeting a single lesion: A randomized comparative evaluation of mild local hyperthermia versus cryotherapy.</a> J Am Acad Dermatol. 87 (6), 1443-1445 (2022).</li><li>Garcia-Oreja, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Topical+treatment+for+plantar+warts:+a+systematic+review.">Topical treatment for plantar warts: a systematic review.</a> Dermatol Ther. 34, e14621 (2021).</li><li>Lipke, M. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+armamentarium+of+wart+treatments.">An armamentarium of wart treatments.</a> Clin Med Res. 4 (4), 273-293 (2006).</li><li>Forcier, M., Musacchio, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+overview+of+human+papillomavirus+infection+for+the+dermatologist:+disease,+diagnosis,+management,+and+prevention.">An overview of human papillomavirus infection for the dermatologist: disease, diagnosis, management, and prevention.</a> Derma Ther. 23 (5), 458-476 (2010).</li><li>Stern, P., Levine, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Controlled+localized+heat+therapy+in+cutaneous+warts.">Controlled localized heat therapy in cutaneous warts.</a> Arch Dermatol. 128 (7), 945-948 (1992).</li><li>Pfau, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nd:YAG+laser+hyperthermia+in+the+treatment+of+recalcitrant+verrucae+vulgares+(Regensburg's+technique).">Nd:YAG laser hyperthermia in the treatment of recalcitrant verrucae vulgares (Regensburg's technique).</a> Acta Dermato-Venereologica. 74 (3), 212-214 (1994).</li><li>Huo, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Local+hyperthermia+versus+cryotherapy+for+treatment+of+plantar+warts:+A+prospective+multi-centre+non-randomized+concurrent+controlled+clinical+trial.">Local hyperthermia versus cryotherapy for treatment of plantar warts: A prospective multi-centre non-randomized concurrent controlled clinical trial.</a> Acta Dermato-Venereologica. 102, adv00655 (2022).</li><li>Yoshioka, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Suppression+of+contact+sensitivity+by+local+hyperthermia+treatment+due+to+reduced+Langerhans+cell+population+in+mice.">Suppression of contact sensitivity by local hyperthermia treatment due to reduced Langerhans cell population in mice.</a> British J Dermatol. 120 (4), 493-501 (1989).</li><li>Jiang, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Successful+treatment+of+periungual+warts+with+local+hyperthermia:+report+of+two+cases.">Successful treatment of periungual warts with local hyperthermia: report of two cases.</a> J Dermatolog Treat. 33 (4), 2380-2382 (2022).</li><li>Huo, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clearance+of+genital+warts+in+pregnant+women+by+mild+local+hyperthermia:+a+pilot+report.">Clearance of genital warts in pregnant women by mild local hyperthermia: a pilot report.</a> Derma Ther. 27 (2), 109-112 (2014).</li><li>Zhao, S. N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+multicenter+realworld+observation+to+evaluate+the+efficacy+of+cryotherapy+versus+local+hyperthermia+for+the+treatment+of+plane+warts.">A multicenter realworld observation to evaluate the efficacy of cryotherapy versus local hyperthermia for the treatment of plane warts.</a> Derma Ther. 35 (5), e15403 (2022).</li></ol>

The authors have no conflicts of interest to declare.

Plantar warts, condylomata acuminata, and common warts all include mucocutaneous manifestations resulting from human papillomavirus (HPV) infection; these lesions can present as solitary skin lesions or, more commonly, as multiple lesions17.
In the continuous effort to manage warts induced by Human Papillomavirus (HPV), a diverse array of therapeutic strategies has been implemented. These include destructive methods, virucidal agents, antimitotic compounds, and immunoth...

