bluuebunny/crossref_metadata_2025 huggingface dataset:
Initiation of aboveground organ primordia depends on combined action of auxin,ERECTAfamily genes, and PINOID
Authors: DeGennaro Daniel , Urquidi Camacho Ricardo Andres , Zhang Liang , Shpak Elena D
Published: June 2022

Leaves and flowers are produced by the shoot apical meristem (SAM) at a certain distance from its center, a process that requires the hormone auxin. The amount of auxin and the pattern of its distribution in the initiation zone determine the size and spatial arrangement of organ primordia. Auxin gradients in the SAM are formed by PIN-FORMED (PIN) auxin efflux carriers whose polar localization in the plasma membrane depends on the protein kinase PINOID (PID). Previous work determined that ERECTA (ER) family genes (ERfs) control initiation of leaves. ERfs are plasma membrane receptors that enable cell-to-cell communication by sensing extracellular small proteins from the EPIDERMAL PATTERNING FACTOR/EPF-LIKE (EPF/EPFL) family. Here, we investigated whether ERfs regulate initiation of organs by altering auxin distribution or signaling in Arabidopsis (Arabidopsis thaliana). Genetic and pharmacological data suggested that ERfs do not regulate organogenesis through PINs while transcriptomics data showed that ERfs do not alter primary transcriptional responses to auxin. Our results indicated that in the absence of ERf signaling the peripheral zone cells inefficiently initiate leaves in response to auxin signals and that increased accumulation of auxin in the er erecta-like1 (erl1) erl2 SAM can partially rescue organ initiation defects. We propose that both auxin and ERfs are essential for leaf initiation and that they have common downstream targets. Genetic data also indicated that the role of PID in initiation of cotyledons and leaves cannot be attributed solely to regulation of PIN polarity and PID is likely to have other functions in addition to regulation of auxin distribution.
Diaporthe spp. Is Confirmed as the Main Fungus Associated with Defective Turkish Hazelnuts
Authors: Arciuolo Roberta , Chiusa Giorgio , Castello Giuseppe , Leggieri Marco Camardo , Spigolon Nicola , Battilani Paola
Published: June 2022

The aim of this study was to identify the fungi associated with Turkish hazelnuts and verify and confirm the role of Diaporthe in causing kernel defects. Hazelnuts were sampled from 10 hazelnut orchards in seven Turkish provinces (Samsun, Ordu, Girensun, Trabzon, Sakarya, Düzce, and Zonguldak) during the early and full ripening stages in 2018, 2019, and 2020. Fungal isolation and identification at the genus level were performed for healthy hazelnut kernels and those with visible or hidden defects. Several fungal genera were isolated; those with a mean incidence greater than 10% were Aspergillus, Botryosphaeria, Diaporthe, Fusarium, and Penicillium. The incidence of Diaporthe spp. was higher in the full ripening stage than in the early ripening stage; it was also higher in kernels with defects than in healthy kernels. A similar pattern was observed for Botryosphaeria, but the opposite pattern was observed for Aspergillus. Diaporthe positively correlated with both hidden (ρ = 0.80) and visible defects (ρ = 0.77), confirming its key role in causing hazelnut defects. The role of Botryosphaeria appears limited to hidden defects; however, additional work is needed to substantiate this last finding. There is also a need to clarify the eventual interaction of Diaporthe with Aspergillus. The low incidence of defective hazelnuts among the 3 years of sampling precluded the role of meteorological factors in the incidence of hazelnut defects from being elucidated.
Endometrial Receptivity Testing and Adjustment to Window of Implantation Timing Improve Pregnancy Rates with Assisted Reproductive Technology (ART) [A334]
Authors: Rose-Reneau Zak , Riggs Ryan N. , Anderson Derica K.
Published: June 2022

INTRODUCTION:

For decades, reproductive endocrinology and infertility (REI) research focused on solely on the creation of a viable embryo to increase pregnancy rates. Recently, research has identified the impact of endometrial adhesion molecule expression during the window of implantation (WOI) as playing a major role in embryo implantation.

METHODS:

This is a retrospective case-control study of women undergoing assisted reproductive technology and the effects of the IgenomixEndometrial Receptivity Assay (ERA) on pregnancy success rates following frozen embryo transfer.

RESULTS:

ERA results showed 29 of 60 patients were normal, 20 of 60 patients were Early Receptive (WOI existing 12 hours later than expected), and 11 of 60 patients were Pre-Receptive (WOI existing 24 hours later than expected). Ninety-one percent of patients with a corrected abnormal ERA had successful pregnancies, whereas only 72% achieved successful pregnancy without using ERA to assess for their WOI (P≤.01; odds ratio, 3.82).

CONCLUSION:

Endometrial Receptivity Assay testing has a significant impact on successful pregnancy rates among patients undergoing ART. Women should be encouraged to undergo ERA testing to ensure accurate timing of their WOI for embryo transfer. Although numerous medication changes can be made by the physician to improve implantation success rates, if the WOI timing is not accounted for, those changes are for naught because the endometrium is not prepared to receive the embryo and subsequent embryo implantation into the endometrium will not occur. The use of ERA could save the patient tens of thousands of dollars and shave years off their time to achieving successful pregnancies.
Prevalence and Risk Factors for Prolonged Persistent Postpartum Urinary Retention [A346]
Authors: Ayyash Mariam , Briskin Rebeccah , Calimente H. Stefan , Kallabat Hana , Estanol Maria Victoria
Published: June 2022

INTRODUCTION:

Prolonged persistent postpartum urinary retention (PPUR) lasting longer than 3 days postpartum is a rare condition, with limited literature available on the topic. This study assesses prevalence and risk factors for PPUR.

