The utility of ChatGPT as a generative medical translator.

PURPOSE: Large language models continue to dramatically change the medical landscape. We aimed to explore the utility of ChatGPT in providing accurate, actionable, and understandable generative medical translations in English, Spanish, and Mandarin pertaining to Otolaryngology. METHODS: Responses of GPT-4 to commonly asked patient questions listed on official otolaryngology clinical practice guidelines (CPG) were evaluated with the Patient Education materials Assessment Tool-printable (PEMAT-P.) Additional critical elements were identified a priori to evaluate ChatGPT's accuracy and thoroughness in its responses. Multiple fluent speakers of English, Mandarin, and Spanish evaluated each response generated by ChatGPT. RESULTS: Total PEMAT-P scores differed between English, Mandarin, and Spanish GPT-4 generated responses depicting a moderate effect size of language, Eta-Square 0.07 with scores ranging from 73 to 77 (P-value = 0.03). Overall understandability scores did not differ between English, Mandarin, and Spanish depicting a small effect size of language, Eta-Square 0.02 scores ranging from 76 to 79 (P-value = 0.17), nor did overall actionability scores Eta-Square 0 score ranging 66-73 (P-value = 0.44). Overall a priori procedure-specific responses similarly did not differ between English, Spanish, and Mandarin Eta-Square 0.02 scores ranging 61-78 (P-value = 0.22). CONCLUSION: GPT-4 produces accurate, understandable, and actionable outputs in English, Spanish, and Mandarin. Responses generated by GPT-4 in Spanish and Mandarin are comparable to English counterparts indicating a novel use for these models within Otolaryngology, and implications for bridging healthcare access and literacy gaps. LEVEL OF EVIDENCE: IV.

Perioperative outcomes of ileorectal anastomosis - an analysis of 823 patients.

AIM: Ileorectal anastomosis (IRA) following total abdominal colectomy (TAC) allows for resortation of bowel continuity but prior studies have reported rates of anastomotic leak (AL) to be as high as 23%. We aimed to report rates of AL and complications in a large cohort of patients undergoing IRA. We hypothesized that AL rates were lower than previously reported and that selective use of diverting loop ileostomy (DLI) is associated with decreased AL rates. METHOD: Patients undergoing TAC or end-ileostomy reversal with IRA, with or without DLI, between 1980 and 2021 were identified from a prospectively maintained institutional database and retrospectively analysed. Redo IRA cases were excluded. Short-term (30-day) surgical outcomes were collected using our database. AL was defined using a combination of imaging and, in the case of return to the operating room, intraoperative findings. RESULTS: Of 823 patients in the study cohort, DLI was performed in 27% and performed more frequently for constipation and inflammatory bowel disease. The overall AL rate was 3% (1% and 4% in those with and without DLI, respectively) and diversion was found to be protective against leak (OR 0.28, 95% CI 0.08-0.94, p = 0.04). However, patients undergoing diversion had a higher overall rate of postoperative complications (51% vs. 36%, p < 0.001) including superficial wound infection, urinary tract infection, dehydration, blood transfusion and portomesenteric venous thrombosis (all p < 0.04). CONCLUSION: Our study represents the largest series of patients undergoing IRA reported to date and demonstrates an AL rate of 3%. While IRA appears to be a viable surgical option for diverse indications, our study underscores the importance of careful patient selection and thoughtful consideration of staging the anastomosis and temporary faecal diversion when necessary.

Exercise and Musculoskeletal Health in Men With Low Bone Mineral Density: A Systematic Review.