Warts, which are benign epidermal proliferations, are a direct result of human papillomavirus (HPV) infection, specifically targeting the keratinocytes within the stratum corneum of the skin1. They are most commonly manifested clinically as the formation of warts, including plantar warts, genital warts, and common warts2. Warts are typically benign in nature, and although they are occasionally subject to spontaneous resolution3, a considerable number of individuals prefer to have them excised primarily due to the discomfort they cause or social embarrassment4.
A variety of therapeutic approaches have been employed to treat warts, including laser therapy, antiviral treatments, antimitotic medications, and immunotherapies5. However, these treatments are often accompanied by adverse effects such as pain, bleeding, secondary infections, and ulceration6. Consequently, there exists an urgent demand for treatment modalities that offer enhanced safety, efficacy, and minimal invasiveness, particularly for special populations, including the elderly, children, and pregnant women, as well as for specific anatomic sites such as the perianal region and the vulva. 
Addressing the demand for effective and minimally invasive treatments, local hyperthermia has emerged as a promising therapeutic strategy. Hyperthermia has been effectively utilized in the treatment of certain neoplasms7, and there are numerous studies that have demonstrated the efficacy of localized hyperthermia in the management of warts, yielding highly satisfactory outcomes8,9. The hyperthermia device used here offers a range of customizable settings, including adjustable levels and modes, designed to meet diverse therapeutic needs. The overall goal of this hyperthermia device is to provide a non-invasive, safe, and efficacious approach for wart management that is suitable for a wide range of patient populations, including those who are not candidates for more invasive procedures. 
This technique of using local hyperthermia for HPV-related warts is positioned within a growing body of literature that explores the role of heat in modulating immune cell function. It builds on a previous study that established the importance of Langerhans cells in the immune response to skin infections and how their balance can be restored through controlled heat application10.
Individuals with diagnosed HPV-related warts, such as common, plantar, or genital, and who are compliant with medical guidance are considered appropriate candidates for local hyperthermia treatment. Although pregnancy is not an absolute contraindication, pregnant patients must be made aware of the associated risks and must provide informed consent to proceed11. This treatment is not recommended for those with periocular lesions, purulent infections, a propensity for severe scarring, coagulation disorders, or known photosensitivity. Additionally, patients with warts in proximity to tumors are not candidates, as this could suggest an underlying neoplastic process.

<table>
	<tbody>
		<tr>
			<td>YY-WRY-V02 infrared specific wave photothermal therapeutic instrument</td>
			<td>Liaoning Yanyang Medical Equipment Co., Ltd</td>
			<td>No. ZL200720185403.3, China Medical University, China)</td>
			<td></td>
		</tr>
	</tbody>
</table>

local hyperthermia for warts treatment

Warts, benign epidermal proliferations, are a direct result of human papillomavirus (HPV) infection, specifically targeting the keratinocytes within the stratum corneum of the skin. The development of warts is the most common clinical manifestation of HPV, with plantar warts, condylomata acuminata, and common warts being the most frequently observed types. These growths can be unsightly and sometimes painful, affecting the quality of life for those afflicted. Although various treatments are available, ranging from topical medications to surgical procedures, the quest for a treatment that is both safe and effective while minimizing invasiveness continues. This is particularly crucial for populations with heightened risk factors, such as immuno-compromised individuals. In the clinical need for minimally invasive treatments, local hyperthermia has emerged as a promising therapeutic strategy for wart management. As demonstrated in various studies, local hyperthermia is effective as a standalone treatment, offering a valuable alternative for patients seeking less intrusive therapeutic options.

Multiple hospitals have contributed to a series of investigations into the therapeutic effects of hyperthermia. This research encompasses single-arm clinical observational studies, placebo-controlled trials, and comparative analyses with cryotherapy, with the findings being published in various articles13,14,15. They found that hyperthermia was also associated with reduced pain during treatment h...

Author Spotlight: Dermatopathology and the Treatment of Sexually Transmitted Diseases

Here, we present a protocol for local hyperthermia, a new and effective therapeutic for treating warts. We also showcase its safety and efficacy as an independent treatment.

