bluuebunny/crossref_metadata_2025 huggingface dataset:
Dilated cardiomyopathy and arrhythmogenic left ventricular cardiomyopathy: a comprehensive genotype-imaging phenotype study
Authors: Augusto João B , Eiros Rocio , Nakou Eleni , Moura-Ferreira Sara , Treibel Thomas A , Captur Gabriella , Akhtar Mohammed M , Protonotarios Alexandros , Gossios Thomas D , Savvatis Konstantinos , Syrris Petros , Mohiddin Saidi , Moon James C , Elliott Perry M , Lopes Luis R
Published: June 2019

Aims 

Myocardial scar detected by cardiovascular magnetic resonance has been associated with sudden cardiac death in dilated cardiomyopathy (DCM). Certain genetic causes of DCM may cause a malignant arrhythmogenic phenotype. The concepts of arrhythmogenic left ventricular (LV) cardiomyopathy (ALVC) and arrhythmogenic DCM are currently ill-defined. We hypothesized that a distinctive imaging phenotype defines ALVC.

Methods and results 

Eighty-nine patients with DCM-associated mutations [desmoplakin (DSP) n = 25, filamin C (FLNC) n = 7, titin n = 30, lamin A/C n = 12, bcl2-associated athanogene 3 n = 3, RNA binding motif protein 20 n = 3, cardiac sodium channel NAv1.5 n = 2, and sarcomeric genes n = 7] were comprehensively phenotyped. Clustering analysis resulted in two groups: ‘DSP/FLNC genotypes’ and ‘non-DSP/FLNC’. There were no significant differences in age, sex, symptoms, baseline electrocardiography, arrhythmia burden, or ventricular volumes between the two groups. Subepicardial LV late gadolinium enhancement with ring-like pattern (at least three contiguous segments in the same short-axis slice) was observed in 78.1% of DSP/FLNC genotypes but was absent in the other DCM genotypes (P < 0.001). Left ventricular ejection fraction (LVEF) and global longitudinal strain were lower in other DCM genotypes (P = 0.053 and P = 0.015, respectively), but LV regional wall motion abnormalities were more common in DSP/FLNC genotypes (P < 0.001). DSP/FLNC patients with non-sustained ventricular tachycardia (NSVT) had more LV scar (P = 0.010), whereas other DCM genotypes patients with NSVT had lower LVEF (P = 0.001) than patients without NSVT.

Conclusion

DSP/FLNC genotypes cause more regionality in LV impairment. The most defining characteristic is a subepicardial ring-like scar pattern in DSP/FLNC, which should be considered in future diagnostic criteria for ALVC.
Disseminated melioidosis with native valve endocarditis: a case report
Authors: Subramony Hariharan , Gunasekaran Sengottuvelu , Paul Pandi Vinodh Kumar
Published: June 2019

Background 

Burkholderia pseudomallei is a Gram negative, soil-water saprophytic bacterium endemic in South-East Asia and Northern Australia. Melioidosis is being increasingly diagnosed in other regions like India, China, and Sri Lanka during recent years. The clinical presentation of melioidosis is extremely variable.

Case summary 

We present a case of melioidosis presenting as native valve infective endocarditis with concomitant hepatic and splenic abscesses. This is the second case of melioidosis with infective endocarditis reported from India.

Discussion 

Melioidosis can present with pneumonia, pleural effusion, subcutaneous abscesses, visceral abscesses, osteomyelitis, and septicaemia, but cardiac involvement is rare. Endocarditis due to melioidosis is rare (∼1%) and is rarely reported in literature. This case highlights the unusual presentation of this emerging disease.
Comparison of effects of cervical headgear treatment on skeletal facial changes when the treatment time is altered: a randomized controlled trial
Authors: Julku Johanna , Pirilä-Parkkinen Kirsi , Tolvanen Mimmi , Pirttiniemi Pertti
Published: June 2019

Background

There is a lack of evidence based on longitudinal information in the field of Class II malocclusion management with cervical headgear (CH), especially in a randomized setting.

Objectives

The main objective of this study was to evaluate skeletal facial changes, particularly in vertical dimensions, after Kloehn-type CH treatment in children when the timing of treatment is altered.

Trial design

Prospective, parallel-group, randomized controlled trial.

Methods

Screened children with Class II malocclusion were randomized in 1:1 ratio to two groups of equal size by sealed-envelope randomization: the early group (EG), where active CH treatment was started at the age of 7.8 years, and the late group (LG), where CH treatment was started at the age of 9.5 years. The active treatment was continued until normal Class I occlusion on first molars was achieved. Cephalograms were taken at three different time points. Changes in cephalometric measurements were compared between groups and genders. Blinding was applicable for outcome evaluation.

Results

Of 67 randomized children, 56 completed the study. Upper face height increased during the CH treatment phase, as the parameter N–ANS increased significantly during the active treatments of EG (P < 0.05) and LG (P < 0.05). Also, the parameter NSL–PL increased significantly during the treatment of EG (P < 0.01) and during the treatment of LG (P < 0.01). The Gonial angle decreased significantly in the early CH treatment group compared to the later treatment group (T0–T2: P < 0.01). CH improved the antero-posterior jaw relationship. No harms were encountered.

Conclusions

Although the upper face height increased, the mandible showed anterior rotation after CH treatment. The Gonial angle was significantly decreased in the EG compared to the LG. There were gender-specific differences in both sagittal and vertical dimensions when examining interrelations in dimensional changes. The differences found between the early and later treatment groups were not clinically important when the cephalometric results are considered.

