bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlative Analyses of the SARC028 Trial Reveal an Association Between Sarcoma-Associated Immune Infiltrate and Response to Pembrolizumab
Authors: Keung Emily Z. , Burgess Melissa , Salazar Ruth , Parra Edwin R. , Rodrigues-Canales Jaime , Bolejack Vanessa , Van Tine Brian A. , Schuetze Scott M. , Attia Steven , Riedel Richard F. , Hu James , Okuno Scott H. , Priebat Dennis A. , Movva Sujana , Davis Lara E. , Reed Damon R. , Reuben Alexandre , Roland Christina L. , Reinke Denise , Lazar Alexander J. , Wang Wei-Lien , Wargo Jennifer A. , Tawbi Hussein A.
Published: January 2020

Purpose:

We recently reported a 17.5% objective RECIST 1.1 response rate in a phase II study of pembrolizumab in patients with advanced sarcoma (SARC028). The majority of responses occurred in undifferentiated pleomorphic sarcoma (UPS) and dedifferentiated liposarcoma (DDLPS). We sought to determine whether we can identify immune features that correlate with clinical outcomes from tumor tissues obtained pre- and on-treatment.

Patients and Methods:

Pretreatment (n = 78) and 8-week on-treatment (n = 68) tumor biopsies were stained for PD-L1 and multiplex immunofluorescence panels. The density of positive cells was quantified to determine associations with anti–PD-1 response.

Results:

Patients that responded to pembrolizumab were more likely to have higher densities of activated T cells (CD8+ CD3+ PD-1+) and increased percentage of tumor-associated macrophages (TAM) expressing PD-L1 pre-treatment compared with non-responders. Pre-treatment tumors from responders also exhibited higher densities of effector memory cytotoxic T cells and regulatory T cells compared with non-responders. In addition, higher density of cytotoxic tumor-infiltrating T cells at baseline correlated with a better progression-free survival (PFS).

Conclusions:

We show that quantitative assessments of CD8+ CD3+ PD-1+ T cells, percentage of TAMs expressing PD-L1, and other T-cell densities correlate with sarcoma response to pembrolizumab and improved PFS. Our findings support that multiple cell types present at the start of treatment may enhance tumor regression following anti–PD-1 therapy in specific advanced sarcomas. Efforts to confirm the activity of pembrolizumab in an expansion cohort of patients with UPS/DDLPS are underway.
“Matching” the “Mismatch” Repair–Deficient Prostate Cancer with Immunotherapy
Authors: Schweizer Michael T. , Yu Evan Y.
Published: January 2020

Mismatch repair gene mutations are uncommon in advanced prostate cancer; however, in those harboring these alterations, immune checkpoint blockade can be effective. As such, assays that can accurately identify these men are critically important. Cell-free circulating tumor DNA–based sequencing approaches appear to be one viable approach for identifying these patients.

See related article by Ritch et al., p. 1114
The Ongoing Search for Biomarkers of CDK4/6 Inhibitor Responsiveness in Breast Cancer
Authors: Schoninger Scott F. , Blain Stacy W.
Published: January 2020

CDK4 inhibitors (CDK4/6i), such as palbociclib, ribociclib, and abemaciclib, are approved in combination with hormonal therapy as a front-line treatment for metastatic HR+, HER2- breast cancer. Their targets, CDK4 and CDK6, are cell-cycle regulatory proteins governing the G1–S phase transition across many tissue types. A key challenge remains to uncover biomarkers to identify those patients that may benefit from this class of drugs. Although CDK4/6i addition to estrogen modulation therapy essentially doubles the median progression-free survival, overall survival is not significantly increased. However, in reality only a subset of treated patients respond. Many patients exhibit primary resistance to CDK4/6 inhibition and do not derive any benefit from these agents, often switching to chemotherapy within 6 months. Some patients initially benefit from treatment, but later develop secondary resistance. This highlights the need for complementary or companion diagnostics to pinpoint patients who would respond. In addition, because CDK4 is a bona fide target in other tumor types where CDK4/6i therapy is currently in clinical trials, the lack of target identification may obscure benefit to a subset of patients there as well. This review summarizes the current status of CDK4/6i biomarker test development, both in clinical trials and at the bench, with particular attention paid to those which have a strong biological basis as well as supportive clinical data.
Early Postendoscopic Transverse Colo-Colonic Intussusception
Authors: He Harry , Rambhujun Vikashsingh , DeMaria Matthew , Ali Mohammad , Vrabie Raluca
Published: January 2020

Intussusception is defined as telescoping of the proximal bowel (intussusceptum) into the lumen of the distal bowel, otherwise called the intussuscipiens. While it is one of the most common causes of intestinal obstruction in children between the ages of 3 months and 6 years, intussusception accounts for about 1% of such cases in adults. Intussusception is idiopathic in 8–20% of patients and most commonly occurs in the small intestines in adults. We describe the unique case of a colo-colonic intussusception in a 54-year-old female patient 1 week after a colonoscopy for suspected inflammatory bowel disease. The discussion focuses on the presentation and management options of intussusception.
Desperdício alimentar
Authors: Rigaud João Paulo De Oliveira , Tavares Filho Rafael Arcanjo
Published: January 2020

