bluuebunny/crossref_metadata_2025 huggingface dataset:
Stereotactic Radiosurgery for Olfactory Groove Meningiomas: An International, Multicenter Study
Authors: Bunevicius Adomas , Ahn Jungeun , Fribance Sarah , Peker Selcuk , Hergunsel Batu , Sheehan Darrah , Sheehan Kimball , Nabeel Ahmed M , Reda Wael A , Tawadros Sameh R , Abdelkarim Khaled , El-Shehaby Amr M N , Emad Reem M , Chytka Tomas , Liscak Roman , Alvarez Roberto Martínez , Moreno Nuria Martínez , Langlois Anne-Marie , Mathieu David , Lee Cheng-chia , Yang Huai-che , Tripathi Manjul , Warnick Ronald E , Speckter Herwin , Albert Camilo , Picozzi Piero , Franzini Andrea , Attuati Luca , Strickland Ben A , Zada Gabriel , Chang Eric L , Feliciano Valls Caleb E , Carbini Carlos H , Patel Samir , Sheehan Jason
Published: July 2021

BACKGROUND

Stereotactic radiosurgery (SRS) is increasingly considered for selected olfactory groove meningiomas (OGMs).

OBJECTIVE

To investigate the safety and efficacy of SRS for OGMs.

METHODS

From 20 institutions participating in the International Radiosurgery Research Foundation, we pooled patients who underwent SRS for histologically confirmed or radiologically suspected WHO grade I OGMs and were followed for 6 mo or more after the SRS.

RESULTS

In total, 278 (median age 57 yr) patients underwent SRS for histologically confirmed (29%) or radiologically suspected (71%) WHO grade I OGMs Median treatment volume was 4.60 cm3 (range: 0.12-27.3 cm3), median prescription dose was 12 Gy, and median dose to the olfactory nerve was 11.20 Gy. During median post-SRS imaging follow-up of 39 mo (range: 6-240 mo), 43% of patients had partial or marginal response, 54% of patients had stable disease, and 3% of patients experienced progression. During median post-SRS clinical follow-up of 51 mo (range: 6-240 mo), 36 (13%) patients experienced clinical and/or radiological adverse radiation events (AREs). Elevated risk of AREs was associated with larger OGM volume (P = .009) and pre-SRS peritumoral T2/fluid-attenuated inversion-recovery signal abnormalities (P < .001). After the SRS, olfaction remained stable, improved, or deteriorated in 90%, 8%, and 2% of patients, respectively. Complete post-SRS anosmia was predicted by partial/complete anosmia before the SRS (odds ratio [OR] = 83.125; 95% CI [24.589-281.01], P < .001) and prior resection of OGM (OR = 3.919; 95% CI [1.713-8.970], P = .001).

CONCLUSION

SRS is associated with durable local control of the majority of OGM patients with acceptable safety profile. SRS allows preservation or improvement of olfactory function in the majority of OGM patients.
The Impact of Syndromic Management of Vaginal Discharge Syndrome on Adverse Birth Outcomes in Botswana
Authors: Fennell Christina , Diseko Modeigi , Zash Rebecca , Mayondi Gloria , Mabuta Judith , Mmalane Mompati , Davey Sonya , Luckett Rebecca , Morroni Chelsea , Dintwa Eldah N , Lockman Shahin , Makhema Joseph , Caniglia Ellen , Shapiro Roger
Published: July 2021

Background

Vaginal discharge syndrome (VDS) is a common clinical diagnosis during pregnancy in Botswana; it is treated with broad-spectrum antibiotics using a syndromic approach. We evaluated associations between the syndromic management of VDS and adverse birth outcomes.

Methods

The Tsepamo Study performs birth outcomes surveillance at government hospitals throughout Botswana. Obstetric record data collected from August 2014 to March 2019 were analyzed. Chi-square tests were conducted to compare proportions of maternal characteristics and infant outcomes. To avoid immortal time bias, all analyses were conducted among women who presented to care before 24 weeks gestation, with VDS categorized as present or absent by 24 weeks gestation. Log-binomial regression models were generated to determine associations between treated VDS and infant outcomes.

Results

VDS was diagnosed in 36 731 (30.7%) pregnant women, of whom 33 328 (90.7%) received antibiotics. Adjusted analyses yielded a harmful association between treated VDS and very preterm delivery (adjusted risk ratio, 1.11; 95% CI, 1.02–1.21). This association remained when restricting to women with VDS who received the recommended antibiotic treatment regimen. Sensitivity analyses produced nonsignificant associations when women with treated VDS were compared with women without VDS who received antibiotics for other indications.

