bluuebunny/crossref_metadata_2025 huggingface dataset:
Advanced Squamous Cell Carcinomas of the Pelvic and Perineal Region: A Comprehensive Genomic Profiling Study
Authors: Necchi Andrea , Spiess Philippe E , Bandini Marco , Basile Giuseppe , Grivas Petros , Bratslavsky Gennady , Jacob Joseph , Danziger Natalie , Lin Douglas , Decker Brennan , Sokol Ethan S , Huang Richard S P , Kulkarni Sanjay B , Ross Jeffrey S
Published: July 2022

Background

Advanced pelvic squamous cell carcinoma (pSCC) is a broad category of cancers affecting different pelvic organs and usually featuring unfavorable clinical outcomes. Thus, we aimed to assess genomic differences among pSCC cases and learn whether pSCC could potentially benefit from targeted therapies and/or immunotherapy.

Materials and Methods

A total of 1917 advanced pSCCs, including penile (penSCC), male urethral (murthSCC), male anal (manSCC), female urethral (furthSCC), vulvar (vulSCC), cervical (crvSCC), female anal (fanSCC), and vaginal (vagSCC), underwent comprehensive genomic profiling (CGP). We used hybrid capture-based CGP to evaluate recurrent genomic alterations (GAs). Tumor mutational burden (TMB) was determined on up to 1.1 Mb of sequenced DNA and microsatellite instability (MSI) was determined on up to 95 loci. Programmed cell-death-ligand-1 (PD-L1) expression was determined by immunohistochemistry (IHC; Dako 22C3).

Results

PIK3CA was the most frequently identified potentially “actionable” GA (22%-43%), followed by mTOR pathway [PTEN (0%-18%), FBXW7 (7%-29%)], and cell-cycle GAs. DNA-damage response (DDR) GAs and receptor-tyrosine kinase (RTK) targeted options were uncommon. NOTCH1 GAs were present in >15% of penSCC and vulvSCC. TMB ≥10 mut/Mb was >15% in manSCC, fanSCC, crvSCC, and vagSCC. PD-L1 high expression was >18% in all pSCC except urthSCC, manSCC, and vagSCC. HPV-16/18 detection was highest in manSCC, fanSCC, and crvSCC.

Conclusion

Despite similar histology, pSCCs can differ in GAs and HPV status. Overall, PIK3CA is the most frequent potentially “targetable” GA followed by mTOR and cell cycle pathway. RTK and DDR GAs are rare in pSCC. Immunotherapy could be considered for pSCC management based on TMB and PD-L1 expression.
Towards better Data Science to address racial bias and health equity
Authors: Nsoesie Elaine O , Galea Sandro
Published: July 2022

Data Science can be used to address racial health inequities. However, a wealth of scholarship has shown that there are many ethical challenges with using Data Science to address social problems. To develop a Data Science focused on racial health equity, we need the data, methods, application, and communication approaches to be antiracist and focused on serving minoritized groups that have long-standing worse health indicators than majority groups. In this perspective, we propose eight tenets that could shape a Data Science for Racial Health Equity research framework.
Reputation Building under Observational Learning
Authors: Pei Harry
Published: July 2022

A patient seller interacts with a sequence of myopic consumers. Each period, the seller chooses the quality of his product, and a consumer decides whether to trust the seller after she observes the seller’s actions in the last $K$ periods (limited memory) and at least one previous consumer’s action (observational learning). However, the consumer cannot observe the seller’s action in the current period. With positive probability, the seller is a commitment type who plays his Stackelberg action in every period. I show that under limited memory and observational learning, consumers are concerned that the seller will not play his Stackelberg action when he has a positive reputation and will play his Stackelberg action after he has lost his reputation. Such a concern leads to equilibria where the seller receives a low payoff from building a reputation. I also show that my reputation failure result hinges on consumers’ observational learning.
Mapping Quantitative Trait Loci for Type II Fusarium Head Blight Resistance in Two Wheat Recombinant Inbred Line Populations Derived from Yangmai 4 and Yangmai 5
Authors: Hu Wenjing , Gao Derong , Zhang Yong , Zheng Xu , Lu Chengbin , Wu Hongya , Xu Weigang , Cheng Shunhe , Jia Jizeng
Published: July 2022

Fusarium head blight (FHB) is a destructive wheat disease worldwide and significantly affects grain yield and quality in wheat. To understand the genetic basis underlying type II FHB resistance in two elite wheat cultivars—Yangmai 4 (YM4) and Yangmai 5 (YM5)—quantitative trait loci (QTL) mapping was conducted in two recombinant inbred line (RIL) populations derived from the crosses of YM4 and YM5 with susceptible cultivar Yanzhan 1 (YZ1), respectively. A survey with markers linked to Fhb1, Fhb2, Fhb4, and Fhb5 in landrace Wangshuibai indicated the nonexistence of these known FHB resistance genes or QTL in YM4, YM5, and YZ1. One overlapped resistance QTL was identified in both RIL populations (namely, QFhb.Y4.2D/QFhb.Y5.2D) with a large effect on FHB resistance. One novel resistance QTL (QFhb.Y4.5A) mapped on chromosome 5A was detected only in the YM4/YZ1 population. The resistance alleles of both QFhb.Y4.2D/QFhb.Y5.2D and QFhb.Y4.5A did not increase the plant height and did not significantly affect the heading date and flowering date. Kompetitive allele-specific PCR markers for QFhb.Y4.2D/QFhb.Y5.2D and QFhb.Y4.5A had been developed to verify in an additional set of 244 geographically diverse cultivars or lines. Pyramiding of the two resistance alleles decreased the percentage of symptomatic spikelets by 51.77% relative to the cultivars or lines without these two resistance alleles. QFhb.Y4.2D/QFhb.Y5.2D and QFhb.Y4.5A were shown to be useful alternatives in FHB resistance breeding programs. The results will facilitate marker-assisted selection for introgression of the favorable alleles for improving FHB resistance in breeding programs.
Optimal Resistance Management for Mixtures of High-Risk Fungicides: Robustness to the Initial Frequency of Resistance and Pathogen Sexual Reproduction
Authors: Taylor Nick P. , Cunniffe Nik J.
Published: July 2022

