bluuebunny/crossref_metadata_2025_split huggingface dataset:
CarcSeq Measurement of Rat Mammary Cancer Driver Mutations and Relation to Spontaneous Mammary Neoplasia
Authors: McKim Karen L , Myers Meagan B , Harris Kelly L , Gong Binsheng , Xu Joshua , Parsons Barbara L 
Published: April 2021

Abstract
The ability to deduce carcinogenic potential from subchronic, repeat dose rodent studies would constitute a major advance in chemical safety assessment and drug development. This study investigated an error-corrected NGS method (CarcSeq) for quantifying cancer driver mutations (CDMs) and deriving a metric of clonal expansion predictive of future neoplastic potential. CarcSeq was designed to interrogate subsets of amplicons encompassing hotspot CDMs applicable to a variety of cancers. Previously, normal human breast DNA was analyzed by CarcSeq and metrics based on mammary-specific CDMs were correlated with tissue donor age, a surrogate of breast cancer risk. Here we report development of parallel methodologies for rat. The utility of the rat CarcSeq method for predicting neoplastic potential was investigated by analyzing mammary tissue of 16-week-old untreated rats with known differences in spontaneous mammary neoplasia (Fischer 344, Wistar Han, and Sprague Dawley). Hundreds of mutants with mutant fractions ≥ 10−4 were quantified in each strain, most were recurrent mutations, and 42.5% of the nonsynonymous mutations have human homologs. Mutants in the mammary-specific target of the most tumor-sensitive strain (Sprague Dawley) showed the greatest nonsynonymous/synonymous mutation ratio, indicative of positive selection consistent with clonal expansion. For the mammary-specific target (Hras, Pik3ca, and Tp53 amplicons), median absolute deviation correlated with percentages of rats that develop spontaneous mammary neoplasia at 104 weeks (Pearson r = 1.0000, 1-tailed p = .0010). Therefore, this study produced evidence CarcSeq analysis of spontaneously occurring CDMs can be used to derive an early metric of clonal expansion relatable to long-term neoplastic outcome.
Anticancer Activity and In Vitro to In Vivo Mechanistic Recapitulation of Novel Ruthenium-Based Metallodrugs in the Zebrafish Model
Authors: Karas Brittany F , Hotz Jordan M , Gural Brian M , Terez Kristin R , DiBona Victoria L , Côrte-Real Leonor , Valente Andreia , Buckley Brian T , Cooper Keith R 
Published: April 2021

Abstract
Ruthenium is popular as a metal core for chemotherapeutics, due to versatile molecular coordination. Because new metallodrugs are synthesized at high rates, our studies included assays in zebrafish to expedite the initial evaluation as anticancer agents. Here we evaluated novel metallodrugs (PMC79 and LCR134), and cisplatin, a widely used platinum-based chemotherapeutic. We hypothesized that this model could characterize anticancer properties and recapitulate previous in vitro results in vivo. Our findings suggest anticancer properties of PMC79 and LCR134 were similar with less toxicity than cisplatin. Exposures from 24 to 72 h at or below the LOAELs of PMC79 and LCR134 (3.9 µM and 13.5 µm, respectively), impaired blood vessel development and tailfin regeneration. Blood vessel examination through live imaging of larvae revealed distinct regional antiangiogenic impacts. The significant decrease in gene expression of the VEGF-HIF pathway and beta-actin could explain the morphological effects observed in the whole organism following exposure. Tailfin amputation in larvae exposed to PMC79 or LCR134 inhibited tissue regrowth and cell division, but did not impact normal cell proliferation unlike cisplatin. This suggests Ru drugs may be more selective in targeting cancerous cells than cisplatin. Additionally, in vitro mechanisms were confirmed. PMC79 disrupted cytoskeleton formation in larvae and P-glycoprotein transporters in vivo was inhibited at low doses which could limit off-target effects of chemotherapeutics. Our results demonstrate the value for using the zebrafish in metallodrug research to evaluate mechanisms and off-target effects. In light of the findings reported in this article, future investigation of PMC79 and LCR134 are warranted in higher vertebrate models.
Finding a New Normal
Authors: Norton Michelle , Hagstrom Amy 
Published: April 2021

Background:
Infants discharged from the neonatal intensive care unit (NICU) dependent on medical technology (eg, respiratory or nutritional support) are a growing vulnerable population. These infants are medically fragile, prone to emergency department visits and readmissions, and require increased caregiver demands at home. The experiences of their maternal caregiver's after NICU discharge however, are not well understood.

