Factors influencing the reduction in quadriceps muscle thickness in the paretic limbs of patients with acute stroke.

BACKGROUND & AIMS: Muscle atrophy is an early event that occurs after stroke, but there are few reports on the changes in skeletal muscle thickness in acute stroke. This study investigated the factors contributing to reduced muscle thickness in patients with acute stroke. METHODS: In total, 51 patients with stroke and the National Institute of the Health Stroke Scale (NIHSS) > 3 were included in our study. They were admitted to our hospital between July 2017 and May 2020. The quadriceps muscle thickness was measured with an ultrasound device within 2 days after admission and 14 days later. The collected data included age, sex, body mass index, stroke type, neuromuscular electrical stimulation, NIHSS, serum albumin at admission, start of enteral nutrition, Functional Oral Intake Scale (FOIS), start of mobilization and ambulation, number of physical and occupational therapy units, C-reactive protein at admission and whether surgery had been performed. These data were retrospectively retrieved from medical documents. A dietician calculated energy intake, protein intake, and energy adequacy. Multiple regression analysis was used to identify the factors associated with reduced quadriceps muscle thickness. The independent variables were NIHSS, date of start of enteral feeding, protein intake, FOIS, date of mobilization, and date of start of ambulation training. RESULTS: The rate of change in quadriceps muscle thickness of the paretic limb was -15.3 % (interquartile range, -46.1-14.8 %). Multiple regression analysis showed that the factors responsible for the decrease in muscle thickness on the paretic side were FOIS (ß: 0.376; 95 % Cl, 0.999 to 4.541) and the start date of ambulation (ß: -0.378; 95 % Cl, -2.575 to -0.543), with a multiple correlation coefficient of 0.456. CONCLUSION: The FOIS and the start date of ambulation after acute stroke were related to the rate of reduction in muscle thickness on the paretic side.

A Case of Hereditary Coproporphyria in which the Patient's Course Improved after the Discontinuation of Givosiran.

Hereditary coproporphyria (HCP) is caused by a partial deficiency of coproporphyrinogen oxidase during heme biosynthesis. Givosiran is approved for the treatment of acute hepatic porphyria. We herein report the case of a 47-year-old woman with HCP. Monthly givosiran administration improved her subjective symptoms and reduced her δ-aminolevulinic acid (ALA) and porphobilinogen (PBG) levels to the normal range. However, givosiran was discontinued after six months due to a decreased renal function. The patient's ALA and PBG levels remained within the normal ranges, and her HCP-related symptoms resolved more than 2 years after the discontinuation of givosiran.

Pioneering the Integration of Artificial Intelligence in Medical Oral Board Examinations.

We evaluated the use of ChatGPT-4, an advanced artificial intelligence (AI) language model, in medical oral examinations, specifically in anesthesiology. Initially proven adept in written examinations, ChatGPT-4's performance was tested against oral board sample sessions of the American Board of Anesthesiology. Modifications were made to ensure responses were concise and conversationally natural, simulating real patient consultations or oral examinations. The results demonstrate ChatGPT-4's impressive adaptability and potential in oral board examinations as a training and assessment tool in medical education, indicating new avenues for AI application in this field.

Quantification of collagen fiber properties in alcoholic liver fibrosis using polarization-resolved second harmonic generation microscopy.

Liver fibrosis is assessed mainly by conventional staining or second harmonic generation (SHG) microscopy, which can only provide collagen content in fibrotic area. We propose to use polarization-resolved SHG (PR-SHG) microscopy to quantify liver fibrosis in terms of collagen fiber orientation and crystallization. Liver samples obtained from autopsy cases with fibrosis stage of F0-F4 were evaluated with an SHG microscope, and 12 consecutive PR-SHG images were acquired while changing the polarization azimuth angle of the irradiated laser from 0° to 165° in 15° increments using polarizer. The fiber orientation angle (φ) and degree (ρ) of collagen were estimated from the images. The SHG-positive area increased as the fibrosis stage progressed, which was well consistent with Sirius Red staining. The value of φ was random regardless of fibrosis stage. The mean value of ρ (ρ-mean), which represents collagen fiber crystallinity, varied more as fibrosis progressed to stage F3, and converged to a significantly higher value in F4 than in other stages. Spatial dispersion of ρ (ρ-entropy) also showed increased variation in the stage F3 and decreased variation in the stage F4. It was shown that PR-SHG could provide new information on the properties of collagen fibers in human liver fibrosis.