METHODS:

This is an institutional review board–approved retrospective cross-sectional study of 60,352 deliveries from 2013 to 2020, at an academic tertiary care center in Detroit, Michigan. Women with non-iatrogenic, PPUR were identified. Demographic and delivery data was analyzed with descriptive statistics.

RESULTS:

There were 14 (0.023%) patients with PPUR, with a mean age of 30.1 ± 6.1, and mean BMI of 27.3 ± 9.5 kg/m2. There were 11 of 14 (79%) vaginal deliveries, all of which were full term (mean gestational age was 39 weeks), and mean birth weight of 3,401 ± 433 g. There were 7 of 14 (50%) primiparous patients, and 12 of 14 (85.7%) received neuraxial anesthesia. The mean length of the second stage of labor was 2.65 ± 2.1 hours. The median onset of urinary retention was 10 hours postpartum. Median duration of resolution was 6.5 days. The mean duration from birth to first void was 5.7 ± 3.7 hours. The mean post-void residual (PVR) was 851 ± 353 mL. There were 6 of 14 (42.8%) patients requiring prolonged Foley catheter insertion, and the remaining 8 of 14 (57.2%) required intermittent catheterization.

CONCLUSION:

PPUR is a rare but relevant condition with a prevalence of 0.023%. Similar to other limited literature, neuraxial anesthesia, vaginal delivery, and prolonged second stage suggest possible risk factors. More research is needed to understand PPUR risk factors. Standard guidelines can be implemented to help with evaluation and to expedite diagnosis and management.
Prolonged Duration of Oxytocin Exposure Increases Obstetric Hemorrhage Risk [A135]
Authors: Alexander Megan , Wang Michelle , Srivastava Akanksha , Tummala Swetha P. , Abbas Diana S. , Comfort Ashley
Published: June 2022

INTRODUCTION:

The relationship between duration of intrapartum oxytocin exposure and obstetric hemorrhage (OBH) is incompletely understood. Prior research is limited by use of estimated, not quantitative, blood loss data. Our objective is to assess whether prolonged duration of intrapartum Pitocin exposure is associated with 1) increased quantitative blood loss (QBL), 2) OBH (QBL greater than or equal to 1,000 mL), or 3) hemorrhage-related maternal morbidity.

METHODS:

We performed a retrospective cohort analysis of all who were exposed to intrapartum exogenous oxytocin for induction or augmentation from January 1, 2018, to December 31, 2019. Women were categorized by hours of intrapartum oxytocin exposure: <12 hours or ≥12 hours of exposure. Groups were compared using t test and chi-square test. Institutional review board approval was obtained from Boston Medical Center and Boston University School of Medicine.

RESULTS:

Of 5,332 patients, 2,232 (41.9%) had intrapartum oxytocin exposure. Compared to patients with intrapartum oxytocin exposure <12 hours, those with ≥12 hours had higher mean QBL (P<.001) and higher probability of OBH (P<.001). Oxytocin exposure of ≥12 hours was not associated with increased hemorrhage-related morbidity.

CONCLUSION:

Prolonged intrapartum exogenous oxytocin exposure, in particular >12 hours, was associated with increased QBL and increased probability of OBH. Future studies should additionally explore the impact of rate and dose of oxytocin on risk of obstetric hemorrhage.
The Association Between Social Determinants of Health and Postpartum Length of Stay During the COVID-19 Pandemic [A139]
Authors: Lewis Ayodele , Bunnell Megan , Easter Sarah Rae , McElrath Thomas , Greenberg James A.
Published: June 2022

INTRODUCTION:

To determine differences in cesarean postpartum length of stay (pLOS) before and during the COVID-19 pandemic as a function of social determinants of health.

METHODS:

Cesarean birth pLOS data between January 1 and June 30, 2020, were reviewed. Births after March 10, 2020, were considered pandemic births. Primary outcome was early discharge <5,760 minutes (96 hours). Rates of early discharge were analyzed by social determinants of health, with socially vulnerable patients defined as Black or Hispanic, publicly insured, or non-English-speaking. We compared rates of early discharge before and during the pandemic overall and then among socially vulnerable patients using probit regression analysis.

RESULTS:

There were 1,885 eligible deliveries: 694 before the start of the pandemic and 1,171 after. Median pLOS pre-pandemic was 5,696 (IQR, 4,686–6,060) minutes versus 4,655 (IQR, 3,897–5,860) minutes during the pandemic. Of the eligible deliveries, 54% had early discharges pre-pandemic compared to 71% afterwards (P<.01). Overall, we found these variables predictive of early discharge pLOS: socially vulnerable (P<.01), payer type (P<.01), English ability (P<.01), and multiparity (P<.01). Race as a variable alone was not found to be significantly predictive of early discharge.

CONCLUSION:

Socially vulnerable patients are more likely to leave the hospital earlier than their counterparts both before and during the COVID-19 pandemic. Our findings suggest that increased early discharges fall disproportionately on socially vulnerable patients. Further research is needed to determine whether these results are due to provider bias or patient driven.
Experiences of Discrimination Are Associated With Risk for Cesarean Delivery [A157]
Authors: Mulla Yamini , Shepard Samantha , Hux Vanessa J.
Published: June 2022

INTRODUCTION:

Discrimination is a chronic stressor associated with poor health outcomes and may contribute to persistent disparities in health and pregnancy outcomes. The purpose of this study is to examine the association between discrimination reported in pregnancy and nulliparous, term, singleton, vertex (NTSV) cesarean birth rates.

