bluuebunny/crossref_metadata_2025 huggingface dataset:
HAlign 3: Fast Multiple Alignment of Ultra-Large Numbers of Similar DNA/RNA Sequences
Authors: Tang Furong , Chao Jiannan , Wei Yanming , Yang Fenglong , Zhai Yixiao , Xu Lei , Zou Quan
Published: August 2022

HAlign is a cross-platform program that performs multiple sequence alignments based on the center star strategy. Here we present two major updates of HAlign 3, which helped improve the time efficiency and the alignment quality, and made HAlign 3 a specialized program to process ultra-large numbers of similar DNA/RNA sequences, such as closely related viral or prokaryotic genomes. HAlign 3 can be easily installed via the Anaconda and Java release package on macOS, Linux, Windows subsystem for Linux, and Windows systems, and the source code is available on GitHub (https://github.com/malabz/HAlign-3).
Single-cell transcriptomes and runx2b−/− mutants reveal the genetic signatures of intermuscular bone formation in zebrafish
Authors: Nie Chun-Hong , Wan Shi-Ming , Chen Yu-Long , Huysseune Ann , Wu Ya-Ming , Zhou Jia-Jia , Hilsdorf Alexandre Wagner Silva , Wang Wei-Min , Witten Paul Eckhard , Lin Qiang , Gao Ze-Xia
Published: August 2022

Intermuscular bones (IBs) are mineralized spicules, present in the myosepta of many, but not all, teleost species. IBs are often small and sharp, and they consequently limit how the fish can be processed; the IBs may cause injury or trauma if lodged in consumers’ throats or mouths, and therefore affect the appeal of the fish to many consumers. The development of IBs in teleosts is still not fully understood and the molecular basis of IB development remains to be established. Here, the characteristics of IB tissue are evaluated based on single-cell transcriptomics in wild-type zebrafish. The analysis defined 18 distinct cell types. Differentiation trajectories showed that IBs are derived from tendons and that a core tendon-osteoblast cell lineage is related to IB formation. In particular, the functions of 10 candidate genes were evaluated via CRISPR-Cas9 mutants. Among those, runx2b−/− mutants completely lost IBs, while swimming performance, growth and bone mineral density were not significantly different from runx2b+/+ zebrafish. Comparative single-cell RNA sequencing (scRNA-seq) analysis in runx2b−/− and runx2b+/+ zebrafish revealed the role of osteoblasts in IB formation. In addition, differentially expressed genes were enriched in the transforming growth factor β/bone morphogenetic protein (TGF-β/BMP) pathway after runx2b deletion. This study provides evidence for the crucial role of runx2b regulation in IB formation. Genetic breeding can target runx2b regulation and generate strains of commercial fish species without IBs, which can improve the safe consumption and economic value of many farmed fish species.
Loss-of-function of SAWTOOTH 1 affects leaf dorsiventrality genes to promote leafy heads in lettuce
Authors: An Guanghui , Yu Changchun , Yan Chenghuan , Wang Menglu , Zhang Weiyi , Jia Yue , Shi Chunmei , Larkin Robert M , Chen Jiongjiong , Lavelle Dean , Michelmore Richard W , Kuang Hanhui
Published: August 2022

The mechanisms underlying leafy heads in vegetables are poorly understood. Here, we cloned a quantitative trait locus (QTL) controlling leafy heads in lettuce (Lactuca sativa). The QTL encodes a transcription factor, SAWTOOTH 1 (LsSAW1), which has a BEL1-like homeodomain and is a homolog of Arabidopsis thaliana. A 1-bp deletion in Lssaw1 contributes to the development of leafy heads. Laser-capture microdissection and RNA-sequencing showed that LsSAW1 regulates leaf dorsiventrality and loss-of-function of Lssaw1 downregulates the expression of many adaxial genes but upregulates abaxial genes. LsSAW1 binds to the promoter region of the adaxial gene ASYMMETRIC LEAVES 1 (LsAS1) to upregulate its expression. Overexpression of LsAS1 compromised the effects of Lssaw1 on heading. LsSAW1 also binds to the promoter region of the abaxial gene YABBY 1 (LsYAB1), but downregulates its expression. Overexpression of LsYAB1 led to bending leaves in LsSAW1 genotypes. LsSAW1 directly interacts with KNOTTED 1 (LsKN1), which is necessary for leafy heads in lettuce. RNA-seq data showed that LsSAW1 and LsKN1 exert antagonistic effects on the expression of thousands of genes. LsSAW1 compromises the ability of LsKN1 to repress LsAS1. Our results suggest that downregulation or loss-of-function of adaxial genes and upregulation of abaxial genes allow for the development of leafy heads.
Alcohol acyl transferase genes at a high-flavor intensity locus contribute to ester biosynthesis in kiwifruit
Authors: Souleyre Edwige J F , Nieuwenhuizen Niels J , Wang Mindy Y , Winz Robert A , Matich Adam J , Ileperuma Nadeesha R , Tang Haidee , Baldwin Samantha J , Wang Tianchi , List Blake W , Hoeata Kirsten A , Popowski Elizabeth A , Atkinson Ross G
Published: August 2022

