Abstract Objective Nasopharyngeal Carcinoma (NPC) is a malignancy of epithelium of epithelium of the nasopharynx, with the highest incidence of otolaryngeal malignancies. A growing number of studies confirm that Circular RNA (circRNA) plays an important role in tumor development, including Hsa_circ_0013561. This study aims to elucidate the process and mechanism of NPC regulation hsa_circ_0013561. Methods In this study, circRNA expression nodes and subcellular localization in NPC tissues were analyzed by fluorescence in situ hybridization. The expression of hsa_circ_0013561 in NPC cells was further clarified by RT-qPCR. At the same time, the lentivirus vector interfered by hsa_circ_0013561 was constructed and transfected. The cell proliferation was detected by CCK-8 method, EdU assay and plate cloning assay. The cell cycle and apoptosis were detected by flow cytometry, and the cell migration ability was detected by wound healing assay and Transwell assay. Western blotting examined the expression of apoptosis, Epithelial-Mesenchymal Transition (EMT)-associated proteins, and Janus Kinase/Signal Transductor and Activator of Transcription (JAK/STAT) signaling pathway-related proteins. Results The results showed that the expression of hsa_circ_0013561 in NPC samples was significantly upregulated and hsa_circ_0013561 localized in the cytoplasm. After down-regulating hsa_circ_0013561 expression, it significantly inhibited the proliferation and metastasis ability of NPC, inhibited EMT progression, and promoted apoptosis. Further studies showed that interference hsa_circ_0013561 significantly inhibited JAK2/STAT3 signaling pathway activation and induced the expression of apoptosis-related proteins. Conclusion In summary, we found that hsa_circ_0013561 is a pro-tumor circRNA in NPC, which can reduce the activation of JAK2/STAT3 pathway by knocking down hsa_circ_0013561, thereby slowing down the malignant progression of NPC. Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence Level 4. (NPC nasopharynx malignancies (circRNA development Hsacirc0013561 Hsacirc Hsa circ 0013561 Hsa_circ_0013561 hsacirc0013561 hsacirc hsa hybridization hsa_circ_001356 RTqPCR. RTqPCR RT qPCR. qPCR RT-qPCR time transfected CCK8 CCK 8 CCK- method cytometry EpithelialMesenchymal Epithelial Mesenchymal EMTassociated associated proteins KinaseSignal Kinase Signal JAK/STAT JAKSTAT JAK STAT (JAK/STAT pathwayrelated related cytoplasm downregulating regulating JAK2STAT3 JAK2 STAT3 JAK2/STAT apoptosisrelated summary protumor pro EvidenceBased Based 201 4 Hsacirc001356 001356 Hsa_circ_001356 hsacirc001356 hsa_circ_00135 JAK2STAT 20 Hsacirc00135 00135 Hsa_circ_00135 hsacirc00135 hsa_circ_0013 2 Hsacirc0013 0013 Hsa_circ_0013 hsacirc0013 hsa_circ_001 Hsacirc001 001 Hsa_circ_001 hsacirc001 hsa_circ_00 Hsacirc00 00 Hsa_circ_00 hsacirc00 hsa_circ_0 Hsacirc0 0 Hsa_circ_0 hsacirc0 hsa_circ_ Hsa_circ_ hsa_circ Hsa_circ

Abstract Objective This study investigated the effects of WN on LE in subjects with chronic tinnitus and normal hearing thresholds. The study was a prospective, non-randomized, before-and-after, intra-participant intervention. Methods Twenty-five subjects performed the following tests: conventional and high-frequency audiometry, acuphenometry, screening questionnaires for depression and anxiety symptoms, Tinnitus Handicap Inventory (THI), Montreal Cognitive Assessment, and high WM test from the Working Memory Assessment Battery, Federal University of Minas Gerais (WMAB) as the LE measure in two conditions: No Added Noise (NAN) and with Added Noise (AN). Results Seventeen participants (68%) performed better on AN condition. Data analysis revealed a 45% improvement in the WMAB total span count on AN setting, with a significant p value (p = 0.001). Conclusion The subgroup of participants without traces of anxiety symptoms, up to mild traces of depressive symptoms, having unilateral tinnitus, and a THI level up to grade 2, had improved WM performance in the presence of WN, which suggests a release of cognitive resources and less auditory effort under these combined conditions. Evidence level 4. thresholds prospective nonrandomized, nonrandomized non randomized, randomized non-randomized beforeandafter, beforeandafter before after, after before-and-after intraparticipant intra participant intervention Twentyfive Twenty five tests highfrequency frequency audiometry acuphenometry symptoms THI, , (THI) Battery (WMAB conditions NAN (NAN AN. . (AN) 68% 68 (68% condition 45 setting 0.001. 0001 0.001 0 001 0.001) 2 4 (THI (AN 6 (68 000 0.00 00 (6 0.0 ( 0.