Conclusions

A clinical diagnosis of VDS is common among pregnant women in Botswana, and the majority receive antibiotics in pregnancy. Although analyses of VDS occurring later in pregnancy are precluded by immortal time bias, a modest association between treated VDS and very preterm delivery was observed among women diagnosed with VDS by 24 weeks gestation.
Retrosigmoid Craniectomy and Suprameatal Drilling—3-Dimensionally Printed Microneurosurgical Simulation: 2-Dimensional Operative Video
Authors: Martinez Jaime L , Damon Aaron , Domingo Ricardo A , Valero-Moreno Fidel , Quiñones-Hinojosa Alfredo
Published: July 2021

Neurosurgical training is being challenged by rigorous work-hour restrictions and the COVID-19 pandemic.
1
Now, more than ever, surgical simulation plays a pivotal role in resident education and psychomotor skill development. Three-dimensional (3D) printing technologies enable the construction of inexpensive, patient-specific, anatomically accurate physical models for a more convenient and realistic simulation of complex skull base approaches in a safe environment.
2
All stages of the surgical procedure can be simulated, from positioning and exposure to deep microdissection, which has an unparalleled educational value. The complex approach-specific anatomy, narrow working angles, and pathoanatomic relationships can be readily explored from the surgeon's perspective or point of view.
2,3
Furthermore, different thermoplastic polymers can be utilized to replicate the visual and tactile feedback of bone (cortical/cancellous), neurological, and vascular tissues.
4
Retrosigmoid craniectomies are widely used in neurosurgery with various applications, including microvascular decompressions in patients with trigeminal neuralgia.
5-7
Removal of the suprameatal tubercle (SMT) extends the retrosigmoid approach superiorly to the middle fossa and Meckel's cave, and anteriorly to the clivus.
8,9
This maneuver may be necessary in patients with prominent SMTs obstructing the view of the trigeminal nerve and in patients with a more anterosuperior neurovascular conflict. This video illustrates a microsurgical training tool for learning and honing the technique of retrosigmoid craniectomy and suprameatal drilling using an affordable (29.00 USD) biomimetic 3D-printed simulator that closely recapitulates not only the anatomy but also the tactile feedback of drilling and manipulating neurological tissues (see Table and Graph 1; minute 07:11) as it happens at the time of surgery.
Promoting healthy lifestyle behaviours in youth: Findings from a novel intervention for children at risk of cardiovascular disease
Authors: Ybarra Marina , Danieles Prince Kevin , Barnett Tracie A , Mathieu Marie-Ève , Van Hulst Andraea , Drouin Olivier , Kakinami Lisa , Bigras Jean-Luc , Henderson Mélanie
Published: July 2021

Objectives

Obesity is the most prevalent risk factor for cardiovascular disease (CVD) in children. We developed a 2-year lifestyle intervention for youth at risk of CVD. We assessed changes in body mass index z-scores (zBMI) and key cardiometabolic risk factors, physical fitness, and capacity among those who completed the program.

Methods

The CIRCUIT program is a multidisciplinary lifestyle intervention for children aged 4 to 18 years at risk of CVD, based on a personalized plan to improve cardiometabolic outcomes by increasing physical activity and reducing sedentary behaviours. Both at baseline and 2-year follow-up, we measured zBMI, blood pressure z-scores (zBP), adiposity (%body and %trunk fat), fasting blood glucose and lipid profile, aerobic (VO2max) and anaerobic (5×5 m shuttle run test) fitness, and physical capacity indicators. Differences between baseline and follow-up were examined using paired t-tests (for age-sex standardized outcomes) and multivariable mixed effect models, adjusted for age and sex (for other outcomes).

Results

Among the 106 participants (53 males) who completed the 2-year program, mean age at baseline was 10.9 years (SD=3.2). After 2 years, zBMI and diastolic zBP decreased by 0.30SD (95% CI: −0.44; −0.16) and 0.43SD (95% CI: −0.65; −0.23), respectively. Participants improved %body and %trunk fat, lipid profile, aerobic and anaerobic fitness levels, and physical capacity (p<0.02). No changes in systolic zBP nor in fasting plasma glucose were observed.

Conclusion

Our findings showed improved zBMI, cardiometabolic outcomes, physical fitness, and capacity among children at risk of CVD, suggesting that CIRCUIT is a promising intervention.
MtExpress, a Comprehensive and Curated RNAseq-based Gene Expression Atlas for the Model Legume Medicago truncatula
Authors: Carrere Sebastien , Verdier Jerome , Gamas Pascal
Published: July 2021

Although RNA sequencing (RNAseq) has been becoming the main transcriptomic approach in the model legume Medicago truncatula, there is currently no genome-wide gene expression atlas covering the whole set of RNAseq data published for this species. Nowadays, such a tool is highly valuable to provide a global view of gene expression in a wide range of conditions and tissues/organs. Here, we present MtExpress, a gene expression atlas that compiles an exhaustive set of published M. truncatula RNAseq data (https://medicago.toulouse.inrae.fr/MtExpress). MtExpress makes use of recent releases of M. truncatula genome sequence and annotation, as well as up-to-date tools to perform mapping, quality control, statistical analysis and normalization of RNAseq data. MtExpress combines semi-automated pipelines with manual re-labeling and organization of samples to produce an attractive and user-friendly interface, fully integrated with other available Medicago genomic resources. Importantly, MtExpress is highly flexible, in terms of both queries, e.g. allowing searches with gene names and orthologous gene IDs from Arabidopsis and other legume species, and outputs, to customize visualization and redirect gene study to relevant Medicago webservers. Thanks to its semi-automated pipeline, MtExpress will be frequently updated to follow the rapid pace of M. truncatula RNAseq data publications, as well as the constant improvement of genome annotation. MtExpress also hosts legacy GeneChip expression data originally stored in the Medicago Gene Expression Atlas, as a very valuable and complementary resource.
Expansion of CD4+CD8+ double-positive T cells in rheumatoid arthritis patients is associated with erosive disease
Authors: Nguyen Phuong , Melzer Marc , Beck Felix , Krasselt Marco , Seifert Olga , Pierer Matthias , Rothe Kathrin , Wagner Ulf
Published: July 2021

Objectives

CD4+CD8+ double-positive (DP) T cells are expanded in the peripheral blood of a subset of patients with RA. This study examines the clinical significance of DP T cells in RA.

