bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Acute Atmospheric Pressure Changes on Dynamic Contour Tonometry and Goldmann Applanation Tonometry in Normal Individuals: A Pilot Study
Authors: Albis-Donado Oscar , Rodríguez-Camacho Brenda , Bhartiya Shibal , Ramírez-Neria Paulina , López-Star Ellery , González-Daher Pamela , Badillo-Fernandez Mariana , Stalmans Ingeborg
Published: July 2020

Précis:

Intraocular pressure (IOP) measurement differences with Goldmann applanation tonometry (GAT) and dynamic contour tonometry (DCT) are affected by atmospheric pressure inside a hyperbaric chamber.

Purpose:

To compare IOP measurements obtained with GAT and DCT in 22 normal individuals at different atmospheric pressures simulated in a hyperbaric chamber.

Methods:

The IOP of both eyes of 22 healthy volunteers was measured using GAT and DCT at 4 different atmospheric pressure levels.

Starting at 1 Queretaro atmospheric pressure (QATM), the IOP was measured with GAT and DCT. The atmospheric pressure was then increased to 1.1 QATM (equivalent to 1032 m above sea level), 1.2 QATM (equivalent to 315 m above sea level), and 1.25 QATM (equivalent to sea level), starting 5 minutes after reaching each level. The limits of agreement between various measurements with each tonometer were calculated using the Bland-Altman plots.

Results:

The first 4 subjects were used to measure feasibility, consistency, variability, and the time needed for IOP to return to baseline after each atmospheric pressure increase.

For the entire 44 eyes, the mean GAT IOP at 1 QATM was 12.23 mm Hg (range, 8 to 20 mm Hg; SD, 2.84) and mean DCT was 16.36 (range, 12.1 to 25.3; SD, 2.84), with a mean 4.14 mm Hg difference (range, −0.1 to 7.5 mm Hg; SD, 1.62; P<0.001).

Using the second measurements of the first 4 subjects and those after 5 minutes of adaptation for the rest of the group at 1.1 QATM, mean GAT IOP was 11.05±2.68 mm Hg and mean DCT IOP was 15.60±3.02 mm Hg, for a mean difference between instruments of 4.56±1.81 mm Hg (P<0.001).

At 1.2 QATM, mean GAT IOP was 11.14±2.53 mm Hg and mean DCT IOP was 15.39±2.91 mm Hg. The difference between instruments was 4.25±2.12 mm Hg (P<0.001).

At 1.25 QATM, the mean GAT IOP was 12.39±3.11 mm Hg and mean DCT IOP was 14.91±2.73 mm Hg. The difference between instruments after 5 minutes of adaptation was 2.53±1.62 mm Hg (P<0.001).

Generalized estimating equations for performing linear regression multivariable analysis using atmospheric pressure, expressed as altitude, and age as covariates, shows that the difference between GAT and DCT increases by 1 mm Hg per 673 m of increase of altitude above sea level. Age was not a significant predictor.

Conclusions:

Acute changes in atmospheric pressure induce changes in IOP measurements for both GAT and DCT and in different directions. Despite the limitation of sample size, it may be postulated that the difference of IOP measurements between the 2 tonometers increases with lower atmospheric pressures.
Profile of Young South African Children Hospitalized With HIV: Cause for Concern
Authors: du Plooy Elri , Frigati Lisa , Slogrove Amy , Cotton Mark F. , Rabie Helena
Published: July 2020

We describe the history of mother-to-child-prevention, time to HIV diagnosis and antiretroviral therapy of 55 hospitalized HIV-positive children (median age, 5.7 months). Of 31 (56%) mothers who knew their HIV status prior to pregnancy, 11 (35%) did not attend antenatal clinics; those who did attend had poor viral suppression. Despite rapid recognition and access to treatment, 13% of hospitalized HIV-positive infants died. Strategies to reach the mothers driving vertical transmission are imperative.
Study 1: Evaluation of the signs of deficient posterior capsule in posterior polar cataracts using anterior segment optical coherence tomography
Authors: Pujari Amar , Yadav Suresh , Sharma Namrata , Khokhar Sudarshan , Sinha Rajesh , Agarwal Tushar , Titiyal Jeewan S. , Sharma Pradeep
Published: July 2020

Purpose:

To systematically observe and analyze the signs of deficient posterior capsule in posterior polar cataracts.

Design:

Ambispective observational study.

Participants:

Cases with posterior polar cataracts.

Methods:

Eyes with diagnosed posterior polar cataracts were imaged on anterior segment optical coherence tomography (AS-OCT). A detailed assessment was performed to note the morphology of the posterior opacity, posterior capsule, and the common patterns to indicate their abnormality. In addition, generalized observation of the morphology was also performed about intraoperative surgical experiences.

Results:

A total of 101 eyes were included. Mean patient age was 52.85 ± 10.72 years. The posterior capsule integrity was identified as intact in 91 eyes and abnormal/deficient in 10 eyes (9 had intraoperative defective capsule). These deficient/abnormal morphologies were classified into 3 categories: conical (n = 2), moth-eaten (n = 5), and (3) ectatic (n = 3). Similarly, depending on the presence of hypoechoic spaces between the opacity and the capsule, remaining posterior polar cataracts were categorized into 2 generalized morphological types: without hypoechoic areas (n = 40) and with hypoechoic areas (n = 51). In the without hypoechoic areas group, 6 cases developed capsular rent; in the with hypoechoic areas group, 1 case developed capsular rent.

