bluuebunny/crossref_metadata_2025 huggingface dataset:
Frailty as a Predictor of Postoperative Outcomes in Invasive Cardiac Surgery
Authors: Peeler Anna , Moser Chandler , Gleason Kelly T. , Davidson Patricia M.
Published: May 2021

Objectives

Frailty is a syndrome characterized by increased vulnerability and reduced ability to maintain homeostasis after stressful events that results in an increased risk for poor outcomes. Frailty screening could potentially be valuable in cardiac surgery risk assessment. The purpose of this review is to evaluate the current literature linking multicomponent frailty assessment and invasive cardiac surgery outcomes.

Methods

We searched PubMed, EMBASE, and CINAHL; 1887 articles met the search criteria, and each was independently reviewed by 2 reviewers.

Results

The 19 eligible studies assessed 52 291 subjects using 17 different frailty measurements. The most commonly used instruments were the Fried Frailty Phenotype and the Clinical Frailty Scale. Between 9% and 61% of participants were found to be frail in each study. All 19 studies included mortality as an outcome, 12 included surgical complications, 12 included hospital length of stay, 3 included quality of life, and 2 included functional status. Nine found statistically significant differences in survival between frail and nonfrail patients, 6 of 12 found that frail patients had a longer length of stay, 4 of 12 found that frail patients were more likely to experience major complications, and 2 of 2 found that frail patients were more likely to have a decrease in functional status.

Conclusion

Although some studies lacked power, the majority confirmed that frail patients are more likely to experience poor outcomes. Further research is needed to determine which frailty measure provides the best predictive validity and to identify interventions to mitigate the risks that major cardiac surgery poses to frail patients.
The Impacts of COVID-19 on Veterans Affairs Catheterization Laboratory Staff During the First Months of the US Response
Authors: Gilmartin Heather M. , Plomondon Mary E. , Mueller Candice , Connelly Brigid , Battaglia Catherine , Waldo Stephen W. , Doll Jacob
Published: May 2021

Background

The COVID-19 pandemic has altered catheterization laboratory (cath lab) practices in diverse ways.

Objective

The aim of this study was to understand the impact of COVID-19 on Veterans Affairs (VA) procedural volume and cath lab team experience.

Methods

Procedural volume and COVID-19 patient data were obtained from the Clinical, Assessment, Reporting and Tracking Program. A mixed methods survey was emailed to VA cath lab staff asking about the COVID-19 response. Descriptive and manifest content analyses were conducted.

Results

Procedural volume decreased from April to September 2020. One hundred four patients with known COVID-19 were treated. Survey response rate was 19% of staff (n = 170/902) from 83% of VA cath labs (n = 67/81). Reassignment to other units, confusion regarding COVID-19 testing, personal protective equipment use, and low patient volume were reported. Anxiety, burnout, and leadership's role on team morale were described.

Conclusions

Some teams adapted. Others expressed frustration over the lack of control over their practice. Leaders should routinely assess staff needs during the current and future crises.
KIAA0753-related skeletal ciliopathy: a ninth case, extending the phenotype and reporting a novel variant
Authors: Sabir Ataf H , Sheikh Jameela , Gowda Vasantha , Wallis Colin , Singham Surendra , Durve Dipalee , Cocca Alessandra , Holder-Espinasse Muriel , Irving Melita
Published: May 2021

KIAA0753
-related skeletal ciliopathy is a recently described recessive disorder causing skeletal dysplasia and overlapping features of certain ciliopathies; Joubert, Jeune and Oro-facial-digital syndromes. We describe a ninth case that expands the phenotype; a 10-year-old girl with rhizomelic short stature (−5.6 SD), macrocephaly, developmental delay, CNS anomalies (thin corpus callosum, bilateral ventriculomegaly), cone-rod dystrophy, nystagmus, mild conductive hearing loss and recurrent chest infections secondary to confirmed ciliary dyskinesia. Testing for
FGFR3
achondroplasia-related hotspots and mucopolysaccharidosis were negative. Whole-exome sequencing, aged eight, via skeletal dysplasia panel analysis and subsequent whole-genome sequencing (via the 100,000 genomes project) found no cause. WGS data reanalysis using exomiser uncovered compound heterozygous pathogenic
KIAA0753
variants (frameshift and splice site). Further clinical and radiological surveys were consistent with the expected phenotype. We discuss the emerging phenotype of this uncommon disorder. This report details the sixth published case of skeletal dysplasia in all cases of
KIAA0753
-related disease and the first case to describe a novel c.1830-2A>G splice variant. Our case is the eldest woman reported to date (aged ten years) and the only known case to report associated hearing loss, leg-length discrepancy, pectus carinatum, respiratory ciliary dyskinesia and late-onset (9 years old) neuro-degenerative regression.
National Trends of Hospitalizations in Cystic Fibrosis Highlight a Need for Pediatric to Adult Transition Clinics
Authors: Ramsey Mitchell L. , Lara Luis F. , Gariepy Cheryl E. , Abu-El-Haija Maisam , Hart Phil A. , Hinton Alice , Kirkby Stephen E. , Krishna Somashekar G. , Li Susan S. , Conwell Darwin L.
Published: May 2021

Objectives

We hypothesized that hospitalizations in cystic fibrosis (CF) would reflect the development of age-related comorbidities.