Local Hyperthermia for Warts Treatment

Warts, benign epidermal proliferations, are a direct result of human papillomavirus (HPV) infection, specifically targeting the keratinocytes within the ...

Research

JoVE Journal

Behavior

1.1K Views.  The First Affiliated Hospital of Chongqing Medical University. Here, we present a protocol for local hyperthermia, a new and effective therapeutic for treating warts. We also showcase its safety and efficacy as an independent treatment.

Video: Author Spotlight: Dermatopathology and the Treatment of Sexually Transmitted Diseases

Contextual and Cued Fear Conditioning Test Using a Video Analyzing System in Mice

The contextual and cued fear conditioning test is one of the behavioral tests that assesses the ability of mice to learn and remember an association between environmental cues and aversive experiences. In this test, mice are placed into a conditioning chamber and are given parings of a conditioned stimulus (an auditory cue) and an aversive unconditioned stimulus (an electric footshock). After a delay time, the mice are exposed to the same conditioning chamber and a differently shaped chamber with presentation of the auditory cue. Freezing behavior during the test is measured as an index of fear memory. To analyze the behavior automatically, we have developed a video analyzing system using the ImageFZ application software program, which is available as a free download at http://www.mouse-phenotype.org/. Here, to show the details of our protocol, we demonstrate our procedure for the contextual and cued fear conditioning test in C57BL/6J mice using the ImageFZ system. In addition, we validated our protocol and the video analyzing system performance by comparing freezing time measured by the ImageFZ system or a photobeam-based computer measurement system with that scored by a human observer. As shown in our representative results, the data obtained by ImageFZ were similar to those analyzed by a human observer, indicating that the behavioral analysis using the ImageFZ system is highly reliable. The present movie article provides detailed information regarding the test procedures and will promote understanding of the experimental situation.

This article presents a protocol for a contextual and cued fear conditioning test using a video analyzing system to assess fear learning and memory in mice.

The contextual and cued fear conditioning test is one of the behavioral tests that assesses the ability of mice to learn and remember an association ...

Studying Food Reward and Motivation in Humans

A key challenge in studying reward processing in humans is to go beyond subjective self-report measures and quantify different aspects of reward such as hedonics, motivation, and goal value in more objective ways. This is particularly relevant for the understanding of overeating and obesity as well as their potential treatments. In this paper are described a set of measures of food-related motivation using handgrip force as a motivational measure. These methods can be used to examine changes in food related motivation with metabolic (satiety) and pharmacological manipulations and can be used to evaluate interventions targeted at overeating and obesity. However to understand food-related decision making in the complex food environment it is essential to be able to ascertain the reward goal values that guide the decisions and behavioral choices that people make. These values are hidden but it is possible to ascertain them more objectively using metrics such as the willingness to pay and a method for this is described. Both these sets of methods provide quantitative measures of motivation and goal value that can be compared within and between individuals.

This article describes a set of methods for the measurement of food related motivation and food related goal values in humans.

A key challenge in studying reward processing in humans is to go beyond subjective self-report measures and quantify different aspects of reward such as ...

A Treatment Package without Escape Extinction to Address Food Selectivity

Feeding difficulties and feeding disorders are a commonly occurring problem for young children, particularly children with developmental delays including autism. Behavior analytic interventions for the treatment of feeding difficulties oftentimes include escape extinction as a primary component of treatment. The use of escape extinction, while effective, may be problematic as it is also associated with the emergence of challenging behavior (e.g., extinction burst). Such challenging behavior may be an acceptable side effect in treatment cases where feeding problems are severe and chronic (e.g., failure to thrive). However, in more acute cases (e.g., selective eating), the negative side effect may be unwarranted and undesired. More recent research on the behavioral treatment of food selectivity has begun to evaluate treatments for feeding difficulties that do not include escape extinction (e.g., demand fading, behavioral momentum), with some success. However, research to date reveals individual differences in responsiveness to such treatments and no clear preferable treatment has emerged. This manuscript describes a multi-component treatment package that includes shaping, sequential presentation and simultaneous presentation, for the treatment of food selectivity in four young children with developmental delays. This treatment package extends the literature on the behavioral treatment for food selectivity and offers a multi-component treatment protocol that may be clinically applicable across a range of treatment scenarios and settings.

