bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexual behaviors and function during menopausal transition—does menopausal hormonal therapy play a role?
Authors: Nowosielski Krzysztof , Sidorowicz Marcin
Published: December 2020

Objectives:

The menopausal transition is a biological adaptation to the variety of life changes (body, comorbidities, relationship), but that biology is not an “end all” in the context of sexual function and overall sexual health. The aim of this study is to evaluate determinants altering the risk of female sexual dysfunction (FSD) and other sexual problems and to establish whether menopausal hormonal therapy (MHT) decreases that risk and modifies sexual behaviors.

Methods:

A cross-sectional observational study was conducted in 210 women between the ages of 45 and 55. Two groups were identified: MHT users (n = 107) and controls—MHT non-users (n = 103). Diagnostic and Statistical Manual of Mental Disorders -five criteria were used to assess sexual dysfunction. Sexual problems were evaluated by the Changes in Sexual Function Questionnaire (CSFQ), body image by Body Exposure during Sexual Activity Questionnaire, and quality of relationship by the Well-Match Relationship Questionnaire. Logistic regression was used to determine the risk factors for FSD and sexual problems.

Results:

Women using MHT had higher body esteem during sexual activities, better sexual function (CSFQ) in all domains except desire/interest, better quality of relationship, and lower prevalence of FSD and sexual complaints (CSFQ) except arousal/excitement problems. However, self-rated effects of MHT on sexual behaviors showed that MHT did not play a major role. Women with secondary and higher education (OR = 0.09, CI: 0.02-0.4; P < 0.01 and OR = 0.2, CI: 0.05-1.0; P < 0.05, respectively) and with a higher number of lifetime sexual partners (OR = 0.6, CI: 0.4-0.9; P < 0.01) were less likely to have FSD. In contrast, individuals with more anxious behaviors during sexual activity (OR = 3.2, CI: 1.3-7.3; P < 0.01) and with more severe menopausal symptoms (OR = 1.1, CI: 1.0-1.2; P < 0.001) were more likely to have FSD. Using MHT was not associated with that risk nor with sexual function.

Conclusion:

In women during menopausal transition, sexual behaviors were different in MHT users compared with non-users. However, in this cross-sectional observational study conducted in 210 women between the ages of 45 to 55 years, using MHT was not associated with modification of sexual function, decreasing the risk of sexual dysfunction, nor sexual problems.

Video Summary:

http://links.lww.com/MENO/A688.
Inverse association between dietary fiber intake and depression in premenopausal women: a nationwide population-based survey
Authors: Kim Yunsun , Hong Minseok , Kim Seonah , Shin Woo-young , Kim Jung-ha
Published: December 2020

Objective:

Depression is among the most common neuropsychiatric disorders, and its prevalence is twofold higher in women than in men. This study aimed to investigate the relationship between dietary fiber intake and depression in women by menopause status using data from a nationwide population-based survey conducted in Korea.

Methods:

We utilized the Korea National Health and Nutritional Examination Survey data for 2014, 2016, and 2018 with a complex sampling design. Dietary fiber intake was calculated according to the 24-hour recall method, and we used Patient Health Questionnaire-9 scores to assess depression. A t test based on the general linear model was used to compare mean dietary fiber intake according to the presence of depression by menopause status. A logistic regression analysis was conducted to compute the odds ratio for depression according to the gradually adjusted model.

Results:

This study included 5,807 women. Among the premenopausal women, dietary fiber intake was higher in the nondepression group than in the depression group (P < 0.001), while there was no significant difference among postmenopausal women. Accordingly, among the premenopausal women, a significantly inverse relationship was observed between a change in daily dietary fiber intake as 1 g/1,000 kcal and the prevalence of depression in the fully adjusted model with an odds ratio of 0.949 (95% confidence interval, 0.906-0.993; P = 0.03). However, among the postmenopausal women, this significant association was not observed.

Conclusions:

Dietary fiber intake was inversely associated with depression in premenopausal but not postmenopausal women.
Trabecular Microbypass Stent and Phacoemulsification in African American Patients With Open-angle Glaucoma: Outcomes and Effect of Prior Laser Trabeculoplasty
Authors: Bargoud Albert R. , Lira Jennifer , An Selena , Walsman Scott M. , Herndon Leon W. , Khouri Albert S.
Published: December 2020

Precis:

In African American patients with glaucoma, iStent/phacoemulsification lowered intraocular pressure and reduced glaucoma medication usage for up to 1 year, even in patients with prior selective laser trabeculoplasty (SLT).

Purpose:

Currently, no studies have examined the outcomes of a trabecular microbypass stent and phacoemulsification in African American patients. Here, the authors investigate whether iStent/phacoemulsification decreases intraocular pressure (IOP) and/or medication usage in African American patients with glaucoma. They are also interested in whether prior SLT would affect outcomes of iStent/phacoemulsification.

Patients and Methods:

A multicenter, retrospective case series of eyes that underwent iStent/phacoemulsification between 2013 and 2017 with up to 1-year follow-up. Eyes with a confirmed diagnosis of glaucoma in African American patients were included. Eyes with neovascular glaucoma or closed angle glaucoma and eyes that underwent previous incisional glaucoma surgery were excluded.