Conclusions:

In posterior polar cataracts, the deficient/abnormal capsular morphology could be specifically categorized into 3 categories, conical, moth-eaten, and ectatic types. In addition, to predict the ease of intraoperative separation between the opacity and the capsule, generalized categorization might help in better case management.
Panorama of mediators in postpancreatitis diabetes mellitus
Authors: Petrov Maxim S.
Published: July 2020

Purpose of review

To provide an overview of mediators involved in the pathogenesis of postacute pancreatitis diabetes mellitus.

Recent findings

The ‘holistic prevention of pancreatitis’ framework has brought to the fore the sequelae of not only end-stage chronic pancreatitis and extensive pancreatic necrosis but also mild acute pancreatitis. Insights from the DORADO project have provided a wealth of information on the signalling molecules that do and do not affect glucose metabolism in individuals after mild acute pancreatitis and have challenged conventional views of the pathogenesis of postpancreatitis diabetes mellitus.

Growing evidence compels a reconsideration of the dogma that mechanical β-cell destruction (and the resulting insulin deficiency) is the only underlying mechanism of postpancreatitis diabetes mellitus. Chronic low-grade inflammation, β-cell compensation, lipolysis, altered secretion of gut hormones, and changes in iron metabolism characterize postacute pancreatitis diabetes mellitus. Some of these are druggable targets that offer novel opportunities to reduce the burden of pancreatitis through tertiary prevention.
Non-HDL or LDL cholesterol in heterozygous familial hypercholesterolaemia: findings of the Simon Broome Register
Authors: Soran Handrean , Cooper Jackie A. , Durrington Paul N. , Capps Nigel , McDowell Ian F.W. , Humphries Steve E. , Neil Andrew
Published: July 2020

Purpose of review

The role of non-HDL-C in the identification and management of lipid disorders is not clearly defined, although UK guidelines recommend its wider use in assessing the need for lipid-lowering therapy and as a treatment target.

Recent findings

We examined the implications of the use of non-HDL-C as opposed to LDL-C in 253 people with hypercholesterolaemia before treatment and 573 after treatment in whom fasting total serum cholesterol, HDL-C and LDL-C had been recorded and the diagnosis of heterozygous familial hypercholesterolemia (heFH) was investigated by genetic testing. The difference and the limits of agreement between non-HDL-C and LDL-C calculated using the Friedewald formula were assessed in those with and without heFH-causing mutations.

There were 147 mutation-positive and 106 mutation-negative pretreatment participants and 395 mutation-positive and 178 mutation-negative patients receiving treatment. The difference between non-HDL-C and LDL-C pretreatment in mutation-positive people (mean LDL-C 7.73 mmol/l) was 0.67 mmol/l (95% CI 0.62–0.73) and posttreatment (mean LDL-C 4.71 mmol/l) was 0.62 mmol/l (95% CI 0.59–0.65) with wide limits of agreement of −0.02 to 1.37 and 0.07–1.18 mmol/l, respectively. Among patients with heterozygous familial hypercholesterolaemia, use of estimated LDL-C derived from non-HDL-C in place of calculated LDL-C may result in diagnostic misclassification and difficulty in assessing the true reduction in LDL-C with treatment, because of the wide inter-individual limits of agreement around the mean difference between non-HDL-C and LDL-C.
Clostridium difficile disease in solid organ transplant recipients: a recommended treatment paradigm
Authors: Wong Darren , Nanda Neha
Published: July 2020

Purpose of review

Organ transplant recipients have an increased incidence ofClostridium difficiledisease and lower clinical response rates compared with the general population. Transplant specific treatment approaches are not defined. Therefore, a review of therapeutics in the transplant population is needed.

Recent findings

A literature review on the current therapies forC. difficilewas performed focusing on the evidence in transplant recipients and immunosuppressed populations.

Transplant patients warrant an aggressive approach to treatment. The authors propose a suggested treatment paradigm for therapy.
The artificial pancreas
Authors: Boughton Charlotte K. , Hovorka Roman
Published: July 2020

Purpose of review

Advances in diabetes technologies have enabled the development of artificial pancreas (closed-loop) systems for people with diabetes. We review the key studies which have led to the adoption of the artificial pancreas in clinical practice and consider ongoing challenges and areas for future enhancements.

Recent findings

Studies have demonstrated safety and efficacy of closed-loop insulin delivery systems in free-living settings over periods of up to 6 months for children and adults with type 1 diabetes. Since 2017, four hybrid closed-loop systems have been approved by regulatory bodies worldwide, but these systems are not entirely automated, requiring user interaction to deliver mealtime insulin boluses. Improving usability of these devices in the real-world setting is an important challenge.

The artificial pancreas has become the gold standard for the treatment of type 1 diabetes. First-generation systems are increasingly being adopted in clinical practice, however further work is required, developing advanced systems and faster acting insulin analogues to allow complete automation and further reduce the burden of type 1 diabetes.
Resilience in Patients With Lung Cancer
Authors: Zhang Jie , Yin Yizhen , Wang Anni , Li Hui , Li Juan , Yang Silan , Wu Yuchen , Zhang Jingping
Published: July 2020

Background

Resilience is important for patients with cancer. However, the relationships among factors affecting the resilience of patients with lung cancer have not been studied sufficiently.

Objective

The aim of this study was to clarify the relationships among social support, resilience, self-efficacy, and symptom distress among patients with lung cancer.

Methods

Through simple random sampling, 303 patients with lung cancer from 4 tertiary hospitals in Changsha, China, were recruited for a cross-sectional descriptive correlational survey. Data were collected using demographic and disease-related information, the Connor-Davidson Resilience Scale, Strategies Used by People to Promote Health, the Perceived Social Support Scale, and the Symptom Distress Scale.