O consumo de alimentos, ainda que seja um hábito que supostamente deveria atender a uma necessidade básica comum a todos os seres humanos, é afetado pelo processo de consolidação do consumismo na sociedade moderna que alterou um princípio fundamental: a definição do que seriam as necessidades básicas comuns; esta afirmativa pode estar atrelada, em definitivo, ao processo de desperdício de alimentos. Por mais básica que possa aparentar ser a necessidade humana de se alimentar, é imprescindível – para a compreensão da situação hodierna dicotômica entre a fome e a opulência – localizar a comercialização e o consumo de alimentos dentro dessa teia de significados reorganizados pela “fome” socialmente imposta por ideias mercantilistas. A partir de revisões de bibliografias que pautam o desperdício de alimentos, a liquidez do consumo, a cultura alimentar moderna e uma fusão com uma vivência etnográfica feita na Feira de São Joaquim na cidade de Salvador, o presente estudo nasceu da necessidade de entender por que, apesar de o desperdício de alimentos se manter como uma realidade crescente e preocupante em todo o mundo, grandes quantidades de alimentos ainda são descartadas por não se encaixarem nos padrões “estéticos” da grande maioria da sociedade? Logo, há-se a necessidade de refletir sobre o que pode ser considerado “lixo” quando se fala em alimentação e de que forma as ideias de consumo na sociedade moderna influenciam o descarte desses alimentos. O consumo parte da intencionalidade dos sujeitos de “vender-se”, ou seja, de, mediante a avaliação externa positiva, galgar posição social superior. Estes, suscetíveis a aceitações e rejeições, inserem-se em parâmetros estabelecidos socialmente numa hierarquia de consumo, na qual quão “melhores” forem os produtos consumidos, melhores sujeito serão; posicionando os indivíduos como mercadorias antes mesmo de se firmarem como sujeitos. Tal contexto contribui para que a população jogue no lixo porções de comida adequadas para o consumo, desperdiçadas pela vaidade em valorizar o consumo constante de comidas industrializadas. Dessa maneira, se desde os primórdios a necessidade básica comum era puramente a satisfação biológica e nutricional do corpo, com a emergência das ideias consumistas na modernidade, esse princípio passa a competir com aquele que valoriza o consumo como um mecanismo de promoção social sob uma lógica da mercantilização da vida e da sobrevalorização do bem individual em detrimento do coletivo. Por fim, sob um enfoque crítico da dinâmica global, é possível identificar que o consumo, em seu auge na era capitalista, nos insere em hábitos forjados que reforçam a estética do produto e mascaram as desigualdades. Hoje, em todo o mundo se produz muito mais do que se consome, provocando um alto índice de desperdício de alimentos; o que, em contrapartida, contribui diretamente para que populações inteiras continuem vivendo sob uma ótica de vulnerabilidade social e insegurança alimentar severa.
TÜRKİYE FUTBOL STADYUMLARI DOLULUK ORANLARININ ANALİZİ ve ÖRNEK GELİR YÖNETİMİ UYGULAMALARI
Authors: METERELLİYOZ KUYZU Melike , LÖKÇÜ Süleyman
Published: December 2019

Çalışmanın
amacı, Türkiye Süper Lig’de mücadele eden kulüplerin gişe
gelirlerini artırmaları için izleyebilecekleri yöntemlerin araştırılması
ve gelir yönetimi yöntemlerinden faydalanarak amaca yönelik bir
uygulama yapılmasıdır. Ekonomik olarak büyüyen futbol sektöründe, futbol
kulüplerinin yaşamını sürdürebilmelerini sağlamak ve rekabet eşitliğini korumak
adına finansal fair play adıyla kısıtlayıcı kurallar konulmuştur ve futbol
kulüplerinin giderlerini kontrol altına alıp gelirlerini artırmaları daha da
fazla önem kazanmıştır. Çalışmada Galatasaray ve Fenerbahçe Futbol Kulüplerinin
2012-2017 yılları arasında kendi stadyumlarında oynadıkları karşılaşmaların
doluluk oranlarına etki eden faktörler tekli ve çoklu regresyon modelleri
kullanılarak analiz edilmiştir. Analiz sonucu doluluğu yüksek oranda etkileyebilecek
faktörlerin bulunamaması nedeniyle, doluluğu değiştirmeden gelirlerin maksimize
edilmesi amaçlanarak “Beklenen
Marjinal Koltuk Geliri” gelir yönetim modeli uygulanmıştır. Çalışma sonucunda
stadyum gelirlerinin yaklaşık %35-40 oranında artırılabileceği ve gelir
yönetimi uygulamalarının futbol kulüpleri için faydalı olacağı görülmüştür.
A new species of Protonemura Kempny, 1898 (Plecoptera: Nemouridae) from the Ishizuchi range, Shikoku, Japan
Authors: MURÁNYI DÁVID , GAMBOA MARIBET , WATANABE KOZO
Published: January 2020

A new species of the genus Protonemura Kempny, 1898 (Plecoptera: Nemouridae: Amphinemurinae) is described from the Ishizuchi Range of Shikoku Island, Japan, based on the male, female and Co1 sequences. Protonemura shimizui Murányi & Gamboa sp. n. belongs to the P. orbiculata species group sensu Shimizu, 1998. The new species appears to be limited to the higher elevations of the Ishizuchi Range. Faunistic survey of the high elevation rheocrenes of the Ishizuchi Range is also presented.
OSSE Assessment of Underwater Glider Arrays to Improve Ocean Model Initialization for Tropical Cyclone Prediction
Authors: Halliwell George R. , Goni Gustavo J. , Mehari Michael F. , Kourafalou Villy H. , Baringer Molly , Atlas Robert
Published: December 2019