Methods

A retrospective analysis was performed using the Nationwide Inpatient Sample (2002–2017). Hospitalizations for which the principal diagnosis was CF were analyzed regarding age at discharge and presence of comorbidities. Trends were assessed for significance using the Cochran-Armitage test.

Results

The mean age of patients hospitalized for CF increased from 19.7 years in 2002 to 23.0 years in 2017 (P = 0.017). Several comorbidities are more than 10 times more prevalent among adults as compared with children, including congestive heart failure, substance abuse, and chronic kidney disease (P < 0.001). In addition, diabetes with chronic complications was more prevalent in adults than children (10.0% vs 3.9%; P < 0.001), as was hypertension (7.2% vs 1.3%; P < 0.001) and osteoporosis (10.2% vs 1.9%; P < 0.001). More than 65% of CF hospitalizations in 2017 were in individuals older than 18 years.

Conclusions

Hospitalizations for adults with CF are increasing, and individuals with CF are developing age-related comorbidities. Providers equipped to manage the health care needs of adults need to be ready and able to care for this unique and growing patient population.
Sex-Based Differences in Prognosis of Patients With Gastroenteropancreatic-Neuroendocrine Neoplasms
Authors: Abdel-Rahman Omar , Fazio Nicola
Published: May 2021

Objectives

The aim of this study was to assess sex-based differences in prognosis of a contemporary cohort of gastroenteropancreatic-neuroendocrine neoplasm (GEP-NEN) patients.

Methods

Surveillance, Epidemiology, and End Results database was accessed, and cases with GEP-NENs were selected. Rates of GEP-NEN diagnosis from 1975 to 2016 for both male patients and female patients were reviewed. Survival outcomes of GEP-NEN patients diagnosed from 2010 to 2014 were determined through Kaplan-Meier estimates and multivariable Cox regression analysis. Overall survival analyses were stratified by stage and histology.

Results

A total of 20,836 GEP-NEN patients were diagnosed from 2010 to 2014, and they were included in the current analysis. These include 10,336 male patients and 10,500 female patients. Annual percent change for the age-adjusted rate for GEP-NENs in the United States (1975–2016) is 5.0 (95% confidence interval [CI], 4.8–5.2). When stratified by sex, annual percent change for male patients was 4.8 (95% CI, 4.6–5.1), whereas for female patients, it was 5.0 (95% CI, 4.8–5.3). Female patients have better overall survival compared with male patients among all substrata of patients (according to stage, histology, and differentiation) (P for all comparisons <0.01).

Conclusions

Female sex seems to be associated with better overall survival among patients with GEP-NENs. It is unclear if this is the result of differences in noncancer mortality or is the result of inherent biological differences.
Prognostic Implications of the Immune Tumor Microenvironment in Patients With Pancreatic and Gastrointestinal Neuroendocrine Tumors
Authors: Baretti Marina , Zhu Qingfeng , Zahurak Marianna , Bhaijee Feriyl , Xu Haiying , Engle Elizabeth L. , Kotte Anil , Pawlik Timothy M. , Anders Robert A. , De Jesus-Acosta Ana
Published: May 2021

Objectives

The aim of this study was to characterize the tumor microenvironment of patients with gastroenteropancreatic neuroendocrine tumors relative to progression-free survival (PFS).

Methods

Immune profiling for CD3, CD8, programmed death-1/programmed death-ligand 1, and indoleamine 2,3-dioxygenase expression in 2 cohorts of gastroenteropancreatic neuroendocrine tumors: patients with short PFS (<4 years, n = 12) versus long PFS (≥4 years, n = 14) after surgery. Immune infiltrates in the tumor and interface were quantified. Programmed death-ligand 1 expression was determined within the tumor, stroma, and interface.

Results

Patients with shorter PFS had larger tumors (P = 0.02), mostly in the pancreas (P = 0.04). We observed a higher mean expression of CD3+, CD8+, programmed death-1+ cells, and indoleamine 2,3-dioxygenase at the interface compared with the tumor: log 10 mean differences 0.56 (95% confidence interval [CI], 0.43–0.68; P < 0.0001), 0.45 (95% CI, 0.32–0.59; P = 0.0002), 0.50 (95% CI, 0.40–0.61; P < 0.0001), and 0.24 (95% CI, 0.03–0.46; P = 0.046), respectively. Patients with longer PFS had higher intratumoral CD3+ T cells, log 10 mean difference 0.38 (95% CI, 0.19–0.57; P = 0.004). Programmed death-ligand 1 expression tended to be higher among patients with shortened PFS (odds ratio, 2.00; 95% CI, 0.68–5.91).

Conclusions

Higher intratumoral CD3+ T-cell infiltrate was associated with longer PFS after resection.
Blood Leukocyte Signaling Pathways as Predictors of Severity of Acute Pancreatitis
Authors: Turunen Antti , Kuuliala Antti , Mustonen Harri , Puolakkainen Pauli , Kylänpää Leena , Kuuliala Krista
Published: May 2021

Objectives

Clinical practice lacks biomarkers to predict the severity of acute pancreatitis (AP). We studied if intracellular signaling of circulating leukocytes could predict persistent organ dysfunction (OD) and secondary infections in AP.

