bluuebunny/crossref_metadata_2025 huggingface dataset:
The ASCEND-ND trial: study design and participant characteristics
Authors: Perkovic Vlado , Blackorby Allison , Cizman Borut , Carroll Kevin , Cobitz Alexander R , Davies Rich , DiMino Tara L , Jha Vivekanand , Johansen Kirsten L , Lopes Renato D , Kler Lata , Macdougall Iain C , McMurray John J V , Meadowcroft Amy M , Obrador Gregorio T , Solomon Scott , Taft Lin , Wanner Christoph , Waikar Sushrut S , Wheeler David C , Wiecek Andrzej , Singh Ajay K
Published: November 2021

Background

Anaemia is common in chronic kidney disease (CKD) and assessment of the risks and benefits of new therapies is important.

Methods

The Anaemia Study in CKD: Erythropoiesis via a Novel prolyl hydroxylase inhibitor Daprodustat-Non-Dialysis (ASCEND-ND) trial includes adult patients with CKD Stages 3–5, not using erythropoiesis-stimulating agents (ESAs) with screening haemoglobin (Hb) 8–10 g/dL or receiving ESAs with screening Hb of 8–12 g/dL. Participants were randomized to daprodustat or darbepoetin alfa (1:1) in an open-label trial (steering committee- and sponsor-blinded), with blinded endpoint assessment. The co-primary endpoints are mean change in Hb between baseline and evaluation period (average over Weeks 28–52) and time to first adjudicated major adverse cardiovascular (CV) event. Baseline characteristics were compared with those of participants in similar anaemia trials.

Results

Overall, 3872 patients were randomized from 39 countries (median age 67 years, 56% female, 56% White, 27% Asian and 10% Black). The median baseline Hb was 9.9 g/dL, blood pressure was 135/74 mmHg and estimated glomerular filtration rate was 18 mL/min/1.73 m2. Among randomized patients, 53% were ESA non-users, 57% had diabetes and 37% had a history of CV disease. At baseline, 61% of participants were using renin–angiotensin system blockers, 55% were taking statins and 49% were taking oral iron. Baseline demographics were similar to those in other large non-dialysis anaemia trials.

Conclusion

ASCEND-ND will define the efficacy and safety of daprodustat compared with darbepoetin alfa in the treatment of patients with anaemia associated with CKD not on dialysis.
Combined immunotherapy with controlled interleukin-12 gene therapy and immune checkpoint blockade in recurrent glioblastoma: An open-label, multi-institutional phase I trial
Authors: Chiocca E Antonio , Gelb Arnold B , Chen Clark C , Rao Ganesh , Reardon David A , Wen Patrick Y , Bi Wenya Linda , Peruzzi Pierpaolo , Amidei Christina , Triggs Dan , Seften Leah , Park Grace , Grant James , Truman Kyla , Buck Jill Y , Hadar Nira , Demars Nathan , Miao John , Estupinan Taylor , Loewy John , Chadha Kamal , Tringali Joseph , Cooper Laurence , Lukas Rimas V
Published: November 2021

Background

Veledimex (VDX)-regulatable interleukin-12 (IL-12) gene therapy in recurrent glioblastoma (rGBM) was reported to show tumor infiltration of CD8+ T cells, encouraging survival, but also up-regulation of immune checkpoint signaling, providing the rationale for a combination trial with immune checkpoint inhibition.

Methods

An open-label, multi-institutional, dose-escalation phase I trial in rGBM subjects (NCT03636477) accrued 21 subjects in 3 dose-escalating cohorts: (1) neoadjuvant then ongoing nivolumab (1mg/kg) and VDX (10 mg) (n = 3); (2) neoadjuvant then ongoing nivolumab (3 mg/kg) and VDX (10 mg) (n = 3); and (3) neoadjuvant then ongoing nivolumab (3 mg/kg) and VDX (20 mg) (n = 15). Nivolumab was administered 7 (±3) days before resection of the rGBM followed by peritumoral injection of IL-12 gene therapy. VDX was administered 3 hours before and then for 14 days after surgery. Nivolumab was administered every two weeks after surgery.

Results

Toxicities of the combination were comparable to IL-12 gene monotherapy and were predictable, dose-related, and reversible upon withholding doses of VDX and/or nivolumab. VDX plasma pharmacokinetics demonstrate a dose-response relationship with effective brain tumor tissue VDX penetration and production of IL-12. IL-12 levels in serum peaked in all subjects at about Day 3 after surgery. Tumor IFNγ increased in post-treatment biopsies. Median overall survival (mOS) for VDX 10 mg with nivolumab was 16.9 months and for all subjects was 9.8 months.

Conclusion

The safety of this combination immunotherapy was established and has led to an ongoing phase II clinical trial of immune checkpoint blockade with controlled IL-12 gene therapy (NCT04006119).
Establishment of patient-derived organoid models of lower-grade glioma
Authors: Abdullah Kalil G , Bird Cylaina E , Buehler Joseph D , Gattie Lauren C , Savani Milan R , Sternisha Alex C , Xiao Yi , Levitt Michael M , Hicks William H , Li Wenhao , Ramirez Denise M O , Patel Toral , Garzon-Muvdi Tomas , Barnett Samuel , Zhang Gao , Ashley David M , Hatanpaa Kimmo J , Richardson Timothy E , McBrayer Samuel K
Published: November 2021

Background

Historically, creating patient-derived models of lower-grade glioma (LGG) has been challenging, contributing to few experimental platforms that support laboratory-based investigations of this disease. Although organoid modeling approaches have recently been employed to create in vitro models of high-grade glioma (HGG), it is unknown whether this approach can be successfully applied to LGG.