Purpose:
This qualitative descriptive study addressed this knowledge gap by interviewing mothers of technology-dependent infants about their experience during their first 2 weeks transitioning to home from the NICU. This is a critical period in which mothers must first assume advanced caretaking responsibilities in the home.

Methods:
Eight mothers participated in semistructured audio-recorded interviews via the Web conferencing system Zoom and completed demographic questionnaires.

Results:
Five themes emerged from the data that described essential features of the mothers' transition to home: (a) needing coordinated discharge care; (b) establishing a routine; (c) being an advocate; (d) having a support system; and (e) finding normalcy. An additional important finding of this study was the presence of maternal posttraumatic stress and postpartum depression.

Implications for Practice:
Results highlight the importance of providing mothers hands-on practice opportunities and identifying social support and home healthcare options prior to discharge of technology-dependent infants.

Implications for Research:
Future research should focus on multidisciplinary interventions targeted toward discharge preparation, transitional support, and understanding maternal psychiatric symptoms among mothers of technology-dependent infants.
Does Local Steroid Reduce Dysphagia After Cervical Disc Replacement? A Prospective, Randomized, Placebo-controlled, Double-blinded Study
Authors: Curto Ryan A. , Edwards Charles C. 
Published: April 2021

Study Design:
A prospective, randomized, placebo-controlled, double-blinded study.

Objective:
To examine the effect of intraoperatively administered local Depo-Medrol on the incidence and severity of postoperative dysphagia in patients undergoing cervical disk replacement (CDR) surgery.

Summary of Background Data:
Dysphagia is often reported as an adverse event after anterior cervical surgeries. One method for reducing the incidence of postoperative dysphagia in patients undergoing anterior cervical discectomy and fusion surgeries is the intraoperative application of topical corticosteroids to the retroesophageal space. There have been no studies examining the effect of local steroids on dysphagia after CDR surgery.

Materials and Methods:
Seventy-three patients underwent CDR surgery by a single surgeon at a single institution. A 1 cm ×3 cm ×3 mm gel foam collagen sponge was saturated by the nurse with either saline (1 cc) or Depo-Medrol (40 mg/1 cc) based on randomization protocol. The sponge was placed ventral to the cervical disk implant in the retroesophageal space. Study follow-up occurred on postoperative day 1, 4, 7, 14 and postoperative month 1, 2, and 3. Dysphagia outcomes were classified using the Bazaz Dysphagia Score and Eating Assessment Tool 10.

Results:
The steroid group, compared with the control group, had significantly reduced incidence of dysphagia (50% vs. 75%; P=0.0427) and severe dysphagia (12% vs. 36% Bazaz score, P=0.0253; 18% vs. 42% Eating Assessment Tool 10, P=0.0378) at POD4. There was no significant long-term difference in rates of dysphagia between the control and the steroid group.

Conclusions:
This study provides level 1 evidence that the use of intraoperative locally administered Depo-Medrol significantly reduces the incidence and severity of dysphagia within the first week after CDR surgery. The use of local steroid may provide patients undergoing CDR surgery with a more pleasant early recovery experience with respect to dysphagia.
The Initial Impact of the Coronavirus Disease 2019 Pandemic on ICU Family Engagement: Lessons Learned From a Collaborative of 27 ICUs
Authors: Hwang David Y. , Zhang Qiang , Andrews Adair , LaRose Kimberly , Gonzalez Martin , Harmon Lori , Vermoch Kathleen 
Published: April 2021

Objectives:
To describe the impact of coronavirus disease 2019 on family engagement among ICUs participating in a multicenter collaborative promoting implementation of family-centered care projects and to report sites’ experiences with the collaborative itself prior to its cancelation due to the pandemic in March 2020.

Design:
Cross-sectional survey.

Setting:
Twenty-seven academic and community ICUs in the United States and South Korea.

Subjects:
Site leaders.

Interventions:
Prior to March 2020, all sites had participated in 6 months of webinars, monthly calls, and listserv communication to facilitate projects and to collect preimplementation family satisfaction and clinician perception data.