Objective: This systematic review aims to determine the effects of exercise on bone and muscle health in men with low bone density. Data Sources: An electronic search in the following databases was performed: Medline, AMED, Embase, Scopus, and SPORTDiscus between January 1940 and September 2021. Study Selection: Randomized or non-randomized trials involving any form of exercise in adult men with a densitometric diagnosis of osteoporosis or osteopenia and reported outcomes relating to bone or muscle health. Two independent reviewers screened 12,018 records, resulting in 13 eligible articles. Data Extraction: One reviewer extracted data into a pre-formed table, including characteristics of the exercise intervention, population examined, and primary and secondary outcomes. Study quality was assessed by 2 independent reviewers using the Tool for assEssment of Study qualiTy and reporting in Exercise (TESTEX). Data Synthesis: Thirteen publications, originating from 6 unique trials, were eligible for inclusion, which assessed the effect of resistance training, impact training, whole body vibration, and traditional Chinese exercises. Resistance training was the most effective: it stimulates the replacement of adipose tissue with muscle, and in some cases, improved bone density. Conclusions: Exercise, especially resistance training, slowed down the natural progression of osteoporosis and sarcopenia in men. These benefits are reflected in enhancements to function, such as improved mobility and balance. Other exercise modalities, such as whole body vibration and traditional Chinese exercises, generated minimal improvements to bone health, strength, and balance.

Design and Evaluation of a Spoke-Based Double-Lumen Pediatric Gastrostomy Tube.

Gastrostomy tubes (G-tubes) are the gold standard for feeding assistance for children with feeding dysfunction. Current G-tubes pose complications that interrupt the delivery of feed, including tube displacement and difficulty of at-home use. This study details an alternative, spoke-based, double-lumen G-tube design and preliminary validation of its function and usability. Pull force testing was performed on spoke G-tube models across three sizes and two classifications (hard/soft). Preliminary models were evaluated against market standards. Though the pull force of the spoke model was found to be lower than that of both market standards, hard modifications to the spoke model improved retentive force. Ease of use was tested amongst users unfamiliar with G-tube placement. The spoke design required 12.3 ± 4.7 s to deploy, less than half the time required for market standards. However, balloon G-tubes were still perceived to be easiest to use by 70% of participants, with indications that a spoke design may be easier to use if sized similarly to current G-tubes, with auxiliary improvements to factors such as grip. While there is a need for improvements in the material properties and manufacturing of the proposed design, this study provides early validation of the potential to address complications of existing G-tubes.

One-Year Results of a Phase I/II Randomized, Double-Masked, Placebo-Controlled Study of Processed Amniotic Fluid Drops After PRK.

PURPOSE: The aim of this study was to evaluate the 1-year outcomes of using processed amniotic fluid (pAF) postoperatively after photorefractive keratectomy (PRK). METHODS: Sixty-one participants were randomized to receive either placebo or pAF drops. The drops were instilled 4 times daily for 1 week after PRK along with routine postoperative medications. The primary outcome measures included uncorrected visual acuity, topographic corneal irregularity measurement, and surface staining over 1 year. RESULTS: A statistically significant difference in uncorrected distance visual acuity between the placebo and treatment groups was seen at 1 month post-PRK, with a visual advantage evident in the pAF group. A suggestive difference in corneal irregularity measurement was also seen between the placebo and treatment groups at 1 month postsurgery, with less irregularity noted in the pAF group. No differences in uncorrected distance visual acuity or corneal irregularity measurement were found at 3, 6, and 12 months. There was also no significant difference in corneal staining scores between the 2 groups at any of the measured time points. CONCLUSIONS: This 1-year study evaluating the safety and efficacy of pAF as an additional postoperative topical medication after PRK demonstrated that pAF offered a mild visual advantage at 1 month post-PRK. There were no late adverse events, and the intervention proved safe at 1 year.

Evaluation of the Rothman Index in Predicting Readmission after Colorectal Resection.

The Rothman Index (RI) is a real-time health indicator score that has been used to quantify readmission risk in several fields but has never been studied in gastrointestinal surgery. In this retrospective single-institution study, the association between RI scores and readmissions after unplanned colectomy or proctectomy was evaluated in 427 inpatients. Patient demographics and perioperative measures, including last RI, lowest RI, and increasing/decreasing RI score, were collected. In the selected cohort, 12.4% of patients were readmitted within 30 days of their initial discharge. Last RI, lowest RI, decreasing RI, and increasing RI scores remained significant after controlling for covariates in separate multivariate regression analyses. The last RI score at the time of discharge was found to be the most strongly associated with 30-day readmission risk following colorectal resection. These findings support the RI as a potential tool in the inpatient management of postoperative patients to identify those at high risk of readmission.