Abstract Objective The video otoscope has already proven to be useful for the diagnosis of several pathologies, so the objective of this study was to evaluate the diagnostic accuracy of the video otoscope in cases of tympanic membrane perforation. Methods This is a diagnostic accuracy study performed at the hearing health division of a tertiary-level referral hospital. Patients older than 8 years of age who had any symptom that could be related to perforation (otalgia, otorrhea, tinnitus, and/or hypoacusis) were invited to participate in the study. Participants were evaluated by three different diagnostic methods (otomicroscope, conventional otoscope, and video otoscope) performed by three different evaluators in a blind fashion. The microscope was considered the reference standard. Results 176 patients were evaluated, totaling 352 tympanic membranes. Twenty-seven tympanic membrane perforations were diagnosed by the microscope, a prevalence of 7.7%. The video otoscope showed a sensitivity of 85.2% (95% CI 81.5%‒88.9%), specificity of 98.1% (95% CI 96.7%‒99.5%) and accuracy of 97.1% (95% CI 95.4 %-98.8 %). The conventional otoscope showed a sensitivity of 96.3% (95% CI 94.3-98.3), specificity of 98.8% (95% CI 97.7-99.9) and accuracy of 98.6% (95% CI 97.4-99.8). The Kappa value between the microscope and the video otoscope was 0.8 and between the microscope and the conventional otoscope was 0.9. Regarding the participants' perception, 53.4% (p < 0.001) considered the video otoscope as the best method for understanding the tympanic membrane condition presented by them. Conclusions The video otoscope showed relevant sensitivity and specificity for clinical practice in the diagnosis of tympanic membrane perforation. Moreover, this is an equipment that can facilitate the patient's understanding of the otologic pathology presented by him/her. In this regard, this method may be important for better patient compliance, requiring further studies to evaluate this hypothesis. Level of evidence Is this diagnostic or monitoring test accurate? (Diagnosis)—Level 2 (Individual cross-sectional studies with consistently applied reference standard and blinding). pathologies tertiarylevel tertiary level hospital otalgia, otalgia (otalgia otorrhea tinnitus andor hypoacusis otomicroscope, otomicroscope (otomicroscope fashion 17 35 membranes Twentyseven Twenty seven 77 7 7.7% 852 85 85.2 95% 95 (95 81.5%‒88.9%, 815889 81.5%‒88.9% , 81 5 88 9 81.5%‒88.9%) 981 98 1 98.1 96.7%‒99.5% 967995 96 99 971 97 97.1 954 4 95. %98.8 988 % 98.8 %-98. %. . %) 963 3 96.3 94.398.3, 943983 94.3 98.3 94 94.3-98.3) 97.799.9 977999 97.7 99.9 97.7-99.9 986 6 98.6 97.499.8. 974998 97.4 99.8 97.4-99.8) 08 0 0. 09 0.9 participants perception 534 53 53.4 p 0.001 0001 001 them Moreover s himher him her him/her regard compliance hypothesis accurate DiagnosisLevel Diagnosis Individual crosssectional cross sectional blinding. blinding blinding) 7.7 85. (9 81588 81.5%‒88.9 98. 96.7%‒99.5 96799 97. %98. %-98 96. 398 94.398.3 94398 943 94. 983 94.3-98.3 799 97.799. 97799 977 999 99. 97.7-99. 499 97.499.8 97499 974 998 97.4-99.8 53. 0.00 000 00 7. ( 8158 81.5%‒88. 96.7%‒99. 9679 %98 %-9 39 94.398. 9439 94.3-98. 79 97.799 9779 97.7-99 49 97.499. 9749 97.4-99. 0.0 815 81.5%‒88 96.7%‒99 967 %9 %- 94.398 94.3-98 97.79 97.7-9 97.499 97.4-99 81.5%‒8 96.7%‒9 94.39 94.3-9 97.7- 97.49 97.4-9 81.5%‒ 96.7%‒ 94.3- 97.4- 81.5% 96.7% 81.5 96.7 81.

