bluuebunny/crossref_metadata_2025 huggingface dataset:
Generation of a 100-billion cyclic peptide phage display library having a high skeletal diversity
Authors: Carle Vanessa , Kong Xu-Dong , Comberlato Alice , Edwards Chelsea , Díaz-Perlas Cristina , Heinis Christian
Published: June 2021

Phage display is a powerful technique routinely used for the generation of peptide- or protein-based ligands. The success of phage display selections critically depends on the size and structural diversity of the libraries, but the generation of large libraries remains challenging. In this work, we have succeeded in developing a phage display library comprising around 100 billion different (bi)cyclic peptides and thus more structures than any previously reported cyclic peptide phage display library. Building such a high diversity was achieved by combining a recently reported library cloning technique, based on whole plasmid PCR, with a small plasmid that facilitated bacterial transformation. The library cloned is based on 273 different peptide backbones and thus has a large skeletal diversity. Panning of the peptide repertoire against the important thrombosis target coagulation factor XI enriched high-affinity peptides with long consensus sequences that can only be found if the library diversity is large.
Hall of Mirrors: Corporate Philanthropy and Strategic Advocacy
Authors: Bertrand Marianne , Bombardini Matilde , Fisman Raymond , Hackinen Brad , Trebbi Francesco
Published: June 2021

Information is central to designing effective policy, and policy makers often rely on competing interests to separate useful from biased information. We show how this logic of virtuous competition can break down, using a new and comprehensive data set on U.S. federal regulatory rulemaking for 2003–2016. For-profit corporations and nonprofit entities are active in the rulemaking process and are arguably expected to provide independent viewpoints. Policy makers, however, may not be fully aware of the financial ties between some firms and nonprofits—grants that are legal and tax-exempt but hard to trace. We document three patterns that suggest that these grants may distort policy. First, we show that shortly after a firm donates to a nonprofit, the nonprofit is more likely to comment on rules on which the firm has also commented. Second, when a firm comments on a rule, the comments by nonprofits that recently received grants from the firm’s foundation are systematically closer in content to the firm’s own comments, relative to comments submitted by other nonprofits. Third, the final rule’s discussion by a regulator is more similar to the firm’s comments on that rule when the firm’s recent grantees also commented on it.
Mitochondria-acting carrier-free nanoplatform self-assembled by α-tocopheryl succinate carrying cisplatin for combinational tumor therapy
Authors: Mei Heng , Li Jing , Cai Shengsheng , Zhang Xuequan , Shi Wenqiang , Zhu Hai , Cao Jun , He Bin
Published: June 2021

Unsatisfactory drug loading capability, potential toxicity of the inert carrier and the limited therapeutic effect of a single chemotherapy drug are all vital inhibitory factors of carrier-assisted drug delivery systems for chemotherapy. To address the above obstacles, a series of carrier-free nanoplatforms self-assembled by dual-drug conjugates was constructed to reinforce chemotherapy against tumors by simultaneously disrupting intratumoral DNA activity and inhibiting mitochondria function. In this nanoplatform, the mitochondria-targeting small-molecular drug, α-tocopheryl succinate (TOS), firstly self-assembled into nanoparticles, which then were used as the carrier to conjugate cisplatin (CDDP). Systematic characterization results showed that this nanoplatform exhibited suitable particle size and a negative surface charge with good stability in physicochemical environments, as well as pH-sensitive drug release and efficient cellular uptake. Due to the combined effects of reactive oxygen species (ROS) generation by TOS and DNA damage by CDDP, the developed nanoplatform could induce mitochondrial dysfunction and elevated cell apoptosis, resulting in highly efficient anti-tumor outcomes in vitro. Collectively, the combined design principles adopted for carrier-free nanodrugs construction in this study aimed at targeting different intracellular organelles for facilitating ROS production and DNA disruption can be extended to other carrier-free nanodrugs-dependent therapeutic systems.
Antipsychotics Use Is Associated With Greater Adherence to Cardiometabolic Medications in Patients With Schizophrenia: Results From a Nationwide, Within-subject Design Study
Authors: Solmi Marco , Tiihonen Jari , Lähteenvuo Markku , Tanskanen Antti , Correll Christoph U , Taipale Heidi
Published: June 2021

Background

People with schizophrenia/schizoaffective disorder (schizophrenia) die early, largely due to cardiovascular-related mortality. Antipsychotics are associated with lower mortality. We aimed to explore whether antipsychotic use can reduce discontinuation of medications for cardiovascular risk factors and diseases (“cardiometacolic drugs”), using a within-study design controlling for subject-related factors.

Methods

Persons diagnosed with schizophrenia between 1972 and 2014, aged <65 years at cohort entry were identified in Finnish national databases. Four subcohorts were formed based on cardiometabolic drug use during the follow-up period, 1996–2017, namely statin (n = 14,047), antidiabetic (n = 13,070), antihypertensive (n = 17,227), and beta-blocker (n = 21,464) users. To control for subject-related factors, including likelihood of adherence as a trait characteristic, we conducted a within-subject study comparing the risk of discontinuation of each cardiometabolic drug during periods on vs off antipsychotics within each subject. We also accounted for number of psychiatric and nonpsychiatric visits in sensitivity analyses.