Ethnic determinants of skeletal health in female patients with fragility fracture in a culturally diverse population.

Background: Low bone density leads to fragility fracture, with significant impact on morbidity and mortality. While ethnic differences in bone density have been observed in healthy subjects, this has not yet been explored in fragility fracture patients. Aims: To assess if ethnicity is associated with bone mineral density and serum markers of bone health in female patients who experience fragility fractures. Methods: 219 female patients presenting with at least one fragility fracture at a major tertiary hospital in Western Sydney Australia were studied. Western Sydney is a region with great cultural diversity, comprising people from over 170 ethnicities. Within this cohort, the three largest broad ethnic groups were Caucasians (62.1 %), Asians (22.8 %), and Middle Eastern patients (15.1 %). Location and nature of the presenting fracture and other relevant past medical history were obtained. Bone mineral density, measured by dual-energy X-ray absorptiometry, and bone-related serum markers were compared between ethnicities. Covariates (age, height, weight, diabetes, smoking, and at-risk drinking) were adjusted in multiple linear regression model. Results: Although Asian ethnicity was associated with lower bone mineral density at the lumbar spine in fragility fracture patients, this association was no longer significant after adjustment for weight. Ethnicity (Asian or Middle Eastern) was not a determinant of bone mineral density at any other skeletal site. Caucasians had lower estimated glomerular filtration rate compared to Asian and Middle Eastern subjects. Serum parathyroid hormone concentrations were significantly lower in Asians compared to other ethnicities. Conclusion: Asian ethnicity and Middle Eastern ethnicity were not major determinants of bone mineral density at the lumbar spine, femoral neck, or total hip.

The Role of Technology in Ophthalmic Surgical Education During COVID-19.

Purpose of Review: To describe the effect of COVID-19 on ophthalmic training programs and to review the various roles of technology in ophthalmology surgical education including virtual platforms, novel remote learning curricula, and the use of surgical simulators. Recent Findings: COVID-19 caused significant disruption to in-person clinical and surgical patient encounters. Ophthalmology trainees worldwide faced surgical training challenges due to social distancing restrictions, trainee redeployment, and reduction in surgical case volume. Virtual platforms, such as Zoom and Microsoft Teams, were widely used during the pandemic to conduct remote teaching sessions. Novel virtual wet lab and dry lab curricula were developed. Training programs found utility in virtual reality surgical simulators, such as the Eyesi, to substitute experience lost from live patient surgical cases. Summary: Although several of these described technologies were incorporated into ophthalmology surgical training programs prior to COVID-19, the pandemic highlighted the importance of developing a formal surgical curriculum that can be delivered virtually. Novel telementoring, collaboration between training institutions, and hybrid formats of didactic and practical training sessions should be continued. Future research should investigate the utility of augmented reality and artificial intelligence for trainee learning.

Benchmarks in colorectal surgery: multinational study to define quality thresholds in high and low anterior resection.