Results:

Eighty-nine eyes were included in the study and data for 66 eyes were available at postoperative year 1 (POY1). IOP decreased from 18.3±5.7 mm Hg to 15.9±4.6 (P<0.001) and glaucoma medication usage decreased from 1.9±1.1 to 1.1±1.1 (P<0.001) at POY1. Eyes that underwent prior SLT experienced less of a decrease in IOP when compared with eyes without prior SLT, but IOP at POY1 was not significantly different between these groups. Both groups had a similar reduction in medication usage. The most common complications were IOP spikes on postoperative day 1 and microhyphemas.

Conclusions:

In this cohort, there was a significant decrease in IOP and medication usage 1 year after iStent/phacoemulsification. iStent/phacoemulsification is an effective and safe treatment option in African American patients with glaucoma.
Evaluation of Spin in the Abstracts of Systematic Reviews and Meta-analyses of Treatments for Glaucoma
Authors: Okonya Ochije , Lai Elaine , Ottwell Ryan , Khattab Mostafa , Arthur Wade , Khaimi Mahmoud A. , Wright Drew N. , Hartwell Micah , Vassar Matt
Published: December 2020

Purpose:

Spin—the misrepresentation of the study’s actual findings—carries the ability to distort a reader’s perception of a treatments’ full benefits and risks. Recent studies have suggested that spin is common in abstracts of randomized controlled trials and systematic reviews focused on treatments for a variety of medical disorders. Therefore, our primary objective was to evaluate the prevalence of spin in the abstracts of systematic reviews and meta-analyses related to glaucoma treatments. We further assessed whether specific study characteristics were associated with spin, including the methodological quality of a study.

Patients and Methods:

We used a cross-sectional study design searching MEDLINE and Embase databases all for systematic reviews and meta-analyses focused on glaucoma treatments. Each abstract was assessed for the 9 most severe—severity determined by the likelihood of distorting a reader’s perception—types of spin that occur in systematic review abstracts. The screening and data extraction was performed in a duplicate, masked fashion. The methodological quality of each review was assessed using the A MeaSurement Tool to Assess Systematic Reviews (AMSTAR-2) instrument. To evaluate relationships between spin, AMSTAR-2 appraisals, and other study characteristics, we used unadjusted odds ratios and the Fisher exact test.

Results:

Only 3 of the 102 abstracts contained spin, with spin type 5 being the most prevalent. No abstracts contained spin types 1, 2, 3, 4, 6, or 8, and no association was found between the presence of spin in an abstract and any particular study characteristic. Using the AMSTAR-2 quality appraisal instrument, 35 (34.3%) of the studies received a methodological quality rating as high, 42 (41.2%) as moderate, 11 (10.8%) as low, and 14 (13.7%) as critically low.

Conclusions:

We found that spin is present in only a small proportion of systematic reviews and meta-analyses covering the treatment of glaucoma. In comparison to studies in other fields of medicine, ophthalmology appears to be a leader in publishing systematic reviews and meta-analyses with low rates of spin occurring in the abstract.
Metabolic effects of cross-sex hormone therapy in transgender individuals in Taiwan
Authors: Liu Yu-Hsien , Wu Tsung-Hui , Chu Chia-Huei , Lin Yi-Chun , Lin Liang-Yu
Published: December 2020

Background:

Transgender individuals often require gender-affirming interventions, such as endogenous sex hormone inhibition or gender-affirming hormone therapy (HT), while there is discordance between their body and gender identity. However, a recent study found that the incidence of cardiovascular events is higher in transgender patients receiving cross-sex HT. The aim of this study was to investigate the metabolic effects of an altered sex hormone profile.

Methods:

This retrospective study, conducted in a referral center in Northern Taiwan, analyzed metabolic changes over time in 65 trans masculine and 45 trans feminine persons. The transgender individuals were examined at 4 time points: before the gender affirming HT, as well as 3, 6, and 12 months following treatment.

Results:

Compared with baseline measurements, the trans masculine patients showed significant increases in body mass index (BMI) (22.6 ± 0.3 vs 23.3 ± 0.4 kg/m2; p < 0.001; t = 3M), low-density lipoprotein cholesterol (124.3 ± 3.7 vs 131.3 ± 3.9 mg/dL; p = 0.03; t = 12M), creatinine (0.75 ± 0.01 vs 0.83 ± 0.14 mg/dL; p < 0.001; t = 12M), and hemoglobin (13.5 ± 0.7 vs 15.2 ± 0.2 g/dL; p < 0.001; t = 12M), as well as decreased high-density lipoprotein cholesterol (57 ± 2.1 vs 51 ± 2.0 mg/dL; p < 0.001; t = 12M). The trans feminine patients had reduced low-density lipoprotein cholesterol (104.2 ± 3.2 vs 100.8 ± 3.5 mg/dL; p = 0.05; t = 3M), hemoglobin (14.0 ± 0.1 vs 13.5 ± 0.1 g/dL; p = 0.008; t = 12M), and creatinine (0.82 ± 0.01 vs 0.79 ± 0.14 mg/dL; p < 0.001; t = 3M) compared with baseline data. In addition, most of these metabolic effects persisted during the follow-up period.

Conclusion:

This observational, retrospective study revealed that gender-affirming HT increased the relative cardiovascular risk in trans masculine individuals.
The application of a 70° endoscope in performing transcanal middle ear surgery
Authors: Ting Kuan-Chung , Tu Tzong-Yang
Published: December 2020

Background:

Endoscopes increase the expediency of transcanal middle ear surgery. However, the application of a 70° endoscope is limited and seldom discussed, mainly because of its large angle. We introduce our experiences with the 70° endoscope in transcanal middle ear surgery.