There is a strong consensus that selection for fungicide resistant pathogen strains can be most effectively limited by using applications of mixtures of fungicides designed to balance disease control against selection. However, how to do this in practice is not entirely characterized. Previous work indicates optimal mixtures of pairs of fungicides which are both at a high risk of resistance can be constructed using pairs of doses that select equally for both single resistant strains in the first year of application. What has not been addressed thus far is the important real-world case in which the initial levels of resistance to each fungicide differ, for example because the chemicals have been available for different lengths of time. We show how recommendations based on equal selection in the first year can be suboptimal in this case. We introduce a simple alternative approach, based on equalizing the frequencies of single resistant strains in the year that achieving acceptable levels of control is predicted to become impossible. We show that this strategy is robust to changes in parameters controlling pathogen epidemiology and fungicide efficacy. We develop our recommendation using a preexisting, parameterized model of Zymoseptoria tritici (the pathogen causing Septoria leaf blotch on wheat), which exemplifies the range of plant pathogens that predominantly spread clonally, but for which sexual reproduction forms an important component of the life cycle. We show that pathogen sexual reproduction can influence the rate at which fungicide resistance develops but does not qualitatively affect our optimal resistance management recommendation.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Lower Body Negative Pressure Decreases Intracranial Pressure and Internal Jugular Vein Cross‐Sectional Area
Authors: Watkins William , Baird Shannon , Clary Erika M , Hargens Alan R , Macias Brandon R
Published: July 2022

Introduction

Long‐term space flight subjects astronauts to both adaptive and deleterious health effects. Seven astronauts post six‐month space flight suffered decreased near vision, globe flattening, optic disc edema, choroidal folds, nerve fiber layer thickening, and cotton wool spots within the retinal nerve fiber layer. Additionally, lumbar punctures performed on astronauts diagnosed with optic disc edema after a six‐month mission showed increase in lumbar opening pressure, perhaps suggesting increased intracranial pressure (ICP). Although the mechanisms underlying these pathologies are not well understood, head‐ward fluid shifts experienced in microgravity may initiate these pathophysiologic processes. We hypothesized that during head‐down tilt (HDT), lower body negative pressure (LBNP) of 25 and 50 mmHg lowers ICP and decreases internal jugular vein cross‐sectional area (IJV CSA) due to lower extremity fluid shifts.

Methods

Fifteen (7F, 8M) healthy adult volunteers (age 19–60 years) were positioned at sitting posture (5 min), supine posture (5 min), 15° HDT (5 min), and 15° HDT with 10 min of LBNP of 25 and 50 mmHg with the order of HDT and HDT+LBNP randomized. Noninvasively, ICP was measured with the Cerebral Cochlear Fluid Pressure Analyzer, a device that measures tympanic membrane displacement (Vm). IJV CSA was measured by standard ultrasound.

Results

ICP and IJV CSA both decreased after exposure to LBNP (25 and 50 mmHg) at 15HDT. Compared to Vm at 15HDT (−322.13 ± 419.17 nL), Vm significantly increased to −232.38 ± 445.85 nL and −199.76 ± 429.69 nL during 15HDT with LBNP (25 mmHg) and LBNP (50 mmHg), respectively (Fig. 1). A 40.0% increase in Vm (indicating a reduction in ICP) was evident after 10 minutes of 15HDT+LBNP (50 mmHg) relative to HDT posture. Further, compared to IJV CSA at 15HDT (1.50 ± 0.33 cm2), IJV CSA was significantly reduced to 0.83 ± 0.42 cm2 during 15HDT+LBNP (50 mmHg) (Fig. 2). With respect to 15HDT posture, 15HDT+LBNP (50 mmHg) for 10 minutes decreased IJV CSA by 44.5%. For both ICP and IJV CSA, there were no significant differences among the supine, 15HDT+LBNP (25 mmHg), and 15HDT+LBNP (50 mmHg) conditions.

Discussion

LBNP mitigates the effect of head‐ward fluid shifts experienced during microgravity simulated by HDT and thus, decreases both ICP and IJV CSA. This study is the first to measure ICP and IJV CSA noninvasively during LBNP and also give quantitative evidence for a foot‐ward fluid shift concomitant with decreased ICP. Further studies are necessary to elucidate how LBNP lowers ICP and IJV dimensions.

Support or Funding Information

This study was supported by NSBRI through NCC 9‐58 to BRM, NASA grant NNXAJ12G to ARH, and NIH grant 5 T35 HL 7491‐35 to WW.
Getting to the heart of the opioid crisis
Authors: Daher Nicole , Bohensky Jolene
Published: July 2022

Infective endocarditis is a potentially fatal infection of the endocardium or valves that can result from IV drug abuse. This article describes a patient with infective endocarditis masked by opioid abuse withdrawal symptoms. This challenging presentation brings to the forefront the need for clinicians to be aware of and understand the changing risk factors and demographics of patients with nonspecific infective endocarditis.
Managing a patient with diabetes receiving systemic glucocorticoids
Authors: Petite Sarah E.
Published: July 2022

Limited evidence exists for managing patients with diabetes who are taking systemic glucocorticoids. This article discusses the therapeutic recommendations for patients with diabetes who are receiving systemic glucocorticoid therapy.
The Association of Selective Serotonin Reuptake Inhibitors With Delirium in Critically Ill Adults: A Secondary Analysis of the Bringing to Light the Risk Factors and Incidence of Neuropsychologic Dysfunction in ICU Survivors ICU Study
Authors: Austin C. Adrian , Yi Joe , Lin Feng-Chang , Pandharipande Pratik , Ely E. Wesley , Busby-Whitehead Jan , Carson Shannon S.
Published: July 2022

OBJECTIVES:

To assess the association between selective serotonin reuptake inhibitors (SSRI) and delirium in the subsequent 24 hours after drug administration in critically ill adults.