Optimization of the Attenuation Coefficient for Chang Attenuation Correction in 123I Brain Perfusion SPECT.

N-isopropyl-p-123I-iodoamphetamine brain perfusion SPECT has been used with various attenuation coefficients (µ-values); however, optimization is required. This study aimed to determine the optimal µ-value (µopt-value) for Chang attenuation correction (AC) using clinical data by comparing the Chang method and CT-based AC. Methods: We used 100 patients (reference group, 60; disease group, 40) who underwent N-isopropyl-p-123I-iodoamphetamine SPECT. SPECT images of the reference group were obtained to calculate the AC using the Chang method (µ-values, 0.07-0.20; 0.005 interval) and the CT-based method, both without scatter correction (SC) and with SC. The µopt-value with the smallest mean percentage error for the brain regions of the reference group was calculated. Agreement between the Chang and CT-based methods applying the µopt-value was evaluated using Bland-Altman analysis. Additionally, the percentage error in the region of hypoperfusion in the diseased group was compared with the percentage error in the same region in the reference group when the µopt-value was applied. Results: The µopt-values were 0.140 for Chang without SC and 0.160 for Chang with SC. In the Chang method, with the µopt-value applied, fixed and proportional biases were observed in the Bland-Altman analysis (both P < 0.05), and there was a tendency for the percentage error to be underestimated in the limbic regions and overestimated in the central brain regions. There was no significant difference between the disease group and the reference group in the region of hypoperfusion in either Chang without SC or Chang with SC. Conclusion: The present study revealed that the µopt-values of the Chang method are 0.140 without SC and 0.160 with SC.

Assessment of skin inflammation using near-infrared Raman spectroscopy combined with artificial intelligence analysis in an animal model.

Raman spectroscopy is a powerful method for estimating the molecular structure of a target that can be adapted for biomedical analysis given its non-destructive nature. Inflammatory skin diseases impair the skin's barrier function and interfere with the patient's quality of life. There are limited methods for non-invasive and objective assessment of skin inflammation. We examined whether Raman spectroscopy can be used to predict skin inflammation with high sensitivity and specificity when combined with artificial intelligence (AI) analysis. Inflammation was chemically induced in mouse ears, and Raman spectra induced by a 785 nm laser were recorded. A principal component (PC) analysis of the Raman spectra was performed to extract PCs with the highest percentage of variance and to estimate the statistical score. The accuracy in predicting inflammation based on the Raman spectra with or without AI analysis was assessed using receiver operating characteristic (ROC) curves. We observed some typical changes in the Raman spectra upon skin inflammation, which may have resulted from vasodilation and interstitial oedema. The estimated statistical scores based on spectral changes correlated with the histopathological changes in the skin. The ROC curve based on PC2, which appeared to include some spectral features, revealed a maximum accuracy rate of 80.0% with an area under the curve (AUC) of 0.864. The AI analysis improved the accuracy rate to 93.1% with an AUC of 0.972. The current findings demonstrate that the combination of Raman spectroscopy with near-infrared excitation and AI analysis can provide highly accurate information on the pathology of skin inflammation.

FADS2-dependent fatty acid desaturation dictates cellular sensitivity to ferroptosis and permissiveness for hepatitis C virus replication.

The metabolic oxidative degradation of cellular lipids severely restricts replication of hepatitis C virus (HCV), a leading cause of chronic liver disease, but little is known about the factors regulating this process in infected cells. Here we show that HCV is restricted by an iron-dependent mechanism resembling the one triggering ferroptosis, an iron-dependent form of non-apoptotic cell death, and mediated by the non-canonical desaturation of oleate to Mead acid and other highly unsaturated fatty acids by fatty acid desaturase 2 (FADS2). Genetic depletion and ectopic expression experiments show FADS2 is a key determinant of cellular sensitivity to ferroptosis. Inhibiting FADS2 markedly enhances HCV replication, whereas the ferroptosis-inducing compound erastin alters conformation of the HCV replicase and sensitizes it to direct-acting antiviral agents targeting the viral protease. Our results identify FADS2 as a rate-limiting factor in ferroptosis, and suggest the possibility of pharmacologically manipulating the ferroptosis pathway to attenuate viral replication.