Volatile esters are key compounds contributing to flavor intensity in commonly consumed fruits including apple (Malus domestica), strawberry (Fragaria spp.), and banana (Musa sapientum). In kiwifruit (Actinidia spp.), ethyl butanoate and other esters have been proposed to contribute fruity, sweet notes to commercial cultivars. Here, we investigated the genetic basis for ester production in Actinidia in an A. chinensis mapping population (AcMPO). A major quantitative trait loci for the production of multiple esters was identified at the high-flavor intensity (HiFI) locus on chromosome 20. This locus co-located with eight tandemly arrayed alcohol acyl transferase genes in the Red5 genome that were expressed in a ripening-specific fashion that corresponded with ester production. Biochemical characterization suggested two genes at the HiFI locus, alcohol acyl transferase 16-b/c (AT16-MPb/c), probably contributed most to the production of ethyl butanoate. A third gene, AT16-MPa, probably contributed more to hexyl butanoate and butyl hexanoate production, two esters that segregated in AcMPO. Sensory analysis of AcMPO indicated that fruit from segregating lines with high ester concentrations were more commonly described as being “fruity” as opposed to “beany”. The downregulation of AT16-MPa–c by RNAi reduced ester production in ripe “Hort16A” fruit by >90%. Gas chromatography-olfactometry indicated the loss of the major “fruity” notes contributed by ethyl butanoate. A comparison of unimproved Actinidia germplasm with those of commercial cultivars indicated that the selection of fruit with high concentrations of alkyl esters (but not green note aldehydes) was probably an important selection trait in kiwifruit cultivation. Understanding ester production at the HiFI locus is a critical step toward maintaining and improving flavor intensity in kiwifruit.
Marginal Jobs and Job Surplus: A Test of the Efficiency of Separations
Authors: Jäger Simon , Schoefer Benjamin , Zweimüller Josef
Published: August 2022

We present a test of Coasean theories of efficient separations. We study a cohort of jobs from the introduction through the repeal of a large age- and region-specific unemployment benefit extension in Austria. In the treatment group, 18.5$\%$ fewer jobs survive the program period. According to the Coasean view, the destroyed marginal jobs had low joint surplus. Hence, after the repeal, the treatment survivors should be more resilient than the ineligible control group survivors. Strikingly, the two groups instead exhibit identical post-repeal separation behaviour. We provide, and find suggestive evidence consistent with, an alternative model in which wage rigidity drives the inefficient separation dynamics.
Utility of repeat extractable nuclear antigen antibody testing: a retrospective audit
Authors: Yeo Ai Li , Leech Michelle , Ojaimi Samar , Morand Eric
Published: August 2022

Objectives

Autoantibodies to ENA are frequently ordered during the workup of suspected autoimmune connective tissue diseases. There are no current guidelines for repeat test ordering. The objective of this study was to assess the utility of repeat ENA testing after an initial negative result.

Methods

A retrospective study was conducted in a single, multicentre tertiary health network in Melbourne, Australia. Results of all ENA tests were extracted from the hospital laboratory information system. For patients who had a change in ENA result from negative to positive, clinical information was obtained from the hospital records regarding new diagnosis of an ANA-associated rheumatic disease (AARD).

Results

A total of 23 438 ENA tests were performed in 19 603 patients from 29 July 2013 to 28 September 2020. In total, 20 918 (89.2%) were negative with 215 (0.9%) being equivocal. Of the 2305 positive tests, the most common ENA auto-antibody specificity detected was anti-Ro52 (1185, 51.4%). A total of 2636 of 19 603 patients (13.4%) had more than one ENA test performed during the study period. Of these, most (2523, 95.7%) had stable ENA results with no change compared with the first test. Only 53 patients (2.2%) had an ENA result that changed from negative to positive. Excluding patients with pre-existing rheumatic conditions and those under 18, there were five new AARDs found in the remaining 34 patients.

Conclusion

Repeat ENA test results rarely change or result in a new diagnosis of an AARD, with repeated testing only warranted if there is a change in clinical manifestations.
Syringe Service Program Perspectives on Barriers, Readiness, and Programmatic Needs to Support Rollout of the COVID-19 Vaccine
Authors: Corcorran Maria A. , Austin Elizabeth J. , Behrends Czarina N. , Briggs Elsa S. , Frost Madeline C. , Juarez Alexa M. , Frank Noah D. , Healy Elise , Prohaska Stephanie M. , LaKosky Paul A. , Kapadia Shashi N. , Perlman David C. , Schackman Bruce R. , Des Jarlais Don C. , Williams Emily C. , Glick Sara N.
Published: August 2022

Background

We explored syringe service program (SSP) perspectives on barriers, readiness, and programmatic needs to support coronavirus disease 2019 (COVID-19) vaccine uptake among people who use drugs.

Methods

We conducted an exploratory qualitative study, leveraging an existing sample of SSPs in the United States. Semistructured, in-depth interviews were conducted with SSP staff between February and April 2021. Interviews were analyzed using a Rapid Assessment Process, an intensive, iterative process that allows for rapid analysis of time-sensitive qualitative data.

Results

Twenty-seven SSPs completed a qualitative interview. Many SSP respondents discussed that COVID-19 vaccination was not a priority for their participants because of competing survival priorities, and respondents shared concerns that COVID-19 had deepened participant mistrust of health care. Most SSPs wanted to participate in COVID-19 vaccination efforts; however, they identified needed resources, including adequate space, personnel, and training, to implement successful vaccine programs.

Conclusions

Although SSPs are trusted resources for people who use drugs, many require additional structural and personnel support to address barriers to COVID-19 vaccination among their participants. Funding and supporting SSPs in the provision of COVID-19 prevention education and direct vaccine services should be a top public health priority.
Patient Satisfaction With Standard Methadone and Flexible Buprenorphine/Naloxone Models of Care: Results From a Pragmatic Randomized Controlled Clinical Trial
Authors: Hassan Ahmed N. , Bozinoff Nikki , Jutras-Aswad Didier , Socias M. Eugenia , Stewart Sherry H. , Lim Ron , Le Foll Bernard ,   The OPTIMA Research Group
Published: August 2022

Introduction

Patient satisfaction is a critical measure of quality of care across health disciplines because it may affect clinical outcomes.

