bluuebunny/crossref_metadata_2025 huggingface dataset:
Visual histological assessment of morphological features reflects the underlying molecular profile in invasive breast cancer: a morphomolecular study
Authors: Rakha Emad A , Alsaleem Mansour , ElSharawy Khloud A , Toss Michael S , Raafat Sara , Mihai Raluca , Minhas Fayyaz A , Green Andrew R , Rajpoot Nasir M , Dalton Leslie W , Mongan Nigel P
Published: July 2020

Aims

Tumour genotype and phenotype are related and can predict outcome. In this study, we hypothesised that the visual assessment of breast cancer (BC) morphological features can provide valuable insight into underlying molecular profiles.

Methods and results

The Cancer Genome Atlas (TCGA) BC cohort was used (n = 743) and morphological features, including Nottingham grade and its components and nucleolar prominence, were assessed utilising whole‐slide images (WSIs). Two independent scores were assigned, and discordant cases were utilised to represent cases with intermediate morphological features. Differentially expressed genes (DEGs) were identified for each feature, compared among concordant/discordant cases and tested for specific pathways. Concordant grading was observed in 467 of 743 (63%) of cases. Among concordant case groups, eight common DEGs (UGT8, DDC, RGR, RLBP1, SPRR1B, CXorf49B, PSAPL1 and SPRR2G) were associated with overall tumour grade and its components. These genes are related mainly to cellular proliferation, differentiation and metabolism. The number of DEGs in cases with discordant grading was larger than those identified in concordant cases. The largest number of DEGs was observed in discordant grade 1:3 cases (n = 1185). DEGs were identified for each discordant component. Some DEGs were uniquely associated with well‐defined specific morphological features, whereas expression/co‐expression of other genes was identified across multiple features and underlined intermediate morphological features.

Conclusion

Morphological features are probably related to distinct underlying molecular profiles that drive both morphology and behaviour. This study provides further evidence to support the use of image‐based analysis of WSIs, including artificial intelligence algorithms, to predict tumour molecular profiles and outcome.
Optimizing psychosocial support in prostate cancer patients during active surveillance
Authors: Donachie Kim , Cornel Erik , Adriaansen Marian , Mennes Rosa , van Oort Inge , Bakker Esther , Lechner Lilian
Published: July 2020

What are the psychosocial support needs of prostate cancer (PCa) patients undergoing active surveillance (AS)? The preferred management strategy for low‐risk PCa (LR‐PCa) is AS. Patients remain under close surveillance to monitor disease progression. However, living with untreated disease has psychosocial implications. The objective of this study was to investigate the psychosocial support needs in PCa patients undergoing AS. According to Marzouk (2018) 30% of patients risk developing anxiety during the first year of AS. Parker (2015) and Tan (2016) suggest approximately 10% of AS‐patients request a change to active treatment, often based on anxiety. Pickles (2007) states that psychosocial support can effectively reduce anxiety and uncertainty. A literature based interview guide was used to conduct 17 semi‐structured interviews following an explorative qualitative approach. LR‐PCa patients, eligible for AS, were enrolled from two participating Dutch urology clinics experienced with AS. Written informed consent was obtained. Inclusion ended after attaining data saturation. The interviews were transcribed verbatim. NVIVO 10 was used for open coding. Participants expressed recurring uncertainty and anxiety caused by medical examinations, lower urinary tract symptoms and erectile dysfunction. Various effective and ineffective coping strategies were adopted by participants. The use of specific strategies was associated with patient‐physician relationship, locus‐of‐control and disease‐acceptation. Ineffective coping strategies seemed to impede resilience during stressful situations. Satisfactory decision‐making and disease‐acceptation were promoted by immediate availability of relevant, reliable information regarding disease characteristics and treatment options. Early‐stage reliable and relevant information, assessment and encouragement of effective coping strategies appear to be important psychosocial support needs during AS. Most participants in this study had spousal support and completed higher education. Future research should determine the generalizability of these findings in a more heterogeneous population.
Ectodermal‐neural cortex 1 as a novel biomarker predicts poor prognosis and induces metastasis in breast cancer by promoting Wnt/β‐catenin pathway
Authors: Zhou Yuhui , Tang Xiaojiang , Niu Ligang , Liu Yang , Wang Bin , He Jianjun
Published: July 2020

Breast cancer, as the most common malignancy, is the second leading cause of cancer‐related death in women. One of the kelch family member ENC1 is involved in various pathophysiologic processes. But the role of ENC1 in breast cancer has not been investigated. The present study value the feature, clinical significance and the molecular mechanisms of ENC1 in breast cancer. The expression and prognosis value of ENC1 expression among breast cancer and normal breast tissue were investigated in The Cancer Genome Atlas database and human samples. ENC1 was knockdown to explore its function in various breast cancer cell lines. Western blot was performed to explore the potential molecular mechanisms. We observed that ENC1 was overexpressed in breast cancer tissues. ENC1 overexpression was associated with high metastasis and predicted a poor prognosis in patients with breast cancer. ENC1 Knockdown inhibits the growth, clone formation, migration and invasion of breast cancer cells. Mechanism analysis revealed ENC1 was strong associated with the metastasis by modulating β‐catenin pathway. Our study emphasizes that ENC1 is a potential prognostic and metastasis‐related marker of breast cancer, and may function as a possible therapeutic target against breast cancer.
LIPH promotes metastasis by enriching stem‐like cells in triple‐negative breast cancer
Authors: Zhang Yixiao , Zhu Xudong , Qiao Xinbo , Gu Xi , Xue Jinqi , Han Yanshuo , Sun Lisha , Cui Meizi , Liu Caigang
Published: July 2020