Clinical registration

ClinicalTrials.gov (NCT02010346).
Cognitive and Functional Status of Persons Newly Enrolled at Dementia-Specific Adult Day Centers and Burden of Their Caregivers
Authors: Chiriboga David A , Park Nan S , Gilbert Karen , Molinari Victor A , Barnes Mary
Published: June 2019

Background and Objectives

Recognizing the important role that dementia-specific adult day centers have in maintaining persons with a neurocognitive disorder in their home, this article examines three critical indicators at the time when people first enroll in such a center: cognitive and functional impairment of the enrollee, and burden reported by their family caregivers. We also considered variations in these 3 indicators by race/ethnicity and by the relationship of caregiver to the new enrollee.

Research Design and Methods

We conducted a secondary analysis of data collected by a nonprofit organization operating 11 dementia-specific adult day centers located on the east coast of Florida. Nursing staff conducted intake interviews with enrollees and their caregivers, and assessed functional status within one month of admission. Instruments included the Zarit Burden Scale and components of the Minimum Data Set: the Brief Interview for Mental Status (BIMS) and 4 measures of functional status.

Results

On average the cognitive scores of newly enrollees were well-within the range indicated for severe impairment, and these levels did not differ by race/ethnicity. Burden reported by caregivers however differed significantly, with Latinx caregivers reporting the greatest burden and African American/Black caregivers reporting the least. Further, while daughters generally reported higher levels of burden than other family caregivers, Black daughters reported the least.

Discussion and Implications

Results suggest a need for greater dissemination efforts about adult day programs to the Latinx community, as well as attention to the disparate burden placed upon differing family relationships of caregivers to enrollees.
A continuum model of multi-phase reactive transport in igneous systems
Authors: Keller Tobias , Suckale Jenny
Published: June 2019

Multiphase reactive transport processes are ubiquitous in igneous systems. A challenging aspect of modelling igneous phenomena is that they range from solid-dominated porous to liquid-dominated suspension flows and therefore entail a wide spectrum of rheological conditions, flow speeds and length scales. Most previous models have been restricted to the two-phase limits of porous melt transport in deforming, partially molten rock and crystal settling in convecting magma bodies. The goal of this paper is to develop a framework that can capture igneous system from source to surface at all phase proportions including not only rock and melt but also an exsolved volatile phase. Here, we derive an n-phase reactive transport model building on the concepts of Mixture Theory, along with principles of Rational Thermodynamics and procedures of Non-equilibrium Thermodynamics. Our model operates at the macroscopic system scale and requires constitutive relations for fluxes within and transfers between phases, which are the processes that together give rise to reactive transport phenomena. We introduce a phase- and process-wise symmetrical formulation for fluxes and transfers of entropy, mass, momentum and volume, and propose phenomenological coefficient closures that determine how fluxes and transfers respond to mechanical and thermodynamic forces. Finally, we demonstrate that the known limits of two-phase porous and suspension flow emerge as special cases of our general model and discuss some ramifications for modelling pertinent two- and three-phase flow problems in igneous systems.
A combinatorial approach to determine earthquake magnitude distributions on a variable slip-rate fault
Authors: Geist Eric L , Parsons Tom
Published: June 2019

Combinatorial methods are used to determine the spatial distribution of earthquake magnitudes on a fault whose slip rate varies along strike. Input to the problem is a finite sample of earthquake magnitudes that span 5 kyr drawn from a truncated Pareto distribution. The primary constraints to the problem are maximum and minimum values around the target slip-rate function indicating where feasible solutions can occur. Two methods are used to determine the spatial distribution of earthquakes: integer programming and the greedy-sequential algorithm. For the integer-programming method, the binary decision vector includes all possible locations along the fault where each earthquake can occur. Once a set of solutions that satisfy the constraints is found, the cumulative slip misfit on the fault is globally minimized relative to the target slip-rate function. The greedy algorithm sequentially places earthquakes to locally optimize slip accumulation. As a case study, we calculate how earthquakes are distributed along the megathrust of the Nankai subduction zone, in which the slip rate varies significantly along strike. For both methods, the spatial distribution of magnitudes depends on slip rate, except for the largest magnitude earthquakes that span multiple sections of the fault. The greedy-sequential algorithm, previously applied to this fault (Parsons et al., 2012), tends to produce smoother spatial distributions and fewer lower magnitude earthquakes in the low slip-rate section of the fault compared to the integer-programming method. Differences in results from the two methods relate to how much emphasis is placed on minimizing the misfit to the target slip rate (integer programming) compared to finding a solution within the slip-rate constraints (greedy sequential). Specifics of the spatial distribution of magnitudes also depend on the shape of the target slip-rate function: that is, stepped at the section boundaries versus a smooth function. This study isolates the effects of slip-rate variation along a single fault in determining the spatial distribution of earthquake magnitudes, helping to better interpret results from more complex, interconnected fault systems.
Variables affecting first-year student commitment during the transition to college in Ireland
Authors: Daniels Natasha , Sheahan Jerome , MacNeela Pádraig
Published: June 2019