Methods:

This is a retrospective chart review of 127 patients with chronic otitis media who underwent middle ear surgery performed by the senior author in 2016 at a tertiary referral center. The types of eardrum perforation were classified as central, inferior, posterior, or anterior according to the main location of the hole. The demographics, surgical pictures, and operative records were reviewed.

Results:

In 15 ears of the 127 patients, the ossicles were recognized directly by a microscope. In another 112 ears, the ossicles could not be identified under a microscope. Without elevating the tympanomeatal flap, the ossicles could be recognized in 72 of these 112 ears with endoscopes, especially the 70° endoscope. In 35 of these 112 ears, an incision to extend the drum perforation or creation of a small tympanomeatal flap in the posterior-superior canal was made to observe the ossicles. However, 5 of these 112 ears were still noted to have a narrow and/or curved ear canal and preoperatively needed to undergo endaural incisions. Among the other 122 patients who first underwent attempted transcanal surgery, 15 ears changed to endaural incisions. The drum perforations were repaired directly through the perforation in 107 ears via the transcanal route. One year after surgery, the air-bone gap closure was 16.0 ± 11.8 dB, and the graft take rate was 91.3%.

Conclusion:

With the help of a 70° endoscope, we can use the transcanal transperforation route to evaluate and reconstruct drum perforations and ossicular chains in appropriate patients. Hence, normal tissue injuries to the ear canal can be minimized.
A Physician's Guide for Workers’ Return to Work During COVID-19 Pandemic
Authors: Baptista Marcos C. , Burton Wayne N. , Pawlecki Brent , Pransky Glenn
Published: December 2020

Objective:

Higher probability of developing severe COVID-19 has been associated with health risk factors and medical conditions which are common among workers globally. For at risk workers, return to work may require additional protective policies and procedures.

Methods:

A review of the medical literature was conducted on health risk factors and medical conditions associated with increased COVID-19 morbidity and mortality, standardized measures for community COVID transmission, and occupation-specific risk.

Results:

The relative risk of acquiring and the severity of COVID-19 for workers is associated with three pillars: individual risk, workplace risk, and community risk. Matrices were developed to determine a worker's individual risk based on these three pillars.

Conclusions:

A practical decision tool is proposed for physicians evaluating and managing individual worker COVID-19 risk in the context of returning to work.
Failure and Revision Surgery After Cochlear Implantation in the Adult Population: A 10-year Single-institution Retrospective and Systematic Review of the Literature
Authors: Layfield Eleanor , Hwa Tiffany Peng , Naples James , Maina Ivy , Brant Jason A. , Eliades Steven J. , Bigelow Douglas C. , Ruckenstein Michael J.
Published: December 2020

Objective:

To characterize failure rate and etiology after cochlear implantation; to identify predictors and describe outcomes after implant failure.

Study Design:

Retrospective chart review and systematic review of the literature using PubMed and Embase.

Setting:

Academic Cochlear Implant Center.

Subject Population:

Four hundred ninety-eight devices in 439 distinct adult patients.

Interventions:

Unilateral or bilateral cochlear implantation.

Main Outcome Measures:

Implant failure rate and etiology.

Results:

A total of 32 devices (5.9%) failed in 31 patients encompassing the following failure types in accordance with the European Consensus Statement of Cochlear Implants: 17 device failures (53.1%), 11 failures due to performance decrement/adverse reactions (34.4%), and 4 medical reasons (12.9%). There was no significant difference in age, sex, or manufacturer between patients with and without failures. Twenty-five percent of patients with failure leading to explantation had childhood onset of deafness compared to 12.1% of patients with adult-onset hearing loss (OR = 2.42; p = 0.04). Performance decrement/adverse reaction patients had an older average age at implantation compared to device failure patients (mean 68.5 yr 95% CI: 59.9–77.1 vs mean 47.6 yr, CI: 39.9–55.3, p < 0.01). There was no significant difference in time to failure, sex, or device manufacturer between the different types of failures. Twenty-nine patients who experienced CI failure underwent a revision surgery, while the remaining two opted for explantation without reimplantation. One patient who underwent revision surgery subsequently presented with a second failure and underwent a second revision, which was successful.

In our systematic review, 815 citations were reviewed, and 9 studies were selected for inclusion. Overall failure rate across all studies was 5.5%. Device failure was the leading cause of failure in the majority (6/9) of studies, accounting for 40.8% of all failures. Medical reasons were the second leading cause at 33.6%, followed by performance decrement/adverse reaction (20.9%) and other (4.8%).

Conclusions:

Cochlear implant failure is a rare phenomenon. Childhood-onset of hearing loss appears to be associated with an increased risk of overall failure. Older patients are at increased risk for performance decrement/adverse reaction. Revision surgery success rates remain very high and patients with failure of any cause should be offered explantation with concurrent reimplantation.
Reliability of Primary Health Care Audiograms by Non-qualified Examiners—An Analysis of 1,224 Cases
Authors: Kokkonen Jukka , Varonen Sini
Published: December 2020

Objective:

To evaluate the accuracy of primary health care audiograms conducted by non-qualified examiners in a non-standard acoustic environment.

Study Design:

Retrospective chart review.

Setting:

Referring primary health care institutions and hospital hearing center.