Methods

In 70 RA patients, DP T cells were measured by flow cytometry. Clinical data were obtained, and hand and feet radiographs were scored according to the Sharp/van der Heijde (SvdH) method. The association between DP T cell frequency and erosive joint destruction was analysed by correlation and multiple logistic regression analysis.

Results

Nineteen RA patients (27.1%) displayed increased DP T cell frequencies, which correlated with age (r = 0.288, P =0.016). Expansion of DP T cells was associated with the occurrence of erosions (94,7% vs 43,1%, P <0.001), with a higher SvdH joint damage score (24.5 vs 6, P =0.008) and with more frequent use of biologic or targeted-synthetic DMARDs (68.4% vs 38%, P =0.02). In patients with non-erosive disease, DP T cell frequencies correlated with the joint space narrowing score (n = 28, r = 0.44, P =0.02). Logistic regression revealed DP T cells to be associated with erosive disease (OR 1.90, P <0.05).

Conclusion

Expansion of DP T cells is associated with joint damage and frequent escalation of therapy, possibly suggesting a contribution to more severe RA.
Granule cells in the infrapyramidal blade of the dentate gyrus are activated during paradoxical (REM) sleep hypersomnia but not during wakefulness: a study using TRAP mice
Authors: Yamazaki Risa , Wang Dianru , De Laet Anna , Maciel Renato , Agnorelli Claudio , Cabrera Sébastien , Arthaud Sébastien , Libourel Paul-Antoine , Fort Patrice , Lee Hyunsook , Luppi Pierre-Hervé
Published: July 2021

Study Objectives

Determine whether in the hippocampus and the supramammillary nucleus (SuM) the same neurons are reactivated when mice are exposed 1 week apart to two periods of wakefulness (W-W), paradoxical sleep rebound (PSR-PSR) or a period of W followed by a period of PSR (W-PSR)

Methods

We combined the innovative TRAP2 mice method in which neurons expressing cFos permanently express tdTomato after tamoxifen injection with cFos immunohistochemistry.

Results

We found out that a large number of tdTomato+ and cFos+ cells are localized in the dentate gyrus (DG) after PSR and W while CA1 and CA3 contained both types of neurons only after W. The number of cFos+ cells in the infrapyramidal but not the suprapyramidal blade of the DG was positively correlated with the amount of PS. In addition, we did not find double-labeled cells in the DG whatever the group of mice. In contrast, a high percentage of CA1 neurons were double-labeled in W-W mice. Finally, in the supramammillary nucleus, a large number of cells were double-labeled in W-W, PSR-PSR but not in W-PSR mice.

Conclusions

Altogether, our results are the first to show that different neurons are activated during W and PS in the supramammillary nucleus and the hippocampus. Further, we showed for the first time that granule cells of the infrapyramidal blade of the DG are activated during PS but not during W. Further experiments are now needed to determine whether these granule cells belong to memory engrams inducing memory reactivation during PS.
To Condemn or Not to Condemn: Perceived Climates Concerning Sexual Orientation in Black Churches
Authors: Young Luther
Published: July 2021

Although the United States is becoming more accepting of lesbian, gay, bisexual, and queer (LGBQ) identities, black people are still more likely than the general population to disapprove of non-heterosexuality. Previous research points to the conservative views of the Black Church as a potential explanation for this disparity, but few studies have considered the diversity of perspectives within the Black Church. Drawing upon in-depth interviews with black Christians, this article examines how black congregants experience their churches’ climates concerning sexual orientation. Findings suggest that black congregations tend to foster climates that are not affirming of non-heterosexuality; however, they vary in how they demonstrate non-affirmation. Furthermore, the study finds considerable differences in how congregants perceive and make sense of their perceived church climates concerning non-heterosexuality. These results suggest that the Black Church is not monolithic in its stance concerning sexuality and have implications for efforts to promote LGBQ inclusion within congregations.
Implementation of quality improvement coaching versus physician communication training for improving human papillomavirus vaccination in primary care: a randomized implementation trial
Authors: Grabert Brigid K , Kurtzman Rachel , Heisler-MacKinnon Jennifer , Leeman Jennifer , Bjork Adam , Kameny Maddy , Liu Amy , Todd Karen , Alton Dailey Susan , Smith Kevin , Brewer Noel T , Gilkey Melissa B
Published: July 2021

Lay Summary

Our cluster randomized trial compared two interventions that health departments commonly use to increase HPV vaccination coverage: quality improvement (QI) coaching and physician communication training. We found that QI coaching cost less and was more often adopted by primary care clinics, but communication training reached more staff members per clinic, including vaccine prescribers. Findings provide health departments with data needed to weigh the implementation strengths and challenges of QI coaching and physician communication training for increasing HPV vaccination coverage.
Mediators of relations of obesity treatment-associated changes in mood and weight: extending cross-sectional research
Authors: Annesi James J
Published: July 2021