METHODS:

Participants between the ages of 18 and 39 with singleton pregnancies at 18–27 weeks recruited from obstetrics and gynecology clinics at Tampa General Genesis Health Park and the University of South Florida: South Tampa Center Clinic. Participants completed the Williams Everyday Discrimination Scale (WEDS), Perceived Ethnic Discrimination Questionnaire (PEDQ), and Experiences in Ambivalent Sexism Inventory (EASI). After delivery, pregnancy and delivery outcomes were abstracted from the patient’s electronic medical record. Logistic regression was used to test associations between cesarean delivery and each discrimination measure. Analyses were also adjusted for NTSV status and race.

RESULTS:

A total of 206 participants were recruited; 190 had complete data. The overall cesarean delivery rate was 28.42%. The NTSV cesarean delivery rate was 20.45%. There was a positive association between cesarean delivery rate and both WEDS (P=.049) and PEDQ (P=.029). There was no association between cesarean delivery and EASI.

CONCLUSION:

Lifetime everyday discrimination and ethnic discrimination experiences were associated with higher odds of cesarean delivery. This may reflect that individuals who experience more discrimination may exist in systems with more bias, or that the stress experience of discrimination could affect physiology that leads to increased cesarean rates. More work is needed to further understand how interpersonal, structural, and systemic discrimination influence cesarean delivery rates.
Comparison of the Prevalence of Gestational Diabetes Pre-COVID-19 Pandemic Versus During COVID-19 [A196]
Authors: Mirsky Elizabeth , Mastronardi Alicia , Paudel Alissa M. , Young Megan Lacy , Zite Nikki , Maples Jill M.
Published: June 2022

INTRODUCTION:

Recent studies suggest that the rate of gestational diabetes (GDM) diagnosis has increased following the onset of the COVID-19 pandemic. This study investigated the prevalence of GDM among patients delivering at a single academic institution, prior to and after the onset of the COVID-19 pandemic.

METHODS:

This was a retrospective study of patients with a singleton, full-term birth who delivered pre-COVID-19 (January 2019–May 2020) and during the COVID-19 pandemic (June 2020–July 2021). Institutional review board approval was obtained. Data collected included diagnosis of GDM, maternal age, prepregnancy BMI, and gestational weight gain (GWG). Chi-square tests assessed the relationship between GDM diagnosis (yes, no) and time (pre-COVID-19, during COVID-19). Binary regression further evaluated this relationship, controlling for confounding factors.

RESULTS:

Among the 7,653 patients included in analysis, 58.6% delivered pre-COVID-19 and 41.1% delivered during COVID-19. During COVID-19, 12.5% of patients were diagnosed with GDM, compared to 9.0% pre-COVID-19 (P<.001). When stratified by prepregnancy weight status, the significantly increased prevalence of GDM during COVID-19 remained among those with a lean, overweight, and obese prepregnancy BMI (underweight, 6.2% versus 3.8%, P=.40; lean, 7.4% versus 5.0%, P<.01; overweight, 10.9% versus 7.4%, P<.01; obese, 21.1% versus 17.2%, P=.02). When controlling for maternal age, prepregnancy BMI, and GWG, time (related to COVID-19) remained a significant predictor of GDM diagnosis (P<.001).

CONCLUSION:

This study demonstrates a 38.9% increase in the prevalence of GDM delivering at a single academic institution during the COVID-19 pandemic, compared to pre-COVID-19. Future research is needed to determine the underlying mechanisms potentially contributing to hyperglycemia in pregnancy.
Random Forests for Accurate Prediction of the Risk of Hypertensive Disorders of Pregnancy at Term [A208]
Authors: Kadambi Adesh , Wen Timothy , Nguyen Eliza , Dolisca Sarah , Ebrahim Senan , Ebrahim Ali
Published: June 2022

INTRODUCTION:

Hypertensive disorders of pregnancy (HDP) complicate 10% of all pregnancies and confer elevated risks of subsequent conditions, such as chronic hypertension and diabetes. Risk models that accurately predict HDP can improve clinical management by risk stratification, allowing earlier interventions and closer interval follow-up. This study develops and internally validates a risk prediction model for the development of HDP in the third trimester.

METHODS:

This analysis was conducted using the Eunice Kennedy Shriver Institute of Child Health and Human Development / Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b) data for approximately 9,000 low-risk nulliparous patients. HDP was the primary outcome for this analysis, defined as gestational hypertension, mild/severe preeclampsia, eclampsia, or HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) as an indication for admission. We included 518 potential covariates of interest, including outpatient vital signs, medication usage, patient and family medical history, and laboratory information. We trained a random forest predictor model on 80% of this dataset, and further refined it using recursive feature elimination to restrict the number of input variables to 20 for a reduced model.

RESULTS:

Our full and reduced models predicted HDP with area under the receiver operating characteristic (AUROC) scores of 0.82 and 0.81 respectively. Performance evaluation of the reduced model by race showed poorer performance for non-Hispanic Black (0.76), Hispanic (0.79), and non-Hispanic White (0.80) patients than overall.

CONCLUSION:

The reduced model has been deployed for demonstration at hypertension.delfina.com. Admission for HDP can be predicted with excellent discriminative ability using random forest prediction modeling. External validation and integration with electronic health records is needed to assist providers in triaging and informing at-risk patients.
Beyond Postpartum Hypertension: Improving Access to Care and Community Resources via Telehealth [A215]
Authors: Fermin Oriana , Huber Kimberly , Ben Khallouq Bee , Boardman Lori
Published: June 2022

INTRODUCTION:

Telehealth-consolidated referral services may provide a useful tool to address health disparities in the postpartum period.

METHODS:

A telehealth postpartum hypertension program, consisting of two 20-minute visits during the first week following discharge, was begun in September 2020. In addition to managing blood pressure, patients were screened for clinical indications and social determinants of health and appropriate referrals were made as virtual and/or in-person visits.