Lipase member H (LIPH), a novel member of the triglyceride lipase family. The clinical implications of its expression in breast cancer are still unclear. Therefore, in this study, we investigated the associations between LIPH and the tumorigenic behaviours of 144 triple‐negative breast cancer (TNBC) patients. The ratio and mammosphere‐forming ability of CD44+/CD24− stem‐like cells were tested. The role of LIPH in breast cancer cell migration and invasion was also evaluated. In addition, the effect of LIPH silencing on mitochondrial respiration was determined using the Seahorse assay. Finally, the effect of LIPH silencing on protein expression was determined via tandem mass tag‐based spectrometry and Western blotting. We found that LIPH expression was associated with metastasis in lymph nodes and distant organs (P = 0.025), resulting in poor survival among breast cancer patients (P = 0.027). LIPH knockdown significantly decreased both the ratio of CD44+/CD24− stem‐like cells and their mammosphere‐forming ability. LIPH silencing promoted apoptosis, arrested cell cycle in the G2/M phase, mitigated the oxidation‐related oxygen consumption rate in the mitochondria, and reduced metabolism. LIPH inhibited adhesion between tumour cells and enhanced the epithelial‐mesenchymal transition. Tandem mass spectrometric analysis presented 68 proteins were differentially expressed in LIPH‐silenced cells and LIPH‐mediated modulation of tumour cell adhesion depended on integrin‐related CAPN2 and paxillin signalling. Overall, our findings provided strong evidence that LIPH up‐regulation promoted metastasis and the stemness of TNBC cells. Therefore, targeting LIPH is a potentially viable strategy for preventing metastasis in TNBC.
Isolation and experimental challenge of cultured burbot (Lota lota maculosa) with Flavobacterium columnare and Aeromonas sp. isolates
Authors: Bruce Timothy J. , Ma Jie , Oliver Luke P. , Jones Evan M. , LaFrentz Benjamin R. , Cain Kenneth D.
Published: July 2020

Burbot (Lota lota maculosa) are a potential new species for commercial aquaculture. As burbot culture expands, there is a need to further define pathogen susceptibility and characterize aspects of the burbot immune response in an effort to assess fish health. A recent clinical diagnostic case from juvenile burbot reared at a commercial production facility resulted in the isolation and identification of Flavobacterium columnare along with several Aeromonas spp. The F. columnare isolate was assigned to genetic group 1 via multiplex PCR, a genetic group commonly associated with columnaris disease cases in rainbow trout (Oncorhynchus mykiss). Virulence of the F. columnare isolate was assessed in vivo in both juvenile burbot and rainbow trout. Additionally, several of the Aeromonas sp. case isolates were identified via sequencing (16S rRNA, gyrB and rpoD) and a putative A. sobria isolate (BI‐3) was used to challenge burbot, along with a known virulent Aeromonas sp. (A141), but BI‐3 was not found to be virulent. Burbot were refractory to F. columnare when challenged by immersion, and it is likely that this is a secondary pathogen for burbot. Although refractory in burbot, the identified F. columnare isolate (BI‐1) was found to be virulent in rainbow trout.
Ethylene promotes seed iron storage duringArabidopsisseed maturation via ERF95 transcription factor
Authors: Sun Ying , Li Jia Qi , Yan Jing Ying , Yuan Jun Jie , Li Gui Xin , Wu Yun Rong , Xu Ji Ming , Huang Rong Feng , Harberd Nicholas P. , Ding Zhong Jie , Zheng Shao Jian
Published: July 2020

Because Iron (Fe) is an essential element, Fe storage in plant seeds is necessary for seedling establishment following germination. However, the mechanisms controlling seed Fe storage during seed development remain largely unknown. Here we reveal that an ERF95 transcription factor regulatesArabidopsisseed Fe accumulation. We show that expression ofERF95increases during seed maturation, and that lack of ERF95 reduces seed Fe accumulation, consequently increasing sensitivity to Fe deficiency during seedling establishment. Conversely, overexpression ofERF95has the opposite effects. We show that lack of ERF95 decreases abundance ofFER1messenger RNA in developing seed, which encodes Fe‐sequestering ferritin. Accordingly, afer1‐1loss‐of‐function mutation confers reduced seed Fe accumulation, and suppresses ERF95‐promoted seed Fe accumulation. In addition, ERF95 binds to specificFER1promoter GCC‐boxes and transactivatesFER1expression. We show thatERF95expression in maturing seed is dependent on EIN3, the master transcriptional regulator of ethylene signaling. While lack of EIN3 reduces seed Fe content, overexpression ofERF95rescues Fe accumulation in the seed ofein3loss‐of‐function mutant. Finally, we show that ethylene production increases during seed maturation. We conclude that ethylene promotes seed Fe accumulation during seed maturation via an EIN3‐ERF95‐FER1‐dependent signaling pathway.
An open‐hardware sample mounting solution for inverted light‐sheet microscopes with large detection objective lenses
Authors: RUSSELL C.T. , REES E.J.
Published: July 2020

Implementations of light‐sheet microscopes are often incompatible with standard methods of sample mounting. Light‐sheet microscopy uses orthogonal illumination and detection to create a thin sheet of light which does not illuminate the sample outside of the depth of field of the detection axis. Typically, this configuration involves a pair of orthogonal objectives which constrains the positioning and length of cover slips in the range of the detection objective. Here, we present an open‐hardware sample mounting system for light‐sheet microscopes using large detection objectives, built using 3D printed components and demonstrate the chamber's efficacy on live biological samples in a custom light‐sheet microscope.