Patients:

One thousand two hundred twenty four adult patients evaluated for hearing aid fitting at North Karelia Central hospital in years 2017 and 2018.

Main Outcome Measures:

Intraclass correlation coefficient (ICC), mean threshold differences, and mean absolute errors were used to assess agreement between primary health care and hospital audiograms. Primary health care audiometry sensitivity, specificity and positive (PPV) and negative (NPV) predictive values were calculated for hearing aid candidacy in general and open ear mold candidacy in particular.

Results:

ICC for both better ear hearing level (BEHL0.5,1,2,4 
kHz) and pure-tone average (PTA0.5,1,2,4 
kHz) in frequencies 0.5, 1, 2, and 4 kHz was 0.82, and in individual full octave frequencies from 0.125 to 8 kHz ranged from 0.70 to 0.83. Mean threshold differences in BEHL0.5,1,2,4 
kHz and PTA0.5,1,2,4 
kHz were 1.8 and 1.6 dB and mean absolute errors 4.9 and 5.3 dB, respectively. Sensitivity for hearing aid candidacy was 0.97, specificity 0.58, PPV 0.92, and NPV 0.79.

Conclusions:

Primary health care audiometry is reasonably accurate, allowing preselection of patients to adequate hearing care pathways.
Impact of COVID-19 related unemployment on increased cardiovascular disease in a high-income country: Modeling health loss, cost and equity
Authors: Nghiem Nhung , Wilson Nick
Published: December 2020

Background

Cardiovascular disease (CVD) is a leading cause of health loss and health sector economic burdens in high-income countries. Unemployment is associated with increased risk of CVD, and so there is concern that the economic downturn associated with the COVID-19 pandemic will increase the CVD burden.

Aims

This modeling study aimed to quantify health loss, health cost burden and health inequities among people with CVD due to additional unemployment caused by COVID-19 pandemic-related economic disruption in one high-income country: New Zealand (NZ).

Methods

We adapted an established and validated multi-state life-table model for CVD in the national NZ population. We modeled indirect effects (ie, higher CVD incidence due to high unemployment rates) for various scenarios of pandemic-related unemployment projections.

Results

We estimated the CVD-related heath loss in NZ to range from 23,300 to 36,900 HALYs (health-adjusted life years) for the different unemployment scenarios. Health inequities for Māori (Indigenous population) were 3.7 times greater compared to non-Māori (49.9 vs 13.5 HALYs lost per 1000 people).

Conclusions and policy implications

Unemployment due to the COVID-19 pandemic is likely to cause significant health loss and health inequities from CVD in this high-income country. Prevention measures should be considered by governments to reduce this risk, including job creation programs and measures directed towards CVD prevention.
Epidemiological feature, viral shedding, and antibody seroconversion among asymptomatic SARS-CoV-2 carriers and symptomatic/presymptomatic COVID-19 patients
Authors: Chen Yi , Li Ping , Ding Yi-Bo , Liu Miao , Liu Lei-Jie , Yi Bo , Wu Ting , Dong Hong-Jun , Lao Xu-Ying , Ding Ke-Qing , Wang Hai-Bo , Zhang Dong-Liang , Tan Xiao-Jie , Wang Zhong-Fa , Xu Guo-Zhang , Cao Guang-Wen
Published: December 2020

Novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pandemic. However, data concerning the epidemiological features, viral shedding, and antibody dynamics between asymptomatic SARS-CoV-2 carriers and COVID-19 patients remain controversial. We enrolled 193 subjects infected with SARS-CoV-2 in Ningbo and Zhoushan, Zhejiang, China from January 21 to March 6, 2020. All subjects were followed up to monitor the dynamics of immunoglobulin M (IgM) and IgG against SARS-CoV-2. Of those, 31 were asymptomatic carriers, 149 were symptomatic patients, and 14 were presymptomatic patients. Compared to symptomatic patients, asymptomatic carriers were younger and had higher levels of white blood cell and lymphocyte, lower levels of C-reactive protein and viral load, and shorter viral shedding duration. Conversion of IgM from positive to negative was shorter in asymptomatic carriers than in COVID-19 patients (P=0.030). The proportion of those persistently seropositive for IgG was higher in COVID-19 patients than in asymptomatic carriers (P=0.037). Viral load was higher in symptomatic than presymptomatic patients. Viral shedding was longer in presymptomatic patients than in asymptomatic carriers. Conclusively, asymptomatic carriers have a higher antiviral immunity to clear SARS-CoV-2 than do symptomatic patients and this antiviral immunity is not contributable to humoral immunity.
Simple biochemical features underlie transcriptional activation domain diversity and dynamic, fuzzy binding to Mediator
Authors: Sanborn Adrian L. , Yeh Benjamin T. , Feigerle Jordan T. , Hao Cynthia V. , Townshend Raphael J. L. , Aiden Erez Lieberman , Dror Ron O. , Kornberg Roger D.
Published: December 2020

