bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered functions of platelets during aging
Authors: Montenont Emilie , Rondina Matthew T. , Campbell Robert A.
Published: July 2019

Purpose of review

Platelets are specialized effector cells that rapidly respond to sites of vascular injury. However, emerging data demonstrate that platelets possess diverse functions that also mediate inflammatory responses and neurological diseases. These functions are relevant to disease processes prevalent among older adults and likely influence susceptibility to thrombotic and inflammatory disorders.

Recent findings

Platelet counts decrease in aged individuals whereas platelet reactivity increases. The platelet transcriptome is altered in aged individuals resulting in altered platelet function and exaggerated inflammation. Platelet signaling to monocytes in aging results in significantly more cytokines because of increased platelet-derived granzyme A. Platelet activation in aging appears to be driven, in part, because of increased reactive oxygen species and activation of the mammalian target of rapamycin pathway. Increased platelet hyperactivity in diseases is associated with aging, such cardiovascular disease and sepsis, exaggerate inflammation and thrombosis. Noncanonical functions of platelets influence the development of neurological diseases including Alzheimer's disease.

Although there have been advances dissecting the molecular mechanisms regarding aging-related changes in platelets, many knowledge gaps still remain. Studies filling these gaps are likely to identify new mechanisms driving aging-related changes in platelet gene expression and function, and contributing to injurious thrombo-inflammation in older adults.
Surgical and Oncological Outcomes of Laparoscopic Versus Open Pancreaticoduodenectomy in Patients With Pancreatic Duct Adenocarcinoma
Authors: Yin Zi , Jian Zhixiang , Hou Baohua , Jin Haosheng
Published: July 2019

It is not clear which of the 2 principal treatments for patients with pancreatic duct adenocarcinoma (PDAC), laparoscopic pancreaticoduodenectomy (LPD) and open pancreaticoduodenectomy (OPD), has greater safety and efficacy. We performed the present meta-analysis to assess the efficacy of both treatments for PDAC patients undergoing LPD. Multiple electronic databases were systematically searched to identify studies (up to October 2018) comparing LPD with OPD for PDAC. Short- and long-term oncological outcomes were evaluated. Six studies were qualified for inclusion criteria in this meta-analysis with a total of 9144 PDAC participants. Regarding safety, there were fewer overall postoperative complications associated with LPD (P = 0.005), but the results were similar in terms of pancreatic fistula and mortality. Laparoscopic pancreaticoduodenectomy was associated with a better trend of performance both in R0 resection (relative risk, 1.03; 95% confidence interval [CI], 1.00–1.07; P = 0.07) and preserved lymph nodes (median, 2.14; 95% CI, −0.21 to 4.49; P = 0.07). Long-term overall survival was comparable between LPD and OPD (hazard ratio, 1.03; 95% CI, 0.95–1.13; P = 0.49). In conclusion, LPD was found to be a suitable alternative to OPD in selected PDAC patients with respect to both surgical and oncological outcomes.
Refining Psychological, Substance Use, and Sociodemographic Predictors of Suicide Ideation and Attempts in a National Multiethnic Sample of Adults, 2008–2013
Authors: Cheref Soumia , Benoit Julia S. , Walker Rheeda L.
Published: July 2019

The purpose of this study was to examine psychological, substance use, and sociodemographic predictors of 12-month suicide ideation and attempts across six US racial/ethnic groups—white, Latino/a, Black, Asian or Pacific Islander (A/PI), American Indian or Alaska Native (AI/AN), and multiracial adults. Multiple logistic regression analyses were conducted for 218,765 adults who participated in the 2008–2013 National Survey on Drug Use and Health. Overall, commonly cited factors were associated with increased risk for suicide ideation and attempt for some racial/ethnic groups, but not for others. As one example, 12-month depression was associated with 12-month suicide attempt for A/PI, AI/AN, Latino/a, and white, but not for Black or multiracial adults. Alcohol abuse and dependence were also associated with suicide attempt for AI/AN, Black, and white respondents but not for other racial/ethnic groups. Risk factors for suicide ideation and attempt may not increase risk universally. More theoretically supported research is needed.
The Experience of Being a Millennial Nurse Manager
Authors: Saifman Heather , Sherman Rose O.
Published: July 2019

Objective

The aim of this study was to explore the experience of being a Millennial nurse manager with a goal to better understand the influence of organizational factors on role expectations, satisfaction, support, development, and intent to stay.

Background

Research on Millennial nurse leaders is scarce. Understanding the perception of these young managers is needed to create succession and retention planning that meets the needs of this generation of leaders.

Method

A national sample of 25 Millennial nurse managers participated in a qualitative interpretative phenomenological study. Audio-recorded telephone interviews were conducted and analyzed.

Results

Millennial leaders have a unique perspective on role expectations and support variables. Seven themes of experience emerged: coming into the role, learning as I go, having the support of my director, making an impact, helping staff succeed, and managing change.

