bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term changes in plasma proteomic profiles in premenopausal and postmenopausal Black and White women: the Atherosclerosis Risk in Communities study
Authors: Appiah Duke , Schreiner Pamela J. , Pankow James S. , Brock Guy , Tang Weihong , Norby Faye L. , Michos Erin D. , Ballantyne Christie M. , Folsom Aaron R. 
Published: August 2022

Abstract

Objective
The activity, localization, and turnover of proteins within cells and plasma may contribute to physiologic changes during menopause and may influence disease occurrence. We examined cross-sectional differences and long-term changes in plasma proteins between premenopausal and naturally postmenopausal women.

Methods
We used data from 4,508 (19% Black) women enrolled in the Atherosclerosis Risk in Communities study. SOMAscan multiplexed aptamer technology was used to measure 4,697 plasma proteins. Linear regression models were used to compare differences in proteins at baseline (1993‐1995) and 18-year change in proteins from baseline to 2011‐2013.

Results
At baseline, 472 women reported being premenopausal and 4,036 women reported being postmenopausal, with average ages of 52.3 and 61.4 years, respectively. A greater proportion of postmenopausal women had diabetes (15 vs 9%), used hypertension (38 vs 27%) and lipid-lowering medications (10 vs 3%), and had elevated total cholesterol and waist girth. In multivariable adjusted models, 38 proteins differed significantly between premenopausal and postmenopausal women at baseline, with 29 of the proteins also showing significantly different changes between groups over the 18-year follow-up as the premenopausal women also reached menopause. These proteins were associated with various molecular/cellular functions (cellular development, growth, proliferation and maintenance), physiological system development (skeletal and muscular system development, and cardiovascular system development and function), and diseases/disorders (hematological and metabolic diseases and developmental disorders).

Conclusions
We observed significantly different changes between premenopausal and postmenopausal women in several plasma proteins that reflect many biological processes. These processes may help to understand disease development during the postmenopausal period.
Differing effects of oral conjugated equine estrogen and transdermal estradiol on vitamin D metabolism in postmenopausal women: a 4-year longitudinal study
Authors: Santoro Anna Maria , Simpson Christine A. , Cong Elaine , Haas Andrea , Sullivan Rebecca R. , Parziale Stephen , Deng Yanhong , Insogna Karl L. 
Published: August 2022

Abstract

Objective
The aim of this study was to examine the effect of either conjugated equine estrogen or transdermal estradiol on vitamin D metabolism in postmenopausal women.

Methods
Twenty-five women from the Kronos Early Estrogen Prevention Study who were randomized to conjugated equine estrogen 0.45 mg/d and 20 women who were treated with transdermal estradiol 50 mg/d (patch replaced weekly) were analyzed in the present study. All participants received micronized progesterone for 12 days per month.

Results
There was no significant treatment effect on serum total 25-hydroxyvitamin D over 48 months in either study group, and there were no significant differences between treatment arms. In contrast, at 12 months, directly measured free 25-hydroxyvitamin D was significantly higher in the transdermal estradiol group than in the conjugated equine estrogen group. Directly measured free 25-hydroxyvitamin D subsequently increased significantly from 12 to 48 months in both treatment arms. Calculated free 25-hydroxyvitamin D was also significantly higher in the transdermal estradiol group at 36 months. Vitamin D–binding protein decreased significantly in both treatment groups from 12 to 48 months, but at 48 months, least square mean values were no different based on treatment assignment.

Conclusions
Directly measured free 25-hydroxyvitamin D levels, but not serum total 25-hydroxyvitamin D levels, are different within the first 12 months of estrogen replacement depending on the preparation. However, this difference is transient, in that there were no differences at 36 or 48 months. These findings suggest that there may be a short-term benefit to prescribing transdermal estradiol for women who are either vitamin D deficient or vitamin D insufficient.
Remote multimodality monitoring of maternal physiology from the first trimester to postpartum period: study results
Authors: Zielinska Agata P. , Mullins Edward , Magni Elena , Zamagni Giulia , Kleprlikova Hana , Adams Olive , Stampalija Tamara , Monasta Lorenzo , Lees Christoph 
Published: August 2022

Objectives:
Current antenatal care largely relies on widely spaced appointments, hence only a fraction of the pregnancy period is subject to monitoring. Continuous monitoring of physiological parameters could represent a paradigm shift in obstetric care. Here, we analyse the data from daily home monitoring in pregnancy and consider the implications of this approach for tracking pregnancy health.