BACKGROUND: Benchmark comparisons in surgery allow identification of gaps in the quality of care provided. The aim of this study was to determine quality thresholds for high (HAR) and low (LAR) anterior resections in colorectal cancer surgery by applying the concept of benchmarking. METHODS: This 5-year multinational retrospective study included patients who underwent anterior resection for cancer in 19 high-volume centres on five continents. Benchmarks were defined for 11 relevant postoperative variables at discharge, 3 months, and 6 months (for LAR). Benchmarks were calculated for two separate cohorts: patients without (ideal) and those with (non-ideal) outcome-relevant co-morbidities. Benchmark cut-offs were defined as the 75th percentile of each centre's median value. RESULTS: A total of 3903 patients who underwent HAR and 3726 who had LAR for cancer were analysed. After 3 months' follow-up, the mortality benchmark in HAR for ideal and non-ideal patients was 0.0 versus 3.0 per cent, and in LAR it was 0.0 versus 2.2 per cent. Benchmark results for anastomotic leakage were 5.0 versus 6.9 per cent for HAR, and 13.6 versus 11.8 per cent for LAR. The overall morbidity benchmark in HAR was a Comprehensive Complication Index (CCI®) score of 8.6 versus 14.7, and that for LAR was CCI® score 11.9 versus 18.3. CONCLUSION: Regular comparison of individual-surgeon or -unit outcome data against benchmark thresholds may identify gaps in care quality that can improve patient outcome.

A Study of Postoperative Complications Occurring at Home With Pediatric Gastrostomy Feeding Tubes.

OBJECTIVE: Gastrostomy tubes (G-tubes) provide long-term feeding assistance to children with severe feeding dysfunction. Although there are a host of complications that occur at home with current pediatric G-tube feeding, their prevalences and outcomes remain relatively unstudied. This study aims to identify and describe such complications. METHODS: A dual-round survey was administered to 98 participants through the Feeding Tube Awareness Foundation, a 501(c)(3) organization that supports parents and caretakers of G-tube-fed children. Information was collected broadly regarding G-tube complications, causes, and attitudes toward such complications. RESULTS: Infection (56%), itching/irritation/redness (52%), and leakage (51%) were the leading G-tube related complications. The average time that G-tubes were replaced was 3.4 ± 1.2 months as compared to the typical recommended period of up to 6 months. Of the caretakers who had not experienced G-tube displacement, 7.9% wanted to see a change in current G-tubes to address the issue, compared with 75% of those who had experienced displacement. This 67.1% differential in caretakers' attitudes toward G-tubes based on their prior experience with a particular complication was the largest gap among all other listed complications. CONCLUSIONS: G-tube complications are prevalent and varied. A sizable portion of G-tube users experience complications severe enough to require intervention. Of these, G-tube displacement is particularly critical and frequently precedes other prevalent complications, namely gastric leakage, infection, and tissue granulation.

Pyramidal Inflammatory Deposits of the Retinal Pigment Epithelium and Outer Retina in Ocular Syphilis.

PURPOSE: To evaluate the role of OCT in the diagnosis of uveitis secondary to syphilis. DESIGN: Consecutive, retrospective case series. PARTICIPANTS: All patients 18 years of age or older with ocular syphilis from 2 tertiary referral centers. METHODS: All patients who were diagnosed with intermediate uveitis, posterior uveitis, or panuveitis secondary to syphilis were included in the study (40 patients representing a total of 62 eyes) to identify important imaging features to aid in diagnosis. Patients underwent confirmatory serologic testing, OCT imaging, and dilated examination by a uveitis specialist. MAIN OUTCOME MEASURE: Hyperreflective retinal lesions on OCT. RESULTS: The mean age of the study population was 42.9 ± 12.16 years. Forty-five percent of the eyes included in this study harbored hyperreflective pyramidal lesions of the outer retina and retinal pigment epithelium on OCT. Fifty-four percent of eyes with these imaging findings did not show a placoid retinal lesion on examination. Sixty-eighty percent of the described outer retinal lesions on OCT resolved after treatment for syphilis. Visual acuity ranged from normal (20/20) to no light perception, with a mean of 20/43 at diagnosis, and improved significantly to a mean visual acuity of 20/26 after treatment (P < 0.05). Vision-threatening complications were seen in less than 5% of eyes and included both treatable and irreversible causes of vision loss, including retinal detachment, cystoid macular edema, and optic neuropathy. CONCLUSIONS: Patients treated for uveitis secondary to syphilis achieve good visual recoveries. Outer retinal lesions seen on OCT are common and can serve as an additional imaging finding of the disease.