RESULTS:

In a one-year period (September 4, 2020, to September 2, 2021), 780 patients were enrolled and completed at least one telehealth visit. Demographically, 37% self-identified as non-Hispanic White, 31% non-Hispanic Black, 29% Hispanic, and 3% non-Hispanic Asian, 65% had private insurance, and 31% lived in ZIP codes ≥15% below the poverty level. Of the 780 patients, 147 (19%) received one or more referrals. Privately insured women, compared to those with Medicaid, were more likely to receive referral services (52% versus 48%, P=.03). Of the 170 referrals made, 110 were for clinical indications (lactation support, postpartum depression, wound care), and 60 addressed social determinants of health (economic instability, food insecurity, housing instability, unmet transportation needs). Of the latter, 47% occurred in women living in ZIP codes of ≥15% of poverty level. Non-Hispanic Black and Hispanic women were more likely than non-Hispanic White women to receive referrals related to social determinants of health (76% versus 24%, P=.03).

CONCLUSION:

Maximizing the telehealth platform to include referral services to address social determinants of health has the potential to improve access to much-needed social services, particularly in vulnerable populations.
Barriers and Facilitators of Extended Use of the Contraceptive Arm Implants: A Cross-Sectional Survey of Clinicians [A11]
Authors: Rigler Nicole , Averbach Sarah , Sandoval Selina , Meurice Marielle , Hildebrand Marisa C. , Mody Sheila
Published: June 2022

INTRODUCTION:

The etonogestrel contraceptive implant has U.S. Food and Drug Administration (FDA) approval for 3 years but is effective up to 5 years. It is not known whether clinicians offer the implant up to 5 years for pregnancy prevention. We aimed to explore whether clinicians offer extended use of the implant and the barriers and facilitators to offering extended use.

METHODS:

We conducted a national cross-sectional survey among a diverse group of reproductive health clinicians. The institutional review board‒approved online survey was distributed through email listservs and social media groups.

RESULTS:

We surveyed 300 clinicians, 32.6% (n=98) family medicine physicians, 24.0% (n=72) obstetrics and gynecology generalists, 22.3% (n=67) advanced practice clinicians, and 19.0% (n=57) complex family planning (CFP) subspecialists. Among respondents, 65.0% (n=195) always, 16.7% (n=50) sometimes, and 18.3% (n=55) never offered extended use. After adjusting for age, race, gender, and clinical setting, CFP subspecialists and family medicine physicians were significantly more likely to recommend extended use compared to ob-gyn generalists (aOR=9.32, 95% CI [1.81-48.03] and 4.37 [1.58-12.10]). Key barriers to offering extended use identified were patient and provider concerns that the FDA approval is only for 3 years and patient concerns about pregnancy risk and bleeding. The key facilitators identified were strong evidence supporting extended use, prior counseling from a provider, and patient request for extended use.

CONCLUSION:

One-third of clinicians in this study do not consistently offer extended use of the contraceptive implant. Thus, there is an opportunity to expand access to extended use by focusing interventions on clinician and patient education and extending the FDA approval.
Exploring Match Space: How Medical School and Specialty Characteristics Affect Residency Match Geography in the United States
Authors: Hasnie Usman A. , Hasnie Ammar A. , Preda-Naumescu Ana , Nelson Benjamin J. , Estrada Carlos A. , Williams Winter L.
Published: June 2022

Purpose

To explore how school and specialty characteristics impact the geographic match location of U.S. senior medical students.

Method

The authors collected student match data between 2018 and 2020 from U.S. MD-granting medical schools and calculated the distance between students’ medical schools and residency training programs. They use the term “match space” to describe this distance. Match space was codified on a 5-point ordinal scale by where the student matched: 1 = home institution, 2 = home state, 3 = an adjacent state, 4 = the same or adjacent U.S. Census division (and not adjacent state), and 5 = skipped at least one U.S. Census division. Ordinal logistic regression correlated school and specialty characteristics with match space.

Results

During the study period, 26,102 medical students, representing 66 medical schools from 28 states, matched in 23 specialties. Fifty-nine percent of students were from public institutions, and 27% of schools ranked in the top 40 of National Institutes of Health (NIH) research funding. The match space was higher for students graduating from private institutions (odds ratio [OR] 1.14; 95% confidence interval [CI], 1.06 to 1.22) and matching into more competitive specialties (OR 1.07; 95% CI, 1 to 1.14). The match space was lower for students graduating from top NIH-funded institutions (OR 0.89; 95% CI, 0.85 to 0.94) and from schools with a higher percentage of in-state matriculants (OR 0.75; 95% CI, 0.72 to 0.77).

Conclusions

School characteristics such as region, public/private designation, NIH funding, and percentage of in-state students were associated with residency match geography. Matching into more competitive specialties also showed a marginal increase in match distance. These findings suggest that a student’s choice of specialty and medical school may impact subsequent geographic placement for residency training, which should be considered by students and residency programs alike.
D-dimer may aid in the diagnosis of pediatric musculoskeletal infections: a prospective study
Authors: Topak Duran , Nazik Selçuk , Seyithanoglu Muhammed , Temiz Ahmet , Mutlu Halil , Özdemir Mustafa Abdullah , Doğar Fatih , Bilal Ökkeş
Published: June 2022