Measurements and Main Results:
Planned projects included ICU orientation initiatives (12, 44.4%), structured family care conferences (6, 22.2%), and ICU diaries (5, 18.5%). After cancelation of the collaborative, 22 site leaders (81.5%) were surveyed by phone from June 2020 to July 2020. Twenty (90.1%) reported having stopped their site project; projects that continued were 1) a standardized palliative extubation protocol and 2) daily written clinical summaries for families. Sites described significant variability in visitor restriction policies and uncertainty regarding future policy changes. Four sites (18.2%) reported that their hospital did not provide personal protective equipment to visitors. Regarding video conferencing with families, 11 sites (52.4%) reported clinicians’ using their own personal devices. Two-hundred twelve family surveys and 346 clinician surveys collected prior to cancelation highlighted a broad need for family support. When leaders were asked on a scale from 0 to 10 how helpful collaborative activities had been prior to cancelation, mean response was 8.0 (sd 2.5).

Conclusions:
While the collaborative model can help promote ICU family engagement initiatives, coronavirus disease 2019 has impeded implementation of these initiatives even among motivated units. ICUs need adequate personal protective equipment for visitors and video conferencing capabilities on hospital devices while strict visitor restrictions continue to evolve.
Recent advances in HIV-associated chronic lung disease clinical research
Authors: Kunisaki Ken M. 
Published: April 2021

Purpose of review
To highlight recently published, clinically focused research on chronic lung disease in adult persons with human immunodeficiency virus-1 (HIV) (PWH).

Recent findings
Chronic lung disease was the most common comorbidity in hospitalized PWH in New York and second-most common condition in ambulatory PWH in Canada. The elevated risk of chronic obstructive pulmonary disease in PWH has been widely recognized, but PWH are also at higher risk for asthma and worse asthma outcomes. Expanded assessments of lung structure and function, such as single-breath diffusing capacity of carbon monoxide (DLCO), exhaled nitric oxide (FeNO), and chest computed tomography (CT) have provided new insights into HIV effects on the lungs. New biomarker analyses are emerging, but further studies are needed to validate predictive biomarkers for chronic lung disease in PWH. Clinical trials addressing chronic lung disease in PWH are few in number.

Summary
Chronic lung disease is a common and high-impact comorbidity among PWH. Future studies should collect more comprehensive lung assessments such as DLCO, FeNO, and chest CT in order to better phenotype lung derangements in HIV. Clinical trials are desperately needed to reduce the rising burden of chronic lung disease in PWH.
Green space, air pollution, traffic noise and saliva cortisol in children
Authors: Bloemsma Lizan D. , Wijga Alet H. , Klompmaker Jochem O. , Hoek Gerard , Janssen Nicole A. H. , Oldenwening Marieke , Koppelman Gerard H. , Lebret Erik , Brunekreef Bert , Gehring Ulrike 
Published: April 2021

Background:
Green space, air pollution, and traffic noise exposure may be associated with stress levels in children. A flattened diurnal cortisol slope (the decline in cortisol concentrations from awakening to evening) is an indicator of chronic stress. We examined associations of green space, ambient air pollution, and traffic noise with the diurnal cortisol slope in children 12 years of age.

Methods:
At age 12 years, 1,027 participants of the Dutch PIAMA birth cohort collected three saliva samples during 1 day. We estimated residential exposure to green space (i.e., the average Normalized Difference Vegetation Index [NDVI] and percentages of green space in circular buffers of 300 m and 3,000 m), air pollution, and traffic noise. Associations of these exposures with the diurnal cortisol slope (in nmol/L per hour) were assessed by multiple linear regression, adjusting for potential confounders.

Results:
Higher average NDVI and total percentage of green space in a 3,000 m buffer were associated with a larger diurnal decrease in cortisol levels (adjusted difference [95% confidence interval] = −0.11 nmol/L/hr [−0.21, 0.00 nmol/L/hr] per interquartile range increase in the average NDVI; −0.13 nmol/L/hr [−0.26, 0.00 nmol/L/hr] per interquartile range increase in the total percentage of green space). These associations were largely driven by associations with the percentage of agricultural green space and by associations in children living in nonurban areas. We observed no relationships between air pollution or traffic noise and the diurnal cortisol slope.

Conclusions:
Residential exposure to green space in a buffer of 3,000 m may be associated with lower stress levels in children 12 years of age.
Drinking water contaminants in California and hypertensive disorders in pregnancy
Authors: Padula Amy M. , Ma Chen , Huang Hongtai , Morello-Frosch Rachel , Woodruff Tracey J. , Carmichael Suzan L. 
Published: April 2021

Background:
Environmental pollutants have been associated with hypertensive disorders in pregnancy including gestational hypertension, preeclampsia, and eclampsia, though few have focused on drinking water contamination. Water pollution can be an important source of exposures that may contribute to adverse pregnancy outcomes.