Broadening learning communities during COVID-19: developing a curricular framework for telemedicine education in neurology.

BACKGROUND: In response to the cancellation of clinical clerkships due to COVID-19, the Johns Hopkins (JH) Neurology Education Team developed a virtual elective to enhance medical students' clinical telemedicine skills and foster community between academic institutions. METHODS: This two-week clinical elective, entitled "Virtual Patient Rounds in Neurology," was administered once in April 2020 and once in May 2020. The curriculum included attending/fellow-led Virtual Rounds, Student Presentations, and Asynchronous Educational Activities. We also developed a new lecture series entitled JHNeuroChats, which consisted of live synchronous lectures presented by JH faculty and Virtual Visiting Professors. Trainees and faculty from outside institutions were invited to participate in the JHNeuroChats. Students and faculty completed pre- and post-elective surveys to assess the educational impact of the elective. Student's t-tests were used to compare scores between pre- and post-elective surveys. RESULTS: Seven JH medical students enrolled in each iteration of the elective, and an additional 337 trainees and faculty, representing 14 different countries, registered for the JHNeuroChats. We hosted 48 unique JHNeuroChats, 32 (66.7%) of which were led by invited Virtual Visiting Professors. At the end of the elective, students reported increased confidence in virtually obtaining a history (P < 0.0001) and performing a telehealth neurological physical exam (P < 0.0001), compared to the start of the course. In addition, faculty members reported increased confidence in teaching clinical medicine virtually, although these findings were not statistically significant (P = 0.15). CONCLUSIONS: Despite the constraints imposed by COVID-19, this virtual Neurology elective increased medical students' confidence in certain telemedicine skills and successfully broadened our learning community to encompass learners from around the world. As virtual medical education becomes more prevalent, it is important that we are intentional in creating opportunities for shared learning across institutions. We believe that this elective can serve as a model for these future educational collaborations.

Diabetic Retinopathy and Risk of Stroke: A Secondary Analysis of the ACCORD Eye Study.

BACKGROUND AND PURPOSE: Diabetic retinopathy (DR) is a common microvascular complication of diabetes, which causes damage to the retina and may lead to rapid vision loss. Previous research has shown that the macrovascular complications of diabetes, including stroke, are often comorbid with DR. We sought to explore the association between DR and subsequent stroke events. METHODS: This is a secondary analysis of patients enrolled in the ACCORD Eye study (Action to Control Cardiovascular Risk in Diabetes). The primary outcome was stroke during follow-up. The exposure was presence of DR at study baseline. We fit adjusted Cox proportional hazards models to provide hazard ratios for stroke and included interaction terms with the ACCORD randomization arms. RESULTS: We included 2828 patients, in whom the primary outcome of stroke was met by 117 (4.1%) patients during a mean (SD) of 5.4 (1.8) years of follow-up. DR was present in 874 of 2828 (30.9%) patients at baseline and was more common in patients with than without incident stroke (41.0% versus 30.5%; P=0.016). In an adjusted Cox regression model, DR was independently associated with incident stroke (hazard ratio, 1.52 [95% CI, 1.05-2.20]; P=0.026). This association was not affected by randomization arm in the ACCORD glucose (P=0.300), lipid (P=0.660), or blood pressure interventions (P=0.469). CONCLUSIONS: DR is associated with an increased risk of stroke, which suggests that the microvascular pathology inherent to DR has larger cerebrovascular implications. This association appears not to be mediated by serum glucose, lipid, and blood pressure interventions.

ddRFC: A scalable multiplexed droplet digital nucleic acid amplification test platform.