Methods:
Prospective feasibility study of continuous home monitoring of blood pressure, weight, heart rate, sleep and activity patterns from the first trimester to 6 weeks postpartum.

Results:
Fourteen out of 24 women completed the study (58%). Compared to early pregnancy [week 13, median heart rate (HR) 72/min, interquartile range (IQR) 12.8], heart rate increased by week 35 (HR 78/min, IQR 16.6; P = 0.041) and fell postpartum (HR 66/min, IQR 11.5, P = 0.021). Both systolic and diastolic blood pressure were lower at mid-gestation (week 20: SBP 103 mmHg, IQR 6.6; DPB 63 mmHg, IQR 5.3 P = 0.005 and P = 0.045, respectively) compared to early pregnancy (week 13, SBP 107 mmHg, IQR 12.4; DPB 67 mmHg, IQR 7.1). Weight increased during pregnancy between each time period analyzed, starting from week 15. Smartwatch recordings indicated that activity increased in the prepartum period, while deep sleep declined as pregnancy progressed.

Conclusion:
Home monitoring tracks individual physiological responses to pregnancy in high resolution that routine clinic visits cannot. Changes in the study protocol suggested by the study participants may improve compliance for future studies, which was particularly low in the postpartum period. Future work will investigate whether distinct adaptative patterns predate obstetric complications, or can predict long-term maternal cardiovascular health.
One year of isometric exercise training for blood pressure management in men: a prospective randomized controlled study
Authors: O’Driscoll Jamie M. , Edwards Jamie J. , Coleman Damian A. , Taylor Katrina A. , Sharma Rajan , Wiles Jonathan D. 
Published: August 2022

Objective:
Isometric exercise training (IET) over 4–12 weeks is an effective antihypertensive intervention. However, blood pressure (BP) reductions are reversible if exercise is not maintained. No work to date has investigated the long-term effects of IET on resting BP.

Methods:
We randomized 24 unmedicated patients with high-normal BP to a 1-year wall squat IET intervention or nonintervention control group. Resting BP and various clinically important haemodynamic variables, including heart rate (HR), stroke volume (SV), cardiac output (CO) and total peripheral resistance (TPR) were measured pre and post the 1-year study period.

Results:
One year of IET produced statistically significant reductions in resting systolic (-8.5 ± 5 mmHg, P < 0.001) and diastolic (-7.3 ± 5.8 mmHg, P < 0.001) BP compared with the control group. There was also a significant reduction in resting HR (-4.2 ± 3.7 b/min, P = 0.009) and a significant increase in SV (11.2 ± 2.8 ml, P = 0.012), with no significant change in CO (0.12 ± 2.8 l/min, P = 0.7). TPR significantly decreased following IET (-246 ± 88 dyne·s/cm5, P = 0.011). Adherence to the IET sessions was 77% across all participants (3x IET sessions per week), with no participant withdrawals.

Conclusion:
This novel study supports IET as an effective long-term strategy for the management of resting BP, producing clinically important, chronic BP adaptations in patients at risk of hypertension. Importantly, this work also demonstrates impressive long-term adherence rates, further supporting the implementation of IET as a means of effective BP management in clinical populations.
Comprehensive Analysis of circRNA-Associated-ceRNA Networks in Human Corneal Endothelial Dysfunction
Authors: Qiu Ji-ni , Shan Kun , Xiang Jun , Gu Jia-yu , Zhou Rong-mei , Zhang Xue-ling , Zhang Chao-ran , Xu Jian-jiang 
Published: August 2022

Purpose:
Circular RNAs (circRNAs) are a novel class of endogenous noncoding RNAs that regulate gene expression through the competitive endogenous RNA (ceRNA) mechanism. CircRNA-associated-ceRNA networks are closely related to oxidative stress–related diseases. Oxidative stress–induced dysfunction of the corneal endothelium (CE) is a major pathological feature in many corneal diseases. This study was aimed to analyze circRNA-associated-ceRNA networks in oxidative stress–induced CE dysfunction.