Conclusions

Opportunities to develop and retain Millennial leaders are shaped by understanding the support variables that are important to them.
Bone Marrow Immunohistochemistry and Flow Cytometry in the Diagnosis of Malignant Hematologic Diseases With Emphasis on Lymphomas: A Comparative Retrospective Study
Authors: Landry Maude , Bienz Marc-Nicolas , Sawan Bassem , Temmar Rabia , Beauregard Patrice , Chaunt Francis , Lavigne Jean , Knecht Hans
Published: July 2019

We aim to evaluate the degree of agreement between immunohistochemistry (IHC) and flow cytometry (FC) in the diagnosis of malignant hematologic diseases, mainly lymphomas. A total of 260 bone marrow biopsies, 255 bone marrow aspirates, and 5 other suspensions of 260 patients used for diagnosis of a hematologic malignancy between 2009 and 2012 with both, IHC and FC, were retrospectively analyzed. Overall there is a substantial degree of agreement (κ=0.69) between IHC and FC. Chronic lymphocytic leukemia/small lymphocytic lymphoma, mature T-cell neoplasms, acute leukemias, and myelodysplastic syndromes had the highest concurrence rates (>80%). In nonconcordant cases, an IHC provided diagnosis in 25.4%, and an FC in 4.6%. Lymphomas were diagnosed by an IHC only in 51% of the cases. Both methods have good concurrence rates and are complementary. An IHC has the advantage of combining markers, morphology, and tissue immunoarchitecture, which is beneficial in the diagnosis of lymphomas. An FC is required in leukemias as it is faster and plays an important role in minimal residual disease.
Extramammary Paget Disease of the Scrotum: A Contemporary Clinicopathologic Analysis of 20 Cases in the United States
Authors: Shabihkhani Maryam , Patil Pallavi , Murati Amador Belkiss , Plaza Jose A. , Osunkoya Adeboye O. , Lombardo Kara A. , Epstein Jonathan I. , Matoso Andres
Published: July 2019

Extramammary Paget disease (EMPD) often involves apocrine gland-bearing locations including vulva and perianal area. EMPD of the scrotum is rare. Twenty patients were identified from the pathology files of 4 institutions between 2000 and 2018. Patients were 63- to 87-year-old (mean: 73 y) with a history of symptoms of between 4 months and 10 years. Two patients had a history of prostate cancer. Follow-up was available in 11 patients for a median of 71 months (range: 8 to 126 mo). Nine of 11 patients (82%) had positive margins, and 73% required reexcisions. Three patients had a focal dermal invasion, 1 of whom reportedly died of another etiology 25 months post diagnosis and 2 were disease-free at 24 and 68 months. No patient had inguinal lymphadenopathy. Two patients were alive with disease. Immunohistochemically, GATA3 and GCDFP15 were expressed in 6/6 cases, CK7 in 8/8 cases, and androgen receptor in 13/13 cases. HER2 was positive in 5/12 cases. PSA was positive in 1 patient who had a history of prostate cancer, whereas other prostate markers (NKX3.1 and prostein) were negative, and CK7 and GCDFP15 were positive, rendering primary EMPD diagnosis. Twelve other cases were negative for PSA and NKX3.1. In conclusion, EMPD of the scrotum has an insidious onset and its nonspecific symptoms can be misdiagnosed as dermatitis or fungal infection. Although localized EMPD has a favorable prognosis, the invasive disease is rare and did not predict metastasis or progression. Margins are frequently positive requiring reexcision. Occasionally, cases can be positive for PSA leading to diagnostic pitfalls.
Endoscopic Endonasal Transpterygoid Approach Using Pedicled Nasoseptal Flap for Petrous Apex Cholesterol Granuloma With Intraoperative Video
Authors: Kim Ji-Sun , Kim Dong-Hyun , Yoon Wan-Soo , Kim Yeonji
Published: July 2019

With the development of minimally invasive endoscopic surgery and image-guided navigation systems, the endoscopic endonasal approach to petrous apex lesions has become more favorable. In this case, a petrous apex cholesterol granuloma was successfully treated with an endoscopic endonasal transpterygoid approach. A navigation system was used, and a contralateral nasoseptal flap and silicone tube stent were applied to maintain the cholesterol granuloma drainage pathway. The authors describe the endoscopic endonasal transpterygoid approach using a pedicled nasoseptal flap for petrous apex cholesterol granuloma and provide an intraoperative video and a literature review.
Delay in Cleft Lip and Palate Surgical Repair: An Institutional Review on Cleft Health Disparities in an Urban Population
Authors: Zaluzec Rebekah M. , Rodby Katherine A. , Bradford Perry S. , Danielson Kirstie K. , Patel Pravin K. , Rosenberg Janine
Published: July 2019

Access to specialized medical care is critical to decrease complications and minimize long-term morbidity, yet racial disparities in cleft surgery persist as time to initial reconstruction remains delayed among minority patients. Research has demonstrated an average 3-week delay in surgery for minority patients nationally. A retrospective chart review of patient demographics, visit timing, and surgical history was performed for patients who underwent primary cleft lip with or without palate (CL + P) reconstruction between 2002 and 2016 at an urban craniofacial center. Of the 89 children who underwent surgery, 87% were ethnic minorities (58% Hispanic, 25% African-American, 4% Asian/Other). Caucasian children were the earliest to receive CL (3.5 months) and CP (13-months) repair. Minority children trended toward a delay in CL repair, with surgery for African-Americans at 5-months (P = 0.06) and Hispanics at 4.8-months (P = 0.07). Time from first visit to CL surgery showed significant delays for minority, non-English speaking, and public insurance patients; however, for CP repair, male children were delayed from first visit to surgery compared to females (P = 0.03). While there was no statistical difference in age at CL or CP surgical repair among our racial/ethnic cohorts, there were significant racial/ethnic differences in timing spent in the preoperative period for CL. However, racial/ethnic differences decreased as the patients spent more time within the healthcare system. Thus, established, interdisciplinary cleft/craniofacial centers well versed in minority patients can minimize the complex social and cultural factors that contribute to delays in cleft care.
Computer-Assisted Design and Manufacturing Assists Less Experienced Surgeons in Achieving Equivalent Outcomes in Cranial Vault Reconstruction
Authors: Cho Regina S. , Lopez Joseph , Musavi Leila , Kachniarz Bartlomiej , Macmillan Alexandra , Badiei Beita , Bello Ricardo , Dorafshar Amir H.
Published: July 2019