Abstract Objectives Nasopharyngeal Carcinoma (NPC) is a common malignant tumor of nasopharyngeal mucosal epithelium in clinical practice. Radiotherapy and chemotherapy are the main treatment methods at present, but the therapeutic effect is still unsatisfactory. Studies have shown that exosomes and microRNAs (miRNAs) play an important role in the development of cancer. Therefore, this study aimed to investigate the effects of NPC derived exosomes on NPC and their molecular mechanisms. Methods Serum was collected from healthy subjects, Epstein-Barr Virus (EBV) infected patients and NPC patients (n = 9 group) and exosomes were extracted separately. High-throughput sequencing of exosomes was performed to screen differentially expressed miRNAs. The function of the screened miRNA was identified by treating NPC cells with exosomes. The target gene of miRNA was identified using the dual-luciferase assay. Real-Time quantitative Polymerase Chain Reaction (RT-qPCR) was used to determine the levels of miR-99a-5p and Bromodomain Adjacent Tozinc finger domain protein 2A (BAZ2A). Cell Counting Kit-8 assay, flow cytometry, and wound healing assay were utilized to detect cell viability, cell cycle and apoptosis, and migration ability. The protein levels were evaluated by Western blot. Results MiR-99a-5p was identified as the most significant differentially expressed miRNA in exosomes (p< 0.05). The proliferation and migration of NPC cells were extremely facilitated by exosomes, accompanied by the suppressed apoptosis, upregulated BAZ2A, Monocyte Chemotactic Protein-1 (MCP1), and Vascular Endothelial Growth Factor A (VEGFA), and downregulation of Interleukin (IL)-1β and Nuclear Transcription Factor-κB (NF-κB) (p< 0.05). BAZ2A was a target gene of miR-99a-5p. Furthermore, the regulatory effect of exosomes on the proliferation, migration, and apoptosis was significantly abolished by overexpression of miR-99a-5p or downregulation of BAZ2A (p< 0.05). Conclusion NPC derived exosomes facilitated the proliferation and migration of NPC through regulating the miR-99a-5p/BAZ2A axis. (NPC practice present unsatisfactory miRNAs (miRNAs cancer Therefore mechanisms subjects EpsteinBarr Epstein Barr EBV (EBV n group separately Highthroughput High throughput dualluciferase dual luciferase RealTime Real Time RTqPCR RT qPCR (RT-qPCR miR99a5p miRap miR 99a 5p p BAZ2A. BAZA . BAZ (BAZ2A) Kit8 Kit 8 Kit- cytometry viability ability blot MiR99a5p MiRap MiR p< (p 0.05. 005 0.05 0 05 0.05) Protein1 Protein 1 Protein- MCP1, MCP1 MCP , (MCP1) VEGFA, VEGFA (VEGFA) IL1β ILβ IL 1β β FactorκB κB NFκB NF (NF-κB miR99a5p. 5p. Furthermore miR99a5p/BAZ2A miR99a5pBAZ2A miRapBAZA 5p/BAZ2A axis (BAZ2A 00 0.0 (MCP1 (VEGFA pBAZ 5pBAZ2A pBAZA 0. (MCP

Abstract Objectives Olfactory loss is a recognized long-term dysfunction after Coronavirus Disease 2019 (COVID-19) infection. This investigation aimed to assess the effect of alpha-lipoic acid as an adjuvant treatment of olfactory training on the improvement of smell loss in post-COVID-19 patients. Methods This randomized controlled trial included 128 adult outpatients who had persistent smell loss for more than 3-months after COVID-19 infection. The participants were randomly allocated into two groups: the intervention treatment group, which received alpha-lipoic acid associated to olfactory training, and comparison treatment group, which received placebo pills associated to olfactory training. The participants were followed-up for 12-weeks. Olfactory dysfunction was assessed in terms of Visual Analog Scale (VAS), and the Connecticut Chemosensory Clinical Research Center (CCCRC) test for the Brazilian population. Results A total of 100 participants completed the follow-up period and were analyzed in this study. Both groups have improved CCCRC score (p= 0.000), olfactory threshold (p= 0.000), identification score (p= 0.000) and VAS score (p= 0.000) after 12-weeks follow-up. No significant differences were determined between the intervention and comparison treatment groups in CCCRC score (p= 0.63), olfactory threshold (p= 0.50), identification score (p= 0.96) and VAS score (p= 0.97). In all these criteria, comparison treatment group went slightly worse. At the endpoint of the study, the frequency