Results

Patients’ mean total resilience score was 50.01 ± 15.25. The fit indices for the model indicated a good fit. Social support had multiple effects on resilience; specifically, it had direct and indirect effects through the mediating role of self-efficacy. Symptom distress had only an indirect effect on resilience through self-efficacy.

Conclusions

Social support, symptom distress, and self-efficacy are key factors associated with resilience in patients with lung cancer. These factors had direct and indirect effects on each other and on resilience.

Implications for Practice

To enhance resilience among patients with lung cancer, interventions that strengthen self-efficacy, provide social support, and reduce symptom distress should be developed.
Pediatric Resuscitation Practices During the Coronavirus Disease 2019 Pandemic
Authors: Morgan Ryan W. , Kienzle Martha , Sen Anita I. , Kilbaugh Todd J. , Dewan Maya , Raymond Tia T. , Himebauch Adam S. , Berg Robert A. , Tegtmeyer Ken , Nadkarni Vinay M. , Topjian Alexis A. , Sutton Robert M. , Wolfe Heather A.
Published: July 2020

Objectives:

While most pediatric coronavirus disease 2019 cases are not life threatening, some children have severe disease requiring emergent resuscitative interventions. Resuscitation events present risks to healthcare provider safety and the potential for compromised patient care. Current resuscitation practices and policies for children with suspected/confirmed coronavirus disease 2019 are unknown.

Design:

Multi-institutional survey regarding inpatient resuscitation practices during the coronavirus disease 2019 pandemic.

Setting:

Internet-based survey.

Subjects:

U.S. PICU representatives (one per institution) involved in resuscitation system planning and oversight.

Interventions:

None.

Measurements and Main Results:

Of 130 institutions surveyed, 78 (60%) responded. Forty-eight centers (62%) had admitted coronavirus disease 2019 patients; 26 (33%) reported code team activation for patients with suspected/confirmed coronavirus disease 2019. Sixty-seven respondents (86%) implemented changes to inpatient emergency response systems. The most common changes were as follows: limited number of personnel entering patient rooms (75; 96%), limited resident involvement (71; 91%), and new or refined team roles (74; 95%). New or adapted technology is being used for coronavirus disease 2019 resuscitations in 58 centers (74%). Most institutions (57; 73%) are using enhanced personal protective equipment for all coronavirus disease 2019 resuscitation events; 18 (23%) have personal protective equipment policies dependent on the performance of aerosol generating procedures. Due to coronavirus disease 2019, most respondents are intubating earlier during cardiopulmonary resuscitation (56; 72%), utilizing video laryngoscopy (67; 86%), pausing chest compressions during laryngoscopy (56; 72%), and leaving patients connected to the ventilator during cardiopulmonary resuscitation (56; 72%). Responses were varied regarding airway personnel, prone cardiopulmonary resuscitation, ventilation strategy during cardiopulmonary resuscitation without an airway in place, and extracorporeal cardiopulmonary resuscitation. Most institutions (46; 59%) do not have policies regarding limitations of resuscitation efforts in coronavirus disease 2019 patients.

Conclusions:

Most U.S. pediatric institutions rapidly adapted their resuscitation systems and practices in response to the coronavirus disease 2019 pandemic. Changes were commonly related to team members and roles, personal protective equipment, and airway and breathing management, reflecting attempts to balance quality resuscitation with healthcare provider safety.
Go Gross or Go Home: The Importance of Gross Examination in Lung Cancer Staging and Diagnosis of Nonneoplastic Diseases
Authors: Huang Tao , Hughes Kenneth T. , Myers Jeffrey L.
Published: July 2020

Gross examination is fundamental to the practice of surgical pathology. Accurate diagnosis can often be made based on the classic gross appearance of a lung lesion. On the other hand, inaccurate diagnosis or wrong tumor staging is unavoidable if lesions are missed, unrecognized, or inadequately sampled. Different grossing techniques should be used for grossing neoplastic and nonneoplastic lung specimens.
Vaginimicrobium propionicum gen. nov., sp. nov., a novel propionic acid bacterium derived from human vaginal discharge
Authors: Diop Khoudia , Cadoret Frederic , Nguyen Thi Tien , Baudoin Jean-Pierre , Armstrong Nicholas , Raoult Didier , Bretelle Florence , Fournier Pierre-Edouard , Fenollar Florence
Published: July 2020

A Gram-stain-positive anaerobic rod-shaped bacterium, designated strain Marseille-P3275T, was isolated using culturomics from the vaginal discharge of healthy French woman. Marseille-P3275T was non-motile and did not form spores. Cells had neither catalase nor oxidase activity. The major fatty acids were C16 : 0 (29 %), C18:1ω9 (18 %), and iso-C15 : 0 (17 %). The genomic DNA G+C content was 50.64 mol%. The phylogenetic analysis based on 16S rRNA gene sequence indicated that Marseille-P3275T was related to members of the family

Propionibacteriaceae

(between 90.32–92.92 % sequence similarity) with formation of a clade with the monospecific genus

Propionimicrobium

(type species

Propionimicrobium lymphophilum

). On the basis of these phylogenetic and phenotypic differences, Marseille-P3275T was classified in a novel genus, Vaginimicrobium, as Vaginimicrobium propionicum gen. nov., sp. nov. The type strain is Marseille-P3275T (=CSUR P3275T=CECT 9677T).
Gimesia benthica sp. nov., a planctomycete isolated from a deep-sea water sample of the Northwest Indian Ocean
Authors: Wang Jian , Ruan Chu-Jin , Song Lei , Li Ang , Zhu Ya-Xin , Zheng Xiao-Wei , Wang Li , Lu Zu-Jun , Huang Ying , Du Wenbin , Zhou Yuguang , Huang Li , Dai Xin
Published: July 2020