Purpose:

The purpose of this study was to assess whether long-term outcomes were equivalent between computer-assisted design and manufacturing (CAD/CAM) -assisted cranial vault reconstruction performed by an inexperienced surgeon, with fewer years of surgical experience, and traditional reconstruction performed by senior surgeons with many decades of experience.

Methods:

An Institutional Review Board-approved retrospective cohort study was performed for all patients with nonsyndromic craniosynostosis between the ages of 1 month to 18 years who received primary, open calvarial vault reconstruction at the Johns Hopkins Hospital between 1990 and 2017. The primary outcome variable was the Whitaker category (I-IV) for level of required revision at the 2-year follow-up visit. Secondary outcomes included estimated blood loss, length of stay, operative time, and postoperative complications. CAD/CAM-assisted surgery was considered noninferior if the proportion of cases requiring any revision (Whitaker II, III, or IV) was no more than 10% greater than the proportion in the traditional surgery group with multivariate logistic regression analysis. t tests and fisher exact tests were used for secondary outcomes.

Results:

A total of 335 patients were included, with 35 CAD/CAM-assisted reconstructions. CAD/CAM-assisted reconstruction was noninferior to traditional after accounting for patient demographics, type of surgery, and experience level of the plastic surgeon. The traditional group required revision more frequently at 29.0% compared to CAD/CAM at 14.3%. Secondary outcomes were not significantly different between groups, but CAD/CAM had significantly longer average operative times (5.7 hours for CAD/CAM, 4.3 hours for traditional, P < 0.01).

Conclusion:

CAD/CAM technology may lower the learning curve and assist less experienced plastic surgeons in achieving equivalent long-term outcomes in craniofacial reconstruction.
Pediatric Maxillofacial Trauma Patterns Among Different Types of Road Traffic Accidents
Authors: Yazici Alper , Aytaç Ismail
Published: July 2019

Background:

Traffic accidents are one of the most leading cause of maxillofacial trauma. Defining the bone fracture patterns in different type of traffic accidents may enable for appropriate surgical approach.

Objectives:

This study research the pattern of pediatric maxillofacial fractures in terms of different type of traffic road accidents and age groups.

Methods:

The data on road traffic accidents that caused maxillofacial trauma between May 2014 and January 2019 was gained from the University of Gaziantep hospital data system. Road accident type, age groups, and the type of fractures were the evaluation parameters.

Results:

A total of 61 patients meet the criteria and 41 of those were boys. The midface bones of orbital, maxillar, and frontal are the most fractured structures with a total number of 48. The least fractured bone was mandibula with a number of 4. The comparisons of these fractures among the different type of road traffic accidents and age groups were found to be statistically significant.

Conclusion:

Car-pedestrian and car-passengers type of road traffic accident mostly seem to cause midface fractures at the primary and secondary school-aged children.
Toxic neuropathies: Chemotherapy Induced Peripheral Neurotoxicity
Authors: Alberti Paola , Cavaletti Guido , Cornblath David R.
Published: July 2019

Purpose of review

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common and distressing side-effect of many chemotherapy regimens. Currently, aside from symptomatic treatments for neuropathic pain, there are no treatments to prevent CIPN or treat established CIPN. We discuss recent articles addressing clinimetric issues and treatment of CIPN.

Recent findings

There are important clinimetric issues that need to be addressed so that robust clinical trials in CIPN can be performed. There are new compounds in early development that may treat CIPN, but larger studies are needed.

A multidisciplinary, international approach is needed to unravel CIPN; the Toxic Neuropathy Consortium (TNC) of the Peripheral Nerve Society may be the home for such efforts.
Autoantibodies in chronic inflammatory demyelinating polyradiculoneuropathy
Authors: Pascual-Goñi Elba , Martín-Aguilar Lorena , Querol Luis
Published: July 2019

Purpose of review

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a heterogeneous disorder that includes diverse clinical presentations and immunopathological mechanisms. Antibodies targeting proteins of the node of Ranvier are present in a subset of CIDP patients. These autoantibodies are pathogenic and associate with specific clinical phenotypes and therapeutic peculiarities. This review summarizes the novel insights that the discovery of novel autoantibodies has brought to the understanding of CIDP.