of anosmia reduced to 2% in the intervention treatment group and to 7.8% in the comparison treatment group. Also, 16.8% of the intervention group’ subjects, and 15.7% of comparison treatment group’s patients reached normosmia. Conclusions Overall, there was a strongly significant difference in olfactory function between baseline and endpoint for both groups. However, based on the lack of significant difference between the intervention treatment and the comparison treatment groups in terms of olfactory changes, our study appoints that the alpha-lipoic acid is not better than olfactory training alone to treat olfactory loss after COVID-19. Level of evidence Level 2. longterm long term 201 COVID19 COVID 19 (COVID-19 infection alphalipoic alpha lipoic postCOVID19 postCOVID post post-COVID-1 12 3months months 3 COVID-1 followedup followed up 12weeks. 12weeks weeks weeks. VAS, , (VAS) (CCCRC population 10 followup follow p= p (p 0.000, 0000 0.000 0 000 followup. up. 0.63, 063 0.63 63 0.63) 0.50, 050 0.50 50 0.50) 0.96 096 96 0.97. 097 0.97 . 97 0.97) criteria worse 2 78 7 8 7.8 Also 168 16 16.8 subjects 157 15 15.7 s normosmia Overall However changes COVID19. 19. 20 COVID1 1 (COVID-1 postCOVID1 post-COVID- COVID- (VAS 0.00 00 06 0.6 6 05 0.5 5 0.9 09 9 7. 16. 15. (COVID- post-COVID 0.0 0. (COVID

Abstract Objectives To identify and understand the evidence regarding hearing changes related to acquired Dengue, Chikungunya, and Zika virus infection in adult individuals. Methods A scoping review was performed according to the recommendations of The Joanna Briggs Institute and guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews in the Embase, PubMed/Medline, ScienceDirect, Scopus, and Web of Science databases without restriction on language and year of publication. Case studies, observational studies, and clinical trials reporting hearing loss in adult subjects (>18-60 years of age) of both sexes with DENV, CHIKV, or ZIKV diagnosed by positive molecular/serological examination by RT-PCR or IgM/IgG by ELISA method were included. Results Thirteen studies met the inclusion criteria and were selected for review. The occurrence of auditory symptoms caused by arboviroses and the presence of permanent or transient sensorineural hearing loss was variable in adults. Conclusions Dengue, Chikungunya, and Zika infections in adults are associated with a variety of auditory symptoms. The frequency of permanent or transient sensorineural hearing loss is low but not negligible. Dengue Chikungunya individuals MetaAnalyses Meta Analyses Embase PubMedMedline PubMed Medline PubMed/Medline ScienceDirect Scopus publication >1860 1860 >18 60 18 (>18-6 age DENV CHIKV molecularserological molecular serological RTPCR RT PCR IgMIgG IgM IgG included negligible >186 186 >1 6 1 (>18- > (>18 (>1 (> (

Abstract Objectives Our study aimed to verify the evidence of auditory training employed in the audiological treatment of tinnitus in adults and older adults. Methods Scoping review based on a search for articles in journals available in MEDLINE (PubMed), Embase (Elsevier), LILACS (BVS), and Cochrane Library. Titles and abstracts of the retrieved articles were assessed by peers, following the eligibility criteria; they were afterward read in full text, and the references were hand searched in the results found. Studies’ level of evidence was classified into very high (Level A+), high (Level A), moderate (Level B), limited (Level C), low (Level D), or very low (Level D−) based on the Critically Appraised Topics. Results 2160 records were identified in the searching stage and 15 studies were eligible for data extraction. Study design, sample characterization, auditory training tasks, sound stimuli, outcome measures, and results were extracted. Frequency discrimination training was the most frequent strategy, followed by auditory attentional skills training and multisensory training. Almost all studies with daily auditory training sessions reported significant benefits demonstrated in at least one outcome measure. Studies that used auditory discrimination training and attentional auditory skill stimulation to treat tinnitus obtained quality evidence levels ranging from limited to high (C‒A) and studies that applied multisensory training or attentional training combined with counseling and passive listening in tinnitus patients reached a high-quality evidence level (A). Conclusion Recent studies had higher levels of evidence and considered attentional factors and multisensory pathways in auditory training strategies. PubMed, PubMed , (PubMed) Elsevier, Elsevier (Elsevier) BVS, BVS (BVS) Library peers criteria text found Level A+, A A+ A+) A, A) B, B B) C, C C) D, D D) D− Topics 216 1 extraction design characterization tasks stimuli measures extracted strategy measure C‒A CA (C‒A highquality A. . (A) strategies (PubMed (Elsevier (BVS 21 (A 2