Significant cross-sectional associations between mood and weight have been made in women; however, data on associated longitudinal effects and their psychological and behavioral mechanisms are required to inform obesity treatments that mostly have limited success beyond the very short term. Women participating in behavioral obesity treatments were assessed on psychological and behavioral measures, and weight change over 12 months. A treatment focused on physical activity and self-regulation (n = 67) had significantly better improvements than a treatment centered around weight-loss education (n = 64) on measures of mood (overall mood, depression, anxiety), self-regulation, emotional eating, eating behaviors, physical activity, and weight in women with obesity. Incorporating a lagged variable design, 12-month weight loss was significantly predicted (separately) by changes in overall negative mood, depression, and anxiety. When changes in measures of self-regulation, emotional eating, and eating behaviors were sequentially entered as mediators, mood change–weight change relationships were rendered non-significant. Significant mediation paths were: mood change→self-regulation change→weight change, and mood change→self-regulation change→eating behavior change→weight change. They were unaffected by the treatment group. Findings contributed to both theory and obesity intervention architectures via a design sensitive to the dynamic psychological and behavioral changes occurring within weight-loss processes.
Does acceptance-based treatment moderate the effect of stress on dietary lapses?
Authors: Coffman Donna L , Oliva Isabela Batista , Forman Evan M
Published: July 2021

Weight loss interventions are successful to the extent that participants adhere to calorie-reduced dietary prescriptions and may be undermined by dietary lapses triggered by external or internal factors, such as stress. The purpose of this study was to examine whether an acceptance-based treatment (ABT) versus a standard behavioral treatment (SBT) moderated the effect of stress on dietary lapses. Ecological momentary assessment data were collected from 189 participants who were randomly assigned to either ABT or SBT. Between-subject and within-subject stress were used to predict lapse occurrence along with intervention condition, and the interaction between intervention condition and stress using a generalized linear mixed-effects model. Gender, time of day, and baseline mean lapses/day were included as control variables. Higher mean baseline lapses/day, female gender, and later time of day were significantly associated with increased odds of lapse. Between-subject stress was positively and significantly related to the odds of lapse. Compared to SBT, ABT showed a significant decrease in the odds of lapse at an individual’s average level of within-subject stress, but the interaction of intervention condition with within-subject stress was not statistically significant. Participants with high overall stress levels lapsed more frequently than those with low overall stress levels. There was a significant decrease in the odds of lapse for the ABT group at a participant’s own average stress level, suggesting that ABT may be beneficial at participants’ usual stress levels but when they deviate from their usual stress level, there are no treatment differences.
Anti-Black racism and behavioral medicine: confronting the past to envision the future
Authors: Breland Jessica Y , Stanton Michael V
Published: July 2021

Behavioral medicine research and practice have not traditionally acknowledged the detrimental effects of anti-Black racism (and other forms of systemic oppression) on health, interventions, or research. This commentary describes four ways that behavioral medicine researchers and clinicians can address the past to envision the future of behavioral medicine to promote equitable health for all: 1) name anti-Black racism, 2) ensure interventions address structural inequities, 3) advocate for systemic change, and 4) change expectations for publications.
A multiperspective on the broad dissemination of research findings to past research participants and the community-at-large
Authors: Mayo-Gamble Tilicia L , Cunningham-Erves Jennifer , Kas-Osoka Chioma , Johnson George W , Frazier Nicole , Joosten Yvonne
Published: July 2021

Dissemination of research findings to past research participants and the community-at-large is a critical element to improving health outcomes, yet it is often overlooked by researchers. Few studies have explored how to provide study findings to the community, and no studies have investigated how community members can be involved in this process. This study explored views on the broad dissemination of research findings to community members and the role of the community in the dissemination process. We conducted a comparative analysis from the perspective of researchers, community members, and program officers (POs) from national health research funding agencies. Semistructured interviews were conducted with community members (African American, N = 10; Latino, N = 10), academic researchers (N = 10), and POs (N = 5). Thematic analysis was utilized in which codes and themes were created. One cross-cutting theme was identified, Views on Disseminating Research Findings to Communities. There were three additional themes identified among community members, five among researchers, and four among POs. All groups perceived the value of dissemination to communities as meaningful and ethical. Groups differed in their perceptions of prioritization of dissemination audiences. This study highlighted consensus on the value of broad dissemination to the community-at-large and identified areas of insufficiency in the translational research continuum that could be expanded or improved to ensure targeted groups receive the intended benefits of positive research findings. The long-term benefit of disseminating findings to the community-at-large is increased acceptability of interventions and reduced mistrust in research and researchers.
The Return of Asiatic Citrus Canker to Texas: Surveys and Eradication Efforts
Authors: Perez Emma , Kunta Madhurababu , Ancona Veronica , da Graça John V. , Ayin Caleb , Santillana Gem , Mavrodieva Vessela
Published: July 2021