Methods

In this study, we developed an optimized protocol for the establishment of organoids from LGG primary tissue samples by utilizing physiologic (5%) oxygenation conditions and employed it to produce the first known suite of these models. To assess their fidelity, we surveyed key biological features of patient-derived organoids using metabolic, genomic, histologic, and lineage marker gene expression assays.

Results

Organoid models were created with a success rate of 91% (n = 20/22) from primary tumor samples across glioma histological subtypes and tumor grades (WHO Grades 1–4), and a success rate of 87% (13/15) for WHO Grade 1–3 tumors. Patient-derived organoids recapitulated stemness, proliferative, and tumor-stromal composition profiles of their respective parental tumor specimens. Cytoarchitectural, mutational, and metabolic traits of parental tumors were also conserved. Importantly, LGG organoids were maintained in vitro for weeks to months and reanimated after biobanking without loss of integrity.

Conclusions

We report an efficient method for producing faithful in vitro models of LGG. New experimental platforms generated through this approach are well positioned to support preclinical studies of this disease, particularly those related to tumor immunology, tumor-stroma interactions, identification of novel drug targets, and personalized assessments of treatment response profiles.
Investigating secondary pre-service teachers as teachers and learners of mathematical modeling
Authors: Wickstrom Megan H , Arnold Elizabeth G
Published: November 2021

There is a growing attention around the preparation of pre-service teachers (PSTs) as both learners and teachers of mathematical modeling. Current literature focuses on preparing PSTs as learners of modeling, and we extend current work by examining how PSTs integrate their understanding of modeling into the work of teaching. This study follows two groups of PSTs, concurrently enrolled in a modeling course and a secondary methods of teaching course, as they completed a joint unit of instruction in which they designed, refined and enacted a modeling lesson in a secondary classroom. We explore how PSTs build understanding across learning opportunities with respect to four modeling competencies: theoretical, task related, teaching and diagnostic. Our findings indicate that PSTs were able to grow across all four competencies. Theoretical competencies developed from time spent working with modeling tasks as learners and working collaboratively with instructors and peers. Task related and teaching competencies took time to develop as PSTs often wrestled with their conceptions of modeling as learners with existing conceptions of teaching and task design. Diagnostic competencies developed from structured time to reflect on lesson enactment and changes that could be made to best support student learning. Overall, we found that PSTs benefit from engaging in modeling tasks as learners and in enacting components of teaching modeling lessons.
NIN-Like Proteins: Interesting Players in Rhizobia-Induced Nitrate Signaling Response During Interaction with Non-Legume Host Arabidopsis thaliana
Authors: Hernández-Reyes Casandra , Lichtenberg Elisabeth , Keller Jean , Delaux Pierre-Marc , Ott Thomas , Schenk Sebastian T.
Published: November 2021

Nitrogen is an essential macronutrient and a key cellular messenger. Plants have evolved refined molecular systems to sense the cellular nitrogen status. This is exemplified by the root nodule symbiosis between legumes and symbiotic rhizobia, where nitrate availability inhibits this mutualistic interaction. Additionally, nitrate also functions as a metabolic messenger, resulting in nitrate signaling cascades which intensively crosstalk with other physiological pathways. Nodule inception-like proteins (NLPs) are key players in nitrate signaling and regulate nitrate-dependent transcription during legume–rhizobia interactions. Nevertheless, the coordinated interplay between nitrate signaling pathways and rhizobacteria-induced responses remains to be elucidated. In our study, we investigated rhizobia-induced changes in the root system architecture of the non-legume host arabidopsis under different nitrate conditions. We demonstrate that rhizobium-induced lateral root growth and increased root hair length and density are regulated by a nitrate-related signaling pathway. Key players in this process are AtNLP4 and AtNLP5, because the corresponding mutants failed to respond to rhizobia. At the cellular level, AtNLP4 and AtNLP5 control a rhizobia-induced decrease in cell elongation rates, while additional cell divisions occurred independently of AtNLP4. In summary, our data suggest that root morphological responses to rhizobia are coordinated by a newly considered nitrate-related NLP pathway that is evolutionarily linked to regulatory circuits described in legumes.

[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Ventricular assist device for Fontan: who, when and why?
Authors: Reid Catherine S. , Kaiser Heiko A. , Heinisch Paul Philipp , Bruelisauer Thomas , Michel Sebastian , Siepe Matthias
Published: November 2021

Purpose of review

Since the advent of the Fontan palliation, survival of patients with univentricular congenital heart disease has increased significantly. These patients will, however, ultimately develop heart failure requiring advanced therapies such as heart transplantation. As wait times are long, mechanical circulatory support (MCS) is an attractive therapy, both for bridge to transplantation and destination therapy in patients not suitable for transplantation. This review aims to summarize current thinking about how to determine which patients would benefit from a ventricular assist device (VAD), the optimal time for implantation and which device should be considered.

Recent findings

VAD implantation in end-stage Fontan is still in its infancy; however, case reports and research interest have increased extensively in the past few years. Mortality is significantly higher than in noncongenital heart disease patients. Implantation in patients with primarily systolic dysfunction is indicated, whereas patients with increased transpulmonary gradient may not benefit from a single-VAD solution. When possible, implantation should occur prior to clinical decompensation with evidence of end-organ damage, as outcomes at this point are worse.