Lay Description

Implementations of light‐sheet microscopes are often incompatible with standard methods of sample mounting. Light‐sheet microscopy creates a thin sheet of light at a certain depth of field within a volumetric sample. Typically, this configuration involves a pair of orthogonal objectives which constrains the positioning of samples and sample‐mounting apparatus in range of the detection objective. To overcome the limitations of this setup, we present an open‐hardware sample mounting system for light‐sheet microscopes using large detection objectives, built using 3D printed components and demonstrate the chamber’s efficacy on live biological samples in a custom light‐sheet microscope.
Repackaging Fatherhood: Father Engagement and Cooperative Coparenting in Mid‐Pregnancy Marriages and Cohabitations
Authors: Su Jessica Houston , Dwyer Emory Allison
Published: July 2020

Objective

This study examined how the timing and structure of parents' relationships are related to father engagement and cooperative coparenting in the United States.

Background

Responses to nonmarital pregnancies have shifted; mid‐pregnancy (“shotgun”) marriages have declined while mid‐pregnancy cohabitations have significantly increased. These less institutionalized family forms may create ambiguity about fathers' roles as parents and partners.

Method

Drawing on data from the Fragile Families and Child Well‐Being Study, a longitudinal birth cohort study (n = 2,752), we estimated conditional associations between a five‐category measure of parents' relationship structure and timing at the focal child's birth—(a) mid‐pregnancy cohabitation, (b) mid‐pregnancy marriage, (c) pre‐pregnancy cohabitation, (d) pre‐pregnancy marriage, and (e) nonresident couples—with measures of father engagement and cooperative coparenting when the child was 1 year old. Supplemental analyses evaluated these outcomes at Ages 3 and 5.

Results

At Age 1, fathers in mid‐pregnancy cohabitations reported less cooperative coparenting with the child's mother compared to fathers in pre‐pregnancy cohabitations. In contrast, fathers in mid‐pregnancy marriages were more engaged with their children than fathers in pre‐pregnancy marriages.

Conclusion

Fathers were particularly engaged with young children following mid‐pregnancy relationship transitions but were less cooperative coparents with the child's mother. This study joins research suggesting that fathers with low socioeconomic status may be embracing a new “package deal” in which the father–child relationship is central, and the father–mother relationship is secondary.
Dietary guanidinoacetic acid supplementation improved carcass characteristics, meat quality and muscle fibre traits in growing–finishing gilts
Authors: Zhu Zhengpeng , Gu Changsong , Hu Shengdi , Li Bin , Zeng Xiangfang , Yin Jingdong
Published: July 2020

This study was designed to evaluate the effects of guanidinoacetic acid (GAA) on growth performance, carcass characteristics, meat and muscle fibre traits of growing–finishing gilts. 300 female PIC pigs were randomly divided (30.10 ± 2.94 kg) into 2 treatments with 6 replicates of 25 each for a 100‐day trial. Two dietary treatments were comprised of a control diet and a control diet fortified with 450 mg/kg GAA. Growth performance was evaluated for each phase. Carcass characteristics and meat quality were determined at last phase. Gilts had free access to feed and water during the experiment. The result indicated that GAA did not affect growth performance (p > 0.05). GAA not only increased longissimus dorsi (LM) muscle weight but also decreased its shear force, b*value and drip loss (p < 0.05). Mandibular fat index was decreased by GAA (p < 0.05). GAA upregulated myosin heavy chain (MyHC) I mRNA expression with lower myofibre cross‐sectional area and fibre diameter in LM muscle (p < .05). In conclusion, GAA can improve carcass characteristics and meat quality by changing muscle fibre characteristics and reducing mandibular fat index in finishing gilts.
Effects of sleep modulation during pregnancy in the mother and offspring: Evidences from preclinical research
Authors: Pires Gabriel Natan , Benedetto Luciana , Cortese Rene , Gozal David , Gulia Kamalesh K. , Kumar Velayudhan Mohan , Tufik Sergio , Andersen Monica Levy
Published: July 2020

Disturbed sleep during gestation may lead to adverse outcomes for both mother and child. Animal research plays an important role in providing insights into this research field by enabling ethical and methodological requirements that are not possible in humans. Here, we present an overview and discuss the main research findings related to the effects of prenatal sleep deprivation in animal models. Using systematic review approaches, we retrieved 42 articles dealing with some type of sleep alteration. The most frequent research topics in this context were maternal sleep deprivation, maternal behaviour, offspring behaviour, development of sleep–wake cycles in the offspring, hippocampal neurodevelopment, pregnancy viability, renal physiology, hypertension and metabolism. This overview indicates that the number of basic studies in this field is growing, and provides biological plausibility to suggest that sleep disturbances might be detrimental to both mother and offspring by promoting increased risk at the behavioural, hormonal, electrophysiological, metabolic and epigenetic levels. More studies on the effects of maternal sleep deprivation are needed, in light of their major translational perspective.
Upper digestive tract abnormalities in dogs with chronic idiopathic lymphoplasmacytic rhinitis
Authors: Gianella Paola , Roncone Silvia , Ala Ugo , Bottero Enrico , Cagnasso Federica , Cagnotti Giulia , Bellino Claudio
Published: July 2020

Background

Chronic idiopathic lymphoplasmacytic rhinitis (CILPR) is a common inflammatory disorder of unknown etiology affecting the nasal cavity of dogs. The diagnosis is made by exclusion of other causes of nasal disease and specific therapeutic protocols are lacking. In human medicine, a relationship between CILPR and gastrointestinal clinical signs has been postulated, and remission of respiratory signs after clinical trials with medications for gastrointestinal disorders has been observed.