Objectives

This study aimed to examine longitudinal patient satisfaction in individuals with opioid use disorder (OUD) randomized to receive either standard methadone or flexible buprenorphine/naloxone models of care, its predictors, and association with dropout/illicit drug use.

Methods

This study assessed patient satisfaction, using the 8-item version of the Client Satisfaction Questionnaire (CSQ), as a secondary outcome of a large phase IV pragmatic randomized controlled trial (OPTIMA). The effectiveness of standard methadone model of care was compared with flexible take-home buprenorphine/naloxone dispensation model of care in patients with prescription-type OUD. Of 272 participants recruited and followed up for 24 weeks, 183 were eligible for this study.

Results

Throughout the study, patients were “satisfied” with their treatment. The average CSQ score was not significantly different between weeks 4, 12, and 24 in the total sample (χ2 = 0.35; P = 0.84). There was no significant difference in CSQ based on treatment assignment (methadone vs flexible buprenorphine/naloxone) either overall (z = 0.87; P = 0.38) or over time (χ2 = 0.65; P = 0.72). High levels of depression at baseline and decreased depressive symptoms over the follow-up period predicted positive changes in patient satisfaction (P = 0.03 and P = <0.01, respectively). Satisfaction was significantly associated with treatment retention but not illicit drug use.

Conclusions

This study demonstrates that patients with OUD on either standard methadone or flexible buprenorphine were generally satisfied with their treatment, with no difference in patient satisfaction based on treatment allocation. Given the ongoing opioid crisis, strategies to improve patient satisfaction should be further explored.
Objective Evaluation of Neurogenic Intermittent Claudication for Patients with Lumbar Spinal Stenosis Based on Plantar Pressure Analysis
Authors: Wei Wei , Jin Yufei , Jiang Mingchun , Li Lintao , Yan Weidi , Wang Haixia , Zhao Jianning , Wang Beiyue , Sun Guojing , Yang Xiaojiang
Published: August 2022

Study Design.

A cross-sectional study.

Objective.

To quantify the severity of neurogenic intermittent claudication (NIC) for patients with lumbar spinal stenosis (LSS) based on center of pressure (COP) trajectory.

Summary of Background Data.

NIC is one of the typical symptoms of LSS. So far, the severity level of NIC is mainly evaluated by subjective description of patients, which might be biased by patients’ background differences and thus lead to ineffective diagnosis or inappropriate treatment for LSS. Therefore, it remains necessary to develop a reliable clinical technique for quantitative evaluation of NIC to achieve more effective therapy for LSS.

Methods.

In the present study, the Footscan® pressure system was used to detect the COP trajectory. The real-time walking distance (rtWD) and the corresponding displacement of medial-lateral COP (ML-COP) were calculated based on the trajectory. The differences of ML-COP between LSS group and control group were analyzed using one-way repeated measures ANOVA. Regression and Pearson correlation analysis were used to investigate the correlation between rtWD and ML-COP, as well as the relation between the Oxford Claudication Score (OCS) and clinical evaluation indicators.

Results.

The present study included 31 LSS patients and 31 healthy controls. There were no significant differences in demographic data between the two groups (P>0.05). The results indicated that ML-COP would increase with the number of laps in the LSS group while not in the control group. Also, a linear relationship was identified between the ML-COP and rtWD for LSS patients (R2>0.80, P<0.05). Since the incremental rate of ML-COP for LSS patients was reflected by the regression coefficients of the linear regression analysis, thus the regression coefficients were defined as the claudication correlation coefficients (CCC). In addition, it was indicated by the statistical analysis that there was a strong positive correlation between OCS and CCC (r=0.96; P<0.001), and a medium negative correlation with FWD (r=−0.67; P<0.001). It was also noticed that there was no significant correlation between the average ML-COP and OCS (r=−0.03; P=0.864).

Conclusion.

The ML-COP of LSS patients would increase with the patients’ walking distance. This incremental rate, characterized by the claudication correlation coefficient (CCC), would be used as an effective indicator to quantify the severity level of the NIC, for potentially more accurate and reliable diagnosis, evaluation, and treatment of LSS.

Level of Evidence.

3
The Efficacy of Intense Pulsed Light as a Treatment for Benign Pigmented Lesions on the Dorsal Hand
Authors: Wamsley Christine E. , Parsa Shyon , Culver Abby , Barillas Jennifer , Kenkel Jeffrey M.
Published: August 2022

BACKGROUND

Intense pulsed light (IPL) is a noninvasive therapeutic option to treat benign pigmented lesions by targeting melanin.

OBJECTIVE

The purpose of this study was to assess IPL as a treatment for benign pigmented dorsal hand lesions.

MATERIALS AND METHODS

A total of fifteen subjects, 40 to 73 years old, received 3 monthly IPL treatments over the dorsal hands. Subjects followed up 1 and 3 months after treatment. At every visit, photographs were taken using the VISIA Complexion Analysis System (Canfield Scientific, Fairfield, NJ) and analyzed using the RBX Brown Spots Analysis algorithm. The Clinician Global Aesthetic Improvement Scale and Subject Global Aesthetic Improvement Scale were completed at both follow-up visits.