Credible tropical cyclone (TC) intensity prediction by coupled models requires accurate forecasts of enthalpy flux from ocean to atmosphere, which in turn requires accurate forecasts of sea surface temperature cooling beneath storms. Initial ocean fields must accurately represent ocean mesoscale features and the associated thermal and density structure. Observing system simulation experiments (OSSEs) are performed to quantitatively assess the impact of assimilating profiles collected from multiple underwater gliders deployed over the western North Atlantic Ocean TC region, emphasizing advantages gained by profiling from moving versus stationary platforms. Assimilating ocean profiles collected repeatedly at fixed locations produces large root-mean-square error reduction only within ~50 km of each profiler for two primary reasons. First, corrections performed during individual update cycles tend to introduce unphysical eddy structure resulting from smoothing properties of the background error covariance matrix and the tapering of innovations by a localization radius function. Second, advection produces rapid nonlinear error growth at larger distances from profiler locations. The ability of each individual moving glider to cross gradients and map mesoscale structure in its vicinity substantially reduces this nonlinear error growth. Glider arrays can be deployed with horizontal separation distances that are 50%–100% larger than those of fixed-location profilers to achieve similar mesoscale error reduction. By contrast, substantial larger-scale bias reduction in upper-ocean heat content can be achieved by deploying profiler arrays with separation distances up to several hundred kilometers, with moving gliders providing only modest additional improvement. Expected sensitivity of results to study region and data assimilation method is discussed.
Quantifying Clinical Pharmacist Activities in a Tertiary Care Hospital Using Key Performance Indicators
Authors: Al-Jazairi Abdulrazaq S. , Alnakhli Adel O.
Published: January 2020

Background: Key performance indicators (KPIs) are a set of measures used to help an organization in assessing and achieving goals critical to success. The aim of this study was to quantify the clinical pharmacists’ contribution to patient care in a tertiary care hospital using predefined clinical pharmacy KPIs. Method: This study was a prospective, observational study conducted by the Pharmaceutical Care Division of a tertiary care hospital. Clinical pharmacy KPIs were submitted by each clinical pharmacist on a monthly basis for 12 months during 2017. All clinical pharmacists up to the managerial level were included in the study. Data were analyzed, stratified, and correlated using Microsoft Excel, JMP statistical software, and Spearman correlation. The study was approved by the hospital’s Office of Research Affairs, RAC number 2171-080. Results: A total of 42 clinical pharmacists reviewed 104 728 patient encounters. They performed an adjusted average of 1221 interventions with an acceptance rate of 91.5%, 273 medication reconciliations, 325 discharge consultations, 332 pharmacokinetic consultations, 700 total parenteral nutrition consultations and follow-ups, and 12 688 electronic order verifications per clinical pharmacist per year. These interventions collectively resulted in a cost saving of $316 087.65 per clinical pharmacist per year. Statistical significance with positive correlation was noted for a number of precepted residents/students and clinical pharmacists’ experience ( R = 0.382, P = .013) and board certification ( R = 0.428, P = .0047). Conclusion: Clinical pharmacy KPIs were able to quantify the clinical pharmacists’ contributions to patient care and cost savings, which may lead to improve, standardize, and benchmark clinical pharmacy activities in the region.
Who dissents? Self-efficacy and opposition action after state-sponsored election violence
Authors: Young Lauren E
Published: January 2020

Reactions to acts of state-sponsored election violence and other forms of repression vary greatly across individuals. This article develops a theory that the psychological characteristic of self-efficacy moderates opposition supporters’ reactions to state-sponsored election violence. I use data from an original survey and in-depth qualitative interviews with opposition supporters in Zimbabwe to illustrate and test this theory. Self-efficacy is a strong predictor of intention to take action in support of the opposition after episodes of state-sponsored election violence and is related to the emotional reactions that opposition supporters have after violent events. Specifically, people who are higher in self-efficacy report that they would feel more anger relative to fear after episodes of state-sponsored election violence. The relationship between self-efficacy and persistence in pro-opposition action after violence is similar in magnitude to variables that the existing literature argues are the most important predictors of dissent in repressive environments, including strength of identification with the opposition and gender. These results provide empirical support for the assumption in many collective action theories that psychological characteristics create variation in dissent in repressive environments. Understanding how individual psychological differences can shape reactions to coercive violence may help explain why forms of repression like state-sponsored election violence have such unpredictable effects on subsequent pro-opposition mobilization.
The Role of Market Devices for Price and Loyalty Strategies in 20th Century U.S. Grocery Stores
Authors: Hagberg Johan , Kjellberg Hans , Cochoy Franck
Published: January 2020

This paper explores the competitive dynamics of technical innovations and retailer strategies through a historical study of the role of market devices in contributing to price and loyalty competition strategies in the US grocery retail market during the 20th century. Our findings show that recurrent shifts between emphasizing price and using various customer loyalty arrangements were closely linked to, and supported by, the introduction of seemingly mundane technical devices. Our analysis of retailer competition incorporates the role of technical innovations as endogenous to retail dynamics, which is important to understand historical development, but also highly relevant for contemporary analyses given the current proliferation of digital devices within retailing.
The Role of Maternal Intimate Partner Violence Victimization on Neonatal Mortality in Ethiopia
Authors: Tiruye Tenaw Yimer , Chojenta Catherine , Harris Melissa L. , Holliday Elizabeth , Loxton Deborah
Published: January 2020