Ablation of fatty acid desaturase 2 (FADS2) exacerbates hepatic triacylglycerol and cholesterol accumulation in polyunsaturated fatty acid-depleted mice.

Deficiency of polyunsaturated fatty acids (PUFAs) is known to induce hepatic steatosis. However, it is not clearly understood which type of PUFA is responsible for the worsening of steatosis. This study observed a marked accumulation of hepatic triacylglycerol and cholesterol in fatty acid desaturase 2 knockout (FADS2-/- ) mice lacking both C18 and ≥ C20 PUFAs that were fed a PUFA-depleted diet. Hepatic triacylglycerol accumulation was associated with enhanced sterol regulatory element-binding protein (SREBP)-1-dependent lipogenesis and decreased triacylglycerol secretion into the plasma via very-low-density lipoprotein (VLDL). Furthermore, upregulation of cholesterol synthesis contributed to increased hepatic cholesterol content in FADS2-/- mice. These results suggest that ≥ C20 PUFAs synthesized by FADS2 are important in regulating hepatic triacylglycerol and cholesterol accumulation during PUFA deficiency.

Plexin-B3 Regulates Cellular Motility, Invasiveness, and Metastasis in Pancreatic Cancer.

The Plexins family of proteins are well-characterized transmembrane receptors of semaphorins, axon guidance cue molecules, that mediate the cell attraction or repelling effects for such cues. Plexins and their ligands are involved in numerous cellular activities, such as motility, invasion, and adhesion to the basement membrane. The detachment of cells and the gain in motility and invasion are hallmarks of the cancer metastasis cascade, thus generating interest in exploring the role of plexins in cancer metastasis. Semaphorin-plexin complexes can act as tumor promoters or suppressors, depending upon the cancer type, and are under investigation for therapeutic purposes. Our group has identified Semaphorin-5A (SEMA5A)/Plexin-B3 as an attractive targetable complex for pancreatic cancer (PC) metastasis. However, our understanding of the Plexin-B3 function and pathological expression in PC is limited, and our present study delineates the role of Plexin-B3 in PC malignancy. We examined the pathological expression of Plexin-B3 in PC tumors and metastasis using a human tissue microarray, disease progression model of PDX-Cre-Kras(G12D) (KC) mice, and different metastatic sites obtained from the KrasG12D; Trp53R172H; Pdx1-Cre (KPC) mice model. We observed a higher Plexin-B3 expression in PC tumor cores than the normal pancreas, and different metastatic sites were positive for Plexin-B3 expression. However, in the KC mice model, the Plexin-B3 expression increased initially and then decreased with the disease progression. Next, to evaluate the functional role of Plexin-B3, we utilized T3M-4- and CD18/HPAF-Control and -Plexin B3 knockdown cells for different in vivo and in vitro studies. The knockdown of Plexin-B3 enhanced the in vitro cellular migration, invasiveness, and impaired colony formation in three-dimensional culture, along with an increase in cellular spread and remodeling of the actin filaments. We also observed a higher metastasis in nude mice injected with T3M-4- and CD18/HPAF-shPlexin-B3 cells compared to their respective control cells. Furthermore, we observed a lower number of proliferating Ki-67-positive cells and higher ALDH1-A1-positive cells in the tumors formed by Plexin-B3 knockdown cells compared to tumors formed by the control cells. Together, our data suggest that the loss of Plexin-B3 is associated with the interference of cell division machinery and the induction of stem cell-like characteristics in PC cells.

The effect of polyunsaturated fatty acid deficiency on allergic response in ovalbumin-immunized mice.

Polyunsaturated fatty acids (PUFAs) are present in biological membranes and influence membrane fluidity and immune responses. PUFAs such as 18:2n-6 and 18:3n-3 cannot be synthesized de novo in mammals and are thus called essential fatty acids (EFAs). In addition, PUFAs can be converted to very long-chain PUFAs (VLC-PUFAs), such as arachidonic acid and docosahexaenoic acid, in the body. Although avoiding allergens is an effective strategy for food-allergy patients, the dietary exclusion of several allergens reportedly induces deficiencies in essential nutrients such as PUFAs. In this study, we investigated whether an EFA-deficient (EFAD) diet influenced allergic symptoms in ovalbumin (OVA)-immunized mice. Unexpectedly, no exacerbation of immune responses after OVA-sensitization was observed in mice fed an EFAD diet, and no differences in serum PUFA levels between OVA-immunized and non-immunized mice fed the EFAD diet were detected. However, levels of VLC-PUFAs in the small intestine increased after OVA-sensitization and did not decrease during EFAD diet administration, showing that small intestinal VLC-PUFAs levels were strongly preserved in the food-allergy model mice. Further studies are required to elucidate the mechanisms by which small intestinal VLC-PUFAs are retained in food-allergy model mice.