Recent findings

Several reports have confirmed the association of the antineurofascin 155 (NF155) antibodies with tremor, ataxia and poor response to IVIG, and with novel pathological features in CIDP patients. The association of nephrotic syndrome with anticontactin 1 (CNTN1) and antinodal neurofascin antibodies has also been described. Also, complement-fixing IgG3 antibodies targeting paranodal proteins have been associated with acute-onset CIDP. Importantly, detection of these autoantibodies has helped selecting CIDP patients for rituximab treatment. Finally, anti-CNTN1 and anti-NF155 antibodies have proven to be the first pathogenic autoantibodies described in CIDP.

The discovery of autoantibodies against nodal and paranodal proteins has proven useful in clinical practice, has uncovered novel pathophysiological mechanisms, clinical phenotypes, therapeutic response and prognosis within the CIDP disease spectrum and has boosted the search for other clinically relevant autoantibodies.
The evolution of matrilineal social systems in fissiped carnivores
Authors: Holekamp Kay E. , Sawdy Maggie A.
Published: July 2019

We review matrilineal relationships in the societies of fissiped mammalian carnivores, focusing on how the most complex of these may have evolved from simpler systems. Although competition for food is very intense at the trophic level occupied by most carnivores, and although most species of extant fissiped carnivores therefore lead solitary lives, some species show at least rudimentary clustering of maternal kin and matrilineal resource-sharing or transmission of critical resources between generations. The resources shared or transmitted range from individual food items and territories to entire networks of potential allies. The greatest elaboration of matrilineal relationships has occurred in two large carnivores, lions and spotted hyenas, which occur sympatrically throughout much of Africa. The societies of both these species apparently evolved in response to a shared suite of ecological conditions. The highly matrilineal societies of spotted hyenas are unique among carnivores and closely resemble the societies of many cercopithecine primates. The conditions favouring the evolution of matrilineal societies in carnivores include male-biased dispersal, female philopatry, the need for assistance in protecting or provisioning offspring, reliance on large or abundant prey, particularly in open habitat, high population density and kin-structured cooperative interactions that have strong positive effects on fitness.

This article is part of the theme issue ‘The evolution of female-biased kinship in humans and other mammals’.
Evolutionary significance of maternal kinship in a long-lived mammal
Authors: Lynch Emily C. , Lummaa Virpi , Htut Win , Lahdenperä Mirkka
Published: July 2019

Preferential treatment of kin is widespread across social species and is considered a central prerequisite to the evolution of cooperation through kin selection. Though it is well known that, among most social mammals, females will remain within their natal group and often bias social behaviour towards female maternal kin, less is known about the fitness consequences of these relationships. We test the fitness benefits of living with maternal sisters, measured by age-specific female reproduction, using an unusually large database of a semi-captive Asian elephant (
Elephas maximus
) population. This study system is particularly valuable to an exploration of reproductive trends in a long-lived mammal, because it includes life-history data that span multiple generations, enabling a study of the effects of kinship across a female's lifespan. We find that living near a sister significantly increased the likelihood of annual reproduction among young female elephants, and this effect was strongest when living near a sister 0–5 years younger. Our results show that fitness benefits gained from relationships with kin are age-specific, establish the basis necessary for the formation and maintenance of close social relationships with female kin, and highlight the adaptive importance of matriliny in a long-lived mammal.

This article is part of the theme issue ‘The evolution of female-biased kinship in humans and other mammals'.
Cooperation beyond consanguinity: post-marital residence, delineations of kin and social support among South Indian Tamils
Authors: Power Eleanor A. , Ready Elspeth
Published: July 2019

Evolutionary ecologists have shown that relatives are important providers of support across many species. Among humans, cultural reckonings of kinship are more than just relatedness, as they interact with systems of descent, inheritance, marriage and residence. These cultural aspects of kinship may be particularly important when a person is determining which kin, if any, to call upon for help. Here, we explore the relationship between kinship and cooperation by drawing upon social support network data from two villages in South India. While these Tamil villages have a nominally male-biased kinship system (being patrilocal and patrilineal), matrilateral kin play essential social roles and many women reside in their natal villages, letting us tease apart the relative importance of genetic relatedness, kinship and residence in accessing social support. We find that people often name both their consanguineal and affinal kin as providing them with support, and we see some weakening of support with lesser relatedness. Matrilateral and patrilateral relatives are roughly equally likely to be named, and the greatest distinction instead is in their availability, which is highly contingent on post-marital residence patterns. People residing in their natal village have many more consanguineal relatives present than those who have relocated. Still, relocation has only a small effect on an individual’s network size, as non-natal residents are more reliant on the few kin that they have present, most of whom are affines. In sum, marriage patterns have an important impact on kin availability, but the flexibility offered by the broadening of the concept of kin helps people develop the cooperative relationships that they rely upon, even in the absence of genetic relatives.

This article is part of the theme issue ‘The evolution of female-biased kinship in humans and other mammals’.
The expendable male hypothesis
Authors: Mattison Siobhán M. , Quinlan Robert J. , Hare Darragh
Published: July 2019

Matriliny is a system of kinship in which descent and inheritance are conferred along the female line. The theoretically influential concept of the matrilineal puzzle posits that matriliny poses special problems for understanding men's roles in matrilineal societies. Ethnographic work describes the puzzle as the tension experienced by men between the desire to exert control over their natal kin (i.e. the lineage to which they belong) and over their affinal kin (i.e. their spouses and their biological children). Evolutionary work frames the paradox as one resulting from a man investing in his nieces and nephews at the expense of his own biological offspring. In both cases, the rationale for the puzzle rests on two fundamental assumptions: (i) that men are in positions of authority over women and over resources; and (ii) that men are interested in the outcomes of parenting. In this paper, we posit a novel hypothesis that suggests that certain ecological conditions render men expendable within local kinship configurations, nullifying the above assumptions. This arises when (i) women, without significant assistance from men, are capable of meeting the subsistence needs of their families; and (ii) men have little to gain from parental investment in children. We conclude that the expendable male hypothesis may explain the evolution of matriliny in numerous cases, and by noting that female-centred approaches that call into doubt assumptions inherent to male-centred models of kinship are justified in evolutionary perspective.