DESIGN:

Retrospective cohort study utilizing the Bringing to Light the Risk Factors and Incidence of Neuropsychologic Dysfunction in ICU Survivors dataset.

SETTING:

Two large U.S. ICUs.

PATIENTS:

Critically ill adults admitted to a medical or surgery ICU between March 2007 and May 2010 with respiratory failure or shock.

INTERVENTIONS:

Our primary outcome was the occurrence rate of delirium or coma during each day in the ICU. Our exposure variable was SSRI administration on the prior day in the ICU. As a secondary question, we assessed the association of SSRI administration and delirium the same day of SSRI administration in the ICU.

MEASUREMENTS AND MAIN RESULTS:

We analyzed 821 patients. The median age was 61.2 years old (interquartile range, 50.9–70.7), and 401 (48.8%) were female. A total of 233 patients (28.4%) received prescribed SSRIs at least once during their ICU admission. Delirium was present in 606 (74%) of the patients at some point during hospitalization in the ICU. Coma was present in 532 (64.8%) of the patients at some point during hospitalization in the ICU. After adjusting for multiple potential confounding factors, we found that SSRI administration in the ICU was associated with lower odds of delirium/coma (odds ratio [OR], 0.75; 95% CI, 0.57–1.00) the next day. An SSRI administered on the same day reduced the odds of delirium/coma as well (OR, 0.66; 95% CI, 0.50–0.87).

CONCLUSIONS:

SSRI administration is associated with decreased risk of delirium/coma in 24 hours and on the same day of administration in critically ill patients in a medical or surgical ICU.
Association between trends of mortality and incidence, survival and stage at diagnosis for six digestive and respiratory cancers in United States (2009–2013)
Authors: Teglia Federica , Boffetta Paolo
Published: July 2022

Background

A decrease in cancer mortality has been reported in the USA, possibly due to decreased incidence, downstaging and improved survival. The aim of the present study is to estimate the contribution of these factors on the trend in cancer mortality.

Methods

Data on incidence, mortality, stage at diagnosis, and overall and stage-specific survival for six common digestive and respiratory cancers (esophagus, stomach, colorectal, liver, pancreas and lung) during 2009–2013 in the USA from the surveillance, epidemiology and end results (SEER) program, was analyzed using generalized linear models separately among men and women.

Results

Our study showed a decrease in mortality for esophageal (−0.09/100 000/year and −0.03/100 000/year), stomach (−0.11/100 000/year and −0.05/100 000/year), colorectal (−0.45/100 000/year and −0.29/100 000/year) and lung cancer (−1.89/100 000/year in men and −0.78/100 000/year in women) in men and women, respectively: for all of them, except lung cancer in women, there was a decrease in the incidence of comparable or greater magnitude; stage distribution and survival also contributed to the decrease in mortality for lung and colorectal cancer. Mortality from pancreatic cancer was stable: an increase in incidence was counterbalanced by an improvement in survival. Mortality from liver cancer increased, driven by an increase in mortality that was not offset by favorable trends in stage distribution and survival.

Conclusions

Trends in mortality were primarily affected by changes in incidence; an increase in the proportion of local stage at diagnosis and improved survival, although evident for some cancers, played a lesser role in mortality trends.
Molecular Determinants for the High-Affinity Blockade of Human Ether-à-go-go-Related Gene K+ Channel by Tolterodine
Authors: Wang Na , Yang Yang , Wen Jing , Fan Xin-Rong , Li Jian , Xiong Bing , Zhang Jin , Zeng Bo , Shen Jian-Wu , Chen Gui-Lan
Published: July 2022

Tolterodine is a first-line antimuscarinic drug used to treat overactive bladder. Adverse cardiac effects including tachycardia and palpitations have been observed, presumably because of its inhibition of the human ether-à-go-go-related gene (hERG) K+ channel. However, the molecular mechanism of hERG channel inhibition by tolterodine is largely unclear. In this study, we performed molecular docking to identify potential binding sites of tolterodine in hERG channel, and two-microelectrode voltage-clamp to record the currents of hERG and its mutants expressed in Xenopus oocytes. The results of computational modeling demonstrated that phenylalanine at position 656 (F656) and tyrosine at position 652 (Y652) on the S6 helix of hERG channel are the most favorable binding residues of tolterodine, which was validated by electrophysiological recordings on Y652A and F656A hERG mutants. The Y652A and F656A mutations decreased inhibitory potency of tolterodine 345-fold and 126-fold, respectively. The Y652A mutation significantly altered the voltage dependence of channel inhibition by tolterodine. For both the wild-type and the mutant channels, tolterodine reduced the currents in a time-dependent manner, and the blockade occurred with the channel activated. Tolterodine did not interfere with hERG channel deactivation, whereas channel inactivation greatly impaired its blocking effect. The inhibition of hERG channel by tolterodine is independent of its action on muscarinic acetylcholine receptors. In conclusion, tolterodine is an open-state blocker of hERG K+ channel with nanomolar potency. Y652 and F656, 2 aromatic residues on the inner S6 helix, are responsible for the high-affinity binding of tolterodine to hERG channel.
Association of dietary intake of n-3 polyunsaturated fatty acids with breast cancer risk in pre- and postmenopausal Chinese women
Authors: Zhang Zhuo-Lin , Ho Suzanne C , Liu Kai-Yan , Mo Xiong-Fei , Feng Xiao-Li , Li Lei , Zhang Cai-Xia
Published: July 2022

Objective

This study aimed to evaluate the associations between breast cancer risk and intake of n-3 polyunsaturated fatty acids (PUFAs) and/or n-3 PUFA subclasses in Chinese women, and determine whether these associations varied with menopausal status or clinical characteristics.