Fontan patients demonstrating signs of heart failure should be evaluated early and often for feasibility and optimal timing of VAD implantation. The frequency of this procedure will likely increase significantly in the future.
Passive Recharge Burst Spinal Cord Stimulation Provides Sustainable Improvements in Pain and Psychosocial Function: 2-year Results From the TRIUMPH Study
Authors: Deer Timothy R. , Falowski Steven M. , Moore Gregory A. , Hutcheson J. Kelby , Peña Isaac , Candido Kenneth , Cornidez Eric G. , Fraunberg von und zu , Blomme Bram , Capobianco Robyn A.
Published: November 2021

Study Design.

Prospective, international, multicenter, single-arm, post-market study.

Objective.

The aim of this study was to assess long-term safety and effectiveness of spinal cord stimulation using a passive recharge burst stimulation design for chronic intractable pain in the trunk and/or limbs. Herein we present 24-month outcomes from the TRIUMPH study (NCT03082261).

Summary of Background Data.

Passive recharge burst spinal cord stimulation (B-SCS) uniquely mimics neuronal burst firing patterns in the nervous system and has been shown to modulate the affective and attentional components of pain processing.

Methods.

After a successful trial period, subjects received a permanent SCS implant and returned for follow-up at 6, 12, 18, and 24 months.

Results.

Significant improvements in physical, mental, and emotional functioning observed after 6 months of treatment were maintained at 2 years. Pain catastrophizing scale (PCS) scores dropped below the population norm. Health-related quality of life on EQ-5D improved across all domains and the mean index score was within one standard deviation of norm. Pain reduction (on NRS) was statistically significant (P < 0.001) at all timepoints. Patient reported pain relief, a stated percentage of improvement in pain, was consistent at all timepoints at 60%. Patients reported significant improvements across all measures including activity levels and impact of pain on daily life. At 24 months, 84% of subjects were satisfied and 90% would recommend the procedure. Subjects decreased their chronic pain medication intake for all categories; 38% reduced psychotropic and muscle relaxants, 46% reduced analgesic, anti-convulsant and NSAIDs, and 48% reduced opioid medication. Adverse events occurred at low rates without unanticipated events.

Conclusion.

Early positive results with B-SCS were maintained long term. Evidence across multiple assessment tools show that B-SCS can alleviate pain intensity, psychological distress, and improve physical function and health-related quality of life.

Level of Evidence: 3
Assessment of Adult Spinal Deformity Complication Timing and Impact on 2-Year Outcomes Using a Comprehensive Adult Spinal Deformity Classification System
Authors: Wick Joseph B. , Le Hai V. , Lafage Renaud , Gupta Munish C. , Hart Robert A. , Mundis Gregory M. , Bess Shay , Burton Douglas C. , Ames Christopher P. , Smith Justin S. , Shaffrey Christopher I. , Schwab Frank J. , Passias Peter G. , Protopsaltis Themistocles S. , Lafage Virginie , Klineberg Eric O.
Published: November 2021

Study Design.

Retrospective review of prospectively collected multicenter registry data.

Objective.

To identify rates and timing of postoperative complications in adult spinal deformity (ASD) patients, the impact of complication type and timing on health related quality of life (HRQoL) outcomes, and the impact of complication timing on readmission and reoperation rates. Better understanding of complication timing and impact on HRQoL may improve patient selection, preoperative counseling, and postoperative complication surveillance.

Summary of Background Data.

ASD is common and associated with significant disability. Surgical correction is often pursued, but is associated with high complication rates. The International Spine Study Group, AO Spinal Deformity Forum, and European Spine Study Group have developed a new complication classification system for ASD (ISSG-AO spine complications classification system).

Methods.

The ISSG-AO spine complications classification system was utilized to assess complications occurring over the 2-year postoperative time period amongst a multicenter, prospectively enrolled cohort of patients who underwent surgery for ASD. Kaplan–Meier survival curves were established for each complication type. Propensity score matching was performed to adjust for baseline disability and comorbidities. Associations between each complication type and HRQoL, and reoperation/readmission and complication timing, were assessed.

Results.

Of 584 patients meeting inclusion criteria, cardiopulmonary, gastrointestinal, infection, early adverse events, and operative complications contributed to a rapid initial decrease in complication-free survival. Implant-related, radiographic, and neurologic complications substantially decreased long-term complication-free survival. Only radiographic and implant-related complications were significantly associated with worse 2-year HRQoL outcomes. Need for readmission and/or reoperation was most frequent among those experiencing complications after postoperative day 90.

Conclusion.

Surgeons should recognize that long-term complications have a substantial negative impact on HRQoL, and should carefully monitor for implant-related and radiographic complications over long-term follow-up.