This article is part of the theme issue ‘The evolution of female-biased kinship in humans and other mammals’.
Lineal kinship organization in cross-specific perspective
Authors: Fortunato Laura
Published: July 2019

I draw on insights from anthropology to outline a framework for the study of kinship systems that applies across animal species with biparental sexual reproduction. In particular, I define lineal kinship organization as a social system that emphasizes interactions among lineally related kin—that is, individuals related through females only, if the emphasis is towards matrilineal kin, and individuals related through males only, if the emphasis is towards patrilineal kin. In a given population, the emphasis may be expressed in one or more social domains, corresponding to pathways for the transmission of different resources across generations (e.g. the allocation of food, the transfer of access to the natal territory or household). A lineal bias in any domain can be viewed as a bias in investment towards a particular set of kin—specifically, towards the offspring of daughters if the bias is matrilineal, and towards the offspring of sons if the bias is patrilineal. Effectively, investment is restricted to the offspring of the females in the population in one case, and to the offspring of the males in the other. This is distinct from a bias in investment towards daughters and towards sons, respectively. Overall, I propose a shift in focus—from viewing matrilineal and patrilineal kinship as unitary phenomena, to consideration of the different aspects of the social system featuring a bias towards lineally related kin.

This article is part of the theme issue ‘The evolution of female-biased kinship in humans and other mammals’.
The evolution of female-biased kinship in humans and other mammals
Authors: Mattison Siobhán M. , Shenk Mary K. , Thompson Melissa Emery , Borgerhoff Mulder Monique , Fortunato Laura
Published: July 2019

Female-biased kinship (FBK) arises in numerous species and in diverse human cultures, suggesting deep evolutionary roots to female-oriented social structures. The significance of FBK has been debated for centuries in human studies, where it has often been described as difficult to explain. At the same time, studies of FBK in non-human animals point to its apparent benefits for longevity, social complexity and reproduction. Are female-biased social systems evolutionarily stable and under what circumstances? What are the causes and consequences of FBK? The purpose of this theme issue is to consolidate efforts towards understanding the evolutionary significance and stability of FBK in humans and other mammals. The issue includes broad theoretical and empirical reviews as well as specific case studies addressing the social and ecological correlates of FBK across taxa, time and space. It leverages a comparative approach to test existing hypotheses and presents novel arguments that aim to expand our understanding of how males and females negotiate kinship across diverse contexts in ways that lead to the expression of female biases in kinship behaviour and social structure.

This article is part of the theme issue ‘The evolution of female-biased kinship in humans and other mammals’.
Expert-validated estimation of diagnostic uncertainty for deep neural networks in diabetic retinopathy detection
Authors: Ayhan Murat Seçkin , Kühlewein Laura , Aliyeva Gulnar , Inhoffen Werner , Ziemssen Focke , Berens Philipp
Published: July 2019

Deep learning-based systems can achieve a diagnostic performance comparable to physicians in a variety of medical use cases including the diagnosis of diabetic retinopathy. To be useful in clinical practise, it is necessary to have well calibrated measures of the uncertainty with which these systems report their decisions. However, deep neural networks (DNNs) are being often overconfident in their predictions, and are not amenable to a straightforward probabilistic treatment. Here, we describe an intuitive framework based on test-time data augmentation for quantifying the diagnostic uncertainty of a state-of-the-art DNN for diagnosing diabetic retinopathy. We show that the derived measure of uncertainty is well-calibrated and that experienced physicians likewise find cases with uncertain diagnosis difficult to evaluate. This paves the way for an integrated treatment of uncertainty in DNN-based diagnostic systems.
Population Structure Drives Differential Methicillin-resistantStaphylococcus aureusColonization Dynamics
Authors: Short Christopher T. , Samore Matthew , Lofgren Eric T. ,   for the CDC Modeling Infectious Diseases in Healthcare Program (MInD-Healthcare)
Published: July 2019

Background

Using a model of methicillin-resistantStaphylococcus aureus(MRSA) within an intensive care unit (ICU), we explore how differing hospital population structures impact these infection dynamics.

Methods

Using a stochastic compartmental model of an 18-bed ICU, we compared the rates of MRSA acquisition across three potential population structures: a Single Staff Type (SST) model with nurses and physicians as a single staff type, a model with separate staff types for nurses and physicians (Nurse-MD model), and a Metapopulation model where each nurse was assigned a group of patients. By varying the proportion of time spent with the assigned patient group (γ) within the Metapopulation model, we explored whether simpler models may be acceptable approximations to more realistic patient-healthcare staff contact patterns.