Citrus canker caused by Xanthomonas citri subsp. citri (syn. X. axonopodis pv. citri) was first reported in South Texas during the early 1900s, prompting quarantine and eradication programs by the federal government. Its last reported incidence in Texas was from two trees from Corpus Christi in 1943. In May 2016, USDA Animal and Plant Health Inspection Service-Plant Protection and Quarantine (PPQ) confirmed the presence of the Asiatic A strain, which is by far the most widespread and severe form infecting most citrus varieties, on two sour orange trees in a park in Houston. Subsequently, infected trees were detected in a nursery in Richmond (Fort Bend Co.) in August 2016 and in dooryard trees in Pearland (Brazoria Co.) in 2018. PPQ and Texas Department of Agriculture collected a combined 1,949 positive A strain samples from Harris, Fort Bend, and Brazoria Counties during May 2016 to January 2021. These findings resulted in seven active citrus canker quarantine zones being established in the Upper Gulf Coast area. The Texas Department of Agriculture is removing positive trees, and surveys are continuing.
Comparison of Two Genome-Wide Association Studies for Heart Rate Response to Exercise from the UK Biobank
Authors: Thakral Abhinav , Paterson Andrew D.
Published: July 2021

The short-term changes in heart rate (HR) during and after exercise are important physiologic traits mediated via the autonomic nervous system. Variations in these traits are associated with mortality from cardiovascular causes. We conducted a systematic review of genome-wide association studies for these traits (with >10,000 participants) with the aim of comparing Polygenic Risk Scores (PRS) from different studies. Additionally, we applied theSTrengthening ofReporting ofGeneticAssociation Studies (STREGA) statement for assessing the completeness of reporting of evidence. Our systematic search yielded two studies (Verweij et al. and Ramirez et al.) that met our inclusion criteria. Both were conducted on the UK Biobank. Both defined their exercise traits as the difference between resting HR and the maximum HR during exercise. Their recovery traits were defined differently. Verweij et al. defined 5 recovery traits as the differences between the peak HR during exercise and the HRs at 10-50 sec post exercise cessation. Ramirez et al. defined their recovery trait as the difference between peak HR during exercise and the minimum HR during the minute post exercise cessation. While Ramirez et al. divided their sample into discovery and replication subsets, Verweij et al. analyzed the whole sample together. In terms of results, there were several common SNPs identified between studies and traits. There was evidence for the phenomenon of winner’s curse operating for a SNP from the Ramirez study’s HR recovery analysis. Many of the SNPs were mutually exclusive between the studies. However, there was a good agreement of PRS from the studies. The differences in the results could be attributed to the different exclusion criteria, analytic approaches, and definitions of traits used. Both studies had an under-representation of individuals of non-European ancestry compared to those of European ancestry. Further studies with proportionate representation of individuals of all ancestries would help address this gap.

Graphical Abstract
Assessing neuropathic pain in sickle cell disease: How useful is quantitative sensory testing?
Authors: Ramsay Zachary , Francis Damian , Bartlett Rachel , Ali Amza , Grant Justin , Gordon-Strachan Georgiana , Asnani Monika
Published: July 2021

Quantitative sensory testing (QST) is a psychophysical test of sensory function which may assist in assessing neuropathic pain (NP). This study compares QST findings with a standardized NP questionnaire to assess their agreement among Jamaicans with sickle cell disease (SCD). A cross sectional study consecutively recruited SCD patients 14 years and older, not pregnant, and without history of clinical stroke or acute illness in Kingston, Jamaica. QST identified thresholds for cold detection, heat detection, heat pain and pressure pain at the dominant thenar eminence, opposite dorsolateral foot and the subject’s most frequent pain site. The Douleur Neuropathique 4 (DN4) was interviewer-administered to diagnose NP. Subjects were divided into low and high sensitization groups if below the 5th and above the 95th percentiles, respectively on QST measures. Kappa agreement coefficients, and receiver operator characteristic (ROC) curves were performed to compare QST with the DN4. Two-hundred and fifty-seven SCD subjects were recruited (mean age 31.7 ± 12.2 years, 55.7% female, 75% SS genotype). Kappa agreements were fair (0.2-0.4) to good (0.6-0.8) between DN4 individual items of itching, hypoesthesia to touch, hypoesthesia to pinprick and brush allodynia with various QST sensitization groups. However, kappa agreements between the NP overall diagnosis on the DN4 with sensitization groups were poor (<0.2). Only heat detection (0.75) and heat pain (0.75) at the leg as a pain site showed satisfactory area under the curve (>0.7). QST may assist in assessing individual components of NP but its use should be limited as a tool to augment clinical assessments.
Serum Oxidative Stress Markers in Women with Uterine Fibroids in Lagos, Nigeria
Authors: Soibi-Harry Adaiah Priscillia , Makwe Christian Chigozie , Oluwole Ayodeji Ayotunde , Garba Sunusi Rimi , Ajayi Abisoye Towuromola , Anyanwu Roosevelt , Anorlu Rose Ihuoma
Published: July 2021

Background

Uterine fibroid is the most common benign gynaecological tumour in women of reproductive age group, with significant impact on the quality of life, economy, morbidity and sometimes mortality of affected women. Black women of reproductive age group are more likely to develop uterine fibroids. Although available evidence suggests racial and genetic predisposition to the aetiology of uterine fibroid, oxidative stress has been implicated in the onset and progression of uterine fibroids. Epidemiological and experimental studies have suggested that oxidative stress may play an important role in the pathogenesis of gynaecological diseases including uterine fibroids.

