Nanopore DNA Sequencing Detected Chromothripsis-Induced PAFAH1B1::USP6 Rearrangement in Periosteal Solid Aneurysmal Bone Cyst Initially Diagnosed as Osteosarcoma.

An aneurysmal bone cyst (ABC) is a benign bone neoplasm that typically occurs during the first and second decades of life. ABC usually presents as a rapidly growing intramedullary expansile mass with multiple blood-filled cysts in the metaphysis of the long tubular bones. Here, we report a case of a periosteal solid ABC that was initially diagnosed as a high-grade surface osteosarcoma. A 10-year-old male was referred to our hospital for swelling and tenderness of the left upper arm. Radiography revealed periosteal mass without fluid-fluid levels. On performing open biopsy, the tumor showed hypercellular proliferation of uniform spindle to epithelioid cells with brisk mitotic activity (up to 12/2 mm2) and lace-like osteoid formation, which was diagnosed as a high-grade surface osteosarcoma. After one course of chemotherapy using adriamycin and cisplatin, peripheral sclerosis was conspicuous, which led to pathological review and revision of diagnosis as "possibly osteoblastoma." The patient was disease-free for 4 years after marginal resection and curettage. Retrospective nanopore DNA sequencing unexpectedly detected a PAFAH1B1::USP6 rearrangement. The fusion gene was further validated using reverse transcription-polymerase chain reaction and the diagnosis was revised to ABC. Chromothripsis involving chromosome 17 has also been identified. Methylation analysis classified the present tumor as an ABC or non-ossifying fibroma using t-distributed stochastic neighbor embedding and unsupervised hierarchical clustering. This case report highlights the utility of nanopore DNA sequencing for soft tissue and bone tumor diagnosis.

Allelic loss of HLA class I facilitates evasion from immune surveillance in cervical intraepithelial neoplasia.

Loss of heterozygosity (LOH) has been reported to occur in HLA regions in cervical intraepithelial neoplasia (CIN) and cervical cancer. However, the details of how this is related to the progression of CIN have been unclear. In this study, we examined the human papillomavirus (HPV) antigen-presenting capacity of people with CIN and the significance of LOH of HLA class I in the progression of CIN. It was shown that differences in antigen-presenting capacity among each case depended on HLA types, not HPV genotypes. Focusing on the HLA type, there was a positive correlation between antigen-presenting capacity against HPV and the frequency of allelic loss. Furthermore, the lost HLA-B alleles had a higher HPV antigen-presenting capacity than intact alleles. In addition, frequency of LOH of HLA class I was significantly higher in advanced CIN (CIN2-3) than in cervicitis or early-stage CIN (CIN1): around half of CIN2-3 had LOH of any HLA class I. Moreover, the antigen-presenting capacity against E5, which is the HPV proteins that facilitate viral escape from this immune surveillance by suppressing HLA class I expression, had the most significant impact on the LOH in HLA-B. This study suggests that HPV evades immune surveillance mechanisms when host cells lose the capacity for antigen presentation by HLA class I molecules, resulting in long-term infection and progression to advanced lesions.

Metastasizing aneurysmal dermatofibroma initially diagnosed as angiosarcoma confirmed by CD63::PRKCD fusion gene detection with nanopore sequencing.

Dermatofibroma (DF) is a benign tumor that forms pedunculated lesions ranging in size from a few millimeters to 2 cm, usually affecting the extremities and trunks of young adults. Histopathologically, DF is characterized by the storiform proliferation of monomorphic fibroblast-like spindle cells. In addition to neoplastic cells, secondary elements such as foamy histiocytes, Touton-type giant cells, lymphoplasmacytes, and epidermal hyperplasia are characteristic histological features. Several histological variants, including atypical, cellular, aneurysmal, and lipidized variants, have been reported; cases with variant histologies are sometimes misdiagnosed as sarcomas. We present a case of metastasizing aneurysmal DF that was initially diagnosed as an angiosarcoma on biopsy. A 26-year-old woman was referred to our hospital with a gradually enlarging subcutaneous mass in her lower left leg. Positron emission tomography-computed tomography revealed high fluorodeoxyglucose uptake not only in the tumor but also in the left inguinal region. On biopsy, ERG and CD31-positive atypical spindle cells proliferated in slit-like spaces with extravasation, leading to the diagnosis of angiosarcoma. Histology of the wide-resection specimen was consistent with DF, and lymph node metastasis was also observed. Nanopore DNA sequencing detected CD63::PRKCD fusion and copy number gain, although CD63 was not included in the target region of adaptive sampling. This report highlights the importance of recognizing the unusual clinical, radiological, and pathological features of DF to avoid misdiagnosis, and the potential diagnostic utility of nanopore sequencer.