Musculoskeletal infections, including septic arthritis, osteomyelitis, and soft tissue infections, are critical morbidity factors for children and adolescents. This study investigated the role of D-dimer levels for diagnosing childhood musculoskeletal infections. This single-center prospective study was initiated in April 2020 following approval from the local ethics committee. The study included 54 children, divided into the infection group (n = 21), comprising patients who underwent surgical treatment for childhood musculoskeletal infections and had macroscopically visible purulent discharge during surgery, and the control group (n = 33), comprising healthy children. In the infection group, the mean values of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), plasma D-dimer, and white blood cell (WBC) were 39.42 ± 27.00 mm/h, 101.50 ± 76.90 mg/l, 2.34 ± 2.59 mg/l, and 15.55 ± 6.86 × 109/l, respectively. On comparison, the infection group showed higher levels of WBC, CRP, ESR, D-dimer, and neutrophil-to-lymphocyte ratio than the control group. When the D-dimer cutoff value of 0.43 mg/l was taken, it was observed that it had 95.2% sensitivity and 81.8% specificity. The area under curve (AUC) of the above-mentioned parameters calculated via receiver operating characteristic curves showed CRP levels as the optimum predictor of childhood musculoskeletal infections, followed by the ESR, plasma D-dimer, and WBC levels in descending order (AUC: 0.999, 0.997, 0.986, and 0.935, respectively). D-dimer is another test, which in combination with other conventional established tests (CRP and ESR) can be helpful in diagnosis of pediatric infection. We recommend the addition of D-Dimer to ESR, CRP, and WBC as a first-line investigation in cases with suspected pediatric musculoskeletal infections.
Construct Validity of Pediatric PROMIS Computerized Adaptive Testing Measures in Children With Adolescent Idiopathic Scoliosis
Authors: Mitchell Stuart L. , McLaughlin Kevin H. , Bachmann Keith R. , Sponseller Paul D. , Reider Lisa M.
Published: June 2022

Background:

The use of patient-reported outcome measures, especially Patient-Reported Outcomes Measurement Information System (PROMIS) measures, has increased in recent years. Given this growth, it is imperative to ensure that the measures being used are validated for the intended population(s)/disease(s). Our objective was to assess the construct validity of 8 PROMIS computer adaptive testing (CAT) measures among children with adolescent idiopathic scoliosis (AIS).

Methods:

We prospectively enrolled 200 children (aged 10 to 17 y) with AIS, who completed 8 PROMIS CATs (Anxiety, Depressive Symptoms, Mobility, Pain Behavior, Pain Interference, Peer Relationships, Physical Activity, Physical Stress Experiences) and the Scoliosis Research Society-22r questionnaire (SRS-22r) electronically. Treatment categories were observation, bracing, indicated for surgery, or postoperative from posterior spinal fusion. Construct validity was evaluated using known group analysis and convergent and discriminant validity analyses. Analysis of variance was used to identify differences in PROMIS T-scores by treatment category (known groups). The Spearman rank correlation coefficient (r
s) was calculated between corresponding PROMIS and SRS-22r domains (convergent) and between unrelated PROMIS domains (discriminant). Floor/ceiling effects were calculated.

Results:

Among treatment categories, significant differences were found in PROMIS Mobility, Pain Behavior, Pain Interference, and Physical Stress Experiences and in all SRS-22r domains (P<0.05) except Mental Health (P=0.15). SRS-22r Pain was strongly correlated with PROMIS Pain Interference (r
s=−0.72) and Pain Behavior (r
s=−0.71) and moderately correlated with Physical Stress Experiences (r
s=−0.57). SRS-22r Mental Health was strongly correlated with PROMIS Depressive Symptoms (r
s=−0.72) and moderately correlated with Anxiety (r
s=−0.62). SRS-22r Function was moderately correlated with PROMIS Mobility (r
s=0.64) and weakly correlated with Physical Activity (r
s=0.34). SRS-22r Self-Image was weakly correlated with PROMIS Peer Relationships (r
s=0.33). All unrelated PROMIS CATs were weakly correlated (|r
s|<0.40). PROMIS Anxiety, Mobility, Pain Behavior, and Pain Interference and SRS-22r Function, Pain, and Satisfaction displayed ceiling effects.

Conclusions:

Evidence supports the construct validity of 6 PROMIS CATs in evaluating AIS patients. Ceiling effects should be considered when using specific PROMIS CATs.

Level of Evidence:

Level II, prognostic.
Imaging Modalities to Diagnose, Follow, and Assess Treatment of Chronic Ankle Instability
Authors: Sofka Carolyn M.
Published: June 2022

Mechanical ankle instability can lead to isolated cartilage lesions or early osteoarthritis. Many of the signs and symptoms can be clinically elusive with the need to isolate and define primary and secondary injuries with imaging. Currently available imaging modalities to diagnose chronic ankle instability are presented here.

Level of Evidence: Diagnostic level V.
Sestrin2 Is Increased in Calcific Aortic Disease and Inhibits Osteoblastic Differentiation in Valvular Interstitial Cells via the Nuclear Factor E2–related Factor 2 Pathway
Authors: Wang Haixiong , Xi Jicheng , Zhang Zhibiao , Li Jun , Guo Liping , Li Na , Sun Yuehui , Li Xiaofang , Han Xuebin
Published: June 2022

Sestrin2 (Sesn2) is involved in the progression of cardiovascular diseases, such as hypertension and myocardial infarction. This study aimed to examine Sesn2 expression in human calcific aortic valve disease (CAVD) and explore its possible mechanisms by which Sesn2 participates in this process. CAVD and normal aortic valves were collected. Sesn2 expression and sources were examined, and the results showed that Sesn2 expression was increased in aortic valves from patients with CAVD and was mainly secreted by macrophages. Additionally, U937 macrophages were pretreated with si-Sesn2 or cDNA-Sesn2 and further treated with oxidized low-density lipoprotein (ox-LDL); M1 macrophages and their markers were measured, and we found that pretreatment with si-Sesn2 increased ox-LDL–induced M1 macrophage polarization and marker mRNA levels, whereas pretreatment with cDNA-Sesn2 had the opposite effects. In ox-LDL–treated U937 macrophages, oxidative stress levels were increased in the si-Sesn2 pretreatment group and further increased by si-Nrf2 treatment, whereas oxidative stress levels were decreased in the cDNA-Sesn2 pretreatment group and significantly reversed by ML385, a specific Nrf2 inhibitor. The effects of Sesn2 on ox-LDL-induced oxidative stress and the osteogenic differentiation of ox-LDL-induced valvular interstitial cells (VICs) was examined by down-regulating Nrf2 pathway. When U937 macrophages were co-cultured with VICs, downregulation of Sesn2 increased ox-LDL-induced osteogenic differentiation in VICs, whereas overexpression of Sesn2 exerted the opposite effects. Our study suggests that Sesn2 is increased in CAVD aortic valves and may participate in the development of CAVD by regulating oxidative stress via the Nrf2 pathway.
Puerarin Alleviates LPS-Induced H9C2 Cell Injury by Inducing Mitochondrial Autophagy
Authors: Chang Xiao , He Yanhong , Wang Ling , Luo Chuanjin , Liu Yuntao , Li Rong
Published: June 2022