Results

In 52,607 subjects with schizophrenia, any antipsychotic use vs nonuse was associated with decreased discontinuation risk of antidiabetics (adjusted hazard ratio [aHR] = 0.56, 95% confidence interval [CI] = 0.47–0.66), statins (aHR = 0.61, 95%CI = 0.53–0.70), antihypertensives (aHR = 0.63, 95%CI = 0.56–0.71), and beta-blockers (aHR = 0.79, 95%CI = 0.73–0.87). Antipsychotics ranking best for discontinuation of all cardiometabolic drug categories were clozapine (aHR range = 0.34–0.55), followed by olanzapine (aHR = 0.43–0.71). For statins, aHRs ranged from aHR = 0.30 (95%CI = 0.09–0.98) (flupentixol-long-acting injectable (LAI) to aHR = 0.71 (95%CI = 0.52–0.97) (risperidone-LAI), for anti-diabetic medications from aHR = 0.37 (95%CI = 0.28–0.50) (clozapine) to aHR = 0.70 (95%CI = 0.53–0.92) (quetiapine), for antihypertensives from aHR = 0.14 (95%CI = 0.04–0.46) (paliperidone-LAI) to aHR = 0.69 (95%CI = 0.54–0.88) (perphenazine), for beta-blockers from aHR = 0.55 (95%CI = 0.48–0.63) (clozapine) to aHR = 0.76 (95%CI = 0.59–0.99) (perphenazine-LAI). The decreased risk of discontinuation associated with antipsychotic use somewhat varied between age strata. Sensitivity analyses confirmed main findings.

Discussion

In this national database within-subject design study, current antipsychotic use was associated with substantially decreased risk of discontinuation of statins, anti-diabetics, antihypertensives, and beta-blockers, which might explain reduced cardiovascular mortality observed with antipsychotics in people with schizophrenia.
The virus and the vessel, or: how we learned to stop worrying and love surveillance
Authors: Chorev Nitsan
Published: June 2021

This Society for the Advancement of Socio-Economics (SASE) Presidential address was given (virtually) at the annual SASE conference in July 2020. It is an early analysis of governments’ response to COVID-19, specifically governments’ attempt to reduce the spread of the virus by modifying people’s behaviors. Some of these attempts followed familiar models of power, such as discipline and governmentality. In addition, I show that a new practice of power emerged, addressing subjects who are considered ‘ungovernable’. In the first part of the lecture, I look at how states see their subjects and argue that COVID-19 reveals and normalizes a state’s view of subjects as ‘unresponsive’ and therefore ‘ungovernable’. In the second part, I look at how social media companies constitute us as ‘ungovernable’ and help reshape how states govern. Finally, I discuss instances of resistance, which might save our political agency after all.
Comparison of reproductive performance of AI- and natural service-sired beef females under commercial management
Authors: Marrella Mackenzie A , White Robin R , Dias Nicholas W , Timlin Claire , Pancini Stefania , Currin J , Clark Sherrie , Stewart Jamie L , Mercadante Vitor R G , Bradford Heather L
Published: June 2021

The objective of this study was to assess differences in reproductive performance of natural service and artificial insemination (AI) sired beef females based on pregnancy outcomes, age at first calving, and calving interval. Data were sourced from 8,938 cows sired by AI bulls and 3,320 cows sired by natural service bulls between 2010 and 2017. All cows were in a commercial Angus herd with 17 management units located throughout Virginia and represented spring and fall calving seasons. All calves were born to dams managed with estrus synchronization. Pregnancy was analyzed with generalized linear mixed models and other reproductive measures with linear mixed models in R. Six models were evaluated with the dependent variables of pregnancy status at the first diagnosis, pregnancy status at the second diagnosis, pregnancy type (AI or natural service) at the first diagnosis, pregnancy type at the second diagnosis, calving interval, and age at first calving. Independent variables differed by model but included sire type of the female (AI or natural service), prebreeding measures of age, weight, and body condition score, postpartum interval, sex of the calf nursing the cow, and management group. No differences were observed between AI- and natural service-sired females based on pregnancy status at first and second pregnancy diagnosis (P > 0.05). Sire type was only found to be significant for age at first calving (P < 0.05) with AI-sired females being 26.6 ± 1.6 d older at their first calving, which was expected because AI-sired females were born early in the calving season making them older at breeding. Surprisingly, age and body condition score were not significant predictors of pregnancy (P > 0.05). Body weight at breeding was not significant for pregnancy (P > 0.05) but was significant for age at first calving (P < 0.05). These data suggested that lighter heifers calved earlier which contradicts our original hypothesis. Overall, commercial Angus females sired by AI or natural service bulls had similar reproductive performance. Factors that were commonly associated with reproductive success were not significant in this commercial Angus herd managed with estrus synchronization. Given the size of these data, the importance of body condition, age, and weight should be reassessed in modern genetics and management practices.
Complete Genome Sequence Data of a Novel Streptomyces sp. Strain A2-16, a Potential Biological Control Agent for Potato Late Blight
Authors: Feng Shun , Tang Shicai , Jian Yongfei , Huang Xiaoqing , Jin Liang , Zhu Zhenglin , Dong Pan , Li Zhengguo
Published: June 2021