Methods

A venous blood sample was taken from 174 patients with AP 72 hours or less from onset of symptoms and 31 healthy controls. Phosphorylation levels (p) of appropriately stimulated signal transducer and activator of transcription 1 (STAT1), STAT6, nuclear factor-κB (NF-κB), Akt, and nonstimulated STAT3 in monocytes, neutrophils, and lymphocytes was measured using phosphospecific flow cytometry.

Results

The patients showed higher pSTAT3 and lower pSTAT1, pSTAT6, pNF-κB, and pAkt than healthy controls. pSTAT3 in all leukocyte subtypes studied increased, and pSTAT1 in monocytes and T cells decreased in an AP severity-wise manner. In patients without OD at sampling, high pSTAT3 in monocytes and T lymphocytes were associated with development of persistent OD. In patients with OD, low interleukin-4–stimulated pSTAT6 in monocytes and neutrophils and Escherichia coli–stimulated pNF-κB in neutrophils predicted OD persistence. High pSTAT3 in monocytes, CD8+ T cells, and neutrophils; low pSTAT1 in monocytes and T cells; and low pNF-κB in lymphocytes predicted secondary infections.

Conclusions

Leukocyte STAT3, STAT1, STAT6, and NF-κΒ phosphorylations are potential predictors of AP severity.
Patterns of Palliative Chemotherapy and Survival in Patients With Pancreatic Cancer Focusing on Age
Authors: Rasmussen Louise S. , Fristrup Claus W. , Jensen Benny V. , Pfeiffer Per , Weber Britta , Yilmaz Mette K. , Poulsen Laurids Ø. , Ladekarl Morten , Østerlind Kell , Larsen Jim S. , Skuladottir Halla , Bøgsted Martin , Falkmer Ursula G.
Published: May 2021

Objectives

The aim of this study was to identify patterns of palliative chemotherapy (CTh) and the associated overall survival (OS) in patients with pancreatic cancer, with specific focus on age.

Methods

Between May 1, 2011, and April 30, 2016, 4260 patients were registered in the Danish Pancreatic Cancer Database. The 1715 patients receiving palliative CTh were retrieved. Age was grouped into less than 70, 70 to less than 75, and 75 years or more.

Results

Of the 1715 patients receiving first-line CTh, 586 (34%) underwent second-line CTh and 151 (9%) third-line CTh. First-line gemcitabine resulted in a significant worse survival compared with combination CTh, hazard ratio 1.51. For combination CTh, OS differed between the age groups, P < 0.01. The median OS in the less than 70 years (n = 547), 70 to less than 75 years (n = 163), and 75 years or more (n = 67) groups were 9.3, 9.6, and 7.2 months, respectively. No differences in survival were observed among patients receiving first-line gemcitabine (P = 0.35).

Conclusions

Our findings are useful in treatment-related decision making in patients with pancreatic cancer. A significant survival benefit was observed for all patients after first-line combination CTh. The effect of combination CTh was most prominent among patients aged less than 75 years. By age, no differences in survival were observed in those receiving gemcitabine.
An Overview of Current Knowledge of the Gut Microbiota and Low-Calorie Sweeteners
Authors: Hughes Riley L. , Davis Cindy D. , Lobach Alexandra , Holscher Hannah D.
Published: May 2021

This review provides an overview of the interrelationships among the diet, gut microbiota, and health status and then focuses specifically on published research assessing the relationship of low-/no-calorie sweeteners (LNCSs) to selected aspects of the gut microbiota. Microbiome research is expanding as new data on its role in health and disease vulnerability emerge. The gut microbiome affects health, digestion, and susceptibility to disease. In the last 10 years, investigations of LNCS effects on the gut microbiota have proliferated, although results are conflicting and are often confounded by differences in study design such as study diet, the form of the test article, dosage, and study population. Staying current on microbiome research and the role of dietary inputs, such as LNCSs, will allow healthcare and nutrition practitioners to provide evidence-based guidance to the individuals they serve.
Law and Policy as Tools in Healthy People 2030
Authors: Teitelbaum Joel , McGowan Angela K. , Richmond Therese S. , Kleinman Dushanka V. , Pronk Nico , Ochiai Emmeline , Blakey Carter , Brewer Karen H.
Published: May 2021

Laws and policies are critical determinants of health and well-being. They can encourage positive behaviors and discourage harmful behaviors, and they can enhance or worsen health, health equity, health disparities, and health literacy. Recognizing their contribution to conditions in the environments in which people are born, live, learn, work, play, worship, and age, and people's experiences of these conditions, the US Department of Health and Human Services considered the roles of law and policy throughout its development of Healthy People 2030. Laws and policies often interrelate, but they have different purposes. A law is an established procedure, standard, or system of rules that members of a society must follow. A policy is a decision or set of decisions meant to address a long-term purpose or problem. Healthy People 2030 offers an opportunity for users in diverse sectors and at all levels to use laws and policies to support or inform the initiative's implementation, address health disparities and health inequities, and improve health and well-being in this decade. Introducing new laws and policies or rescinding existing ones to achieve Healthy People 2030 goals offers a chance to rigorously assess outcomes and weigh the balance of good outcomes against unintended consequences.
An Academic–Health Department Community Partnership to Expand Disease Investigation and Contact Tracing Capacity and Efficiency During the COVID-19 Pandemic
Authors: Leser Kendall A. , Hay M. Cameron , Henebry Brian , Virden John , Patel Mita , Luttrell-Freeman Jordan , Bailer Jennifer
Published: May 2021