Methods:
A CE dysfunction model was established using human corneal endothelial cells (HCECs) treated with H2O2 at a concentration of 250 μM for 4 hours at 37°C. High-throughput sequencing was conducted to determine the expression profiles of circRNA, miRNA, and mRNA. Bioinformatic analyses, including Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes analysis, were conducted to identify the potential biological modules and pathologic pathways of dysregulated circRNAs. CircRNA-associated-ceRNA networks were established based on the data of sequencing and bioinformatic analyses.

Results:
We obtained 108 differentially expressed circRNAs, including 77 upregulated and 31 downregulated circRNAs. GO analysis suggested that dysregulated circRNAs were mainly targeted to protein quality control for misfolded or incompletely synthesized proteins (biologic process), nuclear chromatin (cellular component), and ubiquitin protein ligase binding (molecular function). GO terms related to CE functions responding to oxidative stress were also identified. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that dysregulated circRNAs were mostly enriched in the adherens junction pathway. Network analysis identified several potential therapeutic targets for CE dysfunction.

Conclusions:
CircRNAs are significantly dysregulated in HCECs under oxidative stress. The circRNA-associated-ceRNA networks are closely related to HCEC functions. Targeting these networks might provide novel therapies for CE dysfunction.
(Even Off-Label) Cochlear Implantation in Single-Sided Deafness and Asymmetric Hearing Loss Results in Measurable Objective and Subjective Benefit
Authors: Sydlowski Sarah A. , Farrokhian Nathan , Carrozza Marisa , Jamis Carmen , Woodson Erika 
Published: August 2022

Objective
To quantify objective and subjective outcomes in cochlear implant (CI) recipients with asymmetric hearing loss, including single-sided deafness (SSD) whose candidacy was determined on an ear-specific basis when word recognition was 50% or less.

Study Design
Retrospective case review.

Setting
Tertiary referral center.

Background
The effectiveness of CI in cases of SSD and asymmetric hearing loss (AHL) has been described in terms of tinnitus suppression, improved speech recognition in quiet and noise, enhanced localization ability, and improved quality of life. However, CI is not yet routinely offered as a top option or standard of care for these individuals. Recent Food and Drug Administration (FDA) labeling limits aided word recognition in the ear to be implanted to only 5% in cases of AHL/SSD, which is significantly poorer than 40 to 50%, which is often referenced in cases of bilateral hearing loss. Anecdotal experience suggests that patients with much better preoperative word recognition than 5% can benefit from CI.

Methods
We conducted a retrospective chart review of all adult CI candidates, with one ear exhibiting consonant-nucleus-consonant (CNC) word recognition scores at least 50% and one ear not meeting CI candidacy (i.e., CNC word recognition >50%). Outcome variables of interest included word and sentence recognition and subjective handicap questionnaires (hearing, tinnitus, dizziness) and the Speech Spatial Qualities questionnaire.

Results
Statistically and clinically significant improvement in speech understanding (word, sentence, sentence in noise) was noted for both the SSD and AHL groups in the implanted ear. There were statistically and clinically significant subjective improvements noted for both groups on the Hearing Handicap Inventory, the Tinnitus Handicap Inventory, and the Speech Spatial Qualities questionnaire by 1 month after activation. There were no significant differences between the AHL and SSD groups on either objective or subjective measures of the implanted ear. Individual word understanding improved for the majority of recipients across both groups and is not dependent on meeting the FDA criteria of less than 5%.

Conclusions
Cochlear implantation is a viable option with measurable objective and perceived benefits for recipients with preoperative aided CNC word scores exceeding current FDA labeling. There is no significant difference between the AHL and SSD groups, suggesting that candidacy and outcome expectations should be set based on the ear to be implanted alone, without regard for the ability of the better hearing ear.
Surgical Reconsideration of Traumatic Facial Paralysis
Authors: Kim Jin , Lee Jeon Mi , Nam Sung-Il , Baek Moo Jin 
Published: August 2022

Introduction
Despite the different pathophysiological mechanisms underlying Bell's palsy, in assessing severe traumatic facial paralysis, many surgeons rely on electrophysiological criteria to determine whether facial nerve exploration is warranted. To assess the value of preoperative electroneurography (ENoG) and the time of surgery, we analyzed data from three tertiary medical centers.