Streptomyces sp. strain A2-16 was recently isolated from potato root zone soil, and it could inhibit the hyphal growth of Phytophthora infestans. The A2-16 genome consisted of one chromosome of 9,765,518 bp and one plasmid of 30,948 bp with GC contents of 70.88% and 68.39%, respectively. A total of 8,518 predicted coding genes, 3 ncRNA,73 tRNA,18 rRNA genes, and 28 secondary metabolite biosynthesis gene clusters were identified. The products of the gene clusters included bioactive polyketides, terpenes, and siderophores, which might contribute to host plants against disease. The average nucleotide identity (ANI) value (82.88–91.41%) among the genome of A2-16 and other Streptomyces species suggested it might not belong to any previously sequenced species in the Streptomyces genus.
A Predicted Stem Loop in Coat Protein-Coding Sequence of Tobacco Vein Banding Mosaic Virus Is Required for Efficient Replication
Authors: Yan Zhi-Yong , Fang Le , Xu Xiao-Jie , Cheng De-Jie , Yu Cheng-Ming , Wang De-Ya , Tian Yan-Ping , Yuan Xue-Feng , Geng Chao , Li Xiang-Dong
Published: June 2021

Potyviral coat protein (CP) is involved in the replication and movement of potyviruses. However, little information is available on the roles of CP-coding sequence in potyviral infection. Here, we introduced synonymous substitutions to the codon C574G575C576 coding conserved residue arginine at position 192 (R192) of tobacco vein banding mosaic virus (TVBMV) CP. Substitution of the codon C574G575C576 to A574G575A576 or A574G575G576, but not C574G575A576, C574G575T576, or C574G575G576, reduced the replication, cell-to-cell movement, and accumulation of TVBMV in Nicotiana benthamiana plants, suggesting that C574 was critical for replication of TVBMV. Nucleotides 531 to 576 of the TVBMV CP-coding sequence were predicted to form a stem-loop structure, in which four consecutive C-G base pairs (C576-G531, C532-G575, C574-G533, and C534-G573) were located at the stem. Synonymous substitutions of R178-codon C532G533C534 to A532G533A534 and A532G533G534, but not C532G533A534, C532G533T534, or C532G533G534, reduced the replication levels, cell-to-cell, and systemic movement of TVBMV, suggesting that C532 was critical for TVBMV replication. Synonymous substitutions disrupting base pairs C576-G531 and C534-G573 did not affect viral accumulation. After three serial-passage inoculations, the accumulation of spontaneous mutant viruses was restored, and codons A532G533A534, A532G533G534, A574G575A576, or A574G575G576 of mutants were each separately changed to C532G533A534, C532G533G534, C574G575A576, or C574G575G576. Synonymous mutation of R178 and R192 also reduced viral accumulation in N. tabacum plants. Therefore, we concluded that the two consecutive C532-G575 and C574-G533 base pairs played critical roles in TVBMV replication via maintaining the stability of the stem-loop structures formed by nucleotides 531 to 576 of the CP-coding sequence.
Perception of Medical Student Mistreatment: Does Specialty Matter?
Authors: O’Brien Kevin E. , Mechaber Alex J. , Ledford Cynthia H. , Klocksieben Farina A. , Fagan Mark J. , Harrell Heather E. , Kaib Susan , Elnicki Mike , Van Deusen Reed , Moerdler Scott , Jagsi Reshma , Frank Erica ,   the Perceived Abuse of Medical Students (PAMS) Investigators
Published: June 2021

Purpose

Medical student mistreatment is pervasive, yet whether all physicians have a shared understanding of the problem is unclear. The authors presented professionally designed trigger videos to physicians from 6 different specialties to determine if they perceive mistreatment and its severity similarly.

Method

From October 2016 to August 2018, resident and attending physicians from 10 U.S. medical schools viewed 5 trigger videos showing behaviors that could be perceived as mistreatment. They completed a survey exploring their perceptions. The authors compared perceptions of mistreatment across specialties and, for each scenario, evaluated the relationship between specialty and perception of mistreatment.

Results

Six-hundred fifty resident and attending physicians participated. There were statistically significant differences in perception of mistreatment across specialties for 3 of the 5 scenarios: aggressive questioning (range, 74.1%–91.2%), negative feedback (range, 25.4%–63.7%), and assignment of inappropriate tasks (range, 5.5%–25.5%) (P ≤ .001, for all). After adjusting for gender, race, professional role, and prior mistreatment, physicians in surgery viewed 3 scenarios (aggressive questioning, negative feedback, and inappropriate tasks) as less likely to represent mistreatment compared with internal medicine physicians. Physicians from obstetrics–gynecology and “other” specialties perceived less mistreatment in 2 scenarios (aggressive questioning and negative feedback), while family physicians perceived more mistreatment in 1 scenario (negative feedback) compared with internal medicine physicians. The mean severity of perceived mistreatment on a 1 to 7 scale (7 most serious) also varied statistically significantly across the specialties for 3 scenarios: aggressive questioning (range, 4.4–5.4; P < .001), ethnic insensitivity (range, 5.1–6.1; P = .001), and sexual harassment (range, 5.5–6.3; P = .004).

Conclusions

Specialty was associated with differences in the perception of mistreatment and rating of its severity. Further investigation is needed to understand why these perceptions of mistreatment vary among specialties and how to address these differences.
Updated evidence-based recommendations for cervical cancer screening in France
Authors: Hamers Françoise F. , Poullié Anne-Isabelle , Arbyn Marc
Published: June 2021

Introduction

A national organized cytology-based cervical cancer screening program was launched in 2018 and rollout is ongoing. Concomitantly, the High Authority for Health (HAS) recently assessed new evidence on primary HPV testing to update screening recommendations.