Methods

A hospital-based case-control study including 1,589 cases and 1,621 age-frequency-matched controls was conducted. Dietary data were assessed by a validated food frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals were obtained using multiple unconditional logistic regression models after controlling for potential confounders.

Results

Higher intake of marine n-3 PUFAs and total n-3 PUFAs was associated with lower risk of breast cancer, with adjusted OR quartile 4 v.1 (95% confidence intervals) of 0.68 (0.55-0.84) and 0.56 (0.42-0.75), respectively. Dietary a-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid were also inversely associated with breast cancer risk, with adjusted ORs (95% confidence intervals) of 0.51 (0.38-0.70), 0.68 (0.55-0.84), 0.68 (0.55-0.85), and 0.76 (0.61-0.94), respectively. In stratified analyses, these inverse associations between risk and dietary n-3 PUFAs were more evident among premenopausal women and women with ER+, PR+ and ER+PR+ tumors. A decreased risk of breast cancer was significantly associated with increasing n-3 PUFA intake in obese/overweight women, but not in women of normal weight. There was a significant interaction between linoleic acid and marine n-3 PUFAs.

Conclusions

High intake of n-3 PUFAs and n-3 PUFA subtypes was associated with a lower risk of breast cancer, especially among premenopausal women and women with ER+ and/or PR+ subtype breast cancer.
Clinicopathological features of endometrial lesions in asymptomatic postmenopausal women with thickened endometrium
Authors: Ai Fangfang , Wang Yifan , Wang Yiling , Wang Jiayi , Zhou Liane , Wang Shijun
Published: July 2022

Objective

To analyze the clinical and pathological features of asymptomatic postmenopausal women with an incidentally detected increase in endometrial thickness (ET) by transvaginal ultrasound examination and discuss the cutoff value of ET for the timely discovery of endometrial malignancy.

Methods

This was a retrospective study of postmenopausal women with asymptomatic thickened endometrium (greater than or equal to 5 mm) screened by transvaginal ultrasound who were referred to the gynecology department at Xuanwu Hospital between January 2018 and March 2021. Data on participant demographics, clinical characteristics, and histopathology outcomes were collected. We stratified the participants into the benign group and malignant group according to pathology results and assessed differences between the two groups. A receiver operating characteristic curve was used to identify the cutoff value of ET for predicting endometrial malignancy in postmenopausal women with asymptomatic thickened endometrium.

Results

A total of 163 eligible cases were included in the analysis. The results showed that only ET was significantly different between the two groups. The median ET was significantly higher in the malignant group than in the benign group (1.20 vs 0.80, P = 0.023). The optimal cutoff value of ET was 10 mmwith the maximum AUC (0.881, 95% CI 0.810-0.952, P = 0.024), and the sensitivity and specificity for the diagnosis of endometrial malignancy were 100%and 80%, respectively. Among the 47 women with ET ≥ 10mm, the prevalence of endometrial malignancy was 6.3%, which was significantly higher than that among women with ET < 10mm (P = 0.023).

Conclusion

For postmenopausal women with asymptomatic endometrial thickening, the prevalence of endometrial malignancy is significantly higher when ET is ≥ 10 mm. If ET is ≥ 10mm, further histopathological testing should be recommended to exclude endometrial malignancy. Further large-sample and prospective studies are needed to determine the predictive value of ET.
Exercise training and vascular function in postmenopausal individuals: a systematic review and meta-analysis
Authors: Brislane Áine , Sculthorpe Nicholas F. , Davenport Margie H. , Beaumont Alexander
Published: July 2022

Importance

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality for menopausal individuals. Flow-mediated dilation (FMD), a surrogate marker of CVD, improves with aerobic exercise training in healthy and nonhealthy cohorts. However, systematic evaluation and precise estimate of this effect for menopausal individuals are unknown.

Objective

We conducted a systematic review with meta-analysis to evaluate the influence of exercise training on FMD in postmenopausal individuals.

Evidence Review

Studies were identified from systematic search of major electronic databases (PubMed, ScienceDirect, and Cochrane Library) from inception to February 2021. Healthy, postmenopausal individuals were included, following an aerobic exercise intervention assessing FMD. A random-effects meta-analysis was used to calculate a pooled effect size (mean difference [MD]) with 95% confidence interval. Heterogeneity was assessed using I
2 statistics. Metaregression was used to assess the association between changes in FMD and physical characteristics (eg, blood pressure, age, baseline FMD) and intervention details (metabolic equivalents and change in maximal oxygen uptake [∆V˙o
2max]). For variables that significantly correlated, a multiple metaregression model was used to assess the accounted variance in between-study ∆FMD%. Study quality was assessed using the National Heart, Lung, and Blood Institute assessment tool.

Findings

Nine studies, including 11 interventions (6 controlled interventions and 5 pre-post interventions; N = 182), with age range of 52 ± 4 to 64 ± 7 years underwent quantitative pooling of data. Exercise training significantly improved ∆FMD% (MD, 0.99; 95% confidence interval, 0.46-1.52; P < 0.001). Between-study heterogeneity was large and statistically significant (I
2 = 93.8%, P < 0.001). Post hoc analysis based on study design identified significant heterogeneity in the MD in ∆FMD% between controlled and pre-post study interventions (P < 0.05). According to multiple metaregression, diastolic and systolic blood pressure and ∆V˙o
2max significantly predicted ∆FMD% (Q = 15.74, df = 3, P < 0.01, R
2 = 0.72).