Sepsis leads to the damage of multiple organs, and thereby adversely affects the cardiovascular system. At present, no effective method has been found to treat myocardial injury caused by sepsis. Although Puerarin was reported to attenuate lipopolysaccharide (LPS)-induced mitochondrial injury in H9C2 cells, the effects of Puerarin in sepsis-induced myocardial injury remain unclear. In this study, H9C2 cells were stimulated with LPS, CCK-8 assays were performed to assess cell viability, and flow cytometry and TUNEL staining were used to assess cell apoptosis. Levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and enzyme activity were investigated using commercial kits. Reactive oxygen species (ROS) levels in H9C2 cells were detected by flow cytometry. Autophagosomes in the mitochondria of H9C2 cells were observed by transmission electron microscope, and protein expression was assessed by western blotting. Furthermore, in vivo experiments were applied to test the function of Puerarin in sepsis. We found that Puerarin significantly reversed LPS-induced decreases in H9C2 cell viability by inhibiting apoptosis. The ROS levels in H9C2 cells were significantly upregulated by LPS, but that effect was markedly reduced by Puerarin. In addition, Puerarin attenuated LPS-induced mitochondrial injury in H9C2 cells by regulating dynamin-related protein 1 (Drp1) and mitofusin 1 (MFN1). LPS decreased enzyme activity and reduced the levels of ADP, ALP, and AMP in mitochondria; however, those effects were reversed by Puerarin. Puerarin and Torin1 reversed LPS-induced inhibition of autophagy in the mitochondria of H9C2 cells via mediation of p62, LC3B, Pink1, and Parkin. Puerarin notably inhibited the progression of sepsis in vivo. Puerarin inhibited LPS-induced H9C2 cell injury by inducing mitochondrial autophagy, which acts as a mechanism for preventing myocardial injury caused by sepsis.
Population Pharmacokinetics of Nivolumab in Japanese Patients with Nonsmall Cell Lung Cancer
Authors: Tohi Makiko , Irie Kei , Mizuno Tomoyuki , Okuyoshi Hiroyuki , Hirabatake Masaki , Ikesue Hiroaki , Muroi Nobuyuki , Eto Masaaki , Fukushima Shoji , Tomii Keisuke , Hashida Tohru
Published: June 2022

Background:

Nivolumab is an antiprogrammed death-1 (PD-1) antibody used for immuno-oncological therapy of various cancers, including nonsmall cell lung cancer (NSCLC). This study aimed to characterize the real-world population pharmacokinetics (PK) of nivolumab in patients with NSCLC.

Methods:

PK samples were collected by opportunistic sampling of Japanese patients with NSCLC treated with nivolumab monotherapy. Population PK analysis was performed using a two-compartment model in Nonlinear Mixed Effect Model. Patient-specific factors such as body weight, age, sex, serum albumin, estimated glomerular filtration rate, performance status, programmed cell death receptor ligand 1 expression in tumors, and treatment periods were evaluated as potential covariates for clearance.

Results:

A total of 223 serum samples collected from 34 patients were available for analysis. The median (min–max) age and weight were 69 years (38–83 years) and 62.7 kg (36.8–80.5 kg), respectively. The mean (95% confidence interval) clearance estimate was 0.0064 L/h (0.0058–0.0070 L/h). The inclusion of the ALB level, estimated glomerular filtration rate, and treatment period significantly improved the model fit.

Conclusions:

A real-world nivolumab population PK model was developed using an opportunistic sampling strategy in Japanese patients with NSCLC. Further studies are warranted to characterize the exposure–response relationship and determine the optimal dosing regimens for these patients.
Common Complications of Breastfeeding and Lactation: An Overview for Clinicians
Authors: RADKE STEPHANIE M.
Published: June 2022

Lactation and breastfeeding are core components of reproductive health care and obstetrical providers should be familiar with common complications that may arise in lactating individuals. While many breastfeeding challenges are best addressed by a lactation consultant, there are conditions that fall out of their scope and require care from a clinician. The objective of this chapter is to review common complications of breastfeeding and lactation including inflammatory conditions, disorders of lactogenesis, dermatologic conditions, and persistent pain with lactation.
Exogenous Hormones and Breast Cancer Risk: Contraception, Menopausal Hormone Therapy, and Breast Cancer Survivors
Authors: Pearlman Mark D.
Published: June 2022

The use of exogenous estrogen and progesterone/progestin medications spans the reproductive and postreproductive lives of millions of women providing control over pregnancy timing, management of premenopausal and postmenopausal symptoms, and prevention of disease, including endometrial and ovarian cancer. These same hormones can also increase the risk of breast cancer in some settings and their use in breast cancer survivors may increase the risk of breast cancer recurrence. Given both the benefits and risks of these exogenous hormones, a detailed understanding of the available scientific evidence is imperative to help counsel individuals in their use across various settings.
Factors associated with home births in Benin and Mali: evidence from the recent demographic and health surveys
Authors: Bado Aristide R. , Badolo Hermann , Johnson Ermel , Komboigo Béwendin E. , Padonou Sètondji G.R. , Diawara Fatou
Published: June 2022

Introduction:

Identifying and understanding the factors associated with homebirths can contribute to improving maternal and child health and achieving the Sustainable Development Goals. The objective of this study was to conduct a comparative analysis of the factors associated with homebirths in Benin and Mali.