Objectives

To describe history, clinical presentation, endoscopic and histopathologic concurrent respiratory and digestive tract abnormalities, and to evaluate improvement of respiratory signs after treatment for gastrointestinal signs.

Animals

Twenty‐five dogs with CILPR.

Methods

Prospective study. For inclusion, following information had to be available: respiratory and digestive clinical signs, airway and digestive tract endoscopic abnormalities, histologic evaluation of respiratory and gastrointestinal tract biopsy specimens, and clinical response to different treatment strategies.

Results

Twenty‐two dogs had endoscopic gastrointestinal lesions, whereas 13 dogs had concurrent gastrointestinal signs. Most esophageal and duodenal endoscopic abnormalities were classified as moderate or severe. Respiratory and gastrointestinal tract histologic evaluation identified mostly chronic inflammation. Remission or marked improvement of respiratory signs was observed in the majority of dogs treated only for gastrointestinal signs up to 12 months after endoscopy. No significant associations between treatments and follow‐up information were found.

Conclusion and Clinical Importance

Nasal and upper digestive tract abnormalities coexist in some dogs with CILPR. Lack of standardized therapeutic protocols suggests caution when interpreting improvement in nasal clinical signs. Additional studies are needed to explore the possibility of a cause‐effect relationship between the 2 processes.
Review of current state of knowledge of microcystin and its impacts on fish in Lake Victoria
Authors: Onyango David M. , Orina Paul S. , Ramkat Rose C. , Kowenje Chrispine , Githukia Cecilia M. , Lusweti Dorcas , Lung'ayia Henry B. O.
Published: July 2020

Microcystins are part of algal toxins produced intracellularly within algal cells, being in the family of hepatotoxic cyclic peptides from various species of blue‐green algae. Blue‐green algae are widely abundant in many equatorial eutrophic lakes, including Lake Victoria, with microcystin mainly from cyanobacterial blooms released into the water column, with different effects along the aquatic ecosystem trophic levels. Depending on the length of exposure and exposure route, microcystin effects on fish can include embryonic hatching perturbations, reduced survival and growth rates, changes in behavior, osmoregulation, increased liver activities and heart rates, as well as histopathological effects. While bioaccumulation is confirmed among fish, biomagnification along food webs is debatable. Lake Victoria the second largest freshwater lake in the world, and the source of livelihoods to millions reported near the gulf and shore MCs of 190 ± 51 to 543 ± 26 ng MC/g DW, respectively. Little is known, however, on the effects of microcystin on the Lake Victoria fishery and, ultimately, on the human population against the WHO recommended human microcystin intake levels of 0.04 µg/kg, thereby being the basis for this review.
Weather predicates, binding, and radical contextualism
Authors: Elbourne Paul
Published: July 2020

The implicit content indicating location associated with “raining” and other weather predicates is a definite description meaning “the location occupied byx,” where the individual variable “x” can be referential or bound. This position has deleterious consequences for certain varieties of radical contextualism.
Dealing with Dysfunction: Negotiating with Difficult Individuals
Authors: Ingerson Marc‐Charles , DeTienne Kristen Bell , Hooley Jill M. , Black Nathan A.
Published: July 2020

Recent research suggests that many times one or both parties in an interaction will struggle with irrationality or dysfunction. Understanding the types of dysfunctional personalities that negotiators might encounter, and how to deal with them, becomes an important measure of preparation for any professional negotiator. For this reason, this article reviews how better to identify, understand, and negotiate with counterparts who exhibit challenging, difficult, and dysfunctional behaviors.
The critically ill brain after cardiac arrest
Authors: Medicherla Chaitanya B. , Lewis Ariane
Published: July 2020

Cardiac arrest can cause hypoxic–anoxic ischemic brain injury due to signaling cascades that lead to damaged cell membranes and vital cellular organelles, resulting in cell death in the setting of low or no oxygen. Some brain areas are more prone to damage than others, so patients with hypoxic–anoxic ischemic brain injury present with several outcomes, including reduced level of consciousness or alertness, memory deficits, uncoordinated movements, and seizures. Some patients may have mild deficits, while others may have such severe injury that it can progress to brain death. High‐quality cardiopulmonary resuscitation is a proven technique to improve outcome after cardiac arrest, although morbidity and mortality remain high. Induced hypothermia, which involves artificially cooling the body immediately after cardiac arrest, may reduce injury to the brain and improve morbidity and mortality. Neuroprognostication after cardiac arrest is challenging and requires a multimodal approach involving clinical neurologic examinations, brain imaging, electrical studies to assess brain activity, and biomarkers to predict outcome.
Association between access to full‐service restaurants and childhood obesity
Authors: Jia Peng , Yang Hongxi , Cao Xinxi , Yuan Changzheng , Xiao Qian , Yang Shujuan , Wang Yaogang
Published: July 2020