Background: Previous studies have suggested that when intimate partner violence (IPV) tends to be persistent across a woman’s life span, her newborn offspring have a higher risk of ill health and mortality. There is a high prevalence of both IPV and neonatal mortality in Ethiopia, but the issue of IPV has remained largely outside the focus of child survival programs in this country. One of the noticeable reasons is a lack of evidence regarding the effect of IPV on neonatal mortality. Therefore, this study investigated the effect of maternal IPV on neonatal mortality in Ethiopia. Method: This study used nationally representative data from the 2016 Ethiopian Demographic and Health Survey. A total of 2,863 currently married women of reproductive age who gave birth in the preceding 5 years were included in analysis. Regression models using propensity scores were used. Results: The prevalence of physical, emotional, and sexual IPV were 24.5%, 22.9%, and 12.0%, respectively. About 56% of women had also experienced at least one act of partner controlling behavior. Maternal IPV experience (a composite measure of physical, sexual, and emotional abuse) was associated with increased neonatal mortality (adjusted odds ratio [AOR] = 2.58, 95% confidence interval [CI] = [1.03, 6.45]). In addition, the odds of neonatal mortality were 2.75 times (AOR = 2.75; 95% CI = [1.05, 7.2]) higher among women who had experienced three or more partner controlling behaviors than women who had experienced less than three or none. Conclusion and implication: Maternal IPV is significantly associated with risk of neonatal mortality in Ethiopia. There is a clear need for IPV interventions in child survival programs. Therefore, existing neonatal survival strategies should focus beyond the direct causes of neonatal mortality, and they need to target IPV as an underlying factor to neonatal morbidities and mortality.
The Association Between Hours Spent at Work and Obesity Status: Results From NHANES 2015 to 2016
Authors: Doerrmann Caitlin , Oancea S. Cristina , Selya Arielle
Published: January 2020

Purpose:

To determine whether weekly hours worked is associated with obesity among employed adults in the United States.

Design:

Data from the 2015 to 2016 National Health and Nutrition Examination Survey were used for this study. National Health and Nutrition Examination Survey is a cross-sectional study.

Setting:

National Health and Nutrition Examination Survey is conducted annually by the National Center for Health Statistics designed to assess the health and nutritional status of citizens in the United States.

Participants:

The final study sample size was 2,581.

Measures:

The outcome was obesity status (yes/no) and the exposure was the number of hours worked per week (<40, =40, >40 h/wk). Covariates of interest included in the analyses were income, age, education level, race, leisure-time physical activity, and gender.

Analysis:

A weighted and adjusted logistic regression model was conducted in order to investigate the association between the number of hours worked at a job per week and obesity status. Descriptive statistics and weighted and adjusted odds ratios were produced with 95% confidence intervals (CI).

Results:

After controlling for the covariates of interest, people working 40 or 40+ hours a week had 1.403 (95% CI: 1.06-1.85) and 1.409 (95% CI: 1.03-1.93) times significantly greater odds of obesity than those who work <40 hours a week, respectively.

Conclusion:

Obesity is a complex and multifactorial disease with genetic and environmental interactions, including the number of hours a person works/week as a potential risk factor.
Contingency in Business Sustainability Research and in the Sustainability Service Industry: A Problematization and Research Agenda
Authors: Imbrogiano Jean-Pierre
Published: January 2020

A sustainability service industry has emerged that promotes the adoption of management tools, mechanisms, and procedures. This emergence took place despite a knowledge gap of how sustainability performance occurs in businesses. To understand practices amid the knowledge gap, this article explores through problematization how the performance orientations of practitioners and researchers relate to each other in the business sustainability field. The article unearths that like the sustainability service industry in practice, scholarship implicitly accepts assumptions of contingency in research designs. Because these implicit assumptions are unattended, it seems, to date, not possible for researchers to provide evidence-based guidance to practitioners on how to address business unsustainability. In addition, basic concepts of contingency are not yet established in this field to explain performance, rendering the acceptance of corresponding assumptions unfounded. The article concludes with research suggestions for the development of theory of sustainability performance in businesses.
Finite element modeling of face/core interface fracture in homogenized honeycomb core sandwich SCB specimens
Authors: Tauhiduzzaman Mohammad , Carlsson Leif A
Published: January 2020

Fracture mechanics analysis of a face/core interface crack in a honeycomb core sandwich under mode I-dominated loading conditions is considered. The main objective of the study is to examine how to represent the homogenized in-plane extensional properties of hexagonal honeycomb core under deformation constraints due to bonding of the core to the face sheets. 2D parametric finite element analysis is conducted over a wide range of homogenized in-plane extensional properties of the core. The results show that plane stress assumption may lead to crack closure effects and highly distorted core elements for core with low in-plane modulus, while plane strain stabilizes the core deformation. Experimental results from SCB testing of a honeycomb core sandwich support the plane strain constrained modulus approach to face/core debond analysis.
A Heteronomous Consumer Romance
Authors: Molesworth Mike
Published: January 2020

In the spirit of dystopian science fiction, this story imagines marketing in a near future. A reader might recognise that there is a relationship between aesthetic forms (stories) and the dramas that play out in society and so although this is fiction, it is also about the critical concerns that are emerging in the use of corporate technologies. The story draws from theory that suggests our most intimate relationships are embedded in and create market structures, and on theory that accounts for how technology (and especially AI) has significant impact on market practices. Core ideas also reference my previous and ongoing research on the imagination, on marketplace relationships and on digital virtual consumption, and from previous accounts of AI and market/political systems in speculative fictions. I invite the reader to reflect on the sorts of dominating human–technology–market relationships that may be with us soon, and on the risk of perverse instantiations in commercial AI deployment. Overall the tone is critical, but themes are also presented as ambiguous, recognising the seductive quality of marketing technologies.
Altered P3a Modulations to Emotional Faces in Male Patients With Chronic Schizophrenia
Authors: Onitsuka Toshiaki , Spencer Kevin M. , Nakamura Itta , Hirano Yoji , Hirano Shogo , McCarley Robert W. , Shenton Martha E. , Niznikiewicz Margaret A.
Published: January 2020