A Gram-stain-negative, stalked, oval-shaped and budding bacterial strain, designated E7T, was isolated from a deep-sea water sample collected from the Northwest Indian Ocean. The novel strain was strictly aerobic, and catalase- and oxidase-positive. It grew at 6–40 °C (optimum 30 °C) and pH 5.5–8.0 (optimum pH 7.0–7.5). The strain required 0.5–9.0 % (w/v) NaCl (optimum 3.0–5.0 %) for growth. Aesculin, starch, pectin and Tween 20 were hydrolysed. Based on 16S rRNA gene sequence analysis, strain E7T showed the highest similarity with

Gimesia maris

DSM 8797T (97.5 %). The average nucleotide identity and in silico DNA–DNA hybridization values between strain E7T and

G. maris

DSM 8797T were 78.0 and 19.3 %, respectively. The predominant cellular fatty acids of strain E7T were C16 : 0 and summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c). The major respiratory quinone was menaquinone-6 (MK-6) and the major polar lipids were phosphatidylethanolamine (PE), phosphatidylmonomethylethanolamine (PMME), phosphatidyldimethylethanolamine (PDME), phosphatidylcholine (PC) and diphosphatidylglycerol (DPG). The genomic DNA G+C content of strain E7T was 52.8 mol%. On the basis of phylogenetic inference and phenotypic characteristics, it is proposed that strain E7T represents a novel species of the genus

Gimesia

, for which the name Gimesia benthica sp. nov. is proposed. The type strain is E7T (=CGMCC 1.16119T=KCTC 72737T).
The rough colony morphotype of Mycobacterium avium exhibits high virulence in human macrophages and mice
Authors: Nishimura Tomoyasu , Shimoda Masayuki , Tamizu Eiko , Uno Shunsuke , Uwamino Yoshifumi , Kashimura Shoko , Yano Ikuya , Hasegawa Naoki
Published: July 2020

Introduction.The incidence ofMycobacterium aviumcomplex (MAC) pulmonary disease (MAC PD), a refractory chronic respiratory tract infection, is increasing worldwide. MAC has three predominant colony morphotypes: smooth opaque (SmO), smooth transparent (SmT) and rough (Rg).

Aim.To determine whether colony morphotypes can predict the prognosis of MAC PD, we evaluated the virulence of SmO, SmT and Rg in mice and in human macrophages.

Methodology.We compared the characteristics of mice and human macrophages infected with the SmO, SmT, or Rg morphotypes ofM. aviumsubsp.hominissuis104. C57BL/6 mice and human macrophages derived from peripheral mononuclear cells were used in these experiments.

Results.In comparison to SmO- or SmT-infected mice, Rg-infected mice revealed severe pathologically confirmed pneumonia, increased lung weight and increased lung bacterial burden. Rg-infected macrophages revealed significant cytotoxicity, increased bacterial burden, secretion of proinflammatory cytokines (TNF-α and IL-6) and chemokines (CCL5 and CCL3), and formation of cell clusters. Rg formed larger bacterial aggregates than SmO and SmT. Cytotoxicity, bacterial burden and secretion of IL-6, CCL5 and CCL3 were induced strongly by Rg infection, and were decreased by disaggregation of the bacteria.

Conclusion.M. aviumRg, which is associated with bacterial aggregation, has the highest virulence among the predominant colony morphotypes.
Detection of extended-spectrum beta-lactamase (ESBL) genes and plasmid replicons in Enterobacteriaceae using PlasmidSPAdes assembly of short-read sequence data
Authors: Stohr Joep J.J.M. , Kluytmans-van den Bergh Marjolein F.Q. , Wedema Ronald , Friedrich Alexander W. , Kluytmans Jan A.J.W. , Rossen John W.A.
Published: July 2020

Knowledge of the epidemiology of plasmids is essential for understanding the evolution and spread of antimicrobial resistance. PlasmidSPAdes attempts to reconstruct plasmids using short-read sequence data. Accurate detection of extended-spectrum beta-lactamase (ESBL) genes and plasmid replicon genes is a prerequisite for the use of plasmid assembly tools to investigate the role of plasmids in the spread and evolution of ESBL production in

Enterobacteriaceae

. This study evaluated the performance of PlasmidSPAdes plasmid assembly for

Enterobacteriaceae

in terms of detection of ESBL-encoding genes, plasmid replicons and chromosomal wgMLST genes, and assessed the effect of k-mer size. Short-read sequence data for 59 ESBL-producing

Enterobacteriaceae

were assembled with PlasmidSPAdes using different k-mer sizes (21, 33, 55, 77, 99 and 127). For every k-mer size, the presence of ESBL genes, plasmid replicons and a selection of chromosomal wgMLST genes in the plasmid assembly was determined. Out of 241 plasmid replicons and 66 ESBL genes detected by whole-genome assembly, 213 plasmid replicons [88 %; 95 % confidence interval (CI): 83.9–91.9] and 43 ESBL genes (65 %; 95 % CI: 53.1–75.6) were detected in the plasmid assemblies obtained by PlasmidSPAdes. For most ESBL genes (83.3 %) and plasmid replicons (72.0 %), detection results did not differ between the k-mer sizes used in the plasmid assembly. No optimal k-mer size could be defined for the number of ESBL genes and plasmid replicons detected. For most isolates, the number of chromosomal wgMLST genes detected in the plasmid assemblies decreased with increasing k-mer size. Based on our findings, PlasmidSPAdes is not a suitable plasmid assembly tool for short-read sequence data for ESBL-encoding plasmids of