The lack of access to full‐service restaurants (FSRs) is generally thought to be a risk factor for childhood obesity, as it could discourage healthful eating‐out behaviours while increasing the exposure to unhealthful food venues as “compensatory” options. However, the association between FSR access and childhood obesity has not been comprehensively reviewed previously. A literature search was conducted on PubMed and Web of Science for articles published before 1 January 2019 that examined the association between FSR access and weight‐related behaviours and outcomes among children and adolescents. Eighteen studies conducted in three countries were identified, published from 2006 to 2018 with a median sample size of 2352 (ranging from 323 to 529 367). Findings were mixed among these 18 studies that reported on the association between access to FSRs and weight‐related outcomes. Our meta‐analyses showed that there were no significant associations of FSR access with the level of body mass index (BMI) and the BMI z‐score among children. Also, there was no apparent evidence on the association between FSR access and the risk of overweight/obesity. Our results need to be interpreted with caution, considering the menu quality of FSRs and heterogeneity of eligible studies in this meta‐analysis. Well‐designed epidemiologic studies are warranted to further elaborate on the potential association between FSR access and children's weight status.
Muscle loss in COPD: An ‘imploding’ phenotype in need of therapies
Authors: Celli Bartolome R.
Published: July 2020

See related article
The characteristics of palate and upper dental arch can be an anatomical marker for men with schizophrenia? Case‐control study
Authors: Mobile Rafael Zancan , Roussenq Ana Clelia , de Araujo Melissa Rodrigues , Sbalqueiro Ricardo , Maciel José Vinícius Bolognesi , de Lima Antonio Adilson Soares
Published: July 2020

Aims

The aim of this study was to compare individuals with and without schizophrenia through the characteristics of the palate, such as width, length, depth, palate shape, and upper dental arch shape.

Methods and results

The sample was divided into one case group (n = 45) and two control groups (n = 90; 45 individuals each group). Groups were paired by variables: sex, age, and malocclusion type. All analyses were performed on upper dental arch plaster models. All individuals were male and the mean age was 28.56 (SD: 7.82) years. The frequency of the malocclusion type observed was 54.1% (Class I), 22.2% (Class II), and 23.7% (Class III). Statistically significant difference was observed between the case and control groups for the variables palate shape (P = .004) and upper dental arch shape (P = .003). The case group had a higher frequency of the deep or grooved palate shape (57.8%) and parabolic dental arch shape (48.9%). There was no statistically significant difference for the palate width, length, and depth (P > .05).

Conclusions

There was an evidence that the deep or grooved palate shape and parabolic dental arch shape are morphological characteristics of the palate in men with schizophrenia.
Poner la casa (οἶκος) en orden: reconfiguración de relaciones en la Carta a Filemón
Authors: Rodríguez-Moreno Mary Betty
Published: July 2020

El artículo busca esclarecer algunos de los interrogantes recientes propuestos por los investigadores de la Carta a Filemón. En diálogo estrecho con los estudios socioculturales del mundo mediterráneo y el análisis retórico de la Carta, buscamos demostrar cómo la retórica paulina reconfigura los principios básicos de las relaciones humanas de la casa y de la Iglesia a partir de la experiencia vivida en la casa de Filemón con su esclavo Onésimo. La Carta significó seguramente una gran novedad para los miembros de esta iglesia doméstica, dadas las condiciones socioculturales constitutivas de su escenario de lectura.
Experimental Investigation of a Flat-Plate Oscillating Heat Pipe With Groove-Enhanced Minichannels
Authors: Rhodes Matthew J. , Thompson Scott M.
Published: July 2020

The thermal and capillary performance of a groove-enhanced, or “microchannel-embedded,” flat-plate oscillating heat pipe (MC FP-OHP) was experimentally investigated while varying heating width, orientation, working fluid and operating temperature. The copper MC FP-OHP possessed two layers of 1.02 × 1.02 mm2 square channels, with the center 14 channels possessing two embedded microchannels (0.25 × 0.13 mm2) aligned coaxially with the primary minichannels. A FP-OHP without embedded microchannels, but with deeper minichannels (DC FP-OHP), was also tested for comparison. The FP-OHPs were filled with Novec 7200 or water (both at 80% ± 2% by volume), and the heating widths were varied between full-width and localized configurations: 38.71 cm2 and 14.52 cm2, respectively. Experimental results demonstrate that the MC FP-OHP is significantly less sensitive to operating orientation and can perform with less detriment as heat flux increases. The MC FP-OHP has a lower startup heating requirement and provides more fluid wetting along the FP-OHP structure—which is advantageous for pumping liquid from the evaporator to the condenser. The MC FP-OHP has enhanced convective heat transfer during operation, as it was observed to have similar or lower thermal resistances to that of the DC FP-OHP for a wide range of operating conditions. The groove-enhanced minichannel within the MC FP-OHP also provides for enhanced heat transfer because there being more thin-film evaporation sites and vapor–liquid mixing between the minichannel and microchannels.
Three-dimensional chromatin interactions remain stable upon CAG/CTG repeat expansion
Authors: Ruiz Buendía Gustavo A. , Leleu Marion , Marzetta Flavia , Vanzan Ludovica , Tan Jennifer Y. , Ythier Victor , Randall Emma L. , Marques Ana C. , Baubec Tuncay , Murr Rabih , Xenarios Ioannis , Dion Vincent
Published: July 2020

Unexpectedly, the molecular pathogenesis of expanded CAG/CTG diseases does not include changes in 3D chromatin conformation.
Integrator restrains paraspeckles assembly by promoting isoform switching of the lncRNA
NEAT1
Authors: Barra Jasmine , Gaidosh Gabriel S. , Blumenthal Ezra , Beckedorff Felipe , Tayari Mina M. , Kirstein Nina , Karakach Tobias K. , Jensen Torben Heick , Impens Francis , Gevaert Kris , Leucci Eleonora , Shiekhattar Ramin , Marine Jean-Christophe
Published: July 2020