Third-level student attrition rates internationally are a cause for concern. Thus, student retention and academic success are top priorities for colleges, and students alike. In addition to this, student well-being is a growing public health concern. This study explores the need to incorporate well-being as a predictor in traditionally academically focused models of student persistence during the transition to college. A cross-sectional web-based survey was conducted with 574 first-year students aged 17–22 years attending a university in Ireland to examine the effect of student persistence and well-being variables on student commitment during the transition to college. This study highlights the connection between student academic, social and well-being variables during the transition to college within the fitted models that emerged from the data. Student well-being plays a key role ensuring student persistence during the transition to college. The results support our hypothesis that many student variables have the potential to substantially impact student commitment during the first-year transition to college. These variables include student depression, self-rated health, academic environment, peer connections and perceiving the academic programme to be an appropriate personal choice. It is therefore important for education institutions to acknowledge and address student persistence and student well-being in an integrative way and for traditionally academically focused student retention models to orientate to incorporate student well-being.
Whole-exome sequencing identifies a GREB1L variant in a three-generation family with Müllerian and renal agenesis: a novel candidate gene in Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome. A case report
Authors: Herlin Morten K , Le Vang Q , Højland Allan T , Ernst Anja , Okkels Henrik , Petersen Astrid C , Petersen Michael B , Pedersen Inge S
Published: June 2019

The aetiology of Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome, characterized by uterovaginal agenesis in 46,XX women, remains poorly understood. Since familial occurrences are rare, genetic findings reported so far only apply to a minority of mainly sporadic cases and most studies have not included other family members enabling segregation analysis. Herein, we report on the investigation of a unique three-generation family of two female cousins with MRKH syndrome and unilateral renal agenesis (RA) and two deceased male relatives with RA. We performed whole-exome sequencing (WES) in eight family members leading to the identification of a novel pathogenic (CADD = 33) c.705G>T missense variant in GREB1L, a gene recently identified as a novel cause of RA. Previous reports include several cases of female fetuses with bilateral RA and uterus agenesis, which support GREB1L as an important gene in both kidney and female genital tract development. The pedigree is compatible with autosomal dominant inheritance with incomplete penetrance following a parent-origin-specific manner, which could be due to imprinting. To our knowledge, this is the first investigation of a larger MRKH syndrome pedigree using WES, and we suggest GREB1L as a novel and promising candidate gene in the aetiology of MRKH syndrome.
A Theorem of Levinson for Riemannian Symmetric Spaces of Noncompact Type
Authors: Bhowmik Mithun , Ray Swagato K
Published: June 2019

A classical result of N. Levinson characterizes the existence of a nonzero integrable function vanishing on a nonempty open subset of the real line in terms of the pointwise decay of its Fourier transform. We prove an analogue of this result for Riemannian symmetric spaces of noncompact type.
Associations of Cervicovaginal Lactobacilli With High-Risk Human Papillomavirus Infection, Cervical Intraepithelial Neoplasia, and Cancer: A Systematic Review and Meta-Analysis
Authors: Wang Huiyan , Ma Yan , Li Ruonan , Chen Xixi , Wan Lijuan , Zhao Weidong
Published: June 2019

Background

Vaginal dysbiosis characterized by depleted lactobacilli is usually correlated with human papillomavirus (HPV) infection and cervical carcinogenesis, but the effect of the Lactobacillus genus and represented species on this process remains unclear.

Methods

PubMed, EMBASE, and CENTRAL databases were searched up to February 15, 2019. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a fixed-effect model and Review Manager (version 5.3) for Mac.

Results

Eleven studies comprising 1230 cases were included. Lactobacillus spp. was associated with the decreased detection of high-risk subtype (hr)HPV infection (OR = 0.64, 95% CI = 0.48–0.87, I2 = 6%), cervical intraepithelial neoplasia (CIN) (OR = 0.53, 95% CI = 0.34–0.83, I2 = 0%), and cervical cancer (CC) (OR = 0.12, 95% CI = 0.04–0.36, I2 = 0%). At the level of Lactobacillus species, Lactobacillus crispatus, but not Lactobacillus iners, was correlated with the decreased detection of hrHPV infection (OR = 0.49, 95% CI = 0.31–0.79, I2 = 10%) and CIN (OR = 0.50, 95% CI = 0.29–0.88, I2 = 0%).

Conclusions

Cervicovaginal Lactobacillus spp. is associated with the decreased detection of hrHPV infection, CIN, and CC; L. crispatus may be the critical protective factor.
The Effect of Influenza Vaccination History on Changes in Hemagglutination Inhibition Titers After Receipt of the 2015–2016 Influenza Vaccine in Older Adults in Hong Kong
Authors: Ng Tiffany W Y , Perera Ranawaka A P M , Fang Vicky J , Yau Emily M , Peiris J S Malik , Tam Yat Hung , Cowling Benjamin J
Published: June 2019

Background

Immune responses to influenza vaccination can be weaker in older adults than in other age groups. We hypothesized that antibody responses would be particularly weak among repeat vaccinees when the current and prior season vaccine components are the same.

Methods

An observational study was conducted among 827 older adults (aged ≥75 years) in Hong Kong. Serum samples were collected immediately before and 1 month after receipt of the 2015–2016 quadrivalent inactivated influenza vaccine. We measured antibody titers with the hemagglutination inhibition assay and compared the mean fold rise from prevaccination to postvaccination titers and the proportions with postvaccination titers ≥40 or ≥160.

Results

Participants who reported receipt of vaccination during either of the previous 2 years had a lower mean fold rise against all strains than with those who did not. Mean fold rises for A(H3N2) and B/Yamagata were particularly weak after repeated vaccination with the same vaccine strain, but we did not generally find significant differences in the proportions of participants with postvaccination titers ≥40 and ≥160.