Enterobacteriaceae

.
Genomic characterization of Salmonella Uzaramo for human invasive infection
Authors: Xu Xuebin , Chen Yan , Pan Hang , Pang Zaiyuan , Li Fang , Peng Xianqi , Ed-dra Abdelaziz , Li Yan , Yue Min
Published: July 2020

Salmonella

is composed of a wide variety of serovars, causing human self-limited gastrointestinal illnesses or invasive infections. Invasive non-typhoidal

Salmonella

(iNTS) is well documented, with high mortality for children and immunocompromised adults in sub-Saharan Africa and has recently been reported in Southeast Asia. However, iNTS in China remains unknown. In May 2019, a case of invasive infection caused by

Salmonella enterica

serovar Uzaramo (S. Uzaramo) was reported for the first time in China. Phylogenomic analysis was performed by genomic sequencing the available contextualized isolates, which separated the two Chinese strains into different sublineages. Both phenotypic and genomic characterization demonstrated that the S. Uzaramo isolates showed in general low antimicrobial resistance potential, except one isolated from lake-water in China. Additional comparative genomic analysis and Caenorhabditis elegans killing assays suggested a unique combination of virulence factors, including typhoid toxin and tcf fimbrial adhesin, which might play a role in the invasive infection. This study highlights that the transparency of global surveillance genomic data could accelerate understanding of virulence and antimicrobial resistance makeup of a previously unknown threat.
Phenotypic and genetic associations between anhedonia and brain structure in UK Biobank
Authors: Zhu Xingxing , Ward Joey , Cullen Breda , Lyall Donald M. , Strawbridge Rona J. , Smith Daniel J. , Lyall Laura M.
Published: July 2020

Background

Anhedonia is a core symptom of multiple psychiatric disorders and has been associated with changes in brain structure. Genome-wide association studies suggest that anhedonia is heritable with a polygenic architecture but few studies have explored the association between genetic loading for anhedonia - indexed by polygenic risk scores for anhedonia (PRS-anhedonia) - and structural brain imaging phenotypes. We investigated how anhedonia and polygenic risk for anhedonia were associated with brain structure within the UK Biobank cohort.

Methods

Brain measures (including total grey/white matter volumes, subcortical volumes, cortical thickness and white matter integrity) were analysed in relation to the self-reported anhedonia phenotype and PRS-anhedonia for 17,492 participants (8,506 males and 8,986 females; mean age = 62.81 years, SD = 7.43), using linear mixed models and including mediation analyses.

Results

State anhedonia was significantly associated with smaller total grey matter volume (GMV), smaller volumes in thalamus and nucleus accumbens; as well as reduced cortical thickness within the paracentral gyrus, the opercular part of inferior frontal gyrus and the rostral anterior cingulate cortex. PRS-anhedonia was associated with reduced total GMV, increased total white matter volume and reduced white matter integrity; in addition to reduced cortical thickness within the parahippocampal cortex, the superior temporal gyrus and the insula cortex.

Conclusions

Both the state anhedonia phenotype and PRS-anhedonia were associated with differences in multiple brain structures/areas, including within reward-related circuits. These differences may represent vulnerability markers for psychopathology across a range of psychiatric disorders.
The ammonia oxidizing bacteriumNitrosomonas eutrophaD23 blocks T helper 2 cell polarization via IL-10 – mediated interference with dendritic cell activation
Authors: Maura Damien , Elmekki Nazik , Goddard Alex
Published: July 2020

The prevalence of atopic diseases has been steadily increasing since the mid 20thcentury, a rise that has been linked to modern hygienic lifestyles that limit exposure to microbes and immune system maturation. Overactive type 2 CD4+ helper T (Th2) cells are known to be closely associated with atopy and represent a key target for treatment. In this study, we report that the ammonia oxidizing bacteria (AOB)Nitrosomonas eutrophaD23, an environmental microbe that is not associated with human pathology, effectively suppresses the polarization of Th2 cells and production of Th2-associated cytokines (IL-5, IL-13, & IL-4) by human peripheral blood mononuclear cells (PBMC). We show that AOB inhibit Th2 cell polarization not through Th1-mediated suppression, but rather through an IL-10-mediated mechanism that interferes with the activation of dendritic cells, as evidenced by a reduction in Major Histocompatibility Complex Class II (MHC II) and CD86 expression following AOB treatment. This is the first report of immunomodulatory properties of AOB and supports the development of AOB as a potential therapeutic for atopic diseases.

GRAPHICAL ABSTRACT

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More than meets the eye: syntopic and morphologically similar mangrove killifish species show different mating systems and patterns of genetic structure along the Brazilian coast
Authors: Berbel-Filho Waldir M. , Tatarenkov Andrey , Espirito-Santo Helder M. V. , Lira Mateus G. , de Leaniz Carlos Garcia , Lima Sergio M. Q. , Consuegra Sofia
Published: July 2020