Existing evidence suggests that patients with schizophrenia may have a deficit in processing facial expressions. However, the neural basis of this processing deficit remains unclear. A total of 20 men diagnosed with chronic schizophrenia and 13 age- and sex-matched controls participated in the study. We investigated visual N170 and P3a components evoked in response to fearful, happy, and sad faces during an emotion discrimination task. Compared with control subjects, patients showed significantly smaller N170 amplitudes bilaterally ( P = .04). We found no significant main effect of emotion of the presented faces (fearful, happy, or sad) on N170 amplitude. Patients showed significantly smaller P3a amplitudes in response to fearful ( P = .01) and happy ( P = .02) faces, but no significant between-group differences were observed for sad faces ( P = .22). Moreover, we found no significant P3a modulation effect in response to emotional faces in patients with schizophrenia. Our results suggest that altered P3a modulations to emotional faces may be associated with emotion recognition deficits in patients with schizophrenia.
GRK6 regulates the hemostatic response to injury through its rate-limiting effects on GPCR signaling in platelets
Authors: Chen Xi , Gupta Shuchi , Cooper Matthew , DeHelian Daniel , Zhao Xuefei , Naik Meghna U. , Wurtzel Jeremy G. T. , Stalker Timothy J. , Goldfinger Lawrence E. , Benovic Jeffrey , Brass Lawrence F. , McKenzie Steven E. , Naik Ulhas P. , Ma Peisong
Published: January 2020

Key points

GRK6 regulates the hemostatic response by limiting platelet activation via thrombin and adenosine 5′-diphosphate. GRK6 regulates the hemostatic response by reducing PAR1/4- and P2Y12-dependent signaling.
Circulating CD1c+ myeloid dendritic cells are potential precursors to LCH lesion CD1a+CD207+ cells
Authors: Lim Karen Phaik Har , Milne Paul , Poidinger Michael , Duan Kaibo , Lin Howard , McGovern Naomi , Abhyankar Harshal , Zinn Daniel , Burke Thomas M. , Eckstein Olive S. , Chakraborty Rikhia , Sengal Amel , Scull Brooks , Newell Evan , Merad Miriam , McClain Kenneth L. , Man Tsz-Kwong , Ginhoux Florent , Collin Matthew , Allen Carl E.
Published: January 2020

Key Points

Transcriptional profile of LCH CD1a+CD207+ DCs is most closely related to that of CD1c+ mDCs in the blood. Lineage tracing with BRAFV600E and HLA-DQB2 expression supports CD1c+ mDCs as precursors to LCH CD1a+CD207+ DCs.
Trends in postrelapse survival in classic Hodgkin lymphoma patients after experiencing therapy failure following auto-HCT
Authors: Badar Talha , Epperla Narendranath , Szabo Aniko , Borson Steven , Vaughn John , George Gemlyn , Saini Neeraj , Shah Abdul Rashid , Patel Romil D. , Ahmed Sairah , Shah Nirav N. , Cashen Amanda F. , Hamadani Mehdi , Fenske Timothy S.
Published: January 2020

Key Points

PR-OS of cHL patients has improved in recent years, likely due to incorporation of novel therapies and more effective use of allo-HCT. Future research should focus on earlier integration of novel therapies for patients with refractory disease to improve outcomes further.
Eμ and 3′RR transcriptional enhancers of the IgH locus cooperate to promote c-myc–induced mature B-cell lymphomas
Authors: Ghazzaui Nour , Issaoui Hussein , Ferrad Mélissa , Carrion Claire , Cook-Moreau Jeanne , Denizot Yves , Boyer François
Published: January 2020

Key Points

Transcriptional cooperation between IgH Eμ and 3′RR enhancers is found during B-cell lymphomagenesis in IgH-c-myc mice. Transcriptome analysis reveals wide similarities between human and mouse Burkitt B-cell lymphomas.
An Anisotropic Microstructure Evolution in a Solid Oxide Fuel Cell Anode
Authors: Brus Grzegorz , Iwai Hiroshi , Szmyd Janusz S.
Published: January 2020

The presented research shows that the long-term operation of a solid oxide fuel cell can lead to substantial anisotropic changes in anode material. The morphology of microstructure in the investigated stack was observed before and after the aging test using electron nanotomography. The microstructural parameters were estimated based on the obtained digital representation of the anode microstructure. Anisotropy was discovered in two of the three phases that constitute the anode, namely nickel and pores. The third component of the anode, which is yttrium-stabilized zirconia, remains isotropic. The changes appear at the microscale and significantly affect the transport phenomena of electrons and gasses. The obtained results indicate that the reference anode material that represents the microstructure before the aging test has isotropic properties which evolve toward strong anisotropy after 3800 h of constant operation. The presented findings are crucial for a credible numerical simulation of solid oxide fuel cells. They indicate that all homogeneous models must adequately account for the microstructure parameters that define the anisotropy of transport phenomena, especially if microstructural data is taken from a post-operational anode.
Urinary tract infections in pregnancy in a rural population of Bangladesh: population-based prevalence, risk factors, etiology, and antibiotic resistance
Authors: Lee Anne CC , Mullany Luke C. , Koffi Alain K. , Rafiqullah Iftekhar , Khanam Rasheda , Folger Lian V. , Rahman Mahmoodur , Mitra Dipak K. , Labrique Alain , Christian Parul , Uddin Jamal , Ahmed Parvez , Ahmed Salahuddin , Mahmud Arif , DasGupta Sushil K. , Begum Nazma , Quaiyum Mohammad A. , Saha Samir K. , Baqui Abdullah H.
Published: December 2019