Sodium Bicarbonate Decreases Alcohol Consumption in Mice.

We previously reported that mice with low neuronal pH drink more alcohol, demonstrating the importance of pH for alcohol reward and motivation. In this study, we tested whether systemic pH affects alcohol consumption and if so, whether it occurs by changing the alcohol reward. C57BL/6J mice were given NaHCO3 to raise their blood pH, and the animals' alcohol consumption was measured in the drinking-in-the-dark and two-bottle free choice paradigms. Alcohol consumption was also assessed after suppressing the bitterness of NaHCO3 with sucrose. Alcohol reward was evaluated using a conditioned place preference. In addition, taste sensitivity was assessed by determining quinine and sucrose preference. The results revealed that a pH increase by NaHCO3 caused mice to decrease their alcohol consumption. The decrease in high alcohol contents (20%) was significant and observed at different ages, as well as in both males and females. Alcohol consumption was also decreased after suppressing NaHCO3 bitterness. Oral gavage of NaHCO3 did not alter quinine and sucrose preference. In the conditioned place preference, NaHCO3-treated mice spent less time in the alcohol-injected chamber. Conclusively, the results show that raising systemic pH with NaHCO3 decreases alcohol consumption, as it decreases the alcohol reward value.

Lipid-Binding Regions within PKC-Related Serine/Threonine Protein Kinase N1 (PKN1) Required for Its Regulation.

PKC-related serine/threonine protein kinase N1 (PKN1) is a protease/lipid-activated protein kinase that acts downstream of the RhoA and Rac1 pathways. PKN1 comprises unique regulatory, hinge region, and PKC homologous catalytic domains. The regulatory domain harbors two homologous regions, i.e., HR1 and C2-like. HR1 consists of three heptad repeats (HR1a, HR1b, and HR1c), with PKN1-(HR1a) hosting an amphipathic high-affinity cardiolipin-binding site for phospholipid interactions. Cardiolipin and C18:1 oleic acid are the most potent lipid activators of PKN1. PKN1-(C2) contains a pseudosubstrate sequence overlapping that of C20:4 arachidonic acid. However, the cardiolipin-binding site(s) within PKN1-(C2) and the respective binding properties remain unclear. Herein, we reveal (i) that the primary PKN1-(C2) sequence contains conserved amphipathic cardiolipin-binding motif(s); (ii) that trimeric PKN1-(C2) predominantly adopts a ß-stranded conformation; (iii) that two distinct types of cardiolipin (or phosphatidic acid) binding occur, with the hydrophobic component playing a key role at higher salt levels; (iv) the multiplicity of C18 fatty acid binding to PKN1-(C2); and (v) the relevance of our lipid-binding parameters for PKN1-(C2) in terms of kinetic parameters previously determined for the full-length PKN1 enzyme. Thus, our discoveries create opportunities to design specific mammalian cell inhibitors that disrupt the localization of membrane-associated PKN1 signaling molecules.

BRD4-mediated epigenetic regulation of endoplasmic reticulum-mitochondria contact sites is governed by the mitochondrial complex III.

Inter-organellar communication is critical for cellular metabolic homeostasis. One of the most abundant inter-organellar interactions are those at the endoplasmic reticulum and mitochondria contact sites (ERMCS). However, a detailed understanding of the mechanisms governing ERMCS regulation and their roles in cellular metabolism are limited by a lack of tools that permit temporal induction and reversal. Through unbiased screening approaches, we identified fedratinib, an FDA-approved drug, that dramatically increases ERMCS abundance by inhibiting the epigenetic modifier BRD4. Fedratinib rapidly and reversibly modulates mitochondrial and ER morphology and alters metabolic homeostasis. Moreover, ERMCS modulation depends on mitochondria electron transport chain complex III function. Comparison of fedratinib activity to other reported inducers of ERMCS revealed common mechanisms of induction and function, providing clarity and union to a growing body of experimental observations. In total, our results uncovered a novel epigenetic signaling pathway and an endogenous metabolic regulator that connects ERMCS and cellular metabolism.