Gene activator proteins comprise distinct DNA-binding and transcriptional activation domains (ADs). Because few ADs have been described, we tested domains tiling all yeast transcription factors for activationin vivoand identified 150 ADs. By mRNA display, we showed that 73% of ADs bound the Med15 subunit of Mediator, and that binding strength was correlated with activation. AD-Mediator interactionin vitrowas unaffected by a large excess of free activator protein, pointing to a dynamic mechanism of interaction. Structural modeling showed that ADs interact with Med15 without shape complementarity (“fuzzy” binding). ADs shared no sequence motifs, but mutagenesis revealed biochemical and structural constraints. Finally, a neural network trained on AD sequences accurately predicted ADs in human proteins and in other yeast proteins, including chromosomal proteins and chromatin remodeling complexes. These findings solve the longstanding enigma of AD structure and function and provide a rationale for their role in biology.
Modeling the flow of the COVID-19 in Germany: The efficacy of lockdowns and social behavior
Authors: Bahri Muhamad Khairul
Published: December 2020

This study develops a computer simulation in understanding the flow of the COVID-19 in Germany between January 2020 and July 2020. This aims to analyze not only the flow of the COVID-19 but also the efficacy of taken measures during the given period. The computer model is based on the SEIR concept and it is based on the system dynamics approach in which some uncertain parameters are estimated through the calibration process. Moreover, the SEIR computer model is developed by considering different flows of COVID-19 cases in older and young people in Germany. This study successfully reproduces similar patterns of infected, recovered, and death cases. Moreover, as the SEIR model can successfully reproduce similar patterns, the SEIR model can be a basis to estimate other resources such as health workers, and bed capacities.
Independent human mesenchymal stromal cell-derived extracellular vesicle preparations differentially affect symptoms in an advanced murine Graft-versus-Host-Disease model
Authors: Madel Rabea J. , Börger Verena , Dittrich Robin , Bremer Michel , Tertel Tobias , Phuong Nhi Ngo Thi , Baba Hideo A. , Kordelas Lambros , Buer Jan , Horn Peter A. , Westendorf Astrid M. , Brandau Sven , Kirschning Carsten J. , Giebel Bernd
Published: December 2020

Extracellular vesicles (EVs) harvested from cell culture supernatants of human mesenchymal stromal cells (MSCs) suppress acute inflammation in preclinical models of various diseases. Furthermore, they promote regeneration of damaged tissues. Following successful clinical treatment of a steroid-refractory Graft-versus-Host-Disease (GvHD) patient with EVs prepared from conditioned media of human bone marrow (BM)-derived MSCs, we aim to improve MSC-EV production and quality control towards clinical application. Observing functional differences of independent MSC-EV preparationsin vitro, we established an optimized murine GvHD model for the analysis of independent MSC-EV preparationsin vivo. To this end, T cell depleted allogeneic BM cells co-transplanted with naïve allogeneic spleen-derived T cells induced GvHD symptoms with reproducible strengths in mice being preconditioned by ionizing irradiation. Administration of MSC-EV preparations with confirmedin vitroimmune modulatory properties at three consecutive days significantly suppressed GvHD symptoms. In contrast, application of MSC-EV preparations lacking thesein vitroimmune modulating capabilities failed to suppress GvHD symptoms. Thus, our results reveal therapeutic differences among independent MSC-EV preparations that had been produced in a standardized manner. Thus, given this functional heterogeneity, any individual MSC-EV preparation considered for the clinical application should be evaluated for its potency prior to administration to patients.
An introduction to thermodynamic integration and application to dynamic causal models
Authors: Aponte Eduardo A. , Yao Yu , Raman Sudhir , Frässle Stefan , Heinzle Jakob , Penny Will D. , Stephan Klaas E.
Published: December 2020

In generative modeling of neuroimaging data, such as dynamic causal modeling (DCM), one typically considers several alternative models, either to determine the most plausible explanation for observed data (Bayesian model selection) or to account for model uncertainty (Bayesian model averaging). Both procedures rest on estimates of the model evidence, a principled trade-off between model accuracy and complexity. In the context of DCM, the log evidence is usually approximated using variational Bayes. Although this approach is highly efficient, it makes distributional assumptions and is vulnerable to local extrema. This paper introduces the use of thermodynamic integration (TI) for Bayesian model selection and averaging in the context of DCM. TI is based on Markov chain Monte Carlo sampling which is asymptotically exact but orders of magnitude slower than variational Bayes. In this paper, we explain the theoretical foundations of TI, covering key concepts such as the free energy and its origins in statistical physics. Our aim is to convey an in-depth understanding of the method starting from its historical origin in statistical physics. In addition, we demonstrate the practical application of TI via a series of examples which serve to guide the user in applying this method. Furthermore, these examples demonstrate that, given an efficient implementation and hardware capable of parallel processing, the challenge of high computational demand can be overcome successfully. The TI implementation presented in this paper is freely available as part of the open source software TAPAS.

Author summary

When fitting computational models to data in the setting of Bayesian inference, a user has the choice between two broad classes of algorithms: variational inference and Monte Carlo simulation. While both methods have advantages and drawbacks, variational inference has become standard in the domain of modelling directed brain connectivity due to its computational efficiency, especially when the challenges to select between competing hypotheses that explain the observed data. By contrast, the high computational demand by Monte Carlo methods has so far prevented their widespread use for inference on brain connectivity, despite their capability to overcome some of the shortcomings of variational inference. In this paper, we introduce the user to thermodynamic integration (TI), a Monte Carlo method designed for model fitting and model selection. By covering its foundations and historical origins in statistical physics, we hope to convey an in-depth understanding of TI that goes beyond a purely technical treatment. In addition, we also provide examples for concrete applications, demonstrating that, given an efficient implementation and up-to-date hardware, the challenge of high computational demand can be overcome successfully.
DENT-seq for genome-wide strand-specific identification of DNA single-strand break sites with single-nucleotide resolution
Authors: Elacqua Joshua J. , Ranu Navpreet , DiIorio Sarah E. , Blainey Paul C.
Published: December 2020