Aim and Objectives

This study aims to assess the serum levels of antioxidants (catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx)) and oxidants (protein carbonyl (PC), advanced oxidation protein products (AOPP)) in women with uterine fibroids and to identify any association between the size of uterine fibroids and serum levels of the analysed antioxidants and oxidants.

Methods

Forty-four women with ultrasound diagnosis of uterine fibroids and 44 women without uterine fibroids were recruited from a University Teaching Hospital. Blood samples were obtained and analysed for serum levels of selected antioxidants (CAT, SOD, GPx) and oxidants (PC, AOPP). Pelvic ultrasonography was performed on all study participants.

Results

The median serum levels of antioxidants: CAT (2.20 vs 4.32 ng/ml; p < 0.001); SOD (285.54 vs 380.96 ng/ml; p < 0.001) and GPx (9.67 vs 11.26 µU/ml; p < 0.001) were significantly lower in women with uterine fibroids. The median serum levels of oxidants: PC (162.08 vs 142.36 ng/ml; p = 0.04); and AOPP (22.42 vs 13.94 ng/ml; p < 0.001) were significantly higher in women with uterine fibroids. There was a strong negative correlation between serum levels of AOPP and SOD (r = -0.95; p < 0.001) in women with uterine fibroids. The maximum diameter of fibroids showed a significant positive correlation with AOPP (r = 1.000; p < 0.001) and a negative correlation with SOD (r = -1.000; p < 0.001).

Conclusion

Women with uterine fibroids had lower levels of antioxidants and higher levels of oxidants. In women with uterine fibroids, AOPP negatively correlated with SOD. There was a positive correlation between fibroid size and AOPP and a negative correlation between fibroid size and SOD. The findings of this study suggests that AOPP and SOD may play an important role in uterine fibroids.
Investigating Regional Specificity of Alzheimer’s Disease Pathology in the 5xFAD Mouse Model
Authors: Gyan Araba , Glass Emily D , Stevenson Tamara , Murphy Geoffrey G , Moore Shannon J
Published: July 2021

Alzheimer’s disease (AD) is a neurodegenerative disease that affects cognition and memory. Mouse models such as 5xFAD, incorporate mutations found in familial or early-onset (EOAD) AD; these mutations increase the production of the toxic AB species that contributes to plaque formation in the brain. However, not all brain regions in the 5xAD animals accumulate plaques to the same degree. For example, the cerebellum appears to be resistant to AB plaque formation, while other regions such as the cortex and subiculum develop copious plaques. The mechanism(s) underlying this regional specificity remains unclear. Thus, we used a fluorescent antibody to APP/AB to quantify the amount of these proteins in several brain regions of interest, including subiculum, cortex, and cerebellum. We found that the cerebellum had less APP/AB than the other regions quantified, which demonstrates a correlation between the levels of APP/AB and plaque formation. Taken together, this suggests that the regional specificity of AD pathology may be a result of different levels of protein expression.
Obtaining Spatially Resolved Tumor Purity Maps Using Deep Multiple Instance Learning In A Pan-cancer Study
Authors: Oner Mustafa Umit , Chen Jianbin , Revkov Egor , James Anne , Heng Seow Ye , Kaya Arife Neslihan , Alvarez Jacob Josiah Santiago , Takano Angela , Cheng Xin Min , Lim Tony Kiat Hon , Tan Daniel Shao Weng , Zhai Weiwei , Skanderup Anders Jacobsen , Sung Wing-Kin , Lee Hwee Kuan
Published: July 2021

Tumor purity is the proportion of cancer cells in the tumor tissue. An accurate tumor purity estimation is crucial for accurate pathologic evaluation and for sample selection to minimize normal cell contamination in high throughput genomic analysis. We developed a novel deep multiple instance learning model predicting tumor purity from H&E stained digital histopathology slides. Our model successfully predicted tumor purity from slides of fresh-frozen sections in eight different TCGA cohorts and formalin-fixed paraffin-embedded sections in a local Singapore cohort. The predictions were highly consistent with genomic tumor purity values, which were inferred from genomic data and accepted as the golden standard. Besides, we obtained spatially resolved tumor purity maps and showed that tumor purity varies spatially within a sample. Our analyses on tumor purity maps also suggested that pathologists might have chosen high tumor content regions inside the slides during tumor purity estimation in the TCGA cohorts, which resulted in higher values than genomic tumor purity values. In short, our model can be utilized for high throughput sample selection for genomic analysis, which will help reduce pathologists’ workload and decrease inter-observer variability. Moreover, spatial tumor purity maps can help better understand the tumor microenvironment as a key determinant in tumor formation and therapeutic response.
Behaviorally emergent hippocampal place maps remain stable during memory recall
Authors: Zemla Roland , Moore Jason J , Basu Jayeeta
Published: July 2021