Level of Evidence: 4
Efficacy and Safety of Short-Term Dual Antiplatelet Therapy in East Asians: A Systematic Review and a Meta-Analysis of Randomized Clinical Trials
Authors: Ma Ying , Zhong Peng-Yu , Shang Yao-Sheng , Bai Nan , Niu Ying , Wang Zhi-Lu
Published: November 2021

The optimal duration of dual antiplatelet therapy (DAPT) for patients implanted with new-generation drug-eluting stents in East Asians is currently still controversial. The purpose of this meta-analysis was to investigate the efficacy and safety of short-term DAPT in patients with those. In this study, randomized controlled trials from PubMed, EMBASE, and Cochrane Library were searched to compare the efficacy and safety of short-term DAPT (6 months or less) with long-term DAPT (12 months or more) in patients implanted with new-generation drug-eluting stents in East Asian from inception to September 2020. The primary efficacy outcome was all-cause death, the primary safety outcome was major bleeding, and the secondary outcomes included cardiovascular death, myocardial infarction, definite or possible stent thrombosis, and stroke. A total of 6 randomized controlled trials with 15,688 patients met inclusion criteria; there were no significant differences in the incidence of all-cause death [risk ratio (RR), 1.03; 0.76–1.39; P = 0.856)], cardiovascular death (RR, 0.83; 0.55–1.24; P = 0.361), myocardial infarction (RR, 0.97; 0.72–1.31; P = 0.853), definite or possible stent thrombosis (RR, 1.52; 0.83–2.78; P = 0.170), and stroke (RR, 0.90; 0.61–1.31; P = 0.574) between short-term and long-term DAPTs. However, there was a significant difference in the risk of major bleeding (RR, 0.64; 0.49–0.85; P = 0.002) between the 2 groups. Compared with long-term DAPT, the short-term DAPT can reduce the risk of major bleeding without increasing the risk of death or ischemia for East Asians (Registered by PROSPERO, CRD42020213266).
Determining Postdischarge Needs of South African Parents With Premature Infants
Authors: Davis-Strauss Susan L. , Johnson Ensa , Lubbe Welma
Published: November 2021

This study explored the information and support needs of South African parents with premature infants after the initial discharge home from the hospital setting. Asynchronous online focus groups on the Facebook platform were utilized to identify the caregiving needs expressed by 25 South African parents with premature infants and to inform a parent support program in South Africa. The findings concluded that South African parents have unfulfilled information and support needs regarding their caregiving for their premature infants and their overall well-being.
Improving Access for Priority Patient Populations Within Outpatient Specialty Practices
Authors: Godsey Emily L. , Gamble A. Bruce , Palaj Arta , Beliles Gregory R. , Dunn Ajani N. , Keimig Andrew D. , Porter Ivan E.
Published: November 2021

In an outpatient health care practice, it can be challenging to convert patient demand into completed appointments, even for high-priority patients. One of the barriers to higher conversion rates is excessive appointment lag time, which can lead to nonattendance or cancellation for other reasons. In this article, we develop a mechanism for reducing appointment lag time for priority patient populations. We report on a pilot program with 12 practices, split into pilot and control groups, and involving 11001 patients requesting new appointments. The results of the pilot show that statistically significant improvements to conversion rates can be achieved.
Association of IL-10 -819C/T, -592A/C polymorphisms with the risk of preeclampsia
Authors: Che Guanglu , Liu Fang , Chang Li , Jiang Yongmei
Published: November 2021

Objective:

The purpose of our study was to investigate whether IL-10 -819C/T, -592A/C polymorphisms were associated with preeclampsia (PE) susceptibility.

Methods:

A comprehensive and systematic literature search was performed through online databases, including Web of Science, PubMed, EMBASE, and Chinese databases. Then eligible literatures were included according to inclusion criteria and exclusion criteria. Statistical data analysis was performed using Stata 10.0 software. Odds ratios (OR) and 95% confidence interval were applied to evaluated the association between IL-10 -819C/T, -592A/C polymorphisms and PE susceptibility.

Results:

According to inclusion and exclusion criteria, 9 case-control studies, including 1423 cases and 2031 controls, were included in this meta-analysis. Our meta-analysis revealed that no association was found between IL-10 -819C/T, -592A/C polymorphisms and the risk of PE in our study.

Conclusion:

Our meta-analysis suggested that IL-10 -819C/T and -592A/C polymorphisms had no association with PE susceptibility, but had a significant association with PE susceptibility in Asian and Caucasian.
Association between obesity and chronic periodontitis
Authors: Chen Tsung-Po , Yu Hui-Chieh , Lin Tai-Hsin , Wang Yu-Hsun , Chang Yu-Chao
Published: November 2021

Previous studies have suggested that obesity might be associated with chronic periodontitis (CP); however, no clear conclusions have been reached so far. In this retrospective cohort study, we aimed to investigate the association between obesity and CP by using a large population-based dataset in Taiwan.

A population-based retrospective cohort study was conducted using the Longitudinal Health Insurance Database 2010 (LHID2010) derived from the National Health Insurance Research database in Taiwan, from 2000 to 2013. Obesity and non-obesity groups were matched with sex, age, urbanization level, socioeconomic status, and the related comorbidities by using the propensity score method at a 1:2 ratio.

An obese cohort (n = 4140) and a non-obese cohort (n = 8280) were included in this study, with an average age of 41.7 ± 13.8 years and 42.0 ± 14.0 years, respectively. The risk of CP for the patients with obesity was 1.12-fold compared with those without obesity (hazard ratio, 1.12; 95% confidence interval, 1.01–1.25). In the subgroup analysis according to age and sex, the hazard ratio of CP were 1.98 (95% confidence interval, 1.22–3.22) in the subgroup of age equal to or older than 65 years. The risk of CP showed no difference between obesity and non-obesity groups in both sex.

This population-based cohort study demonstrated that obesity was associated with the development of CP in Taiwan.
Association between breakfast consumption frequency and the risk of irritable bowel syndrome among Chinese female college students
Authors: Zhang Chaowei , Zhang Jingyu , Wang Yaru , Lang Rui , Su Linxiu , Yu Miao , Zhao Xiaochen , Yang Guang , Ren Zhongyu
Published: November 2021

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder that affects specific groups of people. The relationship between breakfast consumption frequency and the risk of IBS is unclear. This study aimed to investigate the association between breakfast consumption frequency and the risk of IBS among Chinese female college students.