Massive Hemorrhage From the Aorta on Removal of an Anterior Mediastinal Tumor in Spite of Using an Endovascular Stent Graft: A Case Report.

A 68-year-old man was scheduled for mediastinal tumor resection. Aortic invasion was unclear on preoperative computed tomography. Transesophageal echocardiography showed a smooth endothelial border, but the tumor was contiguous with the distal arch, and the adventitial border was unclear. After median sternotomy, the tumor was found to be adherent to the aorta. An endovascular stent graft was placed in the distal arch to protect the aorta, but excessive bleeding occurred from the aortic defect on tumor removal. This case shows that massive hemorrhage can occur during the resection of an aorta-invading tumor despite the use of an endovascular stent graft.

Semaphorin-5A maintains epithelial phenotype of malignant pancreatic cancer cells.

BACKGROUND: Pancreatic cancer (PC) is a highly aggressive disease, and the lethality of this disease stems from early metastatic dissemination where surgical removal cannot provide a cure. Improvement of the therapeutic outcome and overall survival of PC patients requires to understand the fundamental processes that lead to metastasis such as the gain of cellular migration ability. One such family of proteins, which are essential players of cellular migration, is Semaphorin. Previously, we have identified one of the Semaphorin family member, Semaphorin-5A (SEMA5A) to be involved in organ-specific homing during PC metastasis. We have also demonstrated that SEMA5A has a constitutive expression in PC cell lines derived from metastatic sites in comparison with low endogenous expression in the primary tumor-derived cell line. In this study, we examined whether constitutive SEMA5A expression in metastatic PC cells regulates tumor growth and metastatic potential. METHODS: We generated SEMA5A knockdown in T3M-4 and CD18/HPAF cells and assessed their phenotypes on in vitro motility, tumor growth, and metastatic progression. RESULTS: In contrary to our initial expectations, orthotopic injection of SEMA5A knockdown cells into nude mice resulted in a significant increase in both tumor burden and liver metastases in comparison with the Control cells. Similarly, we observed higher in vitro migratory potential with pronounced morphological changes associated with epithelial-mesenchymal transition (EMT), a decrease in the expression of epithelial marker E-cadherin (E-Cad), increase in the expression of mesenchymal markers N-cadherin (N-Cad) and Snail and the activation of the Wnt-signaling pathway in SEMA5A knockdown cells. Furthermore, re-establishing SEMA5A expression with a knockdown resistant mouse Sema5A in SEMA5A knockdown cells resulted in a reversion to the epithelial state (mesenchymal-epithelial transition; MET), as indicated by the rescue of E-Cad expression and a decrease in N-Cad and Snail expression. CONCLUSIONS: Collectively, our data suggest that SEMA5A expression maintains epithelial phenotype in the metastatic microenvironment.

Pathological and functional significance of Semaphorin-5A in pancreatic cancer progression and metastasis.