Conclusions

Overall, we found that reduced antibody responses in repeat vaccinees were particularly reduced among older adults who had received vaccination against the same strains in preceding years.
Quality health care in extreme adversity—an action framework
Authors: Leatherman Sheila , Tawfik Linda , Jaff Dilshad , Jaworski Grace , Neilson Matthew , Syed Shamsuzzoha Babar , Letaief Mondher
Published: June 2019

Quality problem or issue

There are record-setting numbers of people living in settings of extreme adversity and they continue to increase each year.

Initial assessment

There is a paucity of validated data on quality and safety across settings of extreme adversity.

Choice of solution

This paper argues for an action framework to address the unique challenges of providing quality in extreme adversity.

Implementation

We describe a preliminary Quality in Extreme Adversity framework which has been informed by—and will continue to be validated through—literature, data collection, WHO expert consultations and through working in settings of extreme adversity with national authorities and NGOs.

Lessons learned

Poor quality care costs lives, livelihoods and trust in health services. The recommended framework, based on evidence and experiential lessons, intends to address the WHO goal for 2019–2023 of ‘one billion people better protected from health emergencies’ (9).
A β-lactamase-producing plasmid from Neisseria gonorrhoeae carrying a unique 6 bp deletion in blaTEM-1 encoding a truncated 24 kDa TEM-1 penicillinase that hydrolyses ampicillin slowly
Authors: Singh Reema , Perera Sumudu R , Katselis George S , Chumala Paulos , Martin Irene , Kusalik Anthony , Mitzel Kristen M , Dillon Jo-Anne R
Published: June 2019

Background

Seven structurally related β-lactamase-producing plasmids have been characterized in penicillinase-producing Neisseria gonorrhoeae (PPNG) isolates. We characterized a variant (i.e. pJRD20, Canada type) of the Africa-type (pJD5) plasmid isolated from N. gonorrhoeae strain 8903.

Objectives

To compare the DNA sequence of pJRD20 with that of pJD5 and pJD4 (Asia-type) and their TEM-1 β-lactamases.

Methods

N. gonorrhoeae 8903 was identified as part of the Gonococcal Antimicrobial Surveillance Program in Canada. β-Lactamase production was assessed using nitrocefin. MICs were determined by agar dilution and Etest methods (CLSI). The DNA sequences of pJRD20, pJD5 and pJD4 were assembled and annotated. The structure of TEM-1 and its penicillin-binding properties were determined by in silico molecular modelling and docking. TEM-1 proteins were characterized by western blot, mass spectrometry and ampicillin hydrolysis assays.

Results

N. gonorrhoeae 8903 exhibited intermediate susceptibility to penicillin with slow β-lactamase activity (i.e. 35 min to hydrolyse nitrocefin). Except for a novel 6 bp deletion starting at the G of the ATG start codon of blaTEM-1, the DNA sequence of pJRD20 was identical to that of pJD5. The TEM-1 β-lactamase produced by pJRD20 is 24 kDa and hydrolyses ampicillin only after several hours.

Conclusions

This unusual PPNG isolate might have been characterized as a non-PPNG owing to its low MIC of penicillin and its very slow hydrolysis of nitrocefin. Given the unusual nature of its TEM-1 β-lactamase, laboratories might consider extending the duration of nitrocefin hydrolysis assays.
Broad-spectrum antibiotic use in Europe: more evidence of cultural influences on prescribing behaviour
Authors: Borg Michael A , Camilleri Liberato
Published: June 2019

Objectives

Sociocultural factors have been hypothesized as important drivers of inappropriate antibiotic prescribing in European ambulatory care. This study sought to assess whether they can also explain the reported variation in broad-spectrum antibiotic (Br-Ab) use among EU/European Economic Area (EEA) countries.

Methods

Correlation and regression analysis were performed, using the bootstrap method, between Br-Ab ratios reported from 28 EU countries by the ECDC, and national Hofstede cultural dimensions and control of corruption (CoC) scores.

Results

Significant bootstrapping correlation coefficients were identified between Br-Ab ratios and the dimension of uncertainty avoidance (UAI) as well as CoC. However, following both bootstrapping multiple regression and generalized linear modelling, only UAI was retained as the sole predictor. A logarithmic model explained 58.6% of the variation in European Br-Ab variability solely using national UAI scores (P < 0.001).

Conclusions

Br-Ab prescribing appears to be driven by the level of UAI within the country. Any interventions aimed at reducing Br-Ab in high-consuming EU/EEA countries need to address this cultural perception to maximize their chances of success.
Effects of dietary Clostridium butyricum addition to sows in late gestation and lactation on reproductive performance and intestinal microbiota1
Authors: Cao Meng , Li Yan , Wu Qiujie J , Zhang Pan , Li Wentao T , Mao Zhengyu Y , Wu Dongmei M , Jiang Xuemei M , Zhuo Yong , Fang Zhengfeng F , Che Lianqiang Q , Xu Shengyu Y , Feng Bin , Li Jian , Lin Yan , Wu De
Published: June 2019