DNA single-strand breaks (SSBs), or “nicks,” are the most common form of DNA damage. Oxidative stress, endogenous enzyme activities, and other processes cause tens of thousands of nicks per cell per day. Accumulation of nicks, caused by high rates of occurrence or defects in repair enzymes, has been implicated in multiple diseases. However, improved methods for nick analysis are needed to characterize the mechanisms of these processes and learn how the location and number of nicks affect cells, disease progression, and health outcomes. In addition to natural processes, including DNA repair, leading genome editing technologies rely on nuclease activity, including nick generation, at specific target sites. There is currently a pressing need for methods to study off-target nicking activity genome-wide to evaluate the side effects of emerging genome editing tools on cells and organisms. Here, we developed a new method, DENT-seq, for efficient strand-specific profiling of nicks in complex DNA samples with single-nucleotide resolution and low false-positive rates. DENT-seq produces a single deep sequence data set enriched for reads near nick sites and establishes a readily detectable mutational signal that allows for determination of the nick site and strand with single-base resolution at penetrance as low as one strand per thousand. We apply DENT-seq to profile the off-target activity of the Nb.BsmI nicking endonuclease and an engineered spCas9 nickase. DENT-seq will be useful in exploring the activity of engineered nucleases in genome editing and other biotechnological applications as well as spontaneous and therapeutic-associated strand breaks.
1,2-O-Isopropylidene-β-D-lyxo-furanose
Authors: Doboszewski Bogdan , Nazarenko Alexander Y.
Published: December 2020

In the title compound C8H14O5, the pentofuranose five-membered ring has a twisted conformation on two carbon atoms while the five-membered ring of the isopropylidene group has an envelope conformation on an oxygen atom. Hydroxy groups are involved an infinite network of O—H...O hydrogen bonds that leads to the formation of a layer parallel to the (001) plane. Only weak C—H...O contacts exist between neighboring layers.
Naphthalen-1-ylmethanol
Authors: Nazarenko Alexander Y.
Published: December 2020

Apart from the OH group, the molecule of the title compound, C11H10O, is almost planar with all carbon atoms located within 0.03 Å of their mean plane. In the crystal, the molecules are linked by O—H...O hydrogen bonds, generating infinite chains running parallel to the [100] direction.
Effect of exchange rate uncertainty on bilateral trade performance in SAARC countries: a gravity model analysis
Authors: Banik Banna , Roy Chandan Kumar
Published: December 2020

Purpose

Exchange rate uncertainty leads to an indecisive environment for imports and exports that would condense international trade, foreign direct investment, trade earnings, trade volumes, economic growth and welfare. This study aims to examine, empirically, the effect of exchange rate uncertainty on bilateral trade performance, focusing on eight SAARC member economies using the popular modified gravity model of trade.

Design/methodology/approach

The paper includes eight SAARC members – Afghanistan, Bangladesh, Bhutan, Maldives, Nepal, Pakistan and Sri Lanka panel data set over the period 2005–2018. The authors consider both standardized value (standard deviation) and conditional variance model to determine volatility of exchange rate. Primarily, ordinary least squares, random effects and fixed effects estimation techniques are employed to investigate the impact of exchange rate volatility. Endogeneity and robustness of the findings have been tested using the simultaneity-adjusted model and dynamic panel data two-step system GMM estimation techniques.

Findings

Empirical findings endorse the view that exchange rate volatility lowers trade flows in the SAARC regions. However, this adverse effect of exchange rate uncertainty on trade is pretty small. The negative correlation between exchange rate volatility and bilateral trade remains consistent and significant after controlling of simultaneous causality, autocorrelation, year effects, country-pair heterogeneity and endogeneity irrespective of panel data estimation techniques and different measures of volatility.

Originality/value

The present paper is original work.
Semantic voice search in IETP: filling the gap for maintenance 4.0
Authors: Marques Henrique Costa , Giacotto Alessandro , Scussiatto Carlos Eduardo , Abrahão Fernando Teixeira Mendes
Published: December 2020

Purpose

A framework is being developed to help Integrated Electronic Technical Publications (IETP) consultation inside and outside the aviation maintenance hangar. The expected results are the reduction in time to access the desired IETP and to assist mechanics while performing maintenance tasks using voice recognition.

Design/methodology/approach

The work is being conducted based on literature review and consultation with mechanics from the aviation industry, through questionnaires. The development will be made through study cases by building a core search engine and mobile applications to support the mechanics during the maintenance activities.

Findings

The identified problem in small maintenance shops and defence organizations suggests that IETP are not entirely accessible before and during the maintenance activity. Such organizations suffer from information and communications technology (ICT) low infrastructure capability and demand access to multiple IETP databases as they usually support different aircraft. To have access to the IETP through voice assistant application will help mechanics to access the IETP, including when they would be with dirty hands and having difficulty in using mobile devices with touch displays.