Results

The SST, Nurse-MD, and Metapopulation models had a mean annual number of cumulative MRSA acquisitions of 40.6, 32.2 and 19.6 respectively. All models were sensitive to the same parameters in the same direction, although the Metapopulation model was less sensitive. The number of acquisitions varied non-linearly by values of γ, with values below 0.40 resembling the Nurse-MD model, while values above that converged toward the metapopulation structure.

Discussion

The population structure of a modeled hospital has considerable impact on model results, with the SST model having more than double the acquisition rate of the more structured Metapopulation model. While the direction of parameter sensitivity remained the same, the magnitude of these differences varied, producing different infection rates across relatively similar populations. The non-linearity of the model’s response to differing values of γ suggests only a narrow space of relatively dispersed nursing assignments where simple model approximations are appropriate.

Conclusion

Simplifying assumptions around how a hospital population is modeled, especially assuming random mixing, may overestimate infection rates and the impact of interventions.
An atlas of infiltrated B-lymphocytes in breast cancer revealed by paired single-cell RNA-sequencing and antigen receptor profiling
Authors: Hu Qingtao , Hong Yu , Qi Pan , Lu Guangqing , Mai Xueying , Xu Sheng , He Xiaoying , Guo Yu , Gao Linlin , Jing Zhiyi , Wang Jiawen , Cai Tao , Zhang Yu
Published: July 2019

While it has been well-recognized that T-cell mediated adaptive cellular immunity plays important roles in cancer immune response and tumor control, the roles of B lymphocytes in tumor development and therapy have only been proposed until recently, and are still mostly controversial. To gain mechanistic insights into the origin and dynamics of tumor infiltrated immune cells, especially B lymphocytes, we combine single-cell RNA-sequencing and antigen receptor lineage analysis to characterize a large number of triple-negative breast cancer (TNBC) infiltrated immune cells and present a comprehensive atlas of infiltrated B-lymphocytes in TNBC, the most aggressive breast cancer subtype. We demonstrate that TNBC infiltrated B cells showed more mature and memory B cell characteristics, as well as high clonality and extensive IgH class switching recombination and somatic hypermutations. The B cell signatures based on single-cell RNA-seq results are significantly associated with improved survival for TNBC patients and provide better prognostication than classic single B cell markers (CD19 or CD20). Further dissection of the mechanisms regulating the functions and dynamic distribution of tumor infiltrated B cell populations will provide new clues for tumor immunotherapy.
Chirp analyzer for estimating amplitude and latency of steady-state auditory envelope following responses
Authors: Martínez-Montes Eduardo , García-Puente Yalina , Zañartu Matías , Prado-Gutiérrez Pavel
Published: July 2019

The envelope following response (EFR) is a scalp-recorded evoked potential elicited by carrier tones or noise, modulated in amplitude with a continuous sweep of modulation frequencies. This non-stationary response reflects the phase-locked neural activity of the auditory pathway to the temporal envelope of sounds and has been commonly assessed by fixed-frequency methods based on the discrete Fourier transform, such as the Fourier Analyzer (FA). In this work, we study the estimation of the EFR with the use of explicit time-frequency methods, which offer more information about the energy distribution of the recorded signal, such as the Short-Term Fourier Transform (STFT) and the Morlet Continuous Wavelet Transform (CWT). We further introduce the Chirp Analyzer (CA), which is similar to FA, but using as basis function the same linear chirp that amplitude-modulates the carrier stimulus. In a direct comparison using controlled simulated responses, the CA showed to be able to estimate the correct EFR amplitudes, without the typical bias offered by the estimation using STFT (equivalent to FA) and more robust to noise than the CWT method, although with higher sensitivity to the presence of a delay in the response with respect to the stimulus. For addressing the latter issue, we also propose here a novel methodology for estimating the apparent latency of the response. This method proved to be reliable when using the STFT and the CA methods, as assessed using simulated responses. The estimation of the EFR amplitude with any of the methods, but especially with CA, should be corrected by using the estimated delay when possible. An illustrative application of these methods to small datasets of a rat and a human newborn, suggested that all time-frequency methods can be used to study the EFR amplitudes in a wide range of modulation frequencies, but they should be interpreted in the light of the limitations shown in the simulation studies.
Effects of hM4Di activation in CamKII basolateral amygdala neurons and CNO treatment on Sensory-Specific vs. General-PIT; refining PIT circuits and considerations for using CNO
Authors: Derman Rifka C. , Bass Caroline E. , Ferrario Carrie R.
Published: July 2019