Materials and Methods
The records of 517 patients with a degenerative ratio (DR) greater than 80% on ENoG were collected, and two groups were defined: group A (90% DR ≤ ENoG) and group B (80% DR ≤ ENoG < 90% DR). The difference in effectiveness of surgery versus conservative treatment was analyzed based on the postoperative outcome determined by the House-Brackmann grading system. The independent-samples t test was used to compare surgery with conservative treatment for each day of surgical exploration.

Result
In groups A and B, the average recovery time from facial paralysis was better in patients who had undergone surgical exploration than in those who had been treated conservatively. In group A, the difference was significant only for patients who underwent surgery within 8 days. In group B, a significant difference was found for patients who underwent surgery within 16 days but also for surgery performed 20 and 30 days after the onset of facial paralysis.

Discussion
In the surgical treatment of facial paralysis, the criteria for trauma patients should be distinguished from those of patients with Bell's palsy. In traumatic facial paralysis, some axons are more vulnerable to external collapse, and the degree of Wallerian degeneration of the peripheral nervous system will vary depending on the type of injury. The results of this study will help to identify those patients with traumatic facial paralysis who should be treated surgically and when they should be treated.
Transtympanic Visualization of Cochlear Implant Placement With Optical Coherence Tomography: A Pilot Study
Authors: Wang Junzhe , Chawdhary Gaurav , Farrell Joshua , Yang Xiaojie , Farrell Matthew , MacDougall Dan , Trudel Mathieu , Shoman Nael , Morris David P. , Adamson Robert B. A. 
Published: August 2022

Objective
This study aimed to evaluate the ability of transtympanic middle ear optical coherence tomography (ME-OCT) to assess placement of cochlear implants (CIs) in situ.

Patient
A 72-year-old man with bilateral progressive heredodegenerative sensorineural hearing loss due to work-related noise exposure received a CI with a slim modiolar electrode for his right ear 3 months before his scheduled checkup.

Intervention
A custom-built swept source ME-OCT system (λ
o = 1550 nm, ∆λ = 40 nm) designed for transtympanic middle ear imaging was used to capture a series of two- and three-dimensional images of the patient's CI in situ. Separately, transtympanic OCT two-dimensional video imaging and three-dimensional imaging were used to visualize insertion and removal of a CI with a slim modiolar electrode in a human cadaveric temporal bone through a posterior tympanotomy.

Main Outcome Measure
Images and video were analyzed qualitatively to determine the visibility of implant features under ME-OCT imaging and quantitatively to determine insertion depth of the CI.

Results
After implantation, the CI electrode could be readily visualized in the round window niche under transtympanic ME-OCT in both the patient and the temporal bone. In both cases, characteristic design features of the slim modiolar electrode allowed us to quantify the insertion depth from our images.

Conclusions
ME-OCT could potentially be used in a clinic as a noninvasive, nonionizing means to confirm implant placement. This study shows that features of the CI electrode visible under ME-OCT can be used to quantify insertion depth in the postoperative ear.
Preoperative neoadjuvant targeted therapy with lenvatinib for inoperable thyroid cancer
Authors: Iwasaki Hiroyuki , Toda Soji , Murayama Daisuke , Matsui Ai , Kadoya Mei 
Published: August 2022

Rationale:
Neoadjuvant chemotherapy (NAC) with lenvatinib for inoperable thyroid cancer has not been established. We have previously reported a case of NAC in 2020. Here, we report 5 cases of thyroid cancer treated with NAC from 2019 to 2021, including 3 cases of inoperable differentiated thyroid cancer, 1 case of anaplastic thyroid cancer, and 1 case of concomitant differentiated thyroid cancer and anaplastic thyroid cancer.

Patient concerns and diagnosis:
Four patients were pathologically diagnosed with thyroid cancer by cytology or biopsy, and 1 patient was diagnosed with follicular neoplasm. These patients had pleural, laryngeal, and esophageal invasion, and radical surgery would have required an extended operation and increased surgical risks.

Interventions:
Five patients with thyroid cancer displaying invasion of adjacent organs who were inoperable were preoperatively treated with lenvatinib alone; they underwent surgery when the tumor stopped shrinking.