This study was conducted to investigate the effects of Clostridium butyricum addition to diets in late gestation and lactation on the reproductive performance and gut microbiota for sows. A total of 180 healthy Landrace × Yorkshire sows at 90 d of gestation were randomly assigned to one of four groups, with 45 replicates per group, receiving a basal commercial diet (Control, 0% C. butyricum) or diet added with 0.1% C. butyricum (1 × 108 CFU/kg of feed), 0.2% C. butyricum (2 × 108 CFU/kg of feed), 0.4% C. butyricum (4 × 108 CFU/kg of feed), respectively. The experiment was conducted from 90 d of gestation to weaning at 21 d of lactation. The results showed that the interval between piglet born was linearly (P < 0.05) decreased, and the duration of farrowing was significantly (quadratic, P < 0.05) shortened as C. butyricum addition increased. There was a linear (P < 0.05) increase in litter weight at weaning and litter weight gain. The concentrations of IgG and IgM in colostrum, and IgM in milk were linearly increased (P < 0.05) as C. butyricum addition. Serum MDA concentrations of sows at parturition and 14 d in lactation, and piglets at 14 and 21 d of age were linearly (P < 0.05) decreased, respectively. The serum total antioxidant capacity concentrations of sows at parturition and 14 and 21 d in lactation, and piglets at 14 and 21 d of age were linearly (P < 0.05) increased as C. butyricum addition, respectively. There was a linear decrease in the serum endotoxin concentration of sows on 21 d in lactation (P < 0.05). The serum cortisol concentrations of piglets at 14 and 21 d of age were both significantly (quadratic, P < 0.05) decreased. The 0.2% C. butyricum increased the relative abundance of Bacteroidetes (P = 0.016) at phylum level, Prevotellaceae_NK3B31_group, Prevotella_1, Prevotellaceae_UCG-003, Prevotella_9, Alloprevotella (P < 0.05) at genus level, and decreased the relative abundance of Proteobacteria, Gemmatimonadetes, Actinobacteria (P < 0.001) at phylum level, and Clostridium_sensu_stricto_1, Streptococcus, Escheruchia-Shigella, Sphingomonas, Succinivibrio (P < 0.05) at genus level and Firmicutes/Bacteroidetes ratio (P = 0.020). In conclusion, the present research indicated that dietary addition with C. butyricum could shorten the duration of farrowing and enhance the growth performance of suckling piglets. Moreover, 0.2% C. butyricum administration to sows changed the composition of intestinal microbiota, especially increased the relative abundance of Prevotella.
Current indications of endoscopic submucosal dissection for early gastric cancer in Japan
Authors: Takizawa Kohei , Ono Hiroyuki , Muto Manabu
Published: June 2019

Endoscopic submucosal dissection for early gastric cancer is widely accepted and technically considered to have matured in Japan. Its indications have been expanded on the basis of clinical trial results.
SP1 governs primordial folliculogenesis by regulating pregranulosa cell development in mice
Authors: Cai Han , Liu Bingying , Wang Huarong , Sun Guanghong , Feng Lizhao , Chen Ziqi , Zhou Jiaqi , Zhang Jiawei , Zhang Tuo , He Meina , Yang Tingting , Guo Qirui , Teng Zhen , Xin Qiliang , Zhou Bo , Zhang Hua , Xia Guoliang , Wang Chao
Published: June 2019

Establishment of the primordial follicle (PF) pool is pivotal for the female reproductive lifespan; however, the mechanism of primordial folliculogenesis is poorly understood. Here, the transcription factor SP1 was shown to be essential for PF formation in mice. Our results showed that SP1 is present in both oocytes and somatic cells during PF formation in the ovary. Knockdown of Sp1 expression, especially in pregranulosa cells, significantly suppressed nest breakdown, oocyte apoptosis, and PF formation, suggesting that SP1 expressed by somatic cells functions in the process of primordial folliculogenesis. We further demonstrated that SP1 governs the recruitment and maintenance of Forkhead box L2-positive (FOXL2+) pregranulosa cells using an Lgr5-EGFP-IRES-CreERT2 (Lgr5-KI) reporter mouse model and a FOXL2+ cell-specific knockdown model. At the molecular level, SP1 functioned mainly through manipulation of NOTCH2 expression by binding directly to the promoter of the Notch2 gene. Finally, consistent with the critical role of granulosa cells in follicle survival in vitro, massive loss of oocytes in Sp1 knockdown ovaries was evidenced before puberty after the ovaries were transplanted under the renal capsules. Conclusively, our results reveal that SP1 controls the establishment of the ovarian reserve by regulating pregranulosa cell development in the mammalian ovary.
A convolutional neural network approach for IMRT dose distribution prediction in prostate cancer patients
Authors: Kajikawa Tomohiro , Kadoya Noriyuki , Ito Kengo , Takayama Yoshiki , Chiba Takahito , Tomori Seiji , Nemoto Hikaru , Dobashi Suguru , Takeda Ken , Jingu Keiichi
Published: June 2019