In this cross-sectional study (n = 706) conducted in October 2018, the frequency of breakfast consumption was categorized as 0 to 3 times/week, 4 to 6 times/week, or daily. IBS was diagnosed according to the Rome III criteria and was based on the presence of abdominal pain or discomfort for at least 3 months during the previous 6 months, with at least 2 or more of the following conditions: changes in frequency or form of stool and/or decrease in pain after defecation. We adjusted for confounding factors, including age, only child (yes or no), parents’ educational levels (senior high school or below, college, or postgraduate), parents’ marital status (married, widowed, or divorced), smoking status (smoker or nonsmoker), drinking status (drinker or nondrinker), body mass index, and depressive symptoms. A multiple logistic regression analysis was performed to determine the relationship between breakfast frequency and the risk of IBS.

Among 706 participants, 23.7% were the only child in their family, and the proportion of parents divorced or widowed was 18.5%. The proportion of fathers and mothers with high school education or above was 93.3% and 96.3%, respectively. The prevalence of IBS among the participants was 17.3% (122/706). Multivariate logistic regressions analysis showed that breakfast consumption frequency is negatively associated with the risk of IBS after adjusting for confounding factors. The odds ratios (95% confidence intervals) for IBS in the breakfast frequency category of 0 to 3 times/week, 4 to 6 times/week, and daily were 1.00 (reference), 0.96 (0.58, 1.60), and 0.45 (0.26, 0.78), respectively (P = .002).

Our data revealed that regular breakfast consumption is associated with a lower risk of IBS among Chinese college students. Future cohort and/or interventional studies should be conducted to further explore the association between breakfast consumption frequency and IBS.
The female athlete triad: review of current literature
Authors: Maya Jacqueline , Misra Madhusmita
Published: November 2021

Purpose of review

Adolescence and young adulthood are a critical period in the life of women for optimizing long-term bone health. Young athletes lead a demanding lifestyle with increased dietary requirements to meet the robust demands of energy expenditure to maintain a state of energy balance. During a time of fast paced changes and unpredictable societal demands on young athletes, it is important to review the severe consequences of energy deficiency and options for adequate management.

Recent findings

This review focuses on hormonal adaptations that occur in energy deficient female athletes that lead to menstrual irregularities and impaired bone health, increasing the risk for stress and other fractures. We also describe management strategies to mitigate the consequences of limited energy availability on bone and other outcomes.

These strategies should help guide the management of young female athletes to prevent irreversible changes to their bone health. Identifying current knowledge should help increase awareness among medical providers, which can then be communicated to the sports community, parents, and athletes.
Psychological Distress Profiles of Young Adults With Vulnerable Narcissism Traits
Authors: Casale Silvia
Published: November 2021

The current study hypothesizes a mediating role for shame in the association between vulnerable narcissism (VN) and depressive and social anxiety symptoms. A sample of 600 undergraduates was administered psychometrically sound self-reports to assess the study variables. Structural Equation Modeling supported the mediating effect of shame in the association between VN and depressive symptoms, irrespective of the way VN was assessed (i.e., Hypersensitive Narcissism Scale [HSNS] or Pathological Narcissism Inventory). Conversely, shame did not mediate the association with social anxiety when VN was assessed through the (HSNS). A direct effect of VN on both depressive and social anxiety symptoms was also detected. The results are discussed in the context of their implications, while also focusing on the different findings that emerged via the measures used to assess VN.
Supporting the Health of Our Nurses Using the 4A Model
Authors: Medland Jacqueline , Kolar Brad
Published: November 2021

Despite the well-documented need for nurse-focused efforts on health and wellness, too few healthcare organizations have made a meaningful impact on this issue. Nurse health should be integrated into the strategic and operational workings of the organization. Environments of health and wellness require attention, accountability, action, and accessibility. Although individual choice is the starting point, true success will be achieved when nurse health is a nonnegotiable outcome consistent with quality, safety, finance, and patient experience.
Who Advances Nursing Science in Practice Settings and How?
Authors: Granger Bradi B. , Johnson Karen , Norful Allison , Westlake Cheryl , Tracy Mary Fran
Published: November 2021

Nurse scientist (NS) roles in clinical practice settings are key components of The Future of Nursing and ANCC Magnet® recognition. Despite increased opportunities for NS roles, leveraging these roles to advance nursing science remains at an early stage. We describe opportunities and challenges for NSs in clinical practice settings, highlighting the value of a strong partnership with chief nurse officers as critical for the success of NSs and outcomes associated with these roles.
Patient Demographics and the Utilization of a Novel 3-Anatomic-Site Testing Panel Including Rectal Self-Collection as Compared With Usual Care Testing
Authors: Horberg Michael , Eberhart Lindsay , Bhatia Mamta , Jonas Cabell , Cherico-Hsii Sara , Tamrat Yonas , Bhandari Binamrata , Kadlecik Peter , Gahunia Mona K.
Published: November 2021

Background

At Kaiser Permanente Mid-Atlantic States, we designed a 3-anatomic-site panel (urine, oropharynx, and rectum) with a self-collect feature for rectal sites. We compared the proportion tested at each anatomic site, demographic factors, and HIV status between those who received the 3-site panel versus usual care.