Abstract Objectives To assess the hearing thresholds in acute otitis media, otitis media with effusion and chronic otitis media (non-suppurative, non-cholesteatomatous suppurative and cholesteatomatous) and to compare the hearing outcomes with non-diseased ears (in bilateral cases) or contralateral healthy ears (in unilateral cases), since hearing loss is the most frequent sequel of otitis media and there is no previous study comparing the audiometric thresholds among the different forms of otitis media. Methods Cross sectional, controlled study. We performed conventional audiometry (500-8000 Hz) and tympanometry in patients with otitis media and healthy individuals (control group). Hearing loss was considered when the hearing thresholds were > 25 dBHL. Results Of the 112 patients diagnosed with otitis media (151 ears), 48 were men (42.86%) and 64 were women (57.14%). The average age was 42.72 years. Of those, 25 (22.32%) were diagnosed as AOM, 15 (13.39%) were diagnosed with OME and the remaining 72 (63.28%) were diagnosed with COM (non-suppurative COM, n = 31; suppurative COM, n = 18; cholesteatomatous COM, n = 23). As compared with controls, all forms of otitis media had significantly higher bone-conduction thresholds (500-4000 Hz). Conductive hearing loss was the most frequent type of hearing loss (58.94%). However, the number of patients with mixed hearing loss was also relevant (39.07%). We noted that the presence of sensorioneural component occurred more frequently in 1) Higher frequencies; and 2) In groups of otitis media that were more active or severe in the inflammatory/infective standpoint (AOM, suppurative COM and cholesteatomatous COM). Conclusion All types of otitis media, even those with infrequent episodes of inflammation and otorrhea, had worse bone conduction thresholds as compared with nondiseased ears (p < 0.01). We observed worse hearing outcomes in ears with recurrent episodes of otorrhea and in ears with AOM, especially in high frequencies. nonsuppurative, nonsuppurative non suppurative, noncholesteatomatous diseased cases cases, , sectional 5008000 500 8000 (500-800 Hz control group. group . group) 2 dBHL 11 151 (15 ears, ears) 4 42.86% 4286 42 86 (42.86% 6 57.14%. 5714 57.14% 57 14 (57.14%) 4272 42.7 years 22.32% 2232 22 32 (22.32% AOM 1 13.39% 1339 13 39 (13.39% 7 63.28% 6328 63 28 (63.28% 31 18 23. 23 23) controls boneconduction 5004000 4000 (500-400 Hz. 58.94%. 5894 58.94% 58 94 (58.94%) However 39.07%. 3907 39.07% 07 (39.07%) frequencies inflammatoryinfective inflammatory infective (AOM COM. COM) p 0.01. 001 0.01 0 01 0.01) 500800 50 800 (500-80 (1 42.86 428 8 (42.86 571 57.14 5 (57.14% 427 42. 22.32 223 3 (22.32 13.39 133 (13.39 63.28 632 (63.28 500400 400 (500-40 589 58.94 9 (58.94% 390 39.07 (39.07% 00 0.0 50080 80 (500-8 ( 42.8 (42.8 57.1 (57.14 22.3 (22.3 13.3 (13.3 63.2 (63.2 50040 40 (500-4 58.9 (58.94 39.0 (39.07 0. 5008 (500- (42. 57. (57.1 22. (22. 13. (13. 63. (63. 5004 58. (58.9 39. (39.0 (500 (42 (57. (22 (13 (63 (58. (39. (50 (4 (57 (2 (6 (58 (39 (5 (3