Different mating systems can strongly affect the extent of genetic diversity and population structure among species. Given the increased effects of genetic drift on reduced population size, theory predicts that species undergoing self-fertilization should have greater population structure than outcrossed species, however demographic dynamics may affect this scenario. The mangrove killifish clade is composed of the two only known examples of self-fertilising species among vertebrates(Kryptolebias marmoratusandK. hermaphroditus). A third species in this clade,K. ocellatus,inhabits mangrove forests in southeast Brazil, however its mating system and patterns of genetic structure have been rarely explored. Here, we examined the genetic structure and phylogeographic patterns ofK. ocellatusalong its distribution, using mitochondrial DNA and microsatellites to compare its patterns of genetic structure with the predominantly selfing and often syntopic,K. hermaphroditus. Our results indicate thatK. ocellatusreproduces mainly by outcrossing across much of its known range, with no current evidence of selfing, despite being an androdioecious species. Our results also reveal a stronger population subdivision inK. ocellatuscompared toK. hermaphroditus, contrary to the theoretical predictions based on reproductive biology of the two species Our findings indicate that, although morphologically similar,K. ocellatusandK. hermaphroditushad remarkably different evolutionary histories when colonising the same mangrove areas in south-eastern Brazil, with other factors (e. g. time of colonisation, dispersal/establishment capacity) having more profound effects on the current population structuring of those species than differences in mating systems.
RNA degradation sculpts the maternal transcriptome duringDrosophilaoogenesis
Authors: Blatt Patrick , Wong-Deyrup Siu Wah , McCarthy Alicia , Breznak Shane , Hurton Matthew D. , Upadhyay Maitreyi , Bennink Benjamin , Camacho Justin , Lee Miler T. , Rangan Prashanth
Published: July 2020

In sexually reproducing animals, the oocyte contributes a large supply of RNAs that are essential to launch development upon fertilization. The mechanisms that regulate the composition of the maternal RNA contribution during oogenesis are unclear. Here, we show that a subset of RNAs expressed during the early stages of oogenesis is subjected to regulated degradation during oocyte specification. Failure to remove these RNAs results in oocyte dysfunction and death. We identify the RNA-degrading Super Killer complex and No-Go Decay factor Pelota as key regulators of oogenesis via targeted clearance of RNAs expressed in germline stem cells. These regulators target RNAs enriched for cytidine sequences bound by the protein Half pint. Thus, RNA degradation helps orchestrate a germ cell-to-maternal transition by sculpting the maternal RNA contribution to the zygote.
Genomic and TCR Repertoire Intratumor Heterogeneity of Small-cell Lung Cancer and its Impact on Survival
Authors: Chen Ming , Chen Runzhe , Jin Ying , Li Jun , Zhang Jiexin , Fujimoto Junya , Lee Won-Chul , Hu Xin , Hubert Shawna Maria , George Julie , Hu Xiao , Chen Yamei , Behrens Carmen , Chow Chi-Wan , Pham Hoa H.N. , Fukuoka Junya , Parra Edwin Roger , Gay Carl M. , Little Latasha D. , Gumbs Curtis , Song Xingzhi , Diao Lixia , Wang Qi , Cardnell Robert , Zhang Jianhua , Wang Jing , Gibbons Don L. , Heymach John V. , Lee J. Jack , William William N. , Glisson Bonnie , Wistuba Ignacio , Futreal P. Andrew , Thomas Roman K. , Reuben Alexandre , Byers Lauren A. , Zhang Jianjun
Published: July 2020

Small-cell lung cancer (SCLC) is speculated to harbor complex genomic intratumor heterogeneity (ITH) associated with high recurrence rate and suboptimal response to immunotherapy. Here, we revealed a rather homogeneous mutational landscape but extremely suppressed and heterogeneous T cell receptor (TCR) repertoire in SCLCs. Higher mutational burden, lower chromosomal copy number aberration (CNA) burden, less CNA ITH and less TCR ITH were associated with longer overall survival of SCLC patients. Compared to non-small cell lung cancers (NSCLCs), SCLCs had similar predicted neoantigen burden and mutational ITH, but significantly more suppressed and heterogeneous TCR repertoire that may be associated with higher CNA burden and CNA ITH in SCLC. Novel therapeutic strategies targeting CNA could potentially improve the tumor immune microenvironment and response to immunotherapy in SCLC.
100+ years of bird survey data reveal changes in functional fingerprints indexing ecosystem health of a tropical montane forest through time
Authors: Gómez Camila , Tenorio Elkin A. , Cadena Carlos Daniel
Published: July 2020

Ecologically relevant traits of organisms inhabiting an ecosystem determine its functional fingerprint. Quantifying changes in the shape, volume and shifts in the position of functional fingerprints can provide information about the effects of diversity loss or gain through time, and is a promising means to monitor ecological integrity. This, however, is seldom possible owing to limitations in historical surveys and lack of data on organismal traits, particularly in diverse tropical regions. Using detailed bird surveys from four time periods across more than one century and morphological traits of 233 species, we quantified changes in the avian functional fingerprint of a tropical montane forest site in the Andes of Colombia. We found that 79% of the variation in functional space, regardless of time period, was described by three major axes summarizing body size, dispersal ability, and habitat breadth. Changes in species composition caused significant alterations of the functional fingerprint of the assemblage, with 35 – 60% reductions in functional richness and dispersion. Owing to species extirpations and to novel additions to the assemblage, functional space is currently smaller and at least 11% different to what it was a century ago, with fewer large-sized species, more good dispersers, and fewer habitat specialists. Extirpated species had high values of functional uniqueness and distinctiveness, resulting in large reductions of functional richness and dispersion after their loss, implying potentially important consequences for ecosystem functioning. Conservation efforts aimed at maintaining ecosystem function must move beyond maintaining species numbers to designing strategies for the maintenance of ecological function by identifying and conserving species with traits conferring high vulnerability.
Phenotypic variation in two widespread Caribbean corals —Porites astreoidesandP. divaricata— between mangrove and lagoon habitats
Authors: Lord Karina Scavo , Barcala Anna , Aichelman Hannah E. , Kriefall Nicola G. , Brown Chloe , Knasin Lauren , Secor Riley , Tone Cailey , Tsang Laura , Finnerty John R.
Published: July 2020