The purpose of the study was to compare a 3D convolutional neural network (CNN) with the conventional machine learning method for predicting intensity-modulated radiation therapy (IMRT) dose distribution using only contours in prostate cancer. In this study, which included 95 IMRT-treated prostate cancer patients with available dose distributions and contours for planning target volume (PTVs) and organs at risk (OARs), a supervised-learning approach was used for training, where the dose for a voxel set in the dataset was defined as the label. The adaptive moment estimation algorithm was employed for optimizing a 3D U-net similar network. Eighty cases were used for the training and validation set in 5-fold cross-validation, and the remaining 15 cases were used as the test set. The predicted dose distributions were compared with the clinical dose distributions, and the model performance was evaluated by comparison with RapidPlan™. Dose–volume histogram (DVH) parameters were calculated for each contour as evaluation indexes. The mean absolute errors (MAE) with one standard deviation (1SD) between the clinical and CNN-predicted doses were 1.10% ± 0.64%, 2.50% ± 1.17%, 2.04% ± 1.40%, and 2.08% ± 1.99% for D2, D98 in PTV-1 and V65 in rectum and V65 in bladder, respectively, whereas the MAEs with 1SD between the clinical and the RapidPlan™-generated doses were 1.01% ± 0.66%, 2.15% ± 1.25%, 5.34% ± 2.13% and 3.04% ± 1.79%, respectively. Our CNN model could predict dose distributions that were superior or comparable with that generated by RapidPlan™, suggesting the potential of CNN in dose distribution prediction.
Culturally Sensitive PTSD Screening in Non-Western Youth: Reflections and Indications for Mental Health Practitioners
Authors: Perry James Michael , Modesti Camilla , Talamo Alessandra , Nicolais Giampaolo
Published: June 2019

Children around the world are exposed to traumatic events and research confirms that cultural factors play a central role in the psychological experience of trauma and the manifestation of symptoms in trauma and stress-related disorders. The DSM-5 and ICD-11 call on practitioners to consider the role of culture and context in the manifestation, assessment, and treatment of mental health disorders. This article analyzes peer-reviewed literature involving youth and adolescent PTSD screening in non-Western contexts, revealing only few instruments that have undergone validation for cultural contexts outside those for which they were developed. Studies that include cultural validation show marked differences in methodology and conceptual framework for adaptation, translation, and validation, and disagreement on the scale and scope of tools necessary to assess the impact of trauma in non-Western youth. The discussed studies reveal a need to debate a uniform methodology for cultural adaptation and validation of PTSD screening instruments.
Tuberculosis epididymo-orchitis following intravesical bacillus Calmette-Guérin immunotherapy
Authors: Rezvani Sean , Collins Gerald
Published: June 2019

BCG is a well-established treatment for superficial bladder cancer. Although usually well-tolerated, side effects can range from mild cystitis to life-threatening sepsis. Epididymitis is a rare complication of BCG, with only a handful of cases proven to be caused directly by Mycobacterium bovis. We describe one such case, along with radiological findings for this rare complication.
Are you sure your tool does what it is supposed to do? Validating Arabic root extraction
Authors: van der Zwaan Janneke , Latif Maksim Abdul , van Kuppevelt Dafne , Lyklema Melle , Lange Christian
Published: June 2019

Although in the digital humanities, researchers use software tools to conduct their research, and often apply these tools to data the software was not developed for, there has been little attention for investigating tool performance on this data. This is strange because in order to be able to appraise the results of digital humanities research, it is important to understand to what extent the tool output is correct. To illustrate the importance of the validation of tools, this article presents a case study of validating Arabic root extraction tools. Arabic words are based on root letters; three root letters usually demarcate a semantic field. Thus, roots can be used for studying semantic fields. For example, researchers can gain insight into the relative importance of the different senses (i.e. seeing, hearing, touching, smelling, and tasting) in Arabic jurisprudence (fiqh) by extracting and counting roots. A problem is that there are only a few usable tools available. We take three root extraction tools, Khoja (Khoja and Garside, 1999, Stemming Arabic Text. Lancaster, England: Lancaster University), ISRI (Taghva et al., 2005, Arabic stemming without a root dictionary. In International Conference on Information Technology: Coding and Computing (ITCC’05). Vol. 2. Las Vegas, NV, April 2005 pp. 152–57), and AlKhalil (Boudlal et al., 2010, Alkhalil morpho sys1: a morphosyntactic analysis system for Arabic texts. In International Arab Conference on Information Technology. New York, NY: Elsevier Science Inc., April 2017, pp. 1–6), and create manually annotated gold standard data consisting of three samples of approximately 1,000 words from important books of Islamic jurisprudence. We show that Khoja is the best root extraction tool for our data. We also demonstrate that the relative counts of individual roots differ among tools, which leads to a different interpretation depending on which tool is chosen. This means that findings based on automatically extracted roots should always be interpreted with care.
K3-EDTA differentially inhibits the growth of Candida strains according to their azole resistance status
Authors: Dupont Damien , Tirard-Collet Pauline , Persat Florence , Menotti Jean , Josse Emilie , Wallon Martine , Pichon Maxime
Published: June 2019

The diagnosis of the life-threatening invasive Candida infections is mainly established using culture of specimens that might be collected on different devices including ethylene diamine tetraacetic acid (EDTA)-coated tubes. Despite the knowledge that EDTA inhibits bacterial cultures, and its use to treat oral fungal infections, its impact on Candida cultures has not been completely assessed. This study aimed at assessing it on azole-resistant and azole-susceptible strains. Clinical and American Type Culture Collection (ATCC) strains for Candida albicans (CA), C. glabrata (CGS), C. krusei (CK), azole-susceptible and azole-resistant strains of C. glabrata (CGS and CGR), C. lipolytica (CL), and C. inconspicua (CI) were characterized using MALDI-TOF MS and susceptibility testing and then incubated (1) with serial dilutions of tripotassic EDTA (0%–500% of the concentration in a sample tube) for 2 hours before plating onto ChromID Can2 agar; (2) for 0, 2, 4, 6, 7, or 8 hours at EDTA concentrations at 20% and 33% before seeding; and (3) with sodium citrate or lithium heparinate instead of EDTA for 2 hours before plating. After 48 hours at 35°C, colony-forming units were automatically quantified. An inhibitory effect of EDTA was observed, at different concentrations, for CA (20%), CGS (100%), and CGR (500%) (P < .05), but none was observed for CL, CI, and CK. The effect increased with incubation duration, at a faster rate for azole-susceptible strains. K3-EDTA inhibits Candida growth and EDTA-coated tubes should not be used for mycological culture-based analyses. The correlation between EDTA inhibition and Candida azole-resistance offers perspectives for the development of selective agar and new antifungal strategies.
Globular clusters as probes of dark matter cusp-core transformations
Authors: Orkney M D A , Read J I , Petts J A , Gieles M
Published: June 2019