Feeding difficulties are a common problem for children with developmental disorders, including autism, and behavioral interventions often include escape extinction. Recent research has begun to evaluate treatments that do not include escape extinction. This manuscript describes a multicomponent treatment package that does not use escape extinction to treat feeding difficulties.

Feeding difficulties and feeding disorders are a commonly occurring problem for young children, particularly children with developmental delays including ...

Combined Shuttle-Box Training with Electrophysiological Cortex Recording and Stimulation as a Tool to Study Perception and Learning

Shuttle-box avoidance learning is a well-established method in behavioral neuroscience and experimental setups were traditionally custom-made; the necessary equipment is now available by several commercial companies. This protocol provides a detailed description of a two-way shuttle-box avoidance learning paradigm in rodents (here Mongolian gerbils; Meriones unguiculatus) in combination with site-specific electrical intracortical microstimulation (ICMS) and simultaneous chronical electrophysiological in vivo recordings. The detailed protocol is applicable to study multiple aspects of learning behavior and perception in different rodent species.
Site-specific ICMS of auditory cortical circuits as conditioned stimuli here is used as a tool to test the perceptual relevance of specific afferent, efferent and intracortical connections. Distinct activation patterns can be evoked by using different stimulation electrode arrays for local, layer-dependent ICMS or distant ICMS sites. Utilizing behavioral signal detection analysis it can be determined which stimulation strategy is most effective for eliciting a behaviorally detectable and salient signal. Further, parallel multichannel-recordings using different electrode designs (surface electrodes, depth electrodes, etc.) allow for investigating neuronal observables over the time course of such learning processes. It will be discussed how changes of the behavioral design can increase the cognitive complexity (e.g. detection, discrimination, reversal learning).

Shuttle-box avoidance learning is well-established in behavioral neuroscience. This protocol describes how shuttle-box learning in rodents can be combined with site-specific electrical intracortical microstimulation (ICMS) and simultaneous chronical in vivo recordings as a tool to study multiple aspects of learning and perception.

Shuttle-box avoidance learning is a well-established method in behavioral neuroscience and experimental setups were traditionally custom-made; the ...

Treatment of Ankle Osteoarthritis with Total Ankle Replacement Through a Lateral Transfibular Approach

Total ankle replacement (TAR) is a valid option for the treatment of ankle osteoarthritis. The traditional surgical approach for TAR is the anterior approach. Recently, the lateral transfibular approach to the ankle has gained popularity since a new TAR implant was designed to be performed via this approach that results in an ideal visualization of the center of rotation of the ankle and curved resections that allow for sparing bone cuts. The aim of the present paper is to present our preoperative, operative, and postoperative protocols for the treatment of the osteoarthritis of the ankle with TAR via lateral approach. We present our preoperative clinical and radiographic protocol. In addition, we describe our surgical technique with some technical tips. Finally, we report our follow-up schedule that includes the collection of clinical, functional, and radiographic data. The results of this procedure are encouraging: TAR through a lateral transfibular approach provides reliable pain relief and improvements in functional outcomes in patients with ankle osteoarthritis.

We present our preoperative, operative, and postoperative protocols for the treatment of osteoarthritis of the ankle with total ankle replacement via lateral transfibular approach.

Total ankle replacement (TAR) is a valid option for the treatment of ankle osteoarthritis. The traditional surgical approach for TAR is the anterior ...