Pavlovian stimuli can influence instrumental behaviors, a phenomenon known as Pavlovian-to-instrumental transfer (PIT). PIT arises via psychologically and neurobiologically independent processes as Sensory-Specific-PIT (SS-PIT) and General-PIT. SS-, but not General-PIT, relies on the basolateral amygdala (BLA), however the specific BLA neuronal populations involved are unknown. Therefore, here we determined the contribution of glutamatergic BLA neurons to SS-PIT. The BLA was transduced with virus containing either GFP or hM4Di, driven by the CamKII promoter. Rats were then tested for SS- and General-PIT following Vehicle or Clozapine-n-oxide (CNO, the hM4Di-activating ligand) injection. CNO had no effect on SS-PIT in the GFP control group, but selectively blocked its expression in the hM4Di-expressing group. Furthermore, CNO did not alter the expression of Pavlovian outcome devaluation effects in GFP or hM4Di expressing groups, indicating that the hM4Di-mediated loss of SS-PIT did not result from an inability to recall the sensory-specific details of the Pavlovian stimulus-outcome associations. Unexpectedly, CNO disrupted General-PIT in both GFP and hM4Di expressing groups, indicating that CNO alone is sufficient to disrupt affective, but not sensory-specific processes. Disruption of General-PIT by CNO was not due to generalized motor effects, but instead may be related to shifts in internal state produced by CNO. Together these data identify BLA CamKII neurons as critical for the expression of SS-PIT, and reveal important considerations for using CNO to study general affective motivation.
Synechocystis KaiC3 displays temperature and KaiB dependent ATPase activity and is important for growth in darkness
Authors: Wiegard Anika , Kobler Christin , Oyama Katsuaki , Dorrich Anja Katharina , Azai Chihiro , Terauchi Kazuki , Wilde Annegret , Axmann Ilka Maria
Published: July 2019

Cyanobacteria form a heterogeneous bacterial group with diverse lifestyles, acclimation strategies and differences in the presence of circadian clock proteins. In Synechococcus elongatus PCC 7942, a unique posttranslational KaiABC oscillator drives circadian rhythms. ATPase activity of KaiC correlates with the period of the clock and mediates temperature compensation. Synechocystis sp. PCC 6803 expresses additional Kai proteins, of which KaiB3 and KaiC3 proteins were suggested to fine-tune the standard KaiAB1C1 oscillator. In the present study, we therefore characterized the enzymatic activity of KaiC3 as a representative of non-standard KaiC homologs in vitro. KaiC3 displayed ATPase activity, which were lower compared to the Synechococcus elongatus PCC 7942 KaiC protein. ATP hydrolysis was temperature-dependent. Hence, KaiC3 is missing a defining feature of the model cyanobacterial circadian oscillator. Yeast two-hybrid analysis showed that KaiC3 interacts with KaiB3, KaiC1 and KaiB1. Further, KaiB3 and KaiB1 reduced in vitro ATP hydrolysis by KaiC3. Spot assays showed that chemoheterotrophic growth in constant darkness is completely abolished after deletion of ΔkaiAB1C1 and reduced in the absence of kaiC3. We therefore suggest a role for adaptation to darkness for KaiC3 as well as a crosstalk between the KaiC1 and KaiC3 based systems.
Immune-based mutation classification enables neoantigen prioritization and immune feature discovery in cancer immunotherapy
Authors: Bai Peng , Li Yongzheng , Zhou Qiuping , Xia Jiaqi , Wei Peng-Cheng , Deng Hexiang , Wu Min , Chan Sanny K. , Kappler John W. , Zhou Yu , Tran Eric , Marrack Philippa , Yin Lei
Published: July 2019

Genetic mutations lead to the production of mutated proteins from which peptides are presented to T cells as cancer neoantigens. Evidence suggests that T cells that target neoantigens are the main mediators of effective cancer immunotherapies. Although algorithms have been used to predict neoantigens, only a minority are immunogenic. The factors that influence neoantigen immunogenicity are not completely understood. Here, we classified human neoantigen/neopeptide data into three categories based on their TCR-pMHC binding events. We observed a conservative mutant orientation of the anchor residue from immunogenic neoantigens which we termed the “NP” rule. By integrating this rule with an existing prediction algorithm, we found improved performance in neoantigen prioritization. To better understand this rule, we solved several neoantigen/MHC structures. These structures showed that neoantigens that follow this rule not only increase peptide-MHC binding affinity but also create new TCR-binding features. These molecular insights highlight the value of immune-based classification in neoantigen studies and may enable the design of more effective cancer immunotherapies.
Rhizosphere bacterial communities of wheat vary across the growing season and among dryland farming systems
Authors: Ishaq Suzanne L. , Seipel Tim , Yeoman Carl J. , Menalled Fabian D.
Published: July 2019

Despite knowledge that seasonality and plant phenology impact soil microbiota, farming system effects on soil microbiota are not often evaluated across the growing season. We assessed the bacterial diversity in wheat rhizosphere soil through the spring and summer of 2016 in winter wheat (Triticum aestiviumL.) in Montana, USA, from three contrasting farming systems: a chemically-managed no-tillage system, and two USDA-certified organic systems in their fourth year, one including tillage and one where sheep grazing partially offsets tillage frequency. Bacterial richness (range 605 – 1174 OTUs) and evenness (range 0.80 – 0.92) peaked in early June and dropped by late July (range 92 – 1190, 0.62-0.92, respectively), but was not different by farming systems. Organic tilled plots contained more putative nitrogen-fixing bacterial genera than the other two systems. Bacterial community similarities were significantly altered by sampling date, minimum and maximum temperature at sampling, bacterial abundance at date of sampling, total weed richness, and coverage ofTaraxacum officinale,Lamium ampleuxicaule,andThlaspi arvense. This study highlights that weed diversity, season, and farming management system all influence rhizosphere soil microbial communities. Local environmental conditions will strongly affect any practical applications aimed at improving soil diversity and functionality, especially in semi-arid regions where abiotic stress and seasonal variability in temperature and water availability drive primary production.
Maternal antioxidant treatment prevents behavioural and neural changes in offspring exposed to prenatal social stress
Authors: Scott H , Phillips TJ , Sze Y , Alfieri A , Rogers MF , Case CP , Brunton PJ
Published: July 2019