Conclusions and Relevance

Aerobic exercise training improves FMD for postmenopausal individuals, and this observation was greater among controlled versus pre-post interventions. A higher resting blood pressure and the greatest ∆V˙o
2max yielded the largest improvements in FMD.
Postmenopausal giant ovarian tumor: a rare case report and literature review
Authors: Fu Lingyang , Ren Fang , Ma Xiaoxin , Xu Xiaoxuan , Wang Tifang , Li Meijun , Guo Zhiqiang
Published: July 2022

Objective

A giant ovarian tumor weighing 62 kg and containing 51 L cyst fluid is rare among postmenopausal women, and an early diagnosis contributes to a good prognosis.

Methods

We report a case of a 62-kg giant ovarian tumor, the largest ovarian tumor ever reported in China. A 64-year-old woman with a giant pelvic abdominal mass underwent surgery. Because of the occurrence of serious perioperative and postoperative complications, we then conducted a literature review to investigate possible risk factors for severe complications.

Results

During the operation, 51 L of intratumoral fluid was drained, and a giant ovarian tumor of approximately 62 kg was removed. The pathological examination showed that the tumor was a mucinous borderline one. The patient had perioperative hypotension and postoperative respiratory failure. After a comprehensive literature review, we found that the occurrence of serious complications may not be related to tumor volume and weight but age and the amount of fluid in the tumor.

Conclusions

The high incidence of severe complications should be carefully considered when huge ovarian tumors or tumors containing a large amount of tumor fluid in postmenopausal women are removed.
Impact of the CBT-Meno protocol on menopause-specific beliefs, dysfunctional attitudes, and coping behaviors
Authors: Donegan Eleanor , Frey Benicio N. , McCabe Randi E. , Streiner David L. , Fedorkow Donna M. , Furtado Melissa , Green Sheryl M.
Published: July 2022

Objective

A recent clinical trial demonstrated that a group cognitive-behavioral therapy protocol for menopause (CBT-Meno; Green et al. Menopause 2019;26(9):972-980) was effective in reducing menopausal symptoms, including vasomotor and depressive symptoms. The current analyses evaluated the effectiveness of CBT-Meno in improving menopause-specific beliefs, dysfunctional attitudes associated with depression, and menopause-specific behaviors.

Methods

In a subset of participants from the larger trial, women assigned to CBT-Meno or waitlist and who had completed symptom, cognitive, and behavioral measures at least at baseline were included. Assessments were conducted at baseline, 12 weeks after baseline, and 3 months after treatment. Measures included the Hot Flash Related Daily Interference Scale, the vasomotor subscale of the Greene Climacteric Scale, the Beck Depression Inventory II, the Hot Flush Beliefs Scale, the Dysfunctional Attitudes Scale, and the Hot Flush Behavior Scale (HFBehS).

Results

As reported in the main study outcomes (Green et al. Menopause 2019;26(9):972-980), CBT-Meno participants reported greater improvements than waitlist in terms of vasomotor symptom interference and depressive symptoms (Hot Flash Related Daily Interference Scale, Beck Depression Inventory II; partial eta-squared [η
2
p] = 0.15-0.18), although not in vasomotor severity (Greene Climacteric Scale [vasomotor subscale]; η
2
p = 0.05). CBT-Meno participants reported greater improvements than waitlist in menopause-specific beliefs (Hot Flush Beliefs Scale; η
2
p = 0.08-0.12), dysfunctional attitudes (Dysfunctional Attitudes Scale; η
2
p = 0.09), and menopause-specific behaviors (HFBehS; η
2
p = 0.08-0.12). Within-group analyses showed improvements in CBT-Meno on all variables (d = 0.38-1.26) except in cooling strategies (d = 0.18). Gains in CBT-Meno were maintained from posttreatment to 3-month follow-up, although a decrease in positive coping behaviors was observed (HFBehS—positive behavior subscale; d = 0.99).

Conclusions

The CBT-Meno protocol is effective in improving menopause-related symptoms and a broader range of outcomes, including problematic beliefs about menopause, dysfunctional attitudes related to depression, and menopause-specific behaviors.
New concepts in heart failure with preserved ejection fraction and hypertension
Authors: Joury Abdulaziz , Gupta Tripti , Krim Selim R.
Published: July 2022

Purpose of review

Hypertension (HTN) remains the most common and strongest contributing factor to the development of heart failure with preserved ejection fraction (HFpEF). In this review, we aim to summarize the pathophysiological processes linking HTN to HFpEF and highlight novel concepts in medical and device-based management of HFpEF and HTN.

Recent findings

Despite the global increase in the prevalence of HFpEF, there has been limited benefit in current medication and device-based therapy for this complex syndrome. The hallmark of HFpEF is an elevated left intra-atrial and ventricular pressure and exertional dyspnea. Traditional medications used for treating HTN in patients with reduced left ventricular ejection fraction have unclear benefits in patients with HFpEF. Careful analysis of emerging medications such as angiotensin receptor–neprilysin inhibitor and sodium–glucose co-transporter-2 inhibitors showed benefit in reducing not only blood pressure but also hospitalizations in patients with HFpEF. Current data on device-based therapy aims to reduce left intra-atrial pressure, ventricular pressure and stimulate baroreceptors to lower blood pressure; however, needs further investigation.