Automated, Long-term Behavioral Assay for Cognitive Functions in Multiple Genetic Models of Alzheimer's Disease, Using IntelliCage

Multiple factors&#8212;such as aging and genes&#8212;are frequently associated with cognitive decline. Genetically modified mouse models of cognitive decline, such as Alzheimer&#39;s disease (AD), have become a promising tool to elucidate the underlying mechanisms and promote the therapeutic advances. An important step is the validation and characterization of expected behavioral abnormality in the models, in the case of AD, cognitive decline. The long-term behavioral investigations of laboratory animals to study the effect of aging demand substantial efforts from researchers. The IntelliCage system is a high-throughput and cost-effective test battery for mice that eliminates the need for daily human handling. Here, we describe how the system is utilized in the long-term phenotyping of a genetic Alzheimer&#39;s disease model, specifically focusing on the cognitive functions. The experiment employs repeated battery of tests that assess spatial learning and executive functions. This cost-effective age-dependent phenotyping allows us to identify the transient and/or permanent effects of genes on various cognitive aspects.

This paper describes a protocol for cognitive assessments for genetic models of the Alzheimer&#39;s disease using the IntelliCage system, which is a high throughput automated behavioral monitoring system with operant conditioning.

Multiple factors&#8212;such as aging and genes&#8212;are frequently associated with cognitive decline. Genetically modified mouse models of cognitive ...

A Visual Guide for Studying Behavioral Defenses to Pathogen Attacks in Leaf-Cutting Ants

The complex lifestyle, evolutionary history of advanced cooperation, and disease defenses of leaf-cutting ants are well studied. Although numerous studies have described the behaviors connected with disease defense, and the associated use of chemicals and antimicrobials, no common visual reference has been made. The main aim of this study was to record short clips of behaviors involved in disease defense, both prophylactically and directly targeted towards an antagonist of the colony following infection. To do so we used an infection experiment, with sub-colonies of the leaf-cutting ant species Acromyrmex echinatior, and the most significant known pathogenic threat to the ants&#39; fungal crop (Leucoagaricus gongylophorus), a specialized pathogenic fungus in the genus Escovopsis. We filmed and compared infected and uninfected colonies, at both early and more advanced stages of infection. We quantified key defensive behaviors across treatments and show that the behavioral response to pathogen attack likely varies between different castes of worker ants, and between early and late detection of a threat. Based on these recordings we have made a library of behavioral clips, accompanied by definitions of the main individual defensive behaviors. We anticipate that such a guide can provide a common frame of reference for other researchers working in this field, to recognize and study these behaviors, and also provide greater scope for comparing different studies to ultimately help better understand the role these behaviors play in disease defense.

We present a visual guide to disease defense behaviors in leaf-cutting ants, with individual clips and accompanying definitions, illustrated in an experimental infection scenario. Our main aim is to help other researchers recognize key defensive behaviors and to provide a common understanding for future research in this field.

The complex lifestyle, evolutionary history of advanced cooperation, and disease defenses of leaf-cutting ants are well studied. Although numerous studies ...

Simultaneous Recordings of Cortical Local Field Potentials and Electrocorticograms in Response to Nociceptive Laser Stimuli from Freely Moving Rats

Electrocortical responses, elicited by laser heat pulses that selectively activate nociceptive free nerve endings, are widely used in many animal and human studies to investigate the cortical processing of nociceptive information. These laser-evoked brain potentials (LEPs) consist of several transient responses that are time-locked to the onset of laser stimuli. However, the functional properties of the LEP responses are still largely unknown, due to the lack of a sampling technique that can simultaneously record neural activities at the surface of the cortex (i.e., electrocorticogram [ECoG] and scalp electroencephalogram [scalp EEG]) and inside the brain (i.e., local field potential [LFP]). To address this issue, we present here an animal protocol using freely moving rats. This protocol is composed of three main procedures: (1) animal preparation and surgical procedures, (2) a simultaneous recording of ECoG and LFP in response to nociceptive laser stimuli, and (3) data analysis and feature extraction. Specifically, with the help of a 3D-printed protective shell, both ECoG and LFP electrodes implanted on the rat&#39;s skull were securely held together. During data collection, laser pulses were delivered on the rat&#39;s forepaws through gaps in the bottom of the chamber when the animal was in spontaneous stillness. Ongoing white noise was played to avoid the activation of the auditory system by the laser-generated ultrasounds. As a consequence, only nociceptive responses were selectively recorded. Using the standard analytical procedures (e.g., band-pass filtering, epoch extraction, and baseline correction) to extract stimulus-related brain responses, we obtained results showing that LEPs with a high signal-to-noise ratio were simultaneously recorded from ECoG and LFP electrodes. This methodology makes the simultaneous recording of ECoG and LFP activities possible, which provides a bridge of electrocortical signals at the mesoscopic and macroscopic levels, thereby facilitating the investigation of nociceptive information processing in the brain.