The hippocampus is critical for the formation and recall of episodic memories1, 2which store past experience of events (‘what’) occurring at particular locations (‘where’) in time (‘when’). Hippocampal place cells, pyramidal neurons which show location-specific modulation of firing rates during navigation3, 4, together form a spatial representation of the environment. It has long been hypothesized that place cells serve as the neural substrate for long-term episodic memory of space5, 6. However, recent studies call to question this tenet of the field by demonstrating unexpected levels of representational drift in hippocampal place cells with respect to the duration of episodic memories in mice7, 8. In the present study, we examined behaviorally driven long-term organization of the place map, to resolve the relationship between memory and place cells. Leveraging the stability of two-photon calcium imaging, we tracked activity of the same set of CA1 pyramidal neurons during learning and memory recall in an operant, head-fixed, odorcued spatial navigation task. We found that place cells are rapidly recruited into task-dependent spatial maps, resulting in emergence of orthogonal as well as overlapping representations of space. Further, task-selective place cells used a diverse set of remapping strategies to represent changing task demands that accompany learning. We found behavioral performance dependent divergence of spatial maps between trial types occurs during learning. Finally, imaging during remote recall spanning up to 30 days revealed increased stabilization of learnt place cell maps following memory consolidation. Our findings suggest that a subset of place cells is recruited by rule based spatial learning, actively reconfigured to represent task-relevant spatial relationships, and stabilized following successful learning and consolidation.
Improved prediction of behavioral and neural similarity spaces using pruned DNNs
Authors: Tarigopula Homa Priya , Fairhall Scott Laurence , Hasson Uri
Published: July 2021

Deep Neural Networks (DNNs) have become an important tool for modeling brain and behaviour. One key area of interest has been to apply these networks to model human similarity judgements. Several previous works have used the embeddings from the penultimate layer of vision DNNs and showed that a reweighting of these features improves the fit between human similarity judgments and DNNs. These studies underline the idea that these embeddings form a good basis set but lack the correct level of salience. Here we re-examined the grounds for this idea and on the contrary, we hypothesized that these embeddings, beyond forming a good basis set, also have the correct level of salience to account for similarity judgments. It is just that the huge dimensional embedding needs to be pruned to select those features relevant for the considered domain for which a similarity space is modeled. In Study 1 we supervised DNN pruning based on a subset of human similarity judgments. We found that pruning:i) improved out-of-sample prediction of human similarity judgments from DNN embeddings,ii) produced better alignment with WordNet hierarchy, andiii) retained much higher classification accuracy than reweighting. Study 2 showed that pruning by neurobiological data is highly effective in improving out-of-sample prediction of brain-derived representational dissimilarity matrices from DNN embeddings, at times fleshing out isomorphisms not otherwise observable. Pruning supervised by human brain/behavior therefore effectively identifies alignable dimensions of semantic knowledge between DNNs and humans and constitutes an effective method for understanding the organization of knowledge in neural networks.
Multi-morph eco-evolutionary dynamics in structured populations
Authors: Lion Sébastien , Boots Mike , Sasaki Akira
Published: July 2021

Our understanding of the evolution of quantitative traits in nature is still limited by the challenge of including realistic trait distributions in the context of frequency-dependent selection and ecological feedbacks. We extend to class-structured populations a recently introduced “oligomorphic approximation” which bridges the gap between adaptive dynamics and quantitative genetics approaches and allows for the joint description of the dynamics of ecological variables and of the moments of multimodal trait distributions. Our theoretical framework allows us to analyse the dynamics of populations composed of several morphs and structured into distinct classes (e.g. age, size, habitats, infection status, species…). We also introduce a new approximation to simplify the eco-evolutionary dynamics using reproductive values. We illustrate the effectiveness of this approach by applying it to the important conceptual case of two-habitat migration-selection models. In particular, we show that our approach allows us to predict both the long-term evolutionary endpoints and the short-term transient dynamics of the eco-evolutionary process, including fast evolution regimes. We discuss the theoretical and practical implications of our results and sketch perspectives for future work.
Curcumin micronization by supercritical fluid:in vitroandin vivobiological relevance
Authors: Sachett Adrieli , Gallas-Lopes Matheus , Benvenutti Radharani , Marcon Matheus , Aguiar Gean Pablo S. , Herrmann Ana Paula , Oliveira J. Vladimir , Siebel Anna M. , Piato Angelo
Published: July 2021

Curcumin, a polyphenol extracted from the rhizome ofCurcuma longaL. (Zingiberaceae), is shown to have antioxidant, anti-inflammatory, neuroprotective, anxiolytic, and antidepressant properties in both preclinical and clinical studies. However, its low bioavailability is a limitation for its potential adoption as a therapeutic agent. The process of micronization can overcome this barrier by reducing the particle size and increasing the dissolution rate, potentially improving the bioavailability of the compounds of interest. In this study, we compared thein vitroantioxidant effects of curcumin (CUR) and micronized curcumin (MC) and studied their effects on behavioral and neurochemical parameters in zebrafish submitted to unpredictable chronic stress (UCS). MC (1 g/L) presented higher antioxidant activityin vitroas compared to CUR, as measured by iron-reducing antioxidant power (FRAP), 1,1-diphenyl-2-2-picyryl-hydrazyl radical removal (DPPH), and deoxyribose tests. UCS increased total distance traveled in the social interaction test (SI), while decreased crossings, time, and entries to the top area in the novel tank test (NTT). No effects of UCS were observed in the open tank test (OTT). The behavioral effects induced by UCS were not blocked by any curcumin preparation. UCS also decreased non-protein thiols (NPSH) levels, while increased glutathione reductase (GR) activity and thiobarbituric acid reactive substances (TBARS) levels on zebrafish brain. MC presented superior antioxidant properties than CURin vivo, blocking the stress-induced neurochemical effects. Although this study did not measure the concentration of curcumin on the zebrafish brain, our results suggest that micronization increases the bioavailability of curcumin, potentiating its antioxidant activity bothin vitroandin vivo. Our study also demonstrates that counteracting the oxidative imbalance induced by UCS is not sufficient to block its behavioral effects.
Phylotranscriptomics reveals discordance in the phylogeny of HawaiianDrosophilaandScaptomyza(Diptera: Drosophilidae)
Authors: Church Samuel H. , Extavour Cassandra G.
Published: July 2021