As coral reefs experience dramatic declines in coral cover throughout the tropics, there is an urgent need to understand the role that non-reef habitats such as mangroves play in the ecological niche of corals. Mangrove habitats present a challenge to reef-dwelling corals as they can differ dramatically from adjacent reef habitats with respect to key environmental parameters such as temperature and light. As variation in temperature and light within reef habitats is known to drive intraspecific differences in coral phenotype, we hypothesized that coral species which can exploit both reef and mangrove habitats will exhibit predictable differences in phenotype between habitats. To investigate how intraspecific variation, driven by either local adaptation or phenotypic plasticity, might enable particular coral species to exploit these two qualitatively different habitat types, we compared the phenotypes of two widespread Caribbean corals —Porites divaricataandP. astreoides—in mangrove versus lagoon habitats on Turneffe Atoll, Belize. We document significant differences in colony size, color, structural complexity, and corallite morphology between habitats. In every instance, the difference between mangrove and lagoon corals was consistent inP. divaricataandP. astreoides. This study is the first to document intraspecific phenotypic diversity in corals occupying mangrove versus patch-reef habitats, and it provides a foundation for understanding why some “reef coral” species can exploit mangroves, while others cannot.
Biofabrication of muscle fibers enhanced with plant viral nanoparticles using surface chaotic flows
Authors: Frías-Sánchez Ada I. , Quevedo-Moreno Diego A. , Samandari Mohamadmahdi , Tavares-Negrete Jorge A. , Sánchez-Rodríguez Víctor Hugo , González-Gamboa Ivonne , Ponz Fernando , Alvarez Mario M. , Trujillo-de Santiago Grissel
Published: July 2020

Multiple human tissues exhibit fibrous nature. Therefore, the fabrication of hydrogel filaments for tissue engineering is a trending topic. Current tissue models are made of materials that often require further enhancement for appropriate cell attachment, proliferation and differentiation. Here we present a simple strategy, based on the use surface chaotic flows amenable of mathematical modeling, to fabricate continuous, long and thin filaments of gelatin methacryloyl (GelMA).

The fabrication of these filaments is achieved by chaotic advection in a finely controlled and miniaturized version of the journal bearing (JB) system. A drop of GelMA pregel was injected on a higher-density viscous fluid (glycerin) and a chaotic flow is applied through an iterative process. The hydrogel drop is exponentially deformed and elongated to generate a fiber, which was then polymerized under UV-light exposure. Computational fluid dynamic (CFD) simulations are conducted to determine the characteristics of the flow and design the experimental conditions for fabrication of the fibers. GelMA fibers were effectively used as scaffolds for C2C12 myoblast cells. Experimental results demonstrate an accurate accordance with CFD simulations for the predicted length of the fibers.

Plant-based viral nanoparticles (i.e.,Turnip mosaic virus; TuMV) were then integrated to the hydrogel fibers as a secondary nano-scaffold for cells for enhanced muscle tissue engineering. The addition of TuMV significantly increased the metabolic activity of the cell-seeded fibers (p*<0.05), strengthened cell attachment throughout the first 28 days, improved cell alignment, and promoted the generation of structures that resemble natural mammal muscle tissues.

Chaotic 2D-printing is proven to be a viable method for the fabrication of hydrogel fibers. The combined use of thin and long GelMA hydrogel fibers enhanced with flexuous virions offers a promising alternative for scaffolding of muscle cells and show potential to be used as cost-effective models for muscle tissue engineering purposes.
Comprehensive exploration of the genetic contribution of the dopaminergic and serotonergic pathways to psychiatric disorders
Authors: Cabana-Domínguez Judit , Torrico Bàrbara , Reif Andreas , Fernàndez-Castillo Noèlia , Cormand Bru
Published: July 2020

Psychiatric disorders are highly prevalent and display considerable clinical and genetic overlap. Dopaminergic and serotonergic neurotransmission have been shown to have an important role in many psychiatric disorders. Here we aim to assess the genetic contribution of these systems to eight psychiatric disorders (ADHD, ANO, ASD, BIP, MD, OCD, SCZ and TS) using publicly available GWAS analyses performed by the Psychiatric Genomics Consortium. To do so, we elaborated four different gene sets using the Gene Ontology and KEGG pathways tools: two ‘wide’ selections for dopamine (DA) and for serotonin (SERT), and two ‘core’ selections for the same systems. At the gene level, we found 67 genes from the DA and/or SERT gene sets significantly associated with one of the studied disorders, and 12 of them were associated with two different disorders. Gene-set analysis revealed significant associations for ADHD and ASD with the wide DA gene set, for BIP with the wide SERT gene set, and for MD with both the core DA set and the core SERT set. Interestingly, interrogation of the cross-disorder GWAS meta-analysis displayed association with the wide DA gene set. To our knowledge, this is the first time that these two neurotransmitter systems have systematically been inspected in these disorders. Our results support a cross-disorder contribution of dopaminergic and serotonergic systems in several psychiatric conditions.
Public attention and policy responses to COVID-19 pandemic⋆
Authors: Aksoy Cevat Giray , Ganslmeier Michael , Poutvaara Panu
Published: July 2020