Bursty star formation in dwarf galaxies can slowly transform a steep dark matter cusp into a constant density core. We explore the possibility that globular clusters (GCs) retain a dynamical memory of this transformation. To test this, we use the nbody6df code to simulate the dynamical evolution of GCs, including stellar evolution, orbiting in static and time-varying potentials for a Hubble time. We find that GCs orbiting within a cored dark matter halo, or within a halo that has undergone a cusp-core transformation, grow to a size that is substantially larger (Reff > 10 pc) than those in a static cusped dark matter halo. They also produce much less tidal debris. We find that the cleanest signal of an historic cusp-core transformation is the presence of large GCs with tidal debris. However, the effect is small and will be challenging to observe in real galaxies. Finally, we qualitatively compare our simulated GCs with the observed GC populations in the Fornax, NGC 6822, IKN, and Sagittarius dwarf galaxies. We find that the GCs in these dwarf galaxies are systematically larger (〈Reff〉 ≃ 7.8 pc), and have substantially more scatter in their sizes than in situ metal-rich GCs in the Milky Way and young massive star clusters forming in M83 (〈Reff〉 ≃ 2.5 pc). We show that the size, scatter, and survival of GCs in dwarf galaxies are all consistent with them having evolved in a constant density core, or a potential that has undergone a cusp-core transformation, but not in a dark matter cusp.
How to optimally constrain galaxy assembly bias: supplement projected correlation functions with count-in-cells statistics
Authors: Wang Kuan , Mao Yao-Yuan , Zentner Andrew R , van den Bosch Frank C , Lange Johannes U , Schafer Chad M , Villarreal Antonia Sierra , Hearin Andrew P , Campbell Duncan
Published: June 2019

Most models for the statistical connection between galaxies and their haloes ignore the possibility that galaxy properties may be correlated with halo properties other than halo mass, a phenomenon known as galaxy assembly bias. And yet, it is known that such correlations can lead to systematic errors in the interpretation of survey data that are analysed using traditional halo occupation models. At present, the degree to which galaxy assembly bias may be present in the real Universe, and the best strategies for constraining it remain uncertain. We study the ability of several observables to constrain galaxy assembly bias from redshift survey data using the decorated halo occupation distribution (dHOD), an empirical model of the galaxy–halo connection that incorporates assembly bias. We cover an expansive set of observables, including the projected two-point correlation function $w$p(rp), the galaxy–galaxy lensing signal ΔΣ(rp), the void probability function VPF(r), the distributions of counts-in-cylinders P(NCIC), and counts-in-annuli P(NCIA), and the distribution of the ratio of counts in cylinders of different sizes P(N2/N5). We find that despite the frequent use of the combination $w$p(rp) + ΔΣ(rp) in interpreting galaxy data, the count statistics, P(NCIC) and P(NCIA), are generally more efficient in constraining galaxy assembly bias when combined with $w$p(rp). Constraints based upon $w$p(rp) and ΔΣ(rp) share common degeneracy directions in the parameter space, while combinations of $w$p(rp) with the count statistics are more complementary. Therefore, we strongly suggest that count statistics should be used to complement the canonical observables in future studies of the galaxy–halo connection.
Predictions for the spatial distribution of the dust continuum emission in $\boldsymbol {1\,\lt\, z\,\lt\, 5}$ star-forming galaxies
Authors: Cochrane R K , Hayward C C , Anglés-Alcázar D , Lotz J , Parsotan T , Ma X , Kereš D , Feldmann R , Faucher-Giguère C A , Hopkins P F
Published: June 2019

We present the first detailed study of the spatially resolved dust continuum emission of simulated galaxies at 1 < z < 5. We run the radiative transfer code skirt on a sample of submillimetre-bright galaxies drawn from the Feedback In Realistic Environments (FIRE) project. These simulated galaxies reach Milky Way masses by z = 2. Our modelling provides predictions for the full rest-frame far-ultraviolet-to-far-infrared spectral energy distributions of these simulated galaxies, as well as 25-pc resolution maps of their emission across the wavelength spectrum. The derived morphologies are notably different in different wavebands, with the same galaxy often appearing clumpy and extended in the far-ultraviolet yet an ordered spiral at far-infrared wavelengths. The observed-frame 870-$\mu$m half-light radii of our FIRE-2 galaxies are ${\sim} 0.5\rm {-}4\, \rm {kpc}$, consistent with existing ALMA observations of galaxies with similarly high redshifts and stellar masses. In both simulated and observed galaxies, the dust continuum emission is generally more compact than the cold gas and the dust mass, but more extended than the stellar component. The most extreme cases of compact dust emission seem to be driven by particularly compact recent star formation, which generates steep dust temperature gradients. Our results confirm that the spatial extent of the dust continuum emission is sensitive to both the dust mass and star formation rate distributions.
ZnO nanoparticles-associated mitochondrial stress-induced apoptosis and G2/M arrest in HaCaT cells: a mechanistic approach
Authors: Vallabani N V Srikanth , Sengupta Souvik , Shukla Ritesh Kumar , Kumar Ashutosh
Published: June 2019