Methods

Patients entered our laboratories without a prior appointment and underwent urine (usual care [patient collected]), oropharynx (laboratory technician collected), and rectal site (patient collected) testing. Providers recommended the panel to their patients. Patients then had the choice to accept or to reject the panel. Multivariate and logistic regressions were conducted to explore the relationship of age, sex, race, and HIV status with Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT) test results as well as the type of testing (3-site panel vs. usual care testing) received.

Results

A total of 145,854 patients received usual care testing as compared with 9227 who received the panel. For those who underwent usual care testing, 4.0% tested positive for CT and 0.85% for GC. For those who received the panel, 9.1% tested positive for CT and 6.4% for GC. Those who received the 3-site panel were more likely to test positive for CT (odds ratio [OR], 2.70; confidence interval [CI], 2.46–2.97) and GC (OR, 4.00; CI, 3.59–4.64). White patients were the most likely to receive the panel compared with Black patients (OR, 3.14; CI, 2.96–3.33). Patients with HIV had greater odds of undergoing the panel (OR, 15.62; CI, 14.67–16.64) and of testing positive for CT (OR, 1.27; CI, 1.07–1.51) and GC (OR, 1.39; CI, 1.14–1.68).

Conclusions

Patients who received the panel had higher odds of testing positive for CT and GC compared with patients with usual testing. Physician training may address the racial and sex differences observed in the panel enrollment and increase utilization. Self-collection for rectal sites should lead to higher detection of CT and GC.
Clinical Integration of a Highly Accurate Polymerase Chain Reaction Point-of-Care Test Can Inform Immediate Treatment Decisions for Chlamydia, Gonorrhea, and Trichomonas
Authors: Dawkins Megan , Bishop Lisa , Walker Paula , Otmaskin Danielle , Ying Julia , Schmidt Ryan , Harnett Glenn , Abraham Teresa , Gaydos Charlotte A. , Schoolnik Gary , DiBenedetto Kevin
Published: November 2021

Background

Accurate same-day sexually transmitted infection (STI) diagnostic testing is generally unavailable, leading to syndromic management with high rates of overtreatment and undertreatment. We analyzed the ease of integration of the Visby STI Panel into clinical practice, studied acceptance by patients and clinic personnel, and assessed the potential to inform accurate treatment decisions.

Methods

In a cross-sectional single-visit study of 55 women aged 18 to 56 years, women self-collected vaginal swab samples that were analyzed using the Visby STI Panel for Chlamydia trachomatis, Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV). Results were compared with standard-of-care clinic results from send-out laboratory polymerase chain reaction tests. Surveys assessed patient and device operator experiences with the Visby STI Panel and clinicians' perceived need for and acceptance of the device. Time parameters were measured to evaluate the impact on clinical workflow, and syndromic treatment decisions were compared with anticipated treatment based on the Visby STI Panel results.

Results

Patients strongly agreed that sample self-collection was easy, and operators reported the device easy to use. Clinicians valued the rapid return of results, and patients were comfortable waiting up to 30 minutes to receive them. In 13 of 15 cases, the Visby STI Panel correctly identified undertreated patients as infected and correctly identified all 33 incidences of overtreatment.

Conclusions

Clinical adoption of the Visby STI Panel into primary care clinics and doctors' offices could reduce overtreatment and undertreatment of STIs. If integrated efficiently into the clinical workflow, the test would have minimal impact on staff time and visit duration for patients.
The Most Current Algorithms for the Treatment and Prevention of Hypertrophic Scars and Keloids: A 2020 Update of the Algorithms Published 10 Years Ago
Authors: Ogawa Rei
Published: November 2021

Background:

In 2010, this Journal published my comprehensive review of the literature on hypertrophic scars and keloids. In that article, I presented evidence-based algorithms for the prevention and treatment of these refractory pathologic scars. In the ensuing decade, substantial progress has been made in the field, including many new randomized controlled trials. To reflect this, I have updated my review.

Methods:

All studies were evaluated for methodologic quality. Baseline characteristics of patients were extracted along with the interventions and their outcomes. Systematic reviews, meta-analyses, and comprehensive reviews were included if available.

Results:

Risk factors that promote hypertrophic scar and keloid growth include local factors (tension on the wound/scar), systemic factors (e.g., hypertension), genetic factors (e.g., single-nucleotide polymorphisms), and lifestyle factors. Treatment of hypertrophic scars depends on scar contracture severity: if severe, surgery is the first choice. If not, conservative therapies are indicated. Keloid treatment depends on whether they are small and single or large and multiple. Small and single keloids can be treated radically by surgery with adjuvant therapy (e.g., radiotherapy) or multimodal conservative therapy. For large and multiple keloids, volume- and number-reducing surgery is a choice. Regardless of the treatment(s), patients should be followed up over the long term. Conservative therapies, including gel sheets, tape fixation, topical and injected external agents, oral agents, and makeup therapy, should be administered on a case-by-case basis.

Conclusions:

Randomized controlled trials on pathologic scar management have increased markedly over the past decade. Although these studies suffer from various limitations, they have greatly improved hypertrophic scar and keloid management. Future high-quality trials are likely to improve the current hypertrophic scar and keloid treatment algorithms further.
Factors related to indoor prosthetic use in individuals with unilateral lower limb amputation
Authors: Tezuka Yusuke , Chin Takaaki , Azuma Yuji , Miura Yasushi
Published: November 2021

Background:

The rate of indoor prosthetic use in people with lower limb amputation (LLA) is lower than that of outdoor use. Very few studies of indoor prosthetic use have been conducted, and no studies have focused on the perspective of instrumental activities of daily living (IADLs).