Island radiations present natural laboratories for studying the evolutionary process. The Hawaiian Drosophil-idae are one such radiation, with nearly 600 described species and substantial morphological and ecological diversification. These species are largely divided into a few major clades, but the relationship between these clades remains uncertain. Here we present 12 new assembled transcriptomes from across these clades, and use these transcriptomes to resolve the base of the evolutionary radiation. We recover a new hypothesis for the relationship between clades, and demonstrate its support over previously published hypotheses. We then use the evolutionary radiation to explore dynamics of concordance in phylogenetic support, by analyzing the gene and site concordance factors for every possible topological combination of major groups. We show that high bootstrap values mask low evolutionary concordance, and we demonstrate that the most likely topology is distinct from the topology with the highest support across gene trees and from the topology with highest support across sites. We then combine all previously published genetic data for the group to estimate a time-calibrated tree for over 300 species of drosophilids. Finally, we digitize dozens of published Hawaiian Drosophilidae descriptions, and use this to pinpoint probable evolutionary shifts in reproductive ecology as well as body, wing, and egg size. We show that by examining the entire landscape of tree and trait space, we can gain a more complete understanding of how evolutionary dynamics play out across an island radiation.
Flexible utilization of spatial- and motor-based codes for the storage of visuo-spatial information
Authors: Henderson Margaret , Rademaker Rosanne L. , Serences John T.
Published: July 2021

Working memory provides flexible storage of information in service of upcoming behavioral goals. Some models propose specific fixed loci and mechanisms for the storage of visual information in working memory, such as sustained spiking in parietal and prefrontal cortex during working memory maintenance. An alternative view is that information can be remembered in a flexible format that best suits current behavioral goals. For example, remembered visual information might be stored in sensory areas for easier comparison to future sensory inputs, or might be re-coded into a more abstract action-oriented format and stored in motor areas. Here, we tested this hypothesis using a visuo-spatial working memory task where the required behavioral response was either known or unknown during the memory delay period. Using fMRI and multivariate decoding, we found that there was less information about remembered spatial position in early visual and parietal regions when the required response was known versus unknown. Further, a representation of the planned motor action emerged in primary somatosensory, primary motor, and premotor cortex during the same task condition where spatial information was reduced in early visual cortex. These results suggest that the neural networks supporting working memory can be strategically reconfigured depending on specific behavioral requirements during a canonical visual working memory paradigm.
Dimensionality reduction and data integration for scRNA-seq data based on integrative hierarchical Poisson factorisation
Authors: Wong Thomas , Barahona Mauricio
Published: July 2021

Single-cell RNA sequencing (scRNA-seq) data sets consist of high-dimensional, sparse and noisy feature vectors, and pose a challenge for classic methods for dimensionality reduction. Such problems are compounded when dealing with composite data sets formed by different batches. We introduce Integrative Hierarchical Poisson Factorisation (IHPF), an extension of HPF that makes use of a noise ratio hyper-parameter to tune the variability attributed to batches vs. biological sources (cell phenotypes). We exemplify the application of IHPF under different data integration scenarios with varying alignments of batches and cell diversity, and show that IHPF produces latent factors that can be advantageously applied for cell clustering and visualisation. In addition, the extracted factors have a dual block structure in both cell and gene spaces with enhanced biological interpretability.
Cell-type specific transcriptional adaptations of nucleus accumbens interneurons to amphetamine
Authors: Gallegos David A. , Minto Melyssa , Liu Fang , Hazlett Mariah F. , Yousefzadeh S. Aryana , Bartelt Luke C. , West Anne E.
Published: July 2021

Parvalbumin-expressing (PV+) interneurons of the nucleus accumbens (NAc) play an essential role in the addictive-like behaviors induced by psychostimulant exposure. To identify molecular mechanisms of PV+ neuron plasticity, we isolated interneuron nuclei from the NAc of male and female mice following acute or repeated exposure to amphetamine (AMPH) and sequenced for cell type-specific RNA expression and chromatin accessibility. AMPH regulated the transcription of hundreds of genes in PV+ interneurons, and this program was largely distinct from that regulated in other NAc GABAergic neurons. Chromatin accessibility at enhancers predicted cell-type specific gene regulation, identifying transcriptional mechanisms of differential AMPH responses. Finally, we observed dysregulation of multiple PV-specific, AMPH-regulated genes in an Mecp2 mutant mouse strain that shows heightened behavioral sensitivity to psychostimulants, suggesting the functional importance of this transcriptional program. Together these data provide novel insight into the cell-type specific programs of transcriptional plasticity in NAc neurons that underlie addictive-like behaviors.