Background

Urinary tract infection (UTI) in pregnancy, including asymptomatic bacteriuria, is associated with maternal morbidity and adverse pregnancy outcomes, including preterm birth and low birthweight. In low-middle income countries (LMICs), the capacity for screening and treatment of UTIs is limited. The objective of this study was to describe the population-based prevalence, risk factors, etiology and antimicrobial resistance patterns of UTIs in pregnancy in Bangladesh.

Methods

In a community-based cohort in Sylhet district, Bangladesh, urine specimens were collected at the household level in 4242 pregnant women (< 20 weeks gestation) for culture and antibiotic susceptibility testing. Basic descriptive analysis was performed, as well as logistic regression to calculate adjusted odds ratios (aOR) for UTI risk factors.

Results

The prevalence of UTI was 8.9% (4.4% symptomatic UTI, 4.5% asymptomatic bacteriuria). Risk factors for UTI in this population included maternal undernutrition (mid-upper arm circumference <23 cm: aOR= 1.29, 95% CI: 1.03–1.61), primiparity (aOR= 1.45, 95% CI: 1.15–1.84), and low paternal education (no education: aOR= 1.56, 95% CI: 1.09–2.22). The predominant uro-pathogens were E. coli (38% of isolates), Klebsiella (12%), and staphyloccocal species (23%). Group B streptococcus accounted for 5.3% of uro-pathogens. Rates of antibiotic resistance were high, with only two-thirds of E. coli susceptible to 3rd generation cephalosporins.

Conclusions

In Sylhet, Bangladesh, one in 11 women had a UTI in pregnancy, and approximately half of cases were asymptomatic. There is a need for low-cost and accurate methods for UTI screening in pregnancy and efforts to address increasing rates of antibiotic resistance in LMIC.
Parental attachment and depressive symptoms in pregnancies complicated by twin-twin transfusion syndrome: a cohort study
Authors: Mackie Fiona L. , Pattison Helen , Jankovic Jelena , Morris R. Katie , Kilby Mark D.
Published: December 2019

Background

Twin-twin transfusion syndrome (TTTS) is a highly morbid condition in which treatment exists, but the pregnancy remains high-risk until delivery. It may have serious sequelae, including fetal death, and in the longer term, neurodevelopmental problems. The aim of this study is to assess antenatal and postnatal parental attachment and depressive symptoms in those with pregnancies affected by TTTS.

Methods

Couples attending for fetoscopic laser ablation treatment of TTTS were asked to complete Condon’s Maternal/Paternal Antenatal/Postnatal Attachment Scale as appropriate, and the Edinburgh Depression Scale the day before ablation, 4 weeks post-ablation, and 6–10 weeks postnatally.

Results

25/27 couples completed the pre-ablation questionnaire (median gestational age 19 + 3 weeks [interquartile range 18 + 2–20 + 6]). 8/18 eligible couples returned the post-ablation questionnaire. 5/17 eligible couples returned the postnatal questionnaire. There was no significant difference in parento-fetal attachment when mothers were compared to fathers at each time point, however parento-fetal attachment did increase over time in mothers (p = 0.004), but not fathers. Mothers reported more depressive symptoms antenatally compared to fathers (p < 0.02), but there was no difference postnatally. 50% women reported Edinburgh Depression Scale scores above the cut-off (≥15) 4 weeks post-ablation. Over time maternal depressive symptoms decreased (p = 0.006), however paternal depressive symptoms remained the same.

Conclusions

This is the first attachment and depression study in a UK cohort of parents with pregnancies affected by TTTS. Although this was a small cohort and the questionnaires used had not been validated in these circumstances, the results suggest that centres caring for these couples should be aware of the risk of maternal and paternal antenatal depression, and screen and refer for additional psychological support. Further work is needed in larger cohorts.

Trial registration

ISRCTN 13114861 (retrospectively registered).
The experiences of early postpartum Shenzhen mothers and their need for home visit services: a qualitative exploratory study
Authors: Xiao Xiao , Ngai Fei-wan , Zhu She-ning , Loke Alice Yuen
Published: December 2019

Background

The early postpartum period is the most stressful period for a new mother, who is assuming new roles and responsibilities in life, and must deal with the demands from her newborn baby and her own care needs. Little is known about whether the current postnatal care services provided by hospitals and community centers meet the needs of women. The aim of this study was to identify the experiences of women in Shenzhen and the problems that they encountered during the first 6 weeks after giving birth; and to explore their expressed needs with regard to postnatal care services.

Methods

This is a qualitative exploratory study. Data were collected in November 2018 through in-depth, semi-structured, face-to-face interviews. A purposive sample was recruited from a tertiary maternal hospital in Shenzhen, China. The dataset was analyzed using content analysis.

Results

Twenty-two mothers were interviewed during their postpartum body check on the 30th or 42nd day after giving birth. Six themes were identified: “the self-care needs of women,” “proficiency in infant care,” “involvement of family in postpartum and infant care,” “family conflicts over postpartum and infant care,” “preparing for the transition to parenthood / grandparenthood,” and “the need for comprehensive postpartum home visit services.”