Outcomes:
The best response was achieved after 1.7 to 4.7 months (average 2.9 months) of lenvatinib treatment, and the dose was reduced due to the occurrence of adverse events. Surgery was successfully performed when the tumor stopped shrinking.

Conclusion:
The prognosis of patients with inoperable thyroid cancer is poor; however, patients can undergo surgery safely after NAC treatment with lenvatinib. We hope that NAC will be considered as a treatment option for advanced thyroid cancers and serve as a precedent for safe treatment. This can be a new treatment option to eliminate unresectable thyroid cancers.
Severe iron-deficiency anemia and candida esophagitis
Authors: Zaki Hany A. , Iftikhar Haris , Bashir Khalid , Taha Noheir Moustafa , Elmoheen Amr 
Published: August 2022

Rationale:
Iron deficiency is the commonest cause of anemia globally. Oral candidiasis is a commonest fungal infection while esophageal candidiasis (EC) is the commonest cause of infectious esophagitis. There is limited literature on the association between EC and severe iron-deficiency anemia (IDA).

Patient concerns:
A 38-year-old woman who was previously healthy presented to our emergency facility with pain, swelling, and tenderness in both limbs. The patient appeared extremely pale with conjunctival pallor but no oral ulcers or scleral icterus.

Diagnosis:
A basic blood investigation showed that she had severe IDA (hemoglobin level 2.9 g/dL).

Interventions:
The emergency department management plan involved electrocardiography (ECG), chest radiography (CXR), blood investigations, occult stool analysis, and activation of the blood transfusion protocol. Extensive inpatient work up including further blood investigations, esophagogastroduodenoscopy (EGD), colonoscopy, pan-computed tomography (CT) was performed to determine the cause of IDA. Endoscopic diagnosis was candida esophagitis. Patient was started on fluconazole 200 mg for 14 days.

Outcomes:
The patient remained stable and pain-free while in hospital. She tolerated a full oral diet. She was discharged on oral iron tablets, esomeprazole, and fluconazole. She remained symptom-free. Her hemoglobin and liver function tests remained stable on follow-up.

Lessons:
This case shows that patients with severe IDA might have a higher level of susceptibility to EC or vice versa. This association may exist and needs further research.
Sinonasal Amoebiasis
Authors: McLean Anne C. , Bishop Justin A. , Guarner Jeannette , Montone Kathleen T. , Morris C. Paul , Sloan Philip , Rooper Lisa M. 
Published: August 2022

While amoebic infection is widely known as a cause of gastroenteritis, keratitis, and meningoencephalitis, amoebae are challenging to recognize at unexpected sites. Despite multiple case reports of sinonasal amoebiasis, amoebic infection is not regularly considered in the differential diagnosis of sinonasal necroinflammatory disease. Here, we aim to characterize the pathologic features of sinonasal amoebiasis to facilitate better recognition. We identified sinonasal amoebiasis in 4 men, median age of 67 years (range: 37 to 71 y). All were immunocompromised, including 2 with chronic lymphocytic leukemia, 1 with human immunodeficiency virus, and 1 with human immunodeficiency virus and kidney transplant. Patients presented with nasal mucosal necrosis or polypoid masses, with facial ulceration in 1 patient and distant dermal nodules in another. Biopsies displayed extensive necrotic debris and inflammation. Although amoebic cysts were abundant in 3 cases, they were mistaken for yeast at frozen section in 1 case; 1 case showed only rare trophozoites that were not recognized on initial biopsy. Periodic acid Schiff and Grocott Methenamine Silver stains highlighted the organisms, and polymerase chain reaction confirmed Acanthamoeba species in 3 cases tested. 2 patients responded well to antiprotozoal medications, but 2 died of disease. Overall, sinonasal amoebiasis presents as a necroinflammatory process in patients immunocompromised for various reasons. Amoebae can mimic other organisms or be incredibly scarce, requiring active consideration to recognize amoebiasis and differentiate it from overlapping conditions like invasive fungal sinusitis, granulomatosis with polyangiitis, and natural killer/T-cell lymphoma. Because sinonasal amoebiasis is highly treatable when diagnosed promptly, pathologists play a critical role in the recognition of this rare necroinflammatory disease.