Method:

This study is based on the most recent data from the Demographic Health Surveys conducted in Mali and Benin in 2018. The dependent variable was homebirth, and the explanatory variables were the individual characteristics of the woman, distance to the health center, place of residence, number of prenatal consultations had, frequency of media exposure, and the use of the internet. The primary survey unit was considered in the analysis to measure the effect of context on the choice of place of delivery. Further, descriptive statistics and multilevel logistic regression analysis were used in the study.

Results:

Educational level was associated with homebirth in Benin and Mali; women with either no education or primary education are more likely to give birth at home. Women who did not live close to a health facility were more likely to give birth at home than those who did not face this problem in both countries. Not making visits for antenatal care (ANC) increases the odds of having a homebirth by 31.3 times [confidence interval (CI)=24.10–40.70] in Benin and 12.91 times (CI=10.21–16.33) in Mali. Similarly, women who went on 1–2 ANC visits were more likely to give birth at home compared with women who made 5 or more ANC visits in both countries. The number of children per woman was also a significant factor in both countries. Women who often or regularly paid attention to the media messages were less likely to give birth at home compared with those who did not follow relevant media inputs [adjusted odds ratio=0.42 (CI=0.26–0.67) in Benin and adjusted odds ratio=0.65 (CI=0.50–0.85) in Mali].

Conclusion:

Increasing the demand and uptake of women’s health services by improving the availability and quality of services and establishing community health centers could help reduce the incidence of homebirths that can be risky and, thus, combat maternal and infant mortality.
Reproducibility of masked hypertension and office-based hypertension: a systematic review and meta-analysis
Authors: Antza Christina , Farmakis Ioannis , Doundoulakis Ioannis , Akrivos Evangelos , Stalikas Nikolaos , Zafeiropoulos Stefanos , Kostopoulos Georgios , Stabouli Stella , Giannakoulas George , Kotsis Vasilios
Published: June 2022

Blood pressure (BP) phenotypes have a prognostic significance for target organ damage in long-term studies. However, it remains uncertain whether a single baseline phenotype classification is reproducible over time and represents accurately the patients’ BP status. The aim of this study was to systematically investigate the reproducibility of masked hypertension and office-based hypertension either with ambulatory BP monitoring (ABPM) or home BP monitoring (HBPM). PubMed, Cochrane Library and Web of Science were searched to identify studies with paired baseline office BP and ABPM or HBPM measurements at two timepoints. The outcome of the analysis was the individual phenotype reproducibility between the baseline and follow-up timepoints. The used effect measure was Cohen's kappa coefficient. We found 15 studies eligible for the meta-analysis enrolling a total of 5729 patients. The reproducibility of masked hypertension was better with ABPM, kappa reliability test: 0.41 [95% confidence interval (CI): 0.32–0.49], than with HBPM, kappa reliability test: 0.26 (95% CI: 0.10–0.40). The reproducibility of office-based hypertension with both methods was low, indicating slight agreement. Kappa reliability test was slightly better with ABPM (κ: 0.27, 95% CI: 0.12–0.41) than with HBPM (κ: 0.18, 95% CI: 0.08–0.27). This systematic review and meta-analysis show a slight to fair reproducibility of masked hypertension and office-based hypertension assessed through ABPM and HBPM. Considering that poor reproducibility may be a result of office BP measurements, an ABPM/HBPM-based strategy should be established for the evaluation and treatment of patients with masked hypertension or office-based hypertension.
Hypoxia regulates fibrosis-related genes via histone lactylation in the placentas of patients with preeclampsia
Authors: Li Xiang , Yang Nana , Wu Yue , Wang Xuegu , Sun Junpei , Liu Lei , Zhang Feng , Gong Yingying , Zhang Yan , Li Xueting , Du Danli , Ding Biao
Published: June 2022

Background:

Histone lactylation, a novel epigenetic modification induced by hypoxia and lactate, plays an important role in regulating gene expression. However, the role of histone lactylation in the pathogenesis of preeclampsia remains unknown.

Methods:

Placentas from preeclamptic patients and control pregnant women were collected for protein immunoassay to detect the expression level of histone lactylation, and two trophoblast cell lines were used to simulate the effect of histone lactylation on genes.

Results:

We found that lactate and histone lactylation levels were increased in preeclamptic placentas. In vitro, hypoxia was demonstrated to induce histone lactylation by promoting the production of lactate in human-trophoblast-derived cell line (HTR-8/SVneo) and human first-trimester extravillous trophoblast cell line (TEV-1) cells. In addition, 152 genes were found to be upregulated by both hypoxia exposure and sodium l-lactate treatment in HTR-8/SVneo cells. These genes were mainly enriched in the pathways including the response to hypoxia, cell migration and focal adhesion. Among the 152 genes, nine were upregulated in preeclamptic placentas. Most noteworthy, two upregulated fibrosis-related genes, FN1 and SERPINE1, were promoted by hypoxia through histone lactylation mediated by the production of lactate.