Methods

The HAS commissioned systematic reviews and meta-analyses to evaluate the effectiveness of primary HPV screening; accuracy of HPV testing on self-samples; effectiveness of self-sampling to reach underscreened women; and triage strategies to manage HPV-positive women. Recommendations developed by the HAS were reviewed by a multidisciplinary group.

Results

Compared with cytology screening, HPV screening is more sensitive to detect precancers but less specific. In women aged ≥30, if the test is negative, HPV screening greatly reduces the risk of developing precancer and cancer for at least 5 years. HPV testing, using validated PCR-based assays, is as sensitive and slightly less specific on self-samples than on clinician-taken samples. Self-sampling is more effective to reach underscreened women than sending invitations to have a specimen taken by a clinician. Two-time triage strategies ensure a sufficiently high risk if triage-positive to justify referral and low risk if triage-negative allowing release to routine screening.

Conclusions

The HAS recommends three-yearly cytology screening for women aged 25–29 and HPV screening for those aged 30–65 with an extension of the screening interval to 5 years if the HPV test is negative. Self-sampling should be offered to underscreened women aged ≥30. HPV-positive women should be triaged with cytology. Those with abnormal cytology should be referred for colposcopy and those with normal cytology re-tested for HPV 12 months later. Recommendations for implementation of HPV-based screening in the organized program are provided.
A Pilot Study of Preoperative Vandetanib on Markers of Proliferation and Apoptosis in Breast Cancer
Authors: Spanheimer Philip M. , Bashir Amani , Lorenzen Allison W. , Beck Anna C. , Liao Junlin , Lizarraga Ingrid M. , Erdahl Lillian M. , Sugg Sonia L. , Karwal Mark W. , Weigel Ronald J.
Published: June 2021

Introduction:

Preclinical data supports antitumor activity of tyrosine kinase inhibitor vandetanib with Ret as the therapeutic target in breast cancer. We investigated the effect of preoperative vandetanib on markers of proliferation and apoptosis in breast cancer.

Methods:

Patients with invasive breast cancer were randomly assigned vandetanib 300 mg or placebo PO daily for 2 weeks before operative resection from January 2014 to June 2017. Pretreatment and posttreatment specimens were analyzed by immunohistochemistry for Ki-67, TUNEL, and p-ERK with stratification by Ret expression by immunohistochemistry.

Results:

Ten patients were enrolled. There was no statistically significant difference in ERK activation compared with placebo (P=0.45); however, ERK activation was reduced 74% compared with pretreatment biopsy with vandetinib treatment (P=0.005) without a significant reduction in the placebo group (−29%, P=0.55). Mean change in Ki-67 after vandetanib treatment was +0.3% compared with +2.0% in placebo treated patients, P=0.72. Mean change in TUNEL was +0.48 apoptotic nuclei per HPF in the vandetanib arm compared with +1.02 in the placebo arm, P=0.32. In vandetanib treated patients, Ki-67 was reduced 0.3% in RET-positive tumors compared with increased 1.0% in RET-negative tumors, P=0.43 and TUNEL was increased 0.77 in RET-positive tumors and 0.2 in RET-negative tumors, P=0.21.

Conclusions:

In this pilot study, no statistically significant differences on prespecified markers were seen with vandetanib compared with placebo. In accordance with the investigational hypothesis, there was a nonsignificant trend with vandetanib treatment of reduction in p-ERK and increased effects in Ret expressing tumors.
Racism as an Adverse Childhood Experience: An Interactive Workshop to Train Pediatricians to Address Racism in Clinical Care
Authors: Loe Irene M. , Froehlich Tanya E. , Edrees Hanein H. , Spinks-Franklin Adiaha ,   the R.A.C.E. C.A.R.D. Collaborative
Published: June 2021

Objective:

The objective of this study was to address critical gaps in pediatric medical education by developing and evaluating an interactive educational workshop on racism as an adverse childhood experience (ACE).

Methods:

A team of developmental-behavioral pediatrics professionals used a best-practice curriculum development model of Kern's 6 steps to develop the workshop curriculum. Based on a targeted needs assessment, goals and objectives to address the topics of race and racism in clinical practice were developed. A variety of educational strategies (e.g., audience polls, videos, didactic presentations, experiential activities, and peer-guided case-based discussion and practice) were used to appeal to varied learning styles. Selection of strategies was guided by self-determination theory, an adult learning model that addresses the needs of autonomy, competence, and relatedness. The workshop was implemented at 2 national pediatric meetings and evaluated using participant polls and written program evaluation.

Results:

The workshop curriculum was well-received. Participants endorsed improvements in comfort level in talking about race/racism and demonstrated a significant change in preparation or comfort level for skills-based activities, including counseling families and offering resources to address experiences with racism, postworkshop. Participants endorsed intent to change clinical practice by discussing the issues of race and indicated a desire to receive additional training.

Conclusion:

An interactive educational workshop on racism as an ACE was effective in improving pediatric professionals' comfort level and self-rated skills. Desire for a longer educational session suggests receptivity to longitudinal approaches. Replication and refinement of the educational workshop could clarify effective components of this approach. We advocate for longitudinal training curricula that incorporate observable behavior change and skills to increase and further evaluate the impact. Health care provider education and training to implement antiracism efforts in clinical encounters with patients and families can serve as an entry point to the complex process of addressing racism at multiple levels in health care.
Adolescent Chronic Health Conditions and School Disconnectedness
Authors: James Christine , Corman Hope , Noonan Kelly , Reichman Nancy E. , Jimenez Manuel E.
Published: June 2021

Objective:

The objective of this study was to examine associations between chronic health conditions and school disconnectedness, trouble getting along with others at school, and peer victimization at age 15.