RESULTS

A total of fifteen subjects completed all six visits. The number of brown spots decreased 9.26% (p = .0004) and 7.52% (p = .0132) at each follow-up visit. The mean brown intensity decreased 6.15% (p = .0183) and 7.67% (p = .0178), whereas the mean contrast intensity decreased 8.88% (p < .0001) and 6.60% (p = .0007) 1 and 3 months after treatment, respectively. The mean Clinician Global Aesthetic Improvement Scale was 2.03 and 2.23, whereas the mean Subject Global Aesthetic Improvement Scale 1 and 3 months after treatment was 1.6 and 1.8, respectively.

CONCLUSION

Objective analysis, along with clinician and subject assessments, showed an improvement in the appearance of benign pigmented lesions in the treated area after 3 IPL treatments.
Attitudes on pharmacogenomic results as secondary findings among medical geneticists
Authors: Bartos Meghan N. , Scott Stuart A. , Jabs Ethylin Wang , Naik Hetanshi
Published: August 2022

Objectives

As evidence mounts supporting the utility of pharmacogenomic-guided medication management, incorporating pharmacogenomic genes into secondary finding results from sequencing panels is increasingly under consideration. We studied medical geneticists’ attitudes on receiving pharmacogenomic results as secondary finding.

Methods

Four focus groups with 16 medical geneticists total were conducted followed by thematic analysis.

Results

All participants ordered genetic sequencing tests; however, the majority had rarely or never ordered pharmacogenomic tests (10/16) or prescribed medications with established response variability (11/16). In total 81.3% expressed low comfort interpreting pharmacogenomic results without appropriate clinical resources (13/16). The positives of receiving pharmacogenomic results as secondary finding included prevention of adverse drug reactions in adults, grateful information-seeking patients, the ability to rapidly prescribe more effective treatments and appreciation of the recent advances in both pharmacogenomic knowledge and available guidelines. Negatives included laboratory reporting issues, exclusivity of pharmacogenomic results to certain populations, lengthy reports concealing pharmacogenomic results in patient charts and laboratories marketing to individuals without prior pharmacogenomic knowledge or targeting inappropriate populations. The most desirable pharmacogenomic resources included a universal electronic health record clinical decision support tool to assist identifying and implementing pharmacogenomic results, a specialized pharmacist as part of the care team, additional pharmacogenomic training during medical/graduate school, and a succinct interpretation of pharmacogenomic results included on laboratory reports.

Conclusions

The majority of participants agreed that adding certain actionable pharmacogenomic genes to the American College of Medical Genetics and Genomics SF list is reasonable; however, this was qualified with a need for additional resources to support implementation.
Acute Sodium Oxybate Intoxication: A Case Report and Review of the Literature
Authors: Drevin Guillaume , Briet Marie , Ferec Severine , Demiselle Julien , Beloncle François , Abbara Chadi
Published: August 2022

Purpose:

Despite a better safety profile than illicit γ-hydroxybutyric acid (GHB) and other GHB analogs, sodium oxybate continues to raise serious concerns regarding clinical safety. In this study, the authors report the case of near-fatal intoxication involving sodium oxybate–alcohol combination in a 40-year-old woman. In addition, a review of the literature on published cases of intoxication involving this pharmaceutical form of GHB was conducted. A 40-year-old woman was admitted to the intensive care unit in a coma after voluntary ingestion of 18 g of sodium oxybate and alcohol.

Methods:

The GHB plasma concentration was quantified to be 146 mg/L using liquid chromatography coupled with tandem mass spectrometry. An English literature search was performed using PubMed without any limiting period to identify all available scientific publications involving cases of sodium oxybate intoxication.

Results:

Six cases were identified. Five involved fatal intoxication cases, with GHB postmortem blood concentrations ranging from 11.5 to 3500 mg/L. One involved a nonfatal intoxication case with a GHB serum concentration of 569 mg/L 7 hours postingestion.

Conclusions:

In the present case, the estimated elimination half-life was 154 minutes. The risk of acute poisoning seems to be high considering the pharmacokinetic properties of sodium oxybate. Physicians and toxicologists must take such properties into account.
Relationship Between Plasmatic Metformin Concentration and Renal Replacement Therapy: A Multicenter Cohort Study
Authors: Demaretz Lise , Claisse Guillaume , Fanton-D’Andon Cornélie , Crepet Françoise , Herda Adel , Marin Clémence , Gonzalo Philippe , Mariat Christophe , Delavenne Xavier , Launay Manon
Published: August 2022

Background:

Metformin is the first-line treatment used for type 2 diabetes mellitus for more than 60 years. Metformin-associated lactic acidosis is the most serious adverse effect of metformin and is most widely defined as metabolic acidosis with elevated lactate levels in the presence of metformin. However, there is no consensus regarding the role of metformin in metformin-associated lactic acidosis onset. This study aimed to determine the metformin toxicity threshold (the metformin plasma concentration that predicts the occurrence of lactic acidosis) and the metformin dialysis threshold (the metformin plasma concentration strongly correlated with dialysis introduction).

Methods:

This was a retrospective multicenter cohort study conducted from January 1, 2013, to December 31, 2020. All consecutive adult patients with at least one metformin-detectable blood concentration measurement were included.

Results:

In total, 169 patients (92 men; mean age, 70 ± 11 years) were included in this study. A receiver operating characteristic analysis using Youden index showed that a metformin plasma concentration threshold of 17.9 mg/L was associated with lactic acidosis (sensitivity: 43.8%; specificity: 90.5%). Another receiver operating characteristic analysis using Youden index showed that a metformin plasma concentration threshold of 17.5 mg/L was associated with dialysis (sensitivity, 53.0%; specificity: 94.2%).