Digital nucleic acid amplification tests (digital NAATs) have emerged as a popular tool for nucleic acid detection due to their high sensitivity and specificity. Most current digital NAAT platforms, however, are limited to a "one-color-one-target" approach wherein each target is encoded with a specific fluorescently-labeled probe for single-plex fluorometric detection. This approach is difficult to multiplex due to spectral overlap between any additional fluorophores, and multiplexability of digital NAATs has therefore been limited. As a means to scale multiplexability, we have developed a multiplexed digital NAAT platform, termed Droplet Digital Ratiometric Fluorescence Coding (ddRFC), via a padlock probe-based nucleic acid detection assay which encodes each nucleic acid target with a unique combination of 2 fluorophores. We detect this encoded two-color fluorescence signature of each target by performing digital amplification in microfluidic droplets. To demonstrate the utility of our platform, we have synthesized 6 distinct padlock probes, each rendering a unique two-color fluorescence signature to a nucleic acid target representing a clinically important sexually transmitted infection (STI). We proceed to demonstrate broad-based, two-plex, four-plex, and six-plex detection of the STI targets with single-molecule resolution. Our design offers a cost-effective approach to scale up multiplexability by simply tuning the number of molecular beacon binding sites on the padlock probe without redesigning amplification primers or fluorescent molecular beacons. With further development, our platform has the potential to enable highly multiplexed detection of nucleic acid targets, with potentially unrestricted multiplexability, and serve as a diagnostic tool for many more diseases in the future.

Racial and Ethnic Variation Associated With Human Papillomavirus Genotype in Anal Dysplasia.

BACKGROUND: Human Papillomavirus (HPV) is known to cause dysplasia and cancer. In cervical disease, there are documented differences in prevalence of HPV genotypes among racial/ethnic groups. Little is known about prevalence of HPV genotypes in anal dysplasia. This study aimed to evaluate association between HPV genotypes and race/ethnicity in a racially heterogenous population with anal dysplasia. METHODS: This was a single-institution retrospective review of patients treated for anal dysplasia between 2008 and 2019. HPV genotype, obtained via anal swab testing, was recorded as HPV 16, HPV 18, or other non-16/18 high-risk (HR) HPV genotypes. Univariate and multivariate logistic regression analyses were used to evaluate the association between patient factors and HPV genotype. RESULTS: Of 517 patients meeting inclusion criteria, 46.8% identified as White, 37.1% as Black, 13.2% as Hispanic, and 2.9% as other/unknown. Race/ethnicity (P = 0.016) and sex (P < 0.001) were significantly associated with differences in prevalence of HPV genotypes. Black (odds ratio 1.56, 95% confidence interval 1.00-2.44) and male (odds ratio 2.35, 95% confidence interval 1.42-3.92) patients were significantly more likely to have non-16/18 HR HPV genotypes. CONCLUSIONS: In a racially and socioeconomically diverse cohort of patients with anal dysplasia, Black race and male sex were associated with increased likelihood of infection with a non-16/18 HR HPV genotype. Many of these genotypes are not covered by currently available vaccines. Further study is warranted to evaluate anal HPV genotypes in a larger cohort, as this may have important implications in HPV vaccination and anal dysplasia screening efforts.

Laparoscopic Versus Robotic Proctectomy Outcomes: An ACS-NSQIP Analysis.

BACKGROUND: The robotic platform is increasingly used in colorectal surgery. Recent upgrades in the robotic platform and introduction of proctectomy-specific reports from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) warrant updated evaluation of minimally invasive proctectomy outcomes. The aim of this study was to compare outcomes in robotic versus laparoscopic proctectomy using ACS-NSQIP data. MATERIALS AND METHODS: The ACS-NSQIP data set was used to identify adult patients undergoing elective robotic and laparoscopic proctectomy in 2016 and 2017. Demographics, preoperative and intraoperative data, and postoperative outcomes were collected. Propensity-weighted analysis was used to estimate the effect of robotic versus laparoscopic surgery on outcomes. RESULTS: Of 3845 patients meeting inclusion criteria, 2681 (70%) underwent a laparoscopic approach and 1164 (30%) underwent a robotic approach. Patients undergoing a robotic procedure were more likely to be older, have higher American Society of Anesthesiologists scores, low rectal tumors, and have undergone chemotherapy or radiation before surgery. After propensity adjustment, a robotic approach was associated with a decrease in conversion to open operation (estimated mean difference, -6.7%; P < 0.01), length of stay (-0.6 d; P = 0.01), occurrence of postoperative ileus (-3.7%; P = 0.01), and an increase in operative time (20.3 min; P < 0.01). CONCLUSIONS: Using data from a national cohort, we found that compared with laparoscopy, robotic proctectomy is associated with decreased conversion to open operation, longer operation time, decreased length of stay, and decreased postoperative ileus. Our study identified several advantages to a robotic approach; however, further work is needed to assess cost-effectiveness in conjunction with clinical outcomes.