The Relationship Between Postoperative Patient-Reported Psychological Outcomes and Preoperative Pain Characteristics in Patients Who Underwent Periacetabular Osteotomy.

This study sought to investigate the relationship between multiple preoperative characteristics of pain (maximum pain severity location, the presence of pain in certain locations, the highest level of pain, and the number of pain locations) and psychological outcome measures as reported by patients. Fifty-four hips (50 patients) that underwent periacetabular osteotomy to treat acetabular dysplasia between February 2017 and July 2020 were reviewed using the Depression, Anxiety, and Stress Scale-21 (DASS21), Hospital Anxiety and Depression Scale (HADS), and Pain Catastrophizing Scale (PCS), radiographic analysis, and questionnaires concerning pain severity/location. Twenty-six hips had their worst pain in the groin, whereas 28 hips had greater or equal levels of pain at another location. There was no significant difference between these two locations on any of the postoperative psychological outcomes (HADS, P=.53; DASS21, P=.85; PCS, P=.97). Additionally, there was not a significant relationship between pain in any location other than the groin and any postoperative psychological outcomes (P≥.08). Finally, the highest level of preoperative pain and the number of locations of pain demonstrated no significant relationship with postoperative psychological outcomes (maximum severity: HADS, P=.28; DASS21, P=.49; PCS, P=.57; number of pain locations: HADS, P=.47; DASS21, P=.60; PCS, P=.35). Variance in preoperative pain location, severity, and number of pain locations seemingly does not result in any significant effect on postoperative psychological outcomes. Thus, a large range of patients with acetabular dysplasia may experience similar, favorable psychological outcomes from treatment with periacetabular osteotomy notwithstanding the characteristics of preoperative pain. [Orthopedics. 2024;47(1):28-33.].

Technical considerations for replantation: from bony fixation to soft tissue coverage.

Digital replantation is a challenging and at-time tedious operation, but if approached thoughtfully and with reasonable expectations can be a reliable and rewarding undertaking. This article summarizes technical considerations for digital replantations involving flexor tendon zone II. The article has been ordered according to the recommended sequence of a structure-by-structure repair in a non-thumb digit. Special considerations are described for thumb, multiple digits, and heterotopic replantation.

How Brow Rotation Affects Emotional Expression Utilizing Artificial Intelligence.

BACKGROUND: It is well known that brow position affects emotional expression. However, there is little literature on how and to what degree this change in emotional expression happens. Previous studies on this topic have utilized manual rating; this method of study remains small and labor intensive. Our objective is to correlate manual brow rotations with emotional outcomes using artificial intelligence to objectively determine how specific brow manipulations affected human expression. METHODS: We included 53 brow-lift patients in this study. Pre-operative patients' brows were rotated to - 20, - 10, +10, and +20 degrees in respect to the central axis of their existing brow using PIXLR, a cloud-based set of image editing tools and utilities. These images were analyzed using FaceReader, a validated software package that uses computer vision technology for facial expression recognition. The primary facial emotion and intensity of facial action units (0 = no action unit detected to 4 = most intense action unit detected) generated by the software were recorded. RESULTS: 265 total images [5 images (pre-operative, - 20 degree brow rotation, - 10, +10, and +20) per patient] were analyzed using FaceReader. The primary emotion detected in the majority of images was neutral. The percentage of disgust in patients' expressions, as detected by FaceReader, increased with increased positive brow rotation (1.76% disgust detected at - 20 degrees, 2.09% at - 10 degrees, 2.65% at neutral, 2.61% at +10 degrees, and 2.95% at +20 degrees). In contrast, the percentage of sadness in patients' expressions decreased with increased positive brow rotation (29.92% sadness detected at - 20 degrees, 21.5% at - 10 degrees, 11.42% at neutral, 15.75% at +10 degrees, and 12.86% at +20 degrees). Our facial action unit analysis corresponded with primary emotion analysis. The intensity of the inner brow raiser decreased with increased positive brow rotation 8.54% at - 20 degrees, 4.21% at - 10 degrees, 1.48% at neutral, 0.84% at +10 degrees, and 0.76% at +20 degrees). The intensity of the outer brow raiser increased with increased positive brow rotation (0.97% at - 20 degrees, 0.45% at - 10 degrees, 1.12% at neutral, 5.45% at +10 degrees, and 11.19% at +20 degrees). CONCLUSION: We demonstrated that increasing the degree of brow rotation correlated positively with the percentage of disgust and inversely with the percentage of sadness detected by FaceReader. This study demonstrated how different manipulated brow positions affected emotional outcomes using artificial intelligence. Physicians can use these findings to better understand how brow-lifts can affect the perceived emotion of their patients. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Encapsulation of ZnO and Ho:ZnO Nanoparticles in the Core of Wrinkled Mesoporous Silica.