Objectives:

To assess the indoor prosthetic use of individuals with unilateral LLA from the perspective of IADLs.

Study design:

Cross-sectional study.

Methods:

A total of 162 people with LLA participated in this study. Based on the information obtained from a questionnaire and medical records, the relationships between each outcome and indoor prosthetic use were assessed by univariate analysis and multivariate logistic regression analysis.

Results:

Of the 110 respondents (72.8%), 6 participants did not use the prosthesis or used it for cosmesis. With respect to the prosthetic users (n = 104), 74 (71.2%) used their prosthesis indoors and outdoors and 30 (28.8%) used it only outdoors, but none used it indoors only. On univariate analysis, five items were identified: household size, amputation level, domestic chores and outdoor activities of the Frenchay Activities Index, and difficulty donning/doffing the prosthesis. Small household, transtibial amputation, and a high score on the domestic chores of the Frenchay Activities Index (cutoff value 9.0 points) were independently associated with indoor prosthetic use.

Conclusions:

Training of motions that are desirable to use the prosthesis and participation in domestic chores frequently based on IADLs before hospitalization may increase the frequency of prosthesis use in people with transfemoral amputation who use their prosthesis outdoors.
Development and Preliminary Validation of a Virtual Reality Approach for Measurement of Torsional Strabismus
Authors: Bindiganavale Megha , Buickians David , Lambert Scott R. , Bodnar Zachary M. , Moss Heather E.
Published: November 2021

Background:

Double Maddox rod (DMR), the gold-standard method for in-office measurement of cyclodeviation, requires an examiner and specialized equipment. The objective of this study was to develop a virtual reality (VR) technique for measurement of cyclodeviation and validate this against the DMR.

Methods:

A VR-DMR was implemented using a smartphone and commercially available VR viewer. The app displayed a line to each eye and accepted touch inputs from the user to rotate the lines into perceived alignment. VR-DMR cyclodeviation measurements were compared with traditional DMR (T-DMR) cyclodeviation measurements in adults with and without strabismus and children without strabismus.

Results:

Thirty-one subjects were studied (age 5–88 years, 20 with strabismus). VR-DMR had similar test–retest reliability as T-DMR. VR-DMR was highly correlated with T-DMR (r2 = 0.94, linear regression slope 1.12) with a slight positive bias (linear regression y intercept 1°). VR-DMR was preferred by 54% of subjects with 29% having no preference.

Conclusions:

A VR method of ocular cyclodeviation measurement using sensory techniques was implemented using commercially available hardware. VR measurements compared favorably with gold-standard DMR measurements, and user feedback was positive. The VR methodology has application for in office and home use by nonexperts for purposes of strabismus monitoring.
Isolation and characterisation of quercitrin as a potent anti-sickle cell anaemia agent from Alchornea cordifolia
Authors: Adeniyi Olayemi , Baptista Rafael , Bhowmick Sumana , Cookson Alan , Nash Robert , Winters Ana , Mur Luis A. J.
Published: November 2021

Alchornea cordifolia Müll. Arg. (commonly known as Christmas Bush) has been used traditionally in Africa to treat sickle cell anaemia (a recessive disease, arising from the S haemoglobin [Hb] allele) but the active compounds are yet to be characterised. Herein we describe the use of sequential fractionation coupled with in vitro anti-sickling assays to purify the active component. Sickling was induced in HbSS genotype blood samples using sodium metabisulphite (Na2S2O5) or incubation in 100 % N2. Methanol extracts of A. cordifolia leaves and its sub-fractions showed >70 % suppression of HbSS erythrocyte sickling. Purified compound demonstrated 87.2 ± 2.39 % significant anti-sickling activity and 93.1 ± 2.69 % erythrocyte sickling-inhibition at 0.4 mg/mL. Nuclear magnetic resonance (NMR) spectra and high-resolution mass spectroscopy identified it as quercitrin (quercetin 3-rhamnoside). Purified quercitrin also inhibited the polymerisation of isolated HbS and stabilized sickle erythrocytes membranes. Metabolomic comparisons of blood samples using flow-infusion electrospray-high resolution mass spectrometry indicated that quercitrin could convert HbSS erythrocyte metabolomes to be similar to HbAA. Sickling was associated with changes in anti-oxidants, anaerobic bioenergy and arachidonic acid metabolism, all of which were reversed by quercitrin. The findings described could inform efforts directed to the development of an anti-sickling drug or quality control assessments of A. cordifolia preparations.
Jointly Optimized Spatial Histogram UNET Architecture (JOSHUA) for Adipose Tissue Segmentation
Authors: Peeples Joshua K. , Jameson Julie F. , Kotta Nisha M. , Grasman Jonathan M. , Stoppel Whitney L. , Zare Alina
Published: November 2021

Objective

We quantify adipose tissue deposition at surgical sites as a function of biomaterial implantation.

Impact Statement

To our knowledge, this study is the first investigation to apply convolutional neural network (CNN) models to identify and segment adipose tissue in histological images from silk fibroin biomaterial implants.

Introduction

When designing biomaterials for the treatment of various soft tissue injuries and diseases, one must consider the extent of adipose tissue deposition. In this work, we implant silk fibroin biomaterials in a rodent subcutaneous injury model. Current strategies for quantifying adipose tissue after biomaterial implantation are often tedious and prone to human bias during analysis.