Integrator is a key regulator of
NEAT1
isoform switching and, thereby, paraspeckles biogenesis and chemosensitivity.
Mechanical penetration of β-lactam–resistant Gram-negative bacteria by programmable nanowires
Authors: Liu Lizhi , Chen Sheng , Zhang Xu , Xue Zhenjie , Cui Shengjie , Hua Xiaoting , Yang Baowei , Yan Huiling , Liu Cong , Wang Jing , Zhang Zengfeng , Yu Wei , Wu Fan , Xu Wujun , Lehto Vesa-Pekka , Yue Tianli , Liu Yan , Yu Yunsong , Wang Tie , Wang Jianlong
Published: July 2020

β-lactam–resistant Gram-negative bacteria with decrease in stiffness can be more efficiently penetrated by sharp nanowires.
Human antibodies neutralize enterovirus D68 and protect against infection and paralytic disease
Authors: Vogt Matthew R. , Fu Jianing , Kose Nurgun , Williamson Lauren E. , Bombardi Robin , Setliff Ian , Georgiev Ivelin S. , Klose Thomas , Rossmann Michael G. , Hurst Brett L. , Tarbet E. Bart , Bochkov Yury A. , Gern James E. , Kuhn Richard J. , Crowe James E.
Published: July 2020

A human monoclonal antibody shows potential to prevent or treat acute flaccid myelitis associated with enterovirus D68 infection.
TOX is expressed by exhausted and polyfunctional human effector memory CD8
+
T cells
Authors: Sekine Takuya , Perez-Potti André , Nguyen Son , Gorin Jean-Baptiste , Wu Vincent H. , Gostick Emma , Llewellyn-Lacey Sian , Hammer Quirin , Falck-Jones Sara , Vangeti Sindhu , Yu Meng , Smed-Sörensen Anna , Gaballa Ahmed , Uhlin Michael , Sandberg Johan K. , Brander Christian , Nowak Piotr , Goepfert Paul A. , Price David A. , Betts Michael R. , Buggert Marcus
Published: July 2020

The transcription factor TOX is not exclusively linked to T cell exhaustion (see related Focus by Utzschneider and Kallies).
Human effector T cells express TOX—Not so “TOX”ic after all
Authors: Utzschneider Daniel T. , Kallies Axel
Published: July 2020

TOX expression is not restricted to exhausted T cells but is a characteristic of all human effector CD8
+
T cells (see the related Research Article by

Sekine
et al.

).
Ethionamide Population Pharmacokinetic Model and Target Attainment in Multidrug-Resistant Tuberculosis
Authors: Al-Shaer Mohammad H. , Märtson Anne-Grete , Alghamdi Wael A. , Alsultan Abdullah , An Guohua , Ahmed Shahriar , Alkabab Yosra , Banu Sayera , Houpt Eric R. , Ashkin David , Griffith David E. , Cegielski J. Peter , Heysell Scott K. , Peloquin Charles A.
Published: July 2020

Ethionamide (ETA), an isonicotinic acid derivative, is part of the multidrug-resistant tuberculosis (MDR-TB) regimen. The current guidelines have deprioritized ETA because it is potentially less effective than other agents. Our aim was to develop a population pharmacokinetic (PK) model and simulate ETA dosing regimens in order to assess target attainment. This study included subjects from four different sites, including healthy volunteers and patients with MDR-TB. The TB centers included were two in the United States and one in Bangladesh.
Clinical Trials of Repurposed Antivirals for SARS-CoV-2
Authors: Martinez Miguel Angel
Published: July 2020

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has prompted the repurposing of drugs on the basis of promising
in vitro
and therapeutic results with other human coronavirus diseases, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). These repurposed drugs have mainly included remdesivir, favipiravir, lopinavir-ritonavir, ribavirin, interferons, and hydroxychloroquine.
Clostridioides difficile para
-Cresol Production Is Induced by the Precursor
para
-Hydroxyphenylacetate
Authors: Harrison Mark A. , Faulds-Pain Alexandra , Kaur Harparkash , Dupuy Bruno , Henriques Adriano O. , Martin-Verstraete Isabelle , Wren Brendan W. , Dawson Lisa F.
Published: July 2020

Clostridioides difficile
infection results from antibiotic-associated dysbiosis.
para
-Cresol, a phenolic compound produced by
C. difficile
, selectively targets gammaproteobacteria in the gut, facilitating dysbiosis. Here, we demonstrate that expression of the
hpdBCA
operon, encoding the HpdBCA decarboxylase which converts
p
-HPA to
p
-cresol, is upregulated in response to elevated exogenous
p
-HPA, with induction occurring between >0.1 and ≤0.25 mg/ml. We determined a single promoter and an inverted palindromic repeat responsible for basal and
p
-HPA-inducible
hpdBCA
expression. We identified turnover of tyrosine, a
p
-HPA precursor, does not induce
hpdBCA
expression above basal level, indicating that exogenous
p
-HPA was required for
p
-cresol production. Identifying regulatory controls of
p
-cresol production will provide novel therapeutic targets to prevent
p
-cresol production, reducing
C. difficile
’s competitive advantage.
Cell Fusion Induced by a Fusion-Active Form of Human Cytomegalovirus Glycoprotein B (gB) Is Inhibited by Antibodies Directed at Antigenic Domain 5 in the Ectodomain of gB
Authors: Reuter Nina , Kropff Barbara , Schneiderbanger Julia Karin , Alt Mira , Krawczyk Adalbert , Sinzger Christian , Winkler Thomas H. , Britt William J. , Mach Michael , Thomas Marco
Published: July 2020