Wrinkled mesoporous silica (WMS) has a flower- or dendritic-like morphology, tunable pore size, and highly ordered and accessible three-dimensional (3D) pore structures. In this research, a method to encapsulate semiconductor nanoparticles in the core of the wrinkled mesoporous silica during synthesis is described. Highly uniform zinc oxide and holmium-doped zinc oxide nanoparticles have been synthesized by a sonochemical method. Zinc oxide and holmium-doped zinc oxide nanoparticles have been encapsulated in wrinkled mesoporous silica during synthesis. The ZnO@WMS and Ho:ZnO@WMS particles have been characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), UV-vis spectroscopy, fluorescence, dynamic light scattering (DLS), confocal microscopy, and X-ray diffraction (XRD).

Liraglutide pretreatment attenuates sepsis-induced acute lung injury.

There are no effective targeted therapies to treat acute respiratory distress syndrome (ARDS). Recently, the commonly used diabetes and obesity medications, glucagon-like peptide-1 (GLP-1) receptor agonists, have been found to have anti-inflammatory properties. We, therefore, hypothesized that liraglutide pretreatment would attenuate murine sepsis-induced acute lung injury (ALI). We used a two-hit model of ALI (sepsis+hyperoxia). Sepsis was induced by intraperitoneal injection of cecal slurry (CS; 2.4 mg/g) or 5% dextrose (control) followed by hyperoxia [HO; fraction of inspired oxygen ([Formula: see text]) = 0.95] or room air (control; [Formula: see text] = 0.21). Mice were pretreated twice daily with subcutaneous injections of liraglutide (0.1 mg/kg) or saline for 3 days before initiation of CS+HO. At 24-h post CS+HO, physiological dysfunction was measured by weight loss, severity of illness score, and survival. Animals were euthanized, and bronchoalveolar lavage (BAL) fluid, lung, and spleen tissues were collected. Bacterial burden was assessed in the lung and spleen. Lung inflammation was assessed by BAL inflammatory cell numbers, cytokine concentrations, lung tissue myeloperoxidase activity, and cytokine expression. Disruption of the alveolar-capillary barrier was measured by lung wet-to-dry weight ratios, BAL protein, and epithelial injury markers (receptor for advanced glycation end products and sulfated glycosaminoglycans). Histological evidence of lung injury was quantified using a five-point score with four parameters: inflammation, edema, septal thickening, and red blood cells (RBCs) in the alveolar space. Compared with saline treatment, liraglutide improved sepsis-induced physiological dysfunction and reduced lung inflammation, alveolar-capillary barrier disruption, and lung injury. GLP-1 receptor activation may hold promise as a novel treatment strategy for sepsis-induced ARDS. Additional studies are needed to better elucidate its mechanism of action.NEW & NOTEWORTHY In this study, pretreatment with liraglutide, a commonly used diabetes medication and glucagon-like peptide-1 (GLP-1) receptor agonist, attenuated sepsis-induced acute lung injury in a two-hit mouse model (sepsis + hyperoxia). Septic mice who received the drug were less sick, lived longer, and displayed reduced lung inflammation, edema, and injury. These therapeutic effects were not dependent on weight loss. GLP-1 receptor activation may hold promise as a new treatment strategy for sepsis-induced acute respiratory distress syndrome.

Effect of Omega-3 Rich High-Fat Diet on Markers of Tissue Lipid Metabolism in Glucocorticoid-Treated Mice.