Originality/value

The framework being developed will give mechanics the ability to quickly find any existing IETP to support its maintenance task at any time and in any place with low demanding for ICT infrastructure. The architecture will support different applications, and the identified priority is for IETP viewers to the most demanding functionality of specification ASD S1000D. This approach could also help in troubleshooting activities since COVID-19 brought new demands for the social distancing for mechanics.
Improved sensitivity, accuracy and prediction provided by a high‐performance liquid chromatography screen for the isolation of phytase‐harbouring organisms from environmental samples
Authors: Rix Gregory D. , Todd Jonathan D. , Neal Andrew L. , Brearley Charles A.
Published: December 2020

HPLC methods are shown to be of predictive value for classification of phytase activity of aggregate microbial communities and pure cultures. Applied in initial screens, they obviate the problems of ‘false‐positive’ detection arising from impurity of substrate and imprecision of methodologies that rely on phytate‐specific media. In doing so, they simplify selection of candidates for biotechnological applications. Combined with 16S sequencing and simple bioinformatics, they reveal diversity of the histidine phosphatase class of phytases most commonly exploited for biotechnological use. They reveal contribution of multiple inositol‐polyphosphate phosphatase (MINPP) activity to aggregate soil phytase activity, and they identity Acinetobacter spp. as harbouring this prevalent soil phytase activity. Previously, among bacteria MINPP was described exclusively as an activity of gut commensals. HPLC methods have also identified, in a facile manner, a known commercially successful histidine (acid) phosphatase enzyme. The methods described afford opportunity for isolation of phytases for biotechnological use from other environments. They reveal the position of attack on phytate by diverse histidine phosphatases, something that other methods lack.
War‐Power Reform in Australia: (Re)considering the Options
Authors: Mulherin Peter E.
Published: December 2020

The decision to go to war in Australia remains the prerogative of the Executive. The lack of parliamentary authorisation of perhaps the most significant decision a democracy can make has seen sustained, but unsuccessful, efforts to reform legislation. In the wake of the costly invasion and occupation of Iraq in 2003, repeated calls for legislative reform of Australia's war powers have failed to find traction amongst Coalition and Australian Labor Party (ALP) leadership. Lamenting the lack of transparency and accountability in the current system, those favouring legislative reform would see authorisation of combat missions placed in the hands of Parliament. However, given the lack of support from either of the major parties, any legislative reform remains unlikely. Given this impasse, this article argues that a compromise option, in the form of a new war‐powers convention, may be a small step towards democratising the decision of going to war. While not legally binding, this constitutional convention would represent an agreement by the major parties that overseas combat operations will be properly debated in Parliament.
Factors influencing age at natural menopause
Authors: Arinkan Sevcan Arzu , Gunacti Mert
Published: December 2020

Aim

Women who experience menopause before 45 years, have an increased risk for morbidity and mortality. We aimed to identify the factors influencing the age at natural menopause and to investigate whether tubal ligation alter age at natural menopause.

Methods

This cross‐sectional study was conducted on total 1660 women with natural menopause. The participants were divided into two groups as the ones having menopause before age of 45 years and after 45 years old.

Results

Positive family history, smoking and use of oral contraceptive were found to increase the risk of early menopause by 3.68, 1.34 and 1.04 times, respectively. First pregnancy at older age reduced the risk of early menopause by 0.97 and obesity reduced this risk by 0.65 (95% CI 0.47–0.90). There was no significant difference between menopausal age of patients who underwent BTL (47.46 ± 4.67 years old) and those who did not (47.68 ± 5.18 years old) (P:0.320; P > 0.05). The mean age at menopause of patients who had tubal ligation with laparoscopic cauterization and Pomeroy technique was 46.91 ± 4.07 and 47.55 ± 4.76 years old, respectively (P:0.503; P > 0.05). Besides, there was no significant difference between patients having tubal ligation at the time of cesarean section and those who did not regarding menopausal age (P:0.314; P > 0.05).

Conclusion

We recommend identifying modifiable factors and informing women at risk of early menopause. Tubal ligation, when performed correctly, should not compromise ovarian function. If tubal ligation interferes with vascular supply to the ovaries, it may not be substantial enough to result in an earlier onset of menopause.
Experimental infection of cats with Cystoisospora felis
Authors: Scorza Andrea V. , Tyrrell Phyllis , Jablonski Wennogle Sara A. , Chandrashekar Ramaswamy , Lappin Michael R.
Published: December 2020

Background

Cystoisospora felis is a common parasite of cats and is diagnosed by fecal flotation, but false‐negative results can be common.

Hypothesis/Objectives

To experimentally inoculate cats with C. felis oocysts, to compare fecal flotation and polymerase chain reaction (PCR) results, and to describe any clinical signs consistent with infection.

Animals

Six cats.

Methods

Cystoisospora felis oocysts were identified morphologically from feces of a naturally infected kitten with diarrhea, sporulated oocysts (5000) were inoculated to 6 cats that were negative for fecal parasites by fecal flotation and by a fluorescent antibody assay (FA) for Giardia spp. and Cryptosporidium spp. Cats were observed daily for the presence of clinical signs consistent with infection. Fecal samples were evaluated by fecal flotation and FA up to 3 times per week post inoculation (PI) to Day 27. Thirty‐six samples collected before inoculation and from Days 8, 10, 13, 15, and 20 PI were assayed using an internal transcribed spacer 1 (ITS1) PCR that amplifies DNA of C. felis.

Results

All cats were negative for C. felis by both assays before inoculation. All cats shed C. felis oocysts by Day 10 PI, oocysts were not detected by fecal flotation after Day 15 PI. Cystoisospora felis DNA was amplified from 24/36 (66.6%) fecal samples from 6/6 (100%) of the cats. Oocysts were not detected by fecal flotation in 4 of the samples that were positive for C. felis DNA by PCR. Clinical signs were not recognized in any of the study cats.