Metalloprotoporphyrin Inhibition of HCV NS3-4A Protease: Structure-Activity Relationships.

BACKGROUND: Antiviral actions of tetrapyrroles have been described in a number of systems. Our goal was to evaluate antagonism of the HCV NS3-4A protease by a variety of common porphyrins and characterize structure-activity relationships that may be useful for future drug design of HCV and related Flaviviruses. METHODS: Using fluorometric assays, common metalloprotoporphyrins (MPP) all inhibited NS3-4A protease with IC50 values in low micromolar ranges [CoPP (1.4 µM) < ZnPP = MnPP = SnPP < CuPP < FePP (6.5 µM) = protoporphyrin]. RESULTS: Lineweaver-Burk plots confirmed that MPP: NS3 inhibition was basically competitive. All tested MPPs inhibited HCV genotype 1A, 1B, 2A and 3A recombinant proteases with the same fidelity suggesting wide antagonistic capabilities. However, when the MPPs were tested in cellular incubations with HCV replicons only Zn, Fe and free-base protoporphyrin showed comparable EC50 and IC50 values suggesting that there may be critical differences in MPP uptake and intracellular availability. Meso, deutero, and isohematoporphyrin derivatives, with or without metal substitution, all showed less anti-protease and antiviral activities as compared to protoporphyrins, suggesting that the planar, vinyl side chains are important for protease active site binding. MPPs were also active against three common protease mutants (T54A, A156T, and V36M) with equivalent or better IC50 values as compared to wild type enzyme. CONCLUSION: These findings document the versatility of MPPs as antiviral agents with an expanded sensitivity for HCV genotypes and resistance to some common viral mutations. The results also suggest that further study of MPP structure and function will be useful for the development of new antiviral agents.

A novel sleep stage scoring system: Combining expert-based features with the generalized linear model.

In this study, we aim to automate the sleep stage scoring process of overnight polysomnography (PSG) data while adhering to expert-based rules. We developed a sleep stage scoring algorithm utilizing the generalized linear modelling (GLM) framework and extracted features from electroencephalogram (EEG), electromyography (EMG) and electrooculogram (EOG) signals based on predefined rules of the American Academy of Sleep Medicine (AASM) Manual for Scoring Sleep. Specifically, features were computed in 30-s epochs in the time and frequency domains of the signals and were then used to model the probability of an epoch being in each of five sleep stages: N3, N2, N1, REM or Wake. Finally, each epoch was assigned to a sleep stage based on model predictions. The algorithm was trained and tested on PSG data from 38 healthy individuals with no reported sleep disturbances. The overall scoring accuracy reached on the test set was 81.50 ± 1.14% (Cohen's kappa, κ=0.73±0.02 ). The test set results were highly comparable to the training set, indicating robustness of the algorithm. Furthermore, our algorithm was compared to three well-known commercialized sleep-staging tools and achieved higher accuracies than all of them. Our results suggest that automatic classification is highly consistent with visual scoring. We conclude that our algorithm can reproduce the judgement of a scoring expert and is also highly interpretable. This tool can assist visual scorers to speed up their process (from hours to minutes) and provides a method for a more robust, quantitative, reproducible and cost-effective PSG evaluation, supporting assessment of sleep and sleep disorders.