Disease investigation and contact tracing are long-standing public health strategies used to control the spread of infectious disease. Throughout the COVID-19 pandemic, health departments across the country have lacked the internal workforce capacity and technology needed to efficiently isolate positive cases and quarantine close contacts to slow the spread of SARS-CoV-2. This article describes an innovative disease investigation and contact tracing program developed through a formalized community partnership between a local county health department and local university. This innovative new program added 108 contact tracers to the county's public health workforce, as well as enabled these contact tracers to work remotely using a call center app and secure cloud-based platform to manage the county's caseload of cases and contacts. An overview of the requirements needed to develop this program (eg, hiring, health data security protocols, data source management), as well as lessons learned is discussed.
Kaiser Permanente's Good Health & Great Hair Program: Partnering With Barbershops and Beauty Salons to Advance Health Equity in West Baltimore, Maryland
Authors: Nadison Maya , Flamm Laura J. , Roberts Alma , Staton Troy , Wiener Lisa , Locke Jessica , Bullock Eddye , Loftus Bernadette , Carpenter Carrie , Sadler Michele , Horberg Michael A.
Published: May 2021

Context:

The Good Health & Great Hair program was developed by Kaiser Permanente in partnership with a network of trusted neighborhood barbershops and beauty salons in West Baltimore, Maryland.

Program:

The initiative aimed to increase health awareness and knowledge and reduce health disparities by making no-cost health care services available beyond traditional health care settings in predominantly Black, historically redlined neighborhoods in West Baltimore.

Implementation:

This initiative, established by an integrated health care system, is the first to utilize mobile health clinics into a holistic community health outreach program in partnership with barbershops and beauty salons to provide medical and social services to underserved populations. In addition to the mobile health clinics, key features of this program included lay first responder trainings on topics of physical and behavioral health, on-site medical and social services offered by community partners, and culturally relevant mental health programming. The majority of participants (n = 1823) were male (58%), Black (86%), and between the ages of 45 and 64 years (51%).

Evaluation:

Data presented include the number of clinical and social services provided. More than 8000 clinical and social services were provided between September 2016 and March 2020. Blood pressure (n = 2317), diabetes (n = 469), tobacco (n = 448), and cholesterol (n = 443) were the most accessed clinical screening services. The median number of clinical services provided per client was 2. Fitness (n = 1496), job search support (n = 1123), mental health (n = 603), and health insurance (n = 455) were the most accessed social services.

Discussion:

The initiative delivered critical health and social support services through a partnership with an established integrated health care system, community barbershops and beauty salons, a mobile health team, and social supports. This novel program utilized a mobile health clinic to provide extensive clinical services complemented by on-site social services. Patterns of service utilization and lessons learned could inform the design of similar programs.
Provider Reactions to Opioid-Prescribing Report Cards
Authors: Alishahi Musheng L. , Olson Katie , Brooks-Russell Ashley , Hoppe Jason , Runyan Carol
Published: May 2021

Objective:

To evaluate prescribers' reactions and self-reported intentions to change prescribing behavior in response to opioid-prescribing report cards.

Design:

We surveyed a sample of licensed prescribers in the state of Colorado registered with the state's prescription drug monitoring program (PDMP).

Setting:

In 2018, Colorado disseminated tailored opioid-prescribing report cards to increase use of the PDMP and improve opioid prescribing. Report cards reflected individual prescribing history and compared individuals with an aggregate of others in the same specialty. Surveys were sent to approximately 29 000 prescribers registered with the PDMP 12 weeks after report card distribution. If respondents were not sent a report card, they were shown a sample report. Respondents were asked about their perceptions of the usefulness of the information and intentions to change their prescribing.

Participants:

A total of 3784 prescribers responded to the survey.

Main Outcome Measures:

Respondents were asked about their attitudes and reactions to an opioid-prescribing report card. Answers were given in the form of a 5-point Likert scale or multiple-choice questions.

Results:

Of those who responded, 53.6% were male and nearly half (49.5%) had spent more than 20 years in practice. Among prescribers who recalled receiving a report card, most felt the reports were easy to understand (87.4%) and provided new information (82.8%). Two-thirds of prescribers who saw their reports felt the information accurately reflected their prescribing practices. Overall, 40.0% reported they planned to change their prescribing behaviors as a result of the information provided. The most useful metrics identified by prescribers were the number of patients with multiple providers and the number of patients receiving dangerous combination therapy.

Conclusions:

Overall, perceptions of the usefulness and accuracy of the report cards were positive. Understanding how the reports are perceived is a key factor to their use and influence. Further tailoring of the report to prescribers of different specialties and experience may enhance the effectiveness of the report cards.
Resources Used by Federally Qualified Health Center Leadership to Learn About Preventive Care Interventions
Authors: Stradtman Lindsay R. , Carman Angela L. , Vanderpool Robin C.
Published: May 2021

Federally qualified health centers (FQHCs) serve patient populations that commonly have low preventive care utilization rates. Implementation of preventive care interventions (PCIs) may help decrease these care deficiencies. A survey of Kentucky FQHC leaders was conducted in 2019 to determine resources used to learn about PCIs and how leaders decide to implement them. Nineteen of Kentucky's 24 FQHCs completed the survey for a participation rate of 79%. Among participating FQHC leadership, the 3 resources that were very or somewhat likely to be used to learn about PCIs were advice or consultation from peers (100%), professional associations (95%), and nonacademic conferences/meetings (90%). The state primary care association and statewide community health center network were listed as the most helpful resources. These results highlight the types of resources used by FQHC leadership to learn about PCIs. Understanding preferred learning methods can help researchers improve outreach to FQHCs and facilitate dissemination of PCIs.
Trigger-Site Deactivation Surgery for Nerve Compression Headaches
Authors: Gfrerer Lisa , Dayan Erez , Austen William Gerald
Published: May 2021