The nexus of HTN and HFpEF remains strong and complex. Although traditional medications for treating HFrEF did not affect long-term outcomes, novel therapies with angiotensin receptor neprilysin-inhibitor and sodium-glucose co-transporter-2 inhibitor offer promising results. Many device-based interventions in the HFpEF population are being developed with the aim to reduce left intra-atrial and ventricular pressure; however, their role in HFpEF hypertensive patients needs to be further investigated.
The potential of CRISPR-Cas9 prime editing for cardiovascular disease research and therapy
Authors: Bharucha Nike , Arias Ariel , Karakikes Ioannis
Published: July 2022

Purpose of review

The ability to edit any genomic sequence has led to a better understanding of gene function and holds promise for the development of therapies for genetic diseases. This review describes prime editing - the latest CRISPR-Cas9 genome editing technology. Prime editing enables precise and accurate genome editing in terminally differentiated, postmitotic cells like cardiomyocytes, paving the way for therapeutic applications for genetic cardiomyopathies.

Recent findings

Prime editing has been used to precisely insert up to 40 bases, create deletions up to 80 base pairs, and can perform all 12 possible transition and transversion base mutations with lower indels and off-target effects than other genome editing methods. The development of several software tools has simplified the experimental design and led to increased efficiency of the process. Improvements in methods for in-vivo delivery of the prime editing components should enable this technology to be used to edit the genome in patients.

Prime editing has the potential to revolutionize the future of biomedical research and transform cardiovascular medicine. Improved understanding of the prime editing process and developments in agent design, efficacy and delivery will benefit scientists and patients and could be an effective way to cure cardiovascular diseases.
Influence of the cardio-ankle vascular index on chronic-phase left ventricular dysfunction after ST-segment elevation myocardial infarction
Authors: Kirigaya Jin , Iwahashi Noriaki , Abe Takeru , Gohbara Masaomi , Hanajima Yohei , Horii Mutsuo , Minamimoto Yugo , Okada Kozo , Matsuzawa Yasushi , Hibi Kiyoshi , Kosuge Masami , Ebina Toshiaki , Tamura Kouichi , Kimura Kazuo
Published: July 2022

Objective:

This study aimed to investigate the possible influence of arterial stiffness assessed by the cardio-ankle vascular index (CAVI) on chronic-phase left ventricular dysfunction in patients with ST-segment elevation myocardial infarction (STEMI).

Methods:

A total of 208 consecutive patients with first STEMI (age, 64 ± 11 years; 86% men) who underwent reperfusion therapy within 12 h of onset were enrolled. We analysed arterial stiffness by measuring CAVI in a stable phase after admission and performed two-dimensional echocardiography at baseline and 7 months’ follow-up. Subsequently, we assessed left ventricular global longitudinal strain (LV-GLS) to evaluate left ventricular function. A total of 158 (75.9%) patients underwent baseline cardiac magnetic resonance (CMR). We estimated left ventricular infarct size by measuring peak levels of creatine kinase-myocardial band (CK-MB), and CMR-late gadolinium enhancement (LGE).

Results:

On the basis of the median CAVI value, the patients were allocated into high CAVI (CAVI ≥ 8.575) and low CAVI (CAVI < 8.575) groups. The groups showed no statistically significant differences in LV-GLS at baseline (-13.5% ± 3.1 vs. -13.9% ± 2.7%, P = 0.324). However, LV-GLS was significantly worse in the high CAVI group than in the low-CAVI group at 7 months (-14.0% ± 2.9 vs. -15.6% ± 3.0%, P < 0.001). Stratified by CAVI and peak CK-MB or LGE, the four groups showed significant differences in LV-GLS at 7 months after STEMI (both P < 0.001). Multivariate linear regression analysis with the forced inclusion model showed that CAVI was an independent predictor of LV-GLS at 7 months (P = 0.015).

Conclusion:

CAVI early after STEMI onset was significantly associated with chronic-phase LV-GLS. In addition, combining CAVI with CK-MB or LGE improves its predictive ability for evaluation of chronic-phase LV-GLS. Thus, the arterial stiffness assessment by CAVI was an important factor related to chronic-phase left ventricular dysfunction after the first STEMI.
Antihypertensive treatment effect on exercise blood pressure and exercise capacity in older adults
Authors: Jones Siana , Schultz Martin G. , Park Chloe , Tillin Therese , Chaturvedi Nishi , Hughes Alun D.
Published: July 2022

Background:

An exaggerated blood pressure (BP) response to exercise and low exercise capacity are risk factors for cardiovascular disease (CVD). The effect of pharmacological antihypertensive treatment on exercise BP in older adults is largely unknown. This study investigates these effects accounting for differences in exercise capacity.

Methods:

Participants enrolled in the Southall and Brent Revisited (SABRE) study undertook a 6-min stepper test with expired gas analysis and BP measured throughout exercise. Participants were stratified by antihypertensive treatment status and resting BP control. Exercise systolic and diastolic BP (exSBP and exDBP) were compared between groups using potential outcome means [95% confidence intervals (CIs)] adjusted for exercise capacity. Exercise capacity was also compared by group.

Results:

In total, 659 participants were included (mean age ± SD: 73 ± 6.6 years, 57% male). 31% of normotensive and 23% of hypertensive older adults with controlled resting BP had an exaggerated exercise BP. ExSBP was similar between normotensive and treated/controlled individuals [mean (95%CI): 180 (176 184) mmHg vs. 177 (173 181) mmHg, respectively] but was higher in treated/uncontrolled and untreated/uncontrolled individuals [mean (95% CI): 194 (190 197) mmHg, P < 0.001 and 199 (194 204) mmHg, P < 0.001, respectively]; these differences persisted after adjustment for exercise capacity and other confounders. Exercise capacity was lower in treated vs. normotensive individuals [mean (95% CI) normotensive: 16.7 (16.0,17.4) ml/kg/min]; treated/controlled: 15.5 (14.8,16.1) ml/kg/min, P = 0.009; treated/uncontrolled: [15.1 (14.5,15.7) ml/kg per min, P = 0.001] but was not reduced in untreated/uncontrolled individuals [mean (95% CI): 17.0 (16.1,17.8) ml/kg per min, P = 0.621].