Methods:
We linked water quality data on 13 contaminants and two violations from the California Communities Environmental Health Screening Tool to birth records from vital statistics and hospital discharge records (2007–2012) to examine the relationship between drinking water contamination and hypertensive disorders in pregnancy. We examined contaminants in single- and multipollutant models. Additionally, we examined if the relationship between water contamination and hypertensive disorders in pregnancy differed by neighborhood poverty, individual socioeconomic status, and race/ethnicity.

Results:
Arsenic, nitrate, trihalomethane, hexavalent chromium, and uranium were detected in a majority of water systems. Increased risk of hypertensive disorders in pregnancy was modestly associated with exposure to cadmium, lead, trihalomethane, and hexavalent chromium in drinking water after adjusting for covariates in single pollutant models with odds ratios ranging from 1.01 to 1.08. In multipollutant models, cadmium was consistent, lead and trihalomethane were stronger, and additional contaminants were associated with hypertensive disorders in pregnancy including trichloroethylene, 1,2-Dibromo-3-chloropropane, nitrate, and tetrachloroethylene. Other contaminants either showed null results or modest inverse associations. The relationship between water contaminants and hypertensive disorders in pregnancy did not differ by neighborhood poverty.

Conclusions:
We found increased risk of hypertensive disorders in pregnancy associated with exposure to several contaminants in drinking water in California. Results for cadmium, lead, trihalomethane, and hexavalent chromium were robust in multipollutant models.
Management of Hypertension in Pregnancy
Authors: Magee Laura A. , von Dadelszen Peter 
Published: April 2021

Abstract
Hypertension in pregnancy is currently defined as a systolic blood pressure (BP) of 140 mmHg or more, or a diastolic BP of 90 mmHg or more. This level of BP warrants antihypertensive therapy. Treating to a target BP of 135/85 mmHg halves the risk of severe hypertension that is itself associated with adverse maternal and perinatal outcomes, similar in magnitude to preeclampsia. While based on the results of the Control of Hypertension in Pregnancy Study (CHIPS) trial, this finding is consistent with all antihypertensive trials to date. Also, in the CHIPS trial, “tight” BP control also halved the risk of progression to thrombocytopenia and elevated liver enzymes for the mother, without adverse effects for the fetus or newborn. This was true regardless of the gestational age at which BP control was instituted. While methyldopa, labetalol, and nifedipine are the most commonly-recommended oral antihypertensives, it is not clear that one antihypertensive agent has advantages over the others for treatment of non-severe hypertension in pregnancy. No antihypertensives, including renin-angiotensin-aldosterone system (RAAS) inhibitors, have been shown to be teratogenic, although there may be an increase in malformations associated with the underlying condition of chronic hypertension. Atenolol and RAAS inhibitors should not be used once pregnancy is diagnosed, based on fetotoxicity. At present, BP treatment targets used in clinic are the same as those used at home as the differences are quite variable among hypertensive women. For treatment of acute severe hypertension, the most commonly-recommended antihypertensives are oral nifedipine, IV labetalol, and IV hydralazine, although oral agents have also been shown to be effective in the majority of women; while concerns raised about IV hydralazine-induced maternal hypotension and its consequences have not been confirmed, this medication may be an inferior antihypertensive to oral nifedipine. While treatment recommendations are based on evidence, women should be engaged in decision-making, as their values may alter target BP and antihypertensive choice. Future work will clarify the optimal target BP based on home BP measurements; whether BP targets should be lowered further if the definition of hypertension is based on a lower BP; which, if any, antihypertensive medication for non-severe hypertension is better with regards to maternal and perinatal outcomes; and whether factors beyond BP level (such as variability, race, and other physiological variables) should inform antihypertensive therapy in pregnancy.
Analysis of female demographics in the United States: life expectancy, education, employment, family building decisions, and fertility service utilization
Authors: Esencan Ecem , Simsek Burcin , Seli Emre 
Published: April 2021

Purpose of review
To discuss changes in female demographic parameters in the US and associated increase in utilization of fertility services.