Method:

We conducted a secondary analysis of population-based data from the Fragile Families and Child Wellbeing birth cohort to investigate associations between chronic developmental/behavioral and physical health conditions and school disconnectedness, trouble getting along with others at school, and peer victimization of adolescents using mother-reported child health conditions and youth-reported relationships/experiences at school ascertained from standardized scales. Associations were examined using linear and logistic regression models adjusting for confounding factors.

Results:

Of the 2874 adolescents included, more than one-third had at least 1 chronic health condition. Compared with those with no chronic health conditions, adolescents with developmental/behavioral health conditions felt more disconnected from school (by 0.22 SDs), had more trouble getting along with others at school (0.22 SD), and were more victimized by peers at school (0.20 SD). Teens with physical health conditions also felt more disconnected from school (0.10 SD), had more trouble getting along with others at school (0.12 SD), and were more victimized by peers (0.12 SD). One noteworthy difference was that adolescents with developmental/behavioral conditions were more likely than those with no conditions to report trouble getting along with teachers, but adolescents with physical health conditions were not.

Conclusion:

Chronic health conditions were associated with disconnectedness from school and negative school social interactions in this study of US urban youth, suggesting that targeted resources and interventions for this population are needed.
TWENTY-FIVE AND TWENTY-SEVEN-GAUGE SUTURELESS INTRASCLERAL FIXATION OF INTRAOCULAR LENSES
Authors: Patel Kishan G. , Yazdani Ava , Abbey Ashkan M.
Published: June 2021

Purpose:

To describe the clinical outcomes and surgical technique in transconjunctival sutureless intrascleral fixation of intraocular lenses, including the effectiveness of haptic flanging and peripheral iridotomy.

Method:

Retrospective series of patients who underwent sutureless intrascleral fixation of three-piece intraocular lenses by a single surgeon.

Results:

A total of 488 eyes were included in this study. Mean follow-up was 444 days. Mean preoperative best-corrected visual acuity was 20/355, and mean postoperative best-corrected visual acuity was 20/39 (P < 0.001). Intraocular lens dislocation occurred during the postoperative period in 67 (13.7%), with the majority (65.7%) occurring within 3 months after surgery. Dislocation occurred in 13 of 196 (6.6%) flanged haptics versus 54 of 292 (18.5%) unflanged haptics (P < 0.001). Reverse pupillary block occurred in 7 of 231 eyes (3.0%) without intraoperative peripheral iridotomy but only in 1 of 257 eyes (0.4%) with iridotomy (P = 0.0297). Other complications included haptic exposure (1.2%), retinal detachment (1.0%), and endophthalmitis (0.4%).

Conclusion:

This is the largest reported series of sutureless intrascleral fixation of intraocular lenses using trocar cannulas. This technique is an effective surgical option with low complication rates. The authors recommend that haptic flanging and peripheral iridotomy be performed in all cases.
Preoperative Criteria Predict Operative Time Variability Within Tympanoplasty Procedures
Authors: LeClair Karissa L. , Bessen Sarah Y. , Magro Isabelle L. , Kahng Peter W. , Saunders James E.
Published: June 2021

Objective:

To identify preoperative patient and surgical parameters that predict operative time variability within tympanoplasty current procedural terminology (CPT) codes.

Study Design:

Retrospective.

Setting:

Tertiary referral center.

Patients:

One hundred twenty eight patients who underwent tympanoplasty (CPT code 69631) or tympanoplasty with ossicular chain reconstruction (69633) by a single surgeon over 3 years.

Intervention(s):

Procedures were preoperatively assigned a complexity modifier: Level 1 (small or posterior perforation able to be repaired via transcanal approach), Level 2 (large perforation or other factor requiring postauricular approach), or Level 3 (cholesteatoma or severe infection).

Main Outcome Measure(s):

Total in-room time (nonoperative time plus actual operative time).

Results:

Consideration of preoperative parameters including surgical complexity, surgical facility, use of facial nerve monitoring, laser usage, resident involvement, revision surgery, and underlying patient characteristics (American Society of Anesthesiologists [ASA] score, body mass index [BMI]) accounted for up to 69% of surgical time variance. Across both CPT codes, surgical complexity levels accurately stratified operative times (p < 0.05). Total time was longer (by 30.0 min for 69631, 55.4 min for 69633) in Level 3 procedures compared with Level 2, while Level 1 cases were shorter (27.6, 33.9 min). Resident involvement added 25 and 32 minutes to total time (p < 0.02). Nonoperative preparation times were longer (22.1, 15.4 min) in the main hospital compared with ambulatory surgical center (p < 0.001).

Conclusions:

There is significant surgical time variability within tympanoplasty CPT codes, which can be accurately predicted by the preoperative assignment of complexity level modifiers and consideration of patient and surgical factors. Application of complexity modifiers can enable more efficient surgical scheduling.
The Impact of Superior Canal Dehiscence on Power Absorbance, Otoacoustic Emissions, and Hearing in Fat Sand Rats
Authors: Attias Joseph , Rabinovics Naomi , Nageris Benny , Hilly Ohad
Published: June 2021

Background:

Superior Semicircular Canal Dehiscence (SSCD) may lead to vestibular and auditory impairments.