Abstract Objective Translate and cross-culturally adapt into Brazilian Portuguese the Glasgow Children’s Benefit Inventory instrument used for the quality-of-life assessment after pediatric ENT interventions. Method This is a methodological study of translation and cross-cultural adaptation of the GCBI instrument following seven stages: 1) Translation of two versions by two independent translators, 2) Elaboration of a consensual synthetized version, 3) Assessment of the synthetized version by experts, 4) Assessment by the target audience, 5) Back-translation, 6) Pilot study and 7) Use of the instrument. The final version of the instrument was answered by a sample of 28 people responsible for children aged from 2 to 7 years, submitted to tonsillectomy between January 2019 and December 2021, in a public hospital in Porto Alegre. The collection considered patients with a minimum of 6-months and a maximum of 3-years of postoperative follow-up. Result The instrument final version was compared to the original version showing semantic equivalence, absence of consistent translation difficulties and appropriate cross-cultural adaptation, and well understood by the target audience. The application of the questionnaire in the sample showed a Cronbach alpha coefficient of 0.944 corresponding to a high degree of reliability of the instrument. Conclusion The translation and cross-cultural adaptation showed semantic appropriateness and its use when assessing ENT postoperative results in a pediatric population showed high reliability of the instrument. Level of evidence 4. crossculturally cross culturally Childrens Children s qualityoflife quality life interventions crosscultural cultural stages 1 translators 3 experts 4 audience 5 Backtranslation, Backtranslation Back translation, Back-translation 6 years 201 2021 Alegre 6months months 3years followup. followup follow up. up follow-up equivalence 0944 0 944 0.94 20 202 094 94 0.9 09 9 0.

Abstract Objective Cutaneous Squamous Cell Carcinoma (cSCC), a tumor with a significantly increasing incidence, is mostly diagnosed in the head region, where tumors have a worse prognosis and a higher risk of metastases. The presence of metastases reduces specific five-year survival from 99% to 50%. As the risk of occult metastases does not exceed 10%, elective dissection of the tributary parotid and neck lymph nodes is not recommended. Methods We retrospectively analyzed a group of 12 patients with cSCC of the head after elective dissections of regional (parotid and cervical) nodes by means of superficial parotidectomy and selective neck dissection. Results We diagnosed occult metastases neither in the cervical nor parotid nodes in any patient. None were diagnosed as a regional recurrence during the follow-up period. Conclucion Our negative opinion on elective parotidectomy and neck dissection in cSCC of the head is in agreement with the majority of published studies. These elective procedures are not indicated even for tumors showing the presence of known (clinical and histological) risk factors for lymphogenic spread, as their positive predictive value is too low. Elective parotidectomy is individually considered as safe deep surgical margin. If elective parotidectomy is planned it should include only the superficial lobe. Completion parotidectomy and elective neck dissection are done in rare cases of histologically confirmed parotid metastasis in the parotid specimen. Preoperatively diagnosed parotid metastases without neck involvement are sent for total parotidectomy and elective selective neck dissection. Cases of clinically evident neck metastasis with no parotid involvement, are referred for comprehensive neck dissection and elective superficial parotidectomy. The treatment of concurrent parotid and cervical metastases includes total conservative parotidectomy and comprehensive neck dissection. Level of evidence How common is the problem? Step 4 (Case-series) Is this diagnostic or monitoring test accurate? (Diagnosis) Step 4 (poor or non-independent reference standard) What will happen if we do not add a therapy? (Prognosis) Step 4 (Case-series) Does this intervention help? (Treatment Benefits) Step 4 (Case-series) What are the COMMON harms? (Treatment Harms) Step 4 (Case-series) What are the RARE harms? (Treatment Harms) Step 4 (Case-series) Is this (early detection) test worthwhile? (Screening) Step 4 (Case-series) cSCC, , (cSCC) incidence region fiveyear five year 99 50 50% 10 10% recommended 1 patient followup follow up period studies clinical histological spread low margin lobe specimen problem Caseseries Case series (Case-series accurate Diagnosis (Diagnosis poor nonindependent non independent standard therapy Prognosis (Prognosis help Treatment Benefits harms Harms early detection worthwhile Screening (Screening (cSCC 9 5