Learning Objectives:

After studying this article, the participant should be able to: 1. Identify patients who are candidates for headache surgery. 2. Counsel the patient preoperatively with regard to success rates, recovery, and complications. 3. Develop a surgical plan for primary and secondary nerve decompression. 4. Understand the surgical anatomy at all trigger sites. 5. Select appropriate International Classification of Diseases, Tenth Revision, and CPT codes.

Headache surgery encompasses release of extracranial peripheral sensory nerves at seven sites. Keys to successful surgery include correct patient selection, detailed patient counseling, and meticulous surgical technique. This article is a practical step-by-step guide, from preoperative assessment to surgery and postoperative recovery. International Classification of Diseases, Tenth Revision, and CPT codes, in addition to complications and salvage procedures, are discussed. Intraoperative photographs, videos, and screening questionnaires are provided.
The Impact of Political Advocacy on the Plastic Surgeon: A Data-Driven Analysis
Authors: Ellsworth Warren A. , Hill David A. , Abu-Ghname Amjed , Davis Matthew J. , Buchanan Edward P. , Jalalabadi Faryan
Published: May 2021

Background:

Despite successful legislative efforts by the American Society of Plastic Surgeons (ASPS), the Plastic Surgery Political Action Committee remains underused. Participation in advocacy and financial contributions of ASPS members fall below those of similar surgical subspecialties. This study aims to perform a data-driven investigation into the impact of Plastic Surgery Political Action Committee efforts on the practicing plastic surgeon.

Methods:

A retrospective review of the ASPS procedural database from 1992 to 2018 and Plastic Surgery Political Action Committee contributions from 2012 to 2018 was performed. Postmastectomy breast and congenital anomaly reconstructions were analyzed. To determine significant variations in trends, change-point analyses were conducted. Changes in surgical volume were correlated to implementation of federal legislative efforts.

Results:

Three significant trends of increased breast reconstruction volume were detected with associations to three specific legislative changes: 1992 to 1998, which correlates with the Women’s Health and Cancer Rights Act; 2006 to 2009, which correlates with the U.S. Food and Drug Administration’s approval of silicone breast implant use; and 2013 to 2015, which correlates with the Breast Cancer Patient Education Act. During the study period, breast reconstruction procedures increased substantially compared with all reconstructive procedures (146.6 percent versus 3.6 percent). There were no significant trends detected for birth defect reconstructions. Although contributions were relatively stagnant, resident member contributions increased after 2015, correlating with formation of the Political Action Committee’s Resident’s Club.

Conclusions:

This study demonstrates a correlation in timing between Plastic Surgery Political Action Committee legislative accomplishments and the resulting case volume increase in some areas of plastic surgery. The data highlight the importance of political advocacy and how political action committee activities can directly impact patient access to care and the practice of plastic surgery.
Simultaneous Circumferential Body Lift and Four-Flap Breast Reconstruction Using Deep Inferior Epigastric Perforator and Lumbar Artery Perforator Flaps
Authors: Haddock Nicholas T. , Kelling Joseph A. , Teotia Sumeet S.
Published: May 2021

The ideal autologous breast reconstruction provides a long-lasting and aesthetically pleasing result. The deep inferior epigastric perforator (DIEP) flap remains the gold standard for breast reconstruction; however, in a subset of patients, this flap may not provide adequate soft tissue to achieve the patient’s aesthetic goals. The lumbar artery perforator flap has emerged as a useful adjunct to the DIEP flap for four-flap breast reconstruction, and also provides the patient with circumferential body contouring. From April 1 to July 1, 2019, the authors performed two bilateral stacked DIEP and lumbar artery perforator flap breast reconstructions. The authors retrospectively reviewed patient charts for pertinent data. Patients were chosen for reconstruction based on their physical examination and computed tomographic angiography findings. The operative technique used was unchanged for both reconstructions. The average total length of surgery was 553 minutes. The average DIEP flap weight was 510 g and the average lumbar artery perforator flap weight was 680 g. The average ischemia time for each lumbar artery perforator flap was 62 minutes. Length of stay was 3 days for both patients. This article describes the authors’ approach to total breast reconstruction with stacked lumbar artery perforator flaps and DIEP flaps while also effectively performing a circumferential lower body lift. Critical components for success include appropriate patient selection and using a team approach with appropriately experienced staff at all levels of care.
Topical Application of Conditioned Medium from Hypoxically Cultured Amnion-Derived Mesenchymal Stem Cells Promotes Wound Healing in Diabetic Mice
Authors: Takahashi Hiroko , Ohnishi Shunsuke , Yamamoto Yuhei , Hayashi Toshihiko , Murao Naoki , Osawa Masayuki , Maeda Taku , Ishikawa Kosuke , Sakamoto Naoya , Funayama Emi
Published: May 2021

Background:

Mesenchymal stem cells or their conditioned medium improve chronic wound healing, and their effect is enhanced by hypoxia. Diabetic foot ulcers are chronic wounds characterized by abnormal and delayed healing, which frequently require amputation. The authors evaluated the effect of topical application of conditioned medium from hypoxically cultured amnion-derived mesenchymal stem cells on wound healing in diabetic mice.