Conclusions:

The retrospective study design, lack of clinical data, and selection bias (patients in whom metformin was prescribed owing to pathological conditions) were major limitations, resulting in only preliminary findings. However, this study could serve as a basis for future prospective clinical studies to evaluate the use of these clinical threshold values as therapeutic guides.
Associations of hypertensive disorders of pregnancy and gestational diabetes mellitus with menopausal symptoms at midlife in Project Viva
Authors: Soria-Contreras Diana C. , Perng Wei , Rifas-Shiman Sheryl L. , Mínguez-Alarcón Lidia , Hivert Marie-France , Shifren Jan , Oken Emily , Chavarro Jorge E.
Published: August 2022

Objective

The aim of this study was to evaluate the associations of a lifetime history of hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM) with menopausal symptoms in midlife.

Methods

This was a secondary analysis of women participating in Project Viva, an ongoing cohort enrolled during pregnancy. The exposure was lifetime history of HDP or GDM assessed for the index pregnancy by review of outpatient and hospital medical records and for all other pregnancies by interview or questionnaire at study entry (1999-2002) and the midlife visit (2017-2021). The primary outcome was the Menopause Rating Scale (MRS) applied at the midlife study visit. We used linear or logistic regression models adjusted for covariates such as baseline age, race/ethnicity, education, married/cohabiting, household income, baseline parity, age at menarche, and body mass index at midlife.

Results

Of the 676 included participants, 120 (18%) had a history of HDP, and 47 (7%) had a history of GDM. The mean (SD) age was 52 (3.9) years at the midlife visit, and 48% of the participants had experienced menopause. There were no consistent differences in total, domain-specific, or individual symptoms in women with a history of HDP or GDM. A history of HDP and/or GDM was not associated with age at the onset of natural menopause.

Conclusions

Our findings do not support an association of a history of HDP or GDM with the severity of menopausal symptoms or age at the onset of natural menopause. Larger studies of women with a history of these pregnancy complications are needed to clarify their association with menopausal symptoms.
A survey of medical cannabis use during perimenopause and postmenopause
Authors: Dahlgren M. Kathryn , El-Abboud Celine , Lambros Ashley M. , Sagar Kelly A. , Smith Rosemary T. , Gruber Staci A.
Published: August 2022

Objective

Expanding access to legal cannabis has dovetailed with increased interest in medical cannabis (MC) use; however, there is a paucity of research examining MC use to alleviate menopause-related symptoms. This survey study assessed patterns of MC use in perimenopausal and postmenopausal individuals.

Methods

Participants (perimenopausal, n = 131; postmenopausal, n = 127) completed assessments of menopause-related symptomatology and cannabis use, including modes of use, type of use, and menopause-related symptoms addressed by MC use.

Results

Most participants reported current cannabis use (86.1%) and endorsed using MC for menopause-related symptoms (78.7%). The most common modes of use were smoking (84.3%) and edibles (78.3%), and the top menopause-related symptoms for MC use were sleep disturbance (67.4%) and mood/anxiety (46.1%). Relative to postmenopausal participants, perimenopausal participants reported significantly worse menopause-related symptomatology on the vasomotor and psychosocial subscales of the Menopause-Specific Quality of Life Questionnaire (Ps ≤ 0.04), including greater burden of anxiety (P = 0.01) and hot flash (P = 0.04) symptoms. In addition, perimenopausal participants reported higher incidence of depression (P = 0.03) and anxiety diagnoses (P < 0.01), as well as increased use of MC to treat menopause-related mood/anxiety symptoms relative to postmenopausal participants (P = 0.01).

Conclusions

Results suggest that many individuals are currently using MC as an adjunctive treatment for menopause-related symptoms, particularly sleep disturbance and mood/anxiety. Future research should examine the impact of different MC use characteristics (e.g., cannabinoid profiles) on the efficacy of MC use for menopause-related symptoms. Increased severity and prevalence of mood and anxiety symptoms in perimenopausal participants suggest promising targets for clinical trials of cannabinoid-based therapies.
Risk factors for delayed intrauterine device removal among menopausal women in rural China
Authors: Zong Zhanhong , Sun Xiaoming , Hearst Norman
Published: August 2022

Objective

More women in China have received intrauterine devices (IUDs) than in the rest of the world combined. Recent reports have recognized a growing problem of delayed removal of these IUDs after menopause, especially in rural China, but few studies have examined women's knowledge and other risk factors for delayed removal.

Methods

A total of 1,014 perimenopausal and postmenopausal women aged 45 to 64 years participating in a pilot program providing free IUD removal in rural China completed a questionnaire. We examined their knowledge about when IUDs should be removed and other demographic and reproductive health characteristics and the association of these factors with whether their IUD removal was on time or delayed using bivariate contingency analysis and multivariate logistic regression.

Results

A total of 40.2% of women were having their IUDs removed more than 2 years after menopause, and 67.9% did not know the correct time for IUD removal. Women who were older, less educated, had one child, had their IUD placed in a rural facility, and with no gynecological examination in the past 2 years were less likely to know when an IUD should be removed. In multivariate analysis, knowledge, the facility where the IUD was placed, and a recent gynecological examination were independent predictors of on-time removal. At least 170 women had received a gynecological examination after menopause without the IUD being removed at that time.