Maternal exposure to social stress during pregnancy is associated with an increased risk of psychiatric disorders in the offspring in later life. However, the mechanism through which the effects of maternal stress are transmitted to the foetus is unclear. Using a rat model, we explored the mechanisms by which maternal social stress is conveyed to the foetus and the potential for targeted treatment to prevent disease in the offspring. Maternal stress increased circulating corticosterone in the mother, but not the foetuses. Maternal stress also induced oxidative stress in the placenta, but not in the foetal brain, and this was prevented by administration of a nanoparticle-bound antioxidant. Moreover, antioxidant treatment prevented prenatal stress-induced anxiety-like behaviour in the adult male offspring, along with several stress-induced neuroanatomical, neurochemical and gene expression changes in the offspring brain. Importantly, many of these neural effects were mimicked in neuronal cultures by application of placental-conditioned medium or foetal plasma from stressed pregnancies. Both placental-conditioned medium and foetal plasma contained differentially abundant extracellular microRNAs following prenatal stress. The present study highlights the crucial role of the placenta, and the molecules it secretes, in foetal brain development and provides evidence of the potential for treatment that can prevent maternal stress-induced foetal programming of neurological disease.
Cell Type-Specific Modulation of Layer 6A Excitatory Microcircuits by Acetylcholine in Rat Barrel Cortex
Authors: Yang Danqing , Günter Robert , Qi Guanxiao , Radnikow Gabriele , Feldmeyer Dirk
Published: July 2019

Acetylcholine (ACh) is known to regulate cortical activity during different behavioral states, e.g. wakefulness and attention. Here we show a differential expression of muscarinic ACh receptors (mAChRs) and nicotinic AChRs (nAChRs) in different layer 6A (L6A) pyramidal cell (PC) types of somatosensory cortex. At low concentrations, ACh induced a persistent hyperpolarization in corticocortical (CC) but a depolarization in corticothalamic (CT) L6A PCs via M4 and M1 mAChRs, respectively. At ∼1 mM ACh depolarized exclusively CT PCs via α4β2 subunit-containing nAChRs without affecting CC PCs. Miniature EPSC frequency in CC PCs was decreased by ACh but increased in CT PCs. In synaptic connections with a presynaptic CC PC, glutamate release was suppressed via M4 mAChR activation but enhanced by nAChRs via α4β2 nAChRs when the presynaptic neuron was a CT PC. Thus, in layer 6A the interaction of mAChRs and nAChRs results in an altered excitability and synaptic release, effectively strengthening corticothalamic output while weakening corticocortical synaptic signaling.
Characterisation of cefotaxime-resistant urinary Escherichia coli from primary care in South-West England 2017-2018
Authors: Findlay Jacqueline , Gould Virginia C. , North Paul , Bowker Karen E. , Williams O. Martin , MacGowan Alasdair P. , Avison Matthew B.
Published: July 2019

Objectives

Third-generation cephalosporin-resistant Escherichia coli from community-acquired urinary tract infections (UTI) have been increasingly reported worldwide. In this study we sought to determine and characterise the mechanisms of cefotaxime-resistance (CTX-R) employed by urinary E. coli obtained from primary care over a 12-month period, in Bristol and surrounding counties in the South West of England.

Methods

Cephalexin resistant (Ceph-R) E. coli isolates were identified directly from general practice (GP) referred urine samples using disc susceptibility testing as per standard diagnostic procedures. CTX-R was determined by subsequent plating onto MIC breakpoint plates. β-Lactamase genes were detected by PCR. Whole Genome Sequencing (WGS) was performed on 225 urinary isolates and analyses were performed using the Centre for Genomic Epidemiology platform. Patient information provided by the referring GPs was reviewed.

Results

During the study period, Ceph-R E. coli (n=900) were obtained directly from urines from 146 GPs. Seventy-percent (626/900) of isolates were CTX-R. WGS of 225 non-duplicate isolates identified that the most common mechanism of CTX-R was blaCTX-M carriage (185/225; 82.2%), predominantly blaCTX-M-15 (114/185; 61.6%), followed by carriage of plasmid mediated AmpCs (pAmpCs) (17/225; 7.6%), ESBL blaSHV variants (6/225; 2.7%), AmpC hyperproduction (13/225; 5.8%), or a combination of both blaCTX-M and pAmpC carriage (4/225; 1.8%). Forty-four sequence types (STs) were identified with ST131 representing 101/225 (45.0%) of sequenced isolates, within which the blaCTX-M-15-positive clade C2 was dominant (54/101; 53.5%). Ciprofloxacin-resistance (CIP-R) was observed in 128/225 (56.9%) of sequenced CTX-R isolates – predominantly associated with fluoroquinolone-resistant clones ST131 and ST1193.

Conclusions

Most Ceph-R urinary E. colis were CTX-R, predominantly caused by blaCTX-M carriage. There was a clear correlation between CTX-R and CIP-R, largely attributable to the dominance of the high-risk pandemic clones, ST131 and ST1193 in this study. This localised epidemiological data provides greater resolution than regional data and can be valuable for informing treatment choices in the primary care setting.