Zinc oxide nanoparticles (ZnO NPs) with their wide range of consumer applications in day-to-day life received great attention to evaluate their effects in humans. This study has been attempted to elucidate the DNA damage response mechanism in a dermal model exposed to ZnO NPs through Ataxia Telangiectasia Mutated (ATM)-mediated ChK1-dependent G2/M arrest. Further, viability parameters and mechanism involved in the cell death with special reference to the consequences arising due to DNA damage were explored. Our study showed that ZnO NPs at concentrations 5 and 10 µg/ml induced significant cytotoxic effect in skin cell line. Moreover, the results confirmed generation of reactive oxygen species (ROS) induces the cell death by genotoxic insult, leading to mitochondrial membrane depolarisation and cell cycle arrest. Subsequently, ZnO NPs treatment created DNA damage as confirmed via Comet assay (increase in olive tail moment), micronucleus assay (increase in micronucleus formation), double-strand breaks (increase in ATM and Ataxia Telangiectasia and Rad3 related (ATR) expression), DNA fragmentation and cell cycle (G2/M arrest) studies. Finally, marker proteins analysis concluded the mechanistic approach by demonstrating the key marker expressions HMOX1 and HSP60 (for oxidative stress), cytochrome c, APAF1, BAX, Caspase 9, Caspase 3 and decrease in BCL2 (for activating apoptotic pathway), pATM, ATR and γH2AX (for double-strand breaks), DNA-PK (involved in DNA repair) and decrease in cell cycle regulators. In together, our data revealed the mechanism of ROS generation that triggers apoptosis and DNA damage in HaCaT cell lines exposed to ZnO NPs.
Symmetric activity of DNA polymerases at and recruitment of exonuclease ExoR and of PolA to the Bacillus subtilis replication forks
Authors: Hernández-Tamayo Rogelio , Oviedo-Bocanegra Luis M , Fritz Georg , Graumann Peter L
Published: June 2019

DNA replication forks are intrinsically asymmetric and may arrest during the cell cycle upon encountering modifications in the DNA. We have studied real time dynamics of three DNA polymerases and an exonuclease at a single molecule level in the bacterium Bacillus subtilis. PolC and DnaE work in a symmetric manner and show similar dwell times. After addition of DNA damage, their static fractions and dwell times decreased, in agreement with increased re-establishment of replication forks. Only a minor fraction of replication forks showed a loss of active polymerases, indicating relatively robust activity during DNA repair. Conversely, PolA, homolog of polymerase I and exonuclease ExoR were rarely present at forks during unperturbed replication but were recruited to replications forks after induction of DNA damage. Protein dynamics of PolA or ExoR were altered in the absence of each other during exponential growth and during DNA repair, indicating overlapping functions. Purified ExoR displayed exonuclease activity and preferentially bound to DNA having 5′ overhangs in vitro. Our analyses support the idea that two replicative DNA polymerases work together at the lagging strand whilst only PolC acts at the leading strand, and that PolA and ExoR perform inducible functions at replication forks during DNA repair.
The effect of adenine protonation on RNA phosphodiester backbone bond cleavage elucidated by deaza-nucleobase modifications and mass spectrometry
Authors: Fuchs Elisabeth , Falschlunger Christoph , Micura Ronald , Breuker Kathrin
Published: June 2019

The catalytic strategies of small self-cleaving ribozymes often involve interactions between nucleobases and the ribonucleic acid (RNA) backbone. Here we show that multiply protonated, gaseous RNA has an intrinsic preference for the formation of ionic hydrogen bonds between adenine protonated at N3 and the phosphodiester backbone moiety on its 5′-side that facilitates preferential phosphodiester backbone bond cleavage upon vibrational excitation by low-energy collisionally activated dissociation. Removal of the basic N3 site by deaza-modification of adenine was found to abrogate preferential phosphodiester backbone bond cleavage. No such effects were observed for N1 or N7 of adenine. Importantly, we found that the pH of the solution used for generation of the multiply protonated, gaseous RNA ions by electrospray ionization affects phosphodiester backbone bond cleavage next to adenine, which implies that the protonation patterns in solution are at least in part preserved during and after transfer into the gas phase. Our study suggests that interactions between protonated adenine and phosphodiester moieties of RNA may play a more important mechanistic role in biological processes than considered until now.
DNA nanotechnology approaches for microRNA detection and diagnosis
Authors: Chandrasekaran Arun Richard , Punnoose Jibin Abraham , Zhou Lifeng , Dey Paromita , Dey Bijan K , Halvorsen Ken
Published: June 2019

MicroRNAs are involved in the crucial processes of development and diseases and have emerged as a new class of biomarkers. The field of DNA nanotechnology has shown great promise in the creation of novel microRNA biosensors that have utility in lab-based biosensing and potential for disease diagnostics. In this Survey and Summary, we explore and review DNA nanotechnology approaches for microRNA detection, surveying the literature for microRNA detection in three main areas of DNA nanostructures: DNA tetrahedra, DNA origami, and DNA devices and motifs. We take a critical look at the reviewed approaches, advantages and disadvantages of these methods in general, and a critical comparison of specific approaches. We conclude with a brief outlook on the future of DNA nanotechnology in biosensing for microRNA and beyond.