Methods:

Amnion-derived mesenchymal stem cells were cultured under 21% oxygen to prepare normoxic conditioned medium and under 1% oxygen to prepare hypoxic conditioned medium. Hydrogels containing standard medium, normoxic conditioned medium, or hypoxic conditioned medium were topically applied to excisional wounds of mice with streptozotocin-induced diabetes. Ulcer tissues were harvested on day 9; immunohistochemical and quantitative polymerase chain reaction analyses were performed to analyze angiogenesis, inflammatory cell infiltration, and expression levels of inflammation-related genes.

Results:

Hypoxic conditioned medium significantly enhanced wound closure, increased capillary density and epithelization, and reduced macrophage infiltration. It also tended to reduce the infiltration of neutrophils and enhance the infiltration of regulatory T cells; it showed a tendency to downregulate the expression of the inflammation-related genes interleukin-1β, interleukin-6, chemokine ligand 1, and chemokine ligand 2. Normoxic conditioned medium exhibited similar effects, although they were of lesser magnitude than those of hypoxic conditioned medium.

Conclusions:

Hydrogels containing hypoxically cultured, amnion-derived mesenchymal stem cell conditioned medium accelerated wound healing in diabetic mice by enhancing angiogenesis, accelerating epithelization, and suppressing inflammation. Therefore, topical application of amnion mesenchymal stem cell–derived hypoxic conditioned medium could be a novel treatment for diabetic foot ulcers.
An Algorithm for Management of Cosmetic and Reconstructive Patients with Textured Implants: An Institutional Experience
Authors: Colwell Amy S. , Lamb Leslie R. , Tomczyk Eleanor , Faulkner Heather , Specht Michelle C.
Published: May 2021

Textured anatomic silicone gel breast implants have advantages of gel cohesivity and a natural slope between the upper and lower poles of the breast; however, they have fallen out of favor secondary to their risk of breast implant-associated anaplastic large cell lymphoma. For patients who choose to keep their textured devices, there remains controversy over the best long-term follow-up. This article presents an algorithm from plastic surgery, surgical oncology, and radiology at the Massachusetts General Hospital for management of these patients.
Short Telomeres and a T-Cell Shortfall in COVID-19: The Aging Effect
Authors: Anderson James J. , Susser Ezra , Arbeev Konstantin G. , Yashin Anatoliy I. , Levy Daniel , Verhulst Simon , Aviv Abraham
Published: May 2021

The slow pace of global vaccination and the rapid emergence of SARS-CoV-2 variants suggest recurrent waves of COVID-19 in coming years. Therefore, understanding why deaths from COVID-19 are highly concentrated among older adults is essential for global health. Severe COVID-19 T-cell lymphopenia is more common among older adults, and it entails poor prognosis. Much about the primary etiology of this form of lymphopenia remains unknown, but regardless of its causes, offsetting the decline in T-cell count during SARS-CoV-2 infection demands fast and massive T-cell clonal expansion, which is telomere length (TL)-dependent. We have built a model that captures the effect of age-dependent TL shortening in hematopoietic cells and its effect on T-cell clonal expansion capacity. The model shows that an individual with average hematopoietic cell TL (HCTL) at age twenty years maintains maximal T-cell clonal expansion capacity until the 6th decade of life when this capacity plummets by more than 90% over the next ten years. The collapse coincides with the steep increase in COVID-19 mortality with age. HCTL metrics may thus explain the vulnerability of older adults to COVID-19. That said, the wide inter-individual variation in HCTL across the general population means that some younger adults with inherently short HCTL might be at risk of severe COVID-19 lymphopenia and mortality from the disease.

Significance Statement

Declining immunity with advancing age is a general explanation for the increased mortality from COVID-19 among older adults. This mortality far exceeds that from viral illnesses such as the seasonal influenza, and it thus requires specific explanations. One of these might be diminished ability with age to offset the development of severe T-cell lymphopenia (a low T-cell count in the blood) that often complicates COVID-19. We constructed a model showing that age-dependent shortening of telomeres might constrain the ability of T-cells of some older COVID-19 patients to undertake the massive proliferation required to clear the virus that causes the infection. The model predicts that individuals with short telomeres, principally seniors, might be at a higher risk of death from COVID-19.
Evaluating the effects of second-dose vaccine-delay policies in European countries: A simulation study based on data from Greece
Authors: Barmpounakis P. , Demiris N. , Kontoyiannis I. , Pavlakis G. , Sypsa V.
Published: May 2021