Conclusions

The concerns expressed by the women during the postpartum period were related to their need to recover physically and to their desire to be perceived as proficient in infant care. Support from husbands and grandmothers could facilitate or impede a woman’s transition to motherhood, and the family’s transition to parenthood / grandparenthood. There were disagreements arising from intergenerational beliefs about postpartum and child care. In providing postpartum care services to women in situations where the family is involved in their care, health professionals should consider the family as a whole.
Factors associated with relevant knowledge of intestinal schistosomiasis and intention to participate in treatment campaigns: a cross sectional survey among school children at Ijinga Island on Lake Victoria, North-Western Tanzania
Authors: Parisi Sandra , Mazigo Humphrey D. , Kreibich Saskia , Puchner Karl , Kasang Christa , Mueller Andreas
Published: December 2019

Background

Annual Mass Drug Administration (MDA) using praziquantel targeting primary school children is the main control strategy against schistosomiasis in Tanzania. However, there are concerns about decreasing participation in mass drug administration among primary school children for unknown reasons. Therefore, the aim of this study was to identify factors related to relevant knowledge about schistosomiasis and the intention to participate in mass drug administration among primary school children in order to give recommendations for future projects.

Methods

A cross sectional, extended knowledge, attitudes and practices (KAP) survey was conducted among 356 primary school children aged 5–17 years in February–March 2016 using a pre-tested questionnaire. This survey was part of a baseline assessment for an integrated proof of concept study aiming towards schistosomiasis elimination on Ijinga Island. Outcomes of interest in logistic regression analysis were relevant knowledge and high intention to participate in treatment campaigns. Explanatory variables were sociodemographic information sources and elements aligned to Protection Motivation Theory (PMT).

Results

Only 17% of the children had relevant intestinal schistosomiasis related knowledge and very few of them knew any of the S. mansoni manifestations and complications. Factors associated with relevant schistosomiasis knowledge were previous diagnosis of schistosomiasis (aOR = 2.43, 95%CI: 1.1–5.6), having heard about schistosomiasis at school (aOR = 9.94, 95%CI: 5.0–19.7) and being enrolled in 6th or 7th grade (aOR = 3.94, 95%CI: 1.3–11.8). Only 40% of the children demonstrated high intention to participate in treatment campaigns. Factors associated with high intention to participate in MDA were previous diagnosis (aOR = 2.23, 95%CI: 1.1–4.7), perceived general risk of disease transmission by lake water (aOR = 1.79, 95%CI: 1.0–3.1), perceived own vulnerability of getting infected (aOR = 5.10, 95%CI: 2.1–12.6), perceived danger of the disease (aOR = 2.47, 95%CI: 1.3–4.8) and the perceived effectiveness of medicaments to cure the disease (aOR = 2.86, 95%CI: 1.4–5.7).

Conclusions

The minority of the school children had high level of theoretical knowledge about schistosomiasis and a small proportion of the children demonstrated high intention to participate in mass drug administration. In general, practical knowledge on preventive measures such as taking anti-schistosomiasis drug during MDA need to be impacted in school children to increase their participation in the control program.
First report of Enterobacter hormaechei with respiratory disease in calves
Authors: Wang Zhicheng , Duan Lisha , Liu Fei , Hu Yun , Leng Chaoliang , Kan Yunchao , Yao Lunguang , Shi Hongfei
Published: January 2020

Background

Enterobacter hormaechei is commonly considered a causative pathogen for nosocomial infections and it does not usually cause diseases in animals. However, researchers have recently dissociated the pathogenic Enterobacter hormaechei from foxes and piglets. Here, the Enterobacter hormaechei was first found to be associated with respiratory disease in unweaned calves in China.

Case presentation

A 2-month-old calf was severely sick and diagnosed with respiratory infection by a rural veterinarian, and it died 5 days after treatment with penicillin G. The lung sample was then run through histopathological analysis and pathogen isolation. The sequence analysis and biochemical tests results showed the isolated bacterium strain to be Enterobacter hormaechei, and drug sensitivity tests showed resistance to all β-lactam antimicrobials and sensitivity to quinolones. Thickened alveoli septum, inflammatory cell infiltration, and erythrocyte diapedesis around the pulmonary alveoli septum were visible in lung histopathological sections. One week later, at the same farm, another calf showed similar clinical signs, and the Enterobacter hormaechei strain was isolated from its nasal discharge; after a week of treatment with enrofloxacin, as suggested by the results of drug sensitivity tests, this calf fully recovered.

Conclusions

To the best of our knowledge, this is the first case report of calves with respiratory disease that was associated with E. hormaechei, and multi-drug resistance was observed in isolates.
The role of the bacterial protease Prc in the uropathogenesis of extraintestinal pathogenic Escherichia coli
Authors: Huang Wen-Chun , Lin Chung-Yen , Hashimoto Masayuki , Wu Jiunn-Jong , Wang Ming-Cheng , Lin Wei-Hung , Chen Chang-Shi , Teng Ching-Hao
Published: January 2020

Background

Extraintestinal pathogenic E. coli (ExPEC) remains one of the most prevalent bacterial pathogens that cause extraintestinal infections, including neonatal meningitis, septicemia, and urinary tract (UT) infections (UTIs). Antibiotic therapy has been the conventional treatment for such infections, but its efficacy has decreased due to the emergence of antibiotic-resistant bacteria. Identification and characterization of bacterial factors that contribute to the severity of infection would facilitate the development of novel therapeutic strategies. The ExPEC periplasmic protease Prc contributes to the pathogen’s ability to evade complement-mediated killing in the serum. Here, we further investigated the role of the Prc protease in ExPEC-induced UTIs and the underlying mechanism.