Glucocorticoids (GCs) are some of the most widely prescribed therapies for treating numerous inflammatory diseases and multiple cancer types. With chronic use, GCs' therapeutic benefits are concurrent with deleterious metabolic side effects, which worsen when combined with a high-fat diet (HFD). One characteristic of the common Western HFD is the presence of high omega-6 polyunsaturated fatty acids (PUFAs) and a deficiency in omega-3 PUFAs. The aim of this experiment was to determine whether fat composition resulting from HFD affects glucocorticoid-induced alterations in lipid-handling by the liver and skeletal muscle. Male wild-type C57BL/6 mice were randomized into two groups: n-6 (45% fat 177.5 g lard) and n-3 (45% fat 177.5 g Menhaden oil). After 4 weeks on their diets, groups were divided to receive either daily injections of dexamethasone (3 mg/kg/day) or sterile PBS for 1 week while continuing diets. The n-3 HFD diet attenuated adipose and hepatic fatty accumulation and prevented GC-induced increases in liver lipid metabolism markers Cd36 and Fabp. N-3 HFD had little effect on markers of lipid metabolism in oxidative and glycolytic skeletal muscle and was unable to attenuate GC-induced gene expression in the muscle. The present study's result demonstrated that the change of fat composition in HFD could beneficially alter the fatty acid accumulation and associated lipid metabolism markers in mice treated with dexamethasone.

Artificial Intelligence in Surgical Evaluation: A Study of Facial Rejuvenation Techniques.

Background: Aesthetic facial surgeries historically rely on subjective analysis in determining success; this limits objective comparison of surgical outcomes. Objectives: This case study exemplifies the use of an artificial intelligence software on objectively analyzing facial rejuvenation techniques with the aim of reducing subjective bias. Methods: Retrospectively, all patients who underwent facial rejuvenation surgery with concomitant procedures from 2015 to 2017 were included (n = 32). Patients were categorized into Groups A to C: Group A-10 superficial musculoaponeurotic system (SMAS) plication facelift (n = 10), Group B-SMASectomy facelift (n = 7), and Group C-high SMAS facelift (n = 15). Neutral repose images preoperatively and postoperatively (average >3 months) were analyzed using artificial intelligence for emotion and action unit alterations. Results: Postoperatively, Group A experienced a decrease in happiness by 0.84% and a decrease in anger by 6.87% (P >> .1). Group B had an increase in happiness by 0.77% and an increase in anger by 1.91% (P >> .1). Both Group A and Group B did not show any discernable action unit patterns. In Group C, the lip corner puller AU increased in average intensity from 0% to 18.7%. This correlated with an average increase in detected happiness from 1.03% to 13.17% (P = .008). Conversely, the average detected anger decreased from 14.66% to 0.63% (P = .032). Conclusions: This study provides the first proof of concept for the use of a machine learning software application to objectively assess various aesthetic surgical outcomes in facial rejuvenation. Due to limitations in patient heterogeneity, this study does not claim one technique's superiority but serves as a conceptual foundation for future investigation.

Diffusiophoresis of a Weakly Charged Liquid Metal Droplet.

Diffusiophoresis of a weakly charged liquid metal droplet (LMD) is investigated theoretically, motivated by its potential application in drug delivery. A general analytical formula valid for weakly charged condition is adopted to explore the droplet phoretic behavior. We determined that a liquid metal droplet, which is a special category of the conducting droplet in general, always moves up along the chemical gradient in sole chemiphoresis, contrary to a dielectric droplet where the droplet tends to move down the chemical gradient most of the time. This suggests a therapeutic nanomedicine such as a gallium LMD is inherently superior to a corresponding dielectric liposome droplet in drug delivery in terms of self-guiding to its desired destination. The droplet moving direction can still be manipulated via the polarity dependence; however, there should be an induced diffusion potential present in the electrolyte solution under consideration, which spontaneously generates an extra electrophoresis component. Moreover, the smaller the conducting liquid metal droplet is, the faster it moves in general, which means a smaller LMD nanomedicine is preferred. These findings demonstrate the superior features of an LMD nanomedicine in drug delivery.

Duration of Symptoms Does Not Significantly Influence Short-term Outcomes for Patients Undergoing Periacetabular Osteotomy.

Factors influencing the clinical outcomes after periacetabular osteotomy (PAO) have not been well explored. This study evaluated the influence of symptom duration in developmental dysplasia of the hip on short-term patient-reported outcomes after PAO. A retrospective review of prospectively collected data identified PAOs performed on 139 patients. Sixty-five patients were then stratified into two groups based on preoperative symptom duration: 2 years or less (n=22) vs more than 2 years (n=43). We compared the results of hip-specific patient-reported outcome surveys collected preoperatively and postoperatively. When comparing the two groups, we found no significant differences in clinical outcome scores except for the UCLA Activity Scale. The shorter duration group achieved improvement 6 months postoperatively on the visual analog scale average pain score (from 4.5 to 2.167; P=.0017), International Hip Outcome Tool-12 (from 42.95 to 59.19; P=.0176), and Harris Hip Score (from 53.88 to 69.88; P=.049). The longer duration group also achieved postoperative improvement across multiple surveys. Nevertheless, a multivariate analysis controlling for age, sex, and body mass index and found that symptom duration did not independently affect the change in clinical outcomes. Although PAO leads to improvements in functional status and pain, preoperative symptom duration does not significantly affect these clinical outcomes. [Orthopedics. 2023;46(6):365-372.].