The results of a simulation-based evaluation of several policies for vaccine rollout are reported, particularly focusing on the effects of delaying the second dose of two-dose vaccines. In the presence of limited vaccine supply, the specific policy choice is a pressing issue for several countries worldwide, and the adopted course of action will affect the extension or easing of non-pharmaceutical interventions in the next months. We employ a suitably generalised, age-structure, stochastic SEIR (Susceptible → Exposed → Infectious → Removed) epidemic model that can accommodate quantitative descriptions of the major effects resulting from distinct vaccination strategies. The different rates of social contacts among distinct age-groups (as well as some other model parameters) are informed by a recent survey conducted in Greece, but the conclusions are much more widely applicable. The results are summarised and evaluated in terms of the total number of deaths and infections as well as life years lost. The optimal strategy is found to be one based on fully vaccinating the elderly/at risk as quickly as possible, while extending the time-interval between the two vaccine doses to 12 weeks for all individuals below 75 years old, in agreement with epidemic theory which suggests targeting a combination of susceptibility and infectivity. This policy, which is similar to the approaches adopted in the UK and in Canada, is found to be effective in reducing deaths and life years lost in the period while vaccination is still being carried out.
A multi-scale in silico mouse model for insulin resistance and humanoid type 2 diabetes
Authors: Simonsson Christian , Lövfors William , Bergqvist Niclas , Nyman Elin , Gennemark Peter , Stenkula Karin G , Cedersund Gunnar
Published: May 2021

Insulin resistance (IR) causes compensatory insulin production, which in humans eventually progresses to beta-cell failure and type 2 diabetes (T2D). This disease progression involves multi-scale processes, ranging from intracellular signaling to organ-organ and whole-body level regulations, on timescales from minutes to years. T2D progression is commonly studied using overfed and genetically modified rodents. However, rodents do not exhibit human T2D progression, with IR-driven beta-cell failure, and available multi-scale data is too complex to fully comprehend using traditional analysis. To help resolve these issues, we here present an in silico mouse model. This is the first mathematical model that simultaneously explains multi-scale mouse IR data on all three levels – cells, organs, body – ranging from minutes to months. The model correctly predicts new independent multi-scale validation data and provides insights into non-measured processes. Finally, we present a humanoid in silico mouse exhibiting disease progression from IR to IR-driven T2D.
Locus Coeruleus Stimulation Affects response Adaptation in the Somatosensory Cortex of Whisker-to-barrel Touch System
Authors: Fazlali Zeinab , Ranjbar-Slamloo Yadollah
Published: May 2021

Stimulus-driven responses in the cortex reduce due to prior exposure to sensory stimuli, a phenomenon called sensory adaptation. Depression of synaptic supplies and afterhyperpolarization (AHP) following each action potential are the main proposed mechanisms for adaptation. In vitro studies have shown that the neuronal adaptation in the barrel cortex depends on slow AHPs. Such AHPs can be affected by neuromodulators, such as noradrenaline. This evidence suggests that Locus Coeruleus (LC) noradrenergic system may reduce sensory adaptation through this cellular mechanism. We proposed that LC stimulation before whisker deflection can affect the degree of adaptation in the barrel cortex, depending on the nature of noradrenergic interactions in the barrel cortex. We coupled adapted or non-adapted whisker deflections with LC phasic stimulation with a 400 ms interval. A 50ms sinusoidal vibration was applied to the whisker immediately before the test deflection. Neuronal activity was recorded from the barrel cortex (BC) in a urethane anesthetized rat. We quantified the effect of LC stimulation on the degree of adaptation in BC; a lower adaptation index shows lower adaptation. Our result showed that LC stimulation significantly modulated adapted response in 30 % of units with insignificant modulation on the adaptor or non-adapted response. This modulation was in two directions; adaptation decreased in 5 % of units and increased in 25 % of units.

In addition to LC modulation on adaptor response in the level of individual units, adaptor response was lower modulated in around 70 % of units, on average. This modulation was not correlated by LC modulation on non-adapted response. Although sensory adaptation in BC was attenuate by LC stimulation in the majority of units, there was a limited number of units that showed significant modulation.
TMPs Interaction Domain: A Discovery of Structural Universality Among TMPs Interaction Sites Using Deep Learning Method
Authors: Bao Yihang , Wang Weixi , Dong Minglong , He Fei , Wang Han
Published: May 2021

Transmembrane proteins (TMPs) serve as important drug targets and accounts for nearly half of the drugs currently available in the market. Research into TMPs interactions and their structural basis will provide key information for drug research and new drug development. Based on previous works like a binding pocket or binding site, our main purpose in this study is to find whether the structural universality (Interaction Domain) exists in all kinds of TMPs interaction regions through a computational approach. After implementing the experiments using our 3D deep learning model and achieve the Matthews correlation coefficient (MCC) of 0.36, we found strong evidence for the existence of the structural basis among TMPs interaction regions. That means those regions, or we call them interaction domains, are structural specific distinguishing to the domains without any interaction. According to this, this work provides a new theoretical basis for TMPs interaction research and can greatly boost the development of the drug industry.
Four new threatened species ofRinorea(Violaceae), treelets from the forests of Cameroon
Authors: Achoundong Gaston , van der Burgt Xander , Cheek Martin
Published: May 2021

Four species ofRinoreaare described as new to science; all four species are endemic to evergreen rain forest in Cameroon.Rinorea villiersiiAchound., andRinorea amietiiAchound. are placed in Sect.CrassifloraeWahlert, whileRinorea dewildeiAchound. andRinorea faureiAchound. fall inRinoreasectionDentatae(Engl.) Wahlert. The first species appears to be endemic to the Solé Forest Reserve northeast of Yabassi in Littoral Region. The second and the third species are found mainly in Littoral and South Regions,Rinorea amietiiextending to South West Region andRinorea dewildeiextending to Central Region. The fourth species,Rinorea faureiis an endemic of the Santchou Forest Reserve at the foot of Dschang Plateau in West Region. The affinities of the four species are discussed, they are illustrated and mapped, and their conservation status is assessed. All four species are threatened with extinction according to the 2012 IUCN categories and criteria.
Assessment of CSF biomarkers and microRNA-mediated disease mechanisms in SMA
Authors: Welby Emily , Rehborg Rebecca J. , Harmelink Matthew , Ebert Allison D.
Published: May 2021