Conclusion:

Irrespective of resting BP control and despite performing less exercise, antihypertensive treatment does not fully mitigate an exaggerated BP response to exercise suggesting residual CVD risk in older adults.
Complement factors D and C3 cross-sectionally associate with arterial stiffness, but not independently of metabolic risk factors: The Maastricht Study
Authors: Jin Shunxin , Reesink Koen D. , Kroon Abraham A. , de Galan Bastiaan , van der Kallen Carla J.H. , Wesselius Anke , Schalkwijk Casper G. , Stehouwer Coen D.A. , van Greevenbroek Marleen M.J.
Published: July 2022

Background:

Arterial stiffness predicts cardiovascular outcomes. The complement system, particularly the alternative complement pathway, has been implicated in cardiovascular diseases. We herein investigated the associations of factor D, the rate-limiting protease of the alternative pathway, and C3, the central complement component, with arterial stiffness.

Methods:

In 3019 population-based participants (51.9% men, 60.1 ± 8.2 years, 27.7% type 2 diabetes [T2D], oversampled]), we measured carotid-femoral pulse wave velocity (cfPWV), carotid distensibility coefficient (DC) and carotid Young's elastic modulus (YEM), and plasma concentrations of factors D and C3. We conducted multiple linear regression to investigate the association of factors D and C3 (main independent variables, standardized) with cfPWV (primary outcome) and DC and YEM (secondary outcomes), adjusted for potential confounders.

Results:

Per SD higher factors D and C3, cfPWV was 0.41 m/s [95% confidence interval: 0.34; 0.49] and 0.33 m/s [0.25; 0.41] greater, respectively. These associations were substantially attenuated when adjusted for age, sex, education, mean arterial pressure, and heart rate (0.08 m/s [0.02; 0.15] and 0.11 m/s [0.05; 0.18], respectively), and were not significant when additionally adjusted for T2D, waist circumference and additional cardiovascular risk factors (0.06 m/s [−0.01; 0.13] and 0.01 m/s [−0.06; 0.09], respectively). Results were comparable for carotid YEM and DC. In persons with T2D, but not in those without, the association between factors D and cfPWV was significant in the fully adjusted model (0.14 m/s, [0.01; 0.27], P = 0.038, P
interaction < 0.05).

Conclusion:

The strong association of plasma factors D and C3 with arterial stiffness in this population-based cohort was not independent of T2D and other metabolic risk factors. Our data suggest that a possible causal pathway starting from alternative complement activation may via hypertension and T2D contribute to greater arterial stiffness.
Gonioscopy and Angle-Based Glaucoma Surgical Training on Human Eyes in the Wet Lab
Authors: Pujari Amar , Rakheja Vaishali , Dada Tanuj , Verma Saurabh , Gupta Shikha , Agarwal Tushar , Sharma Namrata , Titiyal Jeewan S.
Published: July 2022

Précis:

Human corneoscleral rims provide a low cost model and resource to enhance angle based glaucoma surgical training skills.

Purpose:

To understand the feasibility, utility, and efficacy of a low-cost model for performing anterior chamber angle gonioscopy and micro-surgery on human corneoscleral tissues in wet lab on resident skill enhancement.

Methods:

Post-keratoplasty residual corneoscleral rims and/or the expired donor corneoscleral buttons were included for the purpose of this study. Initially, inverted rims were used to demonstrate the basic angle anatomy on a slit lamp bio-microscope. Central hazy cornea was then replaced with an artificial cornea and an artificial anterior chamber to simulate indirect gonioscopy, direct gonioscopy, goniotomy, and other angle-based surgeries. Direct gonioscopy and goniotomy exercises (as a means to simulate intraoperative gonioscopy and other angle-based surgeries respectively) were evaluated quantitatively, and the rest qualitatively.

Results:

A total of 65 residents were included in the exercise. The mean age was 26.69±1.74 years. Amongst these, 55 ophthalmology residents performed the basic examination, that is, slit lamp mounted angle anatomy examination (n=55) and artificial chamber mounted indirect gonioscopic examination through artificial cornea (n=55). In the second exercise, 10 glaucoma fellows performed the direct gonioscopic and the goniotomy exercises on artificial chamber. The fellows demonstrated a statistically significant improvement in interpretation and surgical skill enhancement concurrent with reduction in time taken with increasing number of attempts (P<0.05). In the third simulation exercise, micro-stent placement within the Schlemm’s canal, subconjunctival space, and the suprachoroidal space was re-produced successfully on multiple occasions.

Conclusions:

The residual human corneoscleral rims proved to be an important resource for teaching both the basic examination skills and those required for transitioning to advanced intraoperative gonioscopy and goniotomy skills. These low cost, easy to adapt models can be incorporated within the curriculum for improved glaucoma training of both the residents and the glaucoma fellows.
Relationship Between Optical Coherence Tomography and Anterior Chamber Depth After Pupillary Dilation in Primary Angle Closure Suspects
Authors: Kao Brandon Wei-Hsiang , Yonamine Sean , Zhao Mengya , Oatts Julius , Yu Yinxi , Ying Gui-Shuang , Xu Xun , Han Ying
Published: July 2022

Précis:

Anterior chamber depth (ACD) change after pupillary dilation is correlated with lens vault (LV) and anterior chamber width (ACW), as observed by swept-source optical coherence tomography (SS-OCT) at both horizontal and vertical scans in patients with primary angle closure suspect and cataract.