Methods

The uropathogenic role of Prc was determined in a mouse model of UTIs. Using global quantitative proteomic analyses, we revealed that the expression of FliC and other outer membrane-associated proteins was altered by Prc deficiency. Comparative transcriptome analyses identified that Prc deficiency affected expression of the flagellar regulon and genes that are regulated by five extracytoplasmic signaling systems.

Results

A mutant ExPEC with a prc deletion was attenuated in bladder and kidney colonization. Global quantitative proteomic analyses of the prc mutant and wild-type ExPEC strains revealed significantly reduced flagellum expression in the absence of Prc, consequently impairing bacterial motility. The prc deletion triggered downregulation of the flhDC operon encoding the master transcriptional regulator of flagellum biogenesis. Overexpressing flhDC restored the prc mutant’s motility and ability to colonize the UT, suggesting that the impaired motility is responsible for attenuated UT colonization of the mutant. Further comparative transcriptome analyses revealed that Prc deficiency activated the σE and RcsCDB signaling pathways. These pathways were responsible for the diminished flhDC expression. Finally, the activation of the RcsCDB system was attributed to the intracellular accumulation of a known Prc substrate Spr in the prc mutant. Spr is a peptidoglycan hydrolase and its accumulation destabilizes the bacterial envelope.

Conclusions

We demonstrated for the first time that Prc is essential for full ExPEC virulence in UTIs. Our results collectively support the idea that Prc is essential for bacterial envelope integrity, thus explaining how Prc deficiency results in an attenuated ExPEC.
UBQLN4 promotes progression of HCC via activating wnt-β-catenin pathway and is regulated by miR-370
Authors: Yu Yan , Xu Penglin , Cui Guangying , Xu Xiaodong , Li Kongfei , Chen Xiaolong , Bao Jie
Published: January 2020

Background

Ubiquilin-4 (UBQLN4) is a member of the ubiquitin–proteasome system that is usually upregulated in many tumor cells. Its overexpression has been associated with poor disease outcomes in various cancer diseases. However, the underlying mechanism of UBQLN4 in the development of hepatocellular carcinoma (HCC) has not been elucidated.

Methods

Immunochemistry, real-time PCR, and western blotting were used to evaluate the expression levels of UBQLN4 in cancer tissues. Univariate, Cox-regression, and Kaplan–Meier analyses were performed to determine the association between UBQLN4 expression and HCC prognosis. Cell Counting Kit-8 (CCK-8), transwell, EDU and colony formation assays were conducted to evaluate the role of UBQLN4 in HCC cell progression. The gene set enrichment analysis and luciferase reporter experiments were conducted to find the mechanism of UBQLN4 in HCC.

Results

Ubiquilin-4 (UBQLN4) was overexpressed in HCC tissues. Besides, overexpression of UBQLN4 was associated with poor overall survival and disease-free survival rate of HCC patients. The loss-of-function analysis revealed that suppression of UBQLN4 inhibited the proliferation and invasion of HCC cells in vivo and in vitro. The KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis showed that UBQLN4 could regulate activation of the wnt-β-catenin pathway in HCC cells. Furthermore, our results showed that UBQLN4 was downregulated by miR-370, which acted as a tumor suppressor gene in HCC progression.

Conclusion

The results of the present study suggest that the miR-370/UBQLN4 axis may play a critical role in the progression of HCC. These findings may inform future strategies for the development of therapeutic agents against HCC.
Timing of early laparoscopic cholecystectomy for acute calculous cholecystitis revised: Protocol of a systematic review and meta-analysis of results
Authors: Borzellino Giuseppe , Khuri Safi , Pisano Michele , Mansour Subhi , Allievi Niccolò , Ansaloni Luca , Kluger Yoram
Published: January 2020

Background

Early laparoscopic cholecystectomy has been adopted as the treatment of choice for acute cholecystitis due to a shorter hospital length of stay and no increased morbidity when compared to delayed cholecystectomy. However, randomised studies and meta-analysis report a wide array of timings of early cholecystectomy, most of them set at 72 h following admission. Setting early cholecystectomy at 72 h or even later may influence analysis due to a shift towards a more balanced comparison. At this time, the rate of resolving acute cholecystitis and the rate of ongoing acute process because of failed conservative treatment could be not so different when compared to those operated with a delayed timing of 6–12 weeks. As a result, randomised comparison with such timing for early cholecystectomy and meta-analysis including such studies may have missed a possible advantage of an early cholecystectomy performed within 24 h of the admission, when conservative treatment failure has less potential effects on morbidity. This review will explore pooled data focused on randomised studies with a set timing of early cholecystectomy as a maximum of 24 h following admission, with the aim of verifying the hypothesis that cholecystectomy within 24 h may report a lower post-operative complication rate compared to a delayed intervention.

Methods

A systematic review of the literature will identify randomised clinical studies that compared early and delayed cholecystectomy. Pooled data from studies that settled the early intervention within 24 h from admission will be explored and compared in a sub-group analysis with pooled data of studies that settled early intervention as more than 24 h.

Discussion

This paper will not provide evidence strong enough to change the clinical practice, but in case the hypothesis is verified, it will invite to re-consider the timing of early cholecystectomy and might promote future clinical research focusing on an accurate definition of timing for early cholecystectomy for acute cholecystitis.