Early non-pharmaceutical interventions (NPI) significantly reduced the death toll of the COVID-19 pandemic. Yet, there are vast differences in how quickly governments implemented NPIs. In this paper, we analyze the role of public attention, measured as the share of daily Google searches in a country related to COVID-19, in the timing of the NPI responses. We first show that public attention depends strongly on whether there are cases in own country. We then show that countries with high levels of public attention are more likely to implement non-pharmaceutical interventions, even after controlling for the number of cases and deaths. Finally, we show that the extent to which a government responds to public attention is highly dependent on the country’s institutional quality. The positive effect of public attention on policy implementation is driven entirely by countries with good institutions.
Oncogenic H-Ras Signaling Differentially Targets Replicative and Specialized DNA Polymerases for Depletion
Authors: Tsao Wei-chung , Buj Raquel , Aird Katherine M. , Sidorova Julia M. , Eckert Kristin A.
Published: July 2020

Oncogene activation significantly alters DNA replication dynamics, causing replication stress and genome instability. However, little is known about DNA polymerase expression and regulation during oncogene-induced replication stress. We discovered that the Pol α catalytic subunit, Pol δ, Pol η and Pol κ are all depleted in response to H-RasG12Voverexpression in multiple human cell lines. Distinct transcriptional and post-translational mechanisms mediate replicative and specialized DNA polymerase regulation, respectively, and include both MEK-dependent and -independent pathways. Moreover, Pol η depletion is sufficient to induce a senescence-like growth arrest in non-transformed cells. We provide evidence that H-RasG12V-induced polymerase depletion contributes not only to oncogene-induced replication stress, but also to cell cycle checkpoint enforcement. Polymerase degradation is a protective response, associated with improved cell survival in the face of oncogene-induced stress. Our findings significantly impact our understanding of oncogene-induced cellular transformation and suggest that imbalanced polymerase levels may contribute to neoplastic progression.
Design and Development of Point of Care Test and Optical Reader for Early Screening of Kidney Related Disorder
Authors: Shihvare Pankaj , Mohla Satyam , Dube Tejal , Verma Alok , Srivastava Rohit
Published: July 2020

Low-cost, paper-based colorimetric assays for early screening of albumin, creatinine and their ratio have been developed. The developed methods are noninvasive and require only 10µl of the urine sample. A reflectance-based optical reader has also been developed for the quantification of the albumin and creatinine. The developed method is based on spot urine testing which is advantageous when compared to the conventional 24-hour urine collection. The detection range of albumin and creatinine assays is 10-150 mg/dl and 25–400 mg/dl, respectively. The developed assays and optical reader were tested with the chronic kidney diseased patient’s samples at KEM Hospital, Mumbai.
A three dimensional human immune-tumor cell model reveals the importance of isotypes in antibody-based immunotherapy
Authors: Lara Sandra , Anania Jessica C. , Virtanen Alexander , Stenhammar Viktoria , Kleinau Sandra
Published: July 2020

Monoclonal antibodies (mAb) have revolutionized clinical medicine, especially in the field of cancer immunotherapy. The challenge now is to improve the response rates in the patients, as immunotherapy still fails for many patients. Strategies to enhance tumor cell death is a fundamental aim, but relevant model systems for human tumor immunology are lacking. Herein, we have developed a novel pre-clinical human immune – three-dimensional (3D) tumor model (spheroids) to map the efficiency of tumor-specific isotypes for improved tumor cell killing. Different anti-CD20 Rituximab (RTX) isotypes alone or in combination, were evaluated for mediating complement-dependent cytotoxicity and antibody-dependent phagocytosis by human monocytic cells in 3D spheroids, in parallel with monolayer culture, of human CD20+B-cell lymphoma. We show that the IgG3 variant of RTX has the greatest tumoricidal effect over other isotypes, mediating strong infiltration of monocytic effector cells into 3D spheroids. Hence, the human immune-3D tumor model is an attractiveex vivosystem to help filter out mAbs for best efficacy in cancer immunotherapy.
USP19 modulates cancer cell migration and invasion and acts as a novel prognostic marker in patients with early breast cancer
Authors: Rossi Fabiana A , Steinberg Juliana H Enriqué , Roitberg Ezequiel H Calvo , Joshi Molishree , Pandey Ahwan , Abba Martin C , Dufrusine Beatrice , Buglioni Simonetta , De Laurenzi Vincenzo , Sala Gianluca , Lattanzio Rossano , Espinosa Joaquín M , Rossi Mario
Published: July 2020

Tumor cell dissemination in cancer patients is associated with a significant reduction in their survival and quality of life. The ubiquitination pathway plays a fundamental role in the maintenance of protein homeostasis both in normal and stressed conditions and its dysregulation has been associated with malignant transformation and invasive potential of tumor cells, thus highlighting its value as a potential therapeutic target. In order to identify novel molecular targets of tumor cell migration and invasion we performed a genetic screen with an shRNA library against ubiquitination pathway-related genes. To this end, we set up a protocol to specifically enrich positive migration regulator candidates. We identified the deubiquitinase USP19 and demonstrated that its silencing reduces the migratory and invasive potential of highly invasive breast cancer cell lines. We extended our investigationin vivoand confirmed that mice injected with USP19 depleted cells display increased tumor-free survival, as well as a delay in the onset of the tumor formation and a significant reduction in the appearance of metastatic foci, indicating that tumor cell invasion and dissemination is impaired. In contrast, overexpression of USP19 increased cell invasiveness bothin vitroandin vivo, further validating our findings. More importantly, we demonstrated that USP19 catalytic activity is important for the control of tumor cell migration and invasion, and that its molecular mechanism of action involves LRP6, a Wnt co-receptor. Finally, we showed that USP19 overexpression is a surrogate prognostic marker of distant relapse in patients with early breast cancer. Altogether, these findings demonstrate that USP19 might represent a novel therapeutic target in breast cancer.