Conclusions

Lack of knowledge about timing for IUD removal and structural barriers in health service organization must be addressed to improve care for millions of women with IUDs in rural China.
Cross-cultural adaptation and psychometric evaluation of the Brazilian Portuguese version of the Vulvovaginal Symptoms Questionnaire
Authors: Alem Michele Elisabete Rúbio , Chaves Thais Cristina , de Figueiredo Vilena Barros , Beleza Ana Carolina Sartorato , Ferreira Cristine Homsi Jorge , da Silva Jordana Barbosa , Driusso Patricia
Published: August 2022

Objective

The aims of this study were to perform a cross-cultural adaptation of the Vulvovaginal Symptoms Questionnaire (VSQ) into Brazilian Portuguese (VSQ-Br) and evaluate its measurement properties (structural validity, construct validity, internal consistency, and reliability).

Methods

Cross-cultural adaptation was conducted through the translation, synthesis, and back-translation of the VSQ-Br. Subsequently, 314 women completed the Pelvic Floor Impact Questionnaire, Pelvic Floor Disorders Inventory, Medical Outcomes Study 36-Item Short-Form Health Survey, and VSQ-Br. Seven to 10 days later, participants completed the VSQ-Br for the second time. Data were submitted for confirmatory factor analysis. Cronbach α was used to verify internal consistency, and construct validity was assessed using Pearson correlation coefficient (r). Reliability was calculated using the intraclass correlation coefficient.

Results

Confirmatory factor analysis showed that the questions were grouped into four domains (symptoms, emotions, life impact, and sexual impact). The model showed good fit (>0.95). The Cronbach α in this study was 0.85, reflecting adequate internal consistency. Adequate reliability was confirmed, with an intraclass correlation coefficient total score of 0.80. The VSQ-Br had a weak correlation with the pelvic domain of the Pelvic Floor Disorders Inventory, the pelvic organ prolapse domain of the Pelvic Floor Impact Questionnaire, and pain, vitality, and the social aspect domains of the Medical Outcomes Study 36-Item Short-Form Health Survey.

Conclusions

The VSQ-Br was validated and had acceptable measurement properties for assessing vulvovaginal symptoms in Brazilian women.
The American Academy of Ophthalmology IRIS Registry (Intelligent Research In Sight): current and future state of big data analytics
Authors: Pershing Suzann , Lum Flora
Published: August 2022

Purpose of review

To describe the drivers, development, and current state of the American Academy of Ophthalmology IRIS Registry (Intelligent Research In Sight), and analytics involving deidentified aggregate IRIS Registry data.

Recent findings

The IRIS Registry has a core mission of quality improvement and reporting. In addition, analytic projects performed to date have included characterizing patient populations and diseases, incidence, and prevalence; clinical outcomes and complications; risk factors and effect modifiers; practice patterns; and trends over time. Pipeline projects include application of artificial intelligence and machine learning approaches for predictive modeling and analytics, disease mapping, detecting patterns and identifying cohorts, and optimizing treatment based on patient-specific characteristics.

The IRIS Registry is the nation's largest single specialty clinical registry, with unique data elements specific to ophthalmology. It offers a wealth of opportunities involving big data analytics, including traditional inferential statistics as well as machine learning and artificial intelligence approaches scalable on massive amounts of data.
Phakic intraocular lenses: an update and review for the treatment of myopia and myopic astigmatism in the United States
Authors: Moshirfar Majid , Webster Court R. , Ronquillo Yasmyne C.
Published: August 2022

Purpose of review

To review all phakic intraocular lenses (pIOLs) available in the United States for the correction of myopia or myopic astigmatism and offer a clinical approach to their proper use, postoperative follow-up, and analysis of visual and adverse outcomes.

Recent findings

In March 2022, the FDA approved the EVO/EVO+ Visian ICL for widespread use, adding this lens to the two others available (Verisyse, Visian ICL). Cataract formation, endothelial cell loss (ECL) and surgical reintervention remain the most common adverse events. There are discrepancies between studies on ECL following implantation with pIOLs, although trends can be deduced with meta-analysis. Posterior Chamber-pIOLs (PC-pIOLs), especially the EVO/EVO+, have an overall lower mean adverse effect and subjective patient symptom profile when compared to Iris Fixated-pIOLS (IF-pIOLs). Advancements in PC-pIOL sizing have provided a noticeable difference in visual and safety outcomes.

All pIOLs available in the United States provide high-quality visual correction of moderate to high myopia and/or myopia with astigmatism. Proper follow-up for ECL and cataract formation is warranted.
Private equity acquisitions: physician considerations at different stages of career
Authors: Khan Mohammed Ali
Published: August 2022

Purpose of review

To assess the impact of private equity acquisitions on physician career considerations, with particular attention to stage of career.

Recent findings

Recent studies have demonstrated a clear increase in private equity acquisitions in ophthalmology, particularly in retina-oriented practices. Survey-related publications of recent fellow graduates may provide insights regarding considerations of early career ophthalmologists, whereas commentaries from senior ophthalmologists offer insights to considerations of late career physicians. To date, no published evidence exists regarding the differential financial and/or professional effects of private equity acquisitions on ophthalmologists with regards to career stage. Such effects may differ on the specific structure, nature, and terms of the private equity acquisition.