Purpose:

The purpose of this study is to evaluate the association between ACD and other anterior chamber parameters after pharmacological dilation in patients with primary angle closure suspect and cataract.

Patients and Methods:

SS-OCT was performed for 78 patients at baseline and 1 hour after pharmacological dilation. Measurements were taken at 8 evenly spaced axes at 250, 500, and 750 μm from the scleral spur. Pearson correlation coefficient (ρ) was used to evaluate the relationship between averaged ACD change and other SS-OCT parameters. Multivariable regression analyses were performed to determine the parameters that predict ACD change.

Results:

Across all 14 dimension and angle parameters, 12 parameters at the 270-degree axis and 10 parameters at the 0-degree axis yielded significant correlations with ACD change (ρ=0.24–0.55, P<0.05). Angle parameters were most significantly correlated to ACD change 750 µm from the scleral spur. The prediction model for ACD change after pharmacological dilation at 0 degree included decreased LV, wider ACW, and increased trabecular iris space area (all P≤0.001). The prediction model for ACD change at 270 degrees included: decreased LV, wider ACW, larger change in anterior chamber volume, larger baseline anterior chamber volume, and smaller baseline angle opening distance (all P≤0.03).

Conclusions:

LV and ACW, as measured in both vertical and horizontal scans, were found to be determinants of the ACD change after pharmacological pupillary dilation. Examination of these parameters may help identify patients at higher risk of developing angle-closure disease.
Mechanistic insights on the effect of crocin, an active ingredient of saffron, on atherosclerosis in apolipoprotein E knockout mice
Authors: Makaritsis Konstantinos P. , Kotidis Charalampos , Papacharalampous Konstantina , Kouvaras Evangelos , Poulakida Eirini , Tarantilis Petros , Asprodini Eftichia , Ntaios George , Koukoulis George Κ. , Dalekos George Ν. , Ioannou Maria
Published: July 2022

Background

We investigated the effect of crocin treatment on atherosclerosis and serum lipids in apolipoprotein E knockout (ApoE−/−) mice, focusing on the expression of endothelial nitric oxide synthase (eNOS) and hypoxia-induced factor-1 alpha (HIF-1α).

Methods

Sixty-two animals were divided into two groups and randomly allocated to crocin (100 mg/kg/day) in drinking water or no crocin. All mice were maintained on standard chow diet containing 5% fat. Crocin was initiated at the 16th week of age and continued for 16 additional weeks. At 32 weeks of age, after blood sampling for plasma lipid determination and euthanasia, proximal aorta was removed and 3 μm sections were used to measure the atherosclerotic area and determine the expression of eNOS and HIF-1α by immunohistochemistry.

Results

Each group consisted of 31 animals (17 males and 14 females in each group). Crocin significantly reduced the atherosclerotic area (mm2 ± SEM) in treated mice compared to controls, both in males (0.0798 ± 0.017 vs. 0.1918 ± 0.028, P < 0.002, respectively) and females (0.0986 ± 0.023 vs. 0.1765 ± 0.025, P < 0.03, respectively). eNOS expression was significantly increased in crocin-treated mice compared to controls, both in males (2.77 ± 0.24 vs. 1.50 ± 0.34, P=0.004, respectively) and females (3.41 ± 0.37 vs. 1.16 ± 0.44, P=0.003, respectively). HIF-1α expression was significantly decreased in crocin-treated mice compared to controls, both in males (21.25 ± 2.14 vs. 156.5 ± 6.67, P < 0.001, respectively) and females (35.3 ± 7.20 vs. 113.3 ± 9.0, P < 0.01, respectively). No difference was noticed in total, low- and high-density lipoprotein cholesterol between treated and control mice.

Conclusion

Crocin reduces atherosclerosis possibly by modulation of eNOS and HIF-1α expression in ApoE−/− mice without affecting plasma cholesterol.
Does the use of polymer-free drug eluting stents improve clinical outcomes of patients undergoing percutaneous coronary interventions?
Authors: Loewenstein Itamar , Hochstadt Aviram , Merdler Ilan , Chorin Ehud , Wenkert Atalia , Moshkovits Yonatan , Erez Jonathan , Toledano Ella , Arbel Yaron , Halkin Amir , Ben-Shoshan Jeremy , Finkelstein Ariel , Banai Shmuel , Konigstein Maayan
Published: July 2022

Background

Implantation of drug eluting stents (DES) is the mainstay treatment for patients requiring percutaneous coronary intervention (PCI). The polymer coating of DES has been associated with inflammatory response, increased arterial injury and long-term in-stent restenosis and thrombosis. Polymer-free stents (PFS) were designed to overcome limitations of polymer-coated stents (PCS). Our aim was to compare clinical outcomes of patients undergoing PCI with PFS versus contemporary PCS.

Methods

This is a prospective, open-label registry study enrolling consecutive all-comers patients admitted to a single center and undergoing PCI using contemporary DES. Clinical outcomes were compared between patients treated with PFS and PCS. The primary endpoint was target lesion revascularization (TLR) at 12 months. Subgroup analyses were conducted for diabetic and nondiabetic patients.

Results

Overall, 1664 patients were included: 928 (55.8%) of which were treated with PFS and 736 (44.2%) with PCS for 2046 and 1462 lesions, respectively. At 12 months, TLR rates were not significantly different between the groups (1.7% vs. 2.3% for PFS and PCS, respectively, P = 0.48). The use of PFS did not improve clinical outcomes among diabetic patients in comparison with PCS. Target vessel revascularization and major adverse cardiac events rates were also similar between groups, regardless of diabetes status.

Conclusion

Newer generation DES offer excellent results in diabetic and nondiabetic patients without significant differences in outcomes between PCS and PFS.