Objective

Cerebral spinal fluid (CSF) is a promising biospecimen for the detection of central nervous system (CNS) biomarkers to monitor therapeutic efficacy at the cellular level in neurological diseases. Spinal muscular atrophy (SMA) patients receiving intrathecal antisense oligonucleotide (nusinersen) therapy tend to show improved motor function, but the treatment effect on cellular function remains unknown. The objective of this study was to assess the potential of extracellular RNAs and microRNAs in SMA patient CSF as indicators of neuron and glial health following nusinersen treatment.

Methods

CSF samples from SMA Type 1-3 patients were screened using quantitative RT-PCR to assess expression of extracellular RNAs associated with inflammation and cellular stress, and microRNAs previously implicated in SMA pathogenesis. We also used mRNA sequencing and multi-electrode array approaches to assess the transcriptional and functional effects of astrocyte-associated miR-146a on healthy and SMA induced pluripotent stem cell (iPSC)-derived motor neurons.

Results

Extracellular RNA analysis is suggestive of ongoing cellular stress, even in nusinersen treated samples. microRNAs previously associated with SMA pathology tended to show improvement in expression levels in nusinersen treated samples, with the exception of the astrocyte-secreted miR-146a. miR-146a treated iPSC-derived motor neurons showed a downregulation of extracellular matrix genes found in the synaptic perineuronal net and decreased spontaneous activity.

Interpretation

Extracellular RNAs and microRNAs can be detected in SMA patient CSF samples, potentially serving as useful biomarkers to monitor cellular health during nusinersen treatment. Astrocyte health and response to nusinersen are important aspects to address in SMA pathogenesis and treatment strategies.
Synergistic coevolution accelerates genome evolution
Authors: Preussger Daniel , Herbig Alexander , Kost Christian
Published: May 2021

Ecological interactions are key drivers of evolutionary change. Although it is well-documented that antagonistic coevolution can accelerate molecular evolution, the evolutionary consequences of synergistic coevolution remain poorly understood. Here we show experimentally that also synergistic coevolution can speed up the rate of molecular evolution. Pairs of auxotrophic genotypes of the bacterium Escherichia coli, whose growth depended on a reciprocal exchange of amino acids, were experimentally coevolved, and compared to two control groups of independently growing cells. Coevolution drove the rapid emergence of a strong metabolic cooperation that correlated with a significantly increased number of mutations in coevolved auxotrophs as compared to monoculture controls. These results demonstrate that synergistic coevolution can cause rapid evolution that in the long run may drive diversification of mutualistically interacting species.

One-Sentence Summary

Synergistic coevolution among obligate mutualists increases the rate of molecular evolution relative to independent types.
Large-scale field phenotyping using backpack LiDAR and GUI-based CropQuant-3D to measure structural responses to different nitrogen treatments in wheat
Authors: Zhu Yulei , Sun Gang , Ding Guohui , Zhou Jie , Wen Mingxing , Jin Shichao , Zhao Qiang , Colmer Joshua , Ding Yanfeng , Ober Eric S. , Zhou Ji
Published: May 2021

Plant phenomics is widely recognised as a key area to bridge the gap between traits of agricultural importance and genomic information. A wide range of field-based phenotyping solutions have been developed, from aerial-based to ground-based fixed gantry platforms and handheld devices. Nevertheless, several disadvantages of these current systems have been identified by the research community concerning mobility, affordability, throughput, accuracy, scalability, as well as the ability to analyse big data collected. Here, we present a novel phenotyping solution that combines a commercial backpack LiDAR device and our graphical user interface (GUI) based software called CropQuant-3D, which has been applied to phenotyping of wheat and associated 3D trait analysis. To our knowledge, this is the first use of backpack LiDAR for field-based plant research, which can acquire millions of 3D points to represent spatial features of crops. A key feature of the innovation is the GUI software that can extract plot-based traits from large, complex point clouds with limited computing time and power. We describe how we combined backpack LiDAR and CropQuant-3D to accurately quantify crop height and complex 3D traits such as variation in canopy structure, which was not possible to measure through other approaches. Also, we demonstrate the methodological advance and biological relevance of our work in a case study that examines the response of wheat varieties to three different levels of nitrogen fertilisation in field experiments. The results indicate that the combined solution can differentiate significant genotype and treatment effects on key morphological traits, with strong correlations with conventional manual measurements. Hence, we believe that the combined solution presented here could consistently quantify key traits at a larger scale and more quickly than heretofore possible, indicating the system could be used as a reliable research tool in large-scale and multi-location field phenotyping for crop research and breeding activities. We exhibit the system’s capability in addressing challenges in mobility, throughput, and scalability, contributing to the resolution of the phenotyping bottleneck. Furthermore, with the fast maturity of LiDAR technologies, technical advances in image analysis, and open software solutions, it is likely that the solution presented here has the potential for further development in accuracy and affordability, helping us fully exploit available genomic resources.