Objective:

To study the effects of power absorbance (PA), Distortion Product Otoacoustic emissions (DPOAE), and hearing thresholds in normal ears of fat sand rats, after a bullotomy, creation and patching.

Methods:

SSCD was performed unilaterally in eight normal hearing animals while the contra-lateral un-operated ear was used as a control. Measures included auditory brain stem responses thresholds for air and bone conduction stimuli, DPOAEs and PA at peak pressure.

Results:

The normal PA pattern of the animals grossly resembled that of human ears. A bullotomy generated specific, large and significant (p < 0.0001) changes in PA without altering hearing thresholds. SSCD significantly decreased PA at low (p < 0.02) and increased at high frequencies (p < 0.03), but on a smaller scale than the bullotomy. SSCD, induced a mean air-bone gaps of 24.3 for clicks, and 31.2 dB for 1 kHz TB. SSCD also increased the DPOAEs levels by mean of 10.1 dB SPL (p < 0.03). Patching the dehiscence, reversed partially the PA changes, the auditory threshold shifts, and the DPOAEs levels to pre-SSCD values.

Conclusions:

SSCD affects both incoming and emitting sounds from the ear, probably due to its effect on cochlear impedance and stiffness of the middle and inner ear. The presence of DPOAEs and ABGs indicated a “third window” disease, i.e., SSCD. Due to similar PA patterns after bullotomy and SCCD, PA alone has limited diagnostic yield for patients with SCCD.
Quality Indicators for the Diagnosis and Management of Menière's Disease
Authors: Cottrell Justin , Yip Jonathan , Agrawal Sumit , Archibald Jason , Chau Justin , Lea Jane , Lin Vincent , Mick Paul , Morris David , Parnes Lorne , Schramm David , Chan Yvonne , Crowson Matthew , de Almeida John , Eskander Antoine , Witterick Ian J. , Monteiro Eric
Published: June 2021

Objective:

Menière's disease (MD) is a clinical disorder that often provides challenges in diagnosis and management. High-quality evidence to guide care providers is sparse, which can result in significant practice variations. Quality indicators (QIs) are one method that can be used to standardize and measure accepted care practices to improve healthcare quality and patient outcomes. Here, we developed practical, high-yield QIs that serve to measure and inform the quality of care provided to patients with MD.

Study Design:

Modified RAND Corporation University of California, Los Angeles appropriateness methodology for QI development.

Setting:

Multicenter nine-member expert panel.

Patients:

NA.

Interventions:

NA.

Main Outcome Measure:

Final QIs deemed appropriate measures of quality care with agreement by the expert panel.

Results:

Twenty-seven candidate indicators were identified after literature review. After the first round of evaluations, the panel agreed on three candidate indicators as appropriate QIs. A subsequent expert panel meeting provided a platform to discuss disagreements. Two agreed-upon QIs were revised during this discussion before final evaluations. The expert panel ultimately agreed upon five QIs as appropriate measures of high-quality care after completing final evaluations and reviewing updated literature. The five quality indicators measure audiometric documentation, minimization of electrocochleography, use of intratympanic dexamethasone, use of intratympanic gentamycin, and rate of labyrinthectomy/vestibular neurectomy in refractory MD patient.

Conclusions:

This study proposes five QIs that cover key aspects of care for MD, such as accurate diagnosis and management options including initial destructive therapies. These QIs can serve multiple purposes, the most important of which is to galvanize quality improvement initiatives.
A Web-Based Deep Learning Model for Automated Diagnosis of Otoscopic Images
Authors: Tsutsumi Kotaro , Goshtasbi Khodayar , Risbud Adwight , Khosravi Pooya , Pang Jonathan C. , Lin Harrison W. , Djalilian Hamid R. , Abouzari Mehdi
Published: June 2021

Objectives:

To develop a multiclass-classifier deep learning model and website for distinguishing tympanic membrane (TM) pathologies based on otoscopic images.

Methods:

An otoscopic image database developed by utilizing publicly available online images and open databases was assessed by convolutional neural network (CNN) models including ResNet-50, Inception-V3, Inception-Resnet-V2, and MobileNetV2. Training and testing were conducted with a 75:25 breakdown. Area under the curve of receiver operating characteristics (AUC-ROC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were used to compare different CNN models’ performances in classifying TM images.

Results:

Our database included 400 images, organized into normal (n = 196) and abnormal classes (n = 204), including acute otitis media (n = 116), otitis externa (n = 44), chronic suppurative otitis media (n = 23), and cerumen impaction (n = 21). For binary classification between normal versus abnormal TM, the best performing model had average AUC-ROC of 0.902 (MobileNetV2), followed by 0.745 (Inception-Resnet-V2), 0.731 (ResNet-50), and 0.636 (Inception-V3). Accuracy ranged between 0.73–0.77, sensitivity 0.72–0.88, specificity 0.58–0.84, PPV 0.68–0.81, and NPV 0.73–0.83. Macro-AUC-ROC for MobileNetV2 based multiclass-classifier was 0.91, with accuracy of 66%. Binary and multiclass-classifier models based on MobileNetV2 were loaded onto a publicly accessible and user-friendly website (https://headneckml.com/tympanic). This allows the readership to upload TM images for real-time predictions using the developed algorithms.