Private equity acquisitions in ophthalmology may have several short-term, mid-term, and long-term effects on physicians over a variety of financial and career considerations. As such, there may be a differential effect of private equity acquisitions on early, mid, and late career physicians. Future outcome-related data will be necessary to fully understand the impact of private equity acquisitions on physicians both professionally and with regards to clinical care.
Artificial intelligence in dementia
Authors: Richardson Alexander , Robbins Cason B. , Wisely Clayton E. , Henao Ricardo , Grewal Dilraj S. , Fekrat Sharon
Published: August 2022

Purpose of review

Artificial intelligence tools are being rapidly integrated into clinical environments and may soon be incorporated into dementia diagnostic paradigms. A comprehensive review of emerging trends will allow physicians and other healthcare providers to better anticipate and understand these powerful tools.

Recent findings

Machine learning models that utilize cerebral biomarkers are demonstrably effective for dementia identification and prediction; however, cerebral biomarkers are relatively expensive and not widely available. As eye images harbor several ophthalmic biomarkers that mirror the state of the brain and can be clinically observed with routine imaging, eye-based machine learning models are an emerging area, with efficacy comparable with cerebral-based machine learning models. Emerging machine learning architectures like recurrent, convolutional, and partially pretrained neural networks have proven to be promising frontiers for feature extraction and classification with ocular biomarkers.

Machine learning models that can accurately distinguish those with symptomatic Alzheimer's dementia from those with mild cognitive impairment and normal cognition as well as predict progressive disease using relatively inexpensive and accessible ocular imaging inputs are impactful tools for the diagnosis and risk stratification of Alzheimer's dementia continuum. If these machine learning models can be incorporated into clinical care, they may simplify diagnostic efforts. Recent advancements in ocular-based machine learning efforts are promising steps forward.
Anterior segment reconstruction due to cosmetic iris implants placed in the anterior chamber
Authors: Fram Nicole R. , Snyder Michael , Pineda Roberto , Miller Kevin M. , Landreneau James , van den Berg Arthur , Rocha Karolinne Maia
Published: August 2022

A 27-year-old woman had BrightOcular iris implants placed for cosmetic purposes that changed eye color from brown to blue bilaterally. Of note, BrightOcular implants are not approved by the U.S. Food and Drug Administration (FDA) for use in the United States and have been associated with severe ocular complications. In keeping with their design, they were placed in the anterior chamber (AC) in both eyes of this patient; surgery was performed outside the United States.

As has been described previously and tragically in other cases, she developed chronic inflammation, intolerable glare, angle-closure glaucoma, corneal edema, and cataracts in both eyes. For medically unmanageable elevated intraocular pressure (IOP), she underwent diode laser cyclophotocoagulation (CPC) in both eyes, and eventually, an Ahmed tube shunt (New World Medical, Inc.) was placed in the right eye. Although she was advised and urged to have the iris implants removed, despite her ocular issues, she refused removal until intolerable glare and reduced vision ensued. Ultimately, both iris implants were extracted 5 years after implantation by a U.S. surgeon; the procedures resulted in corneal decompensation and progressive cataract development. Subsequent penetrating keratoplasty (PKP) was performed for the right eye, but it failed because of contact with the glaucoma tube shunt. She sought additional consultation and presented with the following findings: corrected distance visual acuity was 20/400 in the right eye and 20/40 in the left eye, IOP of 18 mm Hg in the right eye and 16 mm Hg in the left eye, pupils were nonreactive and fixed, and extraocular muscles and central visual field were normal. Pachymetry was 868 μm in the right eye and 653 μm in the left eye.

Anterior segment examination in the right eye revealed a failed corneal graft with 3+ edema, peripheral anterior synechiae (PAS) for 360 degrees, shallow AC, Ahmed tube shunt at the 11 o'clock position and remnant iris adherent to the graft–host junction for 270 degrees, 3+ posterior subcapsular cataract, and 2+ cortical cataract (Figure 1

JOURNAL/jcrs/04.03/02158034-202208000-00024/figure1/v/2023-08-19T002639Z/r/image-tiff

). The sclera revealed multiple circular and circumferential atrophic blue spots consistent with high-energy transscleral CPC (Figure 2

JOURNAL/jcrs/04.03/02158034-202208000-00024/figure2/v/2023-08-19T002639Z/r/image-tiff

). In the left eye, she had remnant fixed dilated iris for 270 degrees, missing iris superiorly for 3 clock hours, an adequate AC, and 2+ cortical cataract (Figure 3

JOURNAL/jcrs/04.03/02158034-202208000-00024/figure3/v/2023-08-19T002639Z/r/image-tiff

). Posterior segment examination revealed a 0.5 cup-to-disc ratio in both eyes with normal vessels, macula, vitreous, and retinal periphery, bilaterally.

Given this constellation of findings, how would you proceed?
Attaining optimal flange size with 5-0 and 6-0 polypropylene sutures for scleral fixation
Authors: Kronschläger Martin , Blouin Stéphane , Ruiss Manuel , Findl Oliver
Published: August 2022

A technique for achieving an optimal flange size with 5-0 polypropylene and 6-0 polypropylene used for flanged intrascleral intraocular lens fixation is described. Flange size in polypropylene sutures is dependent on heating length and independent of forceps grip during heating. It was identified that heating of 1 mm created the optimal flange size for a 5-0 polypropylene suture when used for a 27-gauge needle scleral tunnel and for a 6-0 polypropylene suture when used for a 30-gauge needle scleral tunnel. Alternatively, 2 mm heating of a 6-0 polypropylene suture fits well for a 27-gauge needle tunnel. Even gentle forceps grip caused flattening of the polypropylene sutures but did not influence shaping and sizing of the flange.
Development and evaluation of the patient-reported outcomes measurement information system (PROMIS) pediatric pain quality item bank and short form
Authors: Mara Constance A. , Carle Adam C. , Goldschneider Kenneth R. , Kashikar-Zuck Susmita , Sherry David D. , Dampier Carlton , Morgan Esi M.
Published: August 2022