HCMV is a major global health concern, and antiviral chemotherapy remains problematic due to toxicity of available compounds and the emergence of drug-resistant viruses. Thus, an HCMV vaccine represents a priority for both governmental and pharmaceutical research programs. A major obstacle for the development of a vaccine is a lack of knowledge of the nature and specificities of protective immune responses that should be induced by such a vaccine. Glycoprotein B of HCMV is an important target for neutralizing antibodies and, hence, is often included as a component of intervention strategies. By generation of fusion-active gB chimeras, we were able to identify target structures of neutralizing antibodies that potently block gB-induced membrane fusion. This experimental system provides an approach to screen for antibodies that interfere with gB’s fusogenic activity. In summary, our data will likely contribute to both rational vaccine design and the development of antibody-based therapies against HCMV.
First report of paracoccidioidomycosis reactivation as a complication of immunosuppressive therapy for acute severe colitis in a caving enthusiast
Authors: Healey Scott , Said Waseem , Fayyaz Faisal , Bell Andrew
Published: July 2020

Treatment for ulcerative colitis often requires the administration of immunosuppressive therapy. Shortly after rescue therapy with infliximab for acute severe colitis, a patient who was also taking corticosteroids, azathioprine and adalimumab became rapidly unwell with atypical pneumonia, which did not respond to conventional antimicrobials. Re-examining the travel history revealed a prior caving trip to Costa Rica. Dimorphic fungal serology was thus tested and a diagnosis of paracoccidioidomycosis was made. After a lengthy intensive care unit admission, the patient made a recovery after the administration of appropriate antifungal therapy and was discharged home on long-term oral antifungals.
E-cigarette, or vaping, product use-associated lung injury (EVALI) treated with veno-venous extracorporeal membrane oxygenation (VV-ECMO) and ultra-protective ventilator settings
Authors: Odish Mazen Faris , Bellinghausen Amy , Golts Eugene , Owens Robert Llewellyn
Published: July 2020

A 19-year-old man vaping with tetrahydrocannabinol presented with dyspnoea and right pneumothorax. History, imaging and negative infectious workup were consistent with E-cigarette, or vaping, product use-associated lung injury (EVALI). Treated with systemic steroids, he developed acute respiratory distress syndrome and was intubated requiring veno-venous extracorporeal membrane oxygenation (VV-ECMO) by hospital day 3. Using VV-ECMO, very-low tidal volume ventilation of 1.5 cc/kg was achieved, as was daily ambulation. VV-ECMO was decannulated on hospital day 9 and the patient was extubated the next day. He was discharged home on hospital day 13 without oxygen. At post-intensive care unit clinic follow-up, he had lost 20 kg of weight while hospitalised and reported nightmares. Patients with EVALI may be supported with VV-ECMO, which allows ultra-lung-protective mechanical ventilation that may minimise ventilator-induced lung injury. Follow-up in patients with EVALI is essential to diagnose and treat comorbidities, follow lung function and prevent relapses.
Factors influencing diagnosis and treatment initiation for multidrug-resistant/rifampicin-resistant tuberculosis in six sub-Saharan African countries: a mixed-methods systematic review
Authors: Oga-Omenka Charity , Tseja-Akinrin Azhee , Sen Paulami , Mac-Seing Muriel , Agbaje Aderonke , Menzies Dick , Zarowsky Christina
Published: July 2020

Background

Drug-resistant tuberculosis burdens fragile health systems in sub-Saharan Africa (SSA), complicated by high prevalence of HIV. Several African countries reported large gaps between estimated incidence and diagnosed or treated cases. Our review aimed to identify barriers and facilitators influencing diagnosis and treatment for drug-resistant tuberculosis (DR-TB) in SSA, which is necessary to develop effective strategies to find the missing incident cases and improve quality of care.

Methods

Using an integrative design, we reviewed and narratively synthesised qualitative, quantitative and mixed-methods studies from nine electronic databases: Medline, Global Health, CINAHL, EMBASE, Scopus, Web of Science, International Journal of Tuberculosis and Lung Disease, PubMed and Google Scholar (January 2006 to June 2019).

Results

Of 3181 original studies identified, 55 full texts were screened, and 29 retained. The studies included were from 6 countries, mostly South Africa. Barriers and facilitators to DR-TB care were identified at the health system and patient levels. Predominant health system barriers were laboratory operational issues, provider knowledge and attitudes and information management. Facilitators included GeneXpert MTB/RIF (Xpert) diagnosis and decentralisation of services. At the patient level, predominant barriers were patients being lost to follow-up or dying due to lengthy diagnostic and treatment delays, negative public sector care perceptions, family, work or school commitments and using private sector care. Some patient-level facilitators were HIV positivity and having more symptoms.

Conclusion

Case detection and treatment for DR -TB in SSA currently relies on individual patients presenting voluntarily to the hospital for care. Specific interventions targeting identified barriers may improve rates and timeliness of detection and treatment.
Adoption of enterprise architecture for healthcare in AeHIN member countries
Authors: Jonnagaddala Jitendra , Guo Guan N , Batongbacal Sean , Marcelo Alvin , Liaw Siaw-Teng
Published: July 2020

Background

Healthcare organisations are undergoing a major transformational shift in the use of information and digital health technologies. Enterprise architecture (EA) has been incrementally adopted in many healthcare organisations globally to facilitate this change. EA can increase the effectiveness of an organisation’s digital health capabilities and resources. However, little is known about the status of EA adoption in low-income and middle-income countries. This study aimed to evaluate the challenges, goals and benefits associated with adoption of EA for healthcare in the Asia eHealth Information Network (AeHIN) member countries .