Conclusions and Clinical Importance

Fecal flotation is a convenient assay for detection of C. felis but could occasionally give false‐negative results when compared to this ITS1 PCR.
Early radiation‐induced oral pain signaling responses are reduced with pentoxifylline treatment
Authors: Price Mikayla L. , Lai Yen‐Hao (Erik) , Marcus Karen L. , Robertson James B. , Lascelles B. Duncan X. , Nolan Michael W.
Published: December 2020

Radiation‐induced acute oral mucositis is associated with inflammation and pain. In other realms of pain research, nociceptors are known to be activated by inflammatory cytokines; for example, tumor necrosis factor alpha (TNF‐α) can activate transient receptor potential ion channels on sensory neurons. But there is an unclear relationship between inflammatory cytokines and molecular mediators of pain in radiation‐induced mucositis (RIM) and radiation‐associated pain (RAP). In this prospective, analytical, experimental pilot study, a common drug (pentoxifylline [PTX]) was used with the goal of inhibiting TNF‐α signaling in mice that underwent lingual irradiation to induce severe acute oral RIM/RAP. Body weight and glossitis scores were recorded daily. Eye wiping behaviors were assayed as a surrogate measure of oral discomfort (which is possible due to cross‐sensitization of the mandibular and ophthalmic branches of the trigeminal nerve). Quantitative real‐time reverse transcription polymerase chain reaction was performed on irradiated tongue tissue to measure changes in expression of TNF‐α, its receptor, nuclear factor kappa‐light‐chain‐enhancer of activated B cells, transient receptor potential vanilloid type 1 (TRPV1), and transient receptor potential vanilloid type 4 (TRPV4). Responsiveness of afferent sensory trigeminal neurons to TNF‐α, a TRPV1 agonist (capsaicin), and a partial TRPV4 agonist (histamine) was measured via calcium imaging. Although PTX treatment did not reduce glossitis severity or mitigate weight loss in mice with RIM/RAP, it did inhibit the upregulation of TNF‐α’s receptor that normally accompanies RIM, and it also reduced neuronal responsiveness to each of the aforementioned chemical stimuli. These results provide provisional evidence that inhibition of TNF‐α signaling with PTX treatment may serve as a useful tool for reducing pain in head and neck cancer patients.
Medidas de excepción previas a la justicia de transición en Colombia y sus efectos de legalidad penal: periodo 1948-1962
Authors: Prieto-Sanjuan Rafael A. , Sandoval-Mesa Jaime A.
Published: December 2020

El objeto del presente artículo consiste en estudiar las medidas de excepción que afectaron la legalidad penal en el período comprendido de 1948 a 1962, que para muchos constituye el punto de partida del conflicto armado en Colombia. De manera específica, se pretende analizar las fórmulas jurídicas que desde entonces fueron ejercidas para mitigar las causas de la violencia, que tarde o temprano devinieron en subversión y luego, en confluencia de diversos escenarios protagonizados por actores armados, representó la ejecución de medidas especiales que afectaron la legalidad penal, el sistema como tal y el orden constitucional vigente en dicho momento. Es decir, el sistema del Código Penal vigente en el momento (1936) y la Constitución de 1886. Lo anterior se desarrolla a partir del método hermenéutico analítico desde la visión de Arthur Kaufmann[i] que considera los cuatro pilares del derecho vigente, a saber: El histórico, necesario para la descripción de las fuentes directas del período bajo examen y sus medidas; el elemento lógico y sistemático, que revela la validez del derecho vigente para la época; y, finalmente, el elemento teleológico, que resulta pertinente para verificar los elementos que sustentaban las medidas de excepción, así como también su contenido material verificable en la actualidad como lesivo de las garantías judiciales y que puede generar los cuestionamientos críticos del sistema actual y su transición desde la Constitución de 1991.
 
[i] Arthur Kauffman, Filosofía del Derecho, 120-125 (1.a ed., Editorial Universidad Externado de Colombia, 1998).
Effectiveness of a Shell and Helically Coiled Tube Heat Exchanger Operated With Gold Nanofluids at Low Concentration: A Multi-Level Factorial Analysis
Authors: Fogaça Marina Borsuk , Dias Daniele Toniolo , Gómez Sergio Leonardo , Behainne Jhon Jairo Ramirez , Turchiello Rozane de Fátima
Published: December 2020

This work assesses the thermal performance of gold nanofluid as a cooling liquid in a shell and helically coiled tube (SHCT) heat exchanger (HE) built at the bench scale. Tests planned under a multi-level factorial experimental design were carried out to evaluate the effects of the volumetric fraction of the gold nanoparticles, the volumetric flowrate of the working fluid, and the inlet temperature of the hot fluid (water) on the SHCT heat exchanger effectiveness. Spherical gold nanoparticles with a mean diameter of 14 ± 2 nm were produced using Turkevich’s method to be used at two concentrations of approximately 10−5 vol%. The heat transfer tests were performed at volumetric flowrates of 20, 30, and 40 l/h for both working fluids using heated water at inlet temperatures of 40, 50, and 60 °C. Results showed that the less concentrated nanofluids were comparatively more efficient, suggesting the presence of a range of gold concentration values for improving the heat transfer effectiveness.