Implications of Transglutaminase-Mediated Protein Serotonylation in the Epigenetic Landscape, Small Cell Lung Cancer, and Beyond.

In the case of small-cell lung carcinoma, the highly metastatic nature of the disease and the propensity for several chromatin modifiers to harbor mutations suggest that epigenetic manipulation may also be a promising route for oncotherapy, but histone deacetylase inhibitors on their own do not appear to be particularly effective, suggesting that there may be other regulatory parameters that dictate the effectiveness of vorinostat's reversal of histone deacetylation. Recent discoveries that serotonylation of histone H3 alters the permissibility of gene expression have led to renewed attention to this rare modification, as facilitated by transglutaminase 2, and at the same time introduce new questions about whether this modification belongs to a part of the concerted cohort of regulator events for modulating the epigenetic landscape. This review explores the mechanistic details behind protein serotonylation and its possible connections to the epigenome via histone modifications and glycan interactions and attempts to elucidate the role of transglutaminase 2, such that optimizations to existing histone deacetylase inhibitor designs or combination therapies may be devised for lung and other types of cancer.

Outbreak.info Research Library: a standardized, searchable platform to discover and explore COVID-19 resources.

Outbreak.info Research Library is a standardized, searchable interface of coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) publications, clinical trials, datasets, protocols and other resources, built with a reusable framework. We developed a rigorous schema to enforce consistency across different sources and resource types and linked related resources. Researchers can quickly search the latest research across data repositories, regardless of resource type or repository location, via a search interface, public application programming interface (API) and R package.

Barriers and motivators to specializing in geriatrics and strategies for recruitment: Scoping review.

While the barriers to specializing in geriatrics are known, motivators behind why medical trainees choose geriatrics are not as well understood. It is also unknown if recruitment strategies in the literature address these barriers and motivators. The aim of this systematic scoping review is to examine the current literature on recruitment strategies alongside motivators and barriers for specializing in geriatrics. Eligible articles for this scoping review either focused on motivators or barriers among trainees (medical students, resident-physicians, fellows) or recruitment strategies. A scoping search was conducted in MEDLINE, Embase, CINAHL, and PsychINFO. Data was extracted on article characteristics and themes. 88 of 2064 articles were eligible and included. Personal fulfillment emerged as the most common theme for motivators, contrary to prior studies that cite positive role modeling. Financial disincentive remained the most common barrier, followed by limited exposure and "futile" practice. Promising interventions beyond financial compensation include defining geriatrics better, emphasizing the high job satisfaction rates, increasing clinical exposure for medical students, and additional funding for academic centers to recruit academic geriatricians. Policymakers and medical educators should consider multiple strategies that target the motivators, as well as the barriers to pursuing geriatrics.

Anticancer effect of a pyrrole-imidazole polyamide-triphenylphosphonium conjugate selectively targeting a common mitochondrial DNA cancer risk variant in cervical cancer cells.

Cervical cancer remains a major threat to women's health, especially in countries with limited medical resources, and new drugs are needed to improve patient survival and minimize adverse effects. Here, we examine the effects of a triphenylphosphonium (TPP)-conjugated pyrrole-imidazole polyamide (CCC-h1005) targeting the common homoplasmic mitochondrial DNA (mtDNA) cancer risk variant (ATP6 8860A>G) on the survival of cervical cancer cell lines, cisplatin-resistant HeLa cells and patient-derived cervical clear cell carcinoma cells as models of cervical cancer treatment. We found that CCC-h1005 induced death in these cells and suppressed the growth of xenografted HeLa tumors with no severe adverse effects. These results suggest that PIP-TPP designed to target mtDNA cancer risk variants can be used to treat many cervical cancers harboring high copies of the target variant, providing a foundation for clinical trials of this class of molecules for treating cervical cancer and other types of cancers.