Methods

We developed an EA Adoption Evaluation framework with four principal layers: governance, strategy, EA and performance. The framework guided the development of a questionnaire to investigate the goals, challenges and benefits faced before and during EA adoption by healthcare organisations.

Sample

26 participants from 18 healthcare organisations in the Asia-Pacific region representing 11 countries. Organisations included Ministries of Health, Universities, Non-Governmental Organisations and Technical Advisory Groups.

Findings

Only 5 of the 18 organisations had begun adopting EA. The goals expressed for EA adoption were to address issues such as interoperability, lack of technical infrastructure and poor alignment of business and information technology strategies. Cost reduction was less emphasised. The main challenges to adopting EA was the lack of EA knowledge, leadership and involvement of senior management.

Conclusion

The adoption of EA is incipient in AeHIN member healthcare organisations. To encourage EA adoption, these organisations need to invest in internal capacity building, senior management training and seek independent EA expert advice to systematically identify and address the barriers to adopting EA.
Scoping review protocol on maternal, newborn and child health research in Ethiopia
Authors: Chan Grace J , Getnet Misrak , Olowojesiku Ronke , Min-Swe Thein , Hunegnaw Bezawit , Bekele Delayehu
Published: July 2020

Introduction

There has been a tremendous reduction in maternal and child mortality in the last decade. However, a significant number of deaths still occur disproportionately in low-income country settings. Ethiopia is the second-most populous nation in sub-Saharan Africa with a high maternal mortality rate of 412 deaths per 100 000 live births and an under-five mortality rate of 55 per 1000 live births. This study presents a scoping review protocol to describe the current knowledge of maternal and child health in Ethiopia to identify gaps for prioritisation of future maternal, newborn and child health research.

Methods and analyses

A search strategy will be conducted in PubMed/MEDLINE, EMBASE and the WHO African Index Medicus. Researchers will independently screen title and abstracts followed by full texts for inclusion. Study characteristics, research topics, exposures and outcomes will be abstracted from articles meeting inclusion criteria using standardised forms. Descriptive analysis of abstracted data will be conducted.

Ethics and dissemination

Data will be abstracted from published manuscripts and no additional ethical approval is required. The results of the review will be shared with maternal and child health experts in Ethiopia through stakeholder meetings to prioritise research questions. Findings will be submitted to a peer-reviewed journal for publication, in addition to national-level and global-level disseminations.
Sex-specific association of serum uric acid dynamics with the incidence of metabolic syndrome in a health check-up Chinese population: a prospective cohort study
Authors: Liu Ying , Fan Yongjun , Liu Qigui , Liu Kehua , Chen Fangfang , Tang Xiao , Li Guorong , Hu Dongmei , Song Guirong
Published: July 2020

Objective

Many studies have demonstrated that elevated serum uric acid (SUA) level is linked with metabolic syndrome (MetS). However, whether there is a sex difference in the association between SUA and MetS has not been determined. This study aimed to accurately explore the impact of SUA longitudinal changes on MetS by sex.

Design

A prospective cohort study.

Setting

The Health Check-up Centre of the Second Hospital affiliated with Dalian Medical University from 2010 to 2016.

Participants

A health check-up cohort of 577 men and 1698 women aged 20–60 years who did not exhibit MetS or hyperuricaemia at baseline and underwent at least two physical examinations from 2010 to 2016.

Primary and secondary outcome measures

Weight, height, blood pressure and blood biochemistry parameters, including SUA, were measured. MetS was defined according to the Joint Interim Statement criteria.

Methods

Based on longitudinal data, a linear mixed-effects model was constructed to explore the characteristics of SUA dynamic changes in males and females, and joint modelling of longitudinal and survival data was done to analyse the association between SUA dynamic changes and MetS occurrence.

Results

The natural logarithm of SUA (LNSUA) in females exhibited a gradually increasing trend, and its annual growth rate in females who developed MetS was greater than that of the non-MetS females. The longitudinal growth of SUA in females was a risk factor for the onset of MetS, and the estimated HR was 13.2580 (95% CI 1.9106 to 91.9957) for each 1-unit rise in LNSUA longitudinally. An association between the longitudinal growth of LNSUA and MetS was not found in males.

Conclusions

The longitudinal increase in SUA in females could increase the risk of MetS, even if the SUA changes within the normal range. The longitudinal increase in SUA in males was not a predictor for MetS.
Against the odds: unlikely COVID-19 recovery
Authors: Bisson Elspeth , Presswood Edward , Kenyon Jasmine , Shelton Fenella , Hall Toby
Published: July 2020

Background

We present a 67-year-old male, with palliative hypopharyngeal squamous cell carcinoma, who contracted COVID-19 infection while in hospital. Cancer diagnosis, among other clinical features, increases the risk of poor outcome of COVID-19 infection. A recently validated risk calculator (COVID-GRAM) can help to guide prognosis.

Events

COVID-19 infection caused significant clinical deterioration in this patient. A Treatment Escalation Plan of ward-based care was put in place and the palliative care team involved. The goal of care was comfort.

Results

The patient improved clinically and retested negative for COVID-19. He was discharged to a nursing home for ongoing supportive care of his malignancy.

Discussion

The validated COVID-GRAM calculator predicted a greater than 99% risk that this patient would require intensive therapy unit admission or die. This patient overcame significant physiological challenges to survive COVID-19, highlighting the challenges of prognostication and suggesting that palliation of COVID-19 is not detrimental to survival.