Conclusions:

The present study demonstrated the elevated levels of histone lactylation in preeclamptic placentas and identified fibrosis-related genes that were promoted by histone lactylation induced by hypoxia in trophoblast cells, which provides novel insights into the mechanism of placental dysfunction in preeclampsia.
Prevalence, time-trends and clinical characteristics of hypertension in young adults: nationwide cross-sectional study of 1.7 million Swedish 18-year-olds, 1969–2010
Authors: Rietz Helene , Pennlert Johanna , Nordström Peter , Brunström Mattias
Published: June 2022

Objective:

The prevalence of hypertension in young adulthood, as well as the clinical characteristics associated with different hypertension subtypes, have been inconsistently described. Our aim was to assess the prevalence, time-trends and characteristics associated with isolated systolic hypertension (ISH), isolated diastolic hypertension and combined systodiastolic hypertension.

Methods:

Serial cross-sectional analysis, using data from the Swedish conscription registry, including 1701 314 (99.2% male) individuals from 1969 to 2010. Risk factor associations were assessed through multivariable logistic regression.

Results:

The prevalence of hypertension increased progressively during the study period, from 20.4% in 1969 to 29.3% in 2010, with ISH being the most common subtype (94.3%). ISH was associated with elevated resting heart rate (odds ratio 1.85, 95% confidence interval 1.84–1.86, per SD), increased exercise capacity (1.37, 1.36–1.39) and increased BMI (1.30, 1.29–1.31). Isolated diastolic hypertension and combined hypertension were also associated with elevated resting heart rate (1.37, 1.32–1.41 and 2.05, 1.99–2.11, respectively) and more strongly associated with increased BMI (1.36, 1.33–1.40 and 1.54, 1.51 – 1.58), but inversely associated with exercise capacity (0.79, 0.75–0.83 and 0.90, 0.86–0.95).

Conclusion:

The prevalence of hypertension in young adulthood has increased substantially over time, predominantly due to an increase in ISH. Risk factor patterns differed between ISH and other forms of hypertension, suggesting potentially different underlying mechanisms.
Distinct transcriptomic profile of small arteries of hypertensive patients with chronic kidney disease identified miR-338-3p targeting GPX3 and PTPRS
Authors: Berillo Olga , Huo Ku-Geng , Richer Chantal , Fraulob-Aquino Júlio C. , Briet Marie , Lipman Mark L. , Sinnett Daniel , Paradis Pierre , Schiffrin Ernesto L.
Published: June 2022

Objective:

Hypertension is associated with vascular injury, which contributes to end-organ damage. MicroRNAs regulating mRNAs have been shown to play a role in vascular injury in hypertensive mice. We aimed to identify differentially expressed microRNAs and their mRNA targets in small arteries of hypertensive patients with/without chronic kidney disease (CKD) to shed light on the pathophysiological molecular mechanisms of vascular remodeling.

Methods and results:

Normotensive individuals and hypertensive patients with/without CKD were recruited (n = 15–16 per group). Differentially expressed microRNAs and mRNAs were identified uniquely associated with hypertension (microRNAs: 10, mRNAs: 68) or CKD (microRNAs: 68, mRNAs: 395), and in both groups (microRNAs: 2, mRNAs: 32) with a P less than 0.05 and a fold change less than or greater than 1.3 in subcutaneous small arteries (n = 14–15). One of the top three differentially expressed microRNAs, miR-338-3p that was down-regulated in CKD, presented the best correlation between RNA sequencing and reverse transcription-quantitative PCR (RT-qPCR, R
2 = 0.328, P < 0.001). Profiling of human aortic vascular cells showed that miR-338-3p was mostly expressed in endothelial cells. Two of the selected top nine up-regulated miR-338-3p predicted targets, glutathione peroxidase 3 (GPX3) and protein tyrosine phosphatase receptor type S (PTPRS), were validated with mimics by RT-qPCR in human aortic endothelial cells (P < 0.05) and by a luciferase assay in HEK293T cells (P < 0.05).

Conclusion:

A distinct transcriptomic profile was observed in gluteal subcutaneous small arteries of hypertensive patients with CKD. Down-regulated miR-338-3p could contribute to GPX3 and PTPRS up-regulation via the canonical microRNA targeting machinery in hypertensive patients with CKD.

Graphical abstract:

http://links.lww.com/HJH/C27
LRP5 BIALLELIC MUTATIONS CAUSE A HIGHER INCIDENCE OF SEVERE PHENOTYPE COMPARED WITH LRP5 MONOALLELIC MUTATION
Authors: Chen Chunli , Zhang Xiang , Peng Xiaoyan , Hu Feng , Cheng Yizhe , Zhao Peiquan
Published: June 2022

Purpose:

To analyze the clinical features of LRP5 gene mutation-related familial exudative vitreoretinopathy and explore the potential phenotype–genotype correlation on LRP5 gene.

Methods:

Eighty-seven familial exudative vitreoretinopathy (FEVR) families with LRP5 mutations were selected from 722 FEVR patients, which were divided into 2 groups, including 22 autosomal-recessive FEVR (ar-FEVR) families and 65 autosomal-dominant FEVR (ad-FEVR) families. Clinical and genetic data were retrospectively analyzed. The potential phenotype–genotype correlation was explored from the mutation type and inheritance pattern.

Results:

No significant difference between the LRP5 null mutation subgroup and the LRP5 missense mutation subgroup was observed in the proportion of FEVR stage and the ratio of ocular involvement. Instead, a significant difference between the LRP5 ar-FEVR subgroup and the LRP5 ad-FEVR subgroup was observed in the proportion of FEVR stage and the ratio of binocularly severe phenotype. The probands with LRP5 gene recessive mutation showed a higher incidence of severe phenotype. Moreover, the ratio of binocularly severe patients in ar-FEVR was nearly 3.5 times higher than that in ad-FEVR.

Conclusion:

The severity of phenotype was more likely to be related to the synergistic effect of the variants.