Recent findings
Fractions of women earning bachelor's, master's, and doctoral degrees increased from 1970 to 2018 (32.6 vs 64.8; 7.9 vs 27.3; 0.54 vs 5.7 per 10,000 women; P < .001; respectively). This was associated with decrease in percentage of married women (61.9% vs 50.8%) and increase in median age at first marriage (20.8 vs 27.8). In parallel, mean age of mothers at first birth increased (21.4 vs 26.8), and pregnancy rates of women aged 35–39 and 40–44 years doubled between 1980 and 2010 (0.036 vs 0.077; 0.009 vs 0.019 per 1,000 women). With later pregnancy attempts, female fertility rates decreased from 1970 to 2017 (87.9% vs 60.3%; P < .001). Women undergoing assisted reproductive technologies (ART) treatment with a DOR diagnosis increased (12% vs 31%), and ART cycles using donor eggs increased (16,161 vs 24,300), between 2005 and 2016.

Summary
Participation of women in education is paralleled by increased female employment, later occurrence of marriage, increased age of childbearing, decreased fertility rates, and increased DOR diagnosis.
Foot Orthoses Enhance the Effectiveness of Exercise, Shockwave, and Ice Therapy in the Management of Medial Tibial Stress Syndrome
Authors: Naderi Aynollah , Bagheri Shahabeddin , Ramazanian Ahoor Fatemeh , Moen Maarten H. , Degens Hans 
Published: April 2021

Objective:
Our aim was to assess the effects of adding arch-support foot-orthoses (ASFO) to a multimodal therapeutic intervention on the perception of pain and improvement of recovery from medial tibial stress syndrome (MTSS) in recreational runners.

Design:
A prospective randomized controlled trial.

Setting:
Sport training and medical centers.

Participants:
Fifty female recreational runners with MTSS were randomized into 2 groups.

Interventions:
Runners either received ASFO or sham flat noncontoured orthoses. Both groups received a multimodal therapeutic intervention, including ice massage, ankle muscle exercises, and extracorporeal shockwave therapy.

Main Outcome Measures:
Pain during bone pressure using a numerical Likert scale (0-10), MTSS severity using an MTSS scale, perceived treatment effect using the global rating of change scale, and quality of life using the short Form-36 questionnaire were determined at week 6, 12, and 18.

Results:
Pain intensity and MTSS severity were lower, and the perceived treatment effect and physical function were better in the ASFO than in the sham flat noncontoured orthoses group at week 6 and week 12. Cohen's dz effect size for between-group differences showed a medium difference. However, arch-support foot-orthoses did not add to the benefits of multimodal therapeutic intervention on pain, MTSS severity and perceived treatment effect at week 18.

Conclusions:
Adding ASFO to a therapeutic intervention leads to an earlier diminishment of pain and MTSS severity, and improved PF and perceived therapeutic effects.
Feasibility and Effectiveness of an Interprofessional Mindfulness-Informed Group-Based Intervention for Treatment of Overactive Bladder: A Pilot Study
Authors: Reisch Rebecca , Zúñiga Ruth , Das Rebekah 
Published: April 2021

Background:
Overactive bladder (OAB) is a common condition that negatively affects quality of life. Urinary urgency is the dominant symptom and behavioral therapy is the first-line approach. Mindfulness practices have been proposed for urgency management, but studies on mindfulness for OAB have not included components of behavioral therapy commonly used in clinical practice.

Objectives:
The primary objective was to examine the feasibility of implementing a novel mindfulness-informed group-based behavioral therapy intervention for OAB, using behavioral therapy specific to OAB. The secondary purpose was to examine the potential clinical utility of the program.

Study Design:
Pilot feasibility study.

Methods:
This was a single-arm pilot study using a convenience sample. The intervention was developed by 2 physical therapists and 1 licensed psychologist. Women with OAB symptoms were recruited from the community for a 6-week, 2 h/wk group-based program that included information on bladder health, urinary tract function, and mindfulness-informed practices. Participants were asked to engage in mindfulness activities between sessions.

Results:
Five women fit the inclusion criteria and 4 completed the study, attending all 6 sessions (retention rate: 80%). Time and resources required to deliver the intervention were deemed feasible. All participants showed improvements on some or all self-reported symptoms questionnaires.

Conclusions:
This novel program appears to be feasible and shows the potential for clinical utility. Future studies should include a longer recruitment period to achieve a larger sample size and should compare this intervention with other established interventions for OAB.