Methods

We used CNN models with novel spatial histogram layer(s) that can more accurately identify and segment regions of adipose tissue in hematoxylin and eosin (H&E) and Masson’s Trichrome stained images, allowing for determination of the optimal biomaterial formulation. We compared the method, Jointly Optimized Spatial Histogram UNET Architecture (JOSHUA), to the baseline UNET model and an extension of the baseline model, Attention UNET, as well as to versions of the models with a supplemental “attention”-inspired mechanism (JOSHUA+ and UNET+).

Results

The inclusion of histogram layer(s) in our models shows improved performance through qualitative and quantitative evaluation.

Conclusion

Our results demonstrate that the proposed methods, JOSHUA and JOSHUA+, are highly beneficial for adipose tissue identification and localization. The new histological dataset and code for our experiments are publicly available.
All-optical electrophysiology with improved genetically encoded voltage indicators reveals interneuron network dynamics in vivo
Authors: Tian He , Davis Hunter C. , Wong-Campos J. David , Fan Linlin Z. , Gmeiner Benjamin , Begum Shahinoor , Werley Christopher A. , Borja Gabriel B. , Upadhyay Hansini , Shah Himali , Jacques Jane , Park Pojeong , Qi Yitong , Parot Vicente , Deisseroth Karl , Cohen Adam E.
Published: November 2021

All-optical electrophysiology can be a powerful tool for studying neural dynamics in vivo, as it offers the ability to image and perturb membrane voltage in multiple cells simultaneously. The “Optopatch” constructs combine a red-shifted archaerhodopsin (Arch)-derived genetically encoded voltage indicator (GEVI) with a blue-shifted channelrhodopsin actuator (ChR). We used a video-based pooled screen to evolve Arch-derived GEVIs with improved signal-to-noise ratio (QuasAr6a) and kinetics (QuasAr6b). By combining optogenetic stimulation of individual cells with high-precision voltage imaging in neighboring cells, we mapped inhibitory and gap junction-mediated connections, in vivo. Optogenetic activation of a single NDNF-expressing neuron in visual cortex Layer 1 significantly suppressed the spike rate in some neighboring NDNF interneurons. Hippocampal PV cells showed near-synchronous spikes across multiple cells at a frequency significantly above what one would expect from independent spiking, suggesting that collective inhibitory spikes may play an important signaling role in vivo. By stimulating individual cells and recording from neighbors, we quantified gap junction coupling strengths. Together, these results demonstrate powerful new tools for all-optical microcircuit dissection in live mice.
Target Recognition in Tandem WW Domains: Complex Structures for Parallel and Antiparallel Ligand Orientation in h-FBP21 Tandem WW
Authors: Wenz Marius T. , Bertazzon Miriam , Sticht Jana , Aleksić Stevan , Gjorgjevikj Daniela , Freund Christian , Keller Bettina G.
Published: November 2021

Protein-protein interactions often rely on specialized recognition domains, such as WW domains, which bind to specific proline-rich sequences. The specificity of these protein-protein interactions can be increased by tandem repeats, i.e. two WW domains connected by a linker. With a flexible linker, the WW domains can move freely with respect to each other. Additionally, the tandem WW domains can bind in two different orientations to their target sequences. This makes the elucidation of complex structures of tandem WW domains extremely challenging. Here, we identify and characterize two complex structures of the tandem WW domain of human formin-binding protein 21 and a peptide sequence from its natural binding partner, the core-splicing protein SmB/B′. The two structures differ in the ligand orientation, and consequently also in the relative orientation of the two WW domains. We analyze and probe the interactions in the complexes by molecular simulations and NMR experiments. The workflow to identify the complex structures uses molecular simulations, density-based clustering and peptide docking. It is designed to systematically generate possible complex structures for repeats of recognition domains. These stuctures will help us to understand the synergistic and multivalency effects that generate the astonishing versatility and specificity of protein-protein interactions.
Influence of different anionic charges in lead compoundsin the remediation of lead byEleusine indica (Gaertn)
Authors: Ikhajiagbe B. , Ehiarinmwian R. I. , Omoregie G.O.
Published: November 2021

The study was carried out to investigate the remediative capacity of Eleusine indica in lead-polluted soil. Soil samples were collected near student hostel (hall 5) in the University of Benin. The soil samples were sun dried to constant weight and was pulverized with wooden roller and sieved with a hand sieve of 2 mm mesh size. The sieved soil was spiked with 0.625 g lead nitrate (PbNO3), lead sulphate (PbSO4), lead carbonate (PbCO3), lead acetetrahydrate (PbC2H6) and lead chloride (PbCl2) separately in three replicate using aqueous standard solutions. Tillers of Eleusine Indica were placed in the metal – polluted soil immediately and the experiment was allowed to stay for 15 weeks. The result showed that the uptake efficiency for Eleusineindica in both shoots and roots for lead nitrate was 0.016% and 0.8%, lead sulphate 0.016 % and 0.352 %, lead carbonate 0.064% and 0.496 %, lead acetetrahydrate 0.032 % and 0.688 %, and lead chloride 0.08 % and 0.72 % respectively, indicating that the plant might have sequestered the metal in the soil rather than accumulating it in the leaves. This was evident in the presentation of the metal sequestration factor of over 70 % irrespective of the nature of the metal. Microbial count of soil before and after contamination with lead nitrate was 1.9×104 and 0.4×104 cfu/g indicating a reduction. The study therefore revealed that Eleusine indica is a high efficient plant in sequestering lead in polluted soil.