We developed a technique that simultaneously records both electrocorticography and local field potentials in response to nociceptive laser stimuli from freely moving rats. This technique helps establish a direct relationship of electrocortical signals at the mesoscopic and macroscopic levels, which facilitates the investigation of nociceptive information processing in the brain.

Electrocortical responses, elicited by laser heat pulses that selectively activate nociceptive free nerve endings, are widely used in many animal and ...

Calcium Imaging in Freely Behaving Caenorhabditis elegans with Well-Controlled, Nonlocalized Vibration

Nonlocalized mechanical forces, such as vibrations and acoustic waves, influence a wide variety of biological processes from development to homeostasis. Animals cope with these stimuli by modifying their behavior. Understanding the mechanisms underlying such behavioral modification requires quantification of neural activity during the behavior of interest. Here, we report a method for calcium imaging in freely behaving Caenorhabditis elegans with nonlocalized vibration of specific frequency, displacement, and duration. This method allows the production of well-controlled, nonlocalized vibration using an acoustic transducer and quantification of evoked calcium responses at single-cell resolution. As a proof of principle, the calcium response of a single interneuron, AVA, during the escape response of C. elegans to vibration is demonstrated. This system will facilitate understanding of neural mechanisms underlying behavioral responses to mechanical stimuli.

Calcium Imaging in Freely Behaving Caenorhabditis elegans with Well-Controlled, Nonlocalized Vibration

Reported here is a system for calcium imaging in freely behaving Caenorhabditis elegans with well-controlled, nonlocalized vibration. This system allows researchers to evoke nonlocalized vibrations with well-controlled properties at nano-scale displacement and to quantify calcium currents during responses of C. elegans to the vibrations.

Nonlocalized mechanical forces, such as vibrations and acoustic waves, influence a wide variety of biological processes from development to homeostasis. ...

Individualized rTMS Treatment for Depression using an fMRI-Based Targeting Method

To achieve greater clinical efficacy, a revolution in treatment for major depressive disorder (MDD) is highly anticipated. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive and safe neuromodulation technique that immediately changes brain activity. Despite its wide application in the treatment for MDD, the treatment response remains different among individuals, which may be attributable to the inaccurate positioning of the stimulation target. Our study aims to examine whether the functional magnetic resonance imaging (fMRI)-assisted positioning improves the efficacy of rTMS in treating depression. We intend to identify and stimulate the subregion of dorsolateral prefrontal cortex (DLPFC) in MDD with strongest anti-correlation with the subgenual anterior cingulate cortex (sgACC), and to conduct a comparative investigation of this novel method and the traditional 5-cm rule. To achieve more precise stimulation, both methods were applied under the guidance of neuronavigation system. We expected that the TMS treatment with individualized positioning based on resting state functional connectivity may show better clinical efficacy than the 5-cm method.

The present protocol describes the application of repetitive transcranial magnetic stimulation (rTMS), where a subregion of the dorsolateral prefrontal cortex (DLPFC) with the strongest functional anticorrelation with the subgenual anterior cingulate cortex (sgACC) was located as the stimulation target under the assistance of a fMRI-based neuronavigation system.