Semaphorin-5A (SEMA5A) has differential cell surface expression between normal and cancer cells and represents an attractive target for therapeutic intervention in pancreatic cancer (PC). In this study, we delineated the pathological expression and significance of SEMA5A during PC progression and metastasis. We utilized human tissue microarrays and different PC mouse models (Pdx1-cre; LSL- Kras(G12D), Pdx1-Cre; LSL-Kras(G12D); LSL-p53(R172H) and RIP1-Tag2) to analyze SEMA5A expression during PC progression. Using human patients and different mouse models, we demonstrated that SEMA5A expression was highest in liver metastases, followed by primary pancreatic tumors, and the lowest expression was found in the normal pancreas. SEMA5A expression was localized on tumor cells with no staining in the surrounding stroma. To understand the functional significance of SEMA5A, we treated PC cell lines with recombinant SEMA5A. We observed an increase in migration, chemotaxis, and scattering of PC cells. To delineate the signaling axis of SEMA5A, we generated SEMA5A receptor-Plexin-B3 knockdown in T3M-4 and CD18/HPAF PC cell lines and observed that the effect of SEMA5A treatment was absent in the Plexin-B3 knockdown counterparts of T3M-4 and CD18/HPAF cells. SEMA5A treatment leads to phosphorylation of cMET in Plexin-B3 dependent manner. Our data demonstrate that there is an increase in SEMA5A expression during PC progression and the elevation of this expression takes place at metastatic sites especially the liver in both exocrine and endocrine tumors. SEMA5A can elicit a migratory response in cells by activating cMET through the Plexin-B3 receptor. In conclusion, SEMA5A signaling represents a potential molecule for targeting metastasis in pancreatic cancer.

FADS2 inhibition in essential fatty acid deficiency induces hepatic lipid accumulation via impairment of very low-density lipoprotein (VLDL) secretion.

Fatty acid desaturase 2 (FADS2) is responsible for the first desaturation reaction in the synthesis of highly unsaturated fatty acids (HUFAs), such as arachidonic acid (20:4n-6) and eicosapentaenoic acid (20:5n-3), and is involved in Mead acid (20:3n-9) production during essential fatty acid deficiency (EFAD). In this study, an obvious hepatic lipid accumulation was observed in EFAD mice treated with a FADS2 inhibitor. FADS2 inhibition in the EFAD state reduced secretion of very low-density lipoprotein (VLDL) and markedly diminished Mead acid in phosphatidylcholine (PC) in the liver and plasma. As the results, the amount of C20 HUFAs in hepatic and plasma PC dramatically reduced in the EFAD mice treated with a FADS2 inhibitor, whereas the decrease of C20 HUFA levels of PC in EFAD mice was not observed because of the increased Mead acid in PC. These results supposed that Mead acid in PC is important as a component of VLDL. It is possible that Mead acid plays the role of a substitute of HUFAs in VLDL secretion during EFAD.

Local control of sphincter-preserving procedures and abdominoperineal resection for locally advanced low rectal cancer: Propensity score matched analysis.

Sphincter-preserving procedures (SPPs) for surgical treatment of low-lying rectal tumors have advanced considerably. However, their oncological safety for locally advanced low rectal cancer compared with abdominoperineal resection (APR) is contentious. We retrospectively analyzed cohort data of 1500 consecutive patients who underwent elective resection for stage II-III rectal cancer between 2010 and 2011. Patients with tumors 2-5 cm from the anal verge and clinical stage T3-4 were eligible. Primary outcome was 3-year local recurrence rate, and confounding effects were minimized by propensity score matching. The study involved 794 patients (456 SPPs and 338 APR). Before matching, candidates for APR were more likely to have lower and advanced lesions, whereas SPPs were carried out more often following preoperative treatment, by laparoscopic approach, and at institutions with higher case volume. After matching, 398 patients (199 each for SPPs and APR) were included in the analysis sample. Postoperative morbidity was similar between the SPPs and APR groups (38% vs 39%; RR 0.98, 95% CI 0.77-1.27). Margin involvement was present in eight patients in the SPPs group (one and seven at the distal and radial margins, respectively) and in 12 patients in the APR group. No difference in 3-year local recurrence rate was noted between the two groups (11% vs 14%; HR 0.77, 95% CI 0.42-1.41). In this observational study, comparability was ensured by adjusting for possible confounding factors. Our results suggest that SPPs and APR for locally advanced low rectal cancer have demonstrably equivalent oncological local control.

[A Case of Cardiopulmonary Arrest due to Difficult Mask Ventilation and Difficult Laryngoscopy in the Ward after Operation: A Case Report].

A 77-year-old man with paroxysmal atrial fibrillation and hypertrophic obstructive cardiomyopathy was scheduled for cervical laminoplasty. He was predicted difficult mask ventilation combined with difficult laryn- goscopy (CICV) because of short thyromental distance. After induction of general anesthesia, we attempted tracheal intubation using McGRATHO and Gum-elastic Bougie and the intubation was successful. After opera- tion, in ward, atrial fibrillation occurred. Because anti- arrhythmic agents were not effective, cardioversion was planned. While under sedation, his breathing stopped. The attending physician could not ventilate with mask and intubate with Macintosh laryngoscope. The patient went into cardiopulmonary arrest After successful intubation using McGRATH? and Gum- elastic Bougie by anesthesiologist The attending physi- cian did not recognize CICV. We should convey infor- mation of CICV surely and perform education about difficult airway management.