Conclusions:

Novel CNN algorithms were developed with high AUC-ROCs for differentiating between various TM pathologies. This was further deployed as a proof-of-concept publicly accessible website for real-time predictions.
Rupture-Like Shrinkage and Regrowth of Endolymphatic Hydrops in Ménière's Disease During Remission
Authors: Fukushima Munehisa , Suekata Yu , Kusumoto Takuya , Akahani Shiro , Okamoto Hidehiko , Inohara Hidenori , Takeda Noriaki
Published: June 2021

Objective:

To clarify pathophysiological characteristics of Ménière's disease during the remission phase.

Patients:

Two Ménière's disease patients with different disease durations, whose endolymphatic hydrops was longitudinally observed using 3-T magnetic resonance imaging.

Interventions:

Diagnostic.

Main Outcomes and Measures:

Morphological changes of endolymphatic hydrops visualized using 3-T magnetic resonance imaging.

Results:

Rupture-like shrinkage and regrowth of endolymphatic hydrops during the remission phase was observed in both patients.

Conclusion:

The remission phase with hearing improvement could be as important as vertigo attacks in Ménière's disease.
A novel mask to prevent aerosolized droplet dispersion in endoscopic procedures during the coronavirus disease pandemic
Authors: Maehata Tadateru , Yasuda Hiroshi , Kiyokawa Hirofumi , Sato Yoshinori , Yamashita Masaki , Matsuo Yasumasa , Nakahara Kazunari , Yamamoto Hiroyuki , Itoh Fumio
Published: June 2021

Endoscopic procedures increase the risk of transmission of severe acute respiratory syndrome coronavirus 2 to medical staff, because aerosols are generated during upper gastrointestinal endoscopy. There have been several reported studies on devices for infection prevention; however, few reports have validated them. Therefore, we developed a novel mask to prevent the diffusion of aerosol droplets from patients undergoing endoscopy.

We compared microdroplet dispersion during coughing episodes when using the novel mask with microdroplet dispersion when using the conventional mouthpiece alone.

The mean number of microdroplets was significantly smaller in the group that used the novel mask (57.9 ± 122.91 vs 933.6 ± 119.80 droplets; P = .01).

The novel mask may aid in reducing the degree of exposure of medical personnel to microdroplets and the risk of subsequent infection.
Evaluation of the proper chest compression depth for neonatal resuscitation using computed tomography
Authors: Lee Juncheol , Lee Dong Keon , Oh Jaehoon , Park Seung Min , Kang Hyunggoo , Lim Tae Ho , Jo You Hwan , Ko Byuk Sung , Cho Yongil
Published: June 2021

This study was created to assess whether a 30-mm depth of chest compression (CC) is sufficient and safe for neonatal cardiopulmonary resuscitation.

This retrospective analysis was performed with chest computed tomography scans of neonates in 2 hospitals between 2004 and 2018. We measured several chest parameters and calculated heart compression fraction (HCF) using the ejection fraction formula. We evaluated whether one-third of the external anterior-posterior (AP) diameter and HCF with them are the equivalent to 25-, 30-, 35 mm and HCF with them, respectively, and the number of individuals with over-compression (internal chest AP diameter − compressed depth <10 mm) to estimate a safe CC depth. We divided the patients into term and preterm groups and compared their outcomes.

In total, 63 of the 75 included individuals were analyzed, and one-third of the external lengths was equivalent to 30 ± 3 mm (P < .001). When the patients were divided into term (n = 53) and preterm (n = 10) groups, the equivalent depth was 30 ± 3 mm in the term group (P < .001) and 25 ± 2.5 mm in the preterm group (P = .004). The HCF with 30 mm was equivalent to that for one-third of the external length (P < .001). When we simulated CCs with a 30-mm depth, over-compression occurred more frequently in the preterm group (20%) compared to the term group (1.9%) (P = .014).

A 30-mm depth could be appropriate for sufficient and safe neonatal resuscitation. Shallower CC should be considered in preterm babies.
Comparative efficacy and dysmenorrhea score of 6 object-separated moxibustions for the treatment of Chinese patients with dysmenorrhea
Authors: Wu Zi-Xuan , Cai Min-Jie , Huang Pei-Dong , Chen Jia-Yun , Lv Zhao-Hui , Huang Xu-Yan
Published: June 2021

Background:

Primary dysmenorrhea (PD), one of the most common diseases in women, is known to be effective with object-separated moxibustion. However, because there is no large sample size for comparison, it is difficult to choose the best method for the clinical treatment of these different treatments. Therefore, our aim was to compare and rank different moxibustion methods to determine the most effective treatment method for PD.

Materials and methods:

A systematic search was carried out in PubMed, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, and Chinese Biomedical Literature, to identify the randomized controlled trials (RCTs) investigated the object-separated moxibustion is associated with dysmenorrhea, as well as we also manually checked the bibliographies of eligible studies and topic-related reviews, RCTs from their inception to May 1, 2020. Three investigators read the citations and excluded quasi-randomized trials and trials that were incomplete. We extracted data following a predefined hierarchy. We assessed the studies’ risk of bias in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. The primary outcomes were efficacy (response rate) and dysmenorrhea scores. We estimated the summary odds ratio (OR) and mean difference (MD) using pairwise and network meta-analyses with random effects. STATA software version 16.0, ADDIS software version 1.16.5, and R software version 3.6.1 were used to statistically analyze all data.