Pain is a common problem among children, particularly those with pediatric chronic diseases. Multifaceted assessment of pain can improve communication about pain and help clinicians characterize, differentiate, and treat a patient's unique experience of pain. Pain quality is an important domain of pain, describing the subjective sensory experiences associated with pain as well as the affective experiences of pain. The aim of the current study was to quantitatively evaluate the measurement properties of the 59 Patient-Reported Outcomes Measurement Information System pediatric pain quality candidate items developed as part of the National Institutes of Health's Patient-Reported Outcomes Measurement Information System initiative with input from children and adolescents with chronic pain. Participants included N = 448 pediatric patients between 8 and 18 years of age with chronic health conditions with a prominent component of chronic or recurrent pain, including juvenile fibromyalgia, juvenile idiopathic arthritis, and sickle cell disease. A confirmatory factor analysis revealed a unidimensional model fit the data best, with 56 of the 59 items demonstrating good psychometric properties for inclusion in the final measure. In addition, a consensus-building method was used to establish 2 versions of a short form measure—one with 8 items focused primarily on the sensory pain qualities and one with 8 items focused on affective pain qualities. The final measure shows good reliability and validity, and is recommended for use in research and clinical care with pediatric populations.
Effectiveness and Tolerability of Lurasidone for Bipolar Types I and II and Other Specified Bipolar Depression
Authors: Takaesu Yoshikazu , Takeshima Minoru , Watanabe Koichiro
Published: August 2022

Background

There are few guidelines on the management of depressive episodes in patients with bipolar type II (BDII) and related disorders (other specified bipolar and related disorders [OSBD]). Lurasidone is a potential option for treating depressive episodes in BDII/OSBD. This retrospective chart review study aimed to examine the effectiveness and tolerability of lurasidone for use in patients with bipolar depression.

Methods

We reviewed 66 consecutive outpatients with bipolar depression who were prescribed lurasidone between June 2020 and January 2021 and examined 12-week outcomes. Fourteen patients were diagnosed with BDI, and 52 patients were diagnosed with BDII/OSBD (42 BDII and 10 OSBD). Depressive symptoms were evaluated by the Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR) at baseline and 2, 4, and 12 weeks. Tolerability was assessed throughout the study period by the incidence of adverse events, such as akathisia, nausea, and manic/hypomanic switch, as well as the lurasidone dropout rate due to adverse events.

Results

The total QIDS-SR score at 2 (P < 0.001), 4 (P < 0.001), and 12 weeks (P < 0.001) was significantly lower than that measured at baseline. Remission rate during study period was 29.1%. Of the 66 participants, 47 (71.2%) continued taking lurasidone and 27 (40.9%) and 16 (24.2%) reported adverse events and akathisia, respectively. No significant difference in total QIDS-SR score, dropout rate due to adverse events, rate of adverse events, or rate of akathisia was found between the BDII/OSBD and BDI groups.

Implications

Lurasidone is tolerated and could be effective for managing depressive episodes in patients with BDII/OSBD and BDI.
Clinical insights into drug-associated pancreatic injury
Authors: Barakat Monique T. , Abu-El-Haija Maisam , Husain Sohail Z.
Published: August 2022

Purpose of review

Drug-induced pancreatitis is one of the top three causes of acute pancreatitis. A drug exposure is traditionally determined to be the cause of pancreatitis only after other possible and common causes of pancreatitis have been excluded.

Recent findings

In this review, we challenge this traditional notion of drug-induced pancreatitis as a diagnosis of exclusion. Instead, we propose to shift the paradigm of conceptualizing what we term drug-associated pancreatic injury (DAPI); as a continuum of pancreatic injury that can be concomitant with other risk factors. The aims of this targeted review are to harness recent literature to build a foundation for conceptualizing DAPI, to highlight specific drugs associated with DAPI, and to describe a framework for future studies of DAPI.

Our hope is that probing and characterizing the mechanisms underlying the various types of DAPI will lead to safer use of the DAPI-inducing drugs by minimizing the adverse event of pancreatitis.
Recent advances in factor XII structure and function
Authors: Shamanaev Aleksandr , Litvak Maxim , Gailani David
Published: August 2022

Purpose of review

Factor XII (FXII), the precursor of the protease FXIIa, contributes to pathologic processes including angioedema and thrombosis. Here, we review recent work on structure-function relationships for FXII based on studies using recombinant FXII variants.

Recent findings

FXII is a homolog of pro-hepatocyte growth factor activator (Pro-HGFA). We prepared FXII in which domains are replaced by corresponding parts of Pro-HGA, and tested them in FXII activation and activity assays. In solution, FXII and prekallikrein undergo reciprocal activation to FXIIa and kallikrein. The rate of this process is restricted by the FXII fibronectin type-2 and kringle domains. Pro-HGA replacements for these domains accelerate FXII and prekallikrein activation. When FXII and prekallikrein bind to negatively charged surfaces, reciprocal activation is enhanced. The FXII EGF1 domain is required for surface binding.

We propose a model in which FXII is normally maintained in a closed conformation resistant to activation by intramolecular interactions involving the fibronectin type-2 and kringle domains. These interactions are disrupted when FXII binds to a surface through EGF1, enhancing FXII activation and prekallikrein activation by FXIIa. These observations have important implications for understanding the contributions of FXII to disease, and for developing therapies to treat thrombo-inflammatory disorders.