Tumor-specific delivery of BSH-3R for boron neutron capture therapy and positron emission tomography imaging in a mouse brain tumor model.

Glioblastoma, a malignant brain tumor with poor disease outcomes, is managed in modern medicine by multimodality therapy. Boron neutron capture therapy (BNCT) is an encouraging treatment under clinical investigation. In malignant cells, BNCT consists of two major factors: neutron radiation and boron uptake. To increase boron uptake in cells, we created a mercapto-closo-undecahydrododecaborate ([B12HnSH](2-)2Na(+), BSH) fused with a short arginine peptide (1R, 2R, 3R) and checked cellular uptake in vitro and in vivo. In a mouse brain tumor model, only BSH with at least three arginine domains could penetrate cell membranes of glioma cells in vitro and in vivo. Furthermore, to monitor the pharmacokinetic properties of these agents in vivo, we fused BSH and BSH-3R with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA); DOTA is a metal chelating agent for labeling positron emission tomography (PET) probe with (64)Cu. We administered BSH-DOTA-(64)Cu and BSH-3R-DOTA-(64)Cu to the tumor model through a mouse tail vein and determined the drugs' pharmacokinetics by PET imaging. BSH-3R showed a high uptake in the tumor area on PET imaging. We concluded that BSH-3R is the ideal boron compound for clinical use during BNCT and that in developing this compound for clinical use, the BSH-3R PET probe is essential for pharmacokinetic imaging.

Acceptance of and attitudes towards human papillomavirus vaccination in Japanese mothers of adolescent girls.

To better understand how to achieve high uptake rates of human papillomavirus (HPV) vaccination in Japan, we investigated acceptance of and attitudes towards HPV vaccination in 2192 mothers of girls aged 11-14 yrs. A school-based survey was conducted in five elementary and fourteen junior high schools in Sapporo, Japan. Responses from 862 participants were analyzed. Ninety-three percent of mothers would accept the vaccine for their daughter if free, but only 1.5% was willing to pay the minimum recommended price of ¥ 40,000. Vaccine acceptance was higher in mothers who had heard of HPV vaccine (adjusted odds ratio, aOR=2.58, confidence interval, CI=1.47-4.53), and who believed susceptibility to (aOR=2.30, CI=1.34-3.92) and severity of (aOR=3.73, CI=1.41-9.88) HPV to be high. Recommendations from a doctor (aOR=12.60, CI=7.06-21.48) and local health board (aOR=27.80, CI=13.88-55.86) were also positively associated with increased HPV vaccine acceptance. Concerns about side effects of both the HPV vaccine (aOR=0.03, CI=0.01-0.08) and routine childhood vaccines in general (aOR=0.11, CI=0.02-0.78) emerged as barriers to vaccination. Not participating in routine cervical screening also emerged as a deterrent (aOR=0.49, CI=0.27-0.91). While most mothers (66.8%) agreed that 10-14 yr was an appropriate age for vaccination, a further 30.6% believed >15 yr to be more appropriate. In conclusion, attitudes of Japanese mothers toward HPV vaccination are encouraging. While lower vaccine acceptance in mothers who do not undergo regular cervical screening needs further investigation, this study indicates that high uptake may be possible in a publically funded HPV vaccination program if physicians actively address safety concerns and justify why the vaccine is needed at a particular age.

[Human papillomavirus vaccination for prevention of cervical cancer].

Persistent infection of human papillomavirus (HPV) is the necessary cause for developing cervical cancer. Now cervical cancer is getting attention as not only early-detectable but also preventable cancer by developing vaccine for HPV. In Japan, the first HPV vaccine, "Cervarix, GlaxoSmithKline (GSK)" was licensed on October 2009 and vaccination was started on December 2009. This is the bivalent vaccine specifically targeting HPV-16 and -18 types. Domestic clinical trial is also about to demonstrate the efficacy, safety, and possibility to keep enough antibody levels. The widespread use of this vaccine will help cervical cancer eliminated.