Results:

Fifty-six RCTs with 5550 patients were included, comparing 6 object-separated moxibustion therapies with acupuncture or oral medicine. All moxibustions were more effective than ibuprofen, with OR ranging between 6.75 (95%CI: 3.58 to 13.22) for moxibustion at the navel. For relieving pain which uses dysmenorrhea score to evaluate, mild moxibustion (MD = −1.42, −4.24 to 0.85) was more effective than others. A total of 24 (42.8%) of 56 trials were rated as having a high risk of bias, 31(55.4%) as moderate, and 1(1.8%) as low, and the certainty of the evidence was moderate.

Conclusions:

Mild moxibustion cannot only effectively treat PD but also relieve pain in comparison with ibuprofen. Although GRADE evidence indicate low to moderate for most comparisons, mild moxibustion seems to be an advisable option for PD treatment to relieve symptoms.
Diagnostic complexity of rifampicin-induced coagulopathy in a patient with spontaneous muscle bleeding
Authors: Vučić Domagoj , Cvitkušić-Lukenda Katica , Dunđer Ivica , Gabaldo Krešimir , Knežević-Praveček Marijana , Miškić Blaženka
Published: June 2021

Introduction:

Rifampicin is currently used to treat various bacterial infections, with the most significant application in the treatment of tuberculosis. Dose-independent side effects of the drug can lead to the development of various coagulation disorders, among which disseminated intravascular coagulation is the most dangerous. The mechanism of coagulopathy itself is multifactorial, but it is thought to be mediated by an immune response (formation of antigen-antibody complexes) and consequent damage to platelets and the vascular endothelium.

Patient concerns:

A 66-year-old woman, with numerous comorbidities including chronic renal failure, condition after implantation of a permanent pacemaker, and a positive blood culture for Staphylococcus aureus, presented with spontaneous bleeding in the muscle wall, and in the clinical picture of hemorrhagic shock.

Diagnosis:

Knowing the multifactorial mechanism of rifampicin-induced coagulopathy, possible factors were considered, such as infections, comorbidities, drug use and drug-drug interactions, pathological laboratory parameters, and coagulograms. Clinical presentation of abdominal pain and intra-abdominal mass, with laboratory verification of prolonged activated partial thromboplastin time and computed tomography-proven hematoma suspected of acute bleeding, redirects clinical suspicion of drug-induced coagulopathy.

Interventions:

By discontinuing rifapicin and administering vitamin K and fresh frozen plasma, normalization of laboratory coagulation parameters was achieved. Bleeding from the muscle wall required correction of acute anemia with red cell concentrates, surgical intervention, and additional antibiotic therapy for secondary infection of the operative wound.

Outcomes:

At the end of 6 weeks of antibiotic (antistaphylococcal) therapy (due to the basic suspicion of possible infectious endocarditis), the normalization of inflammatory parameters occurred with a sterile control blood culture and a normal coagulogram.

Conclusion:

Clinicians should be aware of the possible side effects of the administered drugs, especially taking into account the overall clinical picture of a patient, including comorbidities and possible drug interactions.
Thrombomodulin gene polymorphism and the occurrence and prognostic value of sepsis acute kidney injury
Authors: Li Qin , Yang Wenjuan , Zhao Keming , Sun Xifeng , Bao Liuqian
Published: June 2021

To investigate the relationship between thrombomodulin (THBD) gene single nucleotide polymorphisms (SNPs) and susceptibility to sepsis and the occurrence and prognosis of acute kidney injury (AKI) in sepsis patients.

The genotypes of THBD gene rs1962, rs3176123, and rs1042580 in 178 sepsis patients with AKI, 243 sepsis patients without AKI (No AKI), and 103 healthy controls were analyzed by direct sequencing. Enzyme-linked immunosorbent assay (ELISA) was used to detect the plasma THBD protein levels. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of plasma THBD levels in sepsis, AKI, and death of sepsis patients.

The C allele carriers of THBD gene rs1962 were more likely to develop AKI and sepsis than the T allele carriers (OR = 1.61, 95% CI: 1.18–2.19, P < .01; OR = 2.16, 95% CI: 1.42–3.29, P < .01). The rs3176123 G allele was associated with an increased risk of AKI in sepsis patients (OR = 1.41, 95% CI: 1.06–1.88, P = .02), the G allele had a significant association with a higher risk of sepsis susceptibility (OR = 1.91, 95% CI: 1.33–2.75, P < .01). Sepsis patients of rs1042580 C allele had a lower risk of AKI than those of T allele (OR = 0.58, 95% CI: 0.37–0.91, P = .02), the C allele was related to a reduced risk of sepsis susceptibility (OR = 0.38, 95% CI: 0.26–0.55, P < .01). The THBD gene rs1962, rs3176123, and rs1042580 TGT haplotype was linked to higher risk of AKI in patients with sepsis (OR = 1.96, 95%CI: 1.14–3.38, P = .02). Sepsis patients with the THBD gene rs1962 TC + CC genotype had a higher risk of death than those with TT genotype (OR = 10.93, 95%CI: 5.05–26.96, P < .01), but there was no significant difference in the risk of death in sepsis patients with different genotypes at rs3176123 and rs1042580 (P > .05).

The THBD gene rs1962, rs3176123, and rs1042580 SNPs are significantly associated with sepsis susceptibility and the risk of AKI. The rs1962